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Exploration of New Reactivities ofAzetidinols and Alkynylborates(Dissertation_全文 )

Shimamoto Yasuhiro

Shimamoto Yasuhiro Exploration of New Reactivities of Azetidinols and Alkynylborates京都大学 2014 博士(工学)

2014-03-24

httpsdoiorg1014989doctork18301

Exploration of New Reactivities of Azetidinols and Alkynylborates

Yasuhiro Shimamoto

2014

Preface

The studies presented in this thesis have been carried out under the direction of

Professor Masahiro Murakami at Kyoto University during 2008-2014 The studies

concerned with the development of the new synthetic reactions using azetidinols and

alkynyl borates

The author would like to express his sincerest gratitude to Professor Masahiro

Murakami for his kind guidance powerful encouragement stimulating discussions

throughout this study The author learned a lot of things from Professor Murakami They

are not only chemistry but also important things to live

The author is grateful to Assistant Professor Naoki Ishida for his support and teaching

chemical techniques and discussions The author is also grateful to Associate Professor

Tomoya Miura and Assistant Professor Akira Yada for their discussion and suggestion

The author was fortunate to have had a lot of assistance of Dr David Neĉas Ms

Hanako Sunaba and Mr Takaaki Yano The author acknowledge to them for their

patience earnest and collaborations

The author wishes to express his gratitude to Dr Peter Bruumlchner Dr Akiko Okamoto

Dr Lantao Liu Dr Changkun Li Dr Scott G Stewart Dr Hiroshi Shimizu Dr

Masanori Shigeno Dr Motoshi Yamauchi Dr Takeharu Toyoshima Mr Yoshiteru Ito

Ms Mizuna Narumi Mr Yoshiyuki Yamaguchi Mr Keita Ueda Mr Taisaku Moriya

Mr Tomohiro Igarashi Mr Masao Morimoto Mr Taiga Yamamoto Mr Osamu

Kozawa Ms Paula de Mendoza Bonmati Mr Shota Sawano Mr Wataru Ikemoto Mr

Yusuke Mikano Mr Akira Kosaka Mr Tsuneaki Biyajima Mr Yuuta Nakanishi Mr

Tatsuya Yuhki Mr Kentaro Hiraga Ms Yui Nishida Mr Yusuke Masuda Mr

Takamasa Tanaka Mr Yuuta Funakoshi Mr Tetsuji Fujii Mr Shintaro Okumura Mr

Shoichiro Fujita Mr Yuuki Yamanaka Mr Takayuki Nakamuro Mr Andreas Fetzer

Mr Norikazu Ishikawa Mr Shoki Nishi Mr Kohei Matsumoto Ms Yuki Sakai and all

other members of Murakami Laboratory for their enthusiasm and kind consideration

The author is grateful to Mr Daishi Fujino Mr Kenichiro Nakai Mr Momotaro

Takeda Mr Yosuke Tani and all other friends for stimulating conversation with them

The author thanks Mr Haruo Fujita Mr Tadashi Yamaoka Ms Keiko Kuwata Ms

Midori Yamamura Ms Sakiko Goto Ms Eriko Kusaka Ms Karin Nishimura for the

measurement of NMR spectra and Mass spectra

The author is grateful for Research Fellowships of the Japan Society for the

Promotion of Science for Young Scientists

Finally the author expresses his deep appreciation to his family especially his parents

Mr Takashi Shimamoto Ms Akiyo Shimamoto for their constant assistant and

encouragement

Yasuhiro Shimamoto

Department of Synthetic Chemistry and Biological Chemistry

Graduate School of engineering

Kyoto University

Contents

General Introduction 1

Chapter 1

Solar-Driven Incorporation of Carbon Dioxide into -Amino Ketones 9

Chapter 2

15-Rhodium Shift in Rearrangement of N-Arenesulfonylazetidin-3-ols into

Benzosultams 29

Chapter 3

Stereoselective Synthesis of (E)-(Trisubstituted alkenyl)borinic Esters Stereochemistry

Reversed by Ligand in the Palladium-Catalyzed Reaction of Alkynylborates with Aryl

Halides 67

Chapter 4

Iterative Approach to Oligo(arylenevinylene)s Containing Tetrasubstituted Vinylene

Units 89

Chapter 5

Regioselective Construction of Indene Skeltons by Palladium-Catalyzed Annulation of

Alkynylborates with o-Iodophenyl Ketones 105

List of Publications 127

General Introduction

1


Organic synthesis has contributed to our lives For example various chemical

industries pharmaceutical chemistry material chemistry and others make our lives

more comfortable and convenient

In this thesis the author would like to describe new synthetic reactions which are

directed towards following issues

(1) Solar-driven incorporation of carbon dioxides into -amino ketones

(2) 15-Rhodium shift in rearrangement of N-arenesulfonylazetidinols into benzo-

sultams

(3) Palladium catalyzed reaction of alkynylborates with aryl halides


The utilization of solar energy is an attractive subject in organic synthesis because

solar energy is one of the most sustainable energy in the world1 On the other hand the

utilization of carbon dioxides as the C1 source is still significant challenge because of

its stability2 In chapter 1 the author describs solar-driven incorporation of carbon

dioxide into -amino ketones In first step photoreaction promoted by solar light

produces azetidinols3 This transformation is endergonic thus harvesting the solar

energy as the chemical energy in the form of structural strain In second step carbon

dioxides is incorporated into the azetidinls to afford cyclic carbonates The relief of the

structural strain serves as driving force for the CO2 incorporation reaction This two

phase reaction system demonstrates a simple model of chemical utilization of solar

energy for CO2 incorporation

sun

CO2energy charge

Ph

O

NTs

Me

N

Ts

OHPh

OO

O

Ph

NHTs


2

(2) 15-Rhodium shift in rearrangement of N-arenesulfonylazetidinols into

benzosultams

1n-metal shift is an attractive process which enables unique metal catalyzed reactions

Therefore many reactions have been developed via a 1n-metal shift Especially a lot of

rhodium and palladium catalyzed reactions involving 14-metal shift have been

developed456

However there are much less examples of 15-metal shift than 14-metal

shift7

MH14-metal shift

1

2 3

4

HM

1

2 3

4

H M1

23

4

5

M H1

23

4

515-metal shift

In chapter 2 the author describes rhodium catalyzed rearrangement of

N-arenesulfonylazetidinols into benzosultams via 15-rhodium shift Various

benzosultams were obtained in quantitative yield In addition chiral azetidinols which

are easily available by modified Seebachrsquos procedure8 afford the enatio- and

diastereopure benzosultams quantitatively

N

Ts

Ph OHMe

SN

MeO O

Ph OH

cat Rh

(3) Palladium catalyzed reaction of alkynylborates with aryl halide

Organoboron compounds are versatile synthetic reagents for carbon-carbon bond

formation reactions because they are easily handled and have the well known

reactivities9 In addition their utilizations are increasing in the field of pharmaceutical

chemistry10

and material science11

Therefore it is the important for organic chemists to

develop the new efficient methods to synthesis the organoboron compounds precisely

Alkynylborates react with electrophiles on the -position of boron to afford the

alkenylboranes which are difficult to synthesize by other conventional methods12

We

have focused such reactivities and developed a palladium catalyzed reaction of

alkynylborates13

R1 B

R2

R2

R2

+ R3 Br

R3

R1 R2

B

R2

R2


3

In chapter 3 the author describes the palladium catalyzed reaction of alkynylborates

with aryl halides which provids the trisubstituted alkenylboranes regio- and

stereoselectively The stereochemistry of the alkenylboranes is dependent upon the

ligand employed Using Xantphos as the ligand (Z)-alkenylboranes were obtained

stereoselectively On the other hand in the case of (o-tol)3P (E)-alkenylboranes were

obtained

Et

Ph

Ph

B O+

PhBr LPd(-allyl)Cl

L = XANTPhos

LPd(-allyl)Cl

L = P(o-tol)3 Ph

Et

Ph

B O

B

Et

Ph

Et

Ph

B

Ph

Ph

Et

B

Ph

Me3NO

Me3NO

[Me4N]

Oligo(arylenevinylene)s are important compounds in the field of material science14

Though a wide variety of oligo(arylenevinylene)s have been synthesized

oligo(arylenevinylene)s with tetrasubstituted olefin units have not been synthesized In

chapter 4 the author describes an iterative approach to this class of molecules Various

oligo(arylenevinylene)s are synthesized stereoselectively starting from bromo (iodo)

benzenes and alkynylborates

MeO

Br

I

Br

NaOH

R Ph

MeO Br

B

R

Ph

RB

Ph

OMe

[Me4N]

R Ph

MeOR Ph

Br

R =OMOM

n

B

R

Ph

[Me4N] I

Br

NaOH

R Ph

MeOR Ph

Br

n = 2~4

Pd-XANTPhos

Pd-XANTPhos

Indene skeleton is an important substructure in the field of pharmaceutical chemistry

and material science An annulation reaction of o-halobenzoyl compounds with alkyne

provides an efficient way to synthesize indenols however it is difficult to control the

regioselectivity In chapter 5 the author describs a palladuium-catalyzed reaction of


4

alkynylborates with o-iodophenyl ketones which provides 23-disubstituted indenols

regioselectively

I

Me

O+

MeOH

R2

R1Pd-XANTPhosB

R2

R1

[Me4N]


5

Reference

(1) Armaroli N Balzani V Energy for a Sustainable World From the Oil Age to a

Sun-Powered Future Wiley-VCH Weinheim 2011

(2) (a) DellrsquoAmico D B Calderazzo F Labella L Marchetti F Pampaloni G

Chem Rev 2003 103 3857 (b) Sakakura T Choi J-C Yasuda H Chem Rev

2007 107 2365 (c) Darensbourg D J Chem Rev 2007 107 2388 (d) Carbon

Dioxide as hemical Feedstock (Ed M Aresta) Wiley-VCH Weinheim 2010 (e)

Riduan S N Zhang Y Dalton Trans 2010 39 3347 (f) Behr A Henze G

Green Chem 2011 13 25 (g) Cokoja M Bruckmeier C Rieger B Herrmann

W A Kuumlhn F E Angew Chem 2011 123 8662 Angew Chem Int Ed 2011 50

8510 (h) Omae I Coord Chem Rev 2012 256 1384

(3) (a) Yang N C Yang D-D H J Am Chem Soc 1958 80 2913 (b) Gold E H J

Am Chem Soc 1971 93 2793 (c) Allworth K L El-Hamamy A A Hesabi M

M Hill J J Chem Soc Perkin Trans 1 1980 1671

(4) Reviews (a) Ma S Gu Z Angew Chem Int Ed 2005 44 7512-7517 (b) Shi F

Larock R Top Curr Chem 2010 292 123-164

(5) For a 14-palladium shift (a) Bocelli G Catellani M Chiusoli G P Larocca S J

Organomet Chem 1984 26 C9-C11 (b) Dyker G Chem Ber 1994 127 739-742

(c) Campo M A Larock R C J Am Chem Soc 2002 124 14326-14327 (d)

Baudoin O Herrbach A Gueacuteritte F Angew Chem Int Ed 2003 42 5736-5740

(e) Masselot D Charmant J P H Gallagher T J Am Chem Soc 2005 128

694-695 (f) Barder T E Walker S D Martinelli J R Buchwald S L J Am

Chem Soc 2005 127 4685-4696 (g) Zhao J Yue D Campo M A Larock R

C J Am Chem Soc 2007 129 5288-5295 and references cited therein

(6) For a 14-rhodium shift (a) Oguma K Miura M Satoh T Nomura M J Am

Chem Soc 2000 122 10464-10465 (b) Hayashi T Inoue K Taniguchi N

Ogasawara M J Am Chem Soc 2001 123 9918-9919 (c) Miura T Sasaki T

Nakazawa H Murakami M J Am Chem Soc 2005 127 1390-1391 (d) Shintani

R Okamoto K Hayashi T J Am Chem Soc 2005 127 2872-2873 (e) Yamabe

H Mizuno A Kusama H Iwasawa N J Am Chem Soc 2005 127 3248-3249

(f) Matsuda T Shigeno M Murakami M J Am Chem Soc 2007 129

12086-12087 (g) Panteleev J Menard F Lautens M Adv Synth Catal 2008 350

2893-2902 (h) Seiser T Roth O A Cramer N Angew Chem Int Ed 2009 48

6320-6323 (i) Shigeno M Yamamoto T Murakami M Chem Eur J 2009 15

12929-12931 (j) Seiser T Cramer N Angew Chem Int Ed 2010 49

10163-10167 (k) Sasaki K Nishimura T Shintani R Kantchev E A B


6

Hayashi T Chem Sci 2012 3 1278-1283 (l) Matsuda T Suda Y Takahashi A

Chem Commun 2012 48 2988-2990 and references cited therein

(7) (a) Bour C Suffert J Org Lett 2005 7 653-656 (b) Mota A J Dedieu A

Bour C Suffert J J Am Chem Soc 2005 127 7171-7182 (c) Shintani R

Otomo H Ota K Hayashi T J Am Chem Soc 2012 134 7305-7306 (d)

Tobisu M Hasegawa J Kita Y Kinuta H Chatani N Chem Commun 2012

11437-11439 (d) So C M Kume S Hayashi T J Am Chem Soc 2013 135

10990

(8) (a) Podlech J Seebach D Helv Chim Acta 1995 78 1238-1246 (b) Wang J

Hou Y Wu P J Chem Soc Perkin Trans 1 1999 2277-2280 (c)

(9) Suzuki A Brown H C Organic Synthesis via Boranes Aldrich Milwaukee WI

2003 Vol 3

(10) (a) Rock F L Mao W Yaremchuk A Tukalo M Creacutepin T Zhou H Zhang

Y-K Hernandez V Akama T Baker S J Plattner J J Shapiro L Martinis S

A Benkovic S J Cusack S Alley M R K Science 2007 316 1759 (b) Zhu

Y Zhao X Zhu X Wu G Li W Ma Y Yuan Y Yang J Hu Y Ai L Gao

Q Z J Med Chem 2009 52 4192

(11) (a) Entwistle C D Marder T B Chem Mater 2004 16 4574 (b) Yamaguchi

S Wakamiya A Pure Appl Chem 2006 78 1413 (c) Jaumlkle F Coord Chem Rev

2006 250 1107

(12) (a) Negishi E J Org Chem 1976 108 281 (b) Pelter A Bentley T W

Harrison C R Subrahmanyam C Laub R J J Chem Soc Perkin Trans 1 1976

2419

(13) (a) Ishida N Miura T Murakami M Chem Commun 2006 4381 (b) Ishida

N Narumi M Murakami M Org Lett 2008 10 1279 (c) Ishida N Shinmoto

T Sawano S Miura T Murakami M Bull Chem Soc Jpn 2010 11 1380 (d)

Ishida N Ikemoto W Narumi M Murakami M Org Lett 2011 13 3008 (e)

Ishida N Narumi M Murakami M Helv Chim Acta 2012 95 2474

(14) (a) Tour J M Chem Rev 1996 96 537 (b) Martin R E Diederich F Angew

Chem Int Ed 1999 38 1350 (c) Scherf U Top Curr Chem 1999 201 163

(15) (a) Brogden R N Heel R C Speight T M Avery G S Drugs 1978 16

97ndash114 (b) Nicholson A N Pascoe P A Turner C Ganellin C R Greengrass

P M Casy A F Mercer A D Br J Pharmacol 1991 104 270ndash276 (c)

Huffman J W Padgett L W Curr Med Chem 2005 12 1395ndash1411


7

(16) (a) Zhu X Mitsui C Tsuji H Nakamura E J Am Chem Soc 2009 131

13596ndash13597 (b) Zeng X Ilies L Nakamura E J Am Chem Soc 2011 133

17638ndash17640


8

Chapter 1

9

Chapter 1

Solar-Driven Incorporation of Carbon Dioxide into -Amino

Ketones

Abstract

-Amino ketones react with carbon dioxides to give cyclic carbonates via

photocyclization promoted by solar light This reaction demonstrates a model of

chemical utilization of solar energy for CO2 incorporation

Reproduced with permission from Angew Chem Int Ed 2012 51 11750-11752

Copyright 2012 Wiley-VCH Verlag GmbH amp Co KGaA Weinheim

Chapter 1

10

Introduction

The recent manifestation of the potential risk inherent to nuclear technologies has

incited a strong demand for exploration of innovative means to exploit energy from

natural sources thus increasing the need for research on sustainable energy in many

scientific fields Chemists can contribute by developing chemical systems to utilize

solar light which is undoubtedly the best source of sustainable energy available on the

planet1 Another imperative issue is the establishment of carbon-neutral systems

2 One

synthetic approach to this issue is the incorporation of CO2 into organic compounds as a

chemical feedstock3 High-energy compounds suit energetically low CO2 as the reaction

partner Under these circumstances it presents a significant challenge to simultaneously

tackle the two issues mentioned above Thus we tried to develop a reaction that is

promoted by solar light and utilizes CO2 as a chemical feedstock (Figure 1)

Figure 1 Solar Driven Incorporation of Carbon Dioxide

starting substances

Incorporated products

CO2

sun

CO2energy charge

high energy

intermediates

Results and Discussion

We report herein a solar-driven process that incorporates CO2 into -methylamino

ketones The resulting aminosubstituted cyclic carbonates are expected to be useful

building blocks of pharmaceuticals and fuel additives4 Our attention was initially

directed to a photochemical cyclization reaction observed with a-methylamino ketones5

Of note was that this photoreaction proceeded in an energetically uphill direction A

high-energy four-membered ring6 was constructed through the insertion of a

photo-excited carbonyl group into the carbonndashhydrogen bond of a pendant methyl group

on a nitrogen atom In a formal sense the intrinsically inert carbonndashhydrogen bond was

cleaved7 and added across the carbonndashoxygen double bond in a 4-exo-trig mode

8

Although the reaction was originally reported to require irradiation with a mercury lamp

which used electricity5b

we discovered that natural solar light successfully effected this

energetically uphill reaction -amino ketone 1a cyclized at a reasonable rate upon

exposure to solar light (Scheme 1)

Chapter 1

11

Scheme 1 Solar Light Promoted Cyclization of 1a

Ph

O

NTs

Mesolar light

N

Ph OH

Ts

2a 91

1aDMA

Furthermore ordinary Pyrex glass not quartz was suitable for the reaction vessel

light of wavelengths below 400 nm was required for the photoreaction and Pyrex glass

transmitted a sufficient amount of operative light even on a cloudy day Thus simply

setting a Pyrex tube containing a solution of 1a in NN-dimethylacetamide (DMA) on a

balcony or rooftop brought about the cyclization The conversion was dependent upon

the amount of solar radiation We defined it as ldquosunnyrdquo when an hourly solar radiation

over 04 kWm-2

was observed and as ldquocloudyrdquo when it ranged from 01 to 04 kWm-2

Typically the total amount of solar radiation amounted to 55 kWhm-2

in eight hours on

a sunny day to cause full conversion of 1a on a 01 mmol scale (010 mmolL-1

Figure

2A) The reaction mixture was subsequently applied to conventional column

chromatography on silica gel and analytically pure azetidinol 2a was isolated in 91

yield In contrast an analogous experiment on a cloudy day produced 2a in 54yield

after eight hours (Figure 2B) when the total amount of solar radiation reached 09

kWhm-2

Thus it turned out to be possible to transfer 1a into the product9 by using solar

energy even on a cloudy day

Chapter 1

12

Figure 2 Solar-Light Promoted Cyclization of 1a

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

0

20

40

60

80

100

0 1 2 3 4 5 6

(A) Residual ratio of 1a () and yield of 2a () during solar

radiation (B) Yield of 2a over time on sunny () and cloudy day ()

We next attempted to incorporate CO2 into azetidinol 2a in which energy has been

stored by reacting it with CO2 and a remarkably simple way was found CO2 was

successfully incorporated upon exposure of a solution of 2a in DMA to gaseous CO2 in

the presence of a base For example stirring a heterogeneous mixture of 2a and Cs2CO3

(40 equiv) in DMA under an atmosphere of CO2 (1 atm) at 60degC for ten hours led to the

quantitative production of the cyclic carbonate 3a which was isolated in 93 yield after

purification by chromatography (Scheme 2) Organic bases such as

18-diazabicyclo[540]undec-7-ene (DBU) also afforded 3a albeit in a lower yield

(56)

Chapter 1

13

Scheme 2 Incorporation of Carbon Dioxide

40 equiv Cs2CO3

1 atm CO2

DMA 60 degC

OO

O

Ph

NHTs

3a 93

N

Ph OH

Ts

2a

The formation of 3a is explained by assuming the pathway depicted in Scheme 34

Azetidinol 2a is initially deprotonated by Cs2CO3 to produce alkoxide anion A which

subsequently adds to CO2 to afford carbonate anion B The following nucleophilic

attack of the anionic oxygen onto the 2-carbon atom prompts displacement of the

tosylamide anion through a 5-exo-tet process8 Thus the four-membered ring is opened

thereby releasing the energy originating from sun Finally protonation of C affords 3a

Scheme 3 Plausible Mechanism

N

Ph O

Ts

A

N

Ph O

Ts

B

O

O

OO

O

Ph

NTs

CO2

H

C

Cs2CO3

CsHCO 3

Cs

Cs

Cs

2

1

N

Ph OH

Ts

2a

OO

O

Ph

NHTs

3a

For comparison pyrrolidinol 4 was subjected to the identical reaction

conditions Unlike the four-membered counterpart 2a the five-membered

compound 4 failed to react and was recovered unchanged The contrasting

results observed with 2a and 4 lend support to the explanation that the major

driving force for the CO2-capturing reaction is the release of the energy

stored in the form of the strained four-membered ring

The experimental procedures for both the photochemical cyclization reaction and the

CO2-capturing reaction are so simple that it is possible to carry them out in a single

flask (Scheme 4) Initially a DMA solution of 1a in an atmosphere of CO2 (1 atm) was

irradiated with solar light outside After completion of the photoreaction Cs2CO3 was

simply added to the reaction mixture which was then heated at 60degC for ten hours in a

N

Ts

OHPh

4

Chapter 1

14

fume hood Isolation by chromatography afforded the analytically pure cyclic carbonate

3a in 83 yield based on 1a

Scheme 4 Solar Driven Incorporation of Carbon Dioxide into -Amino Ketone 1a

solar light

CO2Cs2CO3

60degCDMAPh

O

NTs

Me

1a

OO

O

Ph

NHTs

3a 83

The broad generality of this consecutive process was verified by application to

various acetophenone derivatives (Scheme 5) Both an electron-donating methoxy

group and an electron-withdrawing trifluoromethyl group were allowed at the

para-position of the benzoyl group and the corresponding products 3b and 3c were

isolated in reasonable total yields The presence of possibly photoactive bromo and

chloro groups10

had essentially no effect on the reaction (3d and 3e) Sulfonyl groups

other than a p-toluenesulfonyl group were also suitable as the substituent on the

nitrogen atom (3fndashh)

Table 1 Scope of Solar Driven CO2 Incorporation into -Amino Ketone

Ar

O

NR

Me OO

O

Ar

NHR3

1

OO

O

NHTs3b 80

MeO

OO

O

NHTs3c 57

F3C

OO

O

NHTs3d 73

Cl

OO

O

NHTs3e 85

Br

OO

O

Ph

NH

3f 87

O2S OMe

OO

O

Ph

NH

3g 85

O2S CF3

OO

O

Ph

NH

3h 87

O2S

N

solar lightCO2

Cs2CO3

60degCDMA

Overall yields of isolated products are given Reactions were conducted on a 02 mmol

scale with the following reagents and conditions 1 (020 mmol) DMA (10 mL) solar

light ambient temperature CO2 (1 atm) then Cs2CO3 (080 mmol) 60 degC

Chapter 1

15

Conclusions

In summary we have developed the unique solar-driven transformation of -amino

ketones CO2 is incorporated to afford amino-substituted cyclic carbonates which are

potentially useful ingredients in industry

Although photosynthesis is a complex assembly of a number of elementary reactions

it can be divided into two major reactions the light reaction and the dark reaction In the

former reaction solar energy is captured to promote an energetically uphill process with

production of high-energy molecules (adenosine triphosphate (ATP) and nicotinamide

adenine dinucleotide phosphate (NADPH) The dark reaction is an energetically

downhill process that does not require light ATP and NADPH which have chemically

stored solar energy during the former reaction assist in the fixation of CO2 which is

intrinsically low in energy Photosynthesis as a whole reduces CO2 into carbohydrates

Although the present consecutive process does not involve CO2 reduction its

mechanistic profile of energy resembles that of photosynthesis and presents a simple

model of the chemical utilization of solar energy for CO2 incorporation

Chapter 1

16

Experimental Section

General All reactions were carried out with standard Schlenk techniques IR

measurements were performed on a FTIR SHIMADZU DR-8000 spectrometer fitted

with a Pike Technologies MIRacle Single Reflection ATR adapter 1H and 13C NMR

spectra were recorded on a Varian Mercury-vx400 (1H at 40044 MHz and 13C at

10069 MHz) spectrometer NMR data were obtained in CDCl3 Proton chemical shifts

were referenced to the residual proton signal of CHCl3 at 726 ppm Carbon chemical

shifts were referenced to the carbon signal of CDCl3 at 770 ppm High-resolution mass

spectra were recorded on a Thermo Scientific Exactive (ESI) spectrometer Flash

column chromatography was performed with silica gel 60N (Kanto) Preparative

thin-layer chromatography (PTLC) was performed on silica gel plates with PF254

indicator (Merck)

Materials Unless otherwise noted all chemicals and anhydrous solvents were

obtained from commercial suppliers (2-Pyridyl)sulfonyl chloride1 was prepared

according to the reported procedure

Preparation of α-Amino Ketone 1a A Typical Procedure for the Preparation of

α-Amino Ketone 1a-1h

Ph

O

NTs

MeTsClMeNH2 +

Et2OTsNHMe

CH3CN

K2CO3

To an Et2O solution (40 mL) of p-toluenesulfonyl chloride (38 g 20 mmol) was added

an aqueous solution of methylamine (40 wt 40 mL) After being stirred for 6 h at

room temperature water was added to the reaction mixture The organic layer was

separated and the remaining aqueous layer was extracted with AcOEt (3 times) The

combined organic layer was washed with brine (once) dried over MgSO4 and

concentrated The residue was subsequently dissolved in acetonitrile

2-Bromoacetophenone (40 g 20 mmol) and potassium carbonate (28 g 20 mmol)

were added therein After being stirred overnight water was added to the reaction

mixture The aqueous layer was extracted with AcOEt (3 times) washed with brine

(once) dried over MgSO4 and concentrated The residue was purified by Flash column

chromatography on silica gel (hexaneethyl acetate = 51) to afford the α-amino ketone

Chapter 1

17

1a (51 g 17 mmol 84 yield)

Ph

O

NTs

Me

1a 1H NMR δ = 244 (s 3H) 283 (s 3H) 457 (s 2H) 733 (dd J = 88 04 Hz 2H)

745-751 (m 2H) 760 (tt J = 76 12 Hz 1H) 771-775 (m 2H) 795-799 (m 2H)

13C NMR δ = 215 356 560 1275 1282 1288 1297 1338 1347 1348 1436

1937 HRMS (ESI+) Calcd for C16H18NO3S M+H

+ 3041002 Found mz 3040994 IR

(ATR) 1693 1339 1227 1157 743 cm-1

O

NTs

Me

1bMeO

1H NMR δ = 244 (s 3H) 280 (s 3H) 388 (s 3H) 447 (s 2H) 693-697 (m 2H)

733 (d J = 80 Hz 2H) 770-774 (m 2H) 796-802 (m 2H) 13

C NMR δ = 215

355 555 558 1139 1275 1277 1296 1307 1346 1436 1640 1921 HRMS

(ESI+) Calcd for C17H20NO4S M+H

+ 3341108 Found mz 3341101 IR (ATR) 1688

1601 1329 1180 1159 cm-1

O

NTs

Me

1cF3C

1H NMR δ = 245 (s 3H) 280 (s 3H) 453 (s 2H) 735 (d J = 88 Hz 2H) 772 (d J

= 84 Hz 2H) 776 (d J = 84 Hz 2H) 812 (d J = 84 Hz 2H) 13

C NMR δ = 215

357 564 1234 (q JC-F = 2711 Hz) 1259 (q JC-F = 37 Hz) 1276 1288 1298

1344 1350 (q JC-F = 327 Hz) 1373 1439 1932 HRMS (ESI+) Calcd for

C17H17F3NO3S M+H+ 3720876 Found mz 3720865 IR (ATR) 1697 1325 1161

1121 1109 cm-1

Chapter 1

18

O

NTs

Me

1dCl

1H NMR δ = 245 (s 3H) 279 (s 3H) 448 (s 2H) 734 (d J = 80 Hz 2H) 744-748

(m 2H) 771 (d J = 80 Hz 2H) 792-796 (m 2H) 13

C NMR δ = 216 356 561

1276 1292 1297 1298 1330 1344 1404 1438 1928 HRMS (ESI+) Calcd for

C16H17ClNO3S M+H+ 3380612 Found mz 3380600 IR (ATR) 1692 1339 1225

1159 1088 cm-1

O

NTs

Me

1eBr


= 84 Hz 2H) 771 (d J = 84 Hz 2H) 786 (d J = 84 Hz 2H) 13

C NMR δ = 215

356 561 1275 1291 1297 1298 1321 1334 1344 1438 1930 HRMS (ESI+)

Calcd for C16H17BrNO3S M+H+ 3820107 Found mz 3820094 IR (ATR) 1697 1325

1223 1155 810cm-1

Ph

O

NS

Me

1f

OMe

OO

1H NMR δ = 282 (s 3H) 389 (s 3H) 456 (s 2H) 698-703 (m 2H) 746-751 (m

2H) 761 (tt J = 72 12 Hz 1H)776-781 (m 2H) 796-800 (m 2H) 13

C NMR δ =

356 556 561 1142 1283 1288 1294 1297 1338 1348 1630 1938 HRMS


+ 3200951 Found mz 3200943 IR (ATR) 1692

1342 1259 1155 741 cm-1

Chapter 1

19

Ph

O

NS

Me

1g

CF3

OO

1H NMR δ = 294 (s 3H) 474 (s 2H) 747-752 (m 2H) 762 (tt J = 76 12 Hz 1H)

780 (d J = 84 Hz 2H) 790-794 (m 2H) 798 (d J = 80 Hz 2H) 13

C NMR δ =

356 558 1233 (q JC-F = 2711 Hz) 1261 (q JC-F = 36 Hz) 12796 12799 1289



1059 748 cm-1

Ph

O

NS

Me

1h

N

OO

1H NMR δ = 302 (s 3H) 486 (s 2H) 744-753 (m 3H) 757-762 (m 1H)

788-798 (m 4H) 870 (ddd J = 48 16 08 Hz 1H)13

C NMR δ = 363 569 1224


C14H15N2O3S M+H+ 2910798 Found mz 2910785 IR (ATR) 1695 1337 1175 945

752 cm-1

Photoreaction of α-Amino Ketone 1a upon Irradiation with Solar Light

Ph

O

NTs

Mesolar light

N

Ph OH

TsDMA rt

1a

2a

α-Amino ketone 1a (303 mg 010 mmol) was placed in a Pyrex flask which was

subsequently filled with an atmospheric pressure of CO2 by vacuum-refill cycles The

flask was added NN-dimethylacetamide (10 mL) and exposed to solar light outside

After 10 h water was added to the reaction mixture and the aqueous layer was

extracted with Et2O (3 times) washed with water (3 times) brine (once) dried over

MgSO4 and concentrated The residue was purified by preparative thin-layer

chromatography on silica gel (hexaneethyl acetate = 21) to afford the azetidinol 2a

Chapter 1

20

(253 mg 0091 mmol 91 yield)

N

Ph OH

Ts

2a 1H NMR δ = 229 (s 1H) 248 (s 3H) 397 (d J = 96 Hz 2H) 415 (d J = 96 Hz

2H) 728-737 (m 5H) 740 (d J = 80 Hz 2H) 779 (d J = 80 Hz 2H) 13

C NMR δ

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS


+ 3041002 Found mz 3040995 Anal Calcd for

C16H17NO3S C 6334 H 565 N 462 O 1582 S 1057 Found C 6317 H 555

N 458 O 1555 S 1058 IR (ATR) 3477 1333 1184 1148 671 cm-1

Reaction of Azetidinol 2a with Carbon Dioxide

N

Ph OH

Ts

2a

40 equiv Cs2CO3

1 atm CO2

DMA 60 C

OO

O

Ph

NHTs

3a

Under an atmospheric pressure of CO2 an NN-dimethylacetamide solution (10 mL)

containing azetidinol 2a (303 mg 010 mmol) and cesium carbonate (130 mg 040

mmol) were stirred at 60 degC for 10 h The reaction mixture then treated with HCl aq (20

M) and the aqueous layer was extracted with Et2O (3 times) The combined organic

layer was washed with water (3 times) brine (once) dried over MgSO4 and

concentrated The residue was purified by preparative thin-layer chromatography on

silica gel (hexaneethyl acetate = 31) to afford the cyclic carbonate 3a (322 mg 0093

mmol 93 yield)

Chapter 1

21

One-Pot Reaction of α-Amino Ketone 1a with Carbon Dioxide

A Typical Procedure for the CO2-Capturing Reaction of α-Amino Ketones

40 equiv Cs2CO3

60 CPh

O

NR

Me OO

O

Ph

NHR3a

1a

solar light

DMA rt

1 atm CO2




After completion of the photochemical reaction Cs2CO3 (130 mg 040 mmol) was

added to the reaction mixture which was then stirred at 60 degC for 10 h in a room The

reaction mixture was treated with HCl aq (20 M) and the aqueous layer was extracted

with Et2O (3 times) The combined organic layer was washed with water (3 times)

brine (once) dried over MgSO4 and concentrated The residue was purified by

preparative thin-layer chromatography on silica gel (hexaneethyl acetate = 31) to

afford the cyclic carbonate 3a (288 mg 0083 mmol 83 yield)

OO

O

Ph

NHTs

3a 1H NMR δ = 240 (s 3H) 330 (dd J = 144 56 Hz 1H) 340 (dd J = 144 88 Hz

1H) 454 (d J = 84 Hz 1H) 508 (d J = 84 Hz 1H) 570 (dd J = 84 Hz 56 Hz 1H)

726-732 (m 4H) 734-743 (m 3H) 769-773 (m 2H) 13

C NMR δ = 215 503

724 850 1242 1269 1292 1299 1365 1381 1439 1542 HRMS (ESI+) Calcd

for C17H18NO5S M+H+

3480900 Found mz 3480892 Anal Calcd for C17H18NO5S

C 5878 H 493 N 403 O 2303 S 923 Found C 5871 H 496 N 389 O

2284 S 932 IR (ATR) 3261 1773 1435 1319 1045 cm-1

Chapter 1

22

OO

O

NHTs

3b

MeO

1H NMR δ = 240 (s 3H) 327 (dd J = 144 56 Hz 1H) 335 (dd J = 144 88 Hz

1H) 380 (s 3H) 452 (d J = 84 Hz 1H) 504 (d J = 88 Hz 1H) 564 (dd J = 84

56 Hz 1H) 688-693 (m 2H) 719-724 (m 2H) 728 (d J = 80 Hz 2H) 770 (d J =

84 Hz 2H) 13

C NMR δ = 215 503 554 724 848 1145 1256 1269 1298

1299 1365 1440 1541 1601 HRMS (ESI+) Calcd for C18H20NO6S M+H

+

3781006 Found mz 3780996 IR (ATR) 3238 1794 1518 1329 1057 723 cm-1

OO

O

NHTs

3c

F3C


1H) 453 (d J = 88 Hz 1H) 513 (d J = 84 Hz 1H) 565 (dd J = 84 60 Hz 1H)

729 (d J = 84 Hz 2H) 746 (d J = 84 Hz 2H) 765-771 (m 4H) 13

C NMR δ =

215 501 722 846 1235 (q JC-F = 2704 Hz) 1249 1263 (q JC-F = 37 Hz) 1268

1300 1315 (q JC-F = 327 Hz) 1363 1418 1442 1537 HRMS (EI) Calcd for

C18H16F3NO5S M 4150701 Found mz 4150701 IR (ATR) 3244 1801 1323 1157

1067 cm-1

OO

O

NHTs

3d

Cl



722-727 (m 2H) 728 (d J = 84 Hz 2H) 735-739 (m 2H) 769 (d J = 84 Hz 2H)

13C NMR δ = 215 502 723 847 1257 1268 1294 1300 1353 1364 1365

1441 1539 HRMS (ESI+) Calcd for C17H17ClNO5S M+H

+ 3820510 Found mz

Chapter 1

23

3820506 IR (ATR) 3250 1800 1325 1155 1069 cm-1

OO

O

NHTs

3e

Br



716-720 (m 2H) 728 (d J = 80 Hz 2H) 750-755 (m 2H) 766-770 (m 2H) 13

C

NMR δ = 215 501 723 847 1235 1260 1268 1300 1323 1364 1370 1441

1538 HRMS (ESI+) Calcd for C17H17BrNO5S M+H

+ 4260005 Found mz 4260003

IR (ATR) 3252 1800 1331 1175 1057 cm-1

OO

O

Ph

NH

SO

O

OMe

3f 1H NMR δ = 330 (dd J = 144 60 Hz 1H) 339 (dd J = 144 88 Hz 1H) 384 (s


693-698 (m 2H) 727-732 (m 2H) 734-744 (m 3H) 773-778 (m 2H) 13

C NMR

δ = 503 556 724 849 1145 1242 1291 1292 1310 1381 1541 1632 HRMS


+ 3640849 Found mz 3640836 IR (ATR) 3246

1801 1325 1155 1067 cm-1

OO

O

Ph

NH

SO

O

CF3

3g

Chapter 1

24

1H NMR δ = 336 (dd J = 144 52 Hz 1H) 347 (dd J = 144 88 Hz 1H) 459 (d J

= 84 Hz 1H) 510 (d J = 84 Hz 1H) 628 (dd J = 84 52 Hz 1H) 727-731 (m

2H) 735-744 (m 3H) 775 (d J = 88 Hz 2H) 796 (d J = 84 Hz 2H) 13

C NMR δ

= 505 725 851 1231 (q JC-F = 2711 Hz) 1241 1265 (q JC-F = 37 Hz) 1274

1293 1294 1347 (q JC-F = 337 Hz) 1377 1432 1542 HRMS (ESI+) Calcd for


1161 1105 cm-1

OO

O

Ph

NH

SO

O

N

3h 1H NMR δ = 357 (dd J = 148 60 Hz 1H) 365 (dd J = 148 84 Hz 1H) 456 (d J


2H) 735-745 (m 3H) 751 (ddd J = 72 48 12 Hz 1H) 792 (dt J = 80 16 Hz

1H) 798 (d J = 76 Hz 1H) 866 (d J = 44 Hz 1H) 13

C NMR δ = 510 723 849


C15H15N2O5S M+H+ 3350696 Found mz 3350686 IR (ATR) 3258 1801 1337

1175 1063 cm-1

Synthesis of N-Tosyl-3-phenyl-3-pyrrolidinol 4 from N-Tosyl-3-pyrrolidinone

N

Ts

OHPh

N

Ts

O CeCl 3

PhLi

THF -78 C to rt

4

CeCl3 (570 mg 15 mmol) was dried under vacuum at 140 degC for 5 h After cooling the

flask to ambient temperature the vessel was filled with argon THF (50 mL) was added

therein The resulting suspension was cooled to -78 degC and PhLi (10 M in Et2O 15 ml

15 mmol) was added After being stirred for 30 min N-tosyl-3-pyrrolidinone (240 mg

10 mmol) was added The cooling bath was removed to allow the mixture to reach

Chapter 1

25

room temperature The reaction was quenched by adding NH4Cl aq and the aqueous

layer was extracted with AcOEt (3 times) The combined organic layer was washed with

brine (once) dried over MgSO4 and concentrated The residue was purified by flash

column chromatography on silica gel (hexaneethyl acetate = 31) to afford the

N-tosyl-3-phenyl-3-pyrrolidinol 4 (270 mg 085 mmol 85 yield)

N

Ts

OHPh

4 1H NMR δ = 199 (br s 1H) 209-215 (m 1H) 218-227 (m 1H) 243 (s 3H)

351-364 (m 4H) 726-738 (m 7H) 773-777 (m 2H) 13

C NMR δ = 215 396

469 608 804 1250 1276 1280 1286 1297 1339 1418 1435 HRMS (ESI+)

Calcd for C17H23N2O3S M+NH4+ 3351424 Found mz 3351412 IR (ATR) 3491

1325 1159 1101 770 cm-1

Chapter 1

26

References and Notes



(2) (a) Arakawa H Aresta M Armor J N Barteau M A Beckman E J Bell A

T Bercaw J E Creutz C Dinjus E Dixon D A Domen K DuBois D L

Eckert J Fujita E Gibson D H Goddard W A Goodman D W Keller J

Kubas G J Kung H H Lyons J E Manzer L E Marks T J Morokuma K

Nicholas K M Periana R Que L Rostrup-Nielson J Sachtler W M H

Schmidt L D Sen A Somorjai G A Stair P C Stults B R Tumas W Chem

Rev 2001 101 953 (b) Olah G A Prakash G K S Goeppert A J Am Chem

Soc 2011 133 12881









(4) For selected examples of carbonate formation using CO2 see (a) Dimroth P

Pasedach H Ger 1098953 1961 (b) Fujinami T Suzuki T Kamiya M

Fukuzawa S Sakai S Chem Lett 1985 199 (c) Trost B M Angle S R J Am

Chem Soc 1985 107 6123 (d) Iritani K Yanagihara N Uchimoto K J Org

Chem 1986 51 5499 (e) Inoue Y Ishikawa J Taniguchi M Hashimoto H

Bull Chem Soc Jpn 1987 60 1204 (f) Myers A G Widdowson K L

Tetrahedron Lett 1988 29 6389 (g) Fournier J Bruneau C Dixneuf P H

Tetrahedron Lett 1989 30 3981 (h) Kayaki Y Yamamoto M Ikariya T Angew

Chem 2009 121 4258 Angew Chem Int Ed 2009 48 4194 (i) Minakata S

Sasaki I Ide T Angew Chem 2010 122 1331 Angew Chem Int Ed 2010 49

1309 (j) Yoshida S Fukui K Kikuchi S Yamada T J Am Chem Soc 2010

132 4072 For a review Sakakura T Kohno K Chem Commun 2009 1312

(5) (a) Yang N C Yang D-D H J Am Chem Soc 1958 80 2913 (b) Gold E H

J Am Chem Soc 1971 93 2793 (c) Allworth K L El-Hamamy A A Hesabi

M M Hill J J Chem Soc Perkin Trans 1 1980 1671

(6) Winberg K B Angew Chem 1986 98 312 Angew Chem Int Ed Engl 1986

25 312

Chapter 1

27

(7) (a) Activation of Unreactive Bonds and Organic Synthesis (Ed S Murai)

Springer Berlin 1999 (b) Handbook of C-H Transformations (Ed G Dyker)

Wiley-VCH Weinheim 2005 (c) For a special issue on selective functionalization

of C-H bonds see Chem Rev 2010 110 575 (Ed R H Crabtree)

(8) Baldwin J E J Chem Soc Chem Commun 1976 734

(9) Jones II G Chiang S-H Xuan P T J Photochem 1979 10 1

(10) Wagner P J Seldon J H Gudmundsdottir A J Am Chem Soc 1996 118 746

Chapter 1

28

Chapter 2

29

Chapter 2

15-Rhodium Shift in Rearrangement of N-Arenesulfonylazetidin-

3-ols into Benzosultams

Abstract

Benzosultams are synthesized in an enantiopure form starting from -amino acids

through a rhodium-catalyzed rearrangement reaction of N-arenesulfonylazetidin-3-ols

Mechanistically it involves C-C bond cleavage by -carbon elimination and C-H bond

cleavage by 15-rhodium shift

Reproduced with permission from J Am Chem Soc 2013 135 19103-19106

Copyright 2013 American Chemical Society

Chapter 2

30

Introduction

Carbonndashcarbon (CndashC) and carbonndashhydrogen (CndashH) bonds constitute the major

frameworks of organic molecules Such nonpolar -bonds are kinetically inert and

thermodynamically stable in general and therefore remain intact under most

conventional reaction conditions The past few decades however have seen the rise of

methods to selectively transform such intrinsically unreactive bonds with the use of

transition metal catalysts12

A 14-metal shift is defined as an intramolecular metal-hydrogen exchange process

occurring between 1- and 4-positions This process provides a convenient way to

activate a specific CndashH bond and a number of unique reactions involving a 14-metal

shift have been reported3-6

For example Catellani and coworkers have reported a

palladium-catalyzed reaction of bromobenzenes with norbornenes in which multiple

CndashC bonds are introduced on the benzene ring through a 14-palladium shift4a

A

14-rhodium shift has been also successfully exploited5 Phenylboronic acid is multiply

alkylated with norbornene through repetition of a 14-rhodium shift5a

Indanones are

synthesized through rearrangement of 1-arylpropargyl alcohols5cd

A rearrangement

reaction of cyclobutanols affords indanols in an enantio- and diastereoselective way5hi

On the other hand there are significantly less precedents reported for a 15-metal shift7

Herein we report a rearrangement reaction of N-arenesulfonylazetidin-3-ols into

benzosultams8 which involves a 15-rhodium shift as the key mechanistic element It

provides a stereoselective synthetic pathway starting from natural-amino acids

leading to enantiopure benzosultams which are substructures of potent pharmaceuticals

like Piroxicam and Meloxicam9


Initially N-p-toluenesulfonylazetidinol 1a was prepared from commercially available

azetidin-3-ol in 3 steps10

Then the reaction of 1a was examined in the presence of

[Rh(OH)(cod)]2 (2 mol ) and various phosphine ligands (Rh P = 1 25)10

Whereas

almost no reaction occurred when ligands like PPh3 DPPB DPPF were employed the

use of rac-BINAP prompted a rearrangement reaction to give 2a in 46 yield

Rac-DM-BINAP which possessed 35-xylyl groups in place of phenyl groups on

phosphorus exhibited a considerably higher activity to promote quantitative transfor

mation of 1a Simple elution of the reaction mixture through a pad of silica gel afforded

2a in 96 isolated yield (Scheme 1)

Chapter 2

31

Scheme 1 Rhodium-Catalyzed Rearrangement of 1a to 2a

[Rh(OH)(cod)] 2 (2 mol )rac -DM-BINAP (5 mol )K2CO3 (20 equiv)

toluene 60 ordmC 12 h

N

HO Ph

S NS Me

HO PhMe

1a2a 96

Me

O

OO O

A stepwise mechanism involving a 15-rhodium shift from C(sp3) to C(sp

2) is

proposed to explain the formation of 2a from 1a (Scheme 2) Initially the hydroxy

group of 1a is exchanged onto the rhodium hydroxide to generate rhodium alkoxide A

Subsequently -carbon elimination follows to cleave the carbonndashcarbon bond of the

symmetrical azetidine ring thereby relieving the ring strain11

The generated

alkylrhodium B then undergoes a 15-rhodium shift to furnish arylrhodium species C

An intramolecular 6-exo addition to the carbonyl group12

occurs with C to reconstruct

the six-membered ring structure of a benzosultam skeleton Finally the rhodium

alkoxide D is exchanged with the hydroxy group of another azetidinol 1a to release the

benzosultam 2a with regeneration of intermediate A

Scheme 2 Proposed Mechanism for the Rearrangement of 1a to 2a

N

S O

O

O[Rh]

Ph

SN

[Rh]O Ph

O OMe

[Rh] OH

N

S O

O

O Ph

H

[Rh]

H

N

[Rh]O Ph

S O

O

Me Me

Me

Me

1a

H2O

2a

A B

CD

1a

A

We next carried out the reaction of 1a-d whose p-tolyl group was fully deuterated

(Scheme 3) One of the deuterium atoms on the ortho positions of the p-tolyl moiety

was transferred onto the N-methyl group of 2a-d being consistent with the proposed

Chapter 2

32

mechanism The HD ratio of the N-methyl group and the 8-position were 1911 and

0109 respectively The slightly lower and higher HD ratios at the N-methyl and 8-

positions respectively than expected may suggest the microscopic reversibility between

the intermediary arylrhodium C and the alkylrhodium B

Scheme 3 Rhodium-Catalyzed Reaction of 1a-d to 2a-d



N

HO Ph

SN

S CH19D11

HO Ph

D3C

1a-d2a-d 96

D3C

O

O

O O

D

D

D

D

D

D

H01D09

8

Next optically active diphosphine ligands were examined to induce

enantioselectivity at the step of intramolecular carbonyl addition ie from C leading to

D12

Although (R)-DM-BINAP exhibited the best reactivity among the chiral ligands

examined to give 2a in 94 yield the enantiomeric ratio (er) was low (6238)

(R)-DIFLUORPHOS afforded the best selectivity of 928 er (91 yield)10

Application

of this reaction conditions to various azetidinols 1 furnished benzosultams 2 in the range

of 919 to 937 er (Table 1)

Table 1 Enantioselective Rearrangement of 1 to 2ab

1

2

SN

HO Ar

O OMe

N

HO Ar

S O

O

[Rh(OH)(cod)] 2 (5 mol )(R)-DIFLUORPHOS (12 mol )

K2CO 3 (20 equiv)


NS Me

HO PhMe

2a

91 er = 928

O O

NS Me

HO Ph

2b

95 er = 937

O O

S

NS Me

HOMe

2c

90 er = 937

O O

OMe

NS Me

HOMe

2c

92 er = 919

O O

CF3

a Reaction conditions [Rh(OH)(cod)]2 (5 mol ) (R)-DIFLUORPHOS (12

mol ) toluene 60 degC 12 h b Isolated yield

Chapter 2

33

Asymmetrical azetidinol 1e was prepared in an enantiopure form from (L)-alanine

according to the modified Seebachrsquos method (Scheme 4)13

Initially (L)-alanine (3) was

treated with p-toluenesulfonyl chloride to afford N-tosylate 4 Subsequent treatment

with oxalyl chloride followed by coupling with diazomethane gave diazo ketone 5

Copper-catalyzed denitrogenative cyclization of 5 afforded azetidinone 6 Addition of

phenylmagnesium bromide to 6 occurred selectively from the face opposite to the

methyl group to furnish azetidinol 1e in an enantiopure form

Scheme 4 Synthesis of Enantiopure Azetidinol 1e

HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6 84

5 56

1) (COCl) 2 DMF2) CH2N2

Cu(OAc)2H2O (5 mol )

benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3

acetone H2Ort 10 h 4 90

PhMgBr

THF rt 1 h N

HO

Ts

Me

1e 93

er gt 991 dr = 201

Ph

3

The azetidinol 1e was heated at 60 degC in toluene for 8 h in the presence of

[Rh(OH)(cod)]2 (2 mol ) and rac-DM-BINAP (5 mol ) (Scheme 5) The

rearrangement reaction proceeded efficiently to furnish the benzosultam 2e in a

quantitative yield stereoselectively with the enantiopurity retained The stereochemistry

was confirmed by X-ray crystallography10

Scheme 5 Rearrangement of 1e to 2e

SN

HO PhMe

O OMe

MeN

HO Ph

S O

O

Me

Me

1e

er gt 991 dr = 201

2e 99

er gt 991 dr gt 201

[Rh(OH)(cod)] 2 (2 mol )rac-DM-BINAP (5 mol )


The exclusive formation of 2e demonstrates that the -carbon elimination occurs

site-selectively at the methylene side rather than at the methyne side probably due to

Chapter 2

34

steric reasons In addition intramolecular carbonyl addition takes place in a

diastereoselective fashion We assume that the six-membered ring transition state takes

a boat-like conformation in which the CndashRh linkage can align with the C=O bond for

the maximum orbital interaction as shown in Scheme 8 With the conformer E the

methyl group at the -position takes a pseudoequatorial position whereas the -methyl

group of the conformer Ersquo takes a pseudoaxial position Thus the conformer E is

favored over the conformer Ersquo to produce the adduct F diastereoselectively

Scheme 6 Models for Diastereoselective 6-exo-dig Cyclization

SN

PhRhOMe

O OMe

Me

SN

PhRhOMe

O OMe

Me

favored

disfavored

F

F

NSRh

Ph

Me

O

O

MeO

H

Me

E

E

NSRh

Ph

Me

O

O

MeO

Me

H

Various benzosultams were synthesized in an enantio- and diasteropure form (Table

2) The reaction of N-p-toluenesulfonylazetidinol 1f the diastereomer of 1e also

furnished the same stereoisomer 2e exclusively being consistent with the proposed

mechanism the stereochemistry of the alcohol moiety once disappears upon -carbon

elimination to produce the same intermediate C Azetidinols 1g-1j having various aryl

groups on the sulfonyl moiety gave the corresponding products 2g-2j (entries 2-5) The

reaction of N-m-toluenesulfonylazetidinol 1i gave product 2i with complete

regioselectivity (entry 4) suggesting that rhodium preferred the sterically less hindered

position as the destination of its 15-shift Substituted aryl groups were allowed at the

C3-position (entries 6 7)14

Benzosultam 2m was obtained from azetidinol 1m which

was prepared from valine (entry 8) The reaction of methionine-derived 1n successfully

furnished 2n demonstrating the compatibility of a sulfide functionality (entry 9)

Chapter 2

35

Table 2 Rhodium-Catalyzed Rearrangement of 1 to 2a

1

er gt 991 dr gt 201

2

er gt 991 dr gt 201

SN

HO ArR

O OMe

N

HO Ar

S O

O

R [Rh(OH)(cod)] 2 (2 mol )

rac -DM-BINAP (5 mol )


entry 1 2b entry 1 2b

1 N

HO Ph

S O

O

Me

Me

1f

SN

HO PhMe

O OMe

Me

2e 99

6 N

HO

S O

O

Me

1k

OMe

SN

HOMe

O OMe

2k 97

OMe

2

N

HO Ph

S O

O

MeO

Me

1g

SN

HO PhMe

O OMe

MeO

2g 98

7 N

HO

S O

O

Me

Me

1l

CF3

SN

HOMe

O OMe

Me

2l 97

CF3

3 N

HO Ph

S O

O

F3C

Me

1h

SN

HO PhMe

O OMe

F3C

2h 99

8 N

HO Ph

S O

O

Me

i-Pr

1m

SN

HO Phi-Pr

O OMe

Me

2m 97

4

N

HO Ph

S O

O

Me

1iMe

SN

HO PhMe

O OMeMe

2i 99

9 N

HO Ph

S O

O

Me

SMe

SN

HO Ph

O OMe

Me

2n 97

SMe

5 N

HO Ph

S O

O

Me

S

1j

SN

HO PhMe

O OMeS

2j 99

a Reaction conditions [Rh(OH)(cod)]2 (2 mol ) rac-DM-BINAP (5 mol ) toluene

60 degC 8 h b Isolated yield

Chapter 2

36

Conclusions

In summary we have described the rhodium-catalyzed rearrangement reaction of

N-arenesulfonylazetidinols into benzosultams The unique transformation

mechanistically involves reorganization of nonpolar -bonds via 15-rhodium shift and

provides a method to synthesize enantio- and diastereopure benzosultams starting from

natural -amino acids

Chapter 2

37




with a Pike Technologies MIRacle Single Reflection ATR adapter 1H and

13C NMR

spectra were recorded on a Varian Mercury-vx400 (1H at 40044 MHz and

13C at 10069

MHz) and JEOL JNM-ECA600 (1H at 60017 MHz) spectrometer NMR data were

obtained in CDCl3 and C6D6 Proton chemical shifts were referenced to the residual

proton signal of the solvent at 726 ppm (CHCl3) and 716 ppm (C6D6) Carbon

chemical shifts were referenced to the carbon signal of the solvent at 770 ppm (CDCl3)

High-resolution mass spectra were recorded on a Thermo Scientific Exactive (ESI)

spectrometer Flash column chromatography was performed with silica gel 60N (Kanto)

Preparative thin-layer chromatography (PTLC) was performed on silica gel plates with

PF254 indicator (Merck)

Materials Unless otherwise noted all chemicals and anhydrous solvents were obtained

from commercial suppliers

Preparation of N-Toluenesulfonylazetidinol 1a and 1a-d

N

OHNEt3

DCM rt 12 h

1) Dess-Martin ReagentDCM rt 12 h

2) PhMgBrTHF rt 3 h

N

HO Ph

1a

TsCl

N

OH

8a

H HCl

Ts Ts

To a dichloromethane solution (20 mL) of 3-hydroxyazetidine hydrochloride (12 g 11

mmol) and triethylamine (31 mL 22 mmol) was added p-toluenesulfonyl chloride (19

g 10 mmol) After being stirred at room temperature for 12 h HCl aq (2N) was added

to the reaction mixture The organic layer was separated and the remaining aqueous

layer was extracted with dichloromethane (3 times) The combined organic layer was

washed with brine (once) dried over MgSO4 and concentrated under reduced pressure

The residue was purified by Flash column chromatography on silica gel (hexaneethyl

acetate = 11) to afford the N-toluenesulfonylazetidinol 8a (15 g 66 mmol 66 yield)

Chapter 2

38

N

S

Me

O

O

OH

8a 1H NMR = 213 (bs 1H) 245 (s 3H) 350-361 (m 2H) 394-404 (m 2H)

442-452 (m 1H) 737 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR =

216 602 605 1284 1298 1313 1443 HRMS (ESI+) Calcd for C10H14NO3S

M+H+ 2280689 Found mz 2280686 IR (ATR) 3501 1331 1144 1049 665 cm

-1

N

S

D3C

O

O

OH

8a-d

D

D

D

D

1H NMR = 283 (bs 1H) 349-355 (m 2H) 389-396 (m 2H) 435-444 (m 1H)

13C NMR = 195-202 (m) 601 602 1279 (t JC-D = 247 Hz) 1294 (t J = 247 Hz)

1308 1441 HRMS (ESI+) Calcd for C10H7D7NO3S M+H

+ 2351128 Found mz

2351125 IR (ATR) 3503 1333 1142 1059 638 cm-1

N

S O

O

OH

8b

S

1H NMR = 277 (bs 1H) 357-364 (m 2H) 400-407 (m 2H) 441-450 (m 1H)

721 (dd J = 48 40 Hz 1H) 762 (dd J = 36 12 Hz 1H) 771 (dd J = 52 12 Hz

1H) 13

C NMR = 600 606 1279 1332 1335 1338 HRMS (ESI+) Calcd for

C7H10D7NO3S2 M+H+ 2200097 Found mz 2200094 IR (ATR) 3476 1325 1148

1038 737 cm-1

Chapter 2

39

To a dichloromethane solution (20 mL) of N-toluenesulfonylazetidinol 8 (780 mg 34

mmol) was added Dess-Martin reagent (15 g 35 mmol) After being stirred for 12 h at

room temperature saturated Na2CO3 aq was added to the reaction mixture The organic

layer was separated and the remaining aqueous layer was extracted with

dichloromethane (3 times) The combined organic layer was washed with brine (once)

dried over MgSO4 and concentrated

The residue was dissolved in THF (20 mL) PhMgBr (10 M in THF 5 mL 5 mmol)

was added therein at -78 degC and the reaction mixture was then allowed to be at room

temperature After being stirred for 3 h HCl (2N) was added to the reaction mixture at

0 degC The aqueous layer was extracted with AcOEt (3 times) washed with brine (once)

dried over MgSO4 and concentrated The residue was purified by Flash column

chromatography on silica gel (hexaneethyl acetate = 31) to afford the

N-toluenesulfonylazetidinol 1a (600 mg 20 mmol 59 yield)

N

HO Ph

S

1a

Me

O

O

1H NMR = 162 (s 1H) 247 (s 3H) 397 (d J = 92 Hz 2H) 413 (d J = 92 Hz

2H) 728-737 (m 5H) 739 (d J = 84 Hz 2H) 778 (d J = 80 Hz 2H) 13

C NMR

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS


+ 3041002 Found mz 3040995 IR (ATR) 3477

1333 1184 1148 671 cm-1

The spectral characteristics of 1a were in agreement with the previously reported data15

N

HO Ph

S

1a-d

D3C

O

O

D

D

D

D

1H NMR = 250 (bs 1H) 397 (d J = 92 Hz 2H) 413 (d J = 92 Hz 2H) 727-736

(m 5H) 13

C NMR = 203-211 (m) 652 703 1244 1281 (t JC-D = 247 Hz)

1281 1286 1294 (t JC-D = 247 Hz) 1311 1420 1441 HRMS (ESI+) Calcd for

Chapter 2

40

C16H11D7NO3S M+H+ 3111441 Found mz 3111434 IR (ATR) 3481 1335 1142

702 648 cm-1

N

HO Ph

S

S

O

O

1b 1H NMR = 232 (bs 1H) 400-408 (m 2H) 416-424 (m 2H) 724 (dd J = 48 36

Hz 1H) 730-737 (m 5H) 768 (dd J = 40 16 Hz 1H) 773 (dd J = 48 12 Hz

1H) 13

C NMR = 656 702 1244 1280 1283 1288 1331 13387 13392 1417

HRMS (ESI+) Calcd for C13H14NO3S2 M+H

+ 2960410 Found mz 2960404 IR

(ATR) 3524 1333 1161 1148 748 cm-1

N

HO

S

Me

O

O

OMe

1c

1H NMR = 246 (s 3H) 257 (bs 1H) 379 (s 3H) 393 (d J = 84 Hz 2H) 408 (d

J = 88 Hz 2H) 683 (d J = 84 Hz 2H) 723 (d J = 88 Hz 2H) 738 (d J = 80 Hz

2H) 775 (d J = 80 Hz 2H) 13

C NMR =216 553 652 702 1139 1259 1285


+

3341108 Found mz 3341097 IR (ATR) 3460 1518 1331 1250 1146 cm-1

N

HO

S

Me

O

O

CF3

1d 1H NMR = 247 (s 3H) 318 (bs 1H) 396-410 (m 4H) 739 (d J = 80 Hz 2H)

746 (d J = 80 Hz 2H) 754 (d J = 84 Hz 2H) 774 (d J = 80 Hz 2H) 13

C NMR

Chapter 2

41

=216 654 697 1239 (q JC-F = 2704 Hz) 1249 1255 (q JC-F = 37 Hz) 1284



1109 1076 cm-1

Preparation of N-Toluenesulfonylazetidinol 1e A Typical Procedure of 1e and

1l-1n

HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6a

5a

1) (COCl) 2 DMF2) CH 2N2

Cu(OAc) 2H2O (5 mol )

benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3

acetone H2O

rt 10 h 4a

PhMgBr

THF rt 1 h N

OH

Ts

Me

1e

Ph

3a

Preparation of -Diazo Ketone 5a A Typical Procedure for Preparation of 5a-5c

N-toluenesulfonylalanine 4a (24 g 10 mmol) was prepared according to the reported

procedure16

The resulting 4a was dissolved in dichloromethane (50 mL) The mixture

was cooled to 0 degC under argon atmosphere and oxalyl chloride (13 mL 15 mmol) and

one-drop of NN-dimethylformamide were added After being stirred at room

temperature for 12 h solvent was removed under reduced pressure

The residue was dissolved in THF under argon atmosphere Diazomethane (which was

freshly prepared by diazald and KOH 25 mmol) in Et2O was added to the solution at

0 degC After being stirred for 3 h at room temperature water was added to the reaction

mixture The organic layer was separated and the remaining aqueous layer was extracted

with ethyl acetate (3 times) The combined organic layer was washed with brine (once)


chromatography on silica gel (hexaneethyl acetate = 21 to 11) to afford the -diazo

ketone 5a (15 g 56 mmol 56 yield)

Me

NHTs

O

N2

5a 1H NMR = 126 (d J = 72 Hz 3H) 242 (s 3H) 378-390 (m 1H) 537-552 (m

Chapter 2

42

2H) 730 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR = 194 215 539

554 1271 1297 1368 1438 1928 HRMS (ESI+) Calcd for C11H14N3O3S M+H

+

2680750 Found mz 2680747 IR (ATR) 2112 1639 1337 1319 1161 cm-1

[]27

D = -1184 (c = 079 in CHCl3)


i-Pr

NHTs

O

N2

5b 1H NMR = 081 (d J = 68 Hz 3H) 090 (d J = 64 Hz 3H) 190-202 (m 1H) 240

(s 3H) 352-368 (m 1H) 527 (s 1H) 551 (d J = 84 Hz 1H) 727 (d J = 80 Hz

2H) 769 (d J = 84 Hz 2H) 13

C NMR =169 193 215 315 548 647 1273

1296 1367 1436 1922 HRMS (ESI+) Calcd for C13H18N3O3S M+H

+ 2961063

Found mz 2961060 IR (ATR) 2129 1622 1362 1329 1161 cm-1

[]28

D = -730 (c = 071 in CHCl3)

NHTs

O

N2

5c

SMe

1H NMR = 174-196 (m 2H) 204 (s 3H) 242 (s 3H) 244-252 (m 2H)

390-400 (m 1H) 541 (s 1H) 560-572 (m 1H) 730 (d J = 84 Hz 2H) 772 (d J =

84 Hz 2H) 13

C NMR = 153 215 297 323 545 585 1272 1297 1366 1439

1918 HRMS (ESI+) Calcd for C13H18N3O3S2 M+H

+ 3280784 Found mz 3280779

IR (ATR) 2129 1618 1375 1339 1163 cm-1

[]29

D = -506 (c = 063 in CHCl3)

The spectral characteristics of 5c were in agreement with the previously reported data17

Preparation of N-Toluenesulfonylazetidinone 6a A Typical Procedure for

Preparation of 6a-6c

Cu(OAc)2H2O (80 mg 04 mmol) was added to a benzene solution (70 mL) of -diazo

ketone 5a (12 g 45 mmol) at 90 degC After being stirred for 1 min the reaction mixture

was allowed to be at room temperature Solvent was removed under reduced pressure

The residue was purified by column chromatography on silica gel (HexaneAcOEt =

31) to afford N-toluenesulfonylazetidinone 6a (090 g 38 mmol 84 yield)

Chapter 2

43

N

O

Ts

Me

6a

1H NMR = 145 (d J = 68 Hz 3H) 246 (s 3H) 443-454 (m 2H) 473-480 (m

1H) 736-742 (m 2H) 776-781 (m 2H) 13

C NMR = 157 216 696 810 1284

1300 1315 1450 1967 HRMS (ESI+) Calcd for C11H14NO3S M+H

+ 2400689

Found mz 2400688 IR (ATR) 1825 1339 1155 669 cm-1

[]28

D = 614 (c = 081 in CHCl3)


N

O

Ts

i-Pr

6b

1H NMR = 099-111 (m 6H) 206-218 (m 1H) 246 (s 3H) 441 (dd J = 164 36

Hz 1H) 450 (d J = 164 Hz 1H) 461 (dd J = 52 36 Hz 1H) 738 (d J = 84 Hz

2H) 777 (d J = 80 Hz 2H) 13

C NMR = 174 181 216 304 703 903 1284


+ 2681002

Found mz 2680998 IR (ATR) 1815 1340 1155 1007 671 cm-1

[]29

D = 567 (c = 095 in CHCl3)

N

O

Ts

6c

SMe

1H NMR = 204 (s 3H) 209-218 (m 2H) 247 (s 3H) 265-279 (m 2H) 446 (d

J = 156 Hz 1H) 460 (dd J = 156 36 Hz 1H) 482-488 (m 1H) 740 (d J = 84 Hz

2H) 780 (d J = 80 Hz 2H) 13

C NMR = 147 216 291 293 705 832 1286

1301 1311 1451 1963 HRMS (ESI+) Calcd for C13H18NO3S2 M+H

+ 3000723

Found mz 3000718 IR (ATR) 1813 1342 1308 1157 667 cm-1

[]29

D = 1183 (c = 036 in CHCl3)


Chapter 2

44

Preparation of N-Toluenesulfonylazetidinol 1e A Typical Procedure for

Preparation of 1e and 1l-1n

To a THF solution (20 mL) of N-toluenesulfonylazetidinone 6a (12 g 50 mmol) at

-78 degC was added PhMgBr (10 M in THF 55 mL 55 mmol) The reaction mixture

was then allowed to be at room temperature After being stirred for 3 h HCl aq (2N)

was added to the reaction mixture at 0 degC The aqueous layer was extracted with AcOEt

(3 times) washed with brine (once) dried over MgSO4 and concentrated The residue

was purified by Flash column chromatography on silica gel (hexaneethyl acetate = 31)

to afford the N-toluenesulfonylazetidinol 1e (15 mg 47 mmol 93 yield)

N

HO

S O

O

Me

Me

1e

H

NOE

NOE

1H NMR =142 (d J = 68 Hz 3H) 162 (bs 1H) 248 (s 3H) 388 (dd J = 92 08

Hz 1H) 399 (d J = 92 Hz 1H) 419 (q J = 64 Hz 1H) 694-698 (m 2H) 720-722

(m 3H) 739 (d J = 84 Hz 2H) 777 (d J = 84 Hz 2H) 13

C NMR = 144 216

628 702 731 1247 1279 1284 1285 1298 1319 1415 1443 HRMS (ESI+)

Calcd for C17H20NO3S M+H+ 3181158 Found mz 3181154 IR (ATR) 3470 1335

1155 1092 667 cm-1

[]25

D = 364 (c = 106 in CHCl3) Enantiomeric excess was determined by HPLC with

a Daicel Chiralpak IC hexanei-PrOH = 7030 flow rate = 06 mLmin = 260 nm) t1

= 251 min (minor) t2 = 287 min (major) er gt 991

Chapter 2

45

N

HO

S O

O

Me

1l

H

NOE

NOE

CF3

Me

1H NMR = 142 (d J = 64 Hz 3H) 251 (s 3H) 295 (bs 1H) 392 (d J = 92 Hz

1H) 398 (d J = 96 Hz 1H) 416 (q J = 64 Hz 1H) 708 (d J = 84 Hz 2H)

739-747 (m 4H) 777 (d J = 84 Hz 2H) 13

C NMR = 143 216 630 706 727

1238 (JC-F = 2704 Hz) 1253 1254 (JC-F = 36 Hz) 1285 1299 1301 (JC-F = 324

Hz) 1316 1446 1454 HRMS (ESI+) Calcd for C18H19F3NO3S M+H

+ 3861032

Found mz 3861025 IR (ATR) 3422 1327 1151 1109 839 cm-1

[]28




N

HO

S O

O

Me

iPr

1m

H

NOE

NOE

1H NMR = 087 (d J = 68 Hz 3H) 114 (d J = 68 Hz 3H) 161 (bs 1H) 226-240

(m 1H) 245 (s 3H) 386 (d J = 92 Hz 1H) 393 (dd J = 96 08 Hz 1H) 410 (d J

= 100 Hz 1H) 690-696 (m 2H) 712-720 (m 3H) 732 (d J = 80 Hz 2H) 773 (d

J = 80 Hz 2H) 13

C NMR = 190 193 215 291 641 729 801 1247 1275

1284 1285 1297 1324 1428 1441 HRMS (ESI+) Calcd for C19H24NO3S M+H

+

3461471 Found mz 3461466 IR (ATR) 3454 1331 1163 739 669 cm-1

[]27



Chapter 2

46


N

HO Ph

S O

O

1n

Me

SMe

1H NMR = 202 (s 3H) 218-258 (m 8H) 388-394 (m 2H) 427 (dd J = 84 48

Hz 1H) 688-693 (m 2H) 714-721 (m 3H) 740 (d J = 80 Hz 2H) 779 (d J = 80

Hz 2H) 13

C NMR = 154 216 290 297 634 725 733 1246 1277 1284

1286 1299 1318 1424 1443 HRMS (ESI+) Calcd for C19H24NO3S2 M+H

+

3781192 Found mz 3781188 IR (ATR) 3481 1339 1157 702 669 cm-1

[]28


a Daicel Chiralpak IB hexanei-PrOH = 9010 flow rate = 06 mLmin = 260 nm) t1


Preparation of N-Toluenesulfonylazetidinol 1f

A mixture containing N-toluenesulfonylazetidinol 1e (317 mg 010 mmol)

[Rh(OH)(cod)]2 (09 mg 2 mol2 mol ) and (S)-DM-BINAP (37 mg 5 mol 5

mol ) in toluene (10 mL) was heated at 60 degC After being stirred for 1 h the reaction

mixture was passed through a pad of florisil The solvent was removed under reduced

pressure The crude residue was purified by preparative thin-layer chromatography on

silica gel (dichloromethaneethyl acetate = 51) and GPC to afford the

N-toluenesulfonylazetidinol 1f (62 mg 0020 mmol 20 yield)

N

HO

S O

O

Me

Me

1f

H

NOE

NOE

1H NMR = 089 (d J = 64 Hz 3H) 224 (bs 1H) 247 (s 3H) 366 (d J = 84 Hz

1H) 398 (q J = 64 Hz 1H) 424 (dd J = 84 08 Hz 1H) 732-744 (m 5H)

750-755 (m 2H) 774-778 (m 2H) 13

C NMR = 165 216 627 718 739 1257

Chapter 2

47



-1

[]25

D = 68 (c = 030 in CHCl3) Enantiomeric excess was determined by HPLC with a

Daicel Chiralpak IC hexanei-PrOH = 7030 flow rate = 06 mLmin = 260 nm) t1 =

128 min (minor) t2 = 153 min (major) er gt 991

Preparation of N-Toluenesulfonylazetidinol 1g A Typical Procedure for

Preparation of 1g-1k

HO2C Me

NHCbz

Me

NHCbz

O

N2N

O

Cbz

Me

6d5d

1) (COCl) 2 DMF

2) CH2N2 Rh2(OAc)4 (05 mol )

DCM rt 12 h4d

PhMgBr

THF rt 1 h

N

OH

Cbz

Me

7a

Ph

N

OH

H

Me

PhPd C (5 mol )

H2 (1atm)

MeOH rt 12 h

MeO SO2Cl

NEt3

DCM rt 12 h

N

HO Ph

S O

O

MeO

Me

1g

Preparation of -Diazo Ketone 5d

The N-benzyloxycarbonylalanine 4d (67 g 30 mmol) was dissolved in THF (150 mL)

Triethylamine (6 mL) and ethyl chlorocarbonate were added therein at ndash15 degC

Diazomethane in Et2O (which was freshly prepared by diazald and KOH 70 mmol) was

added The mixture was stirred at room temperature for 3 h and then water was added

The mixture was extracted with AcOEt washed with water and brine dried over

MgSO4 and concentrated The residue was washed with Et2O to afford the -diazo

ketone (59 g 24 mmol 80 yield)

Me

NHCbz

O

N2

5d 1H NMR = 134 (d J = 68 Hz 3H) 420-436 (m 1H) 504-516 (m 2H) 534-564

(m 2H) 728-736 (m 5H) 13

C NMR = 184 535 (2C) 669 1280 1282 1285

1361 1556 1938 HRMS (ESI+) Calcd for C12H14N3O3 M+H

+ 2481030 Found mz

2481028 IR (ATR) 2116 1717 1636 1533 1252 cm-1

[]28

D = -434 (c = 085 in CHCl3)

The spectral characteristics of 5d were in agreement with the previously reported data18

Chapter 2

48

Preparation of N-Benzyloxycarbonylazetidinone 6d

To a dichloromethane solution (50 mL) of -diazo ketone 5d (25 g 10 mmol) at 0 degC

was added Rh2(OAc)4 (20 mg 005 mmol 05 mol ) The reaction mixture was then

warmed to room temperature After being stirred for 12 h solvent was removed under

reduced pressure The residue was purified by GPC to afford

N-benzyloxycarbonylazetidinone 6d (12 g 56 mmol 56 yield)

N

O

Cbz

Me

6d

1H NMR = 149 (d J = 72 Hz 3H) 466 (dd J = 164 40 Hz 1H) 477 (d J = 164

Hz 1H) 498-505 (m 1H) 513-521 (m 2H) 731-739 (m 5H) 13

C NMR = 153


C12H14NO3 M+H+ 2200968 Found mz 2200966 IR (ATR) 1811 1690 1410 1342

696 cm-1

[]29

D = 390 (c = 068 in CHCl3)

Preparation of N-Benzyloxycarbonylazetidinol 7a and 7b

To a THF solution (20 mL) of N-benzyloxycarbonylazetidinone 6d (11 g 50 mmol) at


was then warmed to room temperature After being stirred for 3 h HCl aq (2N) was

added at 0 degC The mixture was separated and the aqueous layer was extracted with

AcOEt (3 times) The combined organic phase was washed with brine (once) dried over

MgSO4 and concentrated The residue was purified by Flash column chromatography on

silica gel (hexaneethyl acetate = 11) to afford the N-benzyloxycarbonyl azetidinol 7a

(14 g 48 mmol 96 yield)

N

OH

Cbz

Me

7a

Ph

1H NMR = 150 (d J = 64 Hz 3H) 251 (bs 1H) 411 (d J = 96 Hz 1H) 434 (d J

= 96 Hz 1H) 458 (q J = 64 Hz 1H) 507-518 (m 2H) 729-746 (m 10H) 13

C

NMR = 142 623 667 689 730 1246 1278 1279 1280 1285 1287 1366

Chapter 2

49

1434 1565 HRMS (ESI+) Calcd for C18H20NO3 M+H

+ 2981438 Found mz

2981433 IR (ATR) 1670 1423 1248 1016 702 cm-1

[]29

D = 46 (c = 089 in CHCl3)

N

OH

Cbz

Me

7b

MeO


1H) 432 (d J = 96 Hz 1H) 452-461 (m 1H) 506-518 (m 2H) 687-694 (m 2H)

726-739 (m 7H) 13

C NMR = 143 553 622 666 687 729 1140 1260 1278

1280 1285 1355 1366 1566 1593 HRMS (ESI+) Calcd for C19H22NO4 M+H

+

3281543 Found mz 3281539 IR (ATR) 1682 1418 1352 1024 696 cm-1

[]29

D = 02 (c = 085 in CHCl3)

Preparation of N-Toluenesulfonylazetidinol 1g A Typical procedure for


PdC (100 mg) was placed in a flask A methanol (20 mL) solution of

N-benzyloxycarbonylazetidinol 7a (5 mmol 15 mmol) was added therein and the flask

was purged with hydrogen After being stirred at room temperature for 12 h the reaction

mixture was passed through a pad of celitereg

The solvent was removed under reduced

pressure

The residue was dissolved in dichloromethane (20 mL) and p-methoxyphenylsulfonyl

chloride (10 g 50 mmol) and NEt3 (700 mL 5 mmol) were added The reaction

mixture was stirred for 12 h and then water was added The aqueous layer was extracted

with dichloromethane (3 times) washed with brine (once) dried over MgSO4 and

concentrated The residue was purified by flash column chromatography on silica gel

(hexaneethyl acetate = 31) to afford the p-methoxyphenylazetidinol 1g (960 mg 29

mmol 58 yield)

Chapter 2

50

N

HO

S O

O

MeO

Me

1g

H

NOE

NOE

1H NMR = 141 (d J = 64 Hz 3H) 259 (bs 1H) 387 (dd J = 92 08 Hz 1H)

390 (s 3H) 399 (d J = 92 Hz 1H) 419 (q J = 60 Hz 1H) 698-707 (m 4H)

720-727 (m 3H) 779-785 (m 2H) 13

C NMR = 143 557 627 701 731 1144



-1

[]28




N

HO

S O

O

F3C

Me

1h

H

NOE

NOE


406 (d J = 92 Hz 1H) 430 (qd J = 64 08 Hz 1H) 694-699 (m 2H) 721-727

(m 3H) 784 (d J = 80 Hz 2H) 801 (d J = 84 Hz 2H) 13

C NMR = 145 629

706 729 1232 (JC-F = 2711 Hz) 1245 1263 (JC-F = 37 Hz) 1283 12868 12871

1350 (JC-F = 327 Hz) 1392 1414 HRMS (ESI+) Calcd for C17H17F3NO3S M+H

+

3720876 Found mz 3720870 IR (ATR) 3503 1348 1323 1165 646 cm-1

[]28




Chapter 2

51

N

HO

S O

O

Me

1i

H

NOE

NOE

Me 1H NMR = 144 (d J = 64 Hz 3H) 217 (bs 1H) 245 (s 3H) 389 (d J = 92 Hz

1H) 401 (d J = 88 Hz 1H) 422 (q J = 64 Hz 1H) 694-698 (m 2H) 720-724 (m

3H) 746-750 (m 2H) 767-772 (m 2H) 13

C NMR = 144 214 630 704 730

1247 1256 1279 1285 1286 1291 1341 1347 1395 1416 HRMS (ESI+)


1151 714 700 cm-1

[]29




N

HO

S O

O

Me

1j

H

NOE

NOE

S

1H NMR = 148 (d J = 64 Hz 3H) 259 (bs 1H) 396-401 (m 1H) 406 (d J = 92

Hz 1H) 425 (q J = 64 Hz 1H) 696-701 (m 2H) 720-728 (m 4H) 764-767 (m

1H) 769-772 (m 1H) 13

C NMR = 144 632 709 730 1246 1279 1281 1286


+ 3100566

Found mz 3100559 IR (ATR) 3508 1340 1151 756 669 cm-1

[]29




Chapter 2

52

N

HO

S O

O

Me

1k

H

NOE

NOE

OMe


1H) 394 (d J = 88 Hz 1H) 416 (q J = 64 Hz 1H) 670-675 (m 2H) 684-689 (m

2H) 756-762 (m 2H) 765-770 (m 1H) 786-790 (m 2H) 13

C NMR = 143 553

630 704 729 1138 1259 1283 1292 1332 1337 1348 1592 HRMS (ESI+)


1327 1155 606 cm-1

[]29




Rhodium-Catalyzed Reaction of Azetidinol 1a A Typical Procedure for Ligand

Screening

A mixture containing N-toluenesulfonylazetidinol 1a (303 mg 010 mmol) K2CO3

(276 mg 020 mmol) [Rh(OH)(cod)]2 (09 mg 2 mol 2 mol ) and rac-DM-BINAP

(37 mg 5 mol 5 mol ) in toluene (10 mL) was heated at 60 degC After being stirred

for 12 h the reaction mixture was passed through a pad of florisil The solvent was

removed and the residue was purified by preparative thin-layer chromatography on

silica gel (hexaneethyl acetate = 31) to afford the benzosultam 2a (291 mg 0093

mmol 93 yield)

Chapter 2

53

Table S1 Screening of Achiral Ligands

rac -DM-BINAP

rac-BINAP

dppf

dppb

PPh3

dppe

46

trace

trace

yield

PCy3

Ligand

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

entry

1

2

3

4

5

6

7

8

nd

nd

nd

93

none nd

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a

Table S2 Screening of Chiral Ligands

entry Ligand yield

1

2

3

4

(R)-BINAP

(R)-DM-BINAP

(R)-SEGPHOS

(R)-DIFLUORPHOS

er

94

46

48

43

5

6

(R)-DM-SEGPHOS

(R)-DTBM-SEGPHOS trace -

3862

91

7

8

(R)-MeO-BIPHEP

(R)-MeO-DM-BIPHEP

64

91

892

3169

1288

1486

2476

2575

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a

Rhodium-Catalyzed Reaction of Azetidinol 1a A Typical Procedure for Reactions

of Azetidinols 1a-1d


(276 mg 020 mmol) [Rh(OH)(cod)]2 (23 mg 5 mol 5 mol ) and

(R)-DIFLUORPHOS (82 mg 12 mol 12 mol ) in toluene (10 mL) was heated at

60 degC After being stirred for 12 h the reaction mixture was passed through a pad of

florisil The solvent was removed and the residue was purified by preparative thin-layer

chromatography on silica gel (hexaneethyl acetate = 31) to afford the benzosultam 2a


Chapter 2

54

NS Me

HO PhMe

2a

O O


J = 148 Hz 1H) 683 (s 1H) 727-744 (m 6H) 781 (d J = 84 Hz 1H) 13

C NMR

= 216 361 626 732 1238 1263 1280 1284 1299 1301 1330 1412 1431


+ 3041002 Found mz 3040998 IR

(ATR) 3472 1325 1161 1142 735 cm-1

[]29



= 175 min (minor) t2 = 194 min (major) er = 928

NS CH2D

HO Ph

D3C

2a-d

O O

D

D

D

1H NMR = 293 (bs 1H) 300 (t J = 20 Hz 3H) 347 (d J = 148 Hz 1H) 426 (d

J = 148 Hz 1H) 728-743 (m 5H) 13

C NMR = 201-210 (m) 358 (t JC-D = 212

Hz) 625 731 1234 (t JC-D = 249 Hz) 1262 1279 1283 1291-1300 (m 2C)

1327 1411 1432 1434 HRMS (ESI+) Calcd for C16H11D7NO3S M+H

+ 3111441

Found mz 3111436 IR (ATR) 3524 1318 1290 1150 721 cm-1

NS Me

HO Ph

O O

S

2b

1H NMR = 263 (bs 1H) 310 (s 3H) 359 (d J = 152 Hz 1H) 428 (d J = 156 Hz

1H) 668 (d J = 52 z 1H) 730-738 (m 5H) 750 (d J = 52 Hz 1H) 13

C NMR =

378 630 722 1257 1264 1282 1286 1299 1338 1427 1467 HRMS (ESI+)

Calcd for C13H14NO3S2 M+H+ 2960410 Found mz 2960403 IR (ATR) 3437 1323

1150 1063 748 cm-1

[]29


Chapter 2

55


= 266 min (major) t2 = 306 min (minor) er = 937

NS Me

HOMe

O O

OMe

2c

1H NMR = 227 (s 3H) 290-326 (m 4H) 345 (d J = 148 Hz 1H) 381 (s 3H)

422 (d J = 148 Hz 1H) 684-690 (m 3H) 724-733 (m 3H) 774-779 (m 1H) 13

C

NMR = 216 360 553 626 729 1137 1237 1275 1299 1230 1328 1351

1413 1437 1592 HRMS (ESI+) Calcd for C17H20NO4S M+H

+ 3341108 Found mz

3341098 IR (ATR) 3441 1508 1250 1144 735 cm-1

[]29




NS Me

HOMe

O O

CF3

2d 1H NMR = 229 (s 3H) 304 (s 3H) 347 (d J = 148 Hz 1H) 425 (d J = 148 Hz

1H) 677 (s 1H) 732 (d J = 84 Hz 1H) 756 (d J = 84 Hz 2H) 763 (d J = 84 Hz

2H) 782 (d J = 80 Hz 1H) 13

C NMR = 216 360 625 731 12392 (q JC-F =

2708) 12395 1254 (q JC-F = 36 Hz) 1268 1298 1303 (q JC-F = 352) 1329

1404 1441 1471 HRMS (ESI+) Calcd for C17H17F3NO3S M+H

+ 3720876 Found

mz 3720869 IR (ATR) 3481 1323 1121 1067 733 cm-1

[]29




Chapter 2

56

Rhodium-Catalyzed Reaction of Azetidinol 1e A Typical Procedure for Reactions

of Azetidinols 1e-1n


[Rh(OH)(cod)]2 (09 mg 2 mol 2 mol ) and rac-DM-BINAP (37 mg 5 mol 5

mol ) in toluene (10 mL) was heated at 60 degC After being stirred for 12 h the

reaction mixture was passed through a pad of florisil The solvent was removed under

reduced pressure The crude residue was purified by preparative thin-layer

chromatography on silica gel (hexaneethyl acetate = 31) to afford the benzosultam 2e


SN

HO

Me

O OMe

Me

2e

H

NOE

NOE

1H NMR = 120 (d J = 64 Hz 3H) 224 (s 3H) 226 (s 1H) 297 (s 3H) 468 (q J

= 68 Hz 1H) 675 (s 1H) 723-738 (m 6H) 777 (d J = 84 Hz 1H) 13

C NMR =

119 215 314 608 750 1242 1262 1275 1282 1298 1301 1316 1427

1436 1440 HRMS (ESI+) Calcd for C17H20NO3S M+H

+ 3181158 Found mz

3181155 IR (ATR) 3481 1315 1163 1146 683 cm-1

[]28

D = -640 (c = 093 in CHCl3) Enantiomeric excess was determined by HPLC with



SN

HO

Me

O OMe

MeO

2g

H

NOE

NOE

Chapter 2

57



5H) 782 (d J = 88 Hz 1H) 13

C NMR = 120 314 555 609 752 1144 1151

1261 1262 1268 1276 1282 1439 1450 1626 HRMS (ESI+) Calcd for

C17H20NO4S M+H+ 3341108 Found mz 3341103 IR (ATR) 3487 1327 1161 1142

735 cm-1

[]29




SN

HO

Me

O OMe

F3C

2h

H

NOE

NOE

1H NMR = 124 (d J = 68 Hz 3H) 253 (bs 1H) 300 (s 3H) 473 (q J = 68 Hz

1H) 724 (s 1H) 730-740 (m 5H) 770 (dd J = 84 12 Hz 1H) 802 (d J = 84 Hz

1H) 13

C NMR = 118 314 608 750 1228 (q JC-F = 2711 Hz) 1251 1258 (q

JC-F = 37 Hz) 1260 1274 (q JC-F = 37 Hz) 1281 1286 1346 (q JC-F = 327 Hz)


+ 3720876 Found

mz 3720872 IR (ATR) 3461 1325 1161 1142 739 cm-1

[]29




SN

HO

Me

O OMe

2i

H

NOE

NOE

Me

Chapter 2

58

1H NMR = 121 (d J = 68 Hz 3H) 218 (bs 1H) 238 (s 3H) 300 (s 3H) 468 (q

J = 68 Hz 1H) 684 (d J = 80 Hz 1H) 718-736 (m 6H) 770 (s 1H) 13

C NMR

=119 211 314 607 748 1242 1262 1275 1282 1299 1338 1341 1395


+ 3181158 Found mz

3181155 IR (ATR) 3489 1448 1319 1148 735 cm-1

[]29




SN

HO

Me

O OMe

2j

H

NOE

NOES


1H) 656 (d J = 52 Hz 1H) 726-736 (m 5H) 743 (d J = 48 Hz 1H) 13

C NMR

= 114 319 619 742 1256 1266 1278 1284 1297 1334 1429 1480 HRMS

(ESI+) Calcd for C14H16NO3S2 M+H

+ 3100566 Found mz 3100561 IR (ATR) 3524

1329 1151 1020 729 cm-1

[]29



= 253 min (major) t2 = 273 min (minor) er gt 991

SN

HO

Me

O OMe

2k

H

NOE

NOE

OMe


J = 68 Hz 1H) 685 (d J = 88 Hz 2H) 698-703 (m 1H) 722-730 (m 2H)

738-748 (m 2H) 785-790 (m 1H) 13

C NMR = 119 314 553 608 747 1136

Chapter 2

59



760 cm-1

[]26

D = -1007 (c = 087 in CHCl3) Enantiomeric excess was determined by HPLC

with a Daicel Chiralpak IC hexanei-PrOH = 7030 flow rate = 06 mLmin = 260

nm) t1 = 112 min (minor) t2 = 125 min (major) er gt 991

SN

HO

Me

O OMe

2l

H

NOE

NOE

CF3

Me


= 68 Hz 1H) 670 (s 1H) 729 (d J = 80 Hz 1H) 750 (d J = 80 Hz 2H) 760 (d J

= 84 Hz 2H) 778 (d J = 80 Hz 1H) 13

C NMR = 119 215 313 607 749

1239 (JC-F = 2704 Hz) 1244 1252 (JC-F = 43 Hz) 1268 1299 (JC-F = 316 Hz)

1300 1303 1316 1419 1439 1482 HRMS (ESI+) Calcd for C18H19F3NO3S


-1

[]26




SN

HO

iPr

O OMe

2m

H

NOE

NOE

Me

1H NMR = 056 (d J = 68 Hz 3H) 110 (d J = 64 Hz 3H) 222 (s 3H) 230-241

(m 1H) 264 (s 1H) 285 (s 3H) 441 (d J = 100 Hz 1H) 685 (s 1H) 714-735 (m

4H) 748 (d J = 76 Hz 2H) 772 (d J = 80 Hz 1H) 13

C NMR = 211 214 217

278 330 718 742 1244 1256 1270 1283 1292 1295 1300 1435 1442


+ 3461471 Found mz 3461466 IR

Chapter 2

60

(ATR) 3412 1315 1165 1146 683 cm-1

[]29



nm) t1 = 127 min (major) t2 = 139 min (minor) er gt 991

SN

HO

O OMe

2n

H

Me

NOE

SMe

1H NMR = 160-170 (m 1H) 184 (s 3H) 212-226 (m 4H) 230-242 (m 2H)

254-263 (m 1H) 294 (s 3H) 471 (dd J = 108 28 Hz 1H) 675 (s 1H) 722-738

(m 6H) 776 (d J = 80 Hz 1H) 13

C NMR = 150 215 242 301 321 643 748

1245 1262 1276 1283 12986 12993 1312 1429 1437 1441 HRMS (ESI+)


1165 1134 748 cm-1

[]28




Details for X-ray Crystallography

Single crystal of 2e was obtained from hexanedichloromethane solution and mounted

on a grass capillary The data was collected on a Rigaku R-AXIS imaging plate area

detector with graphite-monochromated Mo K radiation operating at 50 kV and 40 mA

at minus173 degC All the following procedure for analysis Yadokari-XG19

was used as a

graphical interface The structure was solved by direct methods with SIR-9720

and

refined by full-matrix least-squares techniques against F2 (SHELXL-97)

21 All

non-hydrogen atoms were refined anisotropically The positions of hydrogen atoms

were calculated and their contributions in structural factor calculations were included

Chapter 2

61

Figure S1 ORTEP diagram of 2e

Table S3 Crystallographic data and structure refinement details for 2e

2e

formula C17H19NO3S

fw 31739

T (K) 100(2)

cryst syst monoclinic

space group P21c

a (Aring) 105967(5)

b (Aring) 134725(7) c (Aring) 110152(5) (deg) 9000 (deg) 1047740(15) (deg) 9000 V (Aring

3) 152058(13)

Z 4 Dcalc (gcm

3) 1386

(mm-1

) 0225 F(000) 672

cryst size (mm) 120times060times030

radiation (Aring) 071075 reflns collected 14659 indep reflnsRint

348500135

params 203 GOF on F

2 1069

R1 wR2 [Igt2(I)]

00322 00868

R1 wR2 (all data)

00335 00878

Chapter 2

62


(1) For reviews on CndashH activation (a) Crabtree R H Chem Rev 1985 85 245-269

(b) Halpern J Inorg Chim Acta 1985 100 41-48 (c) Shilov A E Shulrsquopin G B

Chem Rev 1997 97 2879-2932 (d) Jones W D Top Organomet Chem 1999

9-46 (e) Kakiuchi F Murai S Top Organomet Chem 1999 47-79 (f) Dyker G

Angew Chem Int Ed 1999 38 1698-1712 (g) Jia C Kitamura T Fujiwara Y

Acc Chem Res 2001 34 633-639 (h) Handbook of CndashH Transformations Dyker

G Ed Wiley-VCH Weinheim Germany 2005 (i) Daugulis O Do H-Q

Shabashov D Acc Chem Res 2009 42 1074-1086 (j) Giri R Shi B-F Engle

K M Maugel N Yu J-Q Chem Soc Rev 2009 38 3242-3272 (k) Colby D

A Bergman R G Ellman J A Chem Rev 2010 110 624-655 (l) Mkhalid I A

I Barnard J H Marder T B Murphy J M Hartwig J F Chem Rev 2010

110 890-931 (m) Lyons T W Sanford M S Chem Rev 2010 110 1147-1169

(n) Ackermann L Chem Commun 2010 46 4866-4877 (o) Newhouse T Baran

P S Angew Chem Int Ed 2011 50 3362-3374 (p) McMurray L OrsquoHara F

Gaunt M J Chem Soc Rev 2011 40 1885-1898 (q) Yeung C S Dong V M

Chem Rev 2011 111 1215-1292 (r) Sun C-L Li B-J Shi Z-J Chem Rev

2011 111 1293-1314 (s) Cho S H Kim J Y Kwak J Chang S Chem Soc

Rev 2011 40 5068-5083 (t) Kuhl N Hopkinson M N Wencel-Delord J

Glorius F Angew Chem Int Ed 2012 51 10236-10254 (u) Yamaguchi J

Yamaguchi A D Itami K Angew Chem Int Ed 2012 51 8960-9009 (v)

Arockiam P B Bruneau C Dixneuf P H Chem Rev 2012 112 5879-5918L

Sun C Liang S Shirazian Y Zhou T Miller J Cui J Y Fukuda J-Y Chu A

Nematalla X Wang H Chen A Sistla T C Luu F Tang J Wei C Tang J

Med Chem 2003 46 1116

(2) For reviews on CndashC activation (a) Rybtchinski B Milstein D Angew Chem Int

Ed 1999 38 870-883 (b) Murakami M Ito Y Top Organomet Chem 1999

97-129 (c) Takahashi T Kotora M Hara R Xi Z Bull Chem Soc Jpn 1999

72 2591-2602 (d) Perthuisot C Edelbach B L Zubris D L Simhai N

Iverson C N Muumlller C Satoh T Jones W D J Mol Cat A 2002 189

157-168 (e) Nishimura T Uemura S Synlett 2004 201-216 (f) Jun C-H Chem

Soc Rev 2004 33 610-618 (g) Miura M Satoh T Top Organomet Chem

Chapter 2

63

2005 14 1-20 (h) Kondo T Mitsudo T Chem Lett 2005 34 1462-1466 (i)

Nečas D Kotora M Curr Org Chem 2007 11 1566-1591 (j) Tobisu M

Chatani N Chem Soc Rev 2008 37 300-307 (k) Nakao Y Hiyama T Pure

Appl Chem 2008 80 1097-1107 (l) Yorimitsu H Oshima K Bull Chem Soc

Jpn 2009 82 778-792 (m) Seiser T Cramer N Org Biomol Chem 2009 7

2835-2840 (n) Bonesi S M Fagnoni M Chem Eur J 2010 16 13572-13589

(o) Murakami M Matsuda T Chem Commun 2011 47 1100-1105 (p) Aїssa C

Synthesis 2011 3389-3407 (q) Ruhland K Eur J Org Chem 2012 2683-2706

(r) Dong G Synlett 2013 24 1-5

(3) Reviews (a) Ma S Gu Z Angew Chem Int Ed 2005 44 7512-7517 (b) Shi

F Larock R Top Curr Chem 2010 292 123-164

(4) For a 14-palladium shift (a) Bocelli G Catellani M Chiusoli G P Larocca S

J Organomet Chem 1984 26 C9-C11 (b) Dyker G Chem Ber 1994 127

739-742 (c) Campo M A Larock R C J Am Chem Soc 2002 124

14326-14327 (d) Baudoin O Herrbach A Gueacuteritte F Angew Chem Int Ed

2003 42 5736-5740 (e) Masselot D Charmant J P H Gallagher T J Am

Chem Soc 2005 128 694-695 (f) Barder T E Walker S D Martinelli J R

Buchwald S L J Am Chem Soc 2005 127 4685-4696 (g) Zhao J Yue D

Campo M A Larock R C J Am Chem Soc 2007 129 5288-5295 and

references cited therein




Nakazawa H Murakami M J Am Chem Soc 2005 127 1390-1391 (d)

Shintani R Okamoto K Hayashi T J Am Chem Soc 2005 127 2872-2873

(e) Yamabe H Mizuno A Kusama H Iwasawa N J Am Chem Soc 2005

127 3248-3249 (f) Matsuda T Shigeno M Murakami M J Am Chem Soc

2007 129 12086-12087 (g) Panteleev J Menard F Lautens M Adv Synth

Catal 2008 350 2893-2902 (h) Seiser T Roth O A Cramer N Angew Chem

Int Ed 2009 48 6320-6323 (i) Shigeno M Yamamoto T Murakami M Chem

Eur J 2009 15 12929-12931 (j) Seiser T Cramer N Angew Chem Int Ed

2010 49 10163-10167 (k) Sasaki K Nishimura T Shintani R Kantchev E A

Chapter 2

64

B Hayashi T Chem Sci 2012 3 1278-1283 (l) Matsuda T Suda Y Takahashi

A Chem Commun 2012 48 2988-2990 and references cited therein

(6) For a 14-cobalt shift Tan B-H Dong J Yoshikai N Angew Chem Int Ed

2012 51 9160





11437-11439

(8) For recent reports on synthesis of benzosultams (a) Zeng W Chemler S R J

Am Chem Soc 2007 129 12948-12949 (b) Miura T Yamauchi M Kosaka

A Murakami M Angew Chem Int Ed 2010 49 4955-4957 (c) Majumdar K

C Mondal S Chem Rev 2011 111 7749-7773 (d) Pham M V Ye B Cramer

N Angew Chem Int Ed 2012 51 10610-10614 (e) Dong W Wang L

Parthasarathy K Pan F Bolm C Angew Chem Int Ed 2013 52 11573-11576

and references cited therein

(9) (a) Lombardino J G Wiseman E H Mclamore W J Med Chem 1971 14

1171ndash1175 (b) Lazer E S Miao C K Cywin C L Sorcek R Wong H-C

Meng Z Potocki I Hoermann M Snow R J Tschantz M A Kelly T A

McNeil D W Coutts S J Churchill L Graham A G David E Grob P M

Engel W Meier H Trummlitz G J Med Chem 1997 40 980ndash989 (c) Wells

G J Tao M Josef K A Bihovsky R J Med Chem 2001 44 3488ndash3503 (d)

Zia-ur-Rehman M Choudary J A Ahmad S Siddiqui H L Chem Pharm

Bull 2006 54 1175-1178 and references cited therein

(10) See Supporting Information for details

(11) For transition metal-catalyzed reactions of cyclobutanolscyclobutenols involving

-carbon elimination (a) Nishimura T Ohe K Uemura S J Am Chem Soc

1999 121 2645-2646 (b) Nishimura T Uemura S J Am Chem Soc 1999 121

11010-11011 (c) Matsuda T Makino M Murakami M Org Lett 2004 6

1257-1259 (d) Seiser T Cramer N Angew Chem Int Ed 2008 47 9294-9297

(e) Seiser T Cramer N J Am Chem Soc 2010 132 5340-5341 (f)

Chtchemelinine A Rosa D Orellana A J Org Chem 2011 76 9157-9162 (g)

Chapter 2

65

Ziadi A Martin R Org Lett 2012 14 1266-1269 (h) Ishida N Sawano S

Masuda Y Murakami M J Am Chem Soc 2012 134 17502-17504 (i)

Matsuda T Miura N Org Biomol Chem 2013 11 3424-3427 (j) Ishida N

Nakanishi Y Murakami M Angew Chem Int Ed in press [DOI

101002anie201306343] and references cited therein

(12) For 6-exo cyclization of arylmetal intermediates having a pendant ketone see (a)

Liu G X Lu X Y J Am Chem Soc 2006 128 16504-16505 (b) Yin L

Kanai M Shibasaki M Angew Chem Int Ed 2011 50 7620-7623 (c)

Sarpong R Gallego G L Chem Sci 2012 3 1338-1342 (d) Low D W

Pattison G Wieczysty M D Churchill G H Lam H W Org Lett 2012 14

2548-2551


Hou Y Wu P J Chem Soc Perkin Trans 1 1999 2277-2280

(14) In case the 3-substituent was a methyl group a 15-rhodium shift occurred onto the

methyl group rather than onto the aryl group to form the rhodium enolate which

was subsequently protonated to give a simple ring-opened product

(15) Ishida N Shimamoto Y Murakami M Angew Chem Int Ed 2012 51

11750

(16) Ghosh D Sahu D Saravanan S Abdi S H R Ganguly B Khan N-u H

Kureshy R I Bajaj H C Org Biomol Chem 2013 11 3451

(17) Wang J Hou Y J Chem Soc Perkin Trans 1 1998 1919

(18) Bures F Kulhanek J Tetrahedron Asymmetry 2005 16 1347

(19) (a) Wakita K Yadokari-XG Software for Crystal Structure Analyses 2001 (b)

Kabuto C Akine S Kwon E J Cryst Soc Jpn 2009 51 218

(20) Altomare A Burla M C Camalli M Cascarano G L Giacovazzo C

Guagliardi A Moliterni A G G Polidori G Spagna R J Appl Cryst 1999

32 115

(21) Sheldrick G M SHELX-97 Programs for Crystal Structure Analysis University

of Goumlttingen Germany 1997

Chapter 2

66

Chapter 3

67

Chapter 3

Stereoselective Synthesis of (E)-(Trisubstituted alkenyl)borinic

Esters Stereochemistry Reversed by Ligand in the

Palladium-Catalyzed Reaction of Alkynylborates with Aryl

Halides

Abstract

The palladium-catalyzed reaction of alkynylborates with aryl halides stereoselectively

gave (E)-(trisubstituted alkenyl)-9-BBNs in which two different aryl groups were

installed trans to each other

Reproduced with permission from Org Lett 2009 11 5434-5437


Chapter 3

68

Introduction

Organoboron compounds are stable and easily handled organometallics with well

understood reactivities rendering them indispensable synthetic reagents for

carbonndashcarbon bond formation1 In addition organoboron compounds have found

increasing applications in the fields of pharmaceutical chemistry2 and materials

science3 Therefore the development of efficient methods to prepare them is of even

higher demand than ever

Well established preparative methods exist for the synthesis of (monosubstituted

alkenyl)(diorganyl)boranes such that these compounds have been widely applied for the

synthesis of unsaturated organic compounds like allylic alcohols4 However the

selective preparation of both stereoisomers of (trisubstituted alkenyl)(diorganyl)boranes

remains a significant challenge56

We have reported that alkynyl(triaryl)borates (aryl =

Ar1) react with aryl halides (Ar

2ndashX) in the presence of a palladium catalyst to afford a

(trisubstituted alkenyl)(diaryl)boranes in which the two aryl groups (Ar1 and Ar

2) are

incorporated cis to each other across the resulting carbonndashcarbon double bond7

Considering the potential utility of these compounds we embarked on the development

of a complementary synthetic method for the (E)-isomers In this communication we

describe the stereoselective synthesis of (E)-(trisubstituted alkenyl)-9-BBNs by a

palladium-catalyzed reaction of alkynylborates with aryl halides in which the two

different aryl groups are installed trans to each other


Alkynylborate 1a was readily prepared by the reaction of Ph-9-BBN with

but-1-ynyllithium in THF8 and subsequent cation exchange with tetramethylammonium

chloride in methanol (Scheme 1) Borate 1a obtained is a white precipitate of high

purity stable to air and moisture and therefore storable without any decomposition for

several months

Scheme 1 Preparation of Alkynyl Borate 1aa

Et LiB

Ph

+B

Ph

Et

1a 74

(a)(b)[Me4N]

a Reagents and conditions (a) THF - 78 degC to rt 1 h (b) Me4NCl MeOH rt 5 min

Chapter 3

69

Alkynylborate 1a thus derived from Ph-9-BBN is preferred over the corresponding

alkynyltriarylborate as the starting substance from a synthetic point of view It was

subjected to the palladium-catalyzed reaction with 4-bromoanisole in the presence of

various phosphine ligands (Table 1) When tri(o-tolyl)phosphine was employed as the

ligand the phenyl group on boron underwent 13-migration onto the palladium in

preference to the bridgehead sp3 carbons of the 9-BBN moiety and the (Z)-isomer was

stereoselectively formed as with the case of the corresponding triphenylborate7a

Although we attempted to isolate the produced triorganoborane 3a it failed because 3a

was prone to decompose in air Instead 3a was immediately hydrolyzed with acetic

acid9 to give the alkene (Z)-4a (EZ = 397 entry 1) The EZ ratio changed in favor of

the (E)-isomer as the steric bulkiness of the monodentate phosphine increased (entries

2-4) Surprisingly the stereochemical preference was reversed for the (E)-isomer (EZ =

928) when bidentate ligand DPEPhos having a large bite angle was used (entry 5)

Finally it was found that XANTPhos possessing an even larger bite angle exclusively

gave (E)-4a in 73 yield (entry 6)

Table 1 Ligand Screeninga

OMe

BrB

Ph

Et

OMe

3a

Ph

Et

OMe

H

4a

Pd-ligand AcOH

2a

+B

Ph

Et

1a

[Me4N]

entry ligand yield of 4a b

EZ of 4ab

1 P(o-tol)3 69 397

2 P(t-Bu)3 47 1783

3 1-[(t-Bu)2P](biphenyl) 18 2872

4 2-[(t-Bu)2P](11-binaphthyl) 21 6733

5 DPEPhos 24 928

6 XANTPhos 73 gt199 a reaction conditions 10 equiv of 1a 105 equiv of 2a 25 mol of [Pd(-allyl)Cl]2 6

mol of Ligand toluene 70 degC 30 min then AcOH rt 3 h b Dtermined by GC

analysis

Thus the stereochemistry of the product depended strongly on the phosphine ligand

employed A proposed mechanism for the trans-addition reaction is shown in Scheme 2

Chapter 3

70

(i) oxidative addition of 4-bromoanisole (2a) to palladium(0) gives arylpalladium

bromide A (ii) arylpalladium species A is coordinated by alkynylborate 1a to form

intermediate B (iii) carbopalladation across the carbonndashcarbon triple bond occurs in a

cis fashion to provide alkenylpalladium C (iv) a phenyl group on boron migrates to the

-carbon with inversion of stereochemistry1011

resulting in the formation of

trans-addition product 3a with regeneration of the palladium(0)12

Scheme 2 Proposed Mechanism

Pd(0)

Pd

MeO

B

PdEt

OMe

Ph

B

Ph

Et

2a

BC

Pd

MeO

Br

A

1a

3a

The ligand-dependent reaction pathway of the phenyl migration is explained as

follows Tri(o-tolyl)phosphine is relatively less stereo-demanding and when located

around the palladium center provides enough space for the phenyl group on boron to

undergo 13-migration to palladium (Scheme 4) On the other hand a bulky bidentate

ligand XANTPhos likely disfavors the 13-phenyl migration from boron to palladium

Instead the direct 12-migration of the phenyl group from boron onto the -carbon

dominates10

giving trans-addition product Tri(t-butyl)phosphine and Buchwald type

ligands which are intermediates between tri(o-tolyl)phosphine and XANTPhos in

sterics may permit both of these pathways resulting in a mixture of EZ isomers

Next we tried to isolate the addition product in a form of an alkenylborane which

was applicable to subsequent synthetic transformations rather than loosing a carbon-

ndashboron linkage by hydrolysis When the reaction mixture was directly subjected to a

migrative oxidation reaction with trimethylamine-N-oxide (trisubstituted

alkenyl)borinic ester 5a in which the bridgehead sp3 carbon migrated onto oxygen was

obtained stereoselectively13

The resulting borinic ester (E)-5a was stable enough to be

isolated by column chromatography on silica gel and could be stored without any

decomposition for a longer period of time than 1 month Most importantly this reagent

could be employed for subsequent carbonndashcarbon bond forming reactions (vide infra)

A wide variety of borinic esters were synthesized using the palladiumXANTPhos

system followed by migrative oxidation with trimethylamine-N-oxide (Scheme 3) Aryl

Chapter 3

71

halides having either an electron-donating or an electron-withdrawing substituent gave

the corresponding borinic esters in good yields (5a and 5b) Phthalimide (5c) chloro (5f

5j and 5l) and ester (5i) groups remained intact under the reaction conditions A

sterically demanding aryl iodide was also reactive (5d) In addition to the substituted

phenyl groups 2- and 3-bromothiophene afforded the desired product in good yield (5e

and 5h) Primary alkyl (5a to 5g 5l and 5m) secondary alkyl (5h to 5k) and aryl (5n)

groups can be used as the substituent of the alkynyl moiety The scope of the aryl group

on boron was also broad electron-rich (5g and 5n) and -deficient (5f) phenyl and

thienyl (5l) groups successfully participated in the migration reaction

Chapter 3

72

Table 2 Synthesis of Borinic Esters

BO

Ph

Et

OMe

5a 83

BO

Ph

Et

CF3

5b 85

BO

Ph

Et

NPhth

5c 82

BO

Ph

Et

5d 72b

BO

Ph

Et

5e 85

S

BO

n-Pr

Me

Cl

5f 74

BO

n-Pr

Ph

OMe

5g 82

BO

Ph

S

5h 83

BO

Ph

CO2Et

5i 81

BO

Ph

5j 82

Cl

BO

Ph

CF3

TBSO

BO

Cl

S

Ph

BO

Ph

Me

OMe

5n 71b

5m 925l 82

BO

Ph

5k 76

Me

+B

Ar

R

1

[Me4N]

2

Ar-Xcat XANTPhos-Pd Me3NO

BO

Ar

R

Ar

5

a Reaction conditions 10 equiv of alkynylborate 1 105 equiv of aryl halide 2 1 mol

of (xantphos)PdCl(-allyl) toluene 70 degC 30 min then 15 equiv of Me3NO DCM rt

2 h Isolated yields were shown The major isomers shown in the table were observed

gt955 ratio by NMR analysis b Aryl iodide was used

Finally we applied this reaction to the synthesis of both isomers of Tamoxifen

(Scheme 5) which has been in clinical use for cancer treatment1415

The reaction of 1a

with bromobenzene with the palladiumtri(o-tolyl)phospine catalyst followed by

oxidation with trimethylamine-N-oxide gave borinic ester (Z)-5o (71 yield EZ =

793) On the other hand the corresponding (E)-isomer was stereoselectively obtained

in 83 yield (EZ = gt955) when the reaction of 1a with bromobenzene was carried out

with the palladiumXANTPhos calatyst the loading of which could be decreased even

Chapter 3

73

to 01 mol The Suzuki-Miyaura coupling reaction of each stereoisomer of 5o with

1-bromo-4-[2-(NN-dimethylamino)ethoxy]benzene (2b) afforded Tamoxifen (6) with

retention of the each stereochemistry Thus the present study made it possible to

synthesize either stereoisomer of tetrasubstituted olefins16

starting from the same

substances by choice of the appropriate ligand

Scheme 3 Synthesis of Tamoxifensa

(E)-5o83 EZ = gt955

BO

Ph

Et

Ph

Ph

Et

PhO

NMe2

(Z)-685 EZ = lt595

Ph

Ph

EtO

NMe 2

(E)-675 EZ = 928

1a

(Z)-5o71 EZ = 793

+ PhBr

BO

Ph

Ph

Et

(a)

(c) (c)

(b)

a Reagents and conditions (a) 1 mol of (o-tol)3PPdCl(-allyl) toluene 70 degC 30

min then 15 equiv of Me3NO DCM rt 2 h (b) 01 mol of (xantphos)PdCl(-allyl)

toluene 70 degC 30 min then 15 equiv of Me3NO DCM rt 2 h (c) 105 equiv of

4-BrC6H4[O(CH2)2NMe2] (2b) 25 mol of Pd(OAc)2 5 mol of SPhos K3PO4

THF 60 degC 12 h for (E)-5o 24 h for (Z)-5o

Conclusions

In summary we have developed a new catalyst system for the palladium-catalyzed

reaction of alkynylborates with aryl halides which produces (E)-(trisubstituted

alkenyl)boranes stereoselectively With both stereoisomers being available the

reinforced palladium-catalyzed reaction of alkynylborates serves as an authentic method

for the synthesis of (trisubstituted alkenyl)boron compounds

Chapter 3

74


General NMR spectra were recorded on a Varian Gemini 2000 (1H at 300 MHz and

13C at 75 MHz) or Varian Mercury-400 (

1H at 400 MHz and

11B at 128 MHz)

spectrometers Unless otherwise noted CDCl3 was used as a solvent Chemical Shifts

are recorded in ppm referenced to a residual CDCl3 (= 726 for 1H 770 for

13C)

CD3CN ( = 194 for 1H =132 for

13C) and BF3OEt2 ( = 000 for

11B)

High-resolution mass spectra were recorded on JEOL JMS-SX102A spectrometer

Infrared spectra were recorded on SHIMADZU FT-IR 8100 Column chromatography

was performed with silica gel 60 N (Kanto) Preparative thin-layer chromatography was

performed with Silica gel 60 PF254 (Merck)


from commercial suppliers and used as received Toluene was dried over

Na-benzophenone ketyl AcOH was degassed by N2 bubbling

(XANTPhos)Pd(-allyl)Cl17

and Ph-9-BBN18

were prepared according to the reported

procedures

Preparation of alkynylborates 1a

Et LiB

Ph

+B

Ph

Et

1a

1) THF -78 degC to rt

2) Me4NCl MeOH

[Me4N]

To a stirred solution of 1-butyne (1 ml) in THF (80 ml) at -78 ˚C was added n-BuLi

(16 M in hexane 34 ml 55 mmol) After 30 minutes at this temperature Ph-9-BBN

(990 mg 50 mmol) was added and the cooling bath was then removed After being

stirred for 1 h at room temperature the reaction was quenched by adding a small

amount of methanol Then volatile materials were removed under reduced pressure

The residue was dissolved in methanol and tetramethylammonium chloride (600 mg

55 mmol) was added with stirring at -78 ˚C resulting in white solid It was collected by

filtration and washed with cold methanol to give alkynylborate 1a (12 g 37 mmol

74 yield)

Chapter 3

75

B

Ph

Et

1a

[Me4N]

1H NMR (CD3CN) = 092 (bs 2H) 097 (t J = 78 Hz 3H) 111-120 (m 1H)

136-207 (m 11H) 236-250 (m 2H) 303 (s 12 H) 679-686 (m 1H) 700-707 (m

2H) 735 (d J = 72 Hz 2H) 13

C NMR (CD3CN) = 149 166 266 (q JC-B = 379

Hz) 271 275 324 349 561 948 1221 1269 1339 11

B NMR = -133 HRMS

(FAB) Calcd for C18H24B [M-(NMe4)] 2511971 Found 2511975

Preparation of alkynylborates 1b A typical procedure for the preparation of

alkynylborates 1b-1h

n-Pr LiB

Ar

+1) THF -78 degC to rt

2) Me4NCl MeOH B

n-Pr

1b

Cl

[Me4N]

To a stirred solution of 1-pentyne (375 mg 55 mmol) in THF (80 ml) at -78 ˚C was

added n-BuLi (16 M in hexane 34 ml 55 mmol) After 30 minutes at this temperature

4-ClC6H4-9-BBN (116 g 50 mmol) was added and the cooling bath was removed

After being stirred for 1 h at room temperature the reaction was quenched by adding a

small amount of methanol Then volatile materials were removed under reduced

pressure The residue was dissolved in methanol and tetramethylammonium chloride

(600 mg 55 mmol) was added with stirring at -78 ˚C resulting in white solid It was

collected by filtration and was washed with cold methanol to give alkynylborate 1b

(105g 28 mmol 56 yield)

Chapter 3

76

B

n-Pr

1b

Cl

[Me4N]

1H NMR (CD3CN) = 084-096 (m 5H) 111-121 (m 1H) 126-200 (m 13H)

235-250 (m 2H) 304 (s 12H) 700-705 (m 2H) 733 (d J = 84 Hz 2H) 13

C NMR

(CD3CN) = 139 234 249 266 (q JC-B = 393 Hz) 270 273 323 348 561

933 1265 1272 1355 11

B NMR = -133 HRMS (FAB) Calcd for C19H25BCl

[M-(NMe4)] 2991738 Found 2991730

B

n-Pr

1c

OMe

[Me4N]


128-201 (m 13H) 237-252 (m 2H) 303 (s 12H) 371 (s 3H) 663-668 (m 2H)

723 (d J = 81 Hz 2H) 13

C NMR (CD3CN) = 140 235 250 268 (q JC-B = 393

Hz) 272 275 324 349 554 561 929 1128 1344 1561 11

B NMR = -135

HRMS (FAB) Calcd for C20H28BO [M-(NMe4)] 2952233 Found 2952231

B

Ph

1d

[Me4N]

1H NMR (CD3CN) = 020-028 (m 2H) 045-053 (m 2H) 089 (bs 2H) 098-119

(m 2H) 134-196 (m 9H) 230-244 (m 2H) 304 (s 12H) 679-686 (m 1H)

699-706 (m 2H) 733 (d J = 72 Hz 2H) 13

C NMR (CD3CN) =23 87 266 (q

JC-B = 393 Hz) 271 274 323 349 562 1222 1269 1338 11

B NMR = -134

HRMS (FAB) Calcd for C19H24B [M-(NMe4)] 2631971 Found 2631976

Chapter 3

77

B

Ph

1e

[Me4N]

1H NMR (CD3CN) = 090 (bs 2H) 110-120 (m 1H) 130-196 (m 17H) 236-254

(m 3H) 302 (s 12H) 679-686 (m 1H) 699-706 (m 2H) 734 (d J = 66 Hz 2H) 13

C NMR (CD3CN) = 253 268 (q JC-B = 379 Hz) 271 275 324 333 349 361

561 980 1221 1269 1339 11

B NMR = -133 HRMS (FAB) Calcd for C21H28B

[M-(NMe4)] 2912284 Found 2912278

B

1f

S

Ph

[Me4N]

1H NMR (CD3CN) = 077 (bs 2H) 117-128 (m 1H) 138-160 (m 5H) 168- 197

(m 4H) 231 (t J = 75 Hz 2H) 234-237 (m 2H) 268 (t J = 75 Hz 2H) 301 (s

12H) 673 (dd J = 30 06 Hz 1H) 689 (dd J = 48 30 Hz 1H) 707 (dd J = 45

09 Hz 1H) 712-730 (m 5H) 13

C NMR (CD3CN) = 240 268-290 (m) 325 347

380 562 928 1225 1261 1265 1271 1289 1297 1434 11

B NMR = -135

HRMS (FAB) Calcd for C22H26BS [M-(NMe4)] 3331848 Found 3331852

B

Ph

1g

TBSO

[Me4N]

1H NMR (CD3CN) = 005 (s 6H) 084-096 (m 11H) 110-120 (m 1H) 134-197

(m 9H) 216-233 (t J = 72 Hz 2H) 235-250 (m 2H) 301 (s 12H) 356 (t J = 78

Hz 2H) 680-687 (m 1H) 700-708 (m 2H) 735 (d J = 66 Hz 2H) 13

C NMR

(CD3CN) = -50 189 254-277 (m) 323 348 561 649 889 1222 1269

1339 11

B NMR = -133 HRMS (FAB) Calcd for C24H38BOSi [M-(NMe4)] 3812785

Found 3812789

Chapter 3

78

B

Ph

1h

OMe

[Me4N]


(m 2H) 298 (s 12H) 373 (s 3H) 668-674 (m 2H) 701-718 (m 5H) 732 (d J =

87 Hz 2H) 13

C NMR (CD3CN) = 255-277 (m) 322 350 554 561 961 1129

1251 1287 1302 1312 1345 1564 11

B NMR = -131 HRMS (FAB) Calcd for

C23H26BO [M-(NMe4)] 3292077 Found 3292081

Palladium-Catalyzed Reaction of Alkynylborate 1a with 4-Bromoanisole Typical

Procedure for the Ligand Screening

Br

+

MeO

25 mol [PdCl(-allyl)]2

6 mol Ligand

toluene 70 degC 30 min

2a

B

Ph

Et

OMe

(E)-3a

AcOH

Ph

Et

OMe

H

Ph

B

Et

OMe

+

+

(Z)-3a

(E)-4a

H

Et

OMe

Ph

(Z)-4a

B

Ph

Et

1a

[Me4N]

Under an argon atmosphere a toluene solution (10 ml) of alkynylborate 1a (651 mg

020 mmol) [Pd(-allyl)Cl]2 (18 mg 5 mol) P(o-tol)3 (37 mg 12 mol) and

4-bromoanisole 2a (393 mg 021 mmol) was stirred for 30 minutes at 70 ˚C To the

reaction mixture was added AcOH at room temperature After being stirred for 3 h the

resulting mixture was neutralized with saturated Na2CO3 solution The aqueous layer

was extracted with AcOEt (3 times) washed with water (once) brine (once) dried over

MgSO4 and concentrated A portion of the sample was taken in a GC tube and diluted

with Et2O to determine the GC yields

Chapter 3

79

PalladiumXANTPhos-Catalyzed Reaction of Alkynylborate 1a with 4-Bromo-

anisole A Typical Procedure for the PalladiumXANTPhos-Catalyzed Reaction of

Alkynylborates with Arylhalides

B

Ph

Et

+

1 mol (xantphos)PdCl(-allyl)

toluene 70 degC

Me3NO

Br

MeO

BO

Ph

Et

OMe

5a

1a

2a

[Me4N]


020 mmol) (XANTPhos)Pd(-allyl)Cl (15 mg 20 mol) and 4-bromoanisole 2a

(393 mg 021 mmol) was stirred for 30 minutes at 70 ˚C To the reaction mixture were

added Me3NO (225 mg 030 mmol) and CH2Cl2 (10 ml) at room temperature After

being stirred for 2 h the resulting mixture was passed through a pad of Florisil and

eluted with ethyl acetate The residue was purified by preparative thin-layer

chromatography on silica gel (hexaneethyl acetate = 501) to afford the (trisubstituted

alkenyl)borinic ester 5a (619 mg 017 mmol 83 yield EZ = gt955)

BO

Ph

Et

OMe

5a 1H NMR = 080 (t J = 78 Hz 3H) 102-171 (m 13H) 227 (q J = 78 Hz 2H)

383 (s 3H) 438-444 (m 1H) 685-691 (m 2H) 714-736 (m 7H) 13

C NMR =

138 221 267 273 (br) 277 312 553 736 1132 1251 1278 1283 1298

1366 1436 1494 1586 11

B NMR = 500 HRMS (EI) Calcd for C25H31BO2 (M+)

3742417 Found 3742410

Chapter 3

80

BO

Ph

Et

CF3

5b

1H NMR = 081 (t J = 75 Hz 3H) 097-170 (m 13H) 231 (q J = 75 Hz 2H)

437-443 (m 1H) 718-726 (m 3H) 734-739 (m 2H) 745-748 (m 2H) 760-763

(m 2H) 13

C NMR = 135 220 266 271 (br) 276 312 738 12429 (q JC-F =

2701 Hz) 1247 (q JC-F = 36 Hz) 1280 1281 1289 (q JC-F = 320 Hz) 1291 1425

1476 1480 11

B NMR = 505 HRMS (EI) Calcd for C25H28BF3O (M+) 4122185

Found 4122186

BO

Ph

Et

NPhth

5c


440-450 (m 1H) 720-727 (m 3H) 734-739 (m 2H) 743-751 (m 4H) 777-783

(m 2H) 794-800 (m 2H) 13

C NMR = 137 221 266 274 (br) 275 312 738

1235 1254 1258 1279 1282 1294 1304 1317 1342 1429 1440 1482

1671 11

B NMR = 502 IR (KBr) = 2928 1742 1509 1381 714 cm-1

HRMS (EI)

Calcd for C32H32BNO3 (M+) 4892475 Found 4892473

BO

Ph

Et

5d

1H NMR = 021-034 (m 1H) 068-100 (m 8H) 120-150 (m 7H) 224-238 (m

1H) 244-258 (m 1H) 424-431 (m 1H) 722-754 (m 9H) 778 (d J = 78 Hz 1H)

783-788 (m 1H) 809-816 (m 1H) 13

C NMR = 137 216 219 259 262 264

(br) 282 309 314 734 1249 12537 12539 1255 1264 1270 1273 12795

Chapter 3

81

12799 1283 1321 1335 1413 1427 1467 11

B NMR = 497 HRMS (EI) Calcd

for C28H31BO (M+) 3942468 Found 3942476

BO

Ph

Et

5e

S


448-456 (m 1H) 702 (dd J = 51 36 Hz 1H) 708 (dd J = 36 12 Hz 1H)

715-730 (m 4H) 732-738 (m 2H) 13

C NMR =141 221 271 289 312 739

1250 1255 1266 1269 1279 1281 1416 1427 1468 11

B NMR = 496

HRMS (EI) Calcd for C22H27BOS (M+) 3501876 Found 3501880

BO

n-Pr

Me

Cl

5f

1H NMR = 070 (t J = 75 Hz 3H) 096-133 (m 9H) 142-172 (m 6H) 220-228

(m 2H) 237 (s 3H) 439-446 (m 1H) 708-735 (m 8H) 13

C NMR = 140 212

219 221 267 274 (br) 313 363 737 1279 12846 12855 1298 1309 1365

1411 1420 1488 11

B NMR = 506 HRMS (EI) Calcd for C26H32BClO (M+)

4062235 Found 4062237

BO

n-Pr

Ph

OMe

5g

Chapter 3

82

1H NMR = 073 (t J = 72 Hz 3H) 095-170 (m 15H) 229 (t J = 78 Hz 2H) 384

(s 3H) 435-450 (m 1H) 690 (d J = 81 Hz 2H) 711 (d J = 81 Hz 2H) 720-740

(m 5H) 13

C NMR = 140 219 221 267 274 (br) 312 362 551 736 1133

1267 1278 1287 1294 1354 1446 1475 1573 11

B NMR = 507 HRMS (EI)

Calcd for C26H33BO2 (M+) 3882754 Found 3882572 The stereochemistry was

assigned by NOE analysis

BO

Ph

S

5h

1H NMR = 027-032 (m 2H) 046-052 (m 2H) 098-130 (m 6H) 140-170 (m

8H) 430-445 (m 1H) 696-700 (m 1H) 704-707 (m 1H) 715-726 (m 2H)

729-738 (m 4H) 13

C NMR = 60 150 222 263 272 (br) 313 736 1241

1243 1253 1278 1290 1295 1410 1425 1431 11


Calcd for C23H27BOS (M+) 3621876 Found 3621881

BO

Ph

CO2Et

5i

1H NMR = 017-023 (m 2H) 045-053 (m 2H) 090-119 (m 6H) 132-173 (m

11H) 427-433 (m 1H) 438 (q J = 75 Hz 2H) 718-738 (m 7H) 798 (dt J = 78

15 Hz 2H) 13

C NMR = 56 144 151 220 263 269 (br) 312 609 735 1255

1279 1284 1287 1289 1303 1423 1453 1469 1665 11

B NMR = 496 IR

(KBr) = 2928 1717 1287 1100 cm-1

HRMS (EI) Calcd for C28H33BO3 (M+) 4282523

Found 4282526

BO

Ph

5j

Cl

Chapter 3

83

1H NMR = 023-029 (m 2H) 048-055 (m 2H) 094-123 (m 6H) 134-171 (m

8H) 432-439 (m 1H) 706-714 (m 1H) 718-726 (m 4H) 728-738 (m 4H) 13

C

NMR = 57 150 220 263 271 (br) 312 736 1255 1267 1279 1283 1284

1289 1304 1332 1423 1424 1461 11

B NMR = 496 HRMS (EI) Calcd for

C25H28BClO (M+) 3901922 Found 3901923

BO

Ph

5k

Me

1H NMR = 082-113 (m 6H) 126-164 (m 15H) 237 (s 3H) 268-280 (m 1H)

434-441 (m 1H) 704-709 (m 3H) 717-725 (m 4H) 730-737 (m 2H) 13

C NMR

= 215 219 248 263 273 (br) 312 315 433 735 1252 12689 12693 1275

1278 1283 1316 1365 1418 1424 1481 11


for C28H35BO (M+) 3982781 Found 3982780

BO

Cl

S

Ph

5l

1H NMR = 106-176 (m 13H) 250-260 (m 2H) 272-280 (m 2H) 441-449 (m

1H) 674 (dd J = 33 12 Hz 1H) 697-703 (m 3H) 709-738 (m 8H) 13

C

NMR(C6D6) =225 272 277 (br) 315 358 375 739 1247 1253 1261 1272

1285 12856 12861 1306 1335 1419 1427 1437 1491 11

B NMR = 495

HRMS (EI) Calcd for C28H30BClOS (M+) 4601799 Found 4601797

BO

Ph

CF3

TBSO

5m

Chapter 3

84

1H NMR = -014 (s 6H) 079 (s 9H) 095-136 (m 6H) 142-168 (m 7H) 255 (t

J = 72 Hz 2H) 343 (t J = 72 Hz 2H) 435-442 (m 1H) 718-726 (m 3H)

731-737 (m 2H) 747 (d J = 81 Hz 2H) 759 (d J = 81 Hz 2H) 13

C NMR = -54

183 220 259 266 271 (br) 311 377 616 739 1242 (q JC-F = 2694 Hz) 1247

(q JC-F = 36 Hz) 1258 1280 1282 1290 (q JC-F = 320 Hz) 1291 1421 1422

1480 11

B NMR = 505 HRMS (FAB) Calcd for C31H42BF3O2Si (M+) 5422999

Found 5422992 The stereochemistry was assigned by NOE analysis

BO

Ph

Me

OMe

5n

1H NMR = 122-130 (m 4H) 138-162 (m 5H) 168-186 (m 4H) 237 (s 3H)

375 (s 3H) 443-450 (m 1H) 670 (dt J = 90 21 Hz 2H) 690-697 (m 4H)

702-708 (m 3H) 710-720 (m 4H) 13

C NMR = 213 222 269 312 550 738

1132 1260 1272 1285 1301 1307 1310 1362 1369 1423 1429 1483

1571 11

B NMR = 510 HRMS (EI) Calcd for C30H33BO2 (M+) 4362574 Found

4362561

PalladiumTri(o-tolyl)phosphine-Catalyzed Reaction of Alkynylborate 1a with

4-Bromobenzene

B

Ph

Et

+

1 mol (o-tol)3PPdCl(-allyl)

toluene 70 degC

Me3NO BO

Ph

Ph

Et

(Z)-5o

1a

Ph Br

[Me4N]


060 mmol) (o-tol)3PPd(-allyl)Cl (30 mg 60 mol) and 4-bromobenzene (989 mg

063 mmol) was stirred for 30 minutes at 70 ˚C To the reaction mixture were added

Chapter 3

85

Me3NO (678 mg 090 mmol) and CH2Cl2 (20 ml) at room temperature After being

stirred for 2 h the resulting mixture was passed through a pad of Florisil and eluted with

ethyl acetate The residue was purified by preparative thin-layer chromatography on

silica gel (hexaneethyl acetate = 501) to afford the (trisubstituted alkenyl)borinic ester

(Z)-5b (1469 mg 043 mmol 71 yield EZ = 793)

BO

Ph

Ph

Et

(Z)-5o 1H NMR = 101 (t J = 72 H 3H) 139-200 (m 13H) 267 (q J = 72 Hz 2H)

470-475 (m 1H) 685-710 (m 10H) 13

C NMR = 139 224 267 313 317 740

1248 1257 1272 127412938 12941 1421 1425 1275 11

B NMR = 512

HRMS (EI) Calcd for C24H29BO (M+) 3442311 Found 344 2310

BO

Ph

Et

Ph

(E)-5o 1H NMR = 081 (t J = 72 Hz 3H) 100-169 (m 13H) 230 (q J = 72 Hz 2H)

438-443 (m 1H) 718-737 (m 10H) 13

C NMR = 137 221 266 274 (br) 277

312 737 1253 1268 1278 1279 1283 1288 1433 1442 1494 11

B NMR =

504 HRMS (EI) Calcd for C24H29BO (M+) 3442311 Found 3442313

Typical Procedure for Palladium-Catalyzed Reaction of Borinic Ester 5o with Aryl

Bromide 2b

+

Br

ONMe2

Ph

Et

PhO

NMe2

25 mol Pd(OAc)25 mol SPhos

THF K3PO4 60 degC

(Z)-Tamoxifen 6

2b

BO

Ph

Et

Ph

(E)-5o

Chapter 3

86

Under an argon atmosphere borinic ester (E)-5o (689 mg 020 mmol) Pd(OAc)2 (11

mg 50 mol) SPhos (41 mg 10 mol) and 2b (512 mg 021 mmol) in THF (10

ml) was stirred for 12 h at 60 ˚C After cooling the reaction mixture to room temperature

water was added The organic layer was separated and extracted with CH2Cl2 (3 times)

and washed with water (once) brine (once) dried over Na2SO4 and concentrated The

residue was purified by preparative thin-layer chromatography on silica gel (CHCl3

EtOHNEt3 = 10051) to afford the (Z)-Tamoxifen 6 (633 mg 017 mmol 85 EZ =

gt595) The spectral data was identical to that reported19

Chapter 3

87



2003 Vol 3


Y-K Hernandez V Akama T Baker S J Plattner J J Shapiro L Martinis

S A Benkovic S J Cusack S Alley M R K Science 2007 316 1759 (b)

Zhu Y Zhao X Zhu X Wu G Li W Ma Y Yuan Y Yang J Hu Y Ai

L Gao Q Z J Med Chem 2009 52 4192


S Wakamiya A Pure Appl Chem 2006 78 1413 (c) Jaumlkle F Coord Chem

Rev 2006 250 1107

(4) Salvi L Jeon S-J Fisher E L Carroll P J Walsh P J J Am Chem Soc

2007 129 16119 and references cited therein

(5) For stereoselective synthesis of (trisubstituted alkenyl)(dialkyl)boranes via

addition of XndashBR2 (X = halogen and thiolate) to alkynes see (a) Suzuki A

Pure Appl Chem 1986 58 629 (b) Ishiyama T Nishijima K Miyaura N

Suzuki A J Am Chem Soc 1993 115 7219

(6) For a review of the reactions of alkynyltriorganylborate with electrophiles giving

(trisubstituted alkenyl)(diorganyl)boranes see Negishi E J Organomet Chem

1976 108 281

(7) (a) Ishida N Miura T Murakami M Chem Commun 2007 4381 See also (b)

Ishida N Narumi M Murakami M Org Lett 2008 10 1279

(8) Whiteley C G S Afr J Chem 1982 35 9

(9) The protonolysis of alkenylboranes with acetic acid proceeds in a stereospecific

fashion Brown H C Zweifel G J Am Chem Soc 1959 81 1512

(10) For substitutive 12- -carbon with inversion of

stereochemistry see Koumlbrich G Merkle H R Angew Chem Int Ed 1967 6

74

(11) Inversion of the stereochemistry was also observed in the palladium-catalyzed

cross-coupling reaction of 2-bromo-13-dienes with organozinc reagents Zeng X

Hu Q Qian M Negishi E J Am Chem Soc 2003 125 13636

(12) An alternative mechanism is conceivable the arylpalladium bromide A acts as an

Chapter 3

88

electrophile to place the palladium on the carbon to boron and induces migration

of a phenyl group on boron to the -carbon A similar mechanism has been

assumed for analogous reactions of alkynylborates with alkyl halides most of

which lacked in stereoselectivity The high stereoselectivity obtained in the present

reaction led us to favor the mechanism proposed in the text

(13) Soderquist J A Najafi M R J Am Chem Soc 1986 51 1330

(14) Wiseman H Tamoxifen Molecular Basis of Use in Cancer Treatment and

Prevention Wiley Chichester UK 1994

(15) For representative Tamoxifen syntheses see (a) Millar R B Al-Hassan M I J

Org Chem 1985 50 2121 (b) Potter G A McCague R J Org Chem 1990 55

6184 (c) Brown S D Armstrong R W J Org Chem 1997 62 7076 (d)

Studemann T Knochel P Angew Chem Int Ed 1997 36 93 (e) Tessier P E

Penwell A J Souza F E S Fallis A G Org Lett 2003 5 2989 (f) Itami K

Kamei T Yoshida J-i J Am Chem Soc 2003 125 14670 (g) Shimizu M

Nakamaki C Shimono K Schelper M Kurahashi T Hiyama T J Am Chem

Soc 2005 127 12506 (h) Nishihara Y Miyasaka M Okamoto M Takahashi

H Inoue E Tanemura K Takagi K J Am Chem Soc 2007 129 12634

(16) (a) Itami K Mineno M Muraoka N Yoshida J J Am Chem Soc 2004 126

11778 (b) Flynn A B Ogilvie W W Chem Rev 2007 107 4698

(17) Johns A M Utsunomiya M Incarvito C D Hartwig J F J Am Chem Soc

2006 128 1828

(18) Kramer G W Brown H C J Organomet Chem 1974 73 1

(19) Nishihara Y Miyasaka M Okamoto M Takahashi H Inoue E Tanemura

K Takagi K J Am Chem Soc 2007 12912634

Chapter 4

89

Chapter 4

Iterative Approach to Oligo(arylenevinylene)s Containing

Tetrasubstituted Vinylene Units

Abstract

Monodispersed oligo(arylenevinylene)s containing tetrasubstituted vinylene units were

stereoselectively synthesized in an efficient manner by iteration of two different kinds

of palladium-catalyzed reactions



Chapter 4

90

Introduction

It is one of current topics in organic synthesis to prepare structurally well-defined

oligomeric compounds of higher molecular weight Among various oligomers

oligo(phenylenevinylene)s (OPVs) are of significant interest and have been extensively

studied in the field of organic electronics1 A wide variety of substituted OPVs have

been synthesized and applied to optoelectronic devices such as organic light-emitting

diodes2 and organic solar cells

3 However it is still a formidable task to synthesize

oligo(arylenevinylene)s containing tetrasubstituted vinylene units due to the difficulty

of constructing sterically congested vinylene units in a stereoselective manner4 In this

paper we report an efficient and high yielding method to synthesize such

oligo(arylenevinylene)s of single molecular weight


Initially 4-bromoanisole was treated with 10 equiv of alkynylborate 1a in the

presence of (xantphos)Pd(-allyl)Cl (1 mol ) and (trisubstituted alkenyl)-9-BBN 2

was formed in a stereoselective manner as we previously reported (Scheme 1)5

Although the product 2 contained an alkenylborane moiety it did not couple with

4-bromoanisole in the absence of a base After completion of the initial reaction with

alkynylborate 1a 10 equiv of 4-bromoiodobenzene and 3 equiv of NaOH were directly

added to the reaction mixture The Suzuki-Miyaura coupling reaction took place

chemoselectively at the iodo site to give tetrasubstituted olefin 3 in 87 yield with

excellent stereoselectivity (EZ = lt199) The bromoaryl moiety was retained in the

coupling product 3 due to the reactivity difference between the iodo and bromo groups6

Thus the PdXANTPHOS catalyst was proved to be active enough to promote the two

different kinds of carbonndashcarbon bond forming reactions in one-pot without the need for

any additional catalyst or ligand Through this sequential one-pot procedure the initial

aryl bromide (ie 4-bromoanisole) grew into the second-generation aryl bromide 3

which is expected to be directly used in the reaction with the borate 1a again without

intervention of any activation or deprotection step

Chapter 4

91

Scheme 1 One-Pot Synthesis of Tetrasubstituted Olefin

B

MOMO

[Me4N] +

MeO

Br

I

Br

MeO Br

B

MeO

MOMO MOMO

1a

2 3 87EZ = lt199

NaOH

50 degC

1 mol

(xantphos)Pd(-allyl)Cl

toluene 50 degC

Next aryl bromide 3 was subjected to the second-round sequential one-pot procedure

Treatment of 3 with alkynylborate 1a (11 equiv) followed by direct addition of

4-bromoiodobenzene (11 equiv) and NaOH to the reaction mixture afforded the

third-generation aryl bromide 4 in 92 yield (Scheme 2) Further application of the

third-round sequential procedure to 4 furnished the fourth-generation aryl bromide 5 in

87 yield The sequential procedure was repeated on 5 once to give the

fifth-generation 6 in 82 yield and twice to give the sixth-generation 7 in 85 yield

These oligomers were readily soluble in common organic solvents like toluene THF

AcOEt and chloroform and therefore were isolated with high purity by column

chromatography on silica gel and identified by 1H and

13C NMR and mass spectroscopy

Importantly the yield of each round did not decrease as the molecular size increased

suggesting that further elongation by the iterative method would be possible Thus one

(tetrasubstituted vinylene)phenylene unit could be added to the chain in a stepwise

manner with high efficiency and stereoselectivity by repetition of the sequential one-pot

procedure

Chapter 4

92

Monodispersed oligomers can be divergently synthesized by repeating an iterative

procedure which generally consists of an extension step and an activation step17

An

extending unit possessing a dormant coupling site is initially added to a main chain (an

extension step) The dormant site is then activated to be subsequently coupled with

another extending unit (an activation step) On the contrary the present method to

synthesize OPVs dispenses with the need for activation8 One cycle adding a

vinylene-phenylene unit consists of two different extension steps one extending a

tetrasubstituted vinylene unit and the other extending a phenylene unit Both extension

steps can be executed by the same catalyst system in one-pot Thus this simple

method makes it practical to synthesize a structurally well-defined oligomer of single

molecular weight in an efficient way

Scheme 2 Repetition of the Sequential Procedure

3

MeO

R

Br

4 92

R

MeO

R

Br

n = 2 5 87

n = 3 6 82n = 4 7 85

n

R

1 mol

(xantphos)Pd(-allyl)Cl1a

toluene 50 degC

I

Br

NaOH

E

EE

R = OMOM

A phenylenevinylene chain could be extended into two directions by using

14-dibromobenzene as the starting aryl bromide (Scheme 3) 14-Dibromobenzene

was reacted with the alkynylborates 1a (21 equiv) under the standard conditions and

the subsequent double cross-coupling reaction with 4-bromoiodobenzene (22 equiv)

furnished the dibromide 8 in 86 yield The dibromide 8 was then reacted with the

alkynylborate 1a (30 equiv) to afford diborylated phenylenevinylene intermediate

which was treated with 4-bromoiodobenzene (40 equiv) and NaOH resulting in the

Chapter 4

93

formation of OPV 9 in 92 yield Interestingly OPV 9 exhibited visible blue

fluorescence in solution whereas OPVs 4-7 did not Thus even a small structural

change of the OPVs may cause a significant influence on their photophysical properties

Scheme 3 Extention into Two Directions

Br

Br

R

R

Br

Br

8 86

R

R

Br

R

R

Br

9 92

E E

R = OMOM

Finally the functional group compatibility of the palladium-catalyzed sequential

procedure was exploited to synthesize the structurally diversified oligo(arylenevinylene)

12 (Scheme 4) 4-Bromotrimethylsilylbenzene was reacted with 10 equiv of the

alkynylborate 1b having a 4-methoxyphenyl group on boron and the reaction mixture

was then treated with 10 equiv of 4-bromo-2-fluoroiodobenzene to give 10 in 88

yield The second-round extension was carried out using the alkynylborate 1a (11

equiv) and then 25-dibromothiophene (30 equiv) and NaOH The bi(arylenevinylene)

11 possesing five different aryl groups and two alkyl groups was obtained in 84 yield

Furthermore 11 was subjected to the third-round extension using 11 equiv of the

alkynylborate 1c with a 4-chlorophenyl group on boron and then 11 equiv of

4-(ethoxycarbonyl)iodobenzene to give the ter(arylenevinylene) 12 in 88 yield The

structure of 12 is highly diversified consisting of seven different aryl groups and three

alkyl groups Thus a wide variety of structural modification could be installed at

desired positions by changing arylene and vinylene modules

Chapter 4

94

Scheme 4 Synthesis of Oligo(arylenevinylene) 12

Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

Me3Si

Br

Ph

F

Me3Si

OMe

Br

Ph

F

S

Br

Me3Si

OMe

B

n-Pr

[Me4N]

Cl

B

Ph

[Me4N]

OMe

Br

S

Br

I

EtO2C

MOMO

MOMO

I

Br

F

1b

10 88

11 84

12 88

1a1c

cat Pd

NaOHcat Pd

cat Pd NaOH

Cs2CO3

Conclusions

In conclusion we have developed an efficient iterative method for the synthesis of

oligo(arylenevinylene)s containing tetrasubstituted vinylene units Of note is that an

aryl bromide grew into the next generation aryl bromide in one-pot through two

different kinds of extending steps The method dispenses with the need of activation

steps and thus rapidly increases the molecular complexity Synthesis of new OPVs

and studies on structural features and photophysical properties are now in progress

Chapter 4

95



13C at 75 MHz) JEOL JNM-A500 (

1H at 500 MHz and

13C at 150 MHz) or Varian

400-MR Auto Tune X5 (11

B at 128 MHz) spectrometers Unless otherwise noted CDCl3

was used as a solvent Chemical Shifts are recorded in ppm referenced to a residual

CDCl3 (= 726 for 1H 770 for

13C) CD3CN ( = 194 for

1H =132 for

13C) and

BF3OEt2 ( = 000 for 11

B) High-resolution mass spectra were recorded on Applied

Biosystems Voyager Elite or JEOL JMS-HX110A spectrometer Infrared spectra were

recorded on a SHIMADZU FT-IR 8100 Column chromatography was performed with

silica gel 60 N (Kanto) Preparative thin-layer chromatography was performed with

Silica gel 60 PF254 (Merck) Gel permeation chromatography (GPC) was carried out

with Japan Analytical Industry LC-908 or LC-9204


obtained from commercial suppliers Toluene was dried over Na-benzophenone ketyl

(XANTPhos)Pd(-allyl)Cl9 Ar-9-BBN

10 and 5-Hexyn-1-yl(methoxymethyl)ether

11

were prepared according to the reported procedure

Preparation of Alkynylborates 1a A Typical Procedure for the Preparation of

Alkynylborates 1a 1b

To a stirred solution of 5-hexyn-1-yl(methoxymethyl)ether (204 g 144 mmol) in THF

(200 ml) at -78 ˚C was added n-BuLi (16 M in hexane 90 ml 144 mmol) After 30

minnutes at this temperature phenyl-9-BBN (260 g 130 mmol) was added and the

cooling bath was removed After being stirred for 1 h at room temperature the

reaction was quenched by adding a small amount of methanol Then volatile

materials were removed under reduced pressure The residue was dissolved in

methanol and tetramethylammonium chloride (160 g 146 mmol) was added with

stirring at -78 ˚C resulting in white solid It was collected by filtration and was

washed with cold methanol to give alkynylborate 1a (320 g 77 mmol 60 yield)

Chapter 4

96

B

MOMO

[Me4N]

1a

1H NMR (CD3CN 300 MHz) = 091 (bs 2H) 110-119 (m 1H) 132-196 (m 15H)

202 (t J = 66 Hz 2H) 236-251 (m 2H) 304 (s 12H) 328 (s 3H) 346 (t J = 69

Hz 2H) 454 (s 2H) 678-685 (m 1H) 698-705 (m 2H) 734 (d J = 72 Hz 2H) 13

C NMR (CD3CN 75 MHz) = 210 267 (br) 271 275 282 297 324 349 551

561 681 928 968 1221 1269 1338 11

B NMR (128 MHz) = -180 HRMS

(FAB) Calcd for C22H32BO2 [M-(NMe4)]- 3392495 Found 3392493

B

Ph

[Me4N]

1b

OMe


225 (t J = 72 Hz 2H) 234-249 (m 2H) 263 (t J = 72 Hz 2H) 303 (s 12H) 372

(s 3H) 663-669 (m 2H) 711-728 (m 7H) 13

C NMR (CD3CN 100 MHz) = 242

272 275 324 349 381 554 560 1129 1266 1289 1298 1346 1434 1563 11

B NMR (128 MHz) = -182 HRMS (FAB) Calcd for C25H30BO [M-(NMe4)]-

3572390 Found 3572383

One-Pot Synthesis of Tetrasubstituted Olefin 3 A Typical Procedure for the

Synthesis of Tetrasubstituted Oligo(arylenevinylene)s 3-12

B

MOMO

[Me4N]

+

MeO

Br

1 mol


toluene 50 degC

I

Br

MeO Br

NaOH

3

1a

MOMO

Chapter 4

97

Under an argon atmosphere a mixture of alkynylborate 1 (XANTPhos)Pd(-allyl)Cl

(X mg Y mmol) and aryl halide A in toluene was stirred for time t1 at 50 ˚C Then

aryl halide B and base C were added to the reaction mixture which was stirred for time

t2 and water was added After addition of water the aqueous layer was extracted with

AcOEt (3 times) washed with water (once) brine (once) dried over Na2SO4 and

concentrated The residue was purified by GPC to afford the tetrasubstituted

oligo(arylenevinylene)s

MeO Br

3

MOMONOE

NOE

alkynylborate 1 1a (827 mg 20 mmol) (XANTPhos)Pd(-allyl)Cl (15 mg 20 micromol)

aryl halide A 4-bromoanisole (393 mg 21 mmol) aryl halide B 4-bromoiodobenzene

(566 mg 20 mmol) base C NaOH (240 mg 60 mmol) t1 05 h t2 6 h 1H NMR (300 MHz) = 130-158 (m 4H) 241 (t J = 78 Hz 2H) 327 (s 3H) 337

(t J = 66 Hz 2H) 376 (s 3H) 452 (s 2H) 667-675 (m 4H) 697-702 (m 2H)

709-736 (m 7H) 13

C NMR (75 MHz) = 255 298 356 5510 5514 676 964

1134 1196 1267 1282 1294 13046 13049 1323 1339 1376 1408 1420

1430 1580 HRMS (MALDI-TOF-MS (DCTB) calcd for C27H29BrO3 [M]+ 4801300

Found 4801269 The (Z)-stereochemistry was determined by the 2D NOESY

spectroscopy

MeO

R

Br

4

R

R = OMOM


aryl halide A 3 (963 mg 20 mmol) aryl halide B 4-bromoiodobenzene (622 mg 22

mmol) base C NaOH (240 mg 60 mmol) t1 05 h t2 6 h

Chapter 4

98

1H NMR (300 MHz) = 124-154 (m 8H) 233 (t J = 78 Hz 2H) 242 (t J = 75 Hz

2H) 325 (s 3H) 329 (s 3H) 331-341 (m 4H) 380 (s 3H) 451 (s 2H) 453 (s

2H) 662-678 (m 8H) 697-703 (m 2H) 706-738 (m 12H) 13

C NMR (150 MHz)

= 252 254 295 296 353 354 5502 5504 552 675 676 9629 9632 1131

1196 1265 1267 1281 1282 1285 12941 12942 1303 1304 1306 1324

1343 1377 1385 1390 1400 1413 1414 1418 1429 1435 1579 HRMS

(MALDI-TOF-MS (DIT)) calcd for C47H51BrO5Na [M+Na]+

7972818 Found

7972849

MeO

R

5

R

R = OMOM

R

Br



mmol) base C NaOH (120 mg 30 mmol) t1 1 h t2 12 h 1H NMR (300 MHz) = 122-155 (m12 H) 228-239 (m4H) 246 (t J = 75 2H)

325 (s 3H) 327 (s 3H) 328 (s 3H) 330-342 (m 6H) 374 (s 3H) 450 (s 2H)

452 (s 2H) 454 (s 2H) 654-662 (m 4H) 666-678 (m 8H) 696-704 (m 4H)

712-737 (m 15H) 13

C NMR (75 MHz) = 254 256 296 297 298 3526 3534

355 551 675 676 963 1130 1196 1264 1267 1280 1281 1286 1294 1301

1302 1304 1306 1324 1344 1377 1384 1387 1392 1393 1398 1402 1409

1414 1415 1417 1428 1433 1435 1577 HRMS (MALDI-TOF-MS (DIT)) calcd

for C67H73BrO7Na [M+Na]+

10914437 Found 10914482

Chapter 4

99

MeO

R

6

R

R = OMOM

R

R

Br



mmol) base C NaOH (120 mg 30 mmol) t1 15 h t2 12 h 1H NMR (300 MHz) = 120-156 (m 16H) 226-248 (m 8H) 322-328 (m 12H)

330-341 (m 8H) 371 (s 3H) 448-454 (m 8H) 648-675 (m 16H) 695-703 (m

4H) 714-737 (m 20H) 13

C NMR (75 MHz) = 253 254 256 257 2969 2974

298 350 354 356 550 551 675 676 963 1131 1196 1264 1267 1279

1280 1281 1283 1288 1293 1294 1300 1301 1302 1305 1306 1323 1342

1377 1385 1387 1389 1391 1394 1396 1397 1401 1405 1409 1411 1413



13856057 Found 13856062

MeO

R

7

R

R = OMOM

R

R

R

Br

alkynylborate 1 1a (227 mg 055 mmol) (XANTPhos)Pd(-allyl)Cl (38 mg 50

micromol) aryl halide A 6 (682 mg 050 mmol) aryl halide B 4-bromoiodobenzene (170

mg 060 mmol) base C NaOH (60 mg 15 mmol) t1 15 h t2 12 h 1H NMR (300 MHz) = 118-155 (m 20H) 224-248 (m 10H) 322-340 (m 25H)

374 (s 3H) 447-452 (m 10 H) 649-679 (m 20 H) 690-695 (m 2H) 701-706 (m

2H) 710-736 (m 25H) 13

C NMR (75 MHz) = 2529 2535 256 257 2968

Chapter 4

100

2971 298 351 354 355 356 550 6746 6755 676 963 1131 1195 1264

1267 12795 1280 1281 1283 1285 1287 1293 12937 12944 1301 1302

1304 1306 1322 1343 1377 1384 1387 1389 1390 1391 1394 13976

13979 1401 1404 1408 1409 1412 1413 1416 1427 14318 14321 1434

1435 1578 HRMS (MALDI-TOF-MS (DIT)) calcd for C107H117BrO11Na [M+Na]+

16797677 Found 16797694

8

R

Br

R

Br

R = OMOM


aryl halide A 14-dibromobenzene (236 mg 10 mmol) aryl halide B

4-bromoiodobenzene (622 mg 22 mmol) base C NaOH (240 mg 60 mmol) t1 10 h

t2 24 h 1H NMR (300 MHz) = 128-154 (m 8H) 240 (t J = 78 Hz 4H) 330 (s 6H) 339

(t J = 66 Hz 4H) 456 (s 4H) 668-673 (m 4H) 691 (s 4H) 710-721 (m 8H)

722-737 (m 6H) 13

C NMR (75 MHz) = 254 297 354 551 676 963 1198

1268 1282 1291 1293 1303 1323 1380 1400 1411 1417 1427 HRMS

(MALDI-TOF-MS (DCTB)) calcd for C46H48Br2O4Na [M+Na]+ 8221919 Found

8221905

9

R

R

R = OMOM

R

R

Br

Br


micromol) aryl halide A 8 (412 mg 0050 mmol) aryl halide B 4-bromoiodobenzene

Chapter 4

101

(566 mg 020 mmol) base C NaOH (180 mg 45 mmol) t1 20 h t2 24 h 1H NMR (300 MHz) = 122-154 (m 16H) 229-245 (m 8H) 322 (s 6H) 329 (s

6H) 330-340 (m 8H) 446 (s 4H) 453 (s 4H) 656-672 (m 12H) 688 (s 4H)

704-710 (m 4H) 714-718 (m 4H) 722-740 (m 16H) 13

C NMR (150 MHz) =

254 2962 2963 356 357 5501 5503 674 676 9629 9631 1197 1266

1268 1281 12818 12822 1290 1295 1296 1304 1308 1324 1379 1385

1394 1403 1405 1409 1416 1417 1427 1434 HRMS (MALDI-TOF-MS

(DIT)) calcd for C86H92Br2O8Na [M+Na]+

14335057 Found 14335040

Ph

F

Me3Si

OMe

Br

10

NOE

NOE

alkynylborate 1 1b (432 mg 10 mmol) (XANTPhos)Pd(-allyl)Cl (76 mg 10 micromol)

aryl halide A 4-bromotrimethylsilylbenzene (241 mg 105 mmol) aryl halide B

4-bromo-2-fluoroiodobenzene (301 mg 10 mmol) base C NaOH (120 mg 30 mmol)

t1 05 h t2 12 h 1H NMR (300 MHz) = 024 (s 9H) 260-267 (m 2H) 276-283 (m 2H) 380 (s

3H) 676-686 (m 3H) 694-707 (m 6H) 709-728 (m 5H) 734 (d J = 84 Hz 2H) 13

C NMR (150 MHz) = -11 349 372 552 1135 1189 (d JC-F = 255 Hz)1202

(d JC-F = 92 Hz) 1258 1268 (d JC-F = 35 Hz) 1280 1283 1284 1300 1304 (d

JC-F = 159 Hz) 1326 1329 1332 (d JC-F = 45 Hz) 1339 1387 1417 1418 1430

1585 1596 (d JC-F = 2493 Hz) HRMS (MALDI-TOF-MS (DCTB)) calcd for

C32H32BrFOSi [M]+ 5581390 Found 5581392 The (Z)-stereochemistry was

determined by the 2D NOESY spectroscopy

Chapter 4

102

Ph

F

S

Br

Me3Si

OMe

11

MOMO


micromol) aryl halide A 10 (279 mg 050 mmol) aryl halide B 25-dibromothiophene

(406 mg 15 mmol) base C NaOH (60 mg 15 mmol) t1 05 h t2 12 h 1H NMR (300 MHz) = 024 (s 9H) 116-126 (m 2H) 130-142 (m 2H) 211 (t J

= 78 2H) 264-272 (m 2H) 282-289 (m 2H) 325 (s 3H) 328 (t J = 66 Hz 2H)

382 (s 3H) 448 (s 2H) 587 (d J = 39 Hz 1H) 660 (d J = 39 Hz 1H) 669-676

(m 2H) 684-696 (m 3H) 705-742 (m 16H) 13

C NMR (150 MHz) = -10 244

293 351 362 372 550 552 673 963 1127 1135 1161 (d JC-F = 225 Hz)

1244 (d JC-F = 32 Hz) 1258 1274 12827 12831 12837 12840 12856 12861

1295 1302 1307 (d JC-F = 155 Hz) 1324 1329 1330 (d JC-F = 45 Hz) 1333

1345 1385 1395 (d JC-F = 12 Hz) 1412 1416 (d JC-F = 80 Hz) 1419 1422

1423 1462 1584 1602 (d JC-F = 2465 Hz) HRMS (MALDI-TOF-MS (DCTB))

calcd for C50H52BrFO3SSiNa [M+Na]+ 8582574 Found 8582600

Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

12MOMO

alkynylborate 1 1c (393 mg 0105 mmol) (XANTPhos)Pd(-allyl)Cl (080 mg 10

micromol) aryl halide A 11 (860 mg 010 mmol) aryl halide B

4-(ethoxycarbonyl)iodobenzene (304 mg 011 mmol) base C Cs2CO3 (977 mg 030

mmol) t1 10 h t2 12 h

Chapter 4

103

1H NMR (300 MHz) = 021 (s 9H) 077 (t J = 72 Hz 3H) 112-143 (m 9H)

210-224 (m 4H) 264-272 (m 2H) 279-287 (m 2H) 323-333 (m 5H) 373 (s

3H) 434 (q J = 69 Hz 2H) 451 (s 2H) 580 (d J = 36 Hz 1H) 613 (d J = 39 Hz

1H) 666-672 (m 2H) 679-694 (m 5H) 703-737 (m 20H) 773 (d J = 84 Hz

2H) 13

C NMR (150 MHz) = -11 141 143 225 244 293 350 359 370 385

550 551 607 674 963 1134 1159 (d JC-F = 224 Hz) 1243 (d JC-F = 29 Hz)

1258 1269 1271 12808 12811 12815 12820 12823 12838 12844 1290

1293 1300 1301 (d JC-F = 158 Hz) 1302 1307 1323 (d JC-F = 47 Hz) 13258

13261 1328 1336 1344 1356 1379 1382 1390 (d JC-F = 12 Hz) 1409 14190

14191 14216 (d JC-F = 80 Hz) 14219 14222 1438 1446 1476 1583 1600 (d

JC-F = 2448 Hz) 1664 IR (KBr) = 2955 1717 1509 1273 1248 1111 837 cm-1

HRMS (MALDI-TOF-MS (DIT)) calcd for C70H72ClFO5SSiNa [M+Na]+

11294440

Found 11294465

Chapter 4

104


(1) For reviews see (a) Tour J M Chem Rev 1996 96 537 (b) Martin R E

Diederich F Angew Chem Int Ed 1999 38 1350 (c) Scherf U Top Curr

Chem 1999 201 163

(2) (a) Burroughs J H Bradley D D Brown A R Marks R N Mackey K

Friend R H Burns P L Holmes A B Nature 1990 347 539 (b) Grimsdale A

G Chan K L Martin R M Jokisz P G Holmes A B Chem Rev 2009 109

897

(3) (a) Yu G Hummelen J C Wudl F Heeger A J Science 1995 270 1789 (b)

Segura J L Martin N Guldi D M Chem Soc Rev 2005 34 31 (c) Guumlnes

S Neugebauer H Sariciftci N S Chem Rev 2007 107 1324 (d) Cheng Y-J

Yang S-H Hsu C-S Chem Rev 2009 109 5868

(4) Flynn A B Ogilvie W W Chem Rev 2007 107 4698 and references therein

(5) Ishida N Shimamoto Y Murakami M Org Lett 2009 11 5434

(6) Unrau C M Campbell M G Snieckus V Tetrahedron Lett 1992 33 2773

(7) For iterative synthesis of OPVs by an extensionactivation sequence see (a)

Schenk R Gregorius H Meerholz K Heinze J Muumlllen K J Am Chem Soc

1991 113 2634 (b) Xue C Luo F-T J Org Chem 2003 68 4417 (c) Iwadate

N Suginome M Org Lett 2009 11 1899

(8) For activation-free iterative synthesis of OPVs by two different extension steps

see (a) Maddux T Li W Yu L J Am Chem Soc 1997 119 844 (b) Itami K

Tonogaki K Nokami T Ohashi Y Yoshida J Angew Chem Int Ed 2006 45

2404


2006 128 1828


(11) Sun W C Ng C S Prestwich G D J Org Chem 1992 57 132

Chapter 5

105

Chapter 5

Regioselective Construction of Indene Skeletons by

Palladium-Catalyzed Annulation of Alkynylborates with

o-Iodophenyl Ketones

Abstract

A palladium-catalyzed annulation reaction of alkynylborates with o-iodophenyl ketones

to form indenes is described Highly substituted indene skeletons are efficiently

constructed with site-specific installation of substituents

Reproduced with permission from Eur J Org Chem 2013 1421-1424


Chapter 5

106

Introduction

Indenes are important structural motif found in a number of biologically active

compounds1 For example an indene framework with an exo-alkylidene moiety is

imbedded in sulindac which is a non-steroidal anti-inflammatory drug1a

Dimethindene an oral antihistamine agent has an indene core tethered to an amine

moiety1b

In addition to these commercial medicines indene derivatives have also

been exploited as materials for optoelectronics2 and ligands for transition metal

complexes3 Consequently development of a new method to construct indene

skeletons has been an attractive subject in organic synthesis4

Alkynylboron compounds have been utilized as useful intermediates in organic

synthesis5 We have previously developed the palladium-catalyzed reaction of

alkynylborates with aryl halides6 (Trisubstituted alkenyl)boranes which are otherwise

difficult to synthesize are readily obtained in a regio- and stereoselective fashion

Now the palladium-catalyzed reaction is extended to the construction of indene

skeletons Alkynylborates react with o-iodophenyl ketones to afford 23-disubstituted

indenols with specific installation of 2- and 3-substituents


Alkynylborate 1a and its constitutional isomer 1b were prepared from the

corresponding B-aryl-9-borabicyclo[331]nonane (Ar-9-BBN) and terminal alkyne

according to the reported method6c

The borate 1a (10 equiv) was treated with

o-iodoacetophenone (2a 105 equiv) in the presence of (dpephos)Pd(p-allyl)Cl (1

mol ) at 50 for 1 h (Scheme 1) The reaction mixture was then treated with

hydrogen peroxide to oxidize the organoboron residue Purification by column

chromatography on silica gel afforded 23-diarylindenol 3a in 85 yield In sharp

contrast the reaction of the borate 1b with 2a selectively provided the regioisomeric

indenol 3b in 88 yield Thus the present palladium-catalyzed reaction makes

possible selective production of both regioisomers of 23-diarylindenols which is

difficult to perform using the conventional annulation reaction of o-halophenyl ketones

with 12-diarylalkynes4b

Chapter 5

107

Scheme 1 Reactions of Alkynylborates 1 and o-Iodoacetophenone 2a

B

Ph

Me

O

I

+

1 mol

(dpephos)Pd(-allyl)Cl

toluene 50 degC 1 h

OHMe

Ph

1a

3a 85

MeO

OMe

2a

B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

1b

OMe

2a

OHMe

Ph

OMe

3b 88

[Me4N]

[Me4N]

The selective formation of 3a from 1a and 2a can be explained by the mechanism

shown in scheme 2 which is based on the proposed mechanism of the

palladium-catalyzed reaction of alkynylborates with simple aryl halides6c

Oxidative

addition of 2a to palladium(0) forms arylpalladium A Regioselective

cis-carbopalladation across the carbonndashcarbon triple bond of 1a gives alkenylpalladium

B so that the phenyl group on the anionic boron migrates onto the a-carbon The

carbonndashpalladium bond is substituted with inversion of the stereochemistry to afford

alkenylborane C7 The ketone moiety remains intact during the course of the

palladium-catalyzed reaction The generated B-alkenyl-9-BBN moiety undergoes

intramolecular addition to the carbonyl group8 to form the boron indenolate B Upon

the following oxidative work-up with NaOHH2O2 B is hydrolyzed to the indenol 3a

Chapter 5

108

Scheme 2 Mechanism Proposed for the Formation of 3a

O

I

O

PdI

Pd(0)

B

1a

C

Pd(0)3a

Ar = p-MeOC6H4-

Me Me

OMe

Ar

Ph

B

D

A

Pd

O

ArB

Me

Ph

B

O

ArPh

Me

Me4NI

2a

The present reaction successfully furnished a wide variety of highly-substituted

indenols (Table 1) For example thiophene-substituted 3d and alkyl-substituted 3e

were obtained in 82 and 92 yield respectively The use of o-iodobenzaldehyde

and o-iodobenzophenone gave the corresponding indenols 3f and 3g The indenols

equipped with alkoxy trifluoromethyl and fluorine groups on the aromatic ring (3h-i)

could also be synthesized

Chapter 5

109

Table 1 Synthesis of Indenols 3a

R3

O

I

B

R2

R1

+1 mol Pd

toluene50 degC 1 h

OHR3

R1

R2

OHMe

Ph

S

OHMe

OMe

OHPh

Ph

OMe

3f 72

3h 763j 80

3g 84

3d 82

3c 83

OHMe

Ph

CF3

1 2 3

OHH

Ph

OMe

OHPh

Ph

OMe

O

O

OHPh

3e 92

F

OMe

OHPh

Ph

OMe

F3C

3i 62

R4R4

MeO

[Me4N]

a Reagents and conditions 10 equiv of alkynylborates 1 105 equiv of o-iodophenyl

ketone 2 1 mol of [(dpephos)PdCl(-allyl)] toluene 50 degC 1 h then aq H2O2 aq

NaOH MeOH room temp 2 h Isolated yields are shown

Alkenyl-substituted 3k and alkyl-substituted 3l were also synthesized from

B-alkenyl-9-BBN 1c and B-alkyl-9-BBN 1d respectively [Eqs (1) and (2)] The

formation of 3l is noteworthy from the mechanistic point of view the n-butyl group on

the anionic boron migrates onto the a-carbon in preference to the bridgehead sp3 carbon

of the 9-BBN framework9 This selectivity stands in sharp contrast to that observed in

the reaction with iodine10

Chapter 5

110

OHMe

t-Bu

S

3k 89

B +1 mol Pd

toluene

50 degC 1 h

2a

t-Bu

S

(1)

1c

[Me4N]

OHMe

n-Bu

Me

3l 80

B

n-Bu

+1 mol Pd

toluene50 degC 1 h

2a

Me

(2)

1d

[Me4N]

It was possible to directly synthesize 23-dialkylindenol 3m in one-pot starting from

1-octene 4-phenylbut-1-yne and o-iodoacetophenone 2a without isolation of the

intermediates (Scheme 3) Hydroboration of 1-octene with H-9-BBN in THF afforded

B-n-octyl-9-BBN which was then treated with 4-phenylbut-1-ynyllithium to form the

corresponding lithium alkynylborate A toluene solution containing

o-iodoacetophenone (2a) and (dpephos)Pd(p-allyl)Cl was added to the reaction mixture

which was heated at 50 for 1 h Oxidative work-up and purification by column

chromatography furnished 3m in 91 isolated yield based on 2a

Scheme 3 Synthesis of indenol 3m from 1-octene

n-Hex

13 equiv

Ph

Li

065 equiv

(H-9-BBN) 2

THF rt 1 h -78 degC to rt 1 h

1 mol Pd

toluene 50 degC 1 h

10 equiv 2aOH

Me

n-Oct

11 equiv

3m 91 (based on 2a)

B

n-Oct

PhLi

Ph

The palladium-catalyzed annulation of 1a with 2b gave indenol 3n in 74 yield

which was subjected to further derivatization (Scheme 4) Oxidation of 3n with

manganese(IV) oxide furnished the indenone 4 The following Wolff-Kishner reaction

Chapter 5

111

reduced the carbonyl group without isomerization of the double bond to give indene 5

in 59 yield11

Scheme 4 Synthesis of Indenone 4 and Indene 5

OHH

Ph

OMe

MnO2

DCM rt

Ph

OMe

O

NH2NH2 KOHPh

OMe

4 96 5 59

3n 74

(CH2OH)2 150 C

1a +

CHO

I2b

1 mol Pd

Conclusions

We have described the palladium-catalyzed annulation reaction of alkynylborates with

o-iodophenyl ketones A wide variety of highly-substituted indenols are

regiospecifically synthesized by this method

Chapter 5

112


General NMR spectra were recorded by a Varian Mercury-vx400 (1H at 40044 MHz

and 13

C at 10069 MHz) or Varian 400-MR Auto Tune X5 (11

B at 128 MHz)


were recorded in δ ppm referenced to a residual CDCl3 (δ = 726 for 1H δ = 770 for

13C) CD3CN (δ = 194 for

1H δ = 132 for

13C) and BF3OEt2 (δ = 000 for

11B) IR

measurements were performed by a FTIR SHIMADZU DR-8000 spectrometer fitted

with a Pike Technologies MIRacle Single Reflection ATR adapter High-resolution mass

spectra were recorded by a Thermo Scientific Exactive (ESI) spectrometer Column

chromatography was performed with silica gel 60N (Kanto) Preparative thin-layer

chromatography (PTLC) was performed on silica gel plates with PF254 indicator

(Merck)



Na-benzophenone ketyl Ar-9-BBN12

(DPEPhos)[Pd(π-allyl)Cl]13

and alkynylborate14

were prepared by according to literature procedure


Alkynylborates 1a1b1d-1f

Li

BPh

+

B

Ph

1a


2) Me4NCl MeOH

[Me4N]

MeO

MeO

To a stirred solution of p-ethynylanisole (145 g 110 mmol) in THF (200 mL) at

-78 was added n-BuLi (16 M in hexane 69 mL 110 mmol) After 30 minutes at

this temperature Ph-9-BBN (198 g 100 mmol) was added and the cooling bath was

removed After being stirred for 1 h at room temperature the reaction was quenched by

adding a small amount of methanol Then volatile materials were removed under

reduced pressure The residue was dissolved in methanol and tetramethylammonium

chloride (121 g 110 mmol) was added with stirring at room temperature resulting in

white precipitates It was collected by filtration and washed with cold methanol to give

alkynylborate 1a (27 g 67 mmol 67 yield)

Chapter 5

113

B

Ph

1a

[Me4N]

MeO

1H NMR (CD3CN) δ = 106 (bs 2H) 116-124 (m 1H) 141-202 (m 9H) 241-254

(m 2H) 296 (s 12H) 372 (s 3H) 668-675 (m 2H) 685-691 (m 1H) 700-712 (m

4H) 743 (d J = 64 Hz 2H) 13

C NMR (CD3CN) δ = 256-272 (m) 270 274 322

350 557 560 955 1145 1227 (2C) 1273 1324 1341 1578 The boron-bound

sp2 and sp carbons were not detected due to quadrupolar relaxation

11B NMR

(CD3CN) δ = -177 HRMS (FAB-) Calcd for C23H26BO [M-(NMe4)] 3292082 Found

3292079

B

Ph

1b

[Me4N]

OMe


(m 2H) 295 (s 12H) 374 (s 3H) 666-675 (m 2H) 702-718 (m 5H) 733 (d J =

84 Hz 2H) 13

C NMR (CD3CN) δ = 254-274 (m) 270 273 321 350 554 560

962 1130 1253 1289 1302 1313 1346 1565 The boron-bound sp2 and sp

carbons were not detected due to quadrupolar relaxation 11

B NMR (CD3CN) δ = -180

HRMS (ESI-) Calcd for C23H26BO [M-(NMe4)]- 3292082 Found 3292088

B

nBu

1d

[Me4N]

Me

1H NMR (CD3CN) δ = 022 (bs 2H) 036 (bs 2H) 089 (t J = 72 Hz 3H) 122-134

(m 4H) 136-157 (m 6H) 170-196 (m 4H) 220-234 (m 5H) 304 (s 12H)

697-701 (m 2H) 704-709 (m 2H) 13

C NMR (CD3CN) δ = 152 212 270

271-290 (m) 282 288 318 324 357 561 1279 1296 1314 1344 The

Chapter 5

114

alkyne carbons and boron-bound sp3 carbon of n-Bu group were not detected due to

quadrupolar relaxation 11

B NMR (CD3CN) δ = -178 HRMS (ESI-) Calcd for C21H30B

[M-(NMe4)]- 2932446 Found 2932454

B

Ph

1e

[Me4N]

F3C


(m 2H) 292 (s 12H) 690-696 (m 1H) 710-718 (m 2H) 728 (dd J = 88 08 Hz

2H) 744-752 (m 4H) 13

C NMR (CD3CN) δ = 252-270 (m) 269 273 321 351

560 958 1230 1256 (q JC-F = 2687 Hz) 1258 (q JC-F = 37 Hz) 1262 (q JC-F =

315 Hz) 1275 1317 1342 1343 The boron-bound sp2 and sp carbons were not

detected due to quadrupolar relaxation 11

B NMR (CD3CN) δ = -176 HRMS (FAB-)

Calcd for C23H23BF3 [M-(NMe4)]- 3671850 Found 3671849

B

Ph

1f

[Me4N]

S


(m 5H) 238-250 (m 2H) 304 (s 12H) 679 (dd J = 88 08 Hz 1H) 691 (dd J =

48 32 Hz 1H) 703-719 (m 6H) 13

C NMR (CD3CN) δ = 266 272 270-286 (m)

323 348 560 962 1231 1256 1266 1274 1290 1300 1314 The boron-bound

sp2 and sp

3 carbons were not detected due to quadrupolar relaxation

11B NMR

(CD3CN) δ = -181 HRMS (ESI-) Calcd for C20H22BS [M-(NMe4)]

- 3051541 Found

3051541

Chapter 5

115

Preparation of Alkynylborates 1c

(H-9BBN) 2

H tBu

THF 0 degC

THF -78 degC to rt

2) Me4NCl MeOH

Li

1)S

B

1c

[Me4N]

S

tBu

Under an argon atmosphere a solution of 33-dimethyl-1-butyne (084 g 10 mmol) in

THF (15 mL) was added to (H-9-BBN)2 (122 g 50 mmol) and then the mixture was

stirred for 1 h at room temperature In another flask nBuLi (156 M in hexane 73 mL

114 mmol) was added dropwise to a solution of 4-phenylbut-1-yne (130 g 100 mmol)

in THF (15 mL) at -78 After stirred for 30 minutes at this temperature the two

solutions were combined and then the cooling bath was removed After being stirred for

1 h at room temperature the reaction was quenched by adding a small amount of

methanol Then volatile materials were removed under reduced pressure The residue

was dissolved in methanol and tetramethylammonium chloride (121 g 110 mmol) was

added with stirring at room temperature After being concentrated under reduced

pressure the residue was dissolved in methanol again and stirred at -78 resulting in


alkynylborate 1c (760 mg 20 mmol 20 yield)

B

1c

[Me4N]

S

tBu

1H NMR (CD3CN) δ= 038 (bs 2H) 096 (s 9H) 136-156 (m 6H) 173-204 (m

4H) 222-235 (m 2H) 306 (s 12H) 552 (d J = 172 Hz 1H) 591 (d J = 176 Hz

1H) 691 (dd J = 52 12 Hz 1H) 698 (dd J = 28 12 Hz 1H) 722 (dd J = 28 50

Hz 1H) 13

C NMR (CD3CN) δ = 273 276 278-296 (m) 311 327 341 352 561

908 1228 1251 1298 1314 1411 The boron-bound sp2 and sp carbons were not


B NMR (CD3CN) δ= -181 HRMS (ESI-)

Calcd for C20H28BS [M-(NMe4)]- 3112010 Found 3112016

Chapter 5

116

PalladiumDPEPhos-Catalyzed Reaction of Alkynylborate 1a with

o-Iodoacetophenone (2a)

Under an argon atmosphere a toluene solution (10 mL) of alkynylborate 1a (8068 mg

020 mmol) dpephos)PdCl(π-allyl) (144 mg 0002 mmol) and o-iodoacetophenone

(2a) was stirred for 1 h at 50 To the reaction mixture were added aqueous H2O2 (05

mL 30 wt) aqueous NaOH (05 mL 20 wt) and MeOH (05 mL) at 0 After

being stirred for 2 h at room temperature the resulting mixture was diluted with water

and extracted with ethyl acetate (3times15 mL) The combined organic layers were washed

by brine dried over MgSO4 and concentrated under reduced pressure The residue was

purified by preparative thin-layer chromatography on silica gel (hexaneethyl acetate =

51) to afford the indenol 3a (559 mg 017 mmol 85 yield)

OHMe

3aOMe

NOE

no NOE

IR (ATR) 3315 1508 1248 752 694 cm-1

1H NMR δ = 159 (s 3H) 204 (bs 1H)

382 (s 3H) 684-690 (m 2H) 721-730 (m 8H) 742-748 (m 2H) 751-755 (m

1H) 13

C NMR δ = 239 552 832 1139 1208 1218 1265 1268 1272 1280


C23H21O2 [M+H]+ 3291536 Found 3291556

OHMe

OMe

3b

NOE

no NOE

IR (ATR) 3319 1508 1248 760 702 cm-1

1H NMR δ = 160 (s 3H) 208 (s 1H)

378 (s 3H) 674-680 (m 2H) 718-723(m 1H) 724-744 (m 9H) 750-755 (m

1H) 13

C NMR δ = 241 551 833 1134 1205 1218 1263 1270 1274 1284

1286 1293 1306 1350 1376 1423 1464 1495 1587 HRMS (ESI-) Calcd for

Chapter 5

117

C23H20O2Cl [M+Cl]- 3631146 Found 3631148

OHMe

Ph

3cCF3

IR (ATR) 3298 1319 1121 750 696 cm-1

1H NMR δ = 160 (s 3H) 210 (bs 1H)

716-722 (m 1H) 723-732 (m 5H) 737-747 (m 4H) 752-764 (m 3H) 13

C NMR

δ = 240 833 1205 1221 1241 (q JC-F = 2701 Hz) 1255 (q JC-F = 37 Hz) 1269

1277 1282 1286 1293 1295 (q JC-F = 322 Hz) 1296 1341 1373 1385 1414

1485 1493 HRMS (APCI-) Calcd for C23H16F3O [M-H]

- 3651159 Found 3651159

OHMe

Ph

3d

S

IR (ATR) 3319 1350 1088 752 694 cm-1

1H NMR δ = 177 (s 3H) 209 (bs 1H)

696-702 (m 2H) 718 (dd J = 52 Hz 12Hz 1H) 723-730 (m 2H) 735-740 (m

3H) 742-752 (m 3H) 753-758 (m 1H) 13

C NMR δ = 254 833 1207 1216

1259 1265 1266 1275 1282 1287 1290 1294 1347 1360 1374 1410 1426

1493 HRMS (ESI+) Calcd for C20H17OS [M+H]

+ 3050995 Found 3050992

OHMe

OMe

3e

IR (ATR) 3310 1508 1244 1034 758 cm-1

1H NMR δ = 144 (s 3H) 158-202 (m

9H) 307 (quintet J = 88 Hz 1H) 385 (s 3H) 696 (d J = 88 Hz 2H) 718-738 (m

5H) 747 (d J = 68 Hz 1H) 13

C NMR δ = 238 266 267 305 311 382 552

822 1136 1211 1219 1257 12789 12793 1304 1406 1409 1467 1499

1588 HRMS (ESI+) Calcd for C22H28O2N [M+NH4]

+ 3382115 Found 3382104

Chapter 5

118

OHH

Ph

3fOMe

MeO

IR (ATR) 3472 1601 1508 1244 704 cm-1

1H NMR δ = 174 (d J = 88 Hz 1H)

379 (s 3H) 386 (s 3H) 563 (d J = 84 Hz 1H) 674 (d J = 24 Hz 1H) 679 (dd J

= 80 Hz 24 Hz 1H) 692-697 (m 2H) 718-730 (m 5H) 732-736 (m 2H) 753 (d

J = 84 Hz 1H) 13

C NMR δ = 552 555 766 1072 1109 1143 1244 1267 1272

1283 1292 1303 1342 1363 1390 1445 1457 1592 1606 HRMS (ESI+)

Calcd for C23H21O3 [M+H]+ 3451485 Found 3451484

OHPh

Ph

3gOMe

IR (ATR) 3422 1508 1244 1028 746 698 cm-1

1H NMR δ = 248 (s 1H) 385 (s

3H) 695 (d J = 88 Hz 2H) 704-714 (m 5H) 715-732 (m 7H) 736-740 (m 2H)

755 (d J = 88 Hz 2H) 13

C NMR δ = 552 868 1141 1210 1231 1250 1268

12698 12702 1271 1278 12836 12844 1294 1304 1340 1402 1417 1427

1466 1508 1591 HRMS (ESI+) Calcd for C28H23O2 [M+H]

+ 3911693 Found

3911718

OHPh

Ph

3hOMe

O

O

IR (ATR) 3362 1470 1244 1034 696 cm-1

1H NMR δ = 239 (s 1H) 385 (s 3H)

591 (dd J = 164 16 Hz 2H) 673 (d J = 44 Hz 2H) 690-696 (m 2H) 702-708

(m 5H) 720-736 (m 5H) 749-754 (m 2H) 13

C NMR δ = 552 863 1012 1024

Chapter 5

119

1049 1142 1249 12690 12692 1270 1278 1285 1292 1304 1340 1367

1398 1420 1450 1458 1469 1478 1592 HRMS (EI+) Calcd for C29H22O4 [M]

+

4341518 Found 4341505

OHPh

Ph

3iOMe

F3C

IR (ATR) 3545 1508 1321 1115 696 cm-1

1H NMR δ = 249 (s 1H) 387 (s 3H)

694-700 (m 2H) 704-715 (m 5H) 723-738 (m 6H) 742-755 (m 4H) 13

C NMR

δ = 553 866 1145 1177 (q JC-F = 37 Hz) 1233 1241 (q JC-F = 36 Hz) 1242 (q

JC-F = 2702 Hz) 1249 1260 1275 1276 1280 1287 1295 1304 1308 (q JC-F =

323 Hz) 1334 1393 1407 1437 1481 1542 1595 HRMS (APCI-) Calcd for

C29H21F3O2Cl [M+Cl]- 4931177 Found 4931192

OHPh

3j

F

OMe

IR (ATR) 3356 1242 1028 741 696 cm-1

1H NMR δ = 164-178 (m 2H) 183-208

(m 7H) 316 (quintet J = 84 Hz 1H) 376 (s 3H) 675-680 (m 2H) 686-698 (m

4H) 719-737 (m 6H) 13

C NMR δ = 2675 2681 308 310 383 551 862 1114

(d JC-F = 233 Hz) 1136 1143 (d JC-F = 218 Hz) 1220 (d JC-F = 80 Hz) 1252

1268 1271 1283 1303 1371 (d JC-F = 29 Hz) 1410 1418 (d JC-F = 15 Hz)

1474 (d JC-F = 43 Hz) 1538 (d JC-F = 73 Hz) 1589 1619 (d JC-F = 2443 Hz)

HRMS (EI+) Calcd for C27H25OF2 [M]

+ 4001839 Found 4001835

OHMe

S

tBu

3k

Chapter 5

120

IR (ATR) 3298 1358 1078 756 689 cm-1

1H NMR δ = 111 (s 9H) 168 (s 3H)

188 (s 1H) 640 (d J = 164 Hz 1H) 656 (d J = 164 Hz 1H) 718-730 (m 4H)

739-751 (m 3H) 13

C NMR δ = 257 295 340 822 1169 1204 1215 1242

1255 1262 1283 1285 1324 1346 1415 1452 1462 1506 HRMS (ESI+)

Calcd for C20H23OS [M+H]+ 3111464 Found 3111464

OHMe

nBu

OMe3l

IR (ATR) 3335 1508 1084 918 758 cm-1

1H NMR δ = 085 (t J = 72 Hz 3H) 130

(tt J = 72 72 Hz 2H) 141-167 (m 6H) 229-250 (m 5H) 702-706 (m 1H)

716-728 (m 6H) 744-748 (m 1H) 13

C NMR δ = 138 213 232 237 252 314

829 1198 1215 1256 1282 1286 1291 1318 1370 1374 1430 1492 1496

HRMS (APCI+) Calcd for C21H25O [M+H]

+ 2931900 Found 2931890

The Synthesis of 23-Dialkylsubstituted Indenol 3m from 1-Octene

4-Phenyl-1-butyne and o-Iodoacetophenone (2a)

nHex

(H-9BBN) 2

THF rt THF -78 degC to rt

Li

Ph

B

nOct

Li

Ph

Me

O

I


toluene 50 degC 1 h

H2O2 aq

NaOH aq

OHMe

nOct

Ph3m

MeOH

Under an nitrogen atmosphere a solution of 1-octene (1459 mg 130 mmol) in THF

(20 mL) was added to (H-9-BBN)2 (1586 mg 065 mmol) and then the mixture was

stirred for 1 h at room temperature In another flask n-BuLi (069 mL 16 M in hexane

Chapter 5

121

110 mmol) was added dropwise to a solution of 4-phenylbut-1-yne (1432 mg 110

mmol) in THF (2 mL) at -78 After stirred for 30 minutes at this temperature the two


1 h at room temperature (dpephos)PdCl(π-allyl) (721 mg 0010 mmol) and a solution

of o-iodoacetophenone (2461 mg 100 mmol) in toluene (2 mL) were added The

reaction mixture was stirred for 1 h at 50 To the mixture were added aqueous H2O2

(1 mL 30 wt) aqueous NaOH (1 mL 20 wt) and MeOH (1 mL) at 0 After

being stirred for 2 h at room temperature the resulting mixture was quenched by adding

water and extracted with ethyl acetate (3times10 mL) The combined organic layers were

washed by brine dreid over MgSO4 and concentrated under reduced pressure The

residue was purified by preparative thin-layer chromatography on silica gel

(hexaneethyl acetate = 101) to afford the indenol 3m (3323 mg 092 mmol 92

yield)

OHMe

nOct

Ph3m

IR (ATR) 3335 1456 1078 752 698 cm-1

1H NMR δ = 096 (t J = 68 Hz 3H)

129-156 (m 15H) 160 (s 1H) 208-227 (m 2H) 274-281 (m 2H) 287-294 (m

2H) 719-728 (m 5H) 729-736 (m 3H) 742 (d J = 72 Hz 1H) 13

C NMR δ = 141

226 234 247 277 293 294 295 304 319 345 825 1186 1213 1252 1260

1282 1283 1284 1351 1417 1425 1489 1494 HRMS (EI+) Calcd for C26H34O4

[M]+ 3622610 Found 3622619

OHH

Ph

OMe

3n

IR (ATR) 3354 1508 1246 764 692 cm-1

1H NMR δ = 185 (bs 1H) 386 (s 3H)

567 (s 1H) 692-697 (m 2H) 718-738 (m 10H) 763-766 (m 1H) 13

C NMR δ =

552 773 1143 1206 1237 1263 1268 1272 1283 1287 1292 1303 1342

1393 1432 1440 1443 1592 HRMS (APCI-) Calcd for C22H17O2 [M-H]

- 3131234

Found 3131237

Chapter 5

122

The 1H

13C NMR and HRMS spectra were agreed with the reported value

15

Synthesis of indenone 4 and indene 5

OHH

Ph

OMe

3n

MnO2

DCM rt

Ph

OMe

4

O

MnO2 (170 mg 2 mmol) was dried under vacuum for 5 h at 120 Under an argon

atomosphere the solution of indenol 3n (314 mg 01 mmol) was added at room

temperature After being stirred for 3 h the reaction mixture was filtered through a pad

of celite and concentrated under reduced pressure The residue was purified by


afford the indenone 4 (299 mg 0096 mmol 96 yield)

The 1H

13C NMR spectra were agreed with the reported value

16

Ph

OMe

4

O

(CH 2OH)2

NH2NH2

KOH Ph

OMe

5

Under an argon atomosphere an ethylene glycol solution (1 mL) of indenone 4 (312

mg 01 mmol) hydrazine (04 mL) and 2N KOH aq (10 L 002 mmol) was stirred for

5 h at 150 and water was added The aqueous layer was extracted with AcOEt (3

times) washed with water (once) brine (once) dried over MgSO4 and concentrated

under reduced pressure The residue was purified by preparative thin-layer

chromatography on silica gel (hexaneethyl acetate = 41) to afford the indene 5 (176

mg 0059 mmol 59 yield)

The 1H


5

Chapter 5

123



97ndash114 (b) Nicholson A N Pascoe P A Turner C Ganellin C R

Greengrass P M Casy A F Mercer A D Br J Pharmacol 1991 104

270ndash276 (c) Huffman J W Padgett L W Curr Med Chem 2005 12

1395ndash1411



17638ndash17640

(3) (a) Cadierno V Diez J Gamasa M P Gimeno J Lastra E Coord Chem Rev

1999 193ndash195 147ndash205 (b) Stradiotto M McGlinchey M J Coord Chem Rev

2001 219ndash221 311ndash378 (c) Zargarian D Coord Chem Rev 2002 233ndash234

157ndash176 (d) Leino R Lehmus P Lehtonen A Eur J Inorg Chem 2004

3201ndash3222

(4) (a) Liebeskind L S Gasdaska J R McCallum J S Tremont S J J Org

Chem 1989 54 669ndash677 (b) Robinson N P Main L Nicholson B K J

Organomet Chem 1989 364 C37ndashC39 (c) Romines K R Lovasz K D

Mizsak S A Morris J K Seest E P Han F Tulinsky J Judge T M

Gammill R B J Org Chem 1999 64 1733ndash1737 (d) Quan L G Gevorgyan

V Yamamoto Y J Am Chem Soc 1999 121 3545ndash3546 (e) Halterman R L

Zhu C Tetrahedron Lett 1999 40 7445ndash7448 (f) Xi Z Guo R Mito S Yan

H Kanno K Nakajima K Takahashi T J Org Chem 2003 68 1252ndash1257

(g) Lautens M Marquardt T J Org Chem 2004 69 4607ndash4614 (h) Chang

K-J Rayabarapu D K Cheng C-H J Org Chem 2004 69 4781ndash4787 (i)

Ming-Yuan L Madhushaw R J Liu R-S J Org Chem 2004 69 7700ndash7704

(j) Miura T Murakami M Org Lett 2005 7 3339ndash3341 (k) Shintani R

Okamoto K Hayashi T Chem Lett 2005 34 1294ndash1295 (l) Kuninobu Y

Kawata A Takai K J Am Chem Soc 2005 127 13498ndash13499 (m) Tsukamoto

H Ueno T Kondo Y Org Lett 2007 9 3033ndash3036 (n) Harada Y Nakanishi

J Fujihara H Tobisu M Fukumoto Y Chatani N J Am Chem Soc 2007

129 5766ndash5771 (o) Tsuchikama K Kasagawa M Endo K Shibata T Synlett

2010 97ndash100 (p) Zhou F Han X Lu X J Org Chem 2011 76 1491ndash1494

Chapter 5

124

(q) Patureau F W Besset T Kuhl N Glorius F J Am Chem Soc 2011 133

2154ndash2156 (r) Tran D N Cramer N Angew Chem Int Ed 2011 50

11098ndash11102 and references cited therein

(5) (a) Negishi E J Organomet Chem 1976 108 281ndash324 (b) Molander G A

Katona B W Machrouhi F J Org Chem 2002 67 8416ndash8423 (c) Goswami

A Maier C-J Pritzkow H Siebert W Eur J Inorg Chem 2004 2635ndash2645

(d) Yamamoto Y Ishii J Nishiyama H Itoh K J Am Chem Soc 2004 126

3712ndash3713 (e) Suginome M Shirakura M Yamamoto A J Am Chem Soc

2006 128 14438ndash14439 (f) Browne D L Vivat J F Plant A Gomez-Bengoa

E Harrity J P A J Am Chem Soc 2009 131 7762ndash7769 (g) Iannazzo L

Vollhardt K P C Malacria M Aubert C Gandon V Eur J Org Chem 2011

3283ndash3292

(6) (a) Ishida N Miura T Murakami M Chem Commun 2007 4381ndash4383 (b)

Ishida N Narumi M Murakami M Org Lett 2008 10 1279ndash1281 (c) Ishida

N Shimamoto Y Murakami M Org Lett 2009 11 5434ndash5437 (d) Ishida N

Shimamoto Y Murakami M Org Lett 2010 12 3179ndash3181 (e) Ishida N

Ikemoto W Murakami M Org Lett 2011 13 3008ndash3011 (f) Ishida N

Narumi M Murakami M Helv Chim Acta 2012 95 2474ndash2480

(7) For substitutive 12-migration from boron to the α-carbon with inversion of


74

(8) Jacob III P Brown H C J Org Chem 1977 42 579ndash580

(9) For related reactions involving the preferential migration of the alkyl groups on

boron over the bridgehead carbon of the 9-BBN framework see (a) Brown H C

Nambu H Rogic M M J Am Chem Soc 1969 91 6852ndash6854 (b) Miyaura

N Tagami H Itoh M Suzuki A Chem Lett 1974 3 1411ndash1414

(10) Slayden S W J Org Chem 1981 46 2311ndash2314

(11) Anstead G M Ensign J L Peterson C S Katzenellenbogen J A J Org

Chem 1989 54 1485ndash1491



2006 128 1828

Chapter 5

125


(15) Chang K-J Rayabarapu D K Cheng C-H J Org Chem 2004 69

4781-4787


Chem 1989 54 1485

Chapter 5

126

127

List of Publication

Chapter 1

Solar-Driven Incorporation of Carbon Dioxide into α-Amino Ketones

Naoki Ishida Yasuhiro Shimamoto and Masahiro Murakami

Angew Chem Int Ed 2012 51 11750-11752

Chapter 2


Benzosultams

Naoki Ishida Yasuhiro Shimamoto Takaaki Yano Masahiro Murakami

J Am Chem Soc 2013 135 19103-19106

Chapter 3

Stereoselective Synthesis of (E)-(Trisubstituted alkenyl)borinic Esters

Stereochemistry Reversed by Ligand in the Palladium-Catalyzed Reaction of

Alkynylborates with Aryl Halides


Org Lett 2009 11 5434-5437

Chapter 4


Units


Org Lett 2010 12 3179-3181

Chapter 5

Regioselective Construction of Indene Skeletons by Palladium-Catalyzed

Annulation of Alkynylborates with o-Iodophenyl Ketones

Yasuhiro Shimamoto Hanako Sunaba Naoki Ishida and Masahiro Murakami

Eur J Org Chem 2013 1421-1424

Other Publication

Construction of Indole Skeletons by Sequential Actions of Sunlight and Rhodium on

α-Amino Acetophenones

Naoki Ishida David Nečas Yasuhiro Shimamoto and Masahiro Murakami

Chem Lett 2013 42 1076

Exploration of New Reactivities of Azetidinols and Alkynylborates

Yasuhiro Shimamoto

2014

Preface




alkynyl borates
































encouragement

Yasuhiro Shimamoto



Kyoto University

Contents


Chapter 1


Chapter 2


Benzosultams 29

Chapter 3



Halides 67

Chapter 4


Units 89

Chapter 5





1









sultams














sun

CO2energy charge

Ph

O

NTs

Me

N

Ts

OHPh

OO

O

Ph

NHTs


2


benzosultams




developed456


shift7

MH14-metal shift

1

2 3

4

HM

1

2 3

4

H M1

23

4

5

M H1

23

4

515-metal shift






N

Ts

Ph OHMe

SN

MeO O

Ph OH

cat Rh





chemistry10






We


alkynylborates13

R1 B

R2

R2

R2

+ R3 Br

R3

R1 R2

B

R2

R2


3






obtained

Et

Ph

Ph

B O+

PhBr LPd(-allyl)Cl

L = XANTPhos

LPd(-allyl)Cl

L = P(o-tol)3 Ph

Et

Ph

B O

B

Et

Ph

Et

Ph

B

Ph

Ph

Et

B

Ph

Me3NO

Me3NO

[Me4N]







MeO

Br

I

Br

NaOH

R Ph

MeO Br

B

R

Ph

RB

Ph

OMe

[Me4N]

R Ph

MeOR Ph

Br

R =OMOM

n

B

R

Ph

[Me4N] I

Br

NaOH

R Ph

MeOR Ph

Br

n = 2~4

Pd-XANTPhos

Pd-XANTPhos






4


regioselectively

I

Me

O+

MeOH

R2

R1Pd-XANTPhosB

R2

R1

[Me4N]


5

Reference





































6








10990




2003 Vol 3





Q Z J Med Chem 2009 52 4192



2006 250 1107



2419













7



17638ndash17640


8

Chapter 1

9

Chapter 1


Ketones

Abstract






Chapter 1

10

Introduction







2 One







starting substances


CO2

sun

CO2energy charge

high energy

intermediates











8






Chapter 1

11


Ph

O

NTs

Mesolar light

N

Ph OH

Ts

2a 91

1aDMA







over 04 kWm-2



in eight hours on


Figure





kWhm-2



Chapter 1

12


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

0

20

40

60

80

100

0 1 2 3 4 5 6











(56)

Chapter 1

13


40 equiv Cs2CO3

1 atm CO2

DMA 60 degC

OO

O

Ph

NHTs

3a 93

N

Ph OH

Ts

2a








N

Ph O

Ts

A

N

Ph O

Ts

B

O

O

OO

O

Ph

NTs

CO2

H

C

Cs2CO3

CsHCO 3

Cs

Cs

Cs

2

1

N

Ph OH

Ts

2a

OO

O

Ph

NHTs

3a












N

Ts

OHPh

4

Chapter 1

14




solar light

CO2Cs2CO3

60degCDMAPh

O

NTs

Me

1a

OO

O

Ph

NHTs

3a 83






chloro groups10





Ar

O

NR

Me OO

O

Ar

NHR3

1

OO

O

NHTs3b 80

MeO

OO

O

NHTs3c 57

F3C

OO

O

NHTs3d 73

Cl

OO

O

NHTs3e 85

Br

OO

O

Ph

NH

3f 87

O2S OMe

OO

O

Ph

NH

3g 85

O2S CF3

OO

O

Ph

NH

3h 87

O2S

N

solar lightCO2

Cs2CO3

60degCDMA




Chapter 1

15

Conclusions















Chapter 1

16












indicator (Merck)






Ph

O

NTs

MeTsClMeNH2 +

Et2OTsNHMe

CH3CN

K2CO3












Chapter 1

17


Ph

O

NTs

Me


745-751 (m 2H) 760 (tt J = 76 12 Hz 1H) 771-775 (m 2H) 795-799 (m 2H)

13C NMR δ = 215 356 560 1275 1282 1288 1297 1338 1347 1348 1436


+ 3041002 Found mz 3040994 IR

(ATR) 1693 1339 1227 1157 743 cm-1

O

NTs

Me

1bMeO


733 (d J = 80 Hz 2H) 770-774 (m 2H) 796-802 (m 2H) 13

C NMR δ = 215

355 555 558 1139 1275 1277 1296 1307 1346 1436 1640 1921 HRMS


+ 3341108 Found mz 3341101 IR (ATR) 1688

1601 1329 1180 1159 cm-1

O

NTs

Me

1cF3C


= 84 Hz 2H) 776 (d J = 84 Hz 2H) 812 (d J = 84 Hz 2H) 13

C NMR δ = 215

357 564 1234 (q JC-F = 2711 Hz) 1259 (q JC-F = 37 Hz) 1276 1288 1298



1121 1109 cm-1

Chapter 1

18

O

NTs

Me

1dCl


(m 2H) 771 (d J = 80 Hz 2H) 792-796 (m 2H) 13

C NMR δ = 216 356 561



1159 1088 cm-1

O

NTs

Me

1eBr


= 84 Hz 2H) 771 (d J = 84 Hz 2H) 786 (d J = 84 Hz 2H) 13

C NMR δ = 215

356 561 1275 1291 1297 1298 1321 1334 1344 1438 1930 HRMS (ESI+)


1223 1155 810cm-1

Ph

O

NS

Me

1f

OMe

OO

1H NMR δ = 282 (s 3H) 389 (s 3H) 456 (s 2H) 698-703 (m 2H) 746-751 (m

2H) 761 (tt J = 72 12 Hz 1H)776-781 (m 2H) 796-800 (m 2H) 13

C NMR δ =

356 556 561 1142 1283 1288 1294 1297 1338 1348 1630 1938 HRMS


+ 3200951 Found mz 3200943 IR (ATR) 1692

1342 1259 1155 741 cm-1

Chapter 1

19

Ph

O

NS

Me

1g

CF3

OO


780 (d J = 84 Hz 2H) 790-794 (m 2H) 798 (d J = 80 Hz 2H) 13

C NMR δ =

356 558 1233 (q JC-F = 2711 Hz) 1261 (q JC-F = 36 Hz) 12796 12799 1289



1059 748 cm-1

Ph

O

NS

Me

1h

N

OO

1H NMR δ = 302 (s 3H) 486 (s 2H) 744-753 (m 3H) 757-762 (m 1H)

788-798 (m 4H) 870 (ddd J = 48 16 08 Hz 1H)13

C NMR δ = 363 569 1224



752 cm-1


Ph

O

NTs

Mesolar light

N

Ph OH

TsDMA rt

1a

2a








Chapter 1

20


N

Ph OH

Ts


2H) 728-737 (m 5H) 740 (d J = 80 Hz 2H) 779 (d J = 80 Hz 2H) 13

C NMR δ

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS




N 458 O 1555 S 1058 IR (ATR) 3477 1333 1184 1148 671 cm-1


N

Ph OH

Ts

2a

40 equiv Cs2CO3

1 atm CO2

DMA 60 C

OO

O

Ph

NHTs

3a








mmol 93 yield)

Chapter 1

21



40 equiv Cs2CO3

60 CPh

O

NR

Me OO

O

Ph

NHR3a

1a

solar light

DMA rt

1 atm CO2











OO

O

Ph

NHTs



726-732 (m 4H) 734-743 (m 3H) 769-773 (m 2H) 13

C NMR δ = 215 503

724 850 1242 1269 1292 1299 1365 1381 1439 1542 HRMS (ESI+) Calcd

for C17H18NO5S M+H+


C 5878 H 493 N 403 O 2303 S 923 Found C 5871 H 496 N 389 O

2284 S 932 IR (ATR) 3261 1773 1435 1319 1045 cm-1

Chapter 1

22

OO

O

NHTs

3b

MeO



56 Hz 1H) 688-693 (m 2H) 719-724 (m 2H) 728 (d J = 80 Hz 2H) 770 (d J =

84 Hz 2H) 13

C NMR δ = 215 503 554 724 848 1145 1256 1269 1298


+

3781006 Found mz 3780996 IR (ATR) 3238 1794 1518 1329 1057 723 cm-1

OO

O

NHTs

3c

F3C



729 (d J = 84 Hz 2H) 746 (d J = 84 Hz 2H) 765-771 (m 4H) 13

C NMR δ =

215 501 722 846 1235 (q JC-F = 2704 Hz) 1249 1263 (q JC-F = 37 Hz) 1268



1067 cm-1

OO

O

NHTs

3d

Cl



722-727 (m 2H) 728 (d J = 84 Hz 2H) 735-739 (m 2H) 769 (d J = 84 Hz 2H)

13C NMR δ = 215 502 723 847 1257 1268 1294 1300 1353 1364 1365


+ 3820510 Found mz

Chapter 1

23

3820506 IR (ATR) 3250 1800 1325 1155 1069 cm-1

OO

O

NHTs

3e

Br



716-720 (m 2H) 728 (d J = 80 Hz 2H) 750-755 (m 2H) 766-770 (m 2H) 13

C

NMR δ = 215 501 723 847 1235 1260 1268 1300 1323 1364 1370 1441


+ 4260005 Found mz 4260003

IR (ATR) 3252 1800 1331 1175 1057 cm-1

OO

O

Ph

NH

SO

O

OMe



693-698 (m 2H) 727-732 (m 2H) 734-744 (m 3H) 773-778 (m 2H) 13

C NMR

δ = 503 556 724 849 1145 1242 1291 1292 1310 1381 1541 1632 HRMS


+ 3640849 Found mz 3640836 IR (ATR) 3246

1801 1325 1155 1067 cm-1

OO

O

Ph

NH

SO

O

CF3

3g

Chapter 1

24



2H) 735-744 (m 3H) 775 (d J = 88 Hz 2H) 796 (d J = 84 Hz 2H) 13

C NMR δ

= 505 725 851 1231 (q JC-F = 2711 Hz) 1241 1265 (q JC-F = 37 Hz) 1274



1161 1105 cm-1

OO

O

Ph

NH

SO

O

N




1H) 798 (d J = 76 Hz 1H) 866 (d J = 44 Hz 1H) 13

C NMR δ = 510 723 849



1175 1063 cm-1


N

Ts

OHPh

N

Ts

O CeCl 3

PhLi

THF -78 C to rt

4






Chapter 1

25






N

Ts

OHPh


351-364 (m 4H) 726-738 (m 7H) 773-777 (m 2H) 13

C NMR δ = 215 396

469 608 804 1250 1276 1280 1286 1297 1339 1418 1435 HRMS (ESI+)


1325 1159 1101 770 cm-1

Chapter 1

26











Soc 2011 133 12881

























25 312

Chapter 1

27








Chapter 1

28

Chapter 2

29

Chapter 2



Abstract







Chapter 2

30

Introduction














A



Indanones are


A rearrangement













Whereas







Chapter 2

31




N

HO Ph

S NS Me

HO PhMe

1a2a 96

Me

O

OO O


2) is





The generated








N

S O

O

O[Rh]

Ph

SN

[Rh]O Ph

O OMe

[Rh] OH

N

S O

O

O Ph

H

[Rh]

H

N

[Rh]O Ph

S O

O

Me Me

Me

Me

1a

H2O

2a

A B

CD

1a

A




Chapter 2

32








N

HO Ph

SN

S CH19D11

HO Ph

D3C

1a-d2a-d 96

D3C

O

O

O O

D

D

D

D

D

D

H01D09

8



D12




Application




1

2

SN

HO Ar

O OMe

N

HO Ar

S O

O


K2CO 3 (20 equiv)


NS Me

HO PhMe

2a

91 er = 928

O O

NS Me

HO Ph

2b

95 er = 937

O O

S

NS Me

HOMe

2c

90 er = 937

O O

OMe

NS Me

HOMe

2c

92 er = 919

O O

CF3



Chapter 2

33










HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6 84

5 56



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3


PhMgBr

THF rt 1 h N

HO

Ts

Me

1e 93

er gt 991 dr = 201

Ph

3







SN

HO PhMe

O OMe

MeN

HO Ph

S O

O

Me

Me

1e

er gt 991 dr = 201

2e 99

er gt 991 dr gt 201





Chapter 2

34









SN

PhRhOMe

O OMe

Me

SN

PhRhOMe

O OMe

Me

favored

disfavored

F

F

NSRh

Ph

Me

O

O

MeO

H

Me

E

E

NSRh

Ph

Me

O

O

MeO

Me

H














Chapter 2

35


1

er gt 991 dr gt 201

2

er gt 991 dr gt 201

SN

HO ArR

O OMe

N

HO Ar

S O

O





1 N

HO Ph

S O

O

Me

Me

1f

SN

HO PhMe

O OMe

Me

2e 99

6 N

HO

S O

O

Me

1k

OMe

SN

HOMe

O OMe

2k 97

OMe

2

N

HO Ph

S O

O

MeO

Me

1g

SN

HO PhMe

O OMe

MeO

2g 98

7 N

HO

S O

O

Me

Me

1l

CF3

SN

HOMe

O OMe

Me

2l 97

CF3

3 N

HO Ph

S O

O

F3C

Me

1h

SN

HO PhMe

O OMe

F3C

2h 99

8 N

HO Ph

S O

O

Me

i-Pr

1m

SN

HO Phi-Pr

O OMe

Me

2m 97

4

N

HO Ph

S O

O

Me

1iMe

SN

HO PhMe

O OMeMe

2i 99

9 N

HO Ph

S O

O

Me

SMe

SN

HO Ph

O OMe

Me

2n 97

SMe

5 N

HO Ph

S O

O

Me

S

1j

SN

HO PhMe

O OMeS

2j 99



Chapter 2

36

Conclusions






Chapter 2

37





13C NMR


13C at 10069












N

OHNEt3

DCM rt 12 h


2) PhMgBrTHF rt 3 h

N

HO Ph

1a

TsCl

N

OH

8a

H HCl

Ts Ts









Chapter 2

38

N

S

Me

O

O

OH

8a 1H NMR = 213 (bs 1H) 245 (s 3H) 350-361 (m 2H) 394-404 (m 2H)

442-452 (m 1H) 737 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR =



-1

N

S

D3C

O

O

OH

8a-d

D

D

D

D

1H NMR = 283 (bs 1H) 349-355 (m 2H) 389-396 (m 2H) 435-444 (m 1H)



+ 2351128 Found mz

2351125 IR (ATR) 3503 1333 1142 1059 638 cm-1

N

S O

O

OH

8b

S

1H NMR = 277 (bs 1H) 357-364 (m 2H) 400-407 (m 2H) 441-450 (m 1H)


1H) 13



1038 737 cm-1

Chapter 2

39














N

HO Ph

S

1a

Me

O

O


2H) 728-737 (m 5H) 739 (d J = 84 Hz 2H) 778 (d J = 80 Hz 2H) 13

C NMR

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS


+ 3041002 Found mz 3040995 IR (ATR) 3477

1333 1184 1148 671 cm-1


N

HO Ph

S

1a-d

D3C

O

O

D

D

D

D


(m 5H) 13

C NMR = 203-211 (m) 652 703 1244 1281 (t JC-D = 247 Hz)


Chapter 2

40


702 648 cm-1

N

HO Ph

S

S

O

O



1H) 13

C NMR = 656 702 1244 1280 1283 1288 1331 13387 13392 1417


+ 2960410 Found mz 2960404 IR

(ATR) 3524 1333 1161 1148 748 cm-1

N

HO

S

Me

O

O

OMe

1c



2H) 775 (d J = 80 Hz 2H) 13

C NMR =216 553 652 702 1139 1259 1285


+

3341108 Found mz 3341097 IR (ATR) 3460 1518 1331 1250 1146 cm-1

N

HO

S

Me

O

O

CF3



C NMR

Chapter 2

41

=216 654 697 1239 (q JC-F = 2704 Hz) 1249 1255 (q JC-F = 37 Hz) 1284



1109 1076 cm-1


1l-1n

HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6a

5a



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3

acetone H2O

rt 10 h 4a

PhMgBr

THF rt 1 h N

OH

Ts

Me

1e

Ph

3a



procedure16













Me

NHTs

O

N2


Chapter 2

42

2H) 730 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR = 194 215 539


+

2680750 Found mz 2680747 IR (ATR) 2112 1639 1337 1319 1161 cm-1

[]27

D = -1184 (c = 079 in CHCl3)


i-Pr

NHTs

O

N2



2H) 769 (d J = 84 Hz 2H) 13

C NMR =169 193 215 315 548 647 1273


+ 2961063

Found mz 2961060 IR (ATR) 2129 1622 1362 1329 1161 cm-1

[]28

D = -730 (c = 071 in CHCl3)

NHTs

O

N2

5c

SMe

1H NMR = 174-196 (m 2H) 204 (s 3H) 242 (s 3H) 244-252 (m 2H)

390-400 (m 1H) 541 (s 1H) 560-572 (m 1H) 730 (d J = 84 Hz 2H) 772 (d J =

84 Hz 2H) 13

C NMR = 153 215 297 323 545 585 1272 1297 1366 1439


+ 3280784 Found mz 3280779

IR (ATR) 2129 1618 1375 1339 1163 cm-1

[]29

D = -506 (c = 063 in CHCl3)









Chapter 2

43

N

O

Ts

Me

6a

1H NMR = 145 (d J = 68 Hz 3H) 246 (s 3H) 443-454 (m 2H) 473-480 (m

1H) 736-742 (m 2H) 776-781 (m 2H) 13

C NMR = 157 216 696 810 1284


+ 2400689

Found mz 2400688 IR (ATR) 1825 1339 1155 669 cm-1

[]28

D = 614 (c = 081 in CHCl3)


N

O

Ts

i-Pr

6b

1H NMR = 099-111 (m 6H) 206-218 (m 1H) 246 (s 3H) 441 (dd J = 164 36


2H) 777 (d J = 80 Hz 2H) 13

C NMR = 174 181 216 304 703 903 1284


+ 2681002

Found mz 2680998 IR (ATR) 1815 1340 1155 1007 671 cm-1

[]29

D = 567 (c = 095 in CHCl3)

N

O

Ts

6c

SMe

1H NMR = 204 (s 3H) 209-218 (m 2H) 247 (s 3H) 265-279 (m 2H) 446 (d


2H) 780 (d J = 80 Hz 2H) 13

C NMR = 147 216 291 293 705 832 1286


+ 3000723

Found mz 3000718 IR (ATR) 1813 1342 1308 1157 667 cm-1

[]29

D = 1183 (c = 036 in CHCl3)


Chapter 2

44










N

HO

S O

O

Me

Me

1e

H

NOE

NOE



(m 3H) 739 (d J = 84 Hz 2H) 777 (d J = 84 Hz 2H) 13

C NMR = 144 216

628 702 731 1247 1279 1284 1285 1298 1319 1415 1443 HRMS (ESI+)


1155 1092 667 cm-1

[]25




Chapter 2

45

N

HO

S O

O

Me

1l

H

NOE

NOE

CF3

Me



739-747 (m 4H) 777 (d J = 84 Hz 2H) 13

C NMR = 143 216 630 706 727

1238 (JC-F = 2704 Hz) 1253 1254 (JC-F = 36 Hz) 1285 1299 1301 (JC-F = 324


+ 3861032

Found mz 3861025 IR (ATR) 3422 1327 1151 1109 839 cm-1

[]28




N

HO

S O

O

Me

iPr

1m

H

NOE

NOE



= 100 Hz 1H) 690-696 (m 2H) 712-720 (m 3H) 732 (d J = 80 Hz 2H) 773 (d

J = 80 Hz 2H) 13

C NMR = 190 193 215 291 641 729 801 1247 1275


+

3461471 Found mz 3461466 IR (ATR) 3454 1331 1163 739 669 cm-1

[]27



Chapter 2

46


N

HO Ph

S O

O

1n

Me

SMe

1H NMR = 202 (s 3H) 218-258 (m 8H) 388-394 (m 2H) 427 (dd J = 84 48

Hz 1H) 688-693 (m 2H) 714-721 (m 3H) 740 (d J = 80 Hz 2H) 779 (d J = 80

Hz 2H) 13

C NMR = 154 216 290 297 634 725 733 1246 1277 1284


+

3781192 Found mz 3781188 IR (ATR) 3481 1339 1157 702 669 cm-1

[]28












N

HO

S O

O

Me

Me

1f

H

NOE

NOE


1H) 398 (q J = 64 Hz 1H) 424 (dd J = 84 08 Hz 1H) 732-744 (m 5H)

750-755 (m 2H) 774-778 (m 2H) 13

C NMR = 165 216 627 718 739 1257

Chapter 2

47



-1

[]25






HO2C Me

NHCbz

Me

NHCbz

O

N2N

O

Cbz

Me

6d5d

1) (COCl) 2 DMF

2) CH2N2 Rh2(OAc)4 (05 mol )

DCM rt 12 h4d

PhMgBr

THF rt 1 h

N

OH

Cbz

Me

7a

Ph

N

OH

H

Me

PhPd C (5 mol )

H2 (1atm)

MeOH rt 12 h

MeO SO2Cl

NEt3

DCM rt 12 h

N

HO Ph

S O

O

MeO

Me

1g









Me

NHCbz

O

N2

5d 1H NMR = 134 (d J = 68 Hz 3H) 420-436 (m 1H) 504-516 (m 2H) 534-564

(m 2H) 728-736 (m 5H) 13

C NMR = 184 535 (2C) 669 1280 1282 1285


+ 2481030 Found mz

2481028 IR (ATR) 2116 1717 1636 1533 1252 cm-1

[]28

D = -434 (c = 085 in CHCl3)


Chapter 2

48







N

O

Cbz

Me

6d


Hz 1H) 498-505 (m 1H) 513-521 (m 2H) 731-739 (m 5H) 13

C NMR = 153



696 cm-1

[]29

D = 390 (c = 068 in CHCl3)










N

OH

Cbz

Me

7a

Ph


= 96 Hz 1H) 458 (q J = 64 Hz 1H) 507-518 (m 2H) 729-746 (m 10H) 13

C

NMR = 142 623 667 689 730 1246 1278 1279 1280 1285 1287 1366

Chapter 2

49


+ 2981438 Found mz

2981433 IR (ATR) 1670 1423 1248 1016 702 cm-1

[]29

D = 46 (c = 089 in CHCl3)

N

OH

Cbz

Me

7b

MeO


1H) 432 (d J = 96 Hz 1H) 452-461 (m 1H) 506-518 (m 2H) 687-694 (m 2H)

726-739 (m 7H) 13

C NMR = 143 553 622 666 687 729 1140 1260 1278


+

3281543 Found mz 3281539 IR (ATR) 1682 1418 1352 1024 696 cm-1

[]29

D = 02 (c = 085 in CHCl3)








pressure







mmol 58 yield)

Chapter 2

50

N

HO

S O

O

MeO

Me

1g

H

NOE

NOE


390 (s 3H) 399 (d J = 92 Hz 1H) 419 (q J = 60 Hz 1H) 698-707 (m 4H)

720-727 (m 3H) 779-785 (m 2H) 13

C NMR = 143 557 627 701 731 1144



-1

[]28




N

HO

S O

O

F3C

Me

1h

H

NOE

NOE


406 (d J = 92 Hz 1H) 430 (qd J = 64 08 Hz 1H) 694-699 (m 2H) 721-727

(m 3H) 784 (d J = 80 Hz 2H) 801 (d J = 84 Hz 2H) 13

C NMR = 145 629

706 729 1232 (JC-F = 2711 Hz) 1245 1263 (JC-F = 37 Hz) 1283 12868 12871


+

3720876 Found mz 3720870 IR (ATR) 3503 1348 1323 1165 646 cm-1

[]28




Chapter 2

51

N

HO

S O

O

Me

1i

H

NOE

NOE


1H) 401 (d J = 88 Hz 1H) 422 (q J = 64 Hz 1H) 694-698 (m 2H) 720-724 (m

3H) 746-750 (m 2H) 767-772 (m 2H) 13

C NMR = 144 214 630 704 730

1247 1256 1279 1285 1286 1291 1341 1347 1395 1416 HRMS (ESI+)


1151 714 700 cm-1

[]29




N

HO

S O

O

Me

1j

H

NOE

NOE

S


Hz 1H) 425 (q J = 64 Hz 1H) 696-701 (m 2H) 720-728 (m 4H) 764-767 (m

1H) 769-772 (m 1H) 13

C NMR = 144 632 709 730 1246 1279 1281 1286


+ 3100566

Found mz 3100559 IR (ATR) 3508 1340 1151 756 669 cm-1

[]29




Chapter 2

52

N

HO

S O

O

Me

1k

H

NOE

NOE

OMe


1H) 394 (d J = 88 Hz 1H) 416 (q J = 64 Hz 1H) 670-675 (m 2H) 684-689 (m

2H) 756-762 (m 2H) 765-770 (m 1H) 786-790 (m 2H) 13

C NMR = 143 553

630 704 729 1138 1259 1283 1292 1332 1337 1348 1592 HRMS (ESI+)


1327 1155 606 cm-1

[]29





Screening







mmol 93 yield)

Chapter 2

53


rac -DM-BINAP

rac-BINAP

dppf

dppb

PPh3

dppe

46

trace

trace

yield

PCy3

Ligand

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

entry

1

2

3

4

5

6

7

8

nd

nd

nd

93

none nd

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a


entry Ligand yield

1

2

3

4

(R)-BINAP

(R)-DM-BINAP

(R)-SEGPHOS

(R)-DIFLUORPHOS

er

94

46

48

43

5

6

(R)-DM-SEGPHOS


3862

91

7

8

(R)-MeO-BIPHEP

(R)-MeO-DM-BIPHEP

64

91

892

3169

1288

1486

2476

2575

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a










Chapter 2

54

NS Me

HO PhMe

2a

O O


J = 148 Hz 1H) 683 (s 1H) 727-744 (m 6H) 781 (d J = 84 Hz 1H) 13

C NMR

= 216 361 626 732 1238 1263 1280 1284 1299 1301 1330 1412 1431


+ 3041002 Found mz 3040998 IR

(ATR) 3472 1325 1161 1142 735 cm-1

[]29




NS CH2D

HO Ph

D3C

2a-d

O O

D

D

D


J = 148 Hz 1H) 728-743 (m 5H) 13

C NMR = 201-210 (m) 358 (t JC-D = 212

Hz) 625 731 1234 (t JC-D = 249 Hz) 1262 1279 1283 1291-1300 (m 2C)


+ 3111441

Found mz 3111436 IR (ATR) 3524 1318 1290 1150 721 cm-1

NS Me

HO Ph

O O

S

2b


1H) 668 (d J = 52 z 1H) 730-738 (m 5H) 750 (d J = 52 Hz 1H) 13

C NMR =

378 630 722 1257 1264 1282 1286 1299 1338 1427 1467 HRMS (ESI+)


1150 1063 748 cm-1

[]29


Chapter 2

55



NS Me

HOMe

O O

OMe

2c


422 (d J = 148 Hz 1H) 684-690 (m 3H) 724-733 (m 3H) 774-779 (m 1H) 13

C

NMR = 216 360 553 626 729 1137 1237 1275 1299 1230 1328 1351


+ 3341108 Found mz

3341098 IR (ATR) 3441 1508 1250 1144 735 cm-1

[]29




NS Me

HOMe

O O

CF3



2H) 782 (d J = 80 Hz 1H) 13

C NMR = 216 360 625 731 12392 (q JC-F =

2708) 12395 1254 (q JC-F = 36 Hz) 1268 1298 1303 (q JC-F = 352) 1329


+ 3720876 Found

mz 3720869 IR (ATR) 3481 1323 1121 1067 733 cm-1

[]29




Chapter 2

56










SN

HO

Me

O OMe

Me

2e

H

NOE

NOE


= 68 Hz 1H) 675 (s 1H) 723-738 (m 6H) 777 (d J = 84 Hz 1H) 13

C NMR =

119 215 314 608 750 1242 1262 1275 1282 1298 1301 1316 1427


+ 3181158 Found mz

3181155 IR (ATR) 3481 1315 1163 1146 683 cm-1

[]28




SN

HO

Me

O OMe

MeO

2g

H

NOE

NOE

Chapter 2

57



5H) 782 (d J = 88 Hz 1H) 13

C NMR = 120 314 555 609 752 1144 1151



735 cm-1

[]29




SN

HO

Me

O OMe

F3C

2h

H

NOE

NOE



1H) 13

C NMR = 118 314 608 750 1228 (q JC-F = 2711 Hz) 1251 1258 (q



+ 3720876 Found

mz 3720872 IR (ATR) 3461 1325 1161 1142 739 cm-1

[]29




SN

HO

Me

O OMe

2i

H

NOE

NOE

Me

Chapter 2

58


J = 68 Hz 1H) 684 (d J = 80 Hz 1H) 718-736 (m 6H) 770 (s 1H) 13

C NMR

=119 211 314 607 748 1242 1262 1275 1282 1299 1338 1341 1395


+ 3181158 Found mz

3181155 IR (ATR) 3489 1448 1319 1148 735 cm-1

[]29




SN

HO

Me

O OMe

2j

H

NOE

NOES


1H) 656 (d J = 52 Hz 1H) 726-736 (m 5H) 743 (d J = 48 Hz 1H) 13

C NMR

= 114 319 619 742 1256 1266 1278 1284 1297 1334 1429 1480 HRMS


+ 3100566 Found mz 3100561 IR (ATR) 3524

1329 1151 1020 729 cm-1

[]29




SN

HO

Me

O OMe

2k

H

NOE

NOE

OMe


J = 68 Hz 1H) 685 (d J = 88 Hz 2H) 698-703 (m 1H) 722-730 (m 2H)

738-748 (m 2H) 785-790 (m 1H) 13

C NMR = 119 314 553 608 747 1136

Chapter 2

59



760 cm-1

[]26




SN

HO

Me

O OMe

2l

H

NOE

NOE

CF3

Me



= 84 Hz 2H) 778 (d J = 80 Hz 1H) 13

C NMR = 119 215 313 607 749




-1

[]26




SN

HO

iPr

O OMe

2m

H

NOE

NOE

Me


(m 1H) 264 (s 1H) 285 (s 3H) 441 (d J = 100 Hz 1H) 685 (s 1H) 714-735 (m

4H) 748 (d J = 76 Hz 2H) 772 (d J = 80 Hz 1H) 13

C NMR = 211 214 217

278 330 718 742 1244 1256 1270 1283 1292 1295 1300 1435 1442


+ 3461471 Found mz 3461466 IR

Chapter 2

60

(ATR) 3412 1315 1165 1146 683 cm-1

[]29




SN

HO

O OMe

2n

H

Me

NOE

SMe

1H NMR = 160-170 (m 1H) 184 (s 3H) 212-226 (m 4H) 230-242 (m 2H)

254-263 (m 1H) 294 (s 3H) 471 (dd J = 108 28 Hz 1H) 675 (s 1H) 722-738

(m 6H) 776 (d J = 80 Hz 1H) 13

C NMR = 150 215 242 301 321 643 748

1245 1262 1276 1283 12986 12993 1312 1429 1437 1441 HRMS (ESI+)


1165 1134 748 cm-1

[]28









was used as a


and


21 All



Chapter 2

61



2e

formula C17H19NO3S

fw 31739

T (K) 100(2)


space group P21c

a (Aring) 105967(5)


3) 152058(13)

Z 4 Dcalc (gcm

3) 1386

(mm-1

) 0225 F(000) 672



348500135

params 203 GOF on F

2 1069

R1 wR2 [Igt2(I)]

00322 00868

R1 wR2 (all data)

00335 00878

Chapter 2

62

























Med Chem 2003 46 1116








Chapter 2

63

































Chapter 2

64




2012 51 9160





11437-11439
























Chapter 2

65











2548-2551







11750









32 115



Chapter 2

66

Chapter 3

67

Chapter 3




Halides

Abstract






Chapter 3

68

Introduction
















2) are












several months


Et LiB

Ph

+B

Ph

Et

1a 74

(a)(b)[Me4N]


Chapter 3

69

















OMe

BrB

Ph

Et

OMe

3a

Ph

Et

OMe

H

4a

Pd-ligand AcOH

2a

+B

Ph

Et

1a

[Me4N]


EZ of 4ab

1 P(o-tol)3 69 397

2 P(t-Bu)3 47 1783

3 1-[(t-Bu)2P](biphenyl) 18 2872

4 2-[(t-Bu)2P](11-binaphthyl) 21 6733

5 DPEPhos 24 928



analysis



Chapter 3

70









Pd(0)

Pd

MeO

B

PdEt

OMe

Ph

B

Ph

Et

2a

BC

Pd

MeO

Br

A

1a

3a







dominates10
















Chapter 3

71










Chapter 3

72


BO

Ph

Et

OMe

5a 83

BO

Ph

Et

CF3

5b 85

BO

Ph

Et

NPhth

5c 82

BO

Ph

Et

5d 72b

BO

Ph

Et

5e 85

S

BO

n-Pr

Me

Cl

5f 74

BO

n-Pr

Ph

OMe

5g 82

BO

Ph

S

5h 83

BO

Ph

CO2Et

5i 81

BO

Ph

5j 82

Cl

BO

Ph

CF3

TBSO

BO

Cl

S

Ph

BO

Ph

Me

OMe

5n 71b

5m 925l 82

BO

Ph

5k 76

Me

+B

Ar

R

1

[Me4N]

2


BO

Ar

R

Ar

5







The reaction of 1a






Chapter 3

73








(E)-5o83 EZ = gt955

BO

Ph

Et

Ph

Ph

Et

PhO

NMe2

(Z)-685 EZ = lt595

Ph

Ph

EtO

NMe 2

(E)-675 EZ = 928

1a

(Z)-5o71 EZ = 793

+ PhBr

BO

Ph

Ph

Et

(a)

(c) (c)

(b)






Conclusions






Chapter 3

74




1H at 400 MHz and

11B at 128 MHz)



13C)

CD3CN ( = 194 for 1H =132 for


11B)









and Ph-9-BBN18


procedures


Et LiB

Ph

+B

Ph

Et

1a


2) Me4NCl MeOH

[Me4N]









74 yield)

Chapter 3

75

B

Ph

Et

1a

[Me4N]


136-207 (m 11H) 236-250 (m 2H) 303 (s 12 H) 679-686 (m 1H) 700-707 (m

2H) 735 (d J = 72 Hz 2H) 13

C NMR (CD3CN) = 149 166 266 (q JC-B = 379

Hz) 271 275 324 349 561 948 1221 1269 1339 11

B NMR = -133 HRMS




n-Pr LiB

Ar


2) Me4NCl MeOH B

n-Pr

1b

Cl

[Me4N]










Chapter 3

76

B

n-Pr

1b

Cl

[Me4N]

1H NMR (CD3CN) = 084-096 (m 5H) 111-121 (m 1H) 126-200 (m 13H)

235-250 (m 2H) 304 (s 12H) 700-705 (m 2H) 733 (d J = 84 Hz 2H) 13

C NMR

(CD3CN) = 139 234 249 266 (q JC-B = 393 Hz) 270 273 323 348 561

933 1265 1272 1355 11


[M-(NMe4)] 2991738 Found 2991730

B

n-Pr

1c

OMe

[Me4N]


128-201 (m 13H) 237-252 (m 2H) 303 (s 12H) 371 (s 3H) 663-668 (m 2H)

723 (d J = 81 Hz 2H) 13

C NMR (CD3CN) = 140 235 250 268 (q JC-B = 393

Hz) 272 275 324 349 554 561 929 1128 1344 1561 11

B NMR = -135


B

Ph

1d

[Me4N]


(m 2H) 134-196 (m 9H) 230-244 (m 2H) 304 (s 12H) 679-686 (m 1H)

699-706 (m 2H) 733 (d J = 72 Hz 2H) 13

C NMR (CD3CN) =23 87 266 (q

JC-B = 393 Hz) 271 274 323 349 562 1222 1269 1338 11

B NMR = -134


Chapter 3

77

B

Ph

1e

[Me4N]


(m 3H) 302 (s 12H) 679-686 (m 1H) 699-706 (m 2H) 734 (d J = 66 Hz 2H) 13

C NMR (CD3CN) = 253 268 (q JC-B = 379 Hz) 271 275 324 333 349 361

561 980 1221 1269 1339 11


[M-(NMe4)] 2912284 Found 2912278

B

1f

S

Ph

[Me4N]




09 Hz 1H) 712-730 (m 5H) 13

C NMR (CD3CN) = 240 268-290 (m) 325 347

380 562 928 1225 1261 1265 1271 1289 1297 1434 11

B NMR = -135


B

Ph

1g

TBSO

[Me4N]

1H NMR (CD3CN) = 005 (s 6H) 084-096 (m 11H) 110-120 (m 1H) 134-197

(m 9H) 216-233 (t J = 72 Hz 2H) 235-250 (m 2H) 301 (s 12H) 356 (t J = 78

Hz 2H) 680-687 (m 1H) 700-708 (m 2H) 735 (d J = 66 Hz 2H) 13

C NMR

(CD3CN) = -50 189 254-277 (m) 323 348 561 649 889 1222 1269

1339 11


Found 3812789

Chapter 3

78

B

Ph

1h

OMe

[Me4N]


(m 2H) 298 (s 12H) 373 (s 3H) 668-674 (m 2H) 701-718 (m 5H) 732 (d J =

87 Hz 2H) 13

C NMR (CD3CN) = 255-277 (m) 322 350 554 561 961 1129

1251 1287 1302 1312 1345 1564 11


C23H26BO [M-(NMe4)] 3292077 Found 3292081



Br

+

MeO


6 mol Ligand


2a

B

Ph

Et

OMe

(E)-3a

AcOH

Ph

Et

OMe

H

Ph

B

Et

OMe

+

+

(Z)-3a

(E)-4a

H

Et

OMe

Ph

(Z)-4a

B

Ph

Et

1a

[Me4N]









Chapter 3

79




B

Ph

Et

+


toluene 70 degC

Me3NO

Br

MeO

BO

Ph

Et

OMe

5a

1a

2a

[Me4N]









BO

Ph

Et

OMe


383 (s 3H) 438-444 (m 1H) 685-691 (m 2H) 714-736 (m 7H) 13

C NMR =

138 221 267 273 (br) 277 312 553 736 1132 1251 1278 1283 1298

1366 1436 1494 1586 11


3742417 Found 3742410

Chapter 3

80

BO

Ph

Et

CF3

5b


437-443 (m 1H) 718-726 (m 3H) 734-739 (m 2H) 745-748 (m 2H) 760-763

(m 2H) 13

C NMR = 135 220 266 271 (br) 276 312 738 12429 (q JC-F =

2701 Hz) 1247 (q JC-F = 36 Hz) 1280 1281 1289 (q JC-F = 320 Hz) 1291 1425

1476 1480 11


Found 4122186

BO

Ph

Et

NPhth

5c


440-450 (m 1H) 720-727 (m 3H) 734-739 (m 2H) 743-751 (m 4H) 777-783

(m 2H) 794-800 (m 2H) 13

C NMR = 137 221 266 274 (br) 275 312 738

1235 1254 1258 1279 1282 1294 1304 1317 1342 1429 1440 1482

1671 11

B NMR = 502 IR (KBr) = 2928 1742 1509 1381 714 cm-1

HRMS (EI)


BO

Ph

Et

5d

1H NMR = 021-034 (m 1H) 068-100 (m 8H) 120-150 (m 7H) 224-238 (m

1H) 244-258 (m 1H) 424-431 (m 1H) 722-754 (m 9H) 778 (d J = 78 Hz 1H)

783-788 (m 1H) 809-816 (m 1H) 13

C NMR = 137 216 219 259 262 264

(br) 282 309 314 734 1249 12537 12539 1255 1264 1270 1273 12795

Chapter 3

81

12799 1283 1321 1335 1413 1427 1467 11


for C28H31BO (M+) 3942468 Found 3942476

BO

Ph

Et

5e

S


448-456 (m 1H) 702 (dd J = 51 36 Hz 1H) 708 (dd J = 36 12 Hz 1H)

715-730 (m 4H) 732-738 (m 2H) 13

C NMR =141 221 271 289 312 739

1250 1255 1266 1269 1279 1281 1416 1427 1468 11

B NMR = 496


BO

n-Pr

Me

Cl

5f

1H NMR = 070 (t J = 75 Hz 3H) 096-133 (m 9H) 142-172 (m 6H) 220-228

(m 2H) 237 (s 3H) 439-446 (m 1H) 708-735 (m 8H) 13

C NMR = 140 212

219 221 267 274 (br) 313 363 737 1279 12846 12855 1298 1309 1365

1411 1420 1488 11


4062235 Found 4062237

BO

n-Pr

Ph

OMe

5g

Chapter 3

82


(s 3H) 435-450 (m 1H) 690 (d J = 81 Hz 2H) 711 (d J = 81 Hz 2H) 720-740

(m 5H) 13

C NMR = 140 219 221 267 274 (br) 312 362 551 736 1133

1267 1278 1287 1294 1354 1446 1475 1573 11




BO

Ph

S

5h

1H NMR = 027-032 (m 2H) 046-052 (m 2H) 098-130 (m 6H) 140-170 (m

8H) 430-445 (m 1H) 696-700 (m 1H) 704-707 (m 1H) 715-726 (m 2H)

729-738 (m 4H) 13

C NMR = 60 150 222 263 272 (br) 313 736 1241

1243 1253 1278 1290 1295 1410 1425 1431 11



BO

Ph

CO2Et

5i

1H NMR = 017-023 (m 2H) 045-053 (m 2H) 090-119 (m 6H) 132-173 (m

11H) 427-433 (m 1H) 438 (q J = 75 Hz 2H) 718-738 (m 7H) 798 (dt J = 78

15 Hz 2H) 13

C NMR = 56 144 151 220 263 269 (br) 312 609 735 1255

1279 1284 1287 1289 1303 1423 1453 1469 1665 11

B NMR = 496 IR

(KBr) = 2928 1717 1287 1100 cm-1


Found 4282526

BO

Ph

5j

Cl

Chapter 3

83

1H NMR = 023-029 (m 2H) 048-055 (m 2H) 094-123 (m 6H) 134-171 (m

8H) 432-439 (m 1H) 706-714 (m 1H) 718-726 (m 4H) 728-738 (m 4H) 13

C

NMR = 57 150 220 263 271 (br) 312 736 1255 1267 1279 1283 1284

1289 1304 1332 1423 1424 1461 11


C25H28BClO (M+) 3901922 Found 3901923

BO

Ph

5k

Me

1H NMR = 082-113 (m 6H) 126-164 (m 15H) 237 (s 3H) 268-280 (m 1H)

434-441 (m 1H) 704-709 (m 3H) 717-725 (m 4H) 730-737 (m 2H) 13

C NMR

= 215 219 248 263 273 (br) 312 315 433 735 1252 12689 12693 1275

1278 1283 1316 1365 1418 1424 1481 11


for C28H35BO (M+) 3982781 Found 3982780

BO

Cl

S

Ph

5l

1H NMR = 106-176 (m 13H) 250-260 (m 2H) 272-280 (m 2H) 441-449 (m

1H) 674 (dd J = 33 12 Hz 1H) 697-703 (m 3H) 709-738 (m 8H) 13

C

NMR(C6D6) =225 272 277 (br) 315 358 375 739 1247 1253 1261 1272

1285 12856 12861 1306 1335 1419 1427 1437 1491 11

B NMR = 495


BO

Ph

CF3

TBSO

5m

Chapter 3

84

1H NMR = -014 (s 6H) 079 (s 9H) 095-136 (m 6H) 142-168 (m 7H) 255 (t

J = 72 Hz 2H) 343 (t J = 72 Hz 2H) 435-442 (m 1H) 718-726 (m 3H)

731-737 (m 2H) 747 (d J = 81 Hz 2H) 759 (d J = 81 Hz 2H) 13

C NMR = -54

183 220 259 266 271 (br) 311 377 616 739 1242 (q JC-F = 2694 Hz) 1247

(q JC-F = 36 Hz) 1258 1280 1282 1290 (q JC-F = 320 Hz) 1291 1421 1422

1480 11



BO

Ph

Me

OMe

5n

1H NMR = 122-130 (m 4H) 138-162 (m 5H) 168-186 (m 4H) 237 (s 3H)

375 (s 3H) 443-450 (m 1H) 670 (dt J = 90 21 Hz 2H) 690-697 (m 4H)

702-708 (m 3H) 710-720 (m 4H) 13

C NMR = 213 222 269 312 550 738

1132 1260 1272 1285 1301 1307 1310 1362 1369 1423 1429 1483

1571 11


4362561


4-Bromobenzene

B

Ph

Et

+


toluene 70 degC

Me3NO BO

Ph

Ph

Et

(Z)-5o

1a

Ph Br

[Me4N]




Chapter 3

85






BO

Ph

Ph

Et


470-475 (m 1H) 685-710 (m 10H) 13

C NMR = 139 224 267 313 317 740

1248 1257 1272 127412938 12941 1421 1425 1275 11

B NMR = 512


BO

Ph

Et

Ph


438-443 (m 1H) 718-737 (m 10H) 13

C NMR = 137 221 266 274 (br) 277

312 737 1253 1268 1278 1279 1283 1288 1433 1442 1494 11

B NMR =



Bromide 2b

+

Br

ONMe2

Ph

Et

PhO

NMe2


THF K3PO4 60 degC

(Z)-Tamoxifen 6

2b

BO

Ph

Et

Ph

(E)-5o

Chapter 3

86









Chapter 3

87



2003 Vol 3








Rev 2006 250 1107









1976 108 281








74





Chapter 3

88





















2006 128 1828




Chapter 4

89

Chapter 4



Abstract






Chapter 4

90

Introduction





























Chapter 4

91


B

MOMO

[Me4N] +

MeO

Br

I

Br

MeO Br

B

MeO

MOMO MOMO

1a

2 3 87EZ = lt199

NaOH

50 degC

1 mol


toluene 50 degC
















procedure

Chapter 4

92



An











3

MeO

R

Br

4 92

R

MeO

R

Br

n = 2 5 87

n = 3 6 82n = 4 7 85

n

R

1 mol


toluene 50 degC

I

Br

NaOH

E

EE

R = OMOM








Chapter 4

93





Br

Br

R

R

Br

Br

8 86

R

R

Br

R

R

Br

9 92

E E

R = OMOM















Chapter 4

94


Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

Me3Si

Br

Ph

F

Me3Si

OMe

Br

Ph

F

S

Br

Me3Si

OMe

B

n-Pr

[Me4N]

Cl

B

Ph

[Me4N]

OMe

Br

S

Br

I

EtO2C

MOMO

MOMO

I

Br

F

1b

10 88

11 84

12 88

1a1c

cat Pd

NaOHcat Pd

cat Pd NaOH

Cs2CO3

Conclusions







Chapter 4

95




1H at 500 MHz and






13C) CD3CN ( = 194 for

1H =132 for

13C) and

BF3OEt2 ( = 000 for 11











11













Chapter 4

96

B

MOMO

[Me4N]

1a


202 (t J = 66 Hz 2H) 236-251 (m 2H) 304 (s 12H) 328 (s 3H) 346 (t J = 69

Hz 2H) 454 (s 2H) 678-685 (m 1H) 698-705 (m 2H) 734 (d J = 72 Hz 2H) 13

C NMR (CD3CN 75 MHz) = 210 267 (br) 271 275 282 297 324 349 551

561 681 928 968 1221 1269 1338 11



B

Ph

[Me4N]

1b

OMe


225 (t J = 72 Hz 2H) 234-249 (m 2H) 263 (t J = 72 Hz 2H) 303 (s 12H) 372

(s 3H) 663-669 (m 2H) 711-728 (m 7H) 13


272 275 324 349 381 554 560 1129 1266 1289 1298 1346 1434 1563 11


3572390 Found 3572383



B

MOMO

[Me4N]

+

MeO

Br

1 mol


toluene 50 degC

I

Br

MeO Br

NaOH

3

1a

MOMO

Chapter 4

97








MeO Br

3

MOMONOE

NOE




(t J = 66 Hz 2H) 376 (s 3H) 452 (s 2H) 667-675 (m 4H) 697-702 (m 2H)

709-736 (m 7H) 13

C NMR (75 MHz) = 255 298 356 5510 5514 676 964

1134 1196 1267 1282 1294 13046 13049 1323 1339 1376 1408 1420



spectroscopy

MeO

R

Br

4

R

R = OMOM




Chapter 4

98


2H) 325 (s 3H) 329 (s 3H) 331-341 (m 4H) 380 (s 3H) 451 (s 2H) 453 (s

2H) 662-678 (m 8H) 697-703 (m 2H) 706-738 (m 12H) 13

C NMR (150 MHz)

= 252 254 295 296 353 354 5502 5504 552 675 676 9629 9632 1131

1196 1265 1267 1281 1282 1285 12941 12942 1303 1304 1306 1324

1343 1377 1385 1390 1400 1413 1414 1418 1429 1435 1579 HRMS


7972818 Found

7972849

MeO

R

5

R

R = OMOM

R

Br




325 (s 3H) 327 (s 3H) 328 (s 3H) 330-342 (m 6H) 374 (s 3H) 450 (s 2H)

452 (s 2H) 454 (s 2H) 654-662 (m 4H) 666-678 (m 8H) 696-704 (m 4H)

712-737 (m 15H) 13

C NMR (75 MHz) = 254 256 296 297 298 3526 3534

355 551 675 676 963 1130 1196 1264 1267 1280 1281 1286 1294 1301

1302 1304 1306 1324 1344 1377 1384 1387 1392 1393 1398 1402 1409



10914437 Found 10914482

Chapter 4

99

MeO

R

6

R

R = OMOM

R

R

Br




330-341 (m 8H) 371 (s 3H) 448-454 (m 8H) 648-675 (m 16H) 695-703 (m

4H) 714-737 (m 20H) 13

C NMR (75 MHz) = 253 254 256 257 2969 2974

298 350 354 356 550 551 675 676 963 1131 1196 1264 1267 1279

1280 1281 1283 1288 1293 1294 1300 1301 1302 1305 1306 1323 1342

1377 1385 1387 1389 1391 1394 1396 1397 1401 1405 1409 1411 1413



13856057 Found 13856062

MeO

R

7

R

R = OMOM

R

R

R

Br




374 (s 3H) 447-452 (m 10 H) 649-679 (m 20 H) 690-695 (m 2H) 701-706 (m

2H) 710-736 (m 25H) 13

C NMR (75 MHz) = 2529 2535 256 257 2968

Chapter 4

100

2971 298 351 354 355 356 550 6746 6755 676 963 1131 1195 1264

1267 12795 1280 1281 1283 1285 1287 1293 12937 12944 1301 1302

1304 1306 1322 1343 1377 1384 1387 1389 1390 1391 1394 13976

13979 1401 1404 1408 1409 1412 1413 1416 1427 14318 14321 1434


16797677 Found 16797694

8

R

Br

R

Br

R = OMOM





(t J = 66 Hz 4H) 456 (s 4H) 668-673 (m 4H) 691 (s 4H) 710-721 (m 8H)

722-737 (m 6H) 13

C NMR (75 MHz) = 254 297 354 551 676 963 1198

1268 1282 1291 1293 1303 1323 1380 1400 1411 1417 1427 HRMS


8221905

9

R

R

R = OMOM

R

R

Br

Br



Chapter 4

101


6H) 330-340 (m 8H) 446 (s 4H) 453 (s 4H) 656-672 (m 12H) 688 (s 4H)

704-710 (m 4H) 714-718 (m 4H) 722-740 (m 16H) 13

C NMR (150 MHz) =

254 2962 2963 356 357 5501 5503 674 676 9629 9631 1197 1266

1268 1281 12818 12822 1290 1295 1296 1304 1308 1324 1379 1385

1394 1403 1405 1409 1416 1417 1427 1434 HRMS (MALDI-TOF-MS


14335057 Found 14335040

Ph

F

Me3Si

OMe

Br

10

NOE

NOE





3H) 676-686 (m 3H) 694-707 (m 6H) 709-728 (m 5H) 734 (d J = 84 Hz 2H) 13

C NMR (150 MHz) = -11 349 372 552 1135 1189 (d JC-F = 255 Hz)1202

(d JC-F = 92 Hz) 1258 1268 (d JC-F = 35 Hz) 1280 1283 1284 1300 1304 (d

JC-F = 159 Hz) 1326 1329 1332 (d JC-F = 45 Hz) 1339 1387 1417 1418 1430




Chapter 4

102

Ph

F

S

Br

Me3Si

OMe

11

MOMO




= 78 2H) 264-272 (m 2H) 282-289 (m 2H) 325 (s 3H) 328 (t J = 66 Hz 2H)

382 (s 3H) 448 (s 2H) 587 (d J = 39 Hz 1H) 660 (d J = 39 Hz 1H) 669-676

(m 2H) 684-696 (m 3H) 705-742 (m 16H) 13

C NMR (150 MHz) = -10 244

293 351 362 372 550 552 673 963 1127 1135 1161 (d JC-F = 225 Hz)

1244 (d JC-F = 32 Hz) 1258 1274 12827 12831 12837 12840 12856 12861

1295 1302 1307 (d JC-F = 155 Hz) 1324 1329 1330 (d JC-F = 45 Hz) 1333

1345 1385 1395 (d JC-F = 12 Hz) 1412 1416 (d JC-F = 80 Hz) 1419 1422



Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

12MOMO




mmol) t1 10 h t2 12 h

Chapter 4

103


210-224 (m 4H) 264-272 (m 2H) 279-287 (m 2H) 323-333 (m 5H) 373 (s


1H) 666-672 (m 2H) 679-694 (m 5H) 703-737 (m 20H) 773 (d J = 84 Hz

2H) 13

C NMR (150 MHz) = -11 141 143 225 244 293 350 359 370 385

550 551 607 674 963 1134 1159 (d JC-F = 224 Hz) 1243 (d JC-F = 29 Hz)

1258 1269 1271 12808 12811 12815 12820 12823 12838 12844 1290

1293 1300 1301 (d JC-F = 158 Hz) 1302 1307 1323 (d JC-F = 47 Hz) 13258

13261 1328 1336 1344 1356 1379 1382 1390 (d JC-F = 12 Hz) 1409 14190

14191 14216 (d JC-F = 80 Hz) 14219 14222 1438 1446 1476 1583 1600 (d

JC-F = 2448 Hz) 1664 IR (KBr) = 2955 1717 1509 1273 1248 1111 837 cm-1


11294440

Found 11294465

Chapter 4

104




Chem 1999 201 163




897















2404


2006 128 1828



Chapter 5

105

Chapter 5




Abstract






Chapter 5

106

Introduction





moiety1b


























Chapter 5

107


B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

OHMe

Ph

1a

3a 85

MeO

OMe

2a

B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

1b

OMe

2a

OHMe

Ph

OMe

3b 88

[Me4N]

[Me4N]




Oxidative









Chapter 5

108


O

I

O

PdI

Pd(0)

B

1a

C

Pd(0)3a

Ar = p-MeOC6H4-

Me Me

OMe

Ar

Ph

B

D

A

Pd

O

ArB

Me

Ph

B

O

ArPh

Me

Me4NI

2a







Chapter 5

109


R3

O

I

B

R2

R1

+1 mol Pd

toluene50 degC 1 h

OHR3

R1

R2

OHMe

Ph

S

OHMe

OMe

OHPh

Ph

OMe

3f 72

3h 763j 80

3g 84

3d 82

3c 83

OHMe

Ph

CF3

1 2 3

OHH

Ph

OMe

OHPh

Ph

OMe

O

O

OHPh

3e 92

F

OMe

OHPh

Ph

OMe

F3C

3i 62

R4R4

MeO

[Me4N]










Chapter 5

110

OHMe

t-Bu

S

3k 89

B +1 mol Pd

toluene

50 degC 1 h

2a

t-Bu

S

(1)

1c

[Me4N]

OHMe

n-Bu

Me

3l 80

B

n-Bu

+1 mol Pd

toluene50 degC 1 h

2a

Me

(2)

1d

[Me4N]










n-Hex

13 equiv

Ph

Li

065 equiv

(H-9-BBN) 2


1 mol Pd

toluene 50 degC 1 h

10 equiv 2aOH

Me

n-Oct

11 equiv

3m 91 (based on 2a)

B

n-Oct

PhLi

Ph




Chapter 5

111


in 59 yield11


OHH

Ph

OMe

MnO2

DCM rt

Ph

OMe

O

NH2NH2 KOHPh

OMe

4 96 5 59

3n 74

(CH2OH)2 150 C

1a +

CHO

I2b

1 mol Pd

Conclusions




Chapter 5

112



and 13


B at 128 MHz)



13C) CD3CN (δ = 194 for

1H δ = 132 for


11B) IR






(Merck)





and alkynylborate14




Li

BPh

+

B

Ph

1a


2) Me4NCl MeOH

[Me4N]

MeO

MeO










Chapter 5

113

B

Ph

1a

[Me4N]

MeO


(m 2H) 296 (s 12H) 372 (s 3H) 668-675 (m 2H) 685-691 (m 1H) 700-712 (m

4H) 743 (d J = 64 Hz 2H) 13

C NMR (CD3CN) δ = 256-272 (m) 270 274 322

350 557 560 955 1145 1227 (2C) 1273 1324 1341 1578 The boron-bound


11B NMR


3292079

B

Ph

1b

[Me4N]

OMe


(m 2H) 295 (s 12H) 374 (s 3H) 666-675 (m 2H) 702-718 (m 5H) 733 (d J =

84 Hz 2H) 13

C NMR (CD3CN) δ = 254-274 (m) 270 273 321 350 554 560





B

nBu

1d

[Me4N]

Me


(m 4H) 136-157 (m 6H) 170-196 (m 4H) 220-234 (m 5H) 304 (s 12H)

697-701 (m 2H) 704-709 (m 2H) 13

C NMR (CD3CN) δ = 152 212 270

271-290 (m) 282 288 318 324 357 561 1279 1296 1314 1344 The

Chapter 5

114




[M-(NMe4)]- 2932446 Found 2932454

B

Ph

1e

[Me4N]

F3C


(m 2H) 292 (s 12H) 690-696 (m 1H) 710-718 (m 2H) 728 (dd J = 88 08 Hz

2H) 744-752 (m 4H) 13

C NMR (CD3CN) δ = 252-270 (m) 269 273 321 351






B

Ph

1f

[Me4N]

S



48 32 Hz 1H) 703-719 (m 6H) 13

C NMR (CD3CN) δ = 266 272 270-286 (m)

323 348 560 962 1231 1256 1266 1274 1290 1300 1314 The boron-bound

sp2 and sp


11B NMR


- 3051541 Found

3051541

Chapter 5

115


(H-9BBN) 2

H tBu

THF 0 degC

THF -78 degC to rt

2) Me4NCl MeOH

Li

1)S

B

1c

[Me4N]

S

tBu














B

1c

[Me4N]

S

tBu


4H) 222-235 (m 2H) 306 (s 12H) 552 (d J = 172 Hz 1H) 591 (d J = 176 Hz


Hz 1H) 13

C NMR (CD3CN) δ = 273 276 278-296 (m) 311 327 341 352 561





Chapter 5

116












OHMe

3aOMe

NOE

no NOE

IR (ATR) 3315 1508 1248 752 694 cm-1

1H NMR δ = 159 (s 3H) 204 (bs 1H)

382 (s 3H) 684-690 (m 2H) 721-730 (m 8H) 742-748 (m 2H) 751-755 (m

1H) 13

C NMR δ = 239 552 832 1139 1208 1218 1265 1268 1272 1280


C23H21O2 [M+H]+ 3291536 Found 3291556

OHMe

OMe

3b

NOE

no NOE

IR (ATR) 3319 1508 1248 760 702 cm-1

1H NMR δ = 160 (s 3H) 208 (s 1H)

378 (s 3H) 674-680 (m 2H) 718-723(m 1H) 724-744 (m 9H) 750-755 (m

1H) 13

C NMR δ = 241 551 833 1134 1205 1218 1263 1270 1274 1284


Chapter 5

117

C23H20O2Cl [M+Cl]- 3631146 Found 3631148

OHMe

Ph

3cCF3

IR (ATR) 3298 1319 1121 750 696 cm-1

1H NMR δ = 160 (s 3H) 210 (bs 1H)

716-722 (m 1H) 723-732 (m 5H) 737-747 (m 4H) 752-764 (m 3H) 13

C NMR

δ = 240 833 1205 1221 1241 (q JC-F = 2701 Hz) 1255 (q JC-F = 37 Hz) 1269

1277 1282 1286 1293 1295 (q JC-F = 322 Hz) 1296 1341 1373 1385 1414


- 3651159 Found 3651159

OHMe

Ph

3d

S

IR (ATR) 3319 1350 1088 752 694 cm-1

1H NMR δ = 177 (s 3H) 209 (bs 1H)

696-702 (m 2H) 718 (dd J = 52 Hz 12Hz 1H) 723-730 (m 2H) 735-740 (m

3H) 742-752 (m 3H) 753-758 (m 1H) 13

C NMR δ = 254 833 1207 1216

1259 1265 1266 1275 1282 1287 1290 1294 1347 1360 1374 1410 1426


+ 3050995 Found 3050992

OHMe

OMe

3e

IR (ATR) 3310 1508 1244 1034 758 cm-1

1H NMR δ = 144 (s 3H) 158-202 (m


5H) 747 (d J = 68 Hz 1H) 13

C NMR δ = 238 266 267 305 311 382 552

822 1136 1211 1219 1257 12789 12793 1304 1406 1409 1467 1499


+ 3382115 Found 3382104

Chapter 5

118

OHH

Ph

3fOMe

MeO

IR (ATR) 3472 1601 1508 1244 704 cm-1

1H NMR δ = 174 (d J = 88 Hz 1H)


= 80 Hz 24 Hz 1H) 692-697 (m 2H) 718-730 (m 5H) 732-736 (m 2H) 753 (d

J = 84 Hz 1H) 13

C NMR δ = 552 555 766 1072 1109 1143 1244 1267 1272

1283 1292 1303 1342 1363 1390 1445 1457 1592 1606 HRMS (ESI+)


OHPh

Ph

3gOMe

IR (ATR) 3422 1508 1244 1028 746 698 cm-1

1H NMR δ = 248 (s 1H) 385 (s

3H) 695 (d J = 88 Hz 2H) 704-714 (m 5H) 715-732 (m 7H) 736-740 (m 2H)

755 (d J = 88 Hz 2H) 13

C NMR δ = 552 868 1141 1210 1231 1250 1268

12698 12702 1271 1278 12836 12844 1294 1304 1340 1402 1417 1427


+ 3911693 Found

3911718

OHPh

Ph

3hOMe

O

O

IR (ATR) 3362 1470 1244 1034 696 cm-1

1H NMR δ = 239 (s 1H) 385 (s 3H)

591 (dd J = 164 16 Hz 2H) 673 (d J = 44 Hz 2H) 690-696 (m 2H) 702-708

(m 5H) 720-736 (m 5H) 749-754 (m 2H) 13

C NMR δ = 552 863 1012 1024

Chapter 5

119

1049 1142 1249 12690 12692 1270 1278 1285 1292 1304 1340 1367


+

4341518 Found 4341505

OHPh

Ph

3iOMe

F3C

IR (ATR) 3545 1508 1321 1115 696 cm-1

1H NMR δ = 249 (s 1H) 387 (s 3H)

694-700 (m 2H) 704-715 (m 5H) 723-738 (m 6H) 742-755 (m 4H) 13

C NMR

δ = 553 866 1145 1177 (q JC-F = 37 Hz) 1233 1241 (q JC-F = 36 Hz) 1242 (q

JC-F = 2702 Hz) 1249 1260 1275 1276 1280 1287 1295 1304 1308 (q JC-F =


C29H21F3O2Cl [M+Cl]- 4931177 Found 4931192

OHPh

3j

F

OMe

IR (ATR) 3356 1242 1028 741 696 cm-1

1H NMR δ = 164-178 (m 2H) 183-208


4H) 719-737 (m 6H) 13

C NMR δ = 2675 2681 308 310 383 551 862 1114


1268 1271 1283 1303 1371 (d JC-F = 29 Hz) 1410 1418 (d JC-F = 15 Hz)



+ 4001839 Found 4001835

OHMe

S

tBu

3k

Chapter 5

120

IR (ATR) 3298 1358 1078 756 689 cm-1

1H NMR δ = 111 (s 9H) 168 (s 3H)

188 (s 1H) 640 (d J = 164 Hz 1H) 656 (d J = 164 Hz 1H) 718-730 (m 4H)

739-751 (m 3H) 13

C NMR δ = 257 295 340 822 1169 1204 1215 1242

1255 1262 1283 1285 1324 1346 1415 1452 1462 1506 HRMS (ESI+)


OHMe

nBu

OMe3l

IR (ATR) 3335 1508 1084 918 758 cm-1

1H NMR δ = 085 (t J = 72 Hz 3H) 130

(tt J = 72 72 Hz 2H) 141-167 (m 6H) 229-250 (m 5H) 702-706 (m 1H)

716-728 (m 6H) 744-748 (m 1H) 13

C NMR δ = 138 213 232 237 252 314

829 1198 1215 1256 1282 1286 1291 1318 1370 1374 1430 1492 1496


+ 2931900 Found 2931890



nHex

(H-9BBN) 2


Li

Ph

B

nOct

Li

Ph

Me

O

I


toluene 50 degC 1 h

H2O2 aq

NaOH aq

OHMe

nOct

Ph3m

MeOH




Chapter 5

121













yield)

OHMe

nOct

Ph3m

IR (ATR) 3335 1456 1078 752 698 cm-1

1H NMR δ = 096 (t J = 68 Hz 3H)

129-156 (m 15H) 160 (s 1H) 208-227 (m 2H) 274-281 (m 2H) 287-294 (m

2H) 719-728 (m 5H) 729-736 (m 3H) 742 (d J = 72 Hz 1H) 13

C NMR δ = 141

226 234 247 277 293 294 295 304 319 345 825 1186 1213 1252 1260


[M]+ 3622610 Found 3622619

OHH

Ph

OMe

3n

IR (ATR) 3354 1508 1246 764 692 cm-1

1H NMR δ = 185 (bs 1H) 386 (s 3H)

567 (s 1H) 692-697 (m 2H) 718-738 (m 10H) 763-766 (m 1H) 13

C NMR δ =

552 773 1143 1206 1237 1263 1268 1272 1283 1287 1292 1303 1342


- 3131234

Found 3131237

Chapter 5

122

The 1H


15


OHH

Ph

OMe

3n

MnO2

DCM rt

Ph

OMe

4

O







The 1H


16

Ph

OMe

4

O

(CH 2OH)2

NH2NH2

KOH Ph

OMe

5








The 1H


5

Chapter 5

123






1395ndash1411



17638ndash17640





3201ndash3222



















Chapter 5

124












3283ndash3292









74








Chem 1989 54 1485ndash1491



2006 128 1828

Chapter 5

125



4781-4787


Chem 1989 54 1485

Chapter 5

126

127

List of Publication

Chapter 1



Angew Chem Int Ed 2012 51 11750-11752

Chapter 2


Benzosultams


J Am Chem Soc 2013 135 19103-19106

Chapter 3





Org Lett 2009 11 5434-5437

Chapter 4


Units


Org Lett 2010 12 3179-3181

Chapter 5




Eur J Org Chem 2013 1421-1424

Other Publication




Chem Lett 2013 42 1076

Preface




alkynyl borates
































encouragement

Yasuhiro Shimamoto



Kyoto University

Contents


Chapter 1


Chapter 2


Benzosultams 29

Chapter 3



Halides 67

Chapter 4


Units 89

Chapter 5





1









sultams














sun

CO2energy charge

Ph

O

NTs

Me

N

Ts

OHPh

OO

O

Ph

NHTs


2


benzosultams




developed456


shift7

MH14-metal shift

1

2 3

4

HM

1

2 3

4

H M1

23

4

5

M H1

23

4

515-metal shift






N

Ts

Ph OHMe

SN

MeO O

Ph OH

cat Rh





chemistry10






We


alkynylborates13

R1 B

R2

R2

R2

+ R3 Br

R3

R1 R2

B

R2

R2


3






obtained

Et

Ph

Ph

B O+

PhBr LPd(-allyl)Cl

L = XANTPhos

LPd(-allyl)Cl

L = P(o-tol)3 Ph

Et

Ph

B O

B

Et

Ph

Et

Ph

B

Ph

Ph

Et

B

Ph

Me3NO

Me3NO

[Me4N]







MeO

Br

I

Br

NaOH

R Ph

MeO Br

B

R

Ph

RB

Ph

OMe

[Me4N]

R Ph

MeOR Ph

Br

R =OMOM

n

B

R

Ph

[Me4N] I

Br

NaOH

R Ph

MeOR Ph

Br

n = 2~4

Pd-XANTPhos

Pd-XANTPhos






4


regioselectively

I

Me

O+

MeOH

R2

R1Pd-XANTPhosB

R2

R1

[Me4N]


5

Reference





































6








10990




2003 Vol 3





Q Z J Med Chem 2009 52 4192



2006 250 1107



2419













7



17638ndash17640


8

Chapter 1

9

Chapter 1


Ketones

Abstract






Chapter 1

10

Introduction







2 One







starting substances


CO2

sun

CO2energy charge

high energy

intermediates











8






Chapter 1

11


Ph

O

NTs

Mesolar light

N

Ph OH

Ts

2a 91

1aDMA







over 04 kWm-2



in eight hours on


Figure





kWhm-2



Chapter 1

12


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

0

20

40

60

80

100

0 1 2 3 4 5 6











(56)

Chapter 1

13


40 equiv Cs2CO3

1 atm CO2

DMA 60 degC

OO

O

Ph

NHTs

3a 93

N

Ph OH

Ts

2a








N

Ph O

Ts

A

N

Ph O

Ts

B

O

O

OO

O

Ph

NTs

CO2

H

C

Cs2CO3

CsHCO 3

Cs

Cs

Cs

2

1

N

Ph OH

Ts

2a

OO

O

Ph

NHTs

3a












N

Ts

OHPh

4

Chapter 1

14




solar light

CO2Cs2CO3

60degCDMAPh

O

NTs

Me

1a

OO

O

Ph

NHTs

3a 83






chloro groups10





Ar

O

NR

Me OO

O

Ar

NHR3

1

OO

O

NHTs3b 80

MeO

OO

O

NHTs3c 57

F3C

OO

O

NHTs3d 73

Cl

OO

O

NHTs3e 85

Br

OO

O

Ph

NH

3f 87

O2S OMe

OO

O

Ph

NH

3g 85

O2S CF3

OO

O

Ph

NH

3h 87

O2S

N

solar lightCO2

Cs2CO3

60degCDMA




Chapter 1

15

Conclusions















Chapter 1

16












indicator (Merck)






Ph

O

NTs

MeTsClMeNH2 +

Et2OTsNHMe

CH3CN

K2CO3












Chapter 1

17


Ph

O

NTs

Me


745-751 (m 2H) 760 (tt J = 76 12 Hz 1H) 771-775 (m 2H) 795-799 (m 2H)

13C NMR δ = 215 356 560 1275 1282 1288 1297 1338 1347 1348 1436


+ 3041002 Found mz 3040994 IR

(ATR) 1693 1339 1227 1157 743 cm-1

O

NTs

Me

1bMeO


733 (d J = 80 Hz 2H) 770-774 (m 2H) 796-802 (m 2H) 13

C NMR δ = 215

355 555 558 1139 1275 1277 1296 1307 1346 1436 1640 1921 HRMS


+ 3341108 Found mz 3341101 IR (ATR) 1688

1601 1329 1180 1159 cm-1

O

NTs

Me

1cF3C


= 84 Hz 2H) 776 (d J = 84 Hz 2H) 812 (d J = 84 Hz 2H) 13

C NMR δ = 215

357 564 1234 (q JC-F = 2711 Hz) 1259 (q JC-F = 37 Hz) 1276 1288 1298



1121 1109 cm-1

Chapter 1

18

O

NTs

Me

1dCl


(m 2H) 771 (d J = 80 Hz 2H) 792-796 (m 2H) 13

C NMR δ = 216 356 561



1159 1088 cm-1

O

NTs

Me

1eBr


= 84 Hz 2H) 771 (d J = 84 Hz 2H) 786 (d J = 84 Hz 2H) 13

C NMR δ = 215

356 561 1275 1291 1297 1298 1321 1334 1344 1438 1930 HRMS (ESI+)


1223 1155 810cm-1

Ph

O

NS

Me

1f

OMe

OO

1H NMR δ = 282 (s 3H) 389 (s 3H) 456 (s 2H) 698-703 (m 2H) 746-751 (m

2H) 761 (tt J = 72 12 Hz 1H)776-781 (m 2H) 796-800 (m 2H) 13

C NMR δ =

356 556 561 1142 1283 1288 1294 1297 1338 1348 1630 1938 HRMS


+ 3200951 Found mz 3200943 IR (ATR) 1692

1342 1259 1155 741 cm-1

Chapter 1

19

Ph

O

NS

Me

1g

CF3

OO


780 (d J = 84 Hz 2H) 790-794 (m 2H) 798 (d J = 80 Hz 2H) 13

C NMR δ =

356 558 1233 (q JC-F = 2711 Hz) 1261 (q JC-F = 36 Hz) 12796 12799 1289



1059 748 cm-1

Ph

O

NS

Me

1h

N

OO

1H NMR δ = 302 (s 3H) 486 (s 2H) 744-753 (m 3H) 757-762 (m 1H)

788-798 (m 4H) 870 (ddd J = 48 16 08 Hz 1H)13

C NMR δ = 363 569 1224



752 cm-1


Ph

O

NTs

Mesolar light

N

Ph OH

TsDMA rt

1a

2a








Chapter 1

20


N

Ph OH

Ts


2H) 728-737 (m 5H) 740 (d J = 80 Hz 2H) 779 (d J = 80 Hz 2H) 13

C NMR δ

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS




N 458 O 1555 S 1058 IR (ATR) 3477 1333 1184 1148 671 cm-1


N

Ph OH

Ts

2a

40 equiv Cs2CO3

1 atm CO2

DMA 60 C

OO

O

Ph

NHTs

3a








mmol 93 yield)

Chapter 1

21



40 equiv Cs2CO3

60 CPh

O

NR

Me OO

O

Ph

NHR3a

1a

solar light

DMA rt

1 atm CO2











OO

O

Ph

NHTs



726-732 (m 4H) 734-743 (m 3H) 769-773 (m 2H) 13

C NMR δ = 215 503

724 850 1242 1269 1292 1299 1365 1381 1439 1542 HRMS (ESI+) Calcd

for C17H18NO5S M+H+


C 5878 H 493 N 403 O 2303 S 923 Found C 5871 H 496 N 389 O

2284 S 932 IR (ATR) 3261 1773 1435 1319 1045 cm-1

Chapter 1

22

OO

O

NHTs

3b

MeO



56 Hz 1H) 688-693 (m 2H) 719-724 (m 2H) 728 (d J = 80 Hz 2H) 770 (d J =

84 Hz 2H) 13

C NMR δ = 215 503 554 724 848 1145 1256 1269 1298


+

3781006 Found mz 3780996 IR (ATR) 3238 1794 1518 1329 1057 723 cm-1

OO

O

NHTs

3c

F3C



729 (d J = 84 Hz 2H) 746 (d J = 84 Hz 2H) 765-771 (m 4H) 13

C NMR δ =

215 501 722 846 1235 (q JC-F = 2704 Hz) 1249 1263 (q JC-F = 37 Hz) 1268



1067 cm-1

OO

O

NHTs

3d

Cl



722-727 (m 2H) 728 (d J = 84 Hz 2H) 735-739 (m 2H) 769 (d J = 84 Hz 2H)

13C NMR δ = 215 502 723 847 1257 1268 1294 1300 1353 1364 1365


+ 3820510 Found mz

Chapter 1

23

3820506 IR (ATR) 3250 1800 1325 1155 1069 cm-1

OO

O

NHTs

3e

Br



716-720 (m 2H) 728 (d J = 80 Hz 2H) 750-755 (m 2H) 766-770 (m 2H) 13

C

NMR δ = 215 501 723 847 1235 1260 1268 1300 1323 1364 1370 1441


+ 4260005 Found mz 4260003

IR (ATR) 3252 1800 1331 1175 1057 cm-1

OO

O

Ph

NH

SO

O

OMe



693-698 (m 2H) 727-732 (m 2H) 734-744 (m 3H) 773-778 (m 2H) 13

C NMR

δ = 503 556 724 849 1145 1242 1291 1292 1310 1381 1541 1632 HRMS


+ 3640849 Found mz 3640836 IR (ATR) 3246

1801 1325 1155 1067 cm-1

OO

O

Ph

NH

SO

O

CF3

3g

Chapter 1

24



2H) 735-744 (m 3H) 775 (d J = 88 Hz 2H) 796 (d J = 84 Hz 2H) 13

C NMR δ

= 505 725 851 1231 (q JC-F = 2711 Hz) 1241 1265 (q JC-F = 37 Hz) 1274



1161 1105 cm-1

OO

O

Ph

NH

SO

O

N




1H) 798 (d J = 76 Hz 1H) 866 (d J = 44 Hz 1H) 13

C NMR δ = 510 723 849



1175 1063 cm-1


N

Ts

OHPh

N

Ts

O CeCl 3

PhLi

THF -78 C to rt

4






Chapter 1

25






N

Ts

OHPh


351-364 (m 4H) 726-738 (m 7H) 773-777 (m 2H) 13

C NMR δ = 215 396

469 608 804 1250 1276 1280 1286 1297 1339 1418 1435 HRMS (ESI+)


1325 1159 1101 770 cm-1

Chapter 1

26











Soc 2011 133 12881

























25 312

Chapter 1

27








Chapter 1

28

Chapter 2

29

Chapter 2



Abstract







Chapter 2

30

Introduction














A



Indanones are


A rearrangement













Whereas







Chapter 2

31




N

HO Ph

S NS Me

HO PhMe

1a2a 96

Me

O

OO O


2) is





The generated








N

S O

O

O[Rh]

Ph

SN

[Rh]O Ph

O OMe

[Rh] OH

N

S O

O

O Ph

H

[Rh]

H

N

[Rh]O Ph

S O

O

Me Me

Me

Me

1a

H2O

2a

A B

CD

1a

A




Chapter 2

32








N

HO Ph

SN

S CH19D11

HO Ph

D3C

1a-d2a-d 96

D3C

O

O

O O

D

D

D

D

D

D

H01D09

8



D12




Application




1

2

SN

HO Ar

O OMe

N

HO Ar

S O

O


K2CO 3 (20 equiv)


NS Me

HO PhMe

2a

91 er = 928

O O

NS Me

HO Ph

2b

95 er = 937

O O

S

NS Me

HOMe

2c

90 er = 937

O O

OMe

NS Me

HOMe

2c

92 er = 919

O O

CF3



Chapter 2

33










HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6 84

5 56



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3


PhMgBr

THF rt 1 h N

HO

Ts

Me

1e 93

er gt 991 dr = 201

Ph

3







SN

HO PhMe

O OMe

MeN

HO Ph

S O

O

Me

Me

1e

er gt 991 dr = 201

2e 99

er gt 991 dr gt 201





Chapter 2

34









SN

PhRhOMe

O OMe

Me

SN

PhRhOMe

O OMe

Me

favored

disfavored

F

F

NSRh

Ph

Me

O

O

MeO

H

Me

E

E

NSRh

Ph

Me

O

O

MeO

Me

H














Chapter 2

35


1

er gt 991 dr gt 201

2

er gt 991 dr gt 201

SN

HO ArR

O OMe

N

HO Ar

S O

O





1 N

HO Ph

S O

O

Me

Me

1f

SN

HO PhMe

O OMe

Me

2e 99

6 N

HO

S O

O

Me

1k

OMe

SN

HOMe

O OMe

2k 97

OMe

2

N

HO Ph

S O

O

MeO

Me

1g

SN

HO PhMe

O OMe

MeO

2g 98

7 N

HO

S O

O

Me

Me

1l

CF3

SN

HOMe

O OMe

Me

2l 97

CF3

3 N

HO Ph

S O

O

F3C

Me

1h

SN

HO PhMe

O OMe

F3C

2h 99

8 N

HO Ph

S O

O

Me

i-Pr

1m

SN

HO Phi-Pr

O OMe

Me

2m 97

4

N

HO Ph

S O

O

Me

1iMe

SN

HO PhMe

O OMeMe

2i 99

9 N

HO Ph

S O

O

Me

SMe

SN

HO Ph

O OMe

Me

2n 97

SMe

5 N

HO Ph

S O

O

Me

S

1j

SN

HO PhMe

O OMeS

2j 99



Chapter 2

36

Conclusions






Chapter 2

37





13C NMR


13C at 10069












N

OHNEt3

DCM rt 12 h


2) PhMgBrTHF rt 3 h

N

HO Ph

1a

TsCl

N

OH

8a

H HCl

Ts Ts









Chapter 2

38

N

S

Me

O

O

OH

8a 1H NMR = 213 (bs 1H) 245 (s 3H) 350-361 (m 2H) 394-404 (m 2H)

442-452 (m 1H) 737 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR =



-1

N

S

D3C

O

O

OH

8a-d

D

D

D

D

1H NMR = 283 (bs 1H) 349-355 (m 2H) 389-396 (m 2H) 435-444 (m 1H)



+ 2351128 Found mz

2351125 IR (ATR) 3503 1333 1142 1059 638 cm-1

N

S O

O

OH

8b

S

1H NMR = 277 (bs 1H) 357-364 (m 2H) 400-407 (m 2H) 441-450 (m 1H)


1H) 13



1038 737 cm-1

Chapter 2

39














N

HO Ph

S

1a

Me

O

O


2H) 728-737 (m 5H) 739 (d J = 84 Hz 2H) 778 (d J = 80 Hz 2H) 13

C NMR

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS


+ 3041002 Found mz 3040995 IR (ATR) 3477

1333 1184 1148 671 cm-1


N

HO Ph

S

1a-d

D3C

O

O

D

D

D

D


(m 5H) 13

C NMR = 203-211 (m) 652 703 1244 1281 (t JC-D = 247 Hz)


Chapter 2

40


702 648 cm-1

N

HO Ph

S

S

O

O



1H) 13

C NMR = 656 702 1244 1280 1283 1288 1331 13387 13392 1417


+ 2960410 Found mz 2960404 IR

(ATR) 3524 1333 1161 1148 748 cm-1

N

HO

S

Me

O

O

OMe

1c



2H) 775 (d J = 80 Hz 2H) 13

C NMR =216 553 652 702 1139 1259 1285


+

3341108 Found mz 3341097 IR (ATR) 3460 1518 1331 1250 1146 cm-1

N

HO

S

Me

O

O

CF3



C NMR

Chapter 2

41

=216 654 697 1239 (q JC-F = 2704 Hz) 1249 1255 (q JC-F = 37 Hz) 1284



1109 1076 cm-1


1l-1n

HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6a

5a



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3

acetone H2O

rt 10 h 4a

PhMgBr

THF rt 1 h N

OH

Ts

Me

1e

Ph

3a



procedure16













Me

NHTs

O

N2


Chapter 2

42

2H) 730 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR = 194 215 539


+

2680750 Found mz 2680747 IR (ATR) 2112 1639 1337 1319 1161 cm-1

[]27

D = -1184 (c = 079 in CHCl3)


i-Pr

NHTs

O

N2



2H) 769 (d J = 84 Hz 2H) 13

C NMR =169 193 215 315 548 647 1273


+ 2961063

Found mz 2961060 IR (ATR) 2129 1622 1362 1329 1161 cm-1

[]28

D = -730 (c = 071 in CHCl3)

NHTs

O

N2

5c

SMe

1H NMR = 174-196 (m 2H) 204 (s 3H) 242 (s 3H) 244-252 (m 2H)

390-400 (m 1H) 541 (s 1H) 560-572 (m 1H) 730 (d J = 84 Hz 2H) 772 (d J =

84 Hz 2H) 13

C NMR = 153 215 297 323 545 585 1272 1297 1366 1439


+ 3280784 Found mz 3280779

IR (ATR) 2129 1618 1375 1339 1163 cm-1

[]29

D = -506 (c = 063 in CHCl3)









Chapter 2

43

N

O

Ts

Me

6a

1H NMR = 145 (d J = 68 Hz 3H) 246 (s 3H) 443-454 (m 2H) 473-480 (m

1H) 736-742 (m 2H) 776-781 (m 2H) 13

C NMR = 157 216 696 810 1284


+ 2400689

Found mz 2400688 IR (ATR) 1825 1339 1155 669 cm-1

[]28

D = 614 (c = 081 in CHCl3)


N

O

Ts

i-Pr

6b

1H NMR = 099-111 (m 6H) 206-218 (m 1H) 246 (s 3H) 441 (dd J = 164 36


2H) 777 (d J = 80 Hz 2H) 13

C NMR = 174 181 216 304 703 903 1284


+ 2681002

Found mz 2680998 IR (ATR) 1815 1340 1155 1007 671 cm-1

[]29

D = 567 (c = 095 in CHCl3)

N

O

Ts

6c

SMe

1H NMR = 204 (s 3H) 209-218 (m 2H) 247 (s 3H) 265-279 (m 2H) 446 (d


2H) 780 (d J = 80 Hz 2H) 13

C NMR = 147 216 291 293 705 832 1286


+ 3000723

Found mz 3000718 IR (ATR) 1813 1342 1308 1157 667 cm-1

[]29

D = 1183 (c = 036 in CHCl3)


Chapter 2

44










N

HO

S O

O

Me

Me

1e

H

NOE

NOE



(m 3H) 739 (d J = 84 Hz 2H) 777 (d J = 84 Hz 2H) 13

C NMR = 144 216

628 702 731 1247 1279 1284 1285 1298 1319 1415 1443 HRMS (ESI+)


1155 1092 667 cm-1

[]25




Chapter 2

45

N

HO

S O

O

Me

1l

H

NOE

NOE

CF3

Me



739-747 (m 4H) 777 (d J = 84 Hz 2H) 13

C NMR = 143 216 630 706 727

1238 (JC-F = 2704 Hz) 1253 1254 (JC-F = 36 Hz) 1285 1299 1301 (JC-F = 324


+ 3861032

Found mz 3861025 IR (ATR) 3422 1327 1151 1109 839 cm-1

[]28




N

HO

S O

O

Me

iPr

1m

H

NOE

NOE



= 100 Hz 1H) 690-696 (m 2H) 712-720 (m 3H) 732 (d J = 80 Hz 2H) 773 (d

J = 80 Hz 2H) 13

C NMR = 190 193 215 291 641 729 801 1247 1275


+

3461471 Found mz 3461466 IR (ATR) 3454 1331 1163 739 669 cm-1

[]27



Chapter 2

46


N

HO Ph

S O

O

1n

Me

SMe

1H NMR = 202 (s 3H) 218-258 (m 8H) 388-394 (m 2H) 427 (dd J = 84 48

Hz 1H) 688-693 (m 2H) 714-721 (m 3H) 740 (d J = 80 Hz 2H) 779 (d J = 80

Hz 2H) 13

C NMR = 154 216 290 297 634 725 733 1246 1277 1284


+

3781192 Found mz 3781188 IR (ATR) 3481 1339 1157 702 669 cm-1

[]28












N

HO

S O

O

Me

Me

1f

H

NOE

NOE


1H) 398 (q J = 64 Hz 1H) 424 (dd J = 84 08 Hz 1H) 732-744 (m 5H)

750-755 (m 2H) 774-778 (m 2H) 13

C NMR = 165 216 627 718 739 1257

Chapter 2

47



-1

[]25






HO2C Me

NHCbz

Me

NHCbz

O

N2N

O

Cbz

Me

6d5d

1) (COCl) 2 DMF

2) CH2N2 Rh2(OAc)4 (05 mol )

DCM rt 12 h4d

PhMgBr

THF rt 1 h

N

OH

Cbz

Me

7a

Ph

N

OH

H

Me

PhPd C (5 mol )

H2 (1atm)

MeOH rt 12 h

MeO SO2Cl

NEt3

DCM rt 12 h

N

HO Ph

S O

O

MeO

Me

1g









Me

NHCbz

O

N2

5d 1H NMR = 134 (d J = 68 Hz 3H) 420-436 (m 1H) 504-516 (m 2H) 534-564

(m 2H) 728-736 (m 5H) 13

C NMR = 184 535 (2C) 669 1280 1282 1285


+ 2481030 Found mz

2481028 IR (ATR) 2116 1717 1636 1533 1252 cm-1

[]28

D = -434 (c = 085 in CHCl3)


Chapter 2

48







N

O

Cbz

Me

6d


Hz 1H) 498-505 (m 1H) 513-521 (m 2H) 731-739 (m 5H) 13

C NMR = 153



696 cm-1

[]29

D = 390 (c = 068 in CHCl3)










N

OH

Cbz

Me

7a

Ph


= 96 Hz 1H) 458 (q J = 64 Hz 1H) 507-518 (m 2H) 729-746 (m 10H) 13

C

NMR = 142 623 667 689 730 1246 1278 1279 1280 1285 1287 1366

Chapter 2

49


+ 2981438 Found mz

2981433 IR (ATR) 1670 1423 1248 1016 702 cm-1

[]29

D = 46 (c = 089 in CHCl3)

N

OH

Cbz

Me

7b

MeO


1H) 432 (d J = 96 Hz 1H) 452-461 (m 1H) 506-518 (m 2H) 687-694 (m 2H)

726-739 (m 7H) 13

C NMR = 143 553 622 666 687 729 1140 1260 1278


+

3281543 Found mz 3281539 IR (ATR) 1682 1418 1352 1024 696 cm-1

[]29

D = 02 (c = 085 in CHCl3)








pressure







mmol 58 yield)

Chapter 2

50

N

HO

S O

O

MeO

Me

1g

H

NOE

NOE


390 (s 3H) 399 (d J = 92 Hz 1H) 419 (q J = 60 Hz 1H) 698-707 (m 4H)

720-727 (m 3H) 779-785 (m 2H) 13

C NMR = 143 557 627 701 731 1144



-1

[]28




N

HO

S O

O

F3C

Me

1h

H

NOE

NOE


406 (d J = 92 Hz 1H) 430 (qd J = 64 08 Hz 1H) 694-699 (m 2H) 721-727

(m 3H) 784 (d J = 80 Hz 2H) 801 (d J = 84 Hz 2H) 13

C NMR = 145 629

706 729 1232 (JC-F = 2711 Hz) 1245 1263 (JC-F = 37 Hz) 1283 12868 12871


+

3720876 Found mz 3720870 IR (ATR) 3503 1348 1323 1165 646 cm-1

[]28




Chapter 2

51

N

HO

S O

O

Me

1i

H

NOE

NOE


1H) 401 (d J = 88 Hz 1H) 422 (q J = 64 Hz 1H) 694-698 (m 2H) 720-724 (m

3H) 746-750 (m 2H) 767-772 (m 2H) 13

C NMR = 144 214 630 704 730

1247 1256 1279 1285 1286 1291 1341 1347 1395 1416 HRMS (ESI+)


1151 714 700 cm-1

[]29




N

HO

S O

O

Me

1j

H

NOE

NOE

S


Hz 1H) 425 (q J = 64 Hz 1H) 696-701 (m 2H) 720-728 (m 4H) 764-767 (m

1H) 769-772 (m 1H) 13

C NMR = 144 632 709 730 1246 1279 1281 1286


+ 3100566

Found mz 3100559 IR (ATR) 3508 1340 1151 756 669 cm-1

[]29




Chapter 2

52

N

HO

S O

O

Me

1k

H

NOE

NOE

OMe


1H) 394 (d J = 88 Hz 1H) 416 (q J = 64 Hz 1H) 670-675 (m 2H) 684-689 (m

2H) 756-762 (m 2H) 765-770 (m 1H) 786-790 (m 2H) 13

C NMR = 143 553

630 704 729 1138 1259 1283 1292 1332 1337 1348 1592 HRMS (ESI+)


1327 1155 606 cm-1

[]29





Screening







mmol 93 yield)

Chapter 2

53


rac -DM-BINAP

rac-BINAP

dppf

dppb

PPh3

dppe

46

trace

trace

yield

PCy3

Ligand

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

entry

1

2

3

4

5

6

7

8

nd

nd

nd

93

none nd

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a


entry Ligand yield

1

2

3

4

(R)-BINAP

(R)-DM-BINAP

(R)-SEGPHOS

(R)-DIFLUORPHOS

er

94

46

48

43

5

6

(R)-DM-SEGPHOS


3862

91

7

8

(R)-MeO-BIPHEP

(R)-MeO-DM-BIPHEP

64

91

892

3169

1288

1486

2476

2575

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a










Chapter 2

54

NS Me

HO PhMe

2a

O O


J = 148 Hz 1H) 683 (s 1H) 727-744 (m 6H) 781 (d J = 84 Hz 1H) 13

C NMR

= 216 361 626 732 1238 1263 1280 1284 1299 1301 1330 1412 1431


+ 3041002 Found mz 3040998 IR

(ATR) 3472 1325 1161 1142 735 cm-1

[]29




NS CH2D

HO Ph

D3C

2a-d

O O

D

D

D


J = 148 Hz 1H) 728-743 (m 5H) 13

C NMR = 201-210 (m) 358 (t JC-D = 212

Hz) 625 731 1234 (t JC-D = 249 Hz) 1262 1279 1283 1291-1300 (m 2C)


+ 3111441

Found mz 3111436 IR (ATR) 3524 1318 1290 1150 721 cm-1

NS Me

HO Ph

O O

S

2b


1H) 668 (d J = 52 z 1H) 730-738 (m 5H) 750 (d J = 52 Hz 1H) 13

C NMR =

378 630 722 1257 1264 1282 1286 1299 1338 1427 1467 HRMS (ESI+)


1150 1063 748 cm-1

[]29


Chapter 2

55



NS Me

HOMe

O O

OMe

2c


422 (d J = 148 Hz 1H) 684-690 (m 3H) 724-733 (m 3H) 774-779 (m 1H) 13

C

NMR = 216 360 553 626 729 1137 1237 1275 1299 1230 1328 1351


+ 3341108 Found mz

3341098 IR (ATR) 3441 1508 1250 1144 735 cm-1

[]29




NS Me

HOMe

O O

CF3



2H) 782 (d J = 80 Hz 1H) 13

C NMR = 216 360 625 731 12392 (q JC-F =

2708) 12395 1254 (q JC-F = 36 Hz) 1268 1298 1303 (q JC-F = 352) 1329


+ 3720876 Found

mz 3720869 IR (ATR) 3481 1323 1121 1067 733 cm-1

[]29




Chapter 2

56










SN

HO

Me

O OMe

Me

2e

H

NOE

NOE


= 68 Hz 1H) 675 (s 1H) 723-738 (m 6H) 777 (d J = 84 Hz 1H) 13

C NMR =

119 215 314 608 750 1242 1262 1275 1282 1298 1301 1316 1427


+ 3181158 Found mz

3181155 IR (ATR) 3481 1315 1163 1146 683 cm-1

[]28




SN

HO

Me

O OMe

MeO

2g

H

NOE

NOE

Chapter 2

57



5H) 782 (d J = 88 Hz 1H) 13

C NMR = 120 314 555 609 752 1144 1151



735 cm-1

[]29




SN

HO

Me

O OMe

F3C

2h

H

NOE

NOE



1H) 13

C NMR = 118 314 608 750 1228 (q JC-F = 2711 Hz) 1251 1258 (q



+ 3720876 Found

mz 3720872 IR (ATR) 3461 1325 1161 1142 739 cm-1

[]29




SN

HO

Me

O OMe

2i

H

NOE

NOE

Me

Chapter 2

58


J = 68 Hz 1H) 684 (d J = 80 Hz 1H) 718-736 (m 6H) 770 (s 1H) 13

C NMR

=119 211 314 607 748 1242 1262 1275 1282 1299 1338 1341 1395


+ 3181158 Found mz

3181155 IR (ATR) 3489 1448 1319 1148 735 cm-1

[]29




SN

HO

Me

O OMe

2j

H

NOE

NOES


1H) 656 (d J = 52 Hz 1H) 726-736 (m 5H) 743 (d J = 48 Hz 1H) 13

C NMR

= 114 319 619 742 1256 1266 1278 1284 1297 1334 1429 1480 HRMS


+ 3100566 Found mz 3100561 IR (ATR) 3524

1329 1151 1020 729 cm-1

[]29




SN

HO

Me

O OMe

2k

H

NOE

NOE

OMe


J = 68 Hz 1H) 685 (d J = 88 Hz 2H) 698-703 (m 1H) 722-730 (m 2H)

738-748 (m 2H) 785-790 (m 1H) 13

C NMR = 119 314 553 608 747 1136

Chapter 2

59



760 cm-1

[]26




SN

HO

Me

O OMe

2l

H

NOE

NOE

CF3

Me



= 84 Hz 2H) 778 (d J = 80 Hz 1H) 13

C NMR = 119 215 313 607 749




-1

[]26




SN

HO

iPr

O OMe

2m

H

NOE

NOE

Me


(m 1H) 264 (s 1H) 285 (s 3H) 441 (d J = 100 Hz 1H) 685 (s 1H) 714-735 (m

4H) 748 (d J = 76 Hz 2H) 772 (d J = 80 Hz 1H) 13

C NMR = 211 214 217

278 330 718 742 1244 1256 1270 1283 1292 1295 1300 1435 1442


+ 3461471 Found mz 3461466 IR

Chapter 2

60

(ATR) 3412 1315 1165 1146 683 cm-1

[]29




SN

HO

O OMe

2n

H

Me

NOE

SMe

1H NMR = 160-170 (m 1H) 184 (s 3H) 212-226 (m 4H) 230-242 (m 2H)

254-263 (m 1H) 294 (s 3H) 471 (dd J = 108 28 Hz 1H) 675 (s 1H) 722-738

(m 6H) 776 (d J = 80 Hz 1H) 13

C NMR = 150 215 242 301 321 643 748

1245 1262 1276 1283 12986 12993 1312 1429 1437 1441 HRMS (ESI+)


1165 1134 748 cm-1

[]28









was used as a


and


21 All



Chapter 2

61



2e

formula C17H19NO3S

fw 31739

T (K) 100(2)


space group P21c

a (Aring) 105967(5)


3) 152058(13)

Z 4 Dcalc (gcm

3) 1386

(mm-1

) 0225 F(000) 672



348500135

params 203 GOF on F

2 1069

R1 wR2 [Igt2(I)]

00322 00868

R1 wR2 (all data)

00335 00878

Chapter 2

62

























Med Chem 2003 46 1116








Chapter 2

63

































Chapter 2

64




2012 51 9160





11437-11439
























Chapter 2

65











2548-2551







11750









32 115



Chapter 2

66

Chapter 3

67

Chapter 3




Halides

Abstract






Chapter 3

68

Introduction
















2) are












several months


Et LiB

Ph

+B

Ph

Et

1a 74

(a)(b)[Me4N]


Chapter 3

69

















OMe

BrB

Ph

Et

OMe

3a

Ph

Et

OMe

H

4a

Pd-ligand AcOH

2a

+B

Ph

Et

1a

[Me4N]


EZ of 4ab

1 P(o-tol)3 69 397

2 P(t-Bu)3 47 1783

3 1-[(t-Bu)2P](biphenyl) 18 2872

4 2-[(t-Bu)2P](11-binaphthyl) 21 6733

5 DPEPhos 24 928



analysis



Chapter 3

70









Pd(0)

Pd

MeO

B

PdEt

OMe

Ph

B

Ph

Et

2a

BC

Pd

MeO

Br

A

1a

3a







dominates10
















Chapter 3

71










Chapter 3

72


BO

Ph

Et

OMe

5a 83

BO

Ph

Et

CF3

5b 85

BO

Ph

Et

NPhth

5c 82

BO

Ph

Et

5d 72b

BO

Ph

Et

5e 85

S

BO

n-Pr

Me

Cl

5f 74

BO

n-Pr

Ph

OMe

5g 82

BO

Ph

S

5h 83

BO

Ph

CO2Et

5i 81

BO

Ph

5j 82

Cl

BO

Ph

CF3

TBSO

BO

Cl

S

Ph

BO

Ph

Me

OMe

5n 71b

5m 925l 82

BO

Ph

5k 76

Me

+B

Ar

R

1

[Me4N]

2


BO

Ar

R

Ar

5







The reaction of 1a






Chapter 3

73








(E)-5o83 EZ = gt955

BO

Ph

Et

Ph

Ph

Et

PhO

NMe2

(Z)-685 EZ = lt595

Ph

Ph

EtO

NMe 2

(E)-675 EZ = 928

1a

(Z)-5o71 EZ = 793

+ PhBr

BO

Ph

Ph

Et

(a)

(c) (c)

(b)






Conclusions






Chapter 3

74




1H at 400 MHz and

11B at 128 MHz)



13C)

CD3CN ( = 194 for 1H =132 for


11B)









and Ph-9-BBN18


procedures


Et LiB

Ph

+B

Ph

Et

1a


2) Me4NCl MeOH

[Me4N]









74 yield)

Chapter 3

75

B

Ph

Et

1a

[Me4N]


136-207 (m 11H) 236-250 (m 2H) 303 (s 12 H) 679-686 (m 1H) 700-707 (m

2H) 735 (d J = 72 Hz 2H) 13

C NMR (CD3CN) = 149 166 266 (q JC-B = 379

Hz) 271 275 324 349 561 948 1221 1269 1339 11

B NMR = -133 HRMS




n-Pr LiB

Ar


2) Me4NCl MeOH B

n-Pr

1b

Cl

[Me4N]










Chapter 3

76

B

n-Pr

1b

Cl

[Me4N]

1H NMR (CD3CN) = 084-096 (m 5H) 111-121 (m 1H) 126-200 (m 13H)

235-250 (m 2H) 304 (s 12H) 700-705 (m 2H) 733 (d J = 84 Hz 2H) 13

C NMR

(CD3CN) = 139 234 249 266 (q JC-B = 393 Hz) 270 273 323 348 561

933 1265 1272 1355 11


[M-(NMe4)] 2991738 Found 2991730

B

n-Pr

1c

OMe

[Me4N]


128-201 (m 13H) 237-252 (m 2H) 303 (s 12H) 371 (s 3H) 663-668 (m 2H)

723 (d J = 81 Hz 2H) 13

C NMR (CD3CN) = 140 235 250 268 (q JC-B = 393

Hz) 272 275 324 349 554 561 929 1128 1344 1561 11

B NMR = -135


B

Ph

1d

[Me4N]


(m 2H) 134-196 (m 9H) 230-244 (m 2H) 304 (s 12H) 679-686 (m 1H)

699-706 (m 2H) 733 (d J = 72 Hz 2H) 13

C NMR (CD3CN) =23 87 266 (q

JC-B = 393 Hz) 271 274 323 349 562 1222 1269 1338 11

B NMR = -134


Chapter 3

77

B

Ph

1e

[Me4N]


(m 3H) 302 (s 12H) 679-686 (m 1H) 699-706 (m 2H) 734 (d J = 66 Hz 2H) 13

C NMR (CD3CN) = 253 268 (q JC-B = 379 Hz) 271 275 324 333 349 361

561 980 1221 1269 1339 11


[M-(NMe4)] 2912284 Found 2912278

B

1f

S

Ph

[Me4N]




09 Hz 1H) 712-730 (m 5H) 13

C NMR (CD3CN) = 240 268-290 (m) 325 347

380 562 928 1225 1261 1265 1271 1289 1297 1434 11

B NMR = -135


B

Ph

1g

TBSO

[Me4N]

1H NMR (CD3CN) = 005 (s 6H) 084-096 (m 11H) 110-120 (m 1H) 134-197

(m 9H) 216-233 (t J = 72 Hz 2H) 235-250 (m 2H) 301 (s 12H) 356 (t J = 78

Hz 2H) 680-687 (m 1H) 700-708 (m 2H) 735 (d J = 66 Hz 2H) 13

C NMR

(CD3CN) = -50 189 254-277 (m) 323 348 561 649 889 1222 1269

1339 11


Found 3812789

Chapter 3

78

B

Ph

1h

OMe

[Me4N]


(m 2H) 298 (s 12H) 373 (s 3H) 668-674 (m 2H) 701-718 (m 5H) 732 (d J =

87 Hz 2H) 13

C NMR (CD3CN) = 255-277 (m) 322 350 554 561 961 1129

1251 1287 1302 1312 1345 1564 11


C23H26BO [M-(NMe4)] 3292077 Found 3292081



Br

+

MeO


6 mol Ligand


2a

B

Ph

Et

OMe

(E)-3a

AcOH

Ph

Et

OMe

H

Ph

B

Et

OMe

+

+

(Z)-3a

(E)-4a

H

Et

OMe

Ph

(Z)-4a

B

Ph

Et

1a

[Me4N]









Chapter 3

79




B

Ph

Et

+


toluene 70 degC

Me3NO

Br

MeO

BO

Ph

Et

OMe

5a

1a

2a

[Me4N]









BO

Ph

Et

OMe


383 (s 3H) 438-444 (m 1H) 685-691 (m 2H) 714-736 (m 7H) 13

C NMR =

138 221 267 273 (br) 277 312 553 736 1132 1251 1278 1283 1298

1366 1436 1494 1586 11


3742417 Found 3742410

Chapter 3

80

BO

Ph

Et

CF3

5b


437-443 (m 1H) 718-726 (m 3H) 734-739 (m 2H) 745-748 (m 2H) 760-763

(m 2H) 13

C NMR = 135 220 266 271 (br) 276 312 738 12429 (q JC-F =

2701 Hz) 1247 (q JC-F = 36 Hz) 1280 1281 1289 (q JC-F = 320 Hz) 1291 1425

1476 1480 11


Found 4122186

BO

Ph

Et

NPhth

5c


440-450 (m 1H) 720-727 (m 3H) 734-739 (m 2H) 743-751 (m 4H) 777-783

(m 2H) 794-800 (m 2H) 13

C NMR = 137 221 266 274 (br) 275 312 738

1235 1254 1258 1279 1282 1294 1304 1317 1342 1429 1440 1482

1671 11

B NMR = 502 IR (KBr) = 2928 1742 1509 1381 714 cm-1

HRMS (EI)


BO

Ph

Et

5d

1H NMR = 021-034 (m 1H) 068-100 (m 8H) 120-150 (m 7H) 224-238 (m

1H) 244-258 (m 1H) 424-431 (m 1H) 722-754 (m 9H) 778 (d J = 78 Hz 1H)

783-788 (m 1H) 809-816 (m 1H) 13

C NMR = 137 216 219 259 262 264

(br) 282 309 314 734 1249 12537 12539 1255 1264 1270 1273 12795

Chapter 3

81

12799 1283 1321 1335 1413 1427 1467 11


for C28H31BO (M+) 3942468 Found 3942476

BO

Ph

Et

5e

S


448-456 (m 1H) 702 (dd J = 51 36 Hz 1H) 708 (dd J = 36 12 Hz 1H)

715-730 (m 4H) 732-738 (m 2H) 13

C NMR =141 221 271 289 312 739

1250 1255 1266 1269 1279 1281 1416 1427 1468 11

B NMR = 496


BO

n-Pr

Me

Cl

5f

1H NMR = 070 (t J = 75 Hz 3H) 096-133 (m 9H) 142-172 (m 6H) 220-228

(m 2H) 237 (s 3H) 439-446 (m 1H) 708-735 (m 8H) 13

C NMR = 140 212

219 221 267 274 (br) 313 363 737 1279 12846 12855 1298 1309 1365

1411 1420 1488 11


4062235 Found 4062237

BO

n-Pr

Ph

OMe

5g

Chapter 3

82


(s 3H) 435-450 (m 1H) 690 (d J = 81 Hz 2H) 711 (d J = 81 Hz 2H) 720-740

(m 5H) 13

C NMR = 140 219 221 267 274 (br) 312 362 551 736 1133

1267 1278 1287 1294 1354 1446 1475 1573 11




BO

Ph

S

5h

1H NMR = 027-032 (m 2H) 046-052 (m 2H) 098-130 (m 6H) 140-170 (m

8H) 430-445 (m 1H) 696-700 (m 1H) 704-707 (m 1H) 715-726 (m 2H)

729-738 (m 4H) 13

C NMR = 60 150 222 263 272 (br) 313 736 1241

1243 1253 1278 1290 1295 1410 1425 1431 11



BO

Ph

CO2Et

5i

1H NMR = 017-023 (m 2H) 045-053 (m 2H) 090-119 (m 6H) 132-173 (m

11H) 427-433 (m 1H) 438 (q J = 75 Hz 2H) 718-738 (m 7H) 798 (dt J = 78

15 Hz 2H) 13

C NMR = 56 144 151 220 263 269 (br) 312 609 735 1255

1279 1284 1287 1289 1303 1423 1453 1469 1665 11

B NMR = 496 IR

(KBr) = 2928 1717 1287 1100 cm-1


Found 4282526

BO

Ph

5j

Cl

Chapter 3

83

1H NMR = 023-029 (m 2H) 048-055 (m 2H) 094-123 (m 6H) 134-171 (m

8H) 432-439 (m 1H) 706-714 (m 1H) 718-726 (m 4H) 728-738 (m 4H) 13

C

NMR = 57 150 220 263 271 (br) 312 736 1255 1267 1279 1283 1284

1289 1304 1332 1423 1424 1461 11


C25H28BClO (M+) 3901922 Found 3901923

BO

Ph

5k

Me

1H NMR = 082-113 (m 6H) 126-164 (m 15H) 237 (s 3H) 268-280 (m 1H)

434-441 (m 1H) 704-709 (m 3H) 717-725 (m 4H) 730-737 (m 2H) 13

C NMR

= 215 219 248 263 273 (br) 312 315 433 735 1252 12689 12693 1275

1278 1283 1316 1365 1418 1424 1481 11


for C28H35BO (M+) 3982781 Found 3982780

BO

Cl

S

Ph

5l

1H NMR = 106-176 (m 13H) 250-260 (m 2H) 272-280 (m 2H) 441-449 (m

1H) 674 (dd J = 33 12 Hz 1H) 697-703 (m 3H) 709-738 (m 8H) 13

C

NMR(C6D6) =225 272 277 (br) 315 358 375 739 1247 1253 1261 1272

1285 12856 12861 1306 1335 1419 1427 1437 1491 11

B NMR = 495


BO

Ph

CF3

TBSO

5m

Chapter 3

84

1H NMR = -014 (s 6H) 079 (s 9H) 095-136 (m 6H) 142-168 (m 7H) 255 (t

J = 72 Hz 2H) 343 (t J = 72 Hz 2H) 435-442 (m 1H) 718-726 (m 3H)

731-737 (m 2H) 747 (d J = 81 Hz 2H) 759 (d J = 81 Hz 2H) 13

C NMR = -54

183 220 259 266 271 (br) 311 377 616 739 1242 (q JC-F = 2694 Hz) 1247

(q JC-F = 36 Hz) 1258 1280 1282 1290 (q JC-F = 320 Hz) 1291 1421 1422

1480 11



BO

Ph

Me

OMe

5n

1H NMR = 122-130 (m 4H) 138-162 (m 5H) 168-186 (m 4H) 237 (s 3H)

375 (s 3H) 443-450 (m 1H) 670 (dt J = 90 21 Hz 2H) 690-697 (m 4H)

702-708 (m 3H) 710-720 (m 4H) 13

C NMR = 213 222 269 312 550 738

1132 1260 1272 1285 1301 1307 1310 1362 1369 1423 1429 1483

1571 11


4362561


4-Bromobenzene

B

Ph

Et

+


toluene 70 degC

Me3NO BO

Ph

Ph

Et

(Z)-5o

1a

Ph Br

[Me4N]




Chapter 3

85






BO

Ph

Ph

Et


470-475 (m 1H) 685-710 (m 10H) 13

C NMR = 139 224 267 313 317 740

1248 1257 1272 127412938 12941 1421 1425 1275 11

B NMR = 512


BO

Ph

Et

Ph


438-443 (m 1H) 718-737 (m 10H) 13

C NMR = 137 221 266 274 (br) 277

312 737 1253 1268 1278 1279 1283 1288 1433 1442 1494 11

B NMR =



Bromide 2b

+

Br

ONMe2

Ph

Et

PhO

NMe2


THF K3PO4 60 degC

(Z)-Tamoxifen 6

2b

BO

Ph

Et

Ph

(E)-5o

Chapter 3

86









Chapter 3

87



2003 Vol 3








Rev 2006 250 1107









1976 108 281








74





Chapter 3

88





















2006 128 1828




Chapter 4

89

Chapter 4



Abstract






Chapter 4

90

Introduction





























Chapter 4

91


B

MOMO

[Me4N] +

MeO

Br

I

Br

MeO Br

B

MeO

MOMO MOMO

1a

2 3 87EZ = lt199

NaOH

50 degC

1 mol


toluene 50 degC
















procedure

Chapter 4

92



An











3

MeO

R

Br

4 92

R

MeO

R

Br

n = 2 5 87

n = 3 6 82n = 4 7 85

n

R

1 mol


toluene 50 degC

I

Br

NaOH

E

EE

R = OMOM








Chapter 4

93





Br

Br

R

R

Br

Br

8 86

R

R

Br

R

R

Br

9 92

E E

R = OMOM















Chapter 4

94


Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

Me3Si

Br

Ph

F

Me3Si

OMe

Br

Ph

F

S

Br

Me3Si

OMe

B

n-Pr

[Me4N]

Cl

B

Ph

[Me4N]

OMe

Br

S

Br

I

EtO2C

MOMO

MOMO

I

Br

F

1b

10 88

11 84

12 88

1a1c

cat Pd

NaOHcat Pd

cat Pd NaOH

Cs2CO3

Conclusions







Chapter 4

95




1H at 500 MHz and






13C) CD3CN ( = 194 for

1H =132 for

13C) and

BF3OEt2 ( = 000 for 11











11













Chapter 4

96

B

MOMO

[Me4N]

1a


202 (t J = 66 Hz 2H) 236-251 (m 2H) 304 (s 12H) 328 (s 3H) 346 (t J = 69

Hz 2H) 454 (s 2H) 678-685 (m 1H) 698-705 (m 2H) 734 (d J = 72 Hz 2H) 13

C NMR (CD3CN 75 MHz) = 210 267 (br) 271 275 282 297 324 349 551

561 681 928 968 1221 1269 1338 11



B

Ph

[Me4N]

1b

OMe


225 (t J = 72 Hz 2H) 234-249 (m 2H) 263 (t J = 72 Hz 2H) 303 (s 12H) 372

(s 3H) 663-669 (m 2H) 711-728 (m 7H) 13


272 275 324 349 381 554 560 1129 1266 1289 1298 1346 1434 1563 11


3572390 Found 3572383



B

MOMO

[Me4N]

+

MeO

Br

1 mol


toluene 50 degC

I

Br

MeO Br

NaOH

3

1a

MOMO

Chapter 4

97








MeO Br

3

MOMONOE

NOE




(t J = 66 Hz 2H) 376 (s 3H) 452 (s 2H) 667-675 (m 4H) 697-702 (m 2H)

709-736 (m 7H) 13

C NMR (75 MHz) = 255 298 356 5510 5514 676 964

1134 1196 1267 1282 1294 13046 13049 1323 1339 1376 1408 1420



spectroscopy

MeO

R

Br

4

R

R = OMOM




Chapter 4

98


2H) 325 (s 3H) 329 (s 3H) 331-341 (m 4H) 380 (s 3H) 451 (s 2H) 453 (s

2H) 662-678 (m 8H) 697-703 (m 2H) 706-738 (m 12H) 13

C NMR (150 MHz)

= 252 254 295 296 353 354 5502 5504 552 675 676 9629 9632 1131

1196 1265 1267 1281 1282 1285 12941 12942 1303 1304 1306 1324

1343 1377 1385 1390 1400 1413 1414 1418 1429 1435 1579 HRMS


7972818 Found

7972849

MeO

R

5

R

R = OMOM

R

Br




325 (s 3H) 327 (s 3H) 328 (s 3H) 330-342 (m 6H) 374 (s 3H) 450 (s 2H)

452 (s 2H) 454 (s 2H) 654-662 (m 4H) 666-678 (m 8H) 696-704 (m 4H)

712-737 (m 15H) 13

C NMR (75 MHz) = 254 256 296 297 298 3526 3534

355 551 675 676 963 1130 1196 1264 1267 1280 1281 1286 1294 1301

1302 1304 1306 1324 1344 1377 1384 1387 1392 1393 1398 1402 1409



10914437 Found 10914482

Chapter 4

99

MeO

R

6

R

R = OMOM

R

R

Br




330-341 (m 8H) 371 (s 3H) 448-454 (m 8H) 648-675 (m 16H) 695-703 (m

4H) 714-737 (m 20H) 13

C NMR (75 MHz) = 253 254 256 257 2969 2974

298 350 354 356 550 551 675 676 963 1131 1196 1264 1267 1279

1280 1281 1283 1288 1293 1294 1300 1301 1302 1305 1306 1323 1342

1377 1385 1387 1389 1391 1394 1396 1397 1401 1405 1409 1411 1413



13856057 Found 13856062

MeO

R

7

R

R = OMOM

R

R

R

Br




374 (s 3H) 447-452 (m 10 H) 649-679 (m 20 H) 690-695 (m 2H) 701-706 (m

2H) 710-736 (m 25H) 13

C NMR (75 MHz) = 2529 2535 256 257 2968

Chapter 4

100

2971 298 351 354 355 356 550 6746 6755 676 963 1131 1195 1264

1267 12795 1280 1281 1283 1285 1287 1293 12937 12944 1301 1302

1304 1306 1322 1343 1377 1384 1387 1389 1390 1391 1394 13976

13979 1401 1404 1408 1409 1412 1413 1416 1427 14318 14321 1434


16797677 Found 16797694

8

R

Br

R

Br

R = OMOM





(t J = 66 Hz 4H) 456 (s 4H) 668-673 (m 4H) 691 (s 4H) 710-721 (m 8H)

722-737 (m 6H) 13

C NMR (75 MHz) = 254 297 354 551 676 963 1198

1268 1282 1291 1293 1303 1323 1380 1400 1411 1417 1427 HRMS


8221905

9

R

R

R = OMOM

R

R

Br

Br



Chapter 4

101


6H) 330-340 (m 8H) 446 (s 4H) 453 (s 4H) 656-672 (m 12H) 688 (s 4H)

704-710 (m 4H) 714-718 (m 4H) 722-740 (m 16H) 13

C NMR (150 MHz) =

254 2962 2963 356 357 5501 5503 674 676 9629 9631 1197 1266

1268 1281 12818 12822 1290 1295 1296 1304 1308 1324 1379 1385

1394 1403 1405 1409 1416 1417 1427 1434 HRMS (MALDI-TOF-MS


14335057 Found 14335040

Ph

F

Me3Si

OMe

Br

10

NOE

NOE





3H) 676-686 (m 3H) 694-707 (m 6H) 709-728 (m 5H) 734 (d J = 84 Hz 2H) 13

C NMR (150 MHz) = -11 349 372 552 1135 1189 (d JC-F = 255 Hz)1202

(d JC-F = 92 Hz) 1258 1268 (d JC-F = 35 Hz) 1280 1283 1284 1300 1304 (d

JC-F = 159 Hz) 1326 1329 1332 (d JC-F = 45 Hz) 1339 1387 1417 1418 1430




Chapter 4

102

Ph

F

S

Br

Me3Si

OMe

11

MOMO




= 78 2H) 264-272 (m 2H) 282-289 (m 2H) 325 (s 3H) 328 (t J = 66 Hz 2H)

382 (s 3H) 448 (s 2H) 587 (d J = 39 Hz 1H) 660 (d J = 39 Hz 1H) 669-676

(m 2H) 684-696 (m 3H) 705-742 (m 16H) 13

C NMR (150 MHz) = -10 244

293 351 362 372 550 552 673 963 1127 1135 1161 (d JC-F = 225 Hz)

1244 (d JC-F = 32 Hz) 1258 1274 12827 12831 12837 12840 12856 12861

1295 1302 1307 (d JC-F = 155 Hz) 1324 1329 1330 (d JC-F = 45 Hz) 1333

1345 1385 1395 (d JC-F = 12 Hz) 1412 1416 (d JC-F = 80 Hz) 1419 1422



Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

12MOMO




mmol) t1 10 h t2 12 h

Chapter 4

103


210-224 (m 4H) 264-272 (m 2H) 279-287 (m 2H) 323-333 (m 5H) 373 (s


1H) 666-672 (m 2H) 679-694 (m 5H) 703-737 (m 20H) 773 (d J = 84 Hz

2H) 13

C NMR (150 MHz) = -11 141 143 225 244 293 350 359 370 385

550 551 607 674 963 1134 1159 (d JC-F = 224 Hz) 1243 (d JC-F = 29 Hz)

1258 1269 1271 12808 12811 12815 12820 12823 12838 12844 1290

1293 1300 1301 (d JC-F = 158 Hz) 1302 1307 1323 (d JC-F = 47 Hz) 13258

13261 1328 1336 1344 1356 1379 1382 1390 (d JC-F = 12 Hz) 1409 14190

14191 14216 (d JC-F = 80 Hz) 14219 14222 1438 1446 1476 1583 1600 (d

JC-F = 2448 Hz) 1664 IR (KBr) = 2955 1717 1509 1273 1248 1111 837 cm-1


11294440

Found 11294465

Chapter 4

104




Chem 1999 201 163




897















2404


2006 128 1828



Chapter 5

105

Chapter 5




Abstract






Chapter 5

106

Introduction





moiety1b


























Chapter 5

107


B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

OHMe

Ph

1a

3a 85

MeO

OMe

2a

B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

1b

OMe

2a

OHMe

Ph

OMe

3b 88

[Me4N]

[Me4N]




Oxidative









Chapter 5

108


O

I

O

PdI

Pd(0)

B

1a

C

Pd(0)3a

Ar = p-MeOC6H4-

Me Me

OMe

Ar

Ph

B

D

A

Pd

O

ArB

Me

Ph

B

O

ArPh

Me

Me4NI

2a







Chapter 5

109


R3

O

I

B

R2

R1

+1 mol Pd

toluene50 degC 1 h

OHR3

R1

R2

OHMe

Ph

S

OHMe

OMe

OHPh

Ph

OMe

3f 72

3h 763j 80

3g 84

3d 82

3c 83

OHMe

Ph

CF3

1 2 3

OHH

Ph

OMe

OHPh

Ph

OMe

O

O

OHPh

3e 92

F

OMe

OHPh

Ph

OMe

F3C

3i 62

R4R4

MeO

[Me4N]










Chapter 5

110

OHMe

t-Bu

S

3k 89

B +1 mol Pd

toluene

50 degC 1 h

2a

t-Bu

S

(1)

1c

[Me4N]

OHMe

n-Bu

Me

3l 80

B

n-Bu

+1 mol Pd

toluene50 degC 1 h

2a

Me

(2)

1d

[Me4N]










n-Hex

13 equiv

Ph

Li

065 equiv

(H-9-BBN) 2


1 mol Pd

toluene 50 degC 1 h

10 equiv 2aOH

Me

n-Oct

11 equiv

3m 91 (based on 2a)

B

n-Oct

PhLi

Ph




Chapter 5

111


in 59 yield11


OHH

Ph

OMe

MnO2

DCM rt

Ph

OMe

O

NH2NH2 KOHPh

OMe

4 96 5 59

3n 74

(CH2OH)2 150 C

1a +

CHO

I2b

1 mol Pd

Conclusions




Chapter 5

112



and 13


B at 128 MHz)



13C) CD3CN (δ = 194 for

1H δ = 132 for


11B) IR






(Merck)





and alkynylborate14




Li

BPh

+

B

Ph

1a


2) Me4NCl MeOH

[Me4N]

MeO

MeO










Chapter 5

113

B

Ph

1a

[Me4N]

MeO


(m 2H) 296 (s 12H) 372 (s 3H) 668-675 (m 2H) 685-691 (m 1H) 700-712 (m

4H) 743 (d J = 64 Hz 2H) 13

C NMR (CD3CN) δ = 256-272 (m) 270 274 322

350 557 560 955 1145 1227 (2C) 1273 1324 1341 1578 The boron-bound


11B NMR


3292079

B

Ph

1b

[Me4N]

OMe


(m 2H) 295 (s 12H) 374 (s 3H) 666-675 (m 2H) 702-718 (m 5H) 733 (d J =

84 Hz 2H) 13

C NMR (CD3CN) δ = 254-274 (m) 270 273 321 350 554 560





B

nBu

1d

[Me4N]

Me


(m 4H) 136-157 (m 6H) 170-196 (m 4H) 220-234 (m 5H) 304 (s 12H)

697-701 (m 2H) 704-709 (m 2H) 13

C NMR (CD3CN) δ = 152 212 270

271-290 (m) 282 288 318 324 357 561 1279 1296 1314 1344 The

Chapter 5

114




[M-(NMe4)]- 2932446 Found 2932454

B

Ph

1e

[Me4N]

F3C


(m 2H) 292 (s 12H) 690-696 (m 1H) 710-718 (m 2H) 728 (dd J = 88 08 Hz

2H) 744-752 (m 4H) 13

C NMR (CD3CN) δ = 252-270 (m) 269 273 321 351






B

Ph

1f

[Me4N]

S



48 32 Hz 1H) 703-719 (m 6H) 13

C NMR (CD3CN) δ = 266 272 270-286 (m)

323 348 560 962 1231 1256 1266 1274 1290 1300 1314 The boron-bound

sp2 and sp


11B NMR


- 3051541 Found

3051541

Chapter 5

115


(H-9BBN) 2

H tBu

THF 0 degC

THF -78 degC to rt

2) Me4NCl MeOH

Li

1)S

B

1c

[Me4N]

S

tBu














B

1c

[Me4N]

S

tBu


4H) 222-235 (m 2H) 306 (s 12H) 552 (d J = 172 Hz 1H) 591 (d J = 176 Hz


Hz 1H) 13

C NMR (CD3CN) δ = 273 276 278-296 (m) 311 327 341 352 561





Chapter 5

116












OHMe

3aOMe

NOE

no NOE

IR (ATR) 3315 1508 1248 752 694 cm-1

1H NMR δ = 159 (s 3H) 204 (bs 1H)

382 (s 3H) 684-690 (m 2H) 721-730 (m 8H) 742-748 (m 2H) 751-755 (m

1H) 13

C NMR δ = 239 552 832 1139 1208 1218 1265 1268 1272 1280


C23H21O2 [M+H]+ 3291536 Found 3291556

OHMe

OMe

3b

NOE

no NOE

IR (ATR) 3319 1508 1248 760 702 cm-1

1H NMR δ = 160 (s 3H) 208 (s 1H)

378 (s 3H) 674-680 (m 2H) 718-723(m 1H) 724-744 (m 9H) 750-755 (m

1H) 13

C NMR δ = 241 551 833 1134 1205 1218 1263 1270 1274 1284


Chapter 5

117

C23H20O2Cl [M+Cl]- 3631146 Found 3631148

OHMe

Ph

3cCF3

IR (ATR) 3298 1319 1121 750 696 cm-1

1H NMR δ = 160 (s 3H) 210 (bs 1H)

716-722 (m 1H) 723-732 (m 5H) 737-747 (m 4H) 752-764 (m 3H) 13

C NMR

δ = 240 833 1205 1221 1241 (q JC-F = 2701 Hz) 1255 (q JC-F = 37 Hz) 1269

1277 1282 1286 1293 1295 (q JC-F = 322 Hz) 1296 1341 1373 1385 1414


- 3651159 Found 3651159

OHMe

Ph

3d

S

IR (ATR) 3319 1350 1088 752 694 cm-1

1H NMR δ = 177 (s 3H) 209 (bs 1H)

696-702 (m 2H) 718 (dd J = 52 Hz 12Hz 1H) 723-730 (m 2H) 735-740 (m

3H) 742-752 (m 3H) 753-758 (m 1H) 13

C NMR δ = 254 833 1207 1216

1259 1265 1266 1275 1282 1287 1290 1294 1347 1360 1374 1410 1426


+ 3050995 Found 3050992

OHMe

OMe

3e

IR (ATR) 3310 1508 1244 1034 758 cm-1

1H NMR δ = 144 (s 3H) 158-202 (m


5H) 747 (d J = 68 Hz 1H) 13

C NMR δ = 238 266 267 305 311 382 552

822 1136 1211 1219 1257 12789 12793 1304 1406 1409 1467 1499


+ 3382115 Found 3382104

Chapter 5

118

OHH

Ph

3fOMe

MeO

IR (ATR) 3472 1601 1508 1244 704 cm-1

1H NMR δ = 174 (d J = 88 Hz 1H)


= 80 Hz 24 Hz 1H) 692-697 (m 2H) 718-730 (m 5H) 732-736 (m 2H) 753 (d

J = 84 Hz 1H) 13

C NMR δ = 552 555 766 1072 1109 1143 1244 1267 1272

1283 1292 1303 1342 1363 1390 1445 1457 1592 1606 HRMS (ESI+)


OHPh

Ph

3gOMe

IR (ATR) 3422 1508 1244 1028 746 698 cm-1

1H NMR δ = 248 (s 1H) 385 (s

3H) 695 (d J = 88 Hz 2H) 704-714 (m 5H) 715-732 (m 7H) 736-740 (m 2H)

755 (d J = 88 Hz 2H) 13

C NMR δ = 552 868 1141 1210 1231 1250 1268

12698 12702 1271 1278 12836 12844 1294 1304 1340 1402 1417 1427


+ 3911693 Found

3911718

OHPh

Ph

3hOMe

O

O

IR (ATR) 3362 1470 1244 1034 696 cm-1

1H NMR δ = 239 (s 1H) 385 (s 3H)

591 (dd J = 164 16 Hz 2H) 673 (d J = 44 Hz 2H) 690-696 (m 2H) 702-708

(m 5H) 720-736 (m 5H) 749-754 (m 2H) 13

C NMR δ = 552 863 1012 1024

Chapter 5

119

1049 1142 1249 12690 12692 1270 1278 1285 1292 1304 1340 1367


+

4341518 Found 4341505

OHPh

Ph

3iOMe

F3C

IR (ATR) 3545 1508 1321 1115 696 cm-1

1H NMR δ = 249 (s 1H) 387 (s 3H)

694-700 (m 2H) 704-715 (m 5H) 723-738 (m 6H) 742-755 (m 4H) 13

C NMR

δ = 553 866 1145 1177 (q JC-F = 37 Hz) 1233 1241 (q JC-F = 36 Hz) 1242 (q

JC-F = 2702 Hz) 1249 1260 1275 1276 1280 1287 1295 1304 1308 (q JC-F =


C29H21F3O2Cl [M+Cl]- 4931177 Found 4931192

OHPh

3j

F

OMe

IR (ATR) 3356 1242 1028 741 696 cm-1

1H NMR δ = 164-178 (m 2H) 183-208


4H) 719-737 (m 6H) 13

C NMR δ = 2675 2681 308 310 383 551 862 1114


1268 1271 1283 1303 1371 (d JC-F = 29 Hz) 1410 1418 (d JC-F = 15 Hz)



+ 4001839 Found 4001835

OHMe

S

tBu

3k

Chapter 5

120

IR (ATR) 3298 1358 1078 756 689 cm-1

1H NMR δ = 111 (s 9H) 168 (s 3H)

188 (s 1H) 640 (d J = 164 Hz 1H) 656 (d J = 164 Hz 1H) 718-730 (m 4H)

739-751 (m 3H) 13

C NMR δ = 257 295 340 822 1169 1204 1215 1242

1255 1262 1283 1285 1324 1346 1415 1452 1462 1506 HRMS (ESI+)


OHMe

nBu

OMe3l

IR (ATR) 3335 1508 1084 918 758 cm-1

1H NMR δ = 085 (t J = 72 Hz 3H) 130

(tt J = 72 72 Hz 2H) 141-167 (m 6H) 229-250 (m 5H) 702-706 (m 1H)

716-728 (m 6H) 744-748 (m 1H) 13

C NMR δ = 138 213 232 237 252 314

829 1198 1215 1256 1282 1286 1291 1318 1370 1374 1430 1492 1496


+ 2931900 Found 2931890



nHex

(H-9BBN) 2


Li

Ph

B

nOct

Li

Ph

Me

O

I


toluene 50 degC 1 h

H2O2 aq

NaOH aq

OHMe

nOct

Ph3m

MeOH




Chapter 5

121













yield)

OHMe

nOct

Ph3m

IR (ATR) 3335 1456 1078 752 698 cm-1

1H NMR δ = 096 (t J = 68 Hz 3H)

129-156 (m 15H) 160 (s 1H) 208-227 (m 2H) 274-281 (m 2H) 287-294 (m

2H) 719-728 (m 5H) 729-736 (m 3H) 742 (d J = 72 Hz 1H) 13

C NMR δ = 141

226 234 247 277 293 294 295 304 319 345 825 1186 1213 1252 1260


[M]+ 3622610 Found 3622619

OHH

Ph

OMe

3n

IR (ATR) 3354 1508 1246 764 692 cm-1

1H NMR δ = 185 (bs 1H) 386 (s 3H)

567 (s 1H) 692-697 (m 2H) 718-738 (m 10H) 763-766 (m 1H) 13

C NMR δ =

552 773 1143 1206 1237 1263 1268 1272 1283 1287 1292 1303 1342


- 3131234

Found 3131237

Chapter 5

122

The 1H


15


OHH

Ph

OMe

3n

MnO2

DCM rt

Ph

OMe

4

O







The 1H


16

Ph

OMe

4

O

(CH 2OH)2

NH2NH2

KOH Ph

OMe

5








The 1H


5

Chapter 5

123






1395ndash1411



17638ndash17640





3201ndash3222



















Chapter 5

124












3283ndash3292









74








Chem 1989 54 1485ndash1491



2006 128 1828

Chapter 5

125



4781-4787


Chem 1989 54 1485

Chapter 5

126

127

List of Publication

Chapter 1



Angew Chem Int Ed 2012 51 11750-11752

Chapter 2


Benzosultams


J Am Chem Soc 2013 135 19103-19106

Chapter 3





Org Lett 2009 11 5434-5437

Chapter 4


Units


Org Lett 2010 12 3179-3181

Chapter 5




Eur J Org Chem 2013 1421-1424

Other Publication




Chem Lett 2013 42 1076







encouragement

Yasuhiro Shimamoto



Kyoto University

Contents


Chapter 1


Chapter 2


Benzosultams 29

Chapter 3



Halides 67

Chapter 4


Units 89

Chapter 5





1









sultams














sun

CO2energy charge

Ph

O

NTs

Me

N

Ts

OHPh

OO

O

Ph

NHTs


2


benzosultams




developed456


shift7

MH14-metal shift

1

2 3

4

HM

1

2 3

4

H M1

23

4

5

M H1

23

4

515-metal shift






N

Ts

Ph OHMe

SN

MeO O

Ph OH

cat Rh





chemistry10






We


alkynylborates13

R1 B

R2

R2

R2

+ R3 Br

R3

R1 R2

B

R2

R2


3






obtained

Et

Ph

Ph

B O+

PhBr LPd(-allyl)Cl

L = XANTPhos

LPd(-allyl)Cl

L = P(o-tol)3 Ph

Et

Ph

B O

B

Et

Ph

Et

Ph

B

Ph

Ph

Et

B

Ph

Me3NO

Me3NO

[Me4N]







MeO

Br

I

Br

NaOH

R Ph

MeO Br

B

R

Ph

RB

Ph

OMe

[Me4N]

R Ph

MeOR Ph

Br

R =OMOM

n

B

R

Ph

[Me4N] I

Br

NaOH

R Ph

MeOR Ph

Br

n = 2~4

Pd-XANTPhos

Pd-XANTPhos






4


regioselectively

I

Me

O+

MeOH

R2

R1Pd-XANTPhosB

R2

R1

[Me4N]


5

Reference





































6








10990




2003 Vol 3





Q Z J Med Chem 2009 52 4192



2006 250 1107



2419













7



17638ndash17640


8

Chapter 1

9

Chapter 1


Ketones

Abstract






Chapter 1

10

Introduction







2 One







starting substances


CO2

sun

CO2energy charge

high energy

intermediates











8






Chapter 1

11


Ph

O

NTs

Mesolar light

N

Ph OH

Ts

2a 91

1aDMA







over 04 kWm-2



in eight hours on


Figure





kWhm-2



Chapter 1

12


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

0

20

40

60

80

100

0 1 2 3 4 5 6











(56)

Chapter 1

13


40 equiv Cs2CO3

1 atm CO2

DMA 60 degC

OO

O

Ph

NHTs

3a 93

N

Ph OH

Ts

2a








N

Ph O

Ts

A

N

Ph O

Ts

B

O

O

OO

O

Ph

NTs

CO2

H

C

Cs2CO3

CsHCO 3

Cs

Cs

Cs

2

1

N

Ph OH

Ts

2a

OO

O

Ph

NHTs

3a












N

Ts

OHPh

4

Chapter 1

14




solar light

CO2Cs2CO3

60degCDMAPh

O

NTs

Me

1a

OO

O

Ph

NHTs

3a 83






chloro groups10





Ar

O

NR

Me OO

O

Ar

NHR3

1

OO

O

NHTs3b 80

MeO

OO

O

NHTs3c 57

F3C

OO

O

NHTs3d 73

Cl

OO

O

NHTs3e 85

Br

OO

O

Ph

NH

3f 87

O2S OMe

OO

O

Ph

NH

3g 85

O2S CF3

OO

O

Ph

NH

3h 87

O2S

N

solar lightCO2

Cs2CO3

60degCDMA




Chapter 1

15

Conclusions















Chapter 1

16












indicator (Merck)






Ph

O

NTs

MeTsClMeNH2 +

Et2OTsNHMe

CH3CN

K2CO3












Chapter 1

17


Ph

O

NTs

Me


745-751 (m 2H) 760 (tt J = 76 12 Hz 1H) 771-775 (m 2H) 795-799 (m 2H)

13C NMR δ = 215 356 560 1275 1282 1288 1297 1338 1347 1348 1436


+ 3041002 Found mz 3040994 IR

(ATR) 1693 1339 1227 1157 743 cm-1

O

NTs

Me

1bMeO


733 (d J = 80 Hz 2H) 770-774 (m 2H) 796-802 (m 2H) 13

C NMR δ = 215

355 555 558 1139 1275 1277 1296 1307 1346 1436 1640 1921 HRMS


+ 3341108 Found mz 3341101 IR (ATR) 1688

1601 1329 1180 1159 cm-1

O

NTs

Me

1cF3C


= 84 Hz 2H) 776 (d J = 84 Hz 2H) 812 (d J = 84 Hz 2H) 13

C NMR δ = 215

357 564 1234 (q JC-F = 2711 Hz) 1259 (q JC-F = 37 Hz) 1276 1288 1298



1121 1109 cm-1

Chapter 1

18

O

NTs

Me

1dCl


(m 2H) 771 (d J = 80 Hz 2H) 792-796 (m 2H) 13

C NMR δ = 216 356 561



1159 1088 cm-1

O

NTs

Me

1eBr


= 84 Hz 2H) 771 (d J = 84 Hz 2H) 786 (d J = 84 Hz 2H) 13

C NMR δ = 215

356 561 1275 1291 1297 1298 1321 1334 1344 1438 1930 HRMS (ESI+)


1223 1155 810cm-1

Ph

O

NS

Me

1f

OMe

OO

1H NMR δ = 282 (s 3H) 389 (s 3H) 456 (s 2H) 698-703 (m 2H) 746-751 (m

2H) 761 (tt J = 72 12 Hz 1H)776-781 (m 2H) 796-800 (m 2H) 13

C NMR δ =

356 556 561 1142 1283 1288 1294 1297 1338 1348 1630 1938 HRMS


+ 3200951 Found mz 3200943 IR (ATR) 1692

1342 1259 1155 741 cm-1

Chapter 1

19

Ph

O

NS

Me

1g

CF3

OO


780 (d J = 84 Hz 2H) 790-794 (m 2H) 798 (d J = 80 Hz 2H) 13

C NMR δ =

356 558 1233 (q JC-F = 2711 Hz) 1261 (q JC-F = 36 Hz) 12796 12799 1289



1059 748 cm-1

Ph

O

NS

Me

1h

N

OO

1H NMR δ = 302 (s 3H) 486 (s 2H) 744-753 (m 3H) 757-762 (m 1H)

788-798 (m 4H) 870 (ddd J = 48 16 08 Hz 1H)13

C NMR δ = 363 569 1224



752 cm-1


Ph

O

NTs

Mesolar light

N

Ph OH

TsDMA rt

1a

2a








Chapter 1

20


N

Ph OH

Ts


2H) 728-737 (m 5H) 740 (d J = 80 Hz 2H) 779 (d J = 80 Hz 2H) 13

C NMR δ

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS




N 458 O 1555 S 1058 IR (ATR) 3477 1333 1184 1148 671 cm-1


N

Ph OH

Ts

2a

40 equiv Cs2CO3

1 atm CO2

DMA 60 C

OO

O

Ph

NHTs

3a








mmol 93 yield)

Chapter 1

21



40 equiv Cs2CO3

60 CPh

O

NR

Me OO

O

Ph

NHR3a

1a

solar light

DMA rt

1 atm CO2











OO

O

Ph

NHTs



726-732 (m 4H) 734-743 (m 3H) 769-773 (m 2H) 13

C NMR δ = 215 503

724 850 1242 1269 1292 1299 1365 1381 1439 1542 HRMS (ESI+) Calcd

for C17H18NO5S M+H+


C 5878 H 493 N 403 O 2303 S 923 Found C 5871 H 496 N 389 O

2284 S 932 IR (ATR) 3261 1773 1435 1319 1045 cm-1

Chapter 1

22

OO

O

NHTs

3b

MeO



56 Hz 1H) 688-693 (m 2H) 719-724 (m 2H) 728 (d J = 80 Hz 2H) 770 (d J =

84 Hz 2H) 13

C NMR δ = 215 503 554 724 848 1145 1256 1269 1298


+

3781006 Found mz 3780996 IR (ATR) 3238 1794 1518 1329 1057 723 cm-1

OO

O

NHTs

3c

F3C



729 (d J = 84 Hz 2H) 746 (d J = 84 Hz 2H) 765-771 (m 4H) 13

C NMR δ =

215 501 722 846 1235 (q JC-F = 2704 Hz) 1249 1263 (q JC-F = 37 Hz) 1268



1067 cm-1

OO

O

NHTs

3d

Cl



722-727 (m 2H) 728 (d J = 84 Hz 2H) 735-739 (m 2H) 769 (d J = 84 Hz 2H)

13C NMR δ = 215 502 723 847 1257 1268 1294 1300 1353 1364 1365


+ 3820510 Found mz

Chapter 1

23

3820506 IR (ATR) 3250 1800 1325 1155 1069 cm-1

OO

O

NHTs

3e

Br



716-720 (m 2H) 728 (d J = 80 Hz 2H) 750-755 (m 2H) 766-770 (m 2H) 13

C

NMR δ = 215 501 723 847 1235 1260 1268 1300 1323 1364 1370 1441


+ 4260005 Found mz 4260003

IR (ATR) 3252 1800 1331 1175 1057 cm-1

OO

O

Ph

NH

SO

O

OMe



693-698 (m 2H) 727-732 (m 2H) 734-744 (m 3H) 773-778 (m 2H) 13

C NMR

δ = 503 556 724 849 1145 1242 1291 1292 1310 1381 1541 1632 HRMS


+ 3640849 Found mz 3640836 IR (ATR) 3246

1801 1325 1155 1067 cm-1

OO

O

Ph

NH

SO

O

CF3

3g

Chapter 1

24



2H) 735-744 (m 3H) 775 (d J = 88 Hz 2H) 796 (d J = 84 Hz 2H) 13

C NMR δ

= 505 725 851 1231 (q JC-F = 2711 Hz) 1241 1265 (q JC-F = 37 Hz) 1274



1161 1105 cm-1

OO

O

Ph

NH

SO

O

N




1H) 798 (d J = 76 Hz 1H) 866 (d J = 44 Hz 1H) 13

C NMR δ = 510 723 849



1175 1063 cm-1


N

Ts

OHPh

N

Ts

O CeCl 3

PhLi

THF -78 C to rt

4






Chapter 1

25






N

Ts

OHPh


351-364 (m 4H) 726-738 (m 7H) 773-777 (m 2H) 13

C NMR δ = 215 396

469 608 804 1250 1276 1280 1286 1297 1339 1418 1435 HRMS (ESI+)


1325 1159 1101 770 cm-1

Chapter 1

26











Soc 2011 133 12881

























25 312

Chapter 1

27








Chapter 1

28

Chapter 2

29

Chapter 2



Abstract







Chapter 2

30

Introduction














A



Indanones are


A rearrangement













Whereas







Chapter 2

31




N

HO Ph

S NS Me

HO PhMe

1a2a 96

Me

O

OO O


2) is





The generated








N

S O

O

O[Rh]

Ph

SN

[Rh]O Ph

O OMe

[Rh] OH

N

S O

O

O Ph

H

[Rh]

H

N

[Rh]O Ph

S O

O

Me Me

Me

Me

1a

H2O

2a

A B

CD

1a

A




Chapter 2

32








N

HO Ph

SN

S CH19D11

HO Ph

D3C

1a-d2a-d 96

D3C

O

O

O O

D

D

D

D

D

D

H01D09

8



D12




Application




1

2

SN

HO Ar

O OMe

N

HO Ar

S O

O


K2CO 3 (20 equiv)


NS Me

HO PhMe

2a

91 er = 928

O O

NS Me

HO Ph

2b

95 er = 937

O O

S

NS Me

HOMe

2c

90 er = 937

O O

OMe

NS Me

HOMe

2c

92 er = 919

O O

CF3



Chapter 2

33










HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6 84

5 56



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3


PhMgBr

THF rt 1 h N

HO

Ts

Me

1e 93

er gt 991 dr = 201

Ph

3







SN

HO PhMe

O OMe

MeN

HO Ph

S O

O

Me

Me

1e

er gt 991 dr = 201

2e 99

er gt 991 dr gt 201





Chapter 2

34









SN

PhRhOMe

O OMe

Me

SN

PhRhOMe

O OMe

Me

favored

disfavored

F

F

NSRh

Ph

Me

O

O

MeO

H

Me

E

E

NSRh

Ph

Me

O

O

MeO

Me

H














Chapter 2

35


1

er gt 991 dr gt 201

2

er gt 991 dr gt 201

SN

HO ArR

O OMe

N

HO Ar

S O

O





1 N

HO Ph

S O

O

Me

Me

1f

SN

HO PhMe

O OMe

Me

2e 99

6 N

HO

S O

O

Me

1k

OMe

SN

HOMe

O OMe

2k 97

OMe

2

N

HO Ph

S O

O

MeO

Me

1g

SN

HO PhMe

O OMe

MeO

2g 98

7 N

HO

S O

O

Me

Me

1l

CF3

SN

HOMe

O OMe

Me

2l 97

CF3

3 N

HO Ph

S O

O

F3C

Me

1h

SN

HO PhMe

O OMe

F3C

2h 99

8 N

HO Ph

S O

O

Me

i-Pr

1m

SN

HO Phi-Pr

O OMe

Me

2m 97

4

N

HO Ph

S O

O

Me

1iMe

SN

HO PhMe

O OMeMe

2i 99

9 N

HO Ph

S O

O

Me

SMe

SN

HO Ph

O OMe

Me

2n 97

SMe

5 N

HO Ph

S O

O

Me

S

1j

SN

HO PhMe

O OMeS

2j 99



Chapter 2

36

Conclusions






Chapter 2

37





13C NMR


13C at 10069












N

OHNEt3

DCM rt 12 h


2) PhMgBrTHF rt 3 h

N

HO Ph

1a

TsCl

N

OH

8a

H HCl

Ts Ts









Chapter 2

38

N

S

Me

O

O

OH

8a 1H NMR = 213 (bs 1H) 245 (s 3H) 350-361 (m 2H) 394-404 (m 2H)

442-452 (m 1H) 737 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR =



-1

N

S

D3C

O

O

OH

8a-d

D

D

D

D

1H NMR = 283 (bs 1H) 349-355 (m 2H) 389-396 (m 2H) 435-444 (m 1H)



+ 2351128 Found mz

2351125 IR (ATR) 3503 1333 1142 1059 638 cm-1

N

S O

O

OH

8b

S

1H NMR = 277 (bs 1H) 357-364 (m 2H) 400-407 (m 2H) 441-450 (m 1H)


1H) 13



1038 737 cm-1

Chapter 2

39














N

HO Ph

S

1a

Me

O

O


2H) 728-737 (m 5H) 739 (d J = 84 Hz 2H) 778 (d J = 80 Hz 2H) 13

C NMR

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS


+ 3041002 Found mz 3040995 IR (ATR) 3477

1333 1184 1148 671 cm-1


N

HO Ph

S

1a-d

D3C

O

O

D

D

D

D


(m 5H) 13

C NMR = 203-211 (m) 652 703 1244 1281 (t JC-D = 247 Hz)


Chapter 2

40


702 648 cm-1

N

HO Ph

S

S

O

O



1H) 13

C NMR = 656 702 1244 1280 1283 1288 1331 13387 13392 1417


+ 2960410 Found mz 2960404 IR

(ATR) 3524 1333 1161 1148 748 cm-1

N

HO

S

Me

O

O

OMe

1c



2H) 775 (d J = 80 Hz 2H) 13

C NMR =216 553 652 702 1139 1259 1285


+

3341108 Found mz 3341097 IR (ATR) 3460 1518 1331 1250 1146 cm-1

N

HO

S

Me

O

O

CF3



C NMR

Chapter 2

41

=216 654 697 1239 (q JC-F = 2704 Hz) 1249 1255 (q JC-F = 37 Hz) 1284



1109 1076 cm-1


1l-1n

HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6a

5a



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3

acetone H2O

rt 10 h 4a

PhMgBr

THF rt 1 h N

OH

Ts

Me

1e

Ph

3a



procedure16













Me

NHTs

O

N2


Chapter 2

42

2H) 730 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR = 194 215 539


+

2680750 Found mz 2680747 IR (ATR) 2112 1639 1337 1319 1161 cm-1

[]27

D = -1184 (c = 079 in CHCl3)


i-Pr

NHTs

O

N2



2H) 769 (d J = 84 Hz 2H) 13

C NMR =169 193 215 315 548 647 1273


+ 2961063

Found mz 2961060 IR (ATR) 2129 1622 1362 1329 1161 cm-1

[]28

D = -730 (c = 071 in CHCl3)

NHTs

O

N2

5c

SMe

1H NMR = 174-196 (m 2H) 204 (s 3H) 242 (s 3H) 244-252 (m 2H)

390-400 (m 1H) 541 (s 1H) 560-572 (m 1H) 730 (d J = 84 Hz 2H) 772 (d J =

84 Hz 2H) 13

C NMR = 153 215 297 323 545 585 1272 1297 1366 1439


+ 3280784 Found mz 3280779

IR (ATR) 2129 1618 1375 1339 1163 cm-1

[]29

D = -506 (c = 063 in CHCl3)









Chapter 2

43

N

O

Ts

Me

6a

1H NMR = 145 (d J = 68 Hz 3H) 246 (s 3H) 443-454 (m 2H) 473-480 (m

1H) 736-742 (m 2H) 776-781 (m 2H) 13

C NMR = 157 216 696 810 1284


+ 2400689

Found mz 2400688 IR (ATR) 1825 1339 1155 669 cm-1

[]28

D = 614 (c = 081 in CHCl3)


N

O

Ts

i-Pr

6b

1H NMR = 099-111 (m 6H) 206-218 (m 1H) 246 (s 3H) 441 (dd J = 164 36


2H) 777 (d J = 80 Hz 2H) 13

C NMR = 174 181 216 304 703 903 1284


+ 2681002

Found mz 2680998 IR (ATR) 1815 1340 1155 1007 671 cm-1

[]29

D = 567 (c = 095 in CHCl3)

N

O

Ts

6c

SMe

1H NMR = 204 (s 3H) 209-218 (m 2H) 247 (s 3H) 265-279 (m 2H) 446 (d


2H) 780 (d J = 80 Hz 2H) 13

C NMR = 147 216 291 293 705 832 1286


+ 3000723

Found mz 3000718 IR (ATR) 1813 1342 1308 1157 667 cm-1

[]29

D = 1183 (c = 036 in CHCl3)


Chapter 2

44










N

HO

S O

O

Me

Me

1e

H

NOE

NOE



(m 3H) 739 (d J = 84 Hz 2H) 777 (d J = 84 Hz 2H) 13

C NMR = 144 216

628 702 731 1247 1279 1284 1285 1298 1319 1415 1443 HRMS (ESI+)


1155 1092 667 cm-1

[]25




Chapter 2

45

N

HO

S O

O

Me

1l

H

NOE

NOE

CF3

Me



739-747 (m 4H) 777 (d J = 84 Hz 2H) 13

C NMR = 143 216 630 706 727

1238 (JC-F = 2704 Hz) 1253 1254 (JC-F = 36 Hz) 1285 1299 1301 (JC-F = 324


+ 3861032

Found mz 3861025 IR (ATR) 3422 1327 1151 1109 839 cm-1

[]28




N

HO

S O

O

Me

iPr

1m

H

NOE

NOE



= 100 Hz 1H) 690-696 (m 2H) 712-720 (m 3H) 732 (d J = 80 Hz 2H) 773 (d

J = 80 Hz 2H) 13

C NMR = 190 193 215 291 641 729 801 1247 1275


+

3461471 Found mz 3461466 IR (ATR) 3454 1331 1163 739 669 cm-1

[]27



Chapter 2

46


N

HO Ph

S O

O

1n

Me

SMe

1H NMR = 202 (s 3H) 218-258 (m 8H) 388-394 (m 2H) 427 (dd J = 84 48

Hz 1H) 688-693 (m 2H) 714-721 (m 3H) 740 (d J = 80 Hz 2H) 779 (d J = 80

Hz 2H) 13

C NMR = 154 216 290 297 634 725 733 1246 1277 1284


+

3781192 Found mz 3781188 IR (ATR) 3481 1339 1157 702 669 cm-1

[]28












N

HO

S O

O

Me

Me

1f

H

NOE

NOE


1H) 398 (q J = 64 Hz 1H) 424 (dd J = 84 08 Hz 1H) 732-744 (m 5H)

750-755 (m 2H) 774-778 (m 2H) 13

C NMR = 165 216 627 718 739 1257

Chapter 2

47



-1

[]25






HO2C Me

NHCbz

Me

NHCbz

O

N2N

O

Cbz

Me

6d5d

1) (COCl) 2 DMF

2) CH2N2 Rh2(OAc)4 (05 mol )

DCM rt 12 h4d

PhMgBr

THF rt 1 h

N

OH

Cbz

Me

7a

Ph

N

OH

H

Me

PhPd C (5 mol )

H2 (1atm)

MeOH rt 12 h

MeO SO2Cl

NEt3

DCM rt 12 h

N

HO Ph

S O

O

MeO

Me

1g









Me

NHCbz

O

N2

5d 1H NMR = 134 (d J = 68 Hz 3H) 420-436 (m 1H) 504-516 (m 2H) 534-564

(m 2H) 728-736 (m 5H) 13

C NMR = 184 535 (2C) 669 1280 1282 1285


+ 2481030 Found mz

2481028 IR (ATR) 2116 1717 1636 1533 1252 cm-1

[]28

D = -434 (c = 085 in CHCl3)


Chapter 2

48







N

O

Cbz

Me

6d


Hz 1H) 498-505 (m 1H) 513-521 (m 2H) 731-739 (m 5H) 13

C NMR = 153



696 cm-1

[]29

D = 390 (c = 068 in CHCl3)










N

OH

Cbz

Me

7a

Ph


= 96 Hz 1H) 458 (q J = 64 Hz 1H) 507-518 (m 2H) 729-746 (m 10H) 13

C

NMR = 142 623 667 689 730 1246 1278 1279 1280 1285 1287 1366

Chapter 2

49


+ 2981438 Found mz

2981433 IR (ATR) 1670 1423 1248 1016 702 cm-1

[]29

D = 46 (c = 089 in CHCl3)

N

OH

Cbz

Me

7b

MeO


1H) 432 (d J = 96 Hz 1H) 452-461 (m 1H) 506-518 (m 2H) 687-694 (m 2H)

726-739 (m 7H) 13

C NMR = 143 553 622 666 687 729 1140 1260 1278


+

3281543 Found mz 3281539 IR (ATR) 1682 1418 1352 1024 696 cm-1

[]29

D = 02 (c = 085 in CHCl3)








pressure







mmol 58 yield)

Chapter 2

50

N

HO

S O

O

MeO

Me

1g

H

NOE

NOE


390 (s 3H) 399 (d J = 92 Hz 1H) 419 (q J = 60 Hz 1H) 698-707 (m 4H)

720-727 (m 3H) 779-785 (m 2H) 13

C NMR = 143 557 627 701 731 1144



-1

[]28




N

HO

S O

O

F3C

Me

1h

H

NOE

NOE


406 (d J = 92 Hz 1H) 430 (qd J = 64 08 Hz 1H) 694-699 (m 2H) 721-727

(m 3H) 784 (d J = 80 Hz 2H) 801 (d J = 84 Hz 2H) 13

C NMR = 145 629

706 729 1232 (JC-F = 2711 Hz) 1245 1263 (JC-F = 37 Hz) 1283 12868 12871


+

3720876 Found mz 3720870 IR (ATR) 3503 1348 1323 1165 646 cm-1

[]28




Chapter 2

51

N

HO

S O

O

Me

1i

H

NOE

NOE


1H) 401 (d J = 88 Hz 1H) 422 (q J = 64 Hz 1H) 694-698 (m 2H) 720-724 (m

3H) 746-750 (m 2H) 767-772 (m 2H) 13

C NMR = 144 214 630 704 730

1247 1256 1279 1285 1286 1291 1341 1347 1395 1416 HRMS (ESI+)


1151 714 700 cm-1

[]29




N

HO

S O

O

Me

1j

H

NOE

NOE

S


Hz 1H) 425 (q J = 64 Hz 1H) 696-701 (m 2H) 720-728 (m 4H) 764-767 (m

1H) 769-772 (m 1H) 13

C NMR = 144 632 709 730 1246 1279 1281 1286


+ 3100566

Found mz 3100559 IR (ATR) 3508 1340 1151 756 669 cm-1

[]29




Chapter 2

52

N

HO

S O

O

Me

1k

H

NOE

NOE

OMe


1H) 394 (d J = 88 Hz 1H) 416 (q J = 64 Hz 1H) 670-675 (m 2H) 684-689 (m

2H) 756-762 (m 2H) 765-770 (m 1H) 786-790 (m 2H) 13

C NMR = 143 553

630 704 729 1138 1259 1283 1292 1332 1337 1348 1592 HRMS (ESI+)


1327 1155 606 cm-1

[]29





Screening







mmol 93 yield)

Chapter 2

53


rac -DM-BINAP

rac-BINAP

dppf

dppb

PPh3

dppe

46

trace

trace

yield

PCy3

Ligand

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

entry

1

2

3

4

5

6

7

8

nd

nd

nd

93

none nd

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a


entry Ligand yield

1

2

3

4

(R)-BINAP

(R)-DM-BINAP

(R)-SEGPHOS

(R)-DIFLUORPHOS

er

94

46

48

43

5

6

(R)-DM-SEGPHOS


3862

91

7

8

(R)-MeO-BIPHEP

(R)-MeO-DM-BIPHEP

64

91

892

3169

1288

1486

2476

2575

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a










Chapter 2

54

NS Me

HO PhMe

2a

O O


J = 148 Hz 1H) 683 (s 1H) 727-744 (m 6H) 781 (d J = 84 Hz 1H) 13

C NMR

= 216 361 626 732 1238 1263 1280 1284 1299 1301 1330 1412 1431


+ 3041002 Found mz 3040998 IR

(ATR) 3472 1325 1161 1142 735 cm-1

[]29




NS CH2D

HO Ph

D3C

2a-d

O O

D

D

D


J = 148 Hz 1H) 728-743 (m 5H) 13

C NMR = 201-210 (m) 358 (t JC-D = 212

Hz) 625 731 1234 (t JC-D = 249 Hz) 1262 1279 1283 1291-1300 (m 2C)


+ 3111441

Found mz 3111436 IR (ATR) 3524 1318 1290 1150 721 cm-1

NS Me

HO Ph

O O

S

2b


1H) 668 (d J = 52 z 1H) 730-738 (m 5H) 750 (d J = 52 Hz 1H) 13

C NMR =

378 630 722 1257 1264 1282 1286 1299 1338 1427 1467 HRMS (ESI+)


1150 1063 748 cm-1

[]29


Chapter 2

55



NS Me

HOMe

O O

OMe

2c


422 (d J = 148 Hz 1H) 684-690 (m 3H) 724-733 (m 3H) 774-779 (m 1H) 13

C

NMR = 216 360 553 626 729 1137 1237 1275 1299 1230 1328 1351


+ 3341108 Found mz

3341098 IR (ATR) 3441 1508 1250 1144 735 cm-1

[]29




NS Me

HOMe

O O

CF3



2H) 782 (d J = 80 Hz 1H) 13

C NMR = 216 360 625 731 12392 (q JC-F =

2708) 12395 1254 (q JC-F = 36 Hz) 1268 1298 1303 (q JC-F = 352) 1329


+ 3720876 Found

mz 3720869 IR (ATR) 3481 1323 1121 1067 733 cm-1

[]29




Chapter 2

56










SN

HO

Me

O OMe

Me

2e

H

NOE

NOE


= 68 Hz 1H) 675 (s 1H) 723-738 (m 6H) 777 (d J = 84 Hz 1H) 13

C NMR =

119 215 314 608 750 1242 1262 1275 1282 1298 1301 1316 1427


+ 3181158 Found mz

3181155 IR (ATR) 3481 1315 1163 1146 683 cm-1

[]28




SN

HO

Me

O OMe

MeO

2g

H

NOE

NOE

Chapter 2

57



5H) 782 (d J = 88 Hz 1H) 13

C NMR = 120 314 555 609 752 1144 1151



735 cm-1

[]29




SN

HO

Me

O OMe

F3C

2h

H

NOE

NOE



1H) 13

C NMR = 118 314 608 750 1228 (q JC-F = 2711 Hz) 1251 1258 (q



+ 3720876 Found

mz 3720872 IR (ATR) 3461 1325 1161 1142 739 cm-1

[]29




SN

HO

Me

O OMe

2i

H

NOE

NOE

Me

Chapter 2

58


J = 68 Hz 1H) 684 (d J = 80 Hz 1H) 718-736 (m 6H) 770 (s 1H) 13

C NMR

=119 211 314 607 748 1242 1262 1275 1282 1299 1338 1341 1395


+ 3181158 Found mz

3181155 IR (ATR) 3489 1448 1319 1148 735 cm-1

[]29




SN

HO

Me

O OMe

2j

H

NOE

NOES


1H) 656 (d J = 52 Hz 1H) 726-736 (m 5H) 743 (d J = 48 Hz 1H) 13

C NMR

= 114 319 619 742 1256 1266 1278 1284 1297 1334 1429 1480 HRMS


+ 3100566 Found mz 3100561 IR (ATR) 3524

1329 1151 1020 729 cm-1

[]29




SN

HO

Me

O OMe

2k

H

NOE

NOE

OMe


J = 68 Hz 1H) 685 (d J = 88 Hz 2H) 698-703 (m 1H) 722-730 (m 2H)

738-748 (m 2H) 785-790 (m 1H) 13

C NMR = 119 314 553 608 747 1136

Chapter 2

59



760 cm-1

[]26




SN

HO

Me

O OMe

2l

H

NOE

NOE

CF3

Me



= 84 Hz 2H) 778 (d J = 80 Hz 1H) 13

C NMR = 119 215 313 607 749




-1

[]26




SN

HO

iPr

O OMe

2m

H

NOE

NOE

Me


(m 1H) 264 (s 1H) 285 (s 3H) 441 (d J = 100 Hz 1H) 685 (s 1H) 714-735 (m

4H) 748 (d J = 76 Hz 2H) 772 (d J = 80 Hz 1H) 13

C NMR = 211 214 217

278 330 718 742 1244 1256 1270 1283 1292 1295 1300 1435 1442


+ 3461471 Found mz 3461466 IR

Chapter 2

60

(ATR) 3412 1315 1165 1146 683 cm-1

[]29




SN

HO

O OMe

2n

H

Me

NOE

SMe

1H NMR = 160-170 (m 1H) 184 (s 3H) 212-226 (m 4H) 230-242 (m 2H)

254-263 (m 1H) 294 (s 3H) 471 (dd J = 108 28 Hz 1H) 675 (s 1H) 722-738

(m 6H) 776 (d J = 80 Hz 1H) 13

C NMR = 150 215 242 301 321 643 748

1245 1262 1276 1283 12986 12993 1312 1429 1437 1441 HRMS (ESI+)


1165 1134 748 cm-1

[]28









was used as a


and


21 All



Chapter 2

61



2e

formula C17H19NO3S

fw 31739

T (K) 100(2)


space group P21c

a (Aring) 105967(5)


3) 152058(13)

Z 4 Dcalc (gcm

3) 1386

(mm-1

) 0225 F(000) 672



348500135

params 203 GOF on F

2 1069

R1 wR2 [Igt2(I)]

00322 00868

R1 wR2 (all data)

00335 00878

Chapter 2

62

























Med Chem 2003 46 1116








Chapter 2

63

































Chapter 2

64




2012 51 9160





11437-11439
























Chapter 2

65











2548-2551







11750









32 115



Chapter 2

66

Chapter 3

67

Chapter 3




Halides

Abstract






Chapter 3

68

Introduction
















2) are












several months


Et LiB

Ph

+B

Ph

Et

1a 74

(a)(b)[Me4N]


Chapter 3

69

















OMe

BrB

Ph

Et

OMe

3a

Ph

Et

OMe

H

4a

Pd-ligand AcOH

2a

+B

Ph

Et

1a

[Me4N]


EZ of 4ab

1 P(o-tol)3 69 397

2 P(t-Bu)3 47 1783

3 1-[(t-Bu)2P](biphenyl) 18 2872

4 2-[(t-Bu)2P](11-binaphthyl) 21 6733

5 DPEPhos 24 928



analysis



Chapter 3

70









Pd(0)

Pd

MeO

B

PdEt

OMe

Ph

B

Ph

Et

2a

BC

Pd

MeO

Br

A

1a

3a







dominates10
















Chapter 3

71










Chapter 3

72


BO

Ph

Et

OMe

5a 83

BO

Ph

Et

CF3

5b 85

BO

Ph

Et

NPhth

5c 82

BO

Ph

Et

5d 72b

BO

Ph

Et

5e 85

S

BO

n-Pr

Me

Cl

5f 74

BO

n-Pr

Ph

OMe

5g 82

BO

Ph

S

5h 83

BO

Ph

CO2Et

5i 81

BO

Ph

5j 82

Cl

BO

Ph

CF3

TBSO

BO

Cl

S

Ph

BO

Ph

Me

OMe

5n 71b

5m 925l 82

BO

Ph

5k 76

Me

+B

Ar

R

1

[Me4N]

2


BO

Ar

R

Ar

5







The reaction of 1a






Chapter 3

73








(E)-5o83 EZ = gt955

BO

Ph

Et

Ph

Ph

Et

PhO

NMe2

(Z)-685 EZ = lt595

Ph

Ph

EtO

NMe 2

(E)-675 EZ = 928

1a

(Z)-5o71 EZ = 793

+ PhBr

BO

Ph

Ph

Et

(a)

(c) (c)

(b)






Conclusions






Chapter 3

74




1H at 400 MHz and

11B at 128 MHz)



13C)

CD3CN ( = 194 for 1H =132 for


11B)









and Ph-9-BBN18


procedures


Et LiB

Ph

+B

Ph

Et

1a


2) Me4NCl MeOH

[Me4N]









74 yield)

Chapter 3

75

B

Ph

Et

1a

[Me4N]


136-207 (m 11H) 236-250 (m 2H) 303 (s 12 H) 679-686 (m 1H) 700-707 (m

2H) 735 (d J = 72 Hz 2H) 13

C NMR (CD3CN) = 149 166 266 (q JC-B = 379

Hz) 271 275 324 349 561 948 1221 1269 1339 11

B NMR = -133 HRMS




n-Pr LiB

Ar


2) Me4NCl MeOH B

n-Pr

1b

Cl

[Me4N]










Chapter 3

76

B

n-Pr

1b

Cl

[Me4N]

1H NMR (CD3CN) = 084-096 (m 5H) 111-121 (m 1H) 126-200 (m 13H)

235-250 (m 2H) 304 (s 12H) 700-705 (m 2H) 733 (d J = 84 Hz 2H) 13

C NMR

(CD3CN) = 139 234 249 266 (q JC-B = 393 Hz) 270 273 323 348 561

933 1265 1272 1355 11


[M-(NMe4)] 2991738 Found 2991730

B

n-Pr

1c

OMe

[Me4N]


128-201 (m 13H) 237-252 (m 2H) 303 (s 12H) 371 (s 3H) 663-668 (m 2H)

723 (d J = 81 Hz 2H) 13

C NMR (CD3CN) = 140 235 250 268 (q JC-B = 393

Hz) 272 275 324 349 554 561 929 1128 1344 1561 11

B NMR = -135


B

Ph

1d

[Me4N]


(m 2H) 134-196 (m 9H) 230-244 (m 2H) 304 (s 12H) 679-686 (m 1H)

699-706 (m 2H) 733 (d J = 72 Hz 2H) 13

C NMR (CD3CN) =23 87 266 (q

JC-B = 393 Hz) 271 274 323 349 562 1222 1269 1338 11

B NMR = -134


Chapter 3

77

B

Ph

1e

[Me4N]


(m 3H) 302 (s 12H) 679-686 (m 1H) 699-706 (m 2H) 734 (d J = 66 Hz 2H) 13

C NMR (CD3CN) = 253 268 (q JC-B = 379 Hz) 271 275 324 333 349 361

561 980 1221 1269 1339 11


[M-(NMe4)] 2912284 Found 2912278

B

1f

S

Ph

[Me4N]




09 Hz 1H) 712-730 (m 5H) 13

C NMR (CD3CN) = 240 268-290 (m) 325 347

380 562 928 1225 1261 1265 1271 1289 1297 1434 11

B NMR = -135


B

Ph

1g

TBSO

[Me4N]

1H NMR (CD3CN) = 005 (s 6H) 084-096 (m 11H) 110-120 (m 1H) 134-197

(m 9H) 216-233 (t J = 72 Hz 2H) 235-250 (m 2H) 301 (s 12H) 356 (t J = 78

Hz 2H) 680-687 (m 1H) 700-708 (m 2H) 735 (d J = 66 Hz 2H) 13

C NMR

(CD3CN) = -50 189 254-277 (m) 323 348 561 649 889 1222 1269

1339 11


Found 3812789

Chapter 3

78

B

Ph

1h

OMe

[Me4N]


(m 2H) 298 (s 12H) 373 (s 3H) 668-674 (m 2H) 701-718 (m 5H) 732 (d J =

87 Hz 2H) 13

C NMR (CD3CN) = 255-277 (m) 322 350 554 561 961 1129

1251 1287 1302 1312 1345 1564 11


C23H26BO [M-(NMe4)] 3292077 Found 3292081



Br

+

MeO


6 mol Ligand


2a

B

Ph

Et

OMe

(E)-3a

AcOH

Ph

Et

OMe

H

Ph

B

Et

OMe

+

+

(Z)-3a

(E)-4a

H

Et

OMe

Ph

(Z)-4a

B

Ph

Et

1a

[Me4N]









Chapter 3

79




B

Ph

Et

+


toluene 70 degC

Me3NO

Br

MeO

BO

Ph

Et

OMe

5a

1a

2a

[Me4N]









BO

Ph

Et

OMe


383 (s 3H) 438-444 (m 1H) 685-691 (m 2H) 714-736 (m 7H) 13

C NMR =

138 221 267 273 (br) 277 312 553 736 1132 1251 1278 1283 1298

1366 1436 1494 1586 11


3742417 Found 3742410

Chapter 3

80

BO

Ph

Et

CF3

5b


437-443 (m 1H) 718-726 (m 3H) 734-739 (m 2H) 745-748 (m 2H) 760-763

(m 2H) 13

C NMR = 135 220 266 271 (br) 276 312 738 12429 (q JC-F =

2701 Hz) 1247 (q JC-F = 36 Hz) 1280 1281 1289 (q JC-F = 320 Hz) 1291 1425

1476 1480 11


Found 4122186

BO

Ph

Et

NPhth

5c


440-450 (m 1H) 720-727 (m 3H) 734-739 (m 2H) 743-751 (m 4H) 777-783

(m 2H) 794-800 (m 2H) 13

C NMR = 137 221 266 274 (br) 275 312 738

1235 1254 1258 1279 1282 1294 1304 1317 1342 1429 1440 1482

1671 11

B NMR = 502 IR (KBr) = 2928 1742 1509 1381 714 cm-1

HRMS (EI)


BO

Ph

Et

5d

1H NMR = 021-034 (m 1H) 068-100 (m 8H) 120-150 (m 7H) 224-238 (m

1H) 244-258 (m 1H) 424-431 (m 1H) 722-754 (m 9H) 778 (d J = 78 Hz 1H)

783-788 (m 1H) 809-816 (m 1H) 13

C NMR = 137 216 219 259 262 264

(br) 282 309 314 734 1249 12537 12539 1255 1264 1270 1273 12795

Chapter 3

81

12799 1283 1321 1335 1413 1427 1467 11


for C28H31BO (M+) 3942468 Found 3942476

BO

Ph

Et

5e

S


448-456 (m 1H) 702 (dd J = 51 36 Hz 1H) 708 (dd J = 36 12 Hz 1H)

715-730 (m 4H) 732-738 (m 2H) 13

C NMR =141 221 271 289 312 739

1250 1255 1266 1269 1279 1281 1416 1427 1468 11

B NMR = 496


BO

n-Pr

Me

Cl

5f

1H NMR = 070 (t J = 75 Hz 3H) 096-133 (m 9H) 142-172 (m 6H) 220-228

(m 2H) 237 (s 3H) 439-446 (m 1H) 708-735 (m 8H) 13

C NMR = 140 212

219 221 267 274 (br) 313 363 737 1279 12846 12855 1298 1309 1365

1411 1420 1488 11


4062235 Found 4062237

BO

n-Pr

Ph

OMe

5g

Chapter 3

82


(s 3H) 435-450 (m 1H) 690 (d J = 81 Hz 2H) 711 (d J = 81 Hz 2H) 720-740

(m 5H) 13

C NMR = 140 219 221 267 274 (br) 312 362 551 736 1133

1267 1278 1287 1294 1354 1446 1475 1573 11




BO

Ph

S

5h

1H NMR = 027-032 (m 2H) 046-052 (m 2H) 098-130 (m 6H) 140-170 (m

8H) 430-445 (m 1H) 696-700 (m 1H) 704-707 (m 1H) 715-726 (m 2H)

729-738 (m 4H) 13

C NMR = 60 150 222 263 272 (br) 313 736 1241

1243 1253 1278 1290 1295 1410 1425 1431 11



BO

Ph

CO2Et

5i

1H NMR = 017-023 (m 2H) 045-053 (m 2H) 090-119 (m 6H) 132-173 (m

11H) 427-433 (m 1H) 438 (q J = 75 Hz 2H) 718-738 (m 7H) 798 (dt J = 78

15 Hz 2H) 13

C NMR = 56 144 151 220 263 269 (br) 312 609 735 1255

1279 1284 1287 1289 1303 1423 1453 1469 1665 11

B NMR = 496 IR

(KBr) = 2928 1717 1287 1100 cm-1


Found 4282526

BO

Ph

5j

Cl

Chapter 3

83

1H NMR = 023-029 (m 2H) 048-055 (m 2H) 094-123 (m 6H) 134-171 (m

8H) 432-439 (m 1H) 706-714 (m 1H) 718-726 (m 4H) 728-738 (m 4H) 13

C

NMR = 57 150 220 263 271 (br) 312 736 1255 1267 1279 1283 1284

1289 1304 1332 1423 1424 1461 11


C25H28BClO (M+) 3901922 Found 3901923

BO

Ph

5k

Me

1H NMR = 082-113 (m 6H) 126-164 (m 15H) 237 (s 3H) 268-280 (m 1H)

434-441 (m 1H) 704-709 (m 3H) 717-725 (m 4H) 730-737 (m 2H) 13

C NMR

= 215 219 248 263 273 (br) 312 315 433 735 1252 12689 12693 1275

1278 1283 1316 1365 1418 1424 1481 11


for C28H35BO (M+) 3982781 Found 3982780

BO

Cl

S

Ph

5l

1H NMR = 106-176 (m 13H) 250-260 (m 2H) 272-280 (m 2H) 441-449 (m

1H) 674 (dd J = 33 12 Hz 1H) 697-703 (m 3H) 709-738 (m 8H) 13

C

NMR(C6D6) =225 272 277 (br) 315 358 375 739 1247 1253 1261 1272

1285 12856 12861 1306 1335 1419 1427 1437 1491 11

B NMR = 495


BO

Ph

CF3

TBSO

5m

Chapter 3

84

1H NMR = -014 (s 6H) 079 (s 9H) 095-136 (m 6H) 142-168 (m 7H) 255 (t

J = 72 Hz 2H) 343 (t J = 72 Hz 2H) 435-442 (m 1H) 718-726 (m 3H)

731-737 (m 2H) 747 (d J = 81 Hz 2H) 759 (d J = 81 Hz 2H) 13

C NMR = -54

183 220 259 266 271 (br) 311 377 616 739 1242 (q JC-F = 2694 Hz) 1247

(q JC-F = 36 Hz) 1258 1280 1282 1290 (q JC-F = 320 Hz) 1291 1421 1422

1480 11



BO

Ph

Me

OMe

5n

1H NMR = 122-130 (m 4H) 138-162 (m 5H) 168-186 (m 4H) 237 (s 3H)

375 (s 3H) 443-450 (m 1H) 670 (dt J = 90 21 Hz 2H) 690-697 (m 4H)

702-708 (m 3H) 710-720 (m 4H) 13

C NMR = 213 222 269 312 550 738

1132 1260 1272 1285 1301 1307 1310 1362 1369 1423 1429 1483

1571 11


4362561


4-Bromobenzene

B

Ph

Et

+


toluene 70 degC

Me3NO BO

Ph

Ph

Et

(Z)-5o

1a

Ph Br

[Me4N]




Chapter 3

85






BO

Ph

Ph

Et


470-475 (m 1H) 685-710 (m 10H) 13

C NMR = 139 224 267 313 317 740

1248 1257 1272 127412938 12941 1421 1425 1275 11

B NMR = 512


BO

Ph

Et

Ph


438-443 (m 1H) 718-737 (m 10H) 13

C NMR = 137 221 266 274 (br) 277

312 737 1253 1268 1278 1279 1283 1288 1433 1442 1494 11

B NMR =



Bromide 2b

+

Br

ONMe2

Ph

Et

PhO

NMe2


THF K3PO4 60 degC

(Z)-Tamoxifen 6

2b

BO

Ph

Et

Ph

(E)-5o

Chapter 3

86









Chapter 3

87



2003 Vol 3








Rev 2006 250 1107









1976 108 281








74





Chapter 3

88





















2006 128 1828




Chapter 4

89

Chapter 4



Abstract






Chapter 4

90

Introduction





























Chapter 4

91


B

MOMO

[Me4N] +

MeO

Br

I

Br

MeO Br

B

MeO

MOMO MOMO

1a

2 3 87EZ = lt199

NaOH

50 degC

1 mol


toluene 50 degC
















procedure

Chapter 4

92



An











3

MeO

R

Br

4 92

R

MeO

R

Br

n = 2 5 87

n = 3 6 82n = 4 7 85

n

R

1 mol


toluene 50 degC

I

Br

NaOH

E

EE

R = OMOM








Chapter 4

93





Br

Br

R

R

Br

Br

8 86

R

R

Br

R

R

Br

9 92

E E

R = OMOM















Chapter 4

94


Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

Me3Si

Br

Ph

F

Me3Si

OMe

Br

Ph

F

S

Br

Me3Si

OMe

B

n-Pr

[Me4N]

Cl

B

Ph

[Me4N]

OMe

Br

S

Br

I

EtO2C

MOMO

MOMO

I

Br

F

1b

10 88

11 84

12 88

1a1c

cat Pd

NaOHcat Pd

cat Pd NaOH

Cs2CO3

Conclusions







Chapter 4

95




1H at 500 MHz and






13C) CD3CN ( = 194 for

1H =132 for

13C) and

BF3OEt2 ( = 000 for 11











11













Chapter 4

96

B

MOMO

[Me4N]

1a


202 (t J = 66 Hz 2H) 236-251 (m 2H) 304 (s 12H) 328 (s 3H) 346 (t J = 69

Hz 2H) 454 (s 2H) 678-685 (m 1H) 698-705 (m 2H) 734 (d J = 72 Hz 2H) 13

C NMR (CD3CN 75 MHz) = 210 267 (br) 271 275 282 297 324 349 551

561 681 928 968 1221 1269 1338 11



B

Ph

[Me4N]

1b

OMe


225 (t J = 72 Hz 2H) 234-249 (m 2H) 263 (t J = 72 Hz 2H) 303 (s 12H) 372

(s 3H) 663-669 (m 2H) 711-728 (m 7H) 13


272 275 324 349 381 554 560 1129 1266 1289 1298 1346 1434 1563 11


3572390 Found 3572383



B

MOMO

[Me4N]

+

MeO

Br

1 mol


toluene 50 degC

I

Br

MeO Br

NaOH

3

1a

MOMO

Chapter 4

97








MeO Br

3

MOMONOE

NOE




(t J = 66 Hz 2H) 376 (s 3H) 452 (s 2H) 667-675 (m 4H) 697-702 (m 2H)

709-736 (m 7H) 13

C NMR (75 MHz) = 255 298 356 5510 5514 676 964

1134 1196 1267 1282 1294 13046 13049 1323 1339 1376 1408 1420



spectroscopy

MeO

R

Br

4

R

R = OMOM




Chapter 4

98


2H) 325 (s 3H) 329 (s 3H) 331-341 (m 4H) 380 (s 3H) 451 (s 2H) 453 (s

2H) 662-678 (m 8H) 697-703 (m 2H) 706-738 (m 12H) 13

C NMR (150 MHz)

= 252 254 295 296 353 354 5502 5504 552 675 676 9629 9632 1131

1196 1265 1267 1281 1282 1285 12941 12942 1303 1304 1306 1324

1343 1377 1385 1390 1400 1413 1414 1418 1429 1435 1579 HRMS


7972818 Found

7972849

MeO

R

5

R

R = OMOM

R

Br




325 (s 3H) 327 (s 3H) 328 (s 3H) 330-342 (m 6H) 374 (s 3H) 450 (s 2H)

452 (s 2H) 454 (s 2H) 654-662 (m 4H) 666-678 (m 8H) 696-704 (m 4H)

712-737 (m 15H) 13

C NMR (75 MHz) = 254 256 296 297 298 3526 3534

355 551 675 676 963 1130 1196 1264 1267 1280 1281 1286 1294 1301

1302 1304 1306 1324 1344 1377 1384 1387 1392 1393 1398 1402 1409



10914437 Found 10914482

Chapter 4

99

MeO

R

6

R

R = OMOM

R

R

Br




330-341 (m 8H) 371 (s 3H) 448-454 (m 8H) 648-675 (m 16H) 695-703 (m

4H) 714-737 (m 20H) 13

C NMR (75 MHz) = 253 254 256 257 2969 2974

298 350 354 356 550 551 675 676 963 1131 1196 1264 1267 1279

1280 1281 1283 1288 1293 1294 1300 1301 1302 1305 1306 1323 1342

1377 1385 1387 1389 1391 1394 1396 1397 1401 1405 1409 1411 1413



13856057 Found 13856062

MeO

R

7

R

R = OMOM

R

R

R

Br




374 (s 3H) 447-452 (m 10 H) 649-679 (m 20 H) 690-695 (m 2H) 701-706 (m

2H) 710-736 (m 25H) 13

C NMR (75 MHz) = 2529 2535 256 257 2968

Chapter 4

100

2971 298 351 354 355 356 550 6746 6755 676 963 1131 1195 1264

1267 12795 1280 1281 1283 1285 1287 1293 12937 12944 1301 1302

1304 1306 1322 1343 1377 1384 1387 1389 1390 1391 1394 13976

13979 1401 1404 1408 1409 1412 1413 1416 1427 14318 14321 1434


16797677 Found 16797694

8

R

Br

R

Br

R = OMOM





(t J = 66 Hz 4H) 456 (s 4H) 668-673 (m 4H) 691 (s 4H) 710-721 (m 8H)

722-737 (m 6H) 13

C NMR (75 MHz) = 254 297 354 551 676 963 1198

1268 1282 1291 1293 1303 1323 1380 1400 1411 1417 1427 HRMS


8221905

9

R

R

R = OMOM

R

R

Br

Br



Chapter 4

101


6H) 330-340 (m 8H) 446 (s 4H) 453 (s 4H) 656-672 (m 12H) 688 (s 4H)

704-710 (m 4H) 714-718 (m 4H) 722-740 (m 16H) 13

C NMR (150 MHz) =

254 2962 2963 356 357 5501 5503 674 676 9629 9631 1197 1266

1268 1281 12818 12822 1290 1295 1296 1304 1308 1324 1379 1385

1394 1403 1405 1409 1416 1417 1427 1434 HRMS (MALDI-TOF-MS


14335057 Found 14335040

Ph

F

Me3Si

OMe

Br

10

NOE

NOE





3H) 676-686 (m 3H) 694-707 (m 6H) 709-728 (m 5H) 734 (d J = 84 Hz 2H) 13

C NMR (150 MHz) = -11 349 372 552 1135 1189 (d JC-F = 255 Hz)1202

(d JC-F = 92 Hz) 1258 1268 (d JC-F = 35 Hz) 1280 1283 1284 1300 1304 (d

JC-F = 159 Hz) 1326 1329 1332 (d JC-F = 45 Hz) 1339 1387 1417 1418 1430




Chapter 4

102

Ph

F

S

Br

Me3Si

OMe

11

MOMO




= 78 2H) 264-272 (m 2H) 282-289 (m 2H) 325 (s 3H) 328 (t J = 66 Hz 2H)

382 (s 3H) 448 (s 2H) 587 (d J = 39 Hz 1H) 660 (d J = 39 Hz 1H) 669-676

(m 2H) 684-696 (m 3H) 705-742 (m 16H) 13

C NMR (150 MHz) = -10 244

293 351 362 372 550 552 673 963 1127 1135 1161 (d JC-F = 225 Hz)

1244 (d JC-F = 32 Hz) 1258 1274 12827 12831 12837 12840 12856 12861

1295 1302 1307 (d JC-F = 155 Hz) 1324 1329 1330 (d JC-F = 45 Hz) 1333

1345 1385 1395 (d JC-F = 12 Hz) 1412 1416 (d JC-F = 80 Hz) 1419 1422



Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

12MOMO




mmol) t1 10 h t2 12 h

Chapter 4

103


210-224 (m 4H) 264-272 (m 2H) 279-287 (m 2H) 323-333 (m 5H) 373 (s


1H) 666-672 (m 2H) 679-694 (m 5H) 703-737 (m 20H) 773 (d J = 84 Hz

2H) 13

C NMR (150 MHz) = -11 141 143 225 244 293 350 359 370 385

550 551 607 674 963 1134 1159 (d JC-F = 224 Hz) 1243 (d JC-F = 29 Hz)

1258 1269 1271 12808 12811 12815 12820 12823 12838 12844 1290

1293 1300 1301 (d JC-F = 158 Hz) 1302 1307 1323 (d JC-F = 47 Hz) 13258

13261 1328 1336 1344 1356 1379 1382 1390 (d JC-F = 12 Hz) 1409 14190

14191 14216 (d JC-F = 80 Hz) 14219 14222 1438 1446 1476 1583 1600 (d

JC-F = 2448 Hz) 1664 IR (KBr) = 2955 1717 1509 1273 1248 1111 837 cm-1


11294440

Found 11294465

Chapter 4

104




Chem 1999 201 163




897















2404


2006 128 1828



Chapter 5

105

Chapter 5




Abstract






Chapter 5

106

Introduction





moiety1b


























Chapter 5

107


B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

OHMe

Ph

1a

3a 85

MeO

OMe

2a

B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

1b

OMe

2a

OHMe

Ph

OMe

3b 88

[Me4N]

[Me4N]




Oxidative









Chapter 5

108


O

I

O

PdI

Pd(0)

B

1a

C

Pd(0)3a

Ar = p-MeOC6H4-

Me Me

OMe

Ar

Ph

B

D

A

Pd

O

ArB

Me

Ph

B

O

ArPh

Me

Me4NI

2a







Chapter 5

109


R3

O

I

B

R2

R1

+1 mol Pd

toluene50 degC 1 h

OHR3

R1

R2

OHMe

Ph

S

OHMe

OMe

OHPh

Ph

OMe

3f 72

3h 763j 80

3g 84

3d 82

3c 83

OHMe

Ph

CF3

1 2 3

OHH

Ph

OMe

OHPh

Ph

OMe

O

O

OHPh

3e 92

F

OMe

OHPh

Ph

OMe

F3C

3i 62

R4R4

MeO

[Me4N]










Chapter 5

110

OHMe

t-Bu

S

3k 89

B +1 mol Pd

toluene

50 degC 1 h

2a

t-Bu

S

(1)

1c

[Me4N]

OHMe

n-Bu

Me

3l 80

B

n-Bu

+1 mol Pd

toluene50 degC 1 h

2a

Me

(2)

1d

[Me4N]










n-Hex

13 equiv

Ph

Li

065 equiv

(H-9-BBN) 2


1 mol Pd

toluene 50 degC 1 h

10 equiv 2aOH

Me

n-Oct

11 equiv

3m 91 (based on 2a)

B

n-Oct

PhLi

Ph




Chapter 5

111


in 59 yield11


OHH

Ph

OMe

MnO2

DCM rt

Ph

OMe

O

NH2NH2 KOHPh

OMe

4 96 5 59

3n 74

(CH2OH)2 150 C

1a +

CHO

I2b

1 mol Pd

Conclusions




Chapter 5

112



and 13


B at 128 MHz)



13C) CD3CN (δ = 194 for

1H δ = 132 for


11B) IR






(Merck)





and alkynylborate14




Li

BPh

+

B

Ph

1a


2) Me4NCl MeOH

[Me4N]

MeO

MeO










Chapter 5

113

B

Ph

1a

[Me4N]

MeO


(m 2H) 296 (s 12H) 372 (s 3H) 668-675 (m 2H) 685-691 (m 1H) 700-712 (m

4H) 743 (d J = 64 Hz 2H) 13

C NMR (CD3CN) δ = 256-272 (m) 270 274 322

350 557 560 955 1145 1227 (2C) 1273 1324 1341 1578 The boron-bound


11B NMR


3292079

B

Ph

1b

[Me4N]

OMe


(m 2H) 295 (s 12H) 374 (s 3H) 666-675 (m 2H) 702-718 (m 5H) 733 (d J =

84 Hz 2H) 13

C NMR (CD3CN) δ = 254-274 (m) 270 273 321 350 554 560





B

nBu

1d

[Me4N]

Me


(m 4H) 136-157 (m 6H) 170-196 (m 4H) 220-234 (m 5H) 304 (s 12H)

697-701 (m 2H) 704-709 (m 2H) 13

C NMR (CD3CN) δ = 152 212 270

271-290 (m) 282 288 318 324 357 561 1279 1296 1314 1344 The

Chapter 5

114




[M-(NMe4)]- 2932446 Found 2932454

B

Ph

1e

[Me4N]

F3C


(m 2H) 292 (s 12H) 690-696 (m 1H) 710-718 (m 2H) 728 (dd J = 88 08 Hz

2H) 744-752 (m 4H) 13

C NMR (CD3CN) δ = 252-270 (m) 269 273 321 351






B

Ph

1f

[Me4N]

S



48 32 Hz 1H) 703-719 (m 6H) 13

C NMR (CD3CN) δ = 266 272 270-286 (m)

323 348 560 962 1231 1256 1266 1274 1290 1300 1314 The boron-bound

sp2 and sp


11B NMR


- 3051541 Found

3051541

Chapter 5

115


(H-9BBN) 2

H tBu

THF 0 degC

THF -78 degC to rt

2) Me4NCl MeOH

Li

1)S

B

1c

[Me4N]

S

tBu














B

1c

[Me4N]

S

tBu


4H) 222-235 (m 2H) 306 (s 12H) 552 (d J = 172 Hz 1H) 591 (d J = 176 Hz


Hz 1H) 13

C NMR (CD3CN) δ = 273 276 278-296 (m) 311 327 341 352 561





Chapter 5

116












OHMe

3aOMe

NOE

no NOE

IR (ATR) 3315 1508 1248 752 694 cm-1

1H NMR δ = 159 (s 3H) 204 (bs 1H)

382 (s 3H) 684-690 (m 2H) 721-730 (m 8H) 742-748 (m 2H) 751-755 (m

1H) 13

C NMR δ = 239 552 832 1139 1208 1218 1265 1268 1272 1280


C23H21O2 [M+H]+ 3291536 Found 3291556

OHMe

OMe

3b

NOE

no NOE

IR (ATR) 3319 1508 1248 760 702 cm-1

1H NMR δ = 160 (s 3H) 208 (s 1H)

378 (s 3H) 674-680 (m 2H) 718-723(m 1H) 724-744 (m 9H) 750-755 (m

1H) 13

C NMR δ = 241 551 833 1134 1205 1218 1263 1270 1274 1284


Chapter 5

117

C23H20O2Cl [M+Cl]- 3631146 Found 3631148

OHMe

Ph

3cCF3

IR (ATR) 3298 1319 1121 750 696 cm-1

1H NMR δ = 160 (s 3H) 210 (bs 1H)

716-722 (m 1H) 723-732 (m 5H) 737-747 (m 4H) 752-764 (m 3H) 13

C NMR

δ = 240 833 1205 1221 1241 (q JC-F = 2701 Hz) 1255 (q JC-F = 37 Hz) 1269

1277 1282 1286 1293 1295 (q JC-F = 322 Hz) 1296 1341 1373 1385 1414


- 3651159 Found 3651159

OHMe

Ph

3d

S

IR (ATR) 3319 1350 1088 752 694 cm-1

1H NMR δ = 177 (s 3H) 209 (bs 1H)

696-702 (m 2H) 718 (dd J = 52 Hz 12Hz 1H) 723-730 (m 2H) 735-740 (m

3H) 742-752 (m 3H) 753-758 (m 1H) 13

C NMR δ = 254 833 1207 1216

1259 1265 1266 1275 1282 1287 1290 1294 1347 1360 1374 1410 1426


+ 3050995 Found 3050992

OHMe

OMe

3e

IR (ATR) 3310 1508 1244 1034 758 cm-1

1H NMR δ = 144 (s 3H) 158-202 (m


5H) 747 (d J = 68 Hz 1H) 13

C NMR δ = 238 266 267 305 311 382 552

822 1136 1211 1219 1257 12789 12793 1304 1406 1409 1467 1499


+ 3382115 Found 3382104

Chapter 5

118

OHH

Ph

3fOMe

MeO

IR (ATR) 3472 1601 1508 1244 704 cm-1

1H NMR δ = 174 (d J = 88 Hz 1H)


= 80 Hz 24 Hz 1H) 692-697 (m 2H) 718-730 (m 5H) 732-736 (m 2H) 753 (d

J = 84 Hz 1H) 13

C NMR δ = 552 555 766 1072 1109 1143 1244 1267 1272

1283 1292 1303 1342 1363 1390 1445 1457 1592 1606 HRMS (ESI+)


OHPh

Ph

3gOMe

IR (ATR) 3422 1508 1244 1028 746 698 cm-1

1H NMR δ = 248 (s 1H) 385 (s

3H) 695 (d J = 88 Hz 2H) 704-714 (m 5H) 715-732 (m 7H) 736-740 (m 2H)

755 (d J = 88 Hz 2H) 13

C NMR δ = 552 868 1141 1210 1231 1250 1268

12698 12702 1271 1278 12836 12844 1294 1304 1340 1402 1417 1427


+ 3911693 Found

3911718

OHPh

Ph

3hOMe

O

O

IR (ATR) 3362 1470 1244 1034 696 cm-1

1H NMR δ = 239 (s 1H) 385 (s 3H)

591 (dd J = 164 16 Hz 2H) 673 (d J = 44 Hz 2H) 690-696 (m 2H) 702-708

(m 5H) 720-736 (m 5H) 749-754 (m 2H) 13

C NMR δ = 552 863 1012 1024

Chapter 5

119

1049 1142 1249 12690 12692 1270 1278 1285 1292 1304 1340 1367


+

4341518 Found 4341505

OHPh

Ph

3iOMe

F3C

IR (ATR) 3545 1508 1321 1115 696 cm-1

1H NMR δ = 249 (s 1H) 387 (s 3H)

694-700 (m 2H) 704-715 (m 5H) 723-738 (m 6H) 742-755 (m 4H) 13

C NMR

δ = 553 866 1145 1177 (q JC-F = 37 Hz) 1233 1241 (q JC-F = 36 Hz) 1242 (q

JC-F = 2702 Hz) 1249 1260 1275 1276 1280 1287 1295 1304 1308 (q JC-F =


C29H21F3O2Cl [M+Cl]- 4931177 Found 4931192

OHPh

3j

F

OMe

IR (ATR) 3356 1242 1028 741 696 cm-1

1H NMR δ = 164-178 (m 2H) 183-208


4H) 719-737 (m 6H) 13

C NMR δ = 2675 2681 308 310 383 551 862 1114


1268 1271 1283 1303 1371 (d JC-F = 29 Hz) 1410 1418 (d JC-F = 15 Hz)



+ 4001839 Found 4001835

OHMe

S

tBu

3k

Chapter 5

120

IR (ATR) 3298 1358 1078 756 689 cm-1

1H NMR δ = 111 (s 9H) 168 (s 3H)

188 (s 1H) 640 (d J = 164 Hz 1H) 656 (d J = 164 Hz 1H) 718-730 (m 4H)

739-751 (m 3H) 13

C NMR δ = 257 295 340 822 1169 1204 1215 1242

1255 1262 1283 1285 1324 1346 1415 1452 1462 1506 HRMS (ESI+)


OHMe

nBu

OMe3l

IR (ATR) 3335 1508 1084 918 758 cm-1

1H NMR δ = 085 (t J = 72 Hz 3H) 130

(tt J = 72 72 Hz 2H) 141-167 (m 6H) 229-250 (m 5H) 702-706 (m 1H)

716-728 (m 6H) 744-748 (m 1H) 13

C NMR δ = 138 213 232 237 252 314

829 1198 1215 1256 1282 1286 1291 1318 1370 1374 1430 1492 1496


+ 2931900 Found 2931890



nHex

(H-9BBN) 2


Li

Ph

B

nOct

Li

Ph

Me

O

I


toluene 50 degC 1 h

H2O2 aq

NaOH aq

OHMe

nOct

Ph3m

MeOH




Chapter 5

121













yield)

OHMe

nOct

Ph3m

IR (ATR) 3335 1456 1078 752 698 cm-1

1H NMR δ = 096 (t J = 68 Hz 3H)

129-156 (m 15H) 160 (s 1H) 208-227 (m 2H) 274-281 (m 2H) 287-294 (m

2H) 719-728 (m 5H) 729-736 (m 3H) 742 (d J = 72 Hz 1H) 13

C NMR δ = 141

226 234 247 277 293 294 295 304 319 345 825 1186 1213 1252 1260


[M]+ 3622610 Found 3622619

OHH

Ph

OMe

3n

IR (ATR) 3354 1508 1246 764 692 cm-1

1H NMR δ = 185 (bs 1H) 386 (s 3H)

567 (s 1H) 692-697 (m 2H) 718-738 (m 10H) 763-766 (m 1H) 13

C NMR δ =

552 773 1143 1206 1237 1263 1268 1272 1283 1287 1292 1303 1342


- 3131234

Found 3131237

Chapter 5

122

The 1H


15


OHH

Ph

OMe

3n

MnO2

DCM rt

Ph

OMe

4

O







The 1H


16

Ph

OMe

4

O

(CH 2OH)2

NH2NH2

KOH Ph

OMe

5








The 1H


5

Chapter 5

123






1395ndash1411



17638ndash17640





3201ndash3222



















Chapter 5

124












3283ndash3292









74








Chem 1989 54 1485ndash1491



2006 128 1828

Chapter 5

125



4781-4787


Chem 1989 54 1485

Chapter 5

126

127

List of Publication

Chapter 1



Angew Chem Int Ed 2012 51 11750-11752

Chapter 2


Benzosultams


J Am Chem Soc 2013 135 19103-19106

Chapter 3





Org Lett 2009 11 5434-5437

Chapter 4


Units


Org Lett 2010 12 3179-3181

Chapter 5




Eur J Org Chem 2013 1421-1424

Other Publication




Chem Lett 2013 42 1076

Contents


Chapter 1


Chapter 2


Benzosultams 29

Chapter 3



Halides 67

Chapter 4


Units 89

Chapter 5





1









sultams














sun

CO2energy charge

Ph

O

NTs

Me

N

Ts

OHPh

OO

O

Ph

NHTs


2


benzosultams




developed456


shift7

MH14-metal shift

1

2 3

4

HM

1

2 3

4

H M1

23

4

5

M H1

23

4

515-metal shift






N

Ts

Ph OHMe

SN

MeO O

Ph OH

cat Rh





chemistry10






We


alkynylborates13

R1 B

R2

R2

R2

+ R3 Br

R3

R1 R2

B

R2

R2


3






obtained

Et

Ph

Ph

B O+

PhBr LPd(-allyl)Cl

L = XANTPhos

LPd(-allyl)Cl

L = P(o-tol)3 Ph

Et

Ph

B O

B

Et

Ph

Et

Ph

B

Ph

Ph

Et

B

Ph

Me3NO

Me3NO

[Me4N]







MeO

Br

I

Br

NaOH

R Ph

MeO Br

B

R

Ph

RB

Ph

OMe

[Me4N]

R Ph

MeOR Ph

Br

R =OMOM

n

B

R

Ph

[Me4N] I

Br

NaOH

R Ph

MeOR Ph

Br

n = 2~4

Pd-XANTPhos

Pd-XANTPhos






4


regioselectively

I

Me

O+

MeOH

R2

R1Pd-XANTPhosB

R2

R1

[Me4N]


5

Reference





































6








10990




2003 Vol 3





Q Z J Med Chem 2009 52 4192



2006 250 1107



2419













7



17638ndash17640


8

Chapter 1

9

Chapter 1


Ketones

Abstract






Chapter 1

10

Introduction







2 One







starting substances


CO2

sun

CO2energy charge

high energy

intermediates











8






Chapter 1

11


Ph

O

NTs

Mesolar light

N

Ph OH

Ts

2a 91

1aDMA







over 04 kWm-2



in eight hours on


Figure





kWhm-2



Chapter 1

12


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

0

20

40

60

80

100

0 1 2 3 4 5 6











(56)

Chapter 1

13


40 equiv Cs2CO3

1 atm CO2

DMA 60 degC

OO

O

Ph

NHTs

3a 93

N

Ph OH

Ts

2a








N

Ph O

Ts

A

N

Ph O

Ts

B

O

O

OO

O

Ph

NTs

CO2

H

C

Cs2CO3

CsHCO 3

Cs

Cs

Cs

2

1

N

Ph OH

Ts

2a

OO

O

Ph

NHTs

3a












N

Ts

OHPh

4

Chapter 1

14




solar light

CO2Cs2CO3

60degCDMAPh

O

NTs

Me

1a

OO

O

Ph

NHTs

3a 83






chloro groups10





Ar

O

NR

Me OO

O

Ar

NHR3

1

OO

O

NHTs3b 80

MeO

OO

O

NHTs3c 57

F3C

OO

O

NHTs3d 73

Cl

OO

O

NHTs3e 85

Br

OO

O

Ph

NH

3f 87

O2S OMe

OO

O

Ph

NH

3g 85

O2S CF3

OO

O

Ph

NH

3h 87

O2S

N

solar lightCO2

Cs2CO3

60degCDMA




Chapter 1

15

Conclusions















Chapter 1

16












indicator (Merck)






Ph

O

NTs

MeTsClMeNH2 +

Et2OTsNHMe

CH3CN

K2CO3












Chapter 1

17


Ph

O

NTs

Me


745-751 (m 2H) 760 (tt J = 76 12 Hz 1H) 771-775 (m 2H) 795-799 (m 2H)

13C NMR δ = 215 356 560 1275 1282 1288 1297 1338 1347 1348 1436


+ 3041002 Found mz 3040994 IR

(ATR) 1693 1339 1227 1157 743 cm-1

O

NTs

Me

1bMeO


733 (d J = 80 Hz 2H) 770-774 (m 2H) 796-802 (m 2H) 13

C NMR δ = 215

355 555 558 1139 1275 1277 1296 1307 1346 1436 1640 1921 HRMS


+ 3341108 Found mz 3341101 IR (ATR) 1688

1601 1329 1180 1159 cm-1

O

NTs

Me

1cF3C


= 84 Hz 2H) 776 (d J = 84 Hz 2H) 812 (d J = 84 Hz 2H) 13

C NMR δ = 215

357 564 1234 (q JC-F = 2711 Hz) 1259 (q JC-F = 37 Hz) 1276 1288 1298



1121 1109 cm-1

Chapter 1

18

O

NTs

Me

1dCl


(m 2H) 771 (d J = 80 Hz 2H) 792-796 (m 2H) 13

C NMR δ = 216 356 561



1159 1088 cm-1

O

NTs

Me

1eBr


= 84 Hz 2H) 771 (d J = 84 Hz 2H) 786 (d J = 84 Hz 2H) 13

C NMR δ = 215

356 561 1275 1291 1297 1298 1321 1334 1344 1438 1930 HRMS (ESI+)


1223 1155 810cm-1

Ph

O

NS

Me

1f

OMe

OO

1H NMR δ = 282 (s 3H) 389 (s 3H) 456 (s 2H) 698-703 (m 2H) 746-751 (m

2H) 761 (tt J = 72 12 Hz 1H)776-781 (m 2H) 796-800 (m 2H) 13

C NMR δ =

356 556 561 1142 1283 1288 1294 1297 1338 1348 1630 1938 HRMS


+ 3200951 Found mz 3200943 IR (ATR) 1692

1342 1259 1155 741 cm-1

Chapter 1

19

Ph

O

NS

Me

1g

CF3

OO


780 (d J = 84 Hz 2H) 790-794 (m 2H) 798 (d J = 80 Hz 2H) 13

C NMR δ =

356 558 1233 (q JC-F = 2711 Hz) 1261 (q JC-F = 36 Hz) 12796 12799 1289



1059 748 cm-1

Ph

O

NS

Me

1h

N

OO

1H NMR δ = 302 (s 3H) 486 (s 2H) 744-753 (m 3H) 757-762 (m 1H)

788-798 (m 4H) 870 (ddd J = 48 16 08 Hz 1H)13

C NMR δ = 363 569 1224



752 cm-1


Ph

O

NTs

Mesolar light

N

Ph OH

TsDMA rt

1a

2a








Chapter 1

20


N

Ph OH

Ts


2H) 728-737 (m 5H) 740 (d J = 80 Hz 2H) 779 (d J = 80 Hz 2H) 13

C NMR δ

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS




N 458 O 1555 S 1058 IR (ATR) 3477 1333 1184 1148 671 cm-1


N

Ph OH

Ts

2a

40 equiv Cs2CO3

1 atm CO2

DMA 60 C

OO

O

Ph

NHTs

3a








mmol 93 yield)

Chapter 1

21



40 equiv Cs2CO3

60 CPh

O

NR

Me OO

O

Ph

NHR3a

1a

solar light

DMA rt

1 atm CO2











OO

O

Ph

NHTs



726-732 (m 4H) 734-743 (m 3H) 769-773 (m 2H) 13

C NMR δ = 215 503

724 850 1242 1269 1292 1299 1365 1381 1439 1542 HRMS (ESI+) Calcd

for C17H18NO5S M+H+


C 5878 H 493 N 403 O 2303 S 923 Found C 5871 H 496 N 389 O

2284 S 932 IR (ATR) 3261 1773 1435 1319 1045 cm-1

Chapter 1

22

OO

O

NHTs

3b

MeO



56 Hz 1H) 688-693 (m 2H) 719-724 (m 2H) 728 (d J = 80 Hz 2H) 770 (d J =

84 Hz 2H) 13

C NMR δ = 215 503 554 724 848 1145 1256 1269 1298


+

3781006 Found mz 3780996 IR (ATR) 3238 1794 1518 1329 1057 723 cm-1

OO

O

NHTs

3c

F3C



729 (d J = 84 Hz 2H) 746 (d J = 84 Hz 2H) 765-771 (m 4H) 13

C NMR δ =

215 501 722 846 1235 (q JC-F = 2704 Hz) 1249 1263 (q JC-F = 37 Hz) 1268



1067 cm-1

OO

O

NHTs

3d

Cl



722-727 (m 2H) 728 (d J = 84 Hz 2H) 735-739 (m 2H) 769 (d J = 84 Hz 2H)

13C NMR δ = 215 502 723 847 1257 1268 1294 1300 1353 1364 1365


+ 3820510 Found mz

Chapter 1

23

3820506 IR (ATR) 3250 1800 1325 1155 1069 cm-1

OO

O

NHTs

3e

Br



716-720 (m 2H) 728 (d J = 80 Hz 2H) 750-755 (m 2H) 766-770 (m 2H) 13

C

NMR δ = 215 501 723 847 1235 1260 1268 1300 1323 1364 1370 1441


+ 4260005 Found mz 4260003

IR (ATR) 3252 1800 1331 1175 1057 cm-1

OO

O

Ph

NH

SO

O

OMe



693-698 (m 2H) 727-732 (m 2H) 734-744 (m 3H) 773-778 (m 2H) 13

C NMR

δ = 503 556 724 849 1145 1242 1291 1292 1310 1381 1541 1632 HRMS


+ 3640849 Found mz 3640836 IR (ATR) 3246

1801 1325 1155 1067 cm-1

OO

O

Ph

NH

SO

O

CF3

3g

Chapter 1

24



2H) 735-744 (m 3H) 775 (d J = 88 Hz 2H) 796 (d J = 84 Hz 2H) 13

C NMR δ

= 505 725 851 1231 (q JC-F = 2711 Hz) 1241 1265 (q JC-F = 37 Hz) 1274



1161 1105 cm-1

OO

O

Ph

NH

SO

O

N




1H) 798 (d J = 76 Hz 1H) 866 (d J = 44 Hz 1H) 13

C NMR δ = 510 723 849



1175 1063 cm-1


N

Ts

OHPh

N

Ts

O CeCl 3

PhLi

THF -78 C to rt

4






Chapter 1

25






N

Ts

OHPh


351-364 (m 4H) 726-738 (m 7H) 773-777 (m 2H) 13

C NMR δ = 215 396

469 608 804 1250 1276 1280 1286 1297 1339 1418 1435 HRMS (ESI+)


1325 1159 1101 770 cm-1

Chapter 1

26











Soc 2011 133 12881

























25 312

Chapter 1

27








Chapter 1

28

Chapter 2

29

Chapter 2



Abstract







Chapter 2

30

Introduction














A



Indanones are


A rearrangement













Whereas







Chapter 2

31




N

HO Ph

S NS Me

HO PhMe

1a2a 96

Me

O

OO O


2) is





The generated








N

S O

O

O[Rh]

Ph

SN

[Rh]O Ph

O OMe

[Rh] OH

N

S O

O

O Ph

H

[Rh]

H

N

[Rh]O Ph

S O

O

Me Me

Me

Me

1a

H2O

2a

A B

CD

1a

A




Chapter 2

32








N

HO Ph

SN

S CH19D11

HO Ph

D3C

1a-d2a-d 96

D3C

O

O

O O

D

D

D

D

D

D

H01D09

8



D12




Application




1

2

SN

HO Ar

O OMe

N

HO Ar

S O

O


K2CO 3 (20 equiv)


NS Me

HO PhMe

2a

91 er = 928

O O

NS Me

HO Ph

2b

95 er = 937

O O

S

NS Me

HOMe

2c

90 er = 937

O O

OMe

NS Me

HOMe

2c

92 er = 919

O O

CF3



Chapter 2

33










HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6 84

5 56



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3


PhMgBr

THF rt 1 h N

HO

Ts

Me

1e 93

er gt 991 dr = 201

Ph

3







SN

HO PhMe

O OMe

MeN

HO Ph

S O

O

Me

Me

1e

er gt 991 dr = 201

2e 99

er gt 991 dr gt 201





Chapter 2

34









SN

PhRhOMe

O OMe

Me

SN

PhRhOMe

O OMe

Me

favored

disfavored

F

F

NSRh

Ph

Me

O

O

MeO

H

Me

E

E

NSRh

Ph

Me

O

O

MeO

Me

H














Chapter 2

35


1

er gt 991 dr gt 201

2

er gt 991 dr gt 201

SN

HO ArR

O OMe

N

HO Ar

S O

O





1 N

HO Ph

S O

O

Me

Me

1f

SN

HO PhMe

O OMe

Me

2e 99

6 N

HO

S O

O

Me

1k

OMe

SN

HOMe

O OMe

2k 97

OMe

2

N

HO Ph

S O

O

MeO

Me

1g

SN

HO PhMe

O OMe

MeO

2g 98

7 N

HO

S O

O

Me

Me

1l

CF3

SN

HOMe

O OMe

Me

2l 97

CF3

3 N

HO Ph

S O

O

F3C

Me

1h

SN

HO PhMe

O OMe

F3C

2h 99

8 N

HO Ph

S O

O

Me

i-Pr

1m

SN

HO Phi-Pr

O OMe

Me

2m 97

4

N

HO Ph

S O

O

Me

1iMe

SN

HO PhMe

O OMeMe

2i 99

9 N

HO Ph

S O

O

Me

SMe

SN

HO Ph

O OMe

Me

2n 97

SMe

5 N

HO Ph

S O

O

Me

S

1j

SN

HO PhMe

O OMeS

2j 99



Chapter 2

36

Conclusions






Chapter 2

37





13C NMR


13C at 10069












N

OHNEt3

DCM rt 12 h


2) PhMgBrTHF rt 3 h

N

HO Ph

1a

TsCl

N

OH

8a

H HCl

Ts Ts









Chapter 2

38

N

S

Me

O

O

OH

8a 1H NMR = 213 (bs 1H) 245 (s 3H) 350-361 (m 2H) 394-404 (m 2H)

442-452 (m 1H) 737 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR =



-1

N

S

D3C

O

O

OH

8a-d

D

D

D

D

1H NMR = 283 (bs 1H) 349-355 (m 2H) 389-396 (m 2H) 435-444 (m 1H)



+ 2351128 Found mz

2351125 IR (ATR) 3503 1333 1142 1059 638 cm-1

N

S O

O

OH

8b

S

1H NMR = 277 (bs 1H) 357-364 (m 2H) 400-407 (m 2H) 441-450 (m 1H)


1H) 13



1038 737 cm-1

Chapter 2

39














N

HO Ph

S

1a

Me

O

O


2H) 728-737 (m 5H) 739 (d J = 84 Hz 2H) 778 (d J = 80 Hz 2H) 13

C NMR

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS


+ 3041002 Found mz 3040995 IR (ATR) 3477

1333 1184 1148 671 cm-1


N

HO Ph

S

1a-d

D3C

O

O

D

D

D

D


(m 5H) 13

C NMR = 203-211 (m) 652 703 1244 1281 (t JC-D = 247 Hz)


Chapter 2

40


702 648 cm-1

N

HO Ph

S

S

O

O



1H) 13

C NMR = 656 702 1244 1280 1283 1288 1331 13387 13392 1417


+ 2960410 Found mz 2960404 IR

(ATR) 3524 1333 1161 1148 748 cm-1

N

HO

S

Me

O

O

OMe

1c



2H) 775 (d J = 80 Hz 2H) 13

C NMR =216 553 652 702 1139 1259 1285


+

3341108 Found mz 3341097 IR (ATR) 3460 1518 1331 1250 1146 cm-1

N

HO

S

Me

O

O

CF3



C NMR

Chapter 2

41

=216 654 697 1239 (q JC-F = 2704 Hz) 1249 1255 (q JC-F = 37 Hz) 1284



1109 1076 cm-1


1l-1n

HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6a

5a



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3

acetone H2O

rt 10 h 4a

PhMgBr

THF rt 1 h N

OH

Ts

Me

1e

Ph

3a



procedure16













Me

NHTs

O

N2


Chapter 2

42

2H) 730 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR = 194 215 539


+

2680750 Found mz 2680747 IR (ATR) 2112 1639 1337 1319 1161 cm-1

[]27

D = -1184 (c = 079 in CHCl3)


i-Pr

NHTs

O

N2



2H) 769 (d J = 84 Hz 2H) 13

C NMR =169 193 215 315 548 647 1273


+ 2961063

Found mz 2961060 IR (ATR) 2129 1622 1362 1329 1161 cm-1

[]28

D = -730 (c = 071 in CHCl3)

NHTs

O

N2

5c

SMe

1H NMR = 174-196 (m 2H) 204 (s 3H) 242 (s 3H) 244-252 (m 2H)

390-400 (m 1H) 541 (s 1H) 560-572 (m 1H) 730 (d J = 84 Hz 2H) 772 (d J =

84 Hz 2H) 13

C NMR = 153 215 297 323 545 585 1272 1297 1366 1439


+ 3280784 Found mz 3280779

IR (ATR) 2129 1618 1375 1339 1163 cm-1

[]29

D = -506 (c = 063 in CHCl3)









Chapter 2

43

N

O

Ts

Me

6a

1H NMR = 145 (d J = 68 Hz 3H) 246 (s 3H) 443-454 (m 2H) 473-480 (m

1H) 736-742 (m 2H) 776-781 (m 2H) 13

C NMR = 157 216 696 810 1284


+ 2400689

Found mz 2400688 IR (ATR) 1825 1339 1155 669 cm-1

[]28

D = 614 (c = 081 in CHCl3)


N

O

Ts

i-Pr

6b

1H NMR = 099-111 (m 6H) 206-218 (m 1H) 246 (s 3H) 441 (dd J = 164 36


2H) 777 (d J = 80 Hz 2H) 13

C NMR = 174 181 216 304 703 903 1284


+ 2681002

Found mz 2680998 IR (ATR) 1815 1340 1155 1007 671 cm-1

[]29

D = 567 (c = 095 in CHCl3)

N

O

Ts

6c

SMe

1H NMR = 204 (s 3H) 209-218 (m 2H) 247 (s 3H) 265-279 (m 2H) 446 (d


2H) 780 (d J = 80 Hz 2H) 13

C NMR = 147 216 291 293 705 832 1286


+ 3000723

Found mz 3000718 IR (ATR) 1813 1342 1308 1157 667 cm-1

[]29

D = 1183 (c = 036 in CHCl3)


Chapter 2

44










N

HO

S O

O

Me

Me

1e

H

NOE

NOE



(m 3H) 739 (d J = 84 Hz 2H) 777 (d J = 84 Hz 2H) 13

C NMR = 144 216

628 702 731 1247 1279 1284 1285 1298 1319 1415 1443 HRMS (ESI+)


1155 1092 667 cm-1

[]25




Chapter 2

45

N

HO

S O

O

Me

1l

H

NOE

NOE

CF3

Me



739-747 (m 4H) 777 (d J = 84 Hz 2H) 13

C NMR = 143 216 630 706 727

1238 (JC-F = 2704 Hz) 1253 1254 (JC-F = 36 Hz) 1285 1299 1301 (JC-F = 324


+ 3861032

Found mz 3861025 IR (ATR) 3422 1327 1151 1109 839 cm-1

[]28




N

HO

S O

O

Me

iPr

1m

H

NOE

NOE



= 100 Hz 1H) 690-696 (m 2H) 712-720 (m 3H) 732 (d J = 80 Hz 2H) 773 (d

J = 80 Hz 2H) 13

C NMR = 190 193 215 291 641 729 801 1247 1275


+

3461471 Found mz 3461466 IR (ATR) 3454 1331 1163 739 669 cm-1

[]27



Chapter 2

46


N

HO Ph

S O

O

1n

Me

SMe

1H NMR = 202 (s 3H) 218-258 (m 8H) 388-394 (m 2H) 427 (dd J = 84 48

Hz 1H) 688-693 (m 2H) 714-721 (m 3H) 740 (d J = 80 Hz 2H) 779 (d J = 80

Hz 2H) 13

C NMR = 154 216 290 297 634 725 733 1246 1277 1284


+

3781192 Found mz 3781188 IR (ATR) 3481 1339 1157 702 669 cm-1

[]28












N

HO

S O

O

Me

Me

1f

H

NOE

NOE


1H) 398 (q J = 64 Hz 1H) 424 (dd J = 84 08 Hz 1H) 732-744 (m 5H)

750-755 (m 2H) 774-778 (m 2H) 13

C NMR = 165 216 627 718 739 1257

Chapter 2

47



-1

[]25






HO2C Me

NHCbz

Me

NHCbz

O

N2N

O

Cbz

Me

6d5d

1) (COCl) 2 DMF

2) CH2N2 Rh2(OAc)4 (05 mol )

DCM rt 12 h4d

PhMgBr

THF rt 1 h

N

OH

Cbz

Me

7a

Ph

N

OH

H

Me

PhPd C (5 mol )

H2 (1atm)

MeOH rt 12 h

MeO SO2Cl

NEt3

DCM rt 12 h

N

HO Ph

S O

O

MeO

Me

1g









Me

NHCbz

O

N2

5d 1H NMR = 134 (d J = 68 Hz 3H) 420-436 (m 1H) 504-516 (m 2H) 534-564

(m 2H) 728-736 (m 5H) 13

C NMR = 184 535 (2C) 669 1280 1282 1285


+ 2481030 Found mz

2481028 IR (ATR) 2116 1717 1636 1533 1252 cm-1

[]28

D = -434 (c = 085 in CHCl3)


Chapter 2

48







N

O

Cbz

Me

6d


Hz 1H) 498-505 (m 1H) 513-521 (m 2H) 731-739 (m 5H) 13

C NMR = 153



696 cm-1

[]29

D = 390 (c = 068 in CHCl3)










N

OH

Cbz

Me

7a

Ph


= 96 Hz 1H) 458 (q J = 64 Hz 1H) 507-518 (m 2H) 729-746 (m 10H) 13

C

NMR = 142 623 667 689 730 1246 1278 1279 1280 1285 1287 1366

Chapter 2

49


+ 2981438 Found mz

2981433 IR (ATR) 1670 1423 1248 1016 702 cm-1

[]29

D = 46 (c = 089 in CHCl3)

N

OH

Cbz

Me

7b

MeO


1H) 432 (d J = 96 Hz 1H) 452-461 (m 1H) 506-518 (m 2H) 687-694 (m 2H)

726-739 (m 7H) 13

C NMR = 143 553 622 666 687 729 1140 1260 1278


+

3281543 Found mz 3281539 IR (ATR) 1682 1418 1352 1024 696 cm-1

[]29

D = 02 (c = 085 in CHCl3)








pressure







mmol 58 yield)

Chapter 2

50

N

HO

S O

O

MeO

Me

1g

H

NOE

NOE


390 (s 3H) 399 (d J = 92 Hz 1H) 419 (q J = 60 Hz 1H) 698-707 (m 4H)

720-727 (m 3H) 779-785 (m 2H) 13

C NMR = 143 557 627 701 731 1144



-1

[]28




N

HO

S O

O

F3C

Me

1h

H

NOE

NOE


406 (d J = 92 Hz 1H) 430 (qd J = 64 08 Hz 1H) 694-699 (m 2H) 721-727

(m 3H) 784 (d J = 80 Hz 2H) 801 (d J = 84 Hz 2H) 13

C NMR = 145 629

706 729 1232 (JC-F = 2711 Hz) 1245 1263 (JC-F = 37 Hz) 1283 12868 12871


+

3720876 Found mz 3720870 IR (ATR) 3503 1348 1323 1165 646 cm-1

[]28




Chapter 2

51

N

HO

S O

O

Me

1i

H

NOE

NOE


1H) 401 (d J = 88 Hz 1H) 422 (q J = 64 Hz 1H) 694-698 (m 2H) 720-724 (m

3H) 746-750 (m 2H) 767-772 (m 2H) 13

C NMR = 144 214 630 704 730

1247 1256 1279 1285 1286 1291 1341 1347 1395 1416 HRMS (ESI+)


1151 714 700 cm-1

[]29




N

HO

S O

O

Me

1j

H

NOE

NOE

S


Hz 1H) 425 (q J = 64 Hz 1H) 696-701 (m 2H) 720-728 (m 4H) 764-767 (m

1H) 769-772 (m 1H) 13

C NMR = 144 632 709 730 1246 1279 1281 1286


+ 3100566

Found mz 3100559 IR (ATR) 3508 1340 1151 756 669 cm-1

[]29




Chapter 2

52

N

HO

S O

O

Me

1k

H

NOE

NOE

OMe


1H) 394 (d J = 88 Hz 1H) 416 (q J = 64 Hz 1H) 670-675 (m 2H) 684-689 (m

2H) 756-762 (m 2H) 765-770 (m 1H) 786-790 (m 2H) 13

C NMR = 143 553

630 704 729 1138 1259 1283 1292 1332 1337 1348 1592 HRMS (ESI+)


1327 1155 606 cm-1

[]29





Screening







mmol 93 yield)

Chapter 2

53


rac -DM-BINAP

rac-BINAP

dppf

dppb

PPh3

dppe

46

trace

trace

yield

PCy3

Ligand

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

entry

1

2

3

4

5

6

7

8

nd

nd

nd

93

none nd

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a


entry Ligand yield

1

2

3

4

(R)-BINAP

(R)-DM-BINAP

(R)-SEGPHOS

(R)-DIFLUORPHOS

er

94

46

48

43

5

6

(R)-DM-SEGPHOS


3862

91

7

8

(R)-MeO-BIPHEP

(R)-MeO-DM-BIPHEP

64

91

892

3169

1288

1486

2476

2575

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a










Chapter 2

54

NS Me

HO PhMe

2a

O O


J = 148 Hz 1H) 683 (s 1H) 727-744 (m 6H) 781 (d J = 84 Hz 1H) 13

C NMR

= 216 361 626 732 1238 1263 1280 1284 1299 1301 1330 1412 1431


+ 3041002 Found mz 3040998 IR

(ATR) 3472 1325 1161 1142 735 cm-1

[]29




NS CH2D

HO Ph

D3C

2a-d

O O

D

D

D


J = 148 Hz 1H) 728-743 (m 5H) 13

C NMR = 201-210 (m) 358 (t JC-D = 212

Hz) 625 731 1234 (t JC-D = 249 Hz) 1262 1279 1283 1291-1300 (m 2C)


+ 3111441

Found mz 3111436 IR (ATR) 3524 1318 1290 1150 721 cm-1

NS Me

HO Ph

O O

S

2b


1H) 668 (d J = 52 z 1H) 730-738 (m 5H) 750 (d J = 52 Hz 1H) 13

C NMR =

378 630 722 1257 1264 1282 1286 1299 1338 1427 1467 HRMS (ESI+)


1150 1063 748 cm-1

[]29


Chapter 2

55



NS Me

HOMe

O O

OMe

2c


422 (d J = 148 Hz 1H) 684-690 (m 3H) 724-733 (m 3H) 774-779 (m 1H) 13

C

NMR = 216 360 553 626 729 1137 1237 1275 1299 1230 1328 1351


+ 3341108 Found mz

3341098 IR (ATR) 3441 1508 1250 1144 735 cm-1

[]29




NS Me

HOMe

O O

CF3



2H) 782 (d J = 80 Hz 1H) 13

C NMR = 216 360 625 731 12392 (q JC-F =

2708) 12395 1254 (q JC-F = 36 Hz) 1268 1298 1303 (q JC-F = 352) 1329


+ 3720876 Found

mz 3720869 IR (ATR) 3481 1323 1121 1067 733 cm-1

[]29




Chapter 2

56










SN

HO

Me

O OMe

Me

2e

H

NOE

NOE


= 68 Hz 1H) 675 (s 1H) 723-738 (m 6H) 777 (d J = 84 Hz 1H) 13

C NMR =

119 215 314 608 750 1242 1262 1275 1282 1298 1301 1316 1427


+ 3181158 Found mz

3181155 IR (ATR) 3481 1315 1163 1146 683 cm-1

[]28




SN

HO

Me

O OMe

MeO

2g

H

NOE

NOE

Chapter 2

57



5H) 782 (d J = 88 Hz 1H) 13

C NMR = 120 314 555 609 752 1144 1151



735 cm-1

[]29




SN

HO

Me

O OMe

F3C

2h

H

NOE

NOE



1H) 13

C NMR = 118 314 608 750 1228 (q JC-F = 2711 Hz) 1251 1258 (q



+ 3720876 Found

mz 3720872 IR (ATR) 3461 1325 1161 1142 739 cm-1

[]29




SN

HO

Me

O OMe

2i

H

NOE

NOE

Me

Chapter 2

58


J = 68 Hz 1H) 684 (d J = 80 Hz 1H) 718-736 (m 6H) 770 (s 1H) 13

C NMR

=119 211 314 607 748 1242 1262 1275 1282 1299 1338 1341 1395


+ 3181158 Found mz

3181155 IR (ATR) 3489 1448 1319 1148 735 cm-1

[]29




SN

HO

Me

O OMe

2j

H

NOE

NOES


1H) 656 (d J = 52 Hz 1H) 726-736 (m 5H) 743 (d J = 48 Hz 1H) 13

C NMR

= 114 319 619 742 1256 1266 1278 1284 1297 1334 1429 1480 HRMS


+ 3100566 Found mz 3100561 IR (ATR) 3524

1329 1151 1020 729 cm-1

[]29




SN

HO

Me

O OMe

2k

H

NOE

NOE

OMe


J = 68 Hz 1H) 685 (d J = 88 Hz 2H) 698-703 (m 1H) 722-730 (m 2H)

738-748 (m 2H) 785-790 (m 1H) 13

C NMR = 119 314 553 608 747 1136

Chapter 2

59



760 cm-1

[]26




SN

HO

Me

O OMe

2l

H

NOE

NOE

CF3

Me



= 84 Hz 2H) 778 (d J = 80 Hz 1H) 13

C NMR = 119 215 313 607 749




-1

[]26




SN

HO

iPr

O OMe

2m

H

NOE

NOE

Me


(m 1H) 264 (s 1H) 285 (s 3H) 441 (d J = 100 Hz 1H) 685 (s 1H) 714-735 (m

4H) 748 (d J = 76 Hz 2H) 772 (d J = 80 Hz 1H) 13

C NMR = 211 214 217

278 330 718 742 1244 1256 1270 1283 1292 1295 1300 1435 1442


+ 3461471 Found mz 3461466 IR

Chapter 2

60

(ATR) 3412 1315 1165 1146 683 cm-1

[]29




SN

HO

O OMe

2n

H

Me

NOE

SMe

1H NMR = 160-170 (m 1H) 184 (s 3H) 212-226 (m 4H) 230-242 (m 2H)

254-263 (m 1H) 294 (s 3H) 471 (dd J = 108 28 Hz 1H) 675 (s 1H) 722-738

(m 6H) 776 (d J = 80 Hz 1H) 13

C NMR = 150 215 242 301 321 643 748

1245 1262 1276 1283 12986 12993 1312 1429 1437 1441 HRMS (ESI+)


1165 1134 748 cm-1

[]28









was used as a


and


21 All



Chapter 2

61



2e

formula C17H19NO3S

fw 31739

T (K) 100(2)


space group P21c

a (Aring) 105967(5)


3) 152058(13)

Z 4 Dcalc (gcm

3) 1386

(mm-1

) 0225 F(000) 672



348500135

params 203 GOF on F

2 1069

R1 wR2 [Igt2(I)]

00322 00868

R1 wR2 (all data)

00335 00878

Chapter 2

62

























Med Chem 2003 46 1116








Chapter 2

63

































Chapter 2

64




2012 51 9160





11437-11439
























Chapter 2

65











2548-2551







11750









32 115



Chapter 2

66

Chapter 3

67

Chapter 3




Halides

Abstract






Chapter 3

68

Introduction
















2) are












several months


Et LiB

Ph

+B

Ph

Et

1a 74

(a)(b)[Me4N]


Chapter 3

69

















OMe

BrB

Ph

Et

OMe

3a

Ph

Et

OMe

H

4a

Pd-ligand AcOH

2a

+B

Ph

Et

1a

[Me4N]


EZ of 4ab

1 P(o-tol)3 69 397

2 P(t-Bu)3 47 1783

3 1-[(t-Bu)2P](biphenyl) 18 2872

4 2-[(t-Bu)2P](11-binaphthyl) 21 6733

5 DPEPhos 24 928



analysis



Chapter 3

70









Pd(0)

Pd

MeO

B

PdEt

OMe

Ph

B

Ph

Et

2a

BC

Pd

MeO

Br

A

1a

3a







dominates10
















Chapter 3

71










Chapter 3

72


BO

Ph

Et

OMe

5a 83

BO

Ph

Et

CF3

5b 85

BO

Ph

Et

NPhth

5c 82

BO

Ph

Et

5d 72b

BO

Ph

Et

5e 85

S

BO

n-Pr

Me

Cl

5f 74

BO

n-Pr

Ph

OMe

5g 82

BO

Ph

S

5h 83

BO

Ph

CO2Et

5i 81

BO

Ph

5j 82

Cl

BO

Ph

CF3

TBSO

BO

Cl

S

Ph

BO

Ph

Me

OMe

5n 71b

5m 925l 82

BO

Ph

5k 76

Me

+B

Ar

R

1

[Me4N]

2


BO

Ar

R

Ar

5







The reaction of 1a






Chapter 3

73








(E)-5o83 EZ = gt955

BO

Ph

Et

Ph

Ph

Et

PhO

NMe2

(Z)-685 EZ = lt595

Ph

Ph

EtO

NMe 2

(E)-675 EZ = 928

1a

(Z)-5o71 EZ = 793

+ PhBr

BO

Ph

Ph

Et

(a)

(c) (c)

(b)






Conclusions






Chapter 3

74




1H at 400 MHz and

11B at 128 MHz)



13C)

CD3CN ( = 194 for 1H =132 for


11B)









and Ph-9-BBN18


procedures


Et LiB

Ph

+B

Ph

Et

1a


2) Me4NCl MeOH

[Me4N]









74 yield)

Chapter 3

75

B

Ph

Et

1a

[Me4N]


136-207 (m 11H) 236-250 (m 2H) 303 (s 12 H) 679-686 (m 1H) 700-707 (m

2H) 735 (d J = 72 Hz 2H) 13

C NMR (CD3CN) = 149 166 266 (q JC-B = 379

Hz) 271 275 324 349 561 948 1221 1269 1339 11

B NMR = -133 HRMS




n-Pr LiB

Ar


2) Me4NCl MeOH B

n-Pr

1b

Cl

[Me4N]










Chapter 3

76

B

n-Pr

1b

Cl

[Me4N]

1H NMR (CD3CN) = 084-096 (m 5H) 111-121 (m 1H) 126-200 (m 13H)

235-250 (m 2H) 304 (s 12H) 700-705 (m 2H) 733 (d J = 84 Hz 2H) 13

C NMR

(CD3CN) = 139 234 249 266 (q JC-B = 393 Hz) 270 273 323 348 561

933 1265 1272 1355 11


[M-(NMe4)] 2991738 Found 2991730

B

n-Pr

1c

OMe

[Me4N]


128-201 (m 13H) 237-252 (m 2H) 303 (s 12H) 371 (s 3H) 663-668 (m 2H)

723 (d J = 81 Hz 2H) 13

C NMR (CD3CN) = 140 235 250 268 (q JC-B = 393

Hz) 272 275 324 349 554 561 929 1128 1344 1561 11

B NMR = -135


B

Ph

1d

[Me4N]


(m 2H) 134-196 (m 9H) 230-244 (m 2H) 304 (s 12H) 679-686 (m 1H)

699-706 (m 2H) 733 (d J = 72 Hz 2H) 13

C NMR (CD3CN) =23 87 266 (q

JC-B = 393 Hz) 271 274 323 349 562 1222 1269 1338 11

B NMR = -134


Chapter 3

77

B

Ph

1e

[Me4N]


(m 3H) 302 (s 12H) 679-686 (m 1H) 699-706 (m 2H) 734 (d J = 66 Hz 2H) 13

C NMR (CD3CN) = 253 268 (q JC-B = 379 Hz) 271 275 324 333 349 361

561 980 1221 1269 1339 11


[M-(NMe4)] 2912284 Found 2912278

B

1f

S

Ph

[Me4N]




09 Hz 1H) 712-730 (m 5H) 13

C NMR (CD3CN) = 240 268-290 (m) 325 347

380 562 928 1225 1261 1265 1271 1289 1297 1434 11

B NMR = -135


B

Ph

1g

TBSO

[Me4N]

1H NMR (CD3CN) = 005 (s 6H) 084-096 (m 11H) 110-120 (m 1H) 134-197

(m 9H) 216-233 (t J = 72 Hz 2H) 235-250 (m 2H) 301 (s 12H) 356 (t J = 78

Hz 2H) 680-687 (m 1H) 700-708 (m 2H) 735 (d J = 66 Hz 2H) 13

C NMR

(CD3CN) = -50 189 254-277 (m) 323 348 561 649 889 1222 1269

1339 11


Found 3812789

Chapter 3

78

B

Ph

1h

OMe

[Me4N]


(m 2H) 298 (s 12H) 373 (s 3H) 668-674 (m 2H) 701-718 (m 5H) 732 (d J =

87 Hz 2H) 13

C NMR (CD3CN) = 255-277 (m) 322 350 554 561 961 1129

1251 1287 1302 1312 1345 1564 11


C23H26BO [M-(NMe4)] 3292077 Found 3292081



Br

+

MeO


6 mol Ligand


2a

B

Ph

Et

OMe

(E)-3a

AcOH

Ph

Et

OMe

H

Ph

B

Et

OMe

+

+

(Z)-3a

(E)-4a

H

Et

OMe

Ph

(Z)-4a

B

Ph

Et

1a

[Me4N]









Chapter 3

79




B

Ph

Et

+


toluene 70 degC

Me3NO

Br

MeO

BO

Ph

Et

OMe

5a

1a

2a

[Me4N]









BO

Ph

Et

OMe


383 (s 3H) 438-444 (m 1H) 685-691 (m 2H) 714-736 (m 7H) 13

C NMR =

138 221 267 273 (br) 277 312 553 736 1132 1251 1278 1283 1298

1366 1436 1494 1586 11


3742417 Found 3742410

Chapter 3

80

BO

Ph

Et

CF3

5b


437-443 (m 1H) 718-726 (m 3H) 734-739 (m 2H) 745-748 (m 2H) 760-763

(m 2H) 13

C NMR = 135 220 266 271 (br) 276 312 738 12429 (q JC-F =

2701 Hz) 1247 (q JC-F = 36 Hz) 1280 1281 1289 (q JC-F = 320 Hz) 1291 1425

1476 1480 11


Found 4122186

BO

Ph

Et

NPhth

5c


440-450 (m 1H) 720-727 (m 3H) 734-739 (m 2H) 743-751 (m 4H) 777-783

(m 2H) 794-800 (m 2H) 13

C NMR = 137 221 266 274 (br) 275 312 738

1235 1254 1258 1279 1282 1294 1304 1317 1342 1429 1440 1482

1671 11

B NMR = 502 IR (KBr) = 2928 1742 1509 1381 714 cm-1

HRMS (EI)


BO

Ph

Et

5d

1H NMR = 021-034 (m 1H) 068-100 (m 8H) 120-150 (m 7H) 224-238 (m

1H) 244-258 (m 1H) 424-431 (m 1H) 722-754 (m 9H) 778 (d J = 78 Hz 1H)

783-788 (m 1H) 809-816 (m 1H) 13

C NMR = 137 216 219 259 262 264

(br) 282 309 314 734 1249 12537 12539 1255 1264 1270 1273 12795

Chapter 3

81

12799 1283 1321 1335 1413 1427 1467 11


for C28H31BO (M+) 3942468 Found 3942476

BO

Ph

Et

5e

S


448-456 (m 1H) 702 (dd J = 51 36 Hz 1H) 708 (dd J = 36 12 Hz 1H)

715-730 (m 4H) 732-738 (m 2H) 13

C NMR =141 221 271 289 312 739

1250 1255 1266 1269 1279 1281 1416 1427 1468 11

B NMR = 496


BO

n-Pr

Me

Cl

5f

1H NMR = 070 (t J = 75 Hz 3H) 096-133 (m 9H) 142-172 (m 6H) 220-228

(m 2H) 237 (s 3H) 439-446 (m 1H) 708-735 (m 8H) 13

C NMR = 140 212

219 221 267 274 (br) 313 363 737 1279 12846 12855 1298 1309 1365

1411 1420 1488 11


4062235 Found 4062237

BO

n-Pr

Ph

OMe

5g

Chapter 3

82


(s 3H) 435-450 (m 1H) 690 (d J = 81 Hz 2H) 711 (d J = 81 Hz 2H) 720-740

(m 5H) 13

C NMR = 140 219 221 267 274 (br) 312 362 551 736 1133

1267 1278 1287 1294 1354 1446 1475 1573 11




BO

Ph

S

5h

1H NMR = 027-032 (m 2H) 046-052 (m 2H) 098-130 (m 6H) 140-170 (m

8H) 430-445 (m 1H) 696-700 (m 1H) 704-707 (m 1H) 715-726 (m 2H)

729-738 (m 4H) 13

C NMR = 60 150 222 263 272 (br) 313 736 1241

1243 1253 1278 1290 1295 1410 1425 1431 11



BO

Ph

CO2Et

5i

1H NMR = 017-023 (m 2H) 045-053 (m 2H) 090-119 (m 6H) 132-173 (m

11H) 427-433 (m 1H) 438 (q J = 75 Hz 2H) 718-738 (m 7H) 798 (dt J = 78

15 Hz 2H) 13

C NMR = 56 144 151 220 263 269 (br) 312 609 735 1255

1279 1284 1287 1289 1303 1423 1453 1469 1665 11

B NMR = 496 IR

(KBr) = 2928 1717 1287 1100 cm-1


Found 4282526

BO

Ph

5j

Cl

Chapter 3

83

1H NMR = 023-029 (m 2H) 048-055 (m 2H) 094-123 (m 6H) 134-171 (m

8H) 432-439 (m 1H) 706-714 (m 1H) 718-726 (m 4H) 728-738 (m 4H) 13

C

NMR = 57 150 220 263 271 (br) 312 736 1255 1267 1279 1283 1284

1289 1304 1332 1423 1424 1461 11


C25H28BClO (M+) 3901922 Found 3901923

BO

Ph

5k

Me

1H NMR = 082-113 (m 6H) 126-164 (m 15H) 237 (s 3H) 268-280 (m 1H)

434-441 (m 1H) 704-709 (m 3H) 717-725 (m 4H) 730-737 (m 2H) 13

C NMR

= 215 219 248 263 273 (br) 312 315 433 735 1252 12689 12693 1275

1278 1283 1316 1365 1418 1424 1481 11


for C28H35BO (M+) 3982781 Found 3982780

BO

Cl

S

Ph

5l

1H NMR = 106-176 (m 13H) 250-260 (m 2H) 272-280 (m 2H) 441-449 (m

1H) 674 (dd J = 33 12 Hz 1H) 697-703 (m 3H) 709-738 (m 8H) 13

C

NMR(C6D6) =225 272 277 (br) 315 358 375 739 1247 1253 1261 1272

1285 12856 12861 1306 1335 1419 1427 1437 1491 11

B NMR = 495


BO

Ph

CF3

TBSO

5m

Chapter 3

84

1H NMR = -014 (s 6H) 079 (s 9H) 095-136 (m 6H) 142-168 (m 7H) 255 (t

J = 72 Hz 2H) 343 (t J = 72 Hz 2H) 435-442 (m 1H) 718-726 (m 3H)

731-737 (m 2H) 747 (d J = 81 Hz 2H) 759 (d J = 81 Hz 2H) 13

C NMR = -54

183 220 259 266 271 (br) 311 377 616 739 1242 (q JC-F = 2694 Hz) 1247

(q JC-F = 36 Hz) 1258 1280 1282 1290 (q JC-F = 320 Hz) 1291 1421 1422

1480 11



BO

Ph

Me

OMe

5n

1H NMR = 122-130 (m 4H) 138-162 (m 5H) 168-186 (m 4H) 237 (s 3H)

375 (s 3H) 443-450 (m 1H) 670 (dt J = 90 21 Hz 2H) 690-697 (m 4H)

702-708 (m 3H) 710-720 (m 4H) 13

C NMR = 213 222 269 312 550 738

1132 1260 1272 1285 1301 1307 1310 1362 1369 1423 1429 1483

1571 11


4362561


4-Bromobenzene

B

Ph

Et

+


toluene 70 degC

Me3NO BO

Ph

Ph

Et

(Z)-5o

1a

Ph Br

[Me4N]




Chapter 3

85






BO

Ph

Ph

Et


470-475 (m 1H) 685-710 (m 10H) 13

C NMR = 139 224 267 313 317 740

1248 1257 1272 127412938 12941 1421 1425 1275 11

B NMR = 512


BO

Ph

Et

Ph


438-443 (m 1H) 718-737 (m 10H) 13

C NMR = 137 221 266 274 (br) 277

312 737 1253 1268 1278 1279 1283 1288 1433 1442 1494 11

B NMR =



Bromide 2b

+

Br

ONMe2

Ph

Et

PhO

NMe2


THF K3PO4 60 degC

(Z)-Tamoxifen 6

2b

BO

Ph

Et

Ph

(E)-5o

Chapter 3

86









Chapter 3

87



2003 Vol 3








Rev 2006 250 1107









1976 108 281








74





Chapter 3

88





















2006 128 1828




Chapter 4

89

Chapter 4



Abstract






Chapter 4

90

Introduction





























Chapter 4

91


B

MOMO

[Me4N] +

MeO

Br

I

Br

MeO Br

B

MeO

MOMO MOMO

1a

2 3 87EZ = lt199

NaOH

50 degC

1 mol


toluene 50 degC
















procedure

Chapter 4

92



An











3

MeO

R

Br

4 92

R

MeO

R

Br

n = 2 5 87

n = 3 6 82n = 4 7 85

n

R

1 mol


toluene 50 degC

I

Br

NaOH

E

EE

R = OMOM








Chapter 4

93





Br

Br

R

R

Br

Br

8 86

R

R

Br

R

R

Br

9 92

E E

R = OMOM















Chapter 4

94


Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

Me3Si

Br

Ph

F

Me3Si

OMe

Br

Ph

F

S

Br

Me3Si

OMe

B

n-Pr

[Me4N]

Cl

B

Ph

[Me4N]

OMe

Br

S

Br

I

EtO2C

MOMO

MOMO

I

Br

F

1b

10 88

11 84

12 88

1a1c

cat Pd

NaOHcat Pd

cat Pd NaOH

Cs2CO3

Conclusions







Chapter 4

95




1H at 500 MHz and






13C) CD3CN ( = 194 for

1H =132 for

13C) and

BF3OEt2 ( = 000 for 11











11













Chapter 4

96

B

MOMO

[Me4N]

1a


202 (t J = 66 Hz 2H) 236-251 (m 2H) 304 (s 12H) 328 (s 3H) 346 (t J = 69

Hz 2H) 454 (s 2H) 678-685 (m 1H) 698-705 (m 2H) 734 (d J = 72 Hz 2H) 13

C NMR (CD3CN 75 MHz) = 210 267 (br) 271 275 282 297 324 349 551

561 681 928 968 1221 1269 1338 11



B

Ph

[Me4N]

1b

OMe


225 (t J = 72 Hz 2H) 234-249 (m 2H) 263 (t J = 72 Hz 2H) 303 (s 12H) 372

(s 3H) 663-669 (m 2H) 711-728 (m 7H) 13


272 275 324 349 381 554 560 1129 1266 1289 1298 1346 1434 1563 11


3572390 Found 3572383



B

MOMO

[Me4N]

+

MeO

Br

1 mol


toluene 50 degC

I

Br

MeO Br

NaOH

3

1a

MOMO

Chapter 4

97








MeO Br

3

MOMONOE

NOE




(t J = 66 Hz 2H) 376 (s 3H) 452 (s 2H) 667-675 (m 4H) 697-702 (m 2H)

709-736 (m 7H) 13

C NMR (75 MHz) = 255 298 356 5510 5514 676 964

1134 1196 1267 1282 1294 13046 13049 1323 1339 1376 1408 1420



spectroscopy

MeO

R

Br

4

R

R = OMOM




Chapter 4

98


2H) 325 (s 3H) 329 (s 3H) 331-341 (m 4H) 380 (s 3H) 451 (s 2H) 453 (s

2H) 662-678 (m 8H) 697-703 (m 2H) 706-738 (m 12H) 13

C NMR (150 MHz)

= 252 254 295 296 353 354 5502 5504 552 675 676 9629 9632 1131

1196 1265 1267 1281 1282 1285 12941 12942 1303 1304 1306 1324

1343 1377 1385 1390 1400 1413 1414 1418 1429 1435 1579 HRMS


7972818 Found

7972849

MeO

R

5

R

R = OMOM

R

Br




325 (s 3H) 327 (s 3H) 328 (s 3H) 330-342 (m 6H) 374 (s 3H) 450 (s 2H)

452 (s 2H) 454 (s 2H) 654-662 (m 4H) 666-678 (m 8H) 696-704 (m 4H)

712-737 (m 15H) 13

C NMR (75 MHz) = 254 256 296 297 298 3526 3534

355 551 675 676 963 1130 1196 1264 1267 1280 1281 1286 1294 1301

1302 1304 1306 1324 1344 1377 1384 1387 1392 1393 1398 1402 1409



10914437 Found 10914482

Chapter 4

99

MeO

R

6

R

R = OMOM

R

R

Br




330-341 (m 8H) 371 (s 3H) 448-454 (m 8H) 648-675 (m 16H) 695-703 (m

4H) 714-737 (m 20H) 13

C NMR (75 MHz) = 253 254 256 257 2969 2974

298 350 354 356 550 551 675 676 963 1131 1196 1264 1267 1279

1280 1281 1283 1288 1293 1294 1300 1301 1302 1305 1306 1323 1342

1377 1385 1387 1389 1391 1394 1396 1397 1401 1405 1409 1411 1413



13856057 Found 13856062

MeO

R

7

R

R = OMOM

R

R

R

Br




374 (s 3H) 447-452 (m 10 H) 649-679 (m 20 H) 690-695 (m 2H) 701-706 (m

2H) 710-736 (m 25H) 13

C NMR (75 MHz) = 2529 2535 256 257 2968

Chapter 4

100

2971 298 351 354 355 356 550 6746 6755 676 963 1131 1195 1264

1267 12795 1280 1281 1283 1285 1287 1293 12937 12944 1301 1302

1304 1306 1322 1343 1377 1384 1387 1389 1390 1391 1394 13976

13979 1401 1404 1408 1409 1412 1413 1416 1427 14318 14321 1434


16797677 Found 16797694

8

R

Br

R

Br

R = OMOM





(t J = 66 Hz 4H) 456 (s 4H) 668-673 (m 4H) 691 (s 4H) 710-721 (m 8H)

722-737 (m 6H) 13

C NMR (75 MHz) = 254 297 354 551 676 963 1198

1268 1282 1291 1293 1303 1323 1380 1400 1411 1417 1427 HRMS


8221905

9

R

R

R = OMOM

R

R

Br

Br



Chapter 4

101


6H) 330-340 (m 8H) 446 (s 4H) 453 (s 4H) 656-672 (m 12H) 688 (s 4H)

704-710 (m 4H) 714-718 (m 4H) 722-740 (m 16H) 13

C NMR (150 MHz) =

254 2962 2963 356 357 5501 5503 674 676 9629 9631 1197 1266

1268 1281 12818 12822 1290 1295 1296 1304 1308 1324 1379 1385

1394 1403 1405 1409 1416 1417 1427 1434 HRMS (MALDI-TOF-MS


14335057 Found 14335040

Ph

F

Me3Si

OMe

Br

10

NOE

NOE





3H) 676-686 (m 3H) 694-707 (m 6H) 709-728 (m 5H) 734 (d J = 84 Hz 2H) 13

C NMR (150 MHz) = -11 349 372 552 1135 1189 (d JC-F = 255 Hz)1202

(d JC-F = 92 Hz) 1258 1268 (d JC-F = 35 Hz) 1280 1283 1284 1300 1304 (d

JC-F = 159 Hz) 1326 1329 1332 (d JC-F = 45 Hz) 1339 1387 1417 1418 1430




Chapter 4

102

Ph

F

S

Br

Me3Si

OMe

11

MOMO




= 78 2H) 264-272 (m 2H) 282-289 (m 2H) 325 (s 3H) 328 (t J = 66 Hz 2H)

382 (s 3H) 448 (s 2H) 587 (d J = 39 Hz 1H) 660 (d J = 39 Hz 1H) 669-676

(m 2H) 684-696 (m 3H) 705-742 (m 16H) 13

C NMR (150 MHz) = -10 244

293 351 362 372 550 552 673 963 1127 1135 1161 (d JC-F = 225 Hz)

1244 (d JC-F = 32 Hz) 1258 1274 12827 12831 12837 12840 12856 12861

1295 1302 1307 (d JC-F = 155 Hz) 1324 1329 1330 (d JC-F = 45 Hz) 1333

1345 1385 1395 (d JC-F = 12 Hz) 1412 1416 (d JC-F = 80 Hz) 1419 1422



Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

12MOMO




mmol) t1 10 h t2 12 h

Chapter 4

103


210-224 (m 4H) 264-272 (m 2H) 279-287 (m 2H) 323-333 (m 5H) 373 (s


1H) 666-672 (m 2H) 679-694 (m 5H) 703-737 (m 20H) 773 (d J = 84 Hz

2H) 13

C NMR (150 MHz) = -11 141 143 225 244 293 350 359 370 385

550 551 607 674 963 1134 1159 (d JC-F = 224 Hz) 1243 (d JC-F = 29 Hz)

1258 1269 1271 12808 12811 12815 12820 12823 12838 12844 1290

1293 1300 1301 (d JC-F = 158 Hz) 1302 1307 1323 (d JC-F = 47 Hz) 13258

13261 1328 1336 1344 1356 1379 1382 1390 (d JC-F = 12 Hz) 1409 14190

14191 14216 (d JC-F = 80 Hz) 14219 14222 1438 1446 1476 1583 1600 (d

JC-F = 2448 Hz) 1664 IR (KBr) = 2955 1717 1509 1273 1248 1111 837 cm-1


11294440

Found 11294465

Chapter 4

104




Chem 1999 201 163




897















2404


2006 128 1828



Chapter 5

105

Chapter 5




Abstract






Chapter 5

106

Introduction





moiety1b


























Chapter 5

107


B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

OHMe

Ph

1a

3a 85

MeO

OMe

2a

B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

1b

OMe

2a

OHMe

Ph

OMe

3b 88

[Me4N]

[Me4N]




Oxidative









Chapter 5

108


O

I

O

PdI

Pd(0)

B

1a

C

Pd(0)3a

Ar = p-MeOC6H4-

Me Me

OMe

Ar

Ph

B

D

A

Pd

O

ArB

Me

Ph

B

O

ArPh

Me

Me4NI

2a







Chapter 5

109


R3

O

I

B

R2

R1

+1 mol Pd

toluene50 degC 1 h

OHR3

R1

R2

OHMe

Ph

S

OHMe

OMe

OHPh

Ph

OMe

3f 72

3h 763j 80

3g 84

3d 82

3c 83

OHMe

Ph

CF3

1 2 3

OHH

Ph

OMe

OHPh

Ph

OMe

O

O

OHPh

3e 92

F

OMe

OHPh

Ph

OMe

F3C

3i 62

R4R4

MeO

[Me4N]










Chapter 5

110

OHMe

t-Bu

S

3k 89

B +1 mol Pd

toluene

50 degC 1 h

2a

t-Bu

S

(1)

1c

[Me4N]

OHMe

n-Bu

Me

3l 80

B

n-Bu

+1 mol Pd

toluene50 degC 1 h

2a

Me

(2)

1d

[Me4N]










n-Hex

13 equiv

Ph

Li

065 equiv

(H-9-BBN) 2


1 mol Pd

toluene 50 degC 1 h

10 equiv 2aOH

Me

n-Oct

11 equiv

3m 91 (based on 2a)

B

n-Oct

PhLi

Ph




Chapter 5

111


in 59 yield11


OHH

Ph

OMe

MnO2

DCM rt

Ph

OMe

O

NH2NH2 KOHPh

OMe

4 96 5 59

3n 74

(CH2OH)2 150 C

1a +

CHO

I2b

1 mol Pd

Conclusions




Chapter 5

112



and 13


B at 128 MHz)



13C) CD3CN (δ = 194 for

1H δ = 132 for


11B) IR






(Merck)





and alkynylborate14




Li

BPh

+

B

Ph

1a


2) Me4NCl MeOH

[Me4N]

MeO

MeO










Chapter 5

113

B

Ph

1a

[Me4N]

MeO


(m 2H) 296 (s 12H) 372 (s 3H) 668-675 (m 2H) 685-691 (m 1H) 700-712 (m

4H) 743 (d J = 64 Hz 2H) 13

C NMR (CD3CN) δ = 256-272 (m) 270 274 322

350 557 560 955 1145 1227 (2C) 1273 1324 1341 1578 The boron-bound


11B NMR


3292079

B

Ph

1b

[Me4N]

OMe


(m 2H) 295 (s 12H) 374 (s 3H) 666-675 (m 2H) 702-718 (m 5H) 733 (d J =

84 Hz 2H) 13

C NMR (CD3CN) δ = 254-274 (m) 270 273 321 350 554 560





B

nBu

1d

[Me4N]

Me


(m 4H) 136-157 (m 6H) 170-196 (m 4H) 220-234 (m 5H) 304 (s 12H)

697-701 (m 2H) 704-709 (m 2H) 13

C NMR (CD3CN) δ = 152 212 270

271-290 (m) 282 288 318 324 357 561 1279 1296 1314 1344 The

Chapter 5

114




[M-(NMe4)]- 2932446 Found 2932454

B

Ph

1e

[Me4N]

F3C


(m 2H) 292 (s 12H) 690-696 (m 1H) 710-718 (m 2H) 728 (dd J = 88 08 Hz

2H) 744-752 (m 4H) 13

C NMR (CD3CN) δ = 252-270 (m) 269 273 321 351






B

Ph

1f

[Me4N]

S



48 32 Hz 1H) 703-719 (m 6H) 13

C NMR (CD3CN) δ = 266 272 270-286 (m)

323 348 560 962 1231 1256 1266 1274 1290 1300 1314 The boron-bound

sp2 and sp


11B NMR


- 3051541 Found

3051541

Chapter 5

115


(H-9BBN) 2

H tBu

THF 0 degC

THF -78 degC to rt

2) Me4NCl MeOH

Li

1)S

B

1c

[Me4N]

S

tBu














B

1c

[Me4N]

S

tBu


4H) 222-235 (m 2H) 306 (s 12H) 552 (d J = 172 Hz 1H) 591 (d J = 176 Hz


Hz 1H) 13

C NMR (CD3CN) δ = 273 276 278-296 (m) 311 327 341 352 561





Chapter 5

116












OHMe

3aOMe

NOE

no NOE

IR (ATR) 3315 1508 1248 752 694 cm-1

1H NMR δ = 159 (s 3H) 204 (bs 1H)

382 (s 3H) 684-690 (m 2H) 721-730 (m 8H) 742-748 (m 2H) 751-755 (m

1H) 13

C NMR δ = 239 552 832 1139 1208 1218 1265 1268 1272 1280


C23H21O2 [M+H]+ 3291536 Found 3291556

OHMe

OMe

3b

NOE

no NOE

IR (ATR) 3319 1508 1248 760 702 cm-1

1H NMR δ = 160 (s 3H) 208 (s 1H)

378 (s 3H) 674-680 (m 2H) 718-723(m 1H) 724-744 (m 9H) 750-755 (m

1H) 13

C NMR δ = 241 551 833 1134 1205 1218 1263 1270 1274 1284


Chapter 5

117

C23H20O2Cl [M+Cl]- 3631146 Found 3631148

OHMe

Ph

3cCF3

IR (ATR) 3298 1319 1121 750 696 cm-1

1H NMR δ = 160 (s 3H) 210 (bs 1H)

716-722 (m 1H) 723-732 (m 5H) 737-747 (m 4H) 752-764 (m 3H) 13

C NMR

δ = 240 833 1205 1221 1241 (q JC-F = 2701 Hz) 1255 (q JC-F = 37 Hz) 1269

1277 1282 1286 1293 1295 (q JC-F = 322 Hz) 1296 1341 1373 1385 1414


- 3651159 Found 3651159

OHMe

Ph

3d

S

IR (ATR) 3319 1350 1088 752 694 cm-1

1H NMR δ = 177 (s 3H) 209 (bs 1H)

696-702 (m 2H) 718 (dd J = 52 Hz 12Hz 1H) 723-730 (m 2H) 735-740 (m

3H) 742-752 (m 3H) 753-758 (m 1H) 13

C NMR δ = 254 833 1207 1216

1259 1265 1266 1275 1282 1287 1290 1294 1347 1360 1374 1410 1426


+ 3050995 Found 3050992

OHMe

OMe

3e

IR (ATR) 3310 1508 1244 1034 758 cm-1

1H NMR δ = 144 (s 3H) 158-202 (m


5H) 747 (d J = 68 Hz 1H) 13

C NMR δ = 238 266 267 305 311 382 552

822 1136 1211 1219 1257 12789 12793 1304 1406 1409 1467 1499


+ 3382115 Found 3382104

Chapter 5

118

OHH

Ph

3fOMe

MeO

IR (ATR) 3472 1601 1508 1244 704 cm-1

1H NMR δ = 174 (d J = 88 Hz 1H)


= 80 Hz 24 Hz 1H) 692-697 (m 2H) 718-730 (m 5H) 732-736 (m 2H) 753 (d

J = 84 Hz 1H) 13

C NMR δ = 552 555 766 1072 1109 1143 1244 1267 1272

1283 1292 1303 1342 1363 1390 1445 1457 1592 1606 HRMS (ESI+)


OHPh

Ph

3gOMe

IR (ATR) 3422 1508 1244 1028 746 698 cm-1

1H NMR δ = 248 (s 1H) 385 (s

3H) 695 (d J = 88 Hz 2H) 704-714 (m 5H) 715-732 (m 7H) 736-740 (m 2H)

755 (d J = 88 Hz 2H) 13

C NMR δ = 552 868 1141 1210 1231 1250 1268

12698 12702 1271 1278 12836 12844 1294 1304 1340 1402 1417 1427


+ 3911693 Found

3911718

OHPh

Ph

3hOMe

O

O

IR (ATR) 3362 1470 1244 1034 696 cm-1

1H NMR δ = 239 (s 1H) 385 (s 3H)

591 (dd J = 164 16 Hz 2H) 673 (d J = 44 Hz 2H) 690-696 (m 2H) 702-708

(m 5H) 720-736 (m 5H) 749-754 (m 2H) 13

C NMR δ = 552 863 1012 1024

Chapter 5

119

1049 1142 1249 12690 12692 1270 1278 1285 1292 1304 1340 1367


+

4341518 Found 4341505

OHPh

Ph

3iOMe

F3C

IR (ATR) 3545 1508 1321 1115 696 cm-1

1H NMR δ = 249 (s 1H) 387 (s 3H)

694-700 (m 2H) 704-715 (m 5H) 723-738 (m 6H) 742-755 (m 4H) 13

C NMR

δ = 553 866 1145 1177 (q JC-F = 37 Hz) 1233 1241 (q JC-F = 36 Hz) 1242 (q

JC-F = 2702 Hz) 1249 1260 1275 1276 1280 1287 1295 1304 1308 (q JC-F =


C29H21F3O2Cl [M+Cl]- 4931177 Found 4931192

OHPh

3j

F

OMe

IR (ATR) 3356 1242 1028 741 696 cm-1

1H NMR δ = 164-178 (m 2H) 183-208


4H) 719-737 (m 6H) 13

C NMR δ = 2675 2681 308 310 383 551 862 1114


1268 1271 1283 1303 1371 (d JC-F = 29 Hz) 1410 1418 (d JC-F = 15 Hz)



+ 4001839 Found 4001835

OHMe

S

tBu

3k

Chapter 5

120

IR (ATR) 3298 1358 1078 756 689 cm-1

1H NMR δ = 111 (s 9H) 168 (s 3H)

188 (s 1H) 640 (d J = 164 Hz 1H) 656 (d J = 164 Hz 1H) 718-730 (m 4H)

739-751 (m 3H) 13

C NMR δ = 257 295 340 822 1169 1204 1215 1242

1255 1262 1283 1285 1324 1346 1415 1452 1462 1506 HRMS (ESI+)


OHMe

nBu

OMe3l

IR (ATR) 3335 1508 1084 918 758 cm-1

1H NMR δ = 085 (t J = 72 Hz 3H) 130

(tt J = 72 72 Hz 2H) 141-167 (m 6H) 229-250 (m 5H) 702-706 (m 1H)

716-728 (m 6H) 744-748 (m 1H) 13

C NMR δ = 138 213 232 237 252 314

829 1198 1215 1256 1282 1286 1291 1318 1370 1374 1430 1492 1496


+ 2931900 Found 2931890



nHex

(H-9BBN) 2


Li

Ph

B

nOct

Li

Ph

Me

O

I


toluene 50 degC 1 h

H2O2 aq

NaOH aq

OHMe

nOct

Ph3m

MeOH




Chapter 5

121













yield)

OHMe

nOct

Ph3m

IR (ATR) 3335 1456 1078 752 698 cm-1

1H NMR δ = 096 (t J = 68 Hz 3H)

129-156 (m 15H) 160 (s 1H) 208-227 (m 2H) 274-281 (m 2H) 287-294 (m

2H) 719-728 (m 5H) 729-736 (m 3H) 742 (d J = 72 Hz 1H) 13

C NMR δ = 141

226 234 247 277 293 294 295 304 319 345 825 1186 1213 1252 1260


[M]+ 3622610 Found 3622619

OHH

Ph

OMe

3n

IR (ATR) 3354 1508 1246 764 692 cm-1

1H NMR δ = 185 (bs 1H) 386 (s 3H)

567 (s 1H) 692-697 (m 2H) 718-738 (m 10H) 763-766 (m 1H) 13

C NMR δ =

552 773 1143 1206 1237 1263 1268 1272 1283 1287 1292 1303 1342


- 3131234

Found 3131237

Chapter 5

122

The 1H


15


OHH

Ph

OMe

3n

MnO2

DCM rt

Ph

OMe

4

O







The 1H


16

Ph

OMe

4

O

(CH 2OH)2

NH2NH2

KOH Ph

OMe

5








The 1H


5

Chapter 5

123






1395ndash1411



17638ndash17640





3201ndash3222



















Chapter 5

124












3283ndash3292









74








Chem 1989 54 1485ndash1491



2006 128 1828

Chapter 5

125



4781-4787


Chem 1989 54 1485

Chapter 5

126

127

List of Publication

Chapter 1



Angew Chem Int Ed 2012 51 11750-11752

Chapter 2


Benzosultams


J Am Chem Soc 2013 135 19103-19106

Chapter 3





Org Lett 2009 11 5434-5437

Chapter 4


Units


Org Lett 2010 12 3179-3181

Chapter 5




Eur J Org Chem 2013 1421-1424

Other Publication




Chem Lett 2013 42 1076


1









sultams














sun

CO2energy charge

Ph

O

NTs

Me

N

Ts

OHPh

OO

O

Ph

NHTs


2


benzosultams




developed456


shift7

MH14-metal shift

1

2 3

4

HM

1

2 3

4

H M1

23

4

5

M H1

23

4

515-metal shift






N

Ts

Ph OHMe

SN

MeO O

Ph OH

cat Rh





chemistry10






We


alkynylborates13

R1 B

R2

R2

R2

+ R3 Br

R3

R1 R2

B

R2

R2


3






obtained

Et

Ph

Ph

B O+

PhBr LPd(-allyl)Cl

L = XANTPhos

LPd(-allyl)Cl

L = P(o-tol)3 Ph

Et

Ph

B O

B

Et

Ph

Et

Ph

B

Ph

Ph

Et

B

Ph

Me3NO

Me3NO

[Me4N]







MeO

Br

I

Br

NaOH

R Ph

MeO Br

B

R

Ph

RB

Ph

OMe

[Me4N]

R Ph

MeOR Ph

Br

R =OMOM

n

B

R

Ph

[Me4N] I

Br

NaOH

R Ph

MeOR Ph

Br

n = 2~4

Pd-XANTPhos

Pd-XANTPhos






4


regioselectively

I

Me

O+

MeOH

R2

R1Pd-XANTPhosB

R2

R1

[Me4N]


5

Reference





































6








10990




2003 Vol 3





Q Z J Med Chem 2009 52 4192



2006 250 1107



2419













7



17638ndash17640


8

Chapter 1

9

Chapter 1


Ketones

Abstract






Chapter 1

10

Introduction







2 One







starting substances


CO2

sun

CO2energy charge

high energy

intermediates











8






Chapter 1

11


Ph

O

NTs

Mesolar light

N

Ph OH

Ts

2a 91

1aDMA







over 04 kWm-2



in eight hours on


Figure





kWhm-2



Chapter 1

12


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

0

20

40

60

80

100

0 1 2 3 4 5 6











(56)

Chapter 1

13


40 equiv Cs2CO3

1 atm CO2

DMA 60 degC

OO

O

Ph

NHTs

3a 93

N

Ph OH

Ts

2a








N

Ph O

Ts

A

N

Ph O

Ts

B

O

O

OO

O

Ph

NTs

CO2

H

C

Cs2CO3

CsHCO 3

Cs

Cs

Cs

2

1

N

Ph OH

Ts

2a

OO

O

Ph

NHTs

3a












N

Ts

OHPh

4

Chapter 1

14




solar light

CO2Cs2CO3

60degCDMAPh

O

NTs

Me

1a

OO

O

Ph

NHTs

3a 83






chloro groups10





Ar

O

NR

Me OO

O

Ar

NHR3

1

OO

O

NHTs3b 80

MeO

OO

O

NHTs3c 57

F3C

OO

O

NHTs3d 73

Cl

OO

O

NHTs3e 85

Br

OO

O

Ph

NH

3f 87

O2S OMe

OO

O

Ph

NH

3g 85

O2S CF3

OO

O

Ph

NH

3h 87

O2S

N

solar lightCO2

Cs2CO3

60degCDMA




Chapter 1

15

Conclusions















Chapter 1

16












indicator (Merck)






Ph

O

NTs

MeTsClMeNH2 +

Et2OTsNHMe

CH3CN

K2CO3












Chapter 1

17


Ph

O

NTs

Me


745-751 (m 2H) 760 (tt J = 76 12 Hz 1H) 771-775 (m 2H) 795-799 (m 2H)

13C NMR δ = 215 356 560 1275 1282 1288 1297 1338 1347 1348 1436


+ 3041002 Found mz 3040994 IR

(ATR) 1693 1339 1227 1157 743 cm-1

O

NTs

Me

1bMeO


733 (d J = 80 Hz 2H) 770-774 (m 2H) 796-802 (m 2H) 13

C NMR δ = 215

355 555 558 1139 1275 1277 1296 1307 1346 1436 1640 1921 HRMS


+ 3341108 Found mz 3341101 IR (ATR) 1688

1601 1329 1180 1159 cm-1

O

NTs

Me

1cF3C


= 84 Hz 2H) 776 (d J = 84 Hz 2H) 812 (d J = 84 Hz 2H) 13

C NMR δ = 215

357 564 1234 (q JC-F = 2711 Hz) 1259 (q JC-F = 37 Hz) 1276 1288 1298



1121 1109 cm-1

Chapter 1

18

O

NTs

Me

1dCl


(m 2H) 771 (d J = 80 Hz 2H) 792-796 (m 2H) 13

C NMR δ = 216 356 561



1159 1088 cm-1

O

NTs

Me

1eBr


= 84 Hz 2H) 771 (d J = 84 Hz 2H) 786 (d J = 84 Hz 2H) 13

C NMR δ = 215

356 561 1275 1291 1297 1298 1321 1334 1344 1438 1930 HRMS (ESI+)


1223 1155 810cm-1

Ph

O

NS

Me

1f

OMe

OO

1H NMR δ = 282 (s 3H) 389 (s 3H) 456 (s 2H) 698-703 (m 2H) 746-751 (m

2H) 761 (tt J = 72 12 Hz 1H)776-781 (m 2H) 796-800 (m 2H) 13

C NMR δ =

356 556 561 1142 1283 1288 1294 1297 1338 1348 1630 1938 HRMS


+ 3200951 Found mz 3200943 IR (ATR) 1692

1342 1259 1155 741 cm-1

Chapter 1

19

Ph

O

NS

Me

1g

CF3

OO


780 (d J = 84 Hz 2H) 790-794 (m 2H) 798 (d J = 80 Hz 2H) 13

C NMR δ =

356 558 1233 (q JC-F = 2711 Hz) 1261 (q JC-F = 36 Hz) 12796 12799 1289



1059 748 cm-1

Ph

O

NS

Me

1h

N

OO

1H NMR δ = 302 (s 3H) 486 (s 2H) 744-753 (m 3H) 757-762 (m 1H)

788-798 (m 4H) 870 (ddd J = 48 16 08 Hz 1H)13

C NMR δ = 363 569 1224



752 cm-1


Ph

O

NTs

Mesolar light

N

Ph OH

TsDMA rt

1a

2a








Chapter 1

20


N

Ph OH

Ts


2H) 728-737 (m 5H) 740 (d J = 80 Hz 2H) 779 (d J = 80 Hz 2H) 13

C NMR δ

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS




N 458 O 1555 S 1058 IR (ATR) 3477 1333 1184 1148 671 cm-1


N

Ph OH

Ts

2a

40 equiv Cs2CO3

1 atm CO2

DMA 60 C

OO

O

Ph

NHTs

3a








mmol 93 yield)

Chapter 1

21



40 equiv Cs2CO3

60 CPh

O

NR

Me OO

O

Ph

NHR3a

1a

solar light

DMA rt

1 atm CO2











OO

O

Ph

NHTs



726-732 (m 4H) 734-743 (m 3H) 769-773 (m 2H) 13

C NMR δ = 215 503

724 850 1242 1269 1292 1299 1365 1381 1439 1542 HRMS (ESI+) Calcd

for C17H18NO5S M+H+


C 5878 H 493 N 403 O 2303 S 923 Found C 5871 H 496 N 389 O

2284 S 932 IR (ATR) 3261 1773 1435 1319 1045 cm-1

Chapter 1

22

OO

O

NHTs

3b

MeO



56 Hz 1H) 688-693 (m 2H) 719-724 (m 2H) 728 (d J = 80 Hz 2H) 770 (d J =

84 Hz 2H) 13

C NMR δ = 215 503 554 724 848 1145 1256 1269 1298


+

3781006 Found mz 3780996 IR (ATR) 3238 1794 1518 1329 1057 723 cm-1

OO

O

NHTs

3c

F3C



729 (d J = 84 Hz 2H) 746 (d J = 84 Hz 2H) 765-771 (m 4H) 13

C NMR δ =

215 501 722 846 1235 (q JC-F = 2704 Hz) 1249 1263 (q JC-F = 37 Hz) 1268



1067 cm-1

OO

O

NHTs

3d

Cl



722-727 (m 2H) 728 (d J = 84 Hz 2H) 735-739 (m 2H) 769 (d J = 84 Hz 2H)

13C NMR δ = 215 502 723 847 1257 1268 1294 1300 1353 1364 1365


+ 3820510 Found mz

Chapter 1

23

3820506 IR (ATR) 3250 1800 1325 1155 1069 cm-1

OO

O

NHTs

3e

Br



716-720 (m 2H) 728 (d J = 80 Hz 2H) 750-755 (m 2H) 766-770 (m 2H) 13

C

NMR δ = 215 501 723 847 1235 1260 1268 1300 1323 1364 1370 1441


+ 4260005 Found mz 4260003

IR (ATR) 3252 1800 1331 1175 1057 cm-1

OO

O

Ph

NH

SO

O

OMe



693-698 (m 2H) 727-732 (m 2H) 734-744 (m 3H) 773-778 (m 2H) 13

C NMR

δ = 503 556 724 849 1145 1242 1291 1292 1310 1381 1541 1632 HRMS


+ 3640849 Found mz 3640836 IR (ATR) 3246

1801 1325 1155 1067 cm-1

OO

O

Ph

NH

SO

O

CF3

3g

Chapter 1

24



2H) 735-744 (m 3H) 775 (d J = 88 Hz 2H) 796 (d J = 84 Hz 2H) 13

C NMR δ

= 505 725 851 1231 (q JC-F = 2711 Hz) 1241 1265 (q JC-F = 37 Hz) 1274



1161 1105 cm-1

OO

O

Ph

NH

SO

O

N




1H) 798 (d J = 76 Hz 1H) 866 (d J = 44 Hz 1H) 13

C NMR δ = 510 723 849



1175 1063 cm-1


N

Ts

OHPh

N

Ts

O CeCl 3

PhLi

THF -78 C to rt

4






Chapter 1

25






N

Ts

OHPh


351-364 (m 4H) 726-738 (m 7H) 773-777 (m 2H) 13

C NMR δ = 215 396

469 608 804 1250 1276 1280 1286 1297 1339 1418 1435 HRMS (ESI+)


1325 1159 1101 770 cm-1

Chapter 1

26











Soc 2011 133 12881

























25 312

Chapter 1

27








Chapter 1

28

Chapter 2

29

Chapter 2



Abstract







Chapter 2

30

Introduction














A



Indanones are


A rearrangement













Whereas







Chapter 2

31




N

HO Ph

S NS Me

HO PhMe

1a2a 96

Me

O

OO O


2) is





The generated








N

S O

O

O[Rh]

Ph

SN

[Rh]O Ph

O OMe

[Rh] OH

N

S O

O

O Ph

H

[Rh]

H

N

[Rh]O Ph

S O

O

Me Me

Me

Me

1a

H2O

2a

A B

CD

1a

A




Chapter 2

32








N

HO Ph

SN

S CH19D11

HO Ph

D3C

1a-d2a-d 96

D3C

O

O

O O

D

D

D

D

D

D

H01D09

8



D12




Application




1

2

SN

HO Ar

O OMe

N

HO Ar

S O

O


K2CO 3 (20 equiv)


NS Me

HO PhMe

2a

91 er = 928

O O

NS Me

HO Ph

2b

95 er = 937

O O

S

NS Me

HOMe

2c

90 er = 937

O O

OMe

NS Me

HOMe

2c

92 er = 919

O O

CF3



Chapter 2

33










HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6 84

5 56



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3


PhMgBr

THF rt 1 h N

HO

Ts

Me

1e 93

er gt 991 dr = 201

Ph

3







SN

HO PhMe

O OMe

MeN

HO Ph

S O

O

Me

Me

1e

er gt 991 dr = 201

2e 99

er gt 991 dr gt 201





Chapter 2

34









SN

PhRhOMe

O OMe

Me

SN

PhRhOMe

O OMe

Me

favored

disfavored

F

F

NSRh

Ph

Me

O

O

MeO

H

Me

E

E

NSRh

Ph

Me

O

O

MeO

Me

H














Chapter 2

35


1

er gt 991 dr gt 201

2

er gt 991 dr gt 201

SN

HO ArR

O OMe

N

HO Ar

S O

O





1 N

HO Ph

S O

O

Me

Me

1f

SN

HO PhMe

O OMe

Me

2e 99

6 N

HO

S O

O

Me

1k

OMe

SN

HOMe

O OMe

2k 97

OMe

2

N

HO Ph

S O

O

MeO

Me

1g

SN

HO PhMe

O OMe

MeO

2g 98

7 N

HO

S O

O

Me

Me

1l

CF3

SN

HOMe

O OMe

Me

2l 97

CF3

3 N

HO Ph

S O

O

F3C

Me

1h

SN

HO PhMe

O OMe

F3C

2h 99

8 N

HO Ph

S O

O

Me

i-Pr

1m

SN

HO Phi-Pr

O OMe

Me

2m 97

4

N

HO Ph

S O

O

Me

1iMe

SN

HO PhMe

O OMeMe

2i 99

9 N

HO Ph

S O

O

Me

SMe

SN

HO Ph

O OMe

Me

2n 97

SMe

5 N

HO Ph

S O

O

Me

S

1j

SN

HO PhMe

O OMeS

2j 99



Chapter 2

36

Conclusions






Chapter 2

37





13C NMR


13C at 10069












N

OHNEt3

DCM rt 12 h


2) PhMgBrTHF rt 3 h

N

HO Ph

1a

TsCl

N

OH

8a

H HCl

Ts Ts









Chapter 2

38

N

S

Me

O

O

OH

8a 1H NMR = 213 (bs 1H) 245 (s 3H) 350-361 (m 2H) 394-404 (m 2H)

442-452 (m 1H) 737 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR =



-1

N

S

D3C

O

O

OH

8a-d

D

D

D

D

1H NMR = 283 (bs 1H) 349-355 (m 2H) 389-396 (m 2H) 435-444 (m 1H)



+ 2351128 Found mz

2351125 IR (ATR) 3503 1333 1142 1059 638 cm-1

N

S O

O

OH

8b

S

1H NMR = 277 (bs 1H) 357-364 (m 2H) 400-407 (m 2H) 441-450 (m 1H)


1H) 13



1038 737 cm-1

Chapter 2

39














N

HO Ph

S

1a

Me

O

O


2H) 728-737 (m 5H) 739 (d J = 84 Hz 2H) 778 (d J = 80 Hz 2H) 13

C NMR

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS


+ 3041002 Found mz 3040995 IR (ATR) 3477

1333 1184 1148 671 cm-1


N

HO Ph

S

1a-d

D3C

O

O

D

D

D

D


(m 5H) 13

C NMR = 203-211 (m) 652 703 1244 1281 (t JC-D = 247 Hz)


Chapter 2

40


702 648 cm-1

N

HO Ph

S

S

O

O



1H) 13

C NMR = 656 702 1244 1280 1283 1288 1331 13387 13392 1417


+ 2960410 Found mz 2960404 IR

(ATR) 3524 1333 1161 1148 748 cm-1

N

HO

S

Me

O

O

OMe

1c



2H) 775 (d J = 80 Hz 2H) 13

C NMR =216 553 652 702 1139 1259 1285


+

3341108 Found mz 3341097 IR (ATR) 3460 1518 1331 1250 1146 cm-1

N

HO

S

Me

O

O

CF3



C NMR

Chapter 2

41

=216 654 697 1239 (q JC-F = 2704 Hz) 1249 1255 (q JC-F = 37 Hz) 1284



1109 1076 cm-1


1l-1n

HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6a

5a



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3

acetone H2O

rt 10 h 4a

PhMgBr

THF rt 1 h N

OH

Ts

Me

1e

Ph

3a



procedure16













Me

NHTs

O

N2


Chapter 2

42

2H) 730 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR = 194 215 539


+

2680750 Found mz 2680747 IR (ATR) 2112 1639 1337 1319 1161 cm-1

[]27

D = -1184 (c = 079 in CHCl3)


i-Pr

NHTs

O

N2



2H) 769 (d J = 84 Hz 2H) 13

C NMR =169 193 215 315 548 647 1273


+ 2961063

Found mz 2961060 IR (ATR) 2129 1622 1362 1329 1161 cm-1

[]28

D = -730 (c = 071 in CHCl3)

NHTs

O

N2

5c

SMe

1H NMR = 174-196 (m 2H) 204 (s 3H) 242 (s 3H) 244-252 (m 2H)

390-400 (m 1H) 541 (s 1H) 560-572 (m 1H) 730 (d J = 84 Hz 2H) 772 (d J =

84 Hz 2H) 13

C NMR = 153 215 297 323 545 585 1272 1297 1366 1439


+ 3280784 Found mz 3280779

IR (ATR) 2129 1618 1375 1339 1163 cm-1

[]29

D = -506 (c = 063 in CHCl3)









Chapter 2

43

N

O

Ts

Me

6a

1H NMR = 145 (d J = 68 Hz 3H) 246 (s 3H) 443-454 (m 2H) 473-480 (m

1H) 736-742 (m 2H) 776-781 (m 2H) 13

C NMR = 157 216 696 810 1284


+ 2400689

Found mz 2400688 IR (ATR) 1825 1339 1155 669 cm-1

[]28

D = 614 (c = 081 in CHCl3)


N

O

Ts

i-Pr

6b

1H NMR = 099-111 (m 6H) 206-218 (m 1H) 246 (s 3H) 441 (dd J = 164 36


2H) 777 (d J = 80 Hz 2H) 13

C NMR = 174 181 216 304 703 903 1284


+ 2681002

Found mz 2680998 IR (ATR) 1815 1340 1155 1007 671 cm-1

[]29

D = 567 (c = 095 in CHCl3)

N

O

Ts

6c

SMe

1H NMR = 204 (s 3H) 209-218 (m 2H) 247 (s 3H) 265-279 (m 2H) 446 (d


2H) 780 (d J = 80 Hz 2H) 13

C NMR = 147 216 291 293 705 832 1286


+ 3000723

Found mz 3000718 IR (ATR) 1813 1342 1308 1157 667 cm-1

[]29

D = 1183 (c = 036 in CHCl3)


Chapter 2

44










N

HO

S O

O

Me

Me

1e

H

NOE

NOE



(m 3H) 739 (d J = 84 Hz 2H) 777 (d J = 84 Hz 2H) 13

C NMR = 144 216

628 702 731 1247 1279 1284 1285 1298 1319 1415 1443 HRMS (ESI+)


1155 1092 667 cm-1

[]25




Chapter 2

45

N

HO

S O

O

Me

1l

H

NOE

NOE

CF3

Me



739-747 (m 4H) 777 (d J = 84 Hz 2H) 13

C NMR = 143 216 630 706 727

1238 (JC-F = 2704 Hz) 1253 1254 (JC-F = 36 Hz) 1285 1299 1301 (JC-F = 324


+ 3861032

Found mz 3861025 IR (ATR) 3422 1327 1151 1109 839 cm-1

[]28




N

HO

S O

O

Me

iPr

1m

H

NOE

NOE



= 100 Hz 1H) 690-696 (m 2H) 712-720 (m 3H) 732 (d J = 80 Hz 2H) 773 (d

J = 80 Hz 2H) 13

C NMR = 190 193 215 291 641 729 801 1247 1275


+

3461471 Found mz 3461466 IR (ATR) 3454 1331 1163 739 669 cm-1

[]27



Chapter 2

46


N

HO Ph

S O

O

1n

Me

SMe

1H NMR = 202 (s 3H) 218-258 (m 8H) 388-394 (m 2H) 427 (dd J = 84 48

Hz 1H) 688-693 (m 2H) 714-721 (m 3H) 740 (d J = 80 Hz 2H) 779 (d J = 80

Hz 2H) 13

C NMR = 154 216 290 297 634 725 733 1246 1277 1284


+

3781192 Found mz 3781188 IR (ATR) 3481 1339 1157 702 669 cm-1

[]28












N

HO

S O

O

Me

Me

1f

H

NOE

NOE


1H) 398 (q J = 64 Hz 1H) 424 (dd J = 84 08 Hz 1H) 732-744 (m 5H)

750-755 (m 2H) 774-778 (m 2H) 13

C NMR = 165 216 627 718 739 1257

Chapter 2

47



-1

[]25






HO2C Me

NHCbz

Me

NHCbz

O

N2N

O

Cbz

Me

6d5d

1) (COCl) 2 DMF

2) CH2N2 Rh2(OAc)4 (05 mol )

DCM rt 12 h4d

PhMgBr

THF rt 1 h

N

OH

Cbz

Me

7a

Ph

N

OH

H

Me

PhPd C (5 mol )

H2 (1atm)

MeOH rt 12 h

MeO SO2Cl

NEt3

DCM rt 12 h

N

HO Ph

S O

O

MeO

Me

1g









Me

NHCbz

O

N2

5d 1H NMR = 134 (d J = 68 Hz 3H) 420-436 (m 1H) 504-516 (m 2H) 534-564

(m 2H) 728-736 (m 5H) 13

C NMR = 184 535 (2C) 669 1280 1282 1285


+ 2481030 Found mz

2481028 IR (ATR) 2116 1717 1636 1533 1252 cm-1

[]28

D = -434 (c = 085 in CHCl3)


Chapter 2

48







N

O

Cbz

Me

6d


Hz 1H) 498-505 (m 1H) 513-521 (m 2H) 731-739 (m 5H) 13

C NMR = 153



696 cm-1

[]29

D = 390 (c = 068 in CHCl3)










N

OH

Cbz

Me

7a

Ph


= 96 Hz 1H) 458 (q J = 64 Hz 1H) 507-518 (m 2H) 729-746 (m 10H) 13

C

NMR = 142 623 667 689 730 1246 1278 1279 1280 1285 1287 1366

Chapter 2

49


+ 2981438 Found mz

2981433 IR (ATR) 1670 1423 1248 1016 702 cm-1

[]29

D = 46 (c = 089 in CHCl3)

N

OH

Cbz

Me

7b

MeO


1H) 432 (d J = 96 Hz 1H) 452-461 (m 1H) 506-518 (m 2H) 687-694 (m 2H)

726-739 (m 7H) 13

C NMR = 143 553 622 666 687 729 1140 1260 1278


+

3281543 Found mz 3281539 IR (ATR) 1682 1418 1352 1024 696 cm-1

[]29

D = 02 (c = 085 in CHCl3)








pressure







mmol 58 yield)

Chapter 2

50

N

HO

S O

O

MeO

Me

1g

H

NOE

NOE


390 (s 3H) 399 (d J = 92 Hz 1H) 419 (q J = 60 Hz 1H) 698-707 (m 4H)

720-727 (m 3H) 779-785 (m 2H) 13

C NMR = 143 557 627 701 731 1144



-1

[]28




N

HO

S O

O

F3C

Me

1h

H

NOE

NOE


406 (d J = 92 Hz 1H) 430 (qd J = 64 08 Hz 1H) 694-699 (m 2H) 721-727

(m 3H) 784 (d J = 80 Hz 2H) 801 (d J = 84 Hz 2H) 13

C NMR = 145 629

706 729 1232 (JC-F = 2711 Hz) 1245 1263 (JC-F = 37 Hz) 1283 12868 12871


+

3720876 Found mz 3720870 IR (ATR) 3503 1348 1323 1165 646 cm-1

[]28




Chapter 2

51

N

HO

S O

O

Me

1i

H

NOE

NOE


1H) 401 (d J = 88 Hz 1H) 422 (q J = 64 Hz 1H) 694-698 (m 2H) 720-724 (m

3H) 746-750 (m 2H) 767-772 (m 2H) 13

C NMR = 144 214 630 704 730

1247 1256 1279 1285 1286 1291 1341 1347 1395 1416 HRMS (ESI+)


1151 714 700 cm-1

[]29




N

HO

S O

O

Me

1j

H

NOE

NOE

S


Hz 1H) 425 (q J = 64 Hz 1H) 696-701 (m 2H) 720-728 (m 4H) 764-767 (m

1H) 769-772 (m 1H) 13

C NMR = 144 632 709 730 1246 1279 1281 1286


+ 3100566

Found mz 3100559 IR (ATR) 3508 1340 1151 756 669 cm-1

[]29




Chapter 2

52

N

HO

S O

O

Me

1k

H

NOE

NOE

OMe


1H) 394 (d J = 88 Hz 1H) 416 (q J = 64 Hz 1H) 670-675 (m 2H) 684-689 (m

2H) 756-762 (m 2H) 765-770 (m 1H) 786-790 (m 2H) 13

C NMR = 143 553

630 704 729 1138 1259 1283 1292 1332 1337 1348 1592 HRMS (ESI+)


1327 1155 606 cm-1

[]29





Screening







mmol 93 yield)

Chapter 2

53


rac -DM-BINAP

rac-BINAP

dppf

dppb

PPh3

dppe

46

trace

trace

yield

PCy3

Ligand

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

entry

1

2

3

4

5

6

7

8

nd

nd

nd

93

none nd

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a


entry Ligand yield

1

2

3

4

(R)-BINAP

(R)-DM-BINAP

(R)-SEGPHOS

(R)-DIFLUORPHOS

er

94

46

48

43

5

6

(R)-DM-SEGPHOS


3862

91

7

8

(R)-MeO-BIPHEP

(R)-MeO-DM-BIPHEP

64

91

892

3169

1288

1486

2476

2575

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a










Chapter 2

54

NS Me

HO PhMe

2a

O O


J = 148 Hz 1H) 683 (s 1H) 727-744 (m 6H) 781 (d J = 84 Hz 1H) 13

C NMR

= 216 361 626 732 1238 1263 1280 1284 1299 1301 1330 1412 1431


+ 3041002 Found mz 3040998 IR

(ATR) 3472 1325 1161 1142 735 cm-1

[]29




NS CH2D

HO Ph

D3C

2a-d

O O

D

D

D


J = 148 Hz 1H) 728-743 (m 5H) 13

C NMR = 201-210 (m) 358 (t JC-D = 212

Hz) 625 731 1234 (t JC-D = 249 Hz) 1262 1279 1283 1291-1300 (m 2C)


+ 3111441

Found mz 3111436 IR (ATR) 3524 1318 1290 1150 721 cm-1

NS Me

HO Ph

O O

S

2b


1H) 668 (d J = 52 z 1H) 730-738 (m 5H) 750 (d J = 52 Hz 1H) 13

C NMR =

378 630 722 1257 1264 1282 1286 1299 1338 1427 1467 HRMS (ESI+)


1150 1063 748 cm-1

[]29


Chapter 2

55



NS Me

HOMe

O O

OMe

2c


422 (d J = 148 Hz 1H) 684-690 (m 3H) 724-733 (m 3H) 774-779 (m 1H) 13

C

NMR = 216 360 553 626 729 1137 1237 1275 1299 1230 1328 1351


+ 3341108 Found mz

3341098 IR (ATR) 3441 1508 1250 1144 735 cm-1

[]29




NS Me

HOMe

O O

CF3



2H) 782 (d J = 80 Hz 1H) 13

C NMR = 216 360 625 731 12392 (q JC-F =

2708) 12395 1254 (q JC-F = 36 Hz) 1268 1298 1303 (q JC-F = 352) 1329


+ 3720876 Found

mz 3720869 IR (ATR) 3481 1323 1121 1067 733 cm-1

[]29




Chapter 2

56










SN

HO

Me

O OMe

Me

2e

H

NOE

NOE


= 68 Hz 1H) 675 (s 1H) 723-738 (m 6H) 777 (d J = 84 Hz 1H) 13

C NMR =

119 215 314 608 750 1242 1262 1275 1282 1298 1301 1316 1427


+ 3181158 Found mz

3181155 IR (ATR) 3481 1315 1163 1146 683 cm-1

[]28




SN

HO

Me

O OMe

MeO

2g

H

NOE

NOE

Chapter 2

57



5H) 782 (d J = 88 Hz 1H) 13

C NMR = 120 314 555 609 752 1144 1151



735 cm-1

[]29




SN

HO

Me

O OMe

F3C

2h

H

NOE

NOE



1H) 13

C NMR = 118 314 608 750 1228 (q JC-F = 2711 Hz) 1251 1258 (q



+ 3720876 Found

mz 3720872 IR (ATR) 3461 1325 1161 1142 739 cm-1

[]29




SN

HO

Me

O OMe

2i

H

NOE

NOE

Me

Chapter 2

58


J = 68 Hz 1H) 684 (d J = 80 Hz 1H) 718-736 (m 6H) 770 (s 1H) 13

C NMR

=119 211 314 607 748 1242 1262 1275 1282 1299 1338 1341 1395


+ 3181158 Found mz

3181155 IR (ATR) 3489 1448 1319 1148 735 cm-1

[]29




SN

HO

Me

O OMe

2j

H

NOE

NOES


1H) 656 (d J = 52 Hz 1H) 726-736 (m 5H) 743 (d J = 48 Hz 1H) 13

C NMR

= 114 319 619 742 1256 1266 1278 1284 1297 1334 1429 1480 HRMS


+ 3100566 Found mz 3100561 IR (ATR) 3524

1329 1151 1020 729 cm-1

[]29




SN

HO

Me

O OMe

2k

H

NOE

NOE

OMe


J = 68 Hz 1H) 685 (d J = 88 Hz 2H) 698-703 (m 1H) 722-730 (m 2H)

738-748 (m 2H) 785-790 (m 1H) 13

C NMR = 119 314 553 608 747 1136

Chapter 2

59



760 cm-1

[]26




SN

HO

Me

O OMe

2l

H

NOE

NOE

CF3

Me



= 84 Hz 2H) 778 (d J = 80 Hz 1H) 13

C NMR = 119 215 313 607 749




-1

[]26




SN

HO

iPr

O OMe

2m

H

NOE

NOE

Me


(m 1H) 264 (s 1H) 285 (s 3H) 441 (d J = 100 Hz 1H) 685 (s 1H) 714-735 (m

4H) 748 (d J = 76 Hz 2H) 772 (d J = 80 Hz 1H) 13

C NMR = 211 214 217

278 330 718 742 1244 1256 1270 1283 1292 1295 1300 1435 1442


+ 3461471 Found mz 3461466 IR

Chapter 2

60

(ATR) 3412 1315 1165 1146 683 cm-1

[]29




SN

HO

O OMe

2n

H

Me

NOE

SMe

1H NMR = 160-170 (m 1H) 184 (s 3H) 212-226 (m 4H) 230-242 (m 2H)

254-263 (m 1H) 294 (s 3H) 471 (dd J = 108 28 Hz 1H) 675 (s 1H) 722-738

(m 6H) 776 (d J = 80 Hz 1H) 13

C NMR = 150 215 242 301 321 643 748

1245 1262 1276 1283 12986 12993 1312 1429 1437 1441 HRMS (ESI+)


1165 1134 748 cm-1

[]28









was used as a


and


21 All



Chapter 2

61



2e

formula C17H19NO3S

fw 31739

T (K) 100(2)


space group P21c

a (Aring) 105967(5)


3) 152058(13)

Z 4 Dcalc (gcm

3) 1386

(mm-1

) 0225 F(000) 672



348500135

params 203 GOF on F

2 1069

R1 wR2 [Igt2(I)]

00322 00868

R1 wR2 (all data)

00335 00878

Chapter 2

62

























Med Chem 2003 46 1116








Chapter 2

63

































Chapter 2

64




2012 51 9160





11437-11439
























Chapter 2

65











2548-2551







11750









32 115



Chapter 2

66

Chapter 3

67

Chapter 3




Halides

Abstract






Chapter 3

68

Introduction
















2) are












several months


Et LiB

Ph

+B

Ph

Et

1a 74

(a)(b)[Me4N]


Chapter 3

69

















OMe

BrB

Ph

Et

OMe

3a

Ph

Et

OMe

H

4a

Pd-ligand AcOH

2a

+B

Ph

Et

1a

[Me4N]


EZ of 4ab

1 P(o-tol)3 69 397

2 P(t-Bu)3 47 1783

3 1-[(t-Bu)2P](biphenyl) 18 2872

4 2-[(t-Bu)2P](11-binaphthyl) 21 6733

5 DPEPhos 24 928



analysis



Chapter 3

70









Pd(0)

Pd

MeO

B

PdEt

OMe

Ph

B

Ph

Et

2a

BC

Pd

MeO

Br

A

1a

3a







dominates10
















Chapter 3

71










Chapter 3

72


BO

Ph

Et

OMe

5a 83

BO

Ph

Et

CF3

5b 85

BO

Ph

Et

NPhth

5c 82

BO

Ph

Et

5d 72b

BO

Ph

Et

5e 85

S

BO

n-Pr

Me

Cl

5f 74

BO

n-Pr

Ph

OMe

5g 82

BO

Ph

S

5h 83

BO

Ph

CO2Et

5i 81

BO

Ph

5j 82

Cl

BO

Ph

CF3

TBSO

BO

Cl

S

Ph

BO

Ph

Me

OMe

5n 71b

5m 925l 82

BO

Ph

5k 76

Me

+B

Ar

R

1

[Me4N]

2


BO

Ar

R

Ar

5







The reaction of 1a






Chapter 3

73








(E)-5o83 EZ = gt955

BO

Ph

Et

Ph

Ph

Et

PhO

NMe2

(Z)-685 EZ = lt595

Ph

Ph

EtO

NMe 2

(E)-675 EZ = 928

1a

(Z)-5o71 EZ = 793

+ PhBr

BO

Ph

Ph

Et

(a)

(c) (c)

(b)






Conclusions






Chapter 3

74




1H at 400 MHz and

11B at 128 MHz)



13C)

CD3CN ( = 194 for 1H =132 for


11B)









and Ph-9-BBN18


procedures


Et LiB

Ph

+B

Ph

Et

1a


2) Me4NCl MeOH

[Me4N]









74 yield)

Chapter 3

75

B

Ph

Et

1a

[Me4N]


136-207 (m 11H) 236-250 (m 2H) 303 (s 12 H) 679-686 (m 1H) 700-707 (m

2H) 735 (d J = 72 Hz 2H) 13

C NMR (CD3CN) = 149 166 266 (q JC-B = 379

Hz) 271 275 324 349 561 948 1221 1269 1339 11

B NMR = -133 HRMS




n-Pr LiB

Ar


2) Me4NCl MeOH B

n-Pr

1b

Cl

[Me4N]










Chapter 3

76

B

n-Pr

1b

Cl

[Me4N]

1H NMR (CD3CN) = 084-096 (m 5H) 111-121 (m 1H) 126-200 (m 13H)

235-250 (m 2H) 304 (s 12H) 700-705 (m 2H) 733 (d J = 84 Hz 2H) 13

C NMR

(CD3CN) = 139 234 249 266 (q JC-B = 393 Hz) 270 273 323 348 561

933 1265 1272 1355 11


[M-(NMe4)] 2991738 Found 2991730

B

n-Pr

1c

OMe

[Me4N]


128-201 (m 13H) 237-252 (m 2H) 303 (s 12H) 371 (s 3H) 663-668 (m 2H)

723 (d J = 81 Hz 2H) 13

C NMR (CD3CN) = 140 235 250 268 (q JC-B = 393

Hz) 272 275 324 349 554 561 929 1128 1344 1561 11

B NMR = -135


B

Ph

1d

[Me4N]


(m 2H) 134-196 (m 9H) 230-244 (m 2H) 304 (s 12H) 679-686 (m 1H)

699-706 (m 2H) 733 (d J = 72 Hz 2H) 13

C NMR (CD3CN) =23 87 266 (q

JC-B = 393 Hz) 271 274 323 349 562 1222 1269 1338 11

B NMR = -134


Chapter 3

77

B

Ph

1e

[Me4N]


(m 3H) 302 (s 12H) 679-686 (m 1H) 699-706 (m 2H) 734 (d J = 66 Hz 2H) 13

C NMR (CD3CN) = 253 268 (q JC-B = 379 Hz) 271 275 324 333 349 361

561 980 1221 1269 1339 11


[M-(NMe4)] 2912284 Found 2912278

B

1f

S

Ph

[Me4N]




09 Hz 1H) 712-730 (m 5H) 13

C NMR (CD3CN) = 240 268-290 (m) 325 347

380 562 928 1225 1261 1265 1271 1289 1297 1434 11

B NMR = -135


B

Ph

1g

TBSO

[Me4N]

1H NMR (CD3CN) = 005 (s 6H) 084-096 (m 11H) 110-120 (m 1H) 134-197

(m 9H) 216-233 (t J = 72 Hz 2H) 235-250 (m 2H) 301 (s 12H) 356 (t J = 78

Hz 2H) 680-687 (m 1H) 700-708 (m 2H) 735 (d J = 66 Hz 2H) 13

C NMR

(CD3CN) = -50 189 254-277 (m) 323 348 561 649 889 1222 1269

1339 11


Found 3812789

Chapter 3

78

B

Ph

1h

OMe

[Me4N]


(m 2H) 298 (s 12H) 373 (s 3H) 668-674 (m 2H) 701-718 (m 5H) 732 (d J =

87 Hz 2H) 13

C NMR (CD3CN) = 255-277 (m) 322 350 554 561 961 1129

1251 1287 1302 1312 1345 1564 11


C23H26BO [M-(NMe4)] 3292077 Found 3292081



Br

+

MeO


6 mol Ligand


2a

B

Ph

Et

OMe

(E)-3a

AcOH

Ph

Et

OMe

H

Ph

B

Et

OMe

+

+

(Z)-3a

(E)-4a

H

Et

OMe

Ph

(Z)-4a

B

Ph

Et

1a

[Me4N]









Chapter 3

79




B

Ph

Et

+


toluene 70 degC

Me3NO

Br

MeO

BO

Ph

Et

OMe

5a

1a

2a

[Me4N]









BO

Ph

Et

OMe


383 (s 3H) 438-444 (m 1H) 685-691 (m 2H) 714-736 (m 7H) 13

C NMR =

138 221 267 273 (br) 277 312 553 736 1132 1251 1278 1283 1298

1366 1436 1494 1586 11


3742417 Found 3742410

Chapter 3

80

BO

Ph

Et

CF3

5b


437-443 (m 1H) 718-726 (m 3H) 734-739 (m 2H) 745-748 (m 2H) 760-763

(m 2H) 13

C NMR = 135 220 266 271 (br) 276 312 738 12429 (q JC-F =

2701 Hz) 1247 (q JC-F = 36 Hz) 1280 1281 1289 (q JC-F = 320 Hz) 1291 1425

1476 1480 11


Found 4122186

BO

Ph

Et

NPhth

5c


440-450 (m 1H) 720-727 (m 3H) 734-739 (m 2H) 743-751 (m 4H) 777-783

(m 2H) 794-800 (m 2H) 13

C NMR = 137 221 266 274 (br) 275 312 738

1235 1254 1258 1279 1282 1294 1304 1317 1342 1429 1440 1482

1671 11

B NMR = 502 IR (KBr) = 2928 1742 1509 1381 714 cm-1

HRMS (EI)


BO

Ph

Et

5d

1H NMR = 021-034 (m 1H) 068-100 (m 8H) 120-150 (m 7H) 224-238 (m

1H) 244-258 (m 1H) 424-431 (m 1H) 722-754 (m 9H) 778 (d J = 78 Hz 1H)

783-788 (m 1H) 809-816 (m 1H) 13

C NMR = 137 216 219 259 262 264

(br) 282 309 314 734 1249 12537 12539 1255 1264 1270 1273 12795

Chapter 3

81

12799 1283 1321 1335 1413 1427 1467 11


for C28H31BO (M+) 3942468 Found 3942476

BO

Ph

Et

5e

S


448-456 (m 1H) 702 (dd J = 51 36 Hz 1H) 708 (dd J = 36 12 Hz 1H)

715-730 (m 4H) 732-738 (m 2H) 13

C NMR =141 221 271 289 312 739

1250 1255 1266 1269 1279 1281 1416 1427 1468 11

B NMR = 496


BO

n-Pr

Me

Cl

5f

1H NMR = 070 (t J = 75 Hz 3H) 096-133 (m 9H) 142-172 (m 6H) 220-228

(m 2H) 237 (s 3H) 439-446 (m 1H) 708-735 (m 8H) 13

C NMR = 140 212

219 221 267 274 (br) 313 363 737 1279 12846 12855 1298 1309 1365

1411 1420 1488 11


4062235 Found 4062237

BO

n-Pr

Ph

OMe

5g

Chapter 3

82


(s 3H) 435-450 (m 1H) 690 (d J = 81 Hz 2H) 711 (d J = 81 Hz 2H) 720-740

(m 5H) 13

C NMR = 140 219 221 267 274 (br) 312 362 551 736 1133

1267 1278 1287 1294 1354 1446 1475 1573 11




BO

Ph

S

5h

1H NMR = 027-032 (m 2H) 046-052 (m 2H) 098-130 (m 6H) 140-170 (m

8H) 430-445 (m 1H) 696-700 (m 1H) 704-707 (m 1H) 715-726 (m 2H)

729-738 (m 4H) 13

C NMR = 60 150 222 263 272 (br) 313 736 1241

1243 1253 1278 1290 1295 1410 1425 1431 11



BO

Ph

CO2Et

5i

1H NMR = 017-023 (m 2H) 045-053 (m 2H) 090-119 (m 6H) 132-173 (m

11H) 427-433 (m 1H) 438 (q J = 75 Hz 2H) 718-738 (m 7H) 798 (dt J = 78

15 Hz 2H) 13

C NMR = 56 144 151 220 263 269 (br) 312 609 735 1255

1279 1284 1287 1289 1303 1423 1453 1469 1665 11

B NMR = 496 IR

(KBr) = 2928 1717 1287 1100 cm-1


Found 4282526

BO

Ph

5j

Cl

Chapter 3

83

1H NMR = 023-029 (m 2H) 048-055 (m 2H) 094-123 (m 6H) 134-171 (m

8H) 432-439 (m 1H) 706-714 (m 1H) 718-726 (m 4H) 728-738 (m 4H) 13

C

NMR = 57 150 220 263 271 (br) 312 736 1255 1267 1279 1283 1284

1289 1304 1332 1423 1424 1461 11


C25H28BClO (M+) 3901922 Found 3901923

BO

Ph

5k

Me

1H NMR = 082-113 (m 6H) 126-164 (m 15H) 237 (s 3H) 268-280 (m 1H)

434-441 (m 1H) 704-709 (m 3H) 717-725 (m 4H) 730-737 (m 2H) 13

C NMR

= 215 219 248 263 273 (br) 312 315 433 735 1252 12689 12693 1275

1278 1283 1316 1365 1418 1424 1481 11


for C28H35BO (M+) 3982781 Found 3982780

BO

Cl

S

Ph

5l

1H NMR = 106-176 (m 13H) 250-260 (m 2H) 272-280 (m 2H) 441-449 (m

1H) 674 (dd J = 33 12 Hz 1H) 697-703 (m 3H) 709-738 (m 8H) 13

C

NMR(C6D6) =225 272 277 (br) 315 358 375 739 1247 1253 1261 1272

1285 12856 12861 1306 1335 1419 1427 1437 1491 11

B NMR = 495


BO

Ph

CF3

TBSO

5m

Chapter 3

84

1H NMR = -014 (s 6H) 079 (s 9H) 095-136 (m 6H) 142-168 (m 7H) 255 (t

J = 72 Hz 2H) 343 (t J = 72 Hz 2H) 435-442 (m 1H) 718-726 (m 3H)

731-737 (m 2H) 747 (d J = 81 Hz 2H) 759 (d J = 81 Hz 2H) 13

C NMR = -54

183 220 259 266 271 (br) 311 377 616 739 1242 (q JC-F = 2694 Hz) 1247

(q JC-F = 36 Hz) 1258 1280 1282 1290 (q JC-F = 320 Hz) 1291 1421 1422

1480 11



BO

Ph

Me

OMe

5n

1H NMR = 122-130 (m 4H) 138-162 (m 5H) 168-186 (m 4H) 237 (s 3H)

375 (s 3H) 443-450 (m 1H) 670 (dt J = 90 21 Hz 2H) 690-697 (m 4H)

702-708 (m 3H) 710-720 (m 4H) 13

C NMR = 213 222 269 312 550 738

1132 1260 1272 1285 1301 1307 1310 1362 1369 1423 1429 1483

1571 11


4362561


4-Bromobenzene

B

Ph

Et

+


toluene 70 degC

Me3NO BO

Ph

Ph

Et

(Z)-5o

1a

Ph Br

[Me4N]




Chapter 3

85






BO

Ph

Ph

Et


470-475 (m 1H) 685-710 (m 10H) 13

C NMR = 139 224 267 313 317 740

1248 1257 1272 127412938 12941 1421 1425 1275 11

B NMR = 512


BO

Ph

Et

Ph


438-443 (m 1H) 718-737 (m 10H) 13

C NMR = 137 221 266 274 (br) 277

312 737 1253 1268 1278 1279 1283 1288 1433 1442 1494 11

B NMR =



Bromide 2b

+

Br

ONMe2

Ph

Et

PhO

NMe2


THF K3PO4 60 degC

(Z)-Tamoxifen 6

2b

BO

Ph

Et

Ph

(E)-5o

Chapter 3

86









Chapter 3

87



2003 Vol 3








Rev 2006 250 1107









1976 108 281








74





Chapter 3

88





















2006 128 1828




Chapter 4

89

Chapter 4



Abstract






Chapter 4

90

Introduction





























Chapter 4

91


B

MOMO

[Me4N] +

MeO

Br

I

Br

MeO Br

B

MeO

MOMO MOMO

1a

2 3 87EZ = lt199

NaOH

50 degC

1 mol


toluene 50 degC
















procedure

Chapter 4

92



An











3

MeO

R

Br

4 92

R

MeO

R

Br

n = 2 5 87

n = 3 6 82n = 4 7 85

n

R

1 mol


toluene 50 degC

I

Br

NaOH

E

EE

R = OMOM








Chapter 4

93





Br

Br

R

R

Br

Br

8 86

R

R

Br

R

R

Br

9 92

E E

R = OMOM















Chapter 4

94


Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

Me3Si

Br

Ph

F

Me3Si

OMe

Br

Ph

F

S

Br

Me3Si

OMe

B

n-Pr

[Me4N]

Cl

B

Ph

[Me4N]

OMe

Br

S

Br

I

EtO2C

MOMO

MOMO

I

Br

F

1b

10 88

11 84

12 88

1a1c

cat Pd

NaOHcat Pd

cat Pd NaOH

Cs2CO3

Conclusions







Chapter 4

95




1H at 500 MHz and






13C) CD3CN ( = 194 for

1H =132 for

13C) and

BF3OEt2 ( = 000 for 11











11













Chapter 4

96

B

MOMO

[Me4N]

1a


202 (t J = 66 Hz 2H) 236-251 (m 2H) 304 (s 12H) 328 (s 3H) 346 (t J = 69

Hz 2H) 454 (s 2H) 678-685 (m 1H) 698-705 (m 2H) 734 (d J = 72 Hz 2H) 13

C NMR (CD3CN 75 MHz) = 210 267 (br) 271 275 282 297 324 349 551

561 681 928 968 1221 1269 1338 11



B

Ph

[Me4N]

1b

OMe


225 (t J = 72 Hz 2H) 234-249 (m 2H) 263 (t J = 72 Hz 2H) 303 (s 12H) 372

(s 3H) 663-669 (m 2H) 711-728 (m 7H) 13


272 275 324 349 381 554 560 1129 1266 1289 1298 1346 1434 1563 11


3572390 Found 3572383



B

MOMO

[Me4N]

+

MeO

Br

1 mol


toluene 50 degC

I

Br

MeO Br

NaOH

3

1a

MOMO

Chapter 4

97








MeO Br

3

MOMONOE

NOE




(t J = 66 Hz 2H) 376 (s 3H) 452 (s 2H) 667-675 (m 4H) 697-702 (m 2H)

709-736 (m 7H) 13

C NMR (75 MHz) = 255 298 356 5510 5514 676 964

1134 1196 1267 1282 1294 13046 13049 1323 1339 1376 1408 1420



spectroscopy

MeO

R

Br

4

R

R = OMOM




Chapter 4

98


2H) 325 (s 3H) 329 (s 3H) 331-341 (m 4H) 380 (s 3H) 451 (s 2H) 453 (s

2H) 662-678 (m 8H) 697-703 (m 2H) 706-738 (m 12H) 13

C NMR (150 MHz)

= 252 254 295 296 353 354 5502 5504 552 675 676 9629 9632 1131

1196 1265 1267 1281 1282 1285 12941 12942 1303 1304 1306 1324

1343 1377 1385 1390 1400 1413 1414 1418 1429 1435 1579 HRMS


7972818 Found

7972849

MeO

R

5

R

R = OMOM

R

Br




325 (s 3H) 327 (s 3H) 328 (s 3H) 330-342 (m 6H) 374 (s 3H) 450 (s 2H)

452 (s 2H) 454 (s 2H) 654-662 (m 4H) 666-678 (m 8H) 696-704 (m 4H)

712-737 (m 15H) 13

C NMR (75 MHz) = 254 256 296 297 298 3526 3534

355 551 675 676 963 1130 1196 1264 1267 1280 1281 1286 1294 1301

1302 1304 1306 1324 1344 1377 1384 1387 1392 1393 1398 1402 1409



10914437 Found 10914482

Chapter 4

99

MeO

R

6

R

R = OMOM

R

R

Br




330-341 (m 8H) 371 (s 3H) 448-454 (m 8H) 648-675 (m 16H) 695-703 (m

4H) 714-737 (m 20H) 13

C NMR (75 MHz) = 253 254 256 257 2969 2974

298 350 354 356 550 551 675 676 963 1131 1196 1264 1267 1279

1280 1281 1283 1288 1293 1294 1300 1301 1302 1305 1306 1323 1342

1377 1385 1387 1389 1391 1394 1396 1397 1401 1405 1409 1411 1413



13856057 Found 13856062

MeO

R

7

R

R = OMOM

R

R

R

Br




374 (s 3H) 447-452 (m 10 H) 649-679 (m 20 H) 690-695 (m 2H) 701-706 (m

2H) 710-736 (m 25H) 13

C NMR (75 MHz) = 2529 2535 256 257 2968

Chapter 4

100

2971 298 351 354 355 356 550 6746 6755 676 963 1131 1195 1264

1267 12795 1280 1281 1283 1285 1287 1293 12937 12944 1301 1302

1304 1306 1322 1343 1377 1384 1387 1389 1390 1391 1394 13976

13979 1401 1404 1408 1409 1412 1413 1416 1427 14318 14321 1434


16797677 Found 16797694

8

R

Br

R

Br

R = OMOM





(t J = 66 Hz 4H) 456 (s 4H) 668-673 (m 4H) 691 (s 4H) 710-721 (m 8H)

722-737 (m 6H) 13

C NMR (75 MHz) = 254 297 354 551 676 963 1198

1268 1282 1291 1293 1303 1323 1380 1400 1411 1417 1427 HRMS


8221905

9

R

R

R = OMOM

R

R

Br

Br



Chapter 4

101


6H) 330-340 (m 8H) 446 (s 4H) 453 (s 4H) 656-672 (m 12H) 688 (s 4H)

704-710 (m 4H) 714-718 (m 4H) 722-740 (m 16H) 13

C NMR (150 MHz) =

254 2962 2963 356 357 5501 5503 674 676 9629 9631 1197 1266

1268 1281 12818 12822 1290 1295 1296 1304 1308 1324 1379 1385

1394 1403 1405 1409 1416 1417 1427 1434 HRMS (MALDI-TOF-MS


14335057 Found 14335040

Ph

F

Me3Si

OMe

Br

10

NOE

NOE





3H) 676-686 (m 3H) 694-707 (m 6H) 709-728 (m 5H) 734 (d J = 84 Hz 2H) 13

C NMR (150 MHz) = -11 349 372 552 1135 1189 (d JC-F = 255 Hz)1202

(d JC-F = 92 Hz) 1258 1268 (d JC-F = 35 Hz) 1280 1283 1284 1300 1304 (d

JC-F = 159 Hz) 1326 1329 1332 (d JC-F = 45 Hz) 1339 1387 1417 1418 1430




Chapter 4

102

Ph

F

S

Br

Me3Si

OMe

11

MOMO




= 78 2H) 264-272 (m 2H) 282-289 (m 2H) 325 (s 3H) 328 (t J = 66 Hz 2H)

382 (s 3H) 448 (s 2H) 587 (d J = 39 Hz 1H) 660 (d J = 39 Hz 1H) 669-676

(m 2H) 684-696 (m 3H) 705-742 (m 16H) 13

C NMR (150 MHz) = -10 244

293 351 362 372 550 552 673 963 1127 1135 1161 (d JC-F = 225 Hz)

1244 (d JC-F = 32 Hz) 1258 1274 12827 12831 12837 12840 12856 12861

1295 1302 1307 (d JC-F = 155 Hz) 1324 1329 1330 (d JC-F = 45 Hz) 1333

1345 1385 1395 (d JC-F = 12 Hz) 1412 1416 (d JC-F = 80 Hz) 1419 1422



Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

12MOMO




mmol) t1 10 h t2 12 h

Chapter 4

103


210-224 (m 4H) 264-272 (m 2H) 279-287 (m 2H) 323-333 (m 5H) 373 (s


1H) 666-672 (m 2H) 679-694 (m 5H) 703-737 (m 20H) 773 (d J = 84 Hz

2H) 13

C NMR (150 MHz) = -11 141 143 225 244 293 350 359 370 385

550 551 607 674 963 1134 1159 (d JC-F = 224 Hz) 1243 (d JC-F = 29 Hz)

1258 1269 1271 12808 12811 12815 12820 12823 12838 12844 1290

1293 1300 1301 (d JC-F = 158 Hz) 1302 1307 1323 (d JC-F = 47 Hz) 13258

13261 1328 1336 1344 1356 1379 1382 1390 (d JC-F = 12 Hz) 1409 14190

14191 14216 (d JC-F = 80 Hz) 14219 14222 1438 1446 1476 1583 1600 (d

JC-F = 2448 Hz) 1664 IR (KBr) = 2955 1717 1509 1273 1248 1111 837 cm-1


11294440

Found 11294465

Chapter 4

104




Chem 1999 201 163




897















2404


2006 128 1828



Chapter 5

105

Chapter 5




Abstract






Chapter 5

106

Introduction





moiety1b


























Chapter 5

107


B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

OHMe

Ph

1a

3a 85

MeO

OMe

2a

B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

1b

OMe

2a

OHMe

Ph

OMe

3b 88

[Me4N]

[Me4N]




Oxidative









Chapter 5

108


O

I

O

PdI

Pd(0)

B

1a

C

Pd(0)3a

Ar = p-MeOC6H4-

Me Me

OMe

Ar

Ph

B

D

A

Pd

O

ArB

Me

Ph

B

O

ArPh

Me

Me4NI

2a







Chapter 5

109


R3

O

I

B

R2

R1

+1 mol Pd

toluene50 degC 1 h

OHR3

R1

R2

OHMe

Ph

S

OHMe

OMe

OHPh

Ph

OMe

3f 72

3h 763j 80

3g 84

3d 82

3c 83

OHMe

Ph

CF3

1 2 3

OHH

Ph

OMe

OHPh

Ph

OMe

O

O

OHPh

3e 92

F

OMe

OHPh

Ph

OMe

F3C

3i 62

R4R4

MeO

[Me4N]










Chapter 5

110

OHMe

t-Bu

S

3k 89

B +1 mol Pd

toluene

50 degC 1 h

2a

t-Bu

S

(1)

1c

[Me4N]

OHMe

n-Bu

Me

3l 80

B

n-Bu

+1 mol Pd

toluene50 degC 1 h

2a

Me

(2)

1d

[Me4N]










n-Hex

13 equiv

Ph

Li

065 equiv

(H-9-BBN) 2


1 mol Pd

toluene 50 degC 1 h

10 equiv 2aOH

Me

n-Oct

11 equiv

3m 91 (based on 2a)

B

n-Oct

PhLi

Ph




Chapter 5

111


in 59 yield11


OHH

Ph

OMe

MnO2

DCM rt

Ph

OMe

O

NH2NH2 KOHPh

OMe

4 96 5 59

3n 74

(CH2OH)2 150 C

1a +

CHO

I2b

1 mol Pd

Conclusions




Chapter 5

112



and 13


B at 128 MHz)



13C) CD3CN (δ = 194 for

1H δ = 132 for


11B) IR






(Merck)





and alkynylborate14




Li

BPh

+

B

Ph

1a


2) Me4NCl MeOH

[Me4N]

MeO

MeO










Chapter 5

113

B

Ph

1a

[Me4N]

MeO


(m 2H) 296 (s 12H) 372 (s 3H) 668-675 (m 2H) 685-691 (m 1H) 700-712 (m

4H) 743 (d J = 64 Hz 2H) 13

C NMR (CD3CN) δ = 256-272 (m) 270 274 322

350 557 560 955 1145 1227 (2C) 1273 1324 1341 1578 The boron-bound


11B NMR


3292079

B

Ph

1b

[Me4N]

OMe


(m 2H) 295 (s 12H) 374 (s 3H) 666-675 (m 2H) 702-718 (m 5H) 733 (d J =

84 Hz 2H) 13

C NMR (CD3CN) δ = 254-274 (m) 270 273 321 350 554 560





B

nBu

1d

[Me4N]

Me


(m 4H) 136-157 (m 6H) 170-196 (m 4H) 220-234 (m 5H) 304 (s 12H)

697-701 (m 2H) 704-709 (m 2H) 13

C NMR (CD3CN) δ = 152 212 270

271-290 (m) 282 288 318 324 357 561 1279 1296 1314 1344 The

Chapter 5

114




[M-(NMe4)]- 2932446 Found 2932454

B

Ph

1e

[Me4N]

F3C


(m 2H) 292 (s 12H) 690-696 (m 1H) 710-718 (m 2H) 728 (dd J = 88 08 Hz

2H) 744-752 (m 4H) 13

C NMR (CD3CN) δ = 252-270 (m) 269 273 321 351






B

Ph

1f

[Me4N]

S



48 32 Hz 1H) 703-719 (m 6H) 13

C NMR (CD3CN) δ = 266 272 270-286 (m)

323 348 560 962 1231 1256 1266 1274 1290 1300 1314 The boron-bound

sp2 and sp


11B NMR


- 3051541 Found

3051541

Chapter 5

115


(H-9BBN) 2

H tBu

THF 0 degC

THF -78 degC to rt

2) Me4NCl MeOH

Li

1)S

B

1c

[Me4N]

S

tBu














B

1c

[Me4N]

S

tBu


4H) 222-235 (m 2H) 306 (s 12H) 552 (d J = 172 Hz 1H) 591 (d J = 176 Hz


Hz 1H) 13

C NMR (CD3CN) δ = 273 276 278-296 (m) 311 327 341 352 561





Chapter 5

116












OHMe

3aOMe

NOE

no NOE

IR (ATR) 3315 1508 1248 752 694 cm-1

1H NMR δ = 159 (s 3H) 204 (bs 1H)

382 (s 3H) 684-690 (m 2H) 721-730 (m 8H) 742-748 (m 2H) 751-755 (m

1H) 13

C NMR δ = 239 552 832 1139 1208 1218 1265 1268 1272 1280


C23H21O2 [M+H]+ 3291536 Found 3291556

OHMe

OMe

3b

NOE

no NOE

IR (ATR) 3319 1508 1248 760 702 cm-1

1H NMR δ = 160 (s 3H) 208 (s 1H)

378 (s 3H) 674-680 (m 2H) 718-723(m 1H) 724-744 (m 9H) 750-755 (m

1H) 13

C NMR δ = 241 551 833 1134 1205 1218 1263 1270 1274 1284


Chapter 5

117

C23H20O2Cl [M+Cl]- 3631146 Found 3631148

OHMe

Ph

3cCF3

IR (ATR) 3298 1319 1121 750 696 cm-1

1H NMR δ = 160 (s 3H) 210 (bs 1H)

716-722 (m 1H) 723-732 (m 5H) 737-747 (m 4H) 752-764 (m 3H) 13

C NMR

δ = 240 833 1205 1221 1241 (q JC-F = 2701 Hz) 1255 (q JC-F = 37 Hz) 1269

1277 1282 1286 1293 1295 (q JC-F = 322 Hz) 1296 1341 1373 1385 1414


- 3651159 Found 3651159

OHMe

Ph

3d

S

IR (ATR) 3319 1350 1088 752 694 cm-1

1H NMR δ = 177 (s 3H) 209 (bs 1H)

696-702 (m 2H) 718 (dd J = 52 Hz 12Hz 1H) 723-730 (m 2H) 735-740 (m

3H) 742-752 (m 3H) 753-758 (m 1H) 13

C NMR δ = 254 833 1207 1216

1259 1265 1266 1275 1282 1287 1290 1294 1347 1360 1374 1410 1426


+ 3050995 Found 3050992

OHMe

OMe

3e

IR (ATR) 3310 1508 1244 1034 758 cm-1

1H NMR δ = 144 (s 3H) 158-202 (m


5H) 747 (d J = 68 Hz 1H) 13

C NMR δ = 238 266 267 305 311 382 552

822 1136 1211 1219 1257 12789 12793 1304 1406 1409 1467 1499


+ 3382115 Found 3382104

Chapter 5

118

OHH

Ph

3fOMe

MeO

IR (ATR) 3472 1601 1508 1244 704 cm-1

1H NMR δ = 174 (d J = 88 Hz 1H)


= 80 Hz 24 Hz 1H) 692-697 (m 2H) 718-730 (m 5H) 732-736 (m 2H) 753 (d

J = 84 Hz 1H) 13

C NMR δ = 552 555 766 1072 1109 1143 1244 1267 1272

1283 1292 1303 1342 1363 1390 1445 1457 1592 1606 HRMS (ESI+)


OHPh

Ph

3gOMe

IR (ATR) 3422 1508 1244 1028 746 698 cm-1

1H NMR δ = 248 (s 1H) 385 (s

3H) 695 (d J = 88 Hz 2H) 704-714 (m 5H) 715-732 (m 7H) 736-740 (m 2H)

755 (d J = 88 Hz 2H) 13

C NMR δ = 552 868 1141 1210 1231 1250 1268

12698 12702 1271 1278 12836 12844 1294 1304 1340 1402 1417 1427


+ 3911693 Found

3911718

OHPh

Ph

3hOMe

O

O

IR (ATR) 3362 1470 1244 1034 696 cm-1

1H NMR δ = 239 (s 1H) 385 (s 3H)

591 (dd J = 164 16 Hz 2H) 673 (d J = 44 Hz 2H) 690-696 (m 2H) 702-708

(m 5H) 720-736 (m 5H) 749-754 (m 2H) 13

C NMR δ = 552 863 1012 1024

Chapter 5

119

1049 1142 1249 12690 12692 1270 1278 1285 1292 1304 1340 1367


+

4341518 Found 4341505

OHPh

Ph

3iOMe

F3C

IR (ATR) 3545 1508 1321 1115 696 cm-1

1H NMR δ = 249 (s 1H) 387 (s 3H)

694-700 (m 2H) 704-715 (m 5H) 723-738 (m 6H) 742-755 (m 4H) 13

C NMR

δ = 553 866 1145 1177 (q JC-F = 37 Hz) 1233 1241 (q JC-F = 36 Hz) 1242 (q

JC-F = 2702 Hz) 1249 1260 1275 1276 1280 1287 1295 1304 1308 (q JC-F =


C29H21F3O2Cl [M+Cl]- 4931177 Found 4931192

OHPh

3j

F

OMe

IR (ATR) 3356 1242 1028 741 696 cm-1

1H NMR δ = 164-178 (m 2H) 183-208


4H) 719-737 (m 6H) 13

C NMR δ = 2675 2681 308 310 383 551 862 1114


1268 1271 1283 1303 1371 (d JC-F = 29 Hz) 1410 1418 (d JC-F = 15 Hz)



+ 4001839 Found 4001835

OHMe

S

tBu

3k

Chapter 5

120

IR (ATR) 3298 1358 1078 756 689 cm-1

1H NMR δ = 111 (s 9H) 168 (s 3H)

188 (s 1H) 640 (d J = 164 Hz 1H) 656 (d J = 164 Hz 1H) 718-730 (m 4H)

739-751 (m 3H) 13

C NMR δ = 257 295 340 822 1169 1204 1215 1242

1255 1262 1283 1285 1324 1346 1415 1452 1462 1506 HRMS (ESI+)


OHMe

nBu

OMe3l

IR (ATR) 3335 1508 1084 918 758 cm-1

1H NMR δ = 085 (t J = 72 Hz 3H) 130

(tt J = 72 72 Hz 2H) 141-167 (m 6H) 229-250 (m 5H) 702-706 (m 1H)

716-728 (m 6H) 744-748 (m 1H) 13

C NMR δ = 138 213 232 237 252 314

829 1198 1215 1256 1282 1286 1291 1318 1370 1374 1430 1492 1496


+ 2931900 Found 2931890



nHex

(H-9BBN) 2


Li

Ph

B

nOct

Li

Ph

Me

O

I


toluene 50 degC 1 h

H2O2 aq

NaOH aq

OHMe

nOct

Ph3m

MeOH




Chapter 5

121













yield)

OHMe

nOct

Ph3m

IR (ATR) 3335 1456 1078 752 698 cm-1

1H NMR δ = 096 (t J = 68 Hz 3H)

129-156 (m 15H) 160 (s 1H) 208-227 (m 2H) 274-281 (m 2H) 287-294 (m

2H) 719-728 (m 5H) 729-736 (m 3H) 742 (d J = 72 Hz 1H) 13

C NMR δ = 141

226 234 247 277 293 294 295 304 319 345 825 1186 1213 1252 1260


[M]+ 3622610 Found 3622619

OHH

Ph

OMe

3n

IR (ATR) 3354 1508 1246 764 692 cm-1

1H NMR δ = 185 (bs 1H) 386 (s 3H)

567 (s 1H) 692-697 (m 2H) 718-738 (m 10H) 763-766 (m 1H) 13

C NMR δ =

552 773 1143 1206 1237 1263 1268 1272 1283 1287 1292 1303 1342


- 3131234

Found 3131237

Chapter 5

122

The 1H


15


OHH

Ph

OMe

3n

MnO2

DCM rt

Ph

OMe

4

O







The 1H


16

Ph

OMe

4

O

(CH 2OH)2

NH2NH2

KOH Ph

OMe

5








The 1H


5

Chapter 5

123






1395ndash1411



17638ndash17640





3201ndash3222



















Chapter 5

124












3283ndash3292









74








Chem 1989 54 1485ndash1491



2006 128 1828

Chapter 5

125



4781-4787


Chem 1989 54 1485

Chapter 5

126

127

List of Publication

Chapter 1



Angew Chem Int Ed 2012 51 11750-11752

Chapter 2


Benzosultams


J Am Chem Soc 2013 135 19103-19106

Chapter 3





Org Lett 2009 11 5434-5437

Chapter 4


Units


Org Lett 2010 12 3179-3181

Chapter 5




Eur J Org Chem 2013 1421-1424

Other Publication




Chem Lett 2013 42 1076


2


benzosultams




developed456


shift7

MH14-metal shift

1

2 3

4

HM

1

2 3

4

H M1

23

4

5

M H1

23

4

515-metal shift






N

Ts

Ph OHMe

SN

MeO O

Ph OH

cat Rh





chemistry10






We


alkynylborates13

R1 B

R2

R2

R2

+ R3 Br

R3

R1 R2

B

R2

R2


3






obtained

Et

Ph

Ph

B O+

PhBr LPd(-allyl)Cl

L = XANTPhos

LPd(-allyl)Cl

L = P(o-tol)3 Ph

Et

Ph

B O

B

Et

Ph

Et

Ph

B

Ph

Ph

Et

B

Ph

Me3NO

Me3NO

[Me4N]







MeO

Br

I

Br

NaOH

R Ph

MeO Br

B

R

Ph

RB

Ph

OMe

[Me4N]

R Ph

MeOR Ph

Br

R =OMOM

n

B

R

Ph

[Me4N] I

Br

NaOH

R Ph

MeOR Ph

Br

n = 2~4

Pd-XANTPhos

Pd-XANTPhos






4


regioselectively

I

Me

O+

MeOH

R2

R1Pd-XANTPhosB

R2

R1

[Me4N]


5

Reference





































6








10990




2003 Vol 3





Q Z J Med Chem 2009 52 4192



2006 250 1107



2419













7



17638ndash17640


8

Chapter 1

9

Chapter 1


Ketones

Abstract






Chapter 1

10

Introduction







2 One







starting substances


CO2

sun

CO2energy charge

high energy

intermediates











8






Chapter 1

11


Ph

O

NTs

Mesolar light

N

Ph OH

Ts

2a 91

1aDMA







over 04 kWm-2



in eight hours on


Figure





kWhm-2



Chapter 1

12


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

0

20

40

60

80

100

0 1 2 3 4 5 6











(56)

Chapter 1

13


40 equiv Cs2CO3

1 atm CO2

DMA 60 degC

OO

O

Ph

NHTs

3a 93

N

Ph OH

Ts

2a








N

Ph O

Ts

A

N

Ph O

Ts

B

O

O

OO

O

Ph

NTs

CO2

H

C

Cs2CO3

CsHCO 3

Cs

Cs

Cs

2

1

N

Ph OH

Ts

2a

OO

O

Ph

NHTs

3a












N

Ts

OHPh

4

Chapter 1

14




solar light

CO2Cs2CO3

60degCDMAPh

O

NTs

Me

1a

OO

O

Ph

NHTs

3a 83






chloro groups10





Ar

O

NR

Me OO

O

Ar

NHR3

1

OO

O

NHTs3b 80

MeO

OO

O

NHTs3c 57

F3C

OO

O

NHTs3d 73

Cl

OO

O

NHTs3e 85

Br

OO

O

Ph

NH

3f 87

O2S OMe

OO

O

Ph

NH

3g 85

O2S CF3

OO

O

Ph

NH

3h 87

O2S

N

solar lightCO2

Cs2CO3

60degCDMA




Chapter 1

15

Conclusions















Chapter 1

16












indicator (Merck)






Ph

O

NTs

MeTsClMeNH2 +

Et2OTsNHMe

CH3CN

K2CO3












Chapter 1

17


Ph

O

NTs

Me


745-751 (m 2H) 760 (tt J = 76 12 Hz 1H) 771-775 (m 2H) 795-799 (m 2H)

13C NMR δ = 215 356 560 1275 1282 1288 1297 1338 1347 1348 1436


+ 3041002 Found mz 3040994 IR

(ATR) 1693 1339 1227 1157 743 cm-1

O

NTs

Me

1bMeO


733 (d J = 80 Hz 2H) 770-774 (m 2H) 796-802 (m 2H) 13

C NMR δ = 215

355 555 558 1139 1275 1277 1296 1307 1346 1436 1640 1921 HRMS


+ 3341108 Found mz 3341101 IR (ATR) 1688

1601 1329 1180 1159 cm-1

O

NTs

Me

1cF3C


= 84 Hz 2H) 776 (d J = 84 Hz 2H) 812 (d J = 84 Hz 2H) 13

C NMR δ = 215

357 564 1234 (q JC-F = 2711 Hz) 1259 (q JC-F = 37 Hz) 1276 1288 1298



1121 1109 cm-1

Chapter 1

18

O

NTs

Me

1dCl


(m 2H) 771 (d J = 80 Hz 2H) 792-796 (m 2H) 13

C NMR δ = 216 356 561



1159 1088 cm-1

O

NTs

Me

1eBr


= 84 Hz 2H) 771 (d J = 84 Hz 2H) 786 (d J = 84 Hz 2H) 13

C NMR δ = 215

356 561 1275 1291 1297 1298 1321 1334 1344 1438 1930 HRMS (ESI+)


1223 1155 810cm-1

Ph

O

NS

Me

1f

OMe

OO

1H NMR δ = 282 (s 3H) 389 (s 3H) 456 (s 2H) 698-703 (m 2H) 746-751 (m

2H) 761 (tt J = 72 12 Hz 1H)776-781 (m 2H) 796-800 (m 2H) 13

C NMR δ =

356 556 561 1142 1283 1288 1294 1297 1338 1348 1630 1938 HRMS


+ 3200951 Found mz 3200943 IR (ATR) 1692

1342 1259 1155 741 cm-1

Chapter 1

19

Ph

O

NS

Me

1g

CF3

OO


780 (d J = 84 Hz 2H) 790-794 (m 2H) 798 (d J = 80 Hz 2H) 13

C NMR δ =

356 558 1233 (q JC-F = 2711 Hz) 1261 (q JC-F = 36 Hz) 12796 12799 1289



1059 748 cm-1

Ph

O

NS

Me

1h

N

OO

1H NMR δ = 302 (s 3H) 486 (s 2H) 744-753 (m 3H) 757-762 (m 1H)

788-798 (m 4H) 870 (ddd J = 48 16 08 Hz 1H)13

C NMR δ = 363 569 1224



752 cm-1


Ph

O

NTs

Mesolar light

N

Ph OH

TsDMA rt

1a

2a








Chapter 1

20


N

Ph OH

Ts


2H) 728-737 (m 5H) 740 (d J = 80 Hz 2H) 779 (d J = 80 Hz 2H) 13

C NMR δ

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS




N 458 O 1555 S 1058 IR (ATR) 3477 1333 1184 1148 671 cm-1


N

Ph OH

Ts

2a

40 equiv Cs2CO3

1 atm CO2

DMA 60 C

OO

O

Ph

NHTs

3a








mmol 93 yield)

Chapter 1

21



40 equiv Cs2CO3

60 CPh

O

NR

Me OO

O

Ph

NHR3a

1a

solar light

DMA rt

1 atm CO2











OO

O

Ph

NHTs



726-732 (m 4H) 734-743 (m 3H) 769-773 (m 2H) 13

C NMR δ = 215 503

724 850 1242 1269 1292 1299 1365 1381 1439 1542 HRMS (ESI+) Calcd

for C17H18NO5S M+H+


C 5878 H 493 N 403 O 2303 S 923 Found C 5871 H 496 N 389 O

2284 S 932 IR (ATR) 3261 1773 1435 1319 1045 cm-1

Chapter 1

22

OO

O

NHTs

3b

MeO



56 Hz 1H) 688-693 (m 2H) 719-724 (m 2H) 728 (d J = 80 Hz 2H) 770 (d J =

84 Hz 2H) 13

C NMR δ = 215 503 554 724 848 1145 1256 1269 1298


+

3781006 Found mz 3780996 IR (ATR) 3238 1794 1518 1329 1057 723 cm-1

OO

O

NHTs

3c

F3C



729 (d J = 84 Hz 2H) 746 (d J = 84 Hz 2H) 765-771 (m 4H) 13

C NMR δ =

215 501 722 846 1235 (q JC-F = 2704 Hz) 1249 1263 (q JC-F = 37 Hz) 1268



1067 cm-1

OO

O

NHTs

3d

Cl



722-727 (m 2H) 728 (d J = 84 Hz 2H) 735-739 (m 2H) 769 (d J = 84 Hz 2H)

13C NMR δ = 215 502 723 847 1257 1268 1294 1300 1353 1364 1365


+ 3820510 Found mz

Chapter 1

23

3820506 IR (ATR) 3250 1800 1325 1155 1069 cm-1

OO

O

NHTs

3e

Br



716-720 (m 2H) 728 (d J = 80 Hz 2H) 750-755 (m 2H) 766-770 (m 2H) 13

C

NMR δ = 215 501 723 847 1235 1260 1268 1300 1323 1364 1370 1441


+ 4260005 Found mz 4260003

IR (ATR) 3252 1800 1331 1175 1057 cm-1

OO

O

Ph

NH

SO

O

OMe



693-698 (m 2H) 727-732 (m 2H) 734-744 (m 3H) 773-778 (m 2H) 13

C NMR

δ = 503 556 724 849 1145 1242 1291 1292 1310 1381 1541 1632 HRMS


+ 3640849 Found mz 3640836 IR (ATR) 3246

1801 1325 1155 1067 cm-1

OO

O

Ph

NH

SO

O

CF3

3g

Chapter 1

24



2H) 735-744 (m 3H) 775 (d J = 88 Hz 2H) 796 (d J = 84 Hz 2H) 13

C NMR δ

= 505 725 851 1231 (q JC-F = 2711 Hz) 1241 1265 (q JC-F = 37 Hz) 1274



1161 1105 cm-1

OO

O

Ph

NH

SO

O

N




1H) 798 (d J = 76 Hz 1H) 866 (d J = 44 Hz 1H) 13

C NMR δ = 510 723 849



1175 1063 cm-1


N

Ts

OHPh

N

Ts

O CeCl 3

PhLi

THF -78 C to rt

4






Chapter 1

25






N

Ts

OHPh


351-364 (m 4H) 726-738 (m 7H) 773-777 (m 2H) 13

C NMR δ = 215 396

469 608 804 1250 1276 1280 1286 1297 1339 1418 1435 HRMS (ESI+)


1325 1159 1101 770 cm-1

Chapter 1

26











Soc 2011 133 12881

























25 312

Chapter 1

27








Chapter 1

28

Chapter 2

29

Chapter 2



Abstract







Chapter 2

30

Introduction














A



Indanones are


A rearrangement













Whereas







Chapter 2

31




N

HO Ph

S NS Me

HO PhMe

1a2a 96

Me

O

OO O


2) is





The generated








N

S O

O

O[Rh]

Ph

SN

[Rh]O Ph

O OMe

[Rh] OH

N

S O

O

O Ph

H

[Rh]

H

N

[Rh]O Ph

S O

O

Me Me

Me

Me

1a

H2O

2a

A B

CD

1a

A




Chapter 2

32








N

HO Ph

SN

S CH19D11

HO Ph

D3C

1a-d2a-d 96

D3C

O

O

O O

D

D

D

D

D

D

H01D09

8



D12




Application




1

2

SN

HO Ar

O OMe

N

HO Ar

S O

O


K2CO 3 (20 equiv)


NS Me

HO PhMe

2a

91 er = 928

O O

NS Me

HO Ph

2b

95 er = 937

O O

S

NS Me

HOMe

2c

90 er = 937

O O

OMe

NS Me

HOMe

2c

92 er = 919

O O

CF3



Chapter 2

33










HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6 84

5 56



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3


PhMgBr

THF rt 1 h N

HO

Ts

Me

1e 93

er gt 991 dr = 201

Ph

3







SN

HO PhMe

O OMe

MeN

HO Ph

S O

O

Me

Me

1e

er gt 991 dr = 201

2e 99

er gt 991 dr gt 201





Chapter 2

34









SN

PhRhOMe

O OMe

Me

SN

PhRhOMe

O OMe

Me

favored

disfavored

F

F

NSRh

Ph

Me

O

O

MeO

H

Me

E

E

NSRh

Ph

Me

O

O

MeO

Me

H














Chapter 2

35


1

er gt 991 dr gt 201

2

er gt 991 dr gt 201

SN

HO ArR

O OMe

N

HO Ar

S O

O





1 N

HO Ph

S O

O

Me

Me

1f

SN

HO PhMe

O OMe

Me

2e 99

6 N

HO

S O

O

Me

1k

OMe

SN

HOMe

O OMe

2k 97

OMe

2

N

HO Ph

S O

O

MeO

Me

1g

SN

HO PhMe

O OMe

MeO

2g 98

7 N

HO

S O

O

Me

Me

1l

CF3

SN

HOMe

O OMe

Me

2l 97

CF3

3 N

HO Ph

S O

O

F3C

Me

1h

SN

HO PhMe

O OMe

F3C

2h 99

8 N

HO Ph

S O

O

Me

i-Pr

1m

SN

HO Phi-Pr

O OMe

Me

2m 97

4

N

HO Ph

S O

O

Me

1iMe

SN

HO PhMe

O OMeMe

2i 99

9 N

HO Ph

S O

O

Me

SMe

SN

HO Ph

O OMe

Me

2n 97

SMe

5 N

HO Ph

S O

O

Me

S

1j

SN

HO PhMe

O OMeS

2j 99



Chapter 2

36

Conclusions






Chapter 2

37





13C NMR


13C at 10069












N

OHNEt3

DCM rt 12 h


2) PhMgBrTHF rt 3 h

N

HO Ph

1a

TsCl

N

OH

8a

H HCl

Ts Ts









Chapter 2

38

N

S

Me

O

O

OH

8a 1H NMR = 213 (bs 1H) 245 (s 3H) 350-361 (m 2H) 394-404 (m 2H)

442-452 (m 1H) 737 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR =



-1

N

S

D3C

O

O

OH

8a-d

D

D

D

D

1H NMR = 283 (bs 1H) 349-355 (m 2H) 389-396 (m 2H) 435-444 (m 1H)



+ 2351128 Found mz

2351125 IR (ATR) 3503 1333 1142 1059 638 cm-1

N

S O

O

OH

8b

S

1H NMR = 277 (bs 1H) 357-364 (m 2H) 400-407 (m 2H) 441-450 (m 1H)


1H) 13



1038 737 cm-1

Chapter 2

39














N

HO Ph

S

1a

Me

O

O


2H) 728-737 (m 5H) 739 (d J = 84 Hz 2H) 778 (d J = 80 Hz 2H) 13

C NMR

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS


+ 3041002 Found mz 3040995 IR (ATR) 3477

1333 1184 1148 671 cm-1


N

HO Ph

S

1a-d

D3C

O

O

D

D

D

D


(m 5H) 13

C NMR = 203-211 (m) 652 703 1244 1281 (t JC-D = 247 Hz)


Chapter 2

40


702 648 cm-1

N

HO Ph

S

S

O

O



1H) 13

C NMR = 656 702 1244 1280 1283 1288 1331 13387 13392 1417


+ 2960410 Found mz 2960404 IR

(ATR) 3524 1333 1161 1148 748 cm-1

N

HO

S

Me

O

O

OMe

1c



2H) 775 (d J = 80 Hz 2H) 13

C NMR =216 553 652 702 1139 1259 1285


+

3341108 Found mz 3341097 IR (ATR) 3460 1518 1331 1250 1146 cm-1

N

HO

S

Me

O

O

CF3



C NMR

Chapter 2

41

=216 654 697 1239 (q JC-F = 2704 Hz) 1249 1255 (q JC-F = 37 Hz) 1284



1109 1076 cm-1


1l-1n

HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6a

5a



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3

acetone H2O

rt 10 h 4a

PhMgBr

THF rt 1 h N

OH

Ts

Me

1e

Ph

3a



procedure16













Me

NHTs

O

N2


Chapter 2

42

2H) 730 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR = 194 215 539


+

2680750 Found mz 2680747 IR (ATR) 2112 1639 1337 1319 1161 cm-1

[]27

D = -1184 (c = 079 in CHCl3)


i-Pr

NHTs

O

N2



2H) 769 (d J = 84 Hz 2H) 13

C NMR =169 193 215 315 548 647 1273


+ 2961063

Found mz 2961060 IR (ATR) 2129 1622 1362 1329 1161 cm-1

[]28

D = -730 (c = 071 in CHCl3)

NHTs

O

N2

5c

SMe

1H NMR = 174-196 (m 2H) 204 (s 3H) 242 (s 3H) 244-252 (m 2H)

390-400 (m 1H) 541 (s 1H) 560-572 (m 1H) 730 (d J = 84 Hz 2H) 772 (d J =

84 Hz 2H) 13

C NMR = 153 215 297 323 545 585 1272 1297 1366 1439


+ 3280784 Found mz 3280779

IR (ATR) 2129 1618 1375 1339 1163 cm-1

[]29

D = -506 (c = 063 in CHCl3)









Chapter 2

43

N

O

Ts

Me

6a

1H NMR = 145 (d J = 68 Hz 3H) 246 (s 3H) 443-454 (m 2H) 473-480 (m

1H) 736-742 (m 2H) 776-781 (m 2H) 13

C NMR = 157 216 696 810 1284


+ 2400689

Found mz 2400688 IR (ATR) 1825 1339 1155 669 cm-1

[]28

D = 614 (c = 081 in CHCl3)


N

O

Ts

i-Pr

6b

1H NMR = 099-111 (m 6H) 206-218 (m 1H) 246 (s 3H) 441 (dd J = 164 36


2H) 777 (d J = 80 Hz 2H) 13

C NMR = 174 181 216 304 703 903 1284


+ 2681002

Found mz 2680998 IR (ATR) 1815 1340 1155 1007 671 cm-1

[]29

D = 567 (c = 095 in CHCl3)

N

O

Ts

6c

SMe

1H NMR = 204 (s 3H) 209-218 (m 2H) 247 (s 3H) 265-279 (m 2H) 446 (d


2H) 780 (d J = 80 Hz 2H) 13

C NMR = 147 216 291 293 705 832 1286


+ 3000723

Found mz 3000718 IR (ATR) 1813 1342 1308 1157 667 cm-1

[]29

D = 1183 (c = 036 in CHCl3)


Chapter 2

44










N

HO

S O

O

Me

Me

1e

H

NOE

NOE



(m 3H) 739 (d J = 84 Hz 2H) 777 (d J = 84 Hz 2H) 13

C NMR = 144 216

628 702 731 1247 1279 1284 1285 1298 1319 1415 1443 HRMS (ESI+)


1155 1092 667 cm-1

[]25




Chapter 2

45

N

HO

S O

O

Me

1l

H

NOE

NOE

CF3

Me



739-747 (m 4H) 777 (d J = 84 Hz 2H) 13

C NMR = 143 216 630 706 727

1238 (JC-F = 2704 Hz) 1253 1254 (JC-F = 36 Hz) 1285 1299 1301 (JC-F = 324


+ 3861032

Found mz 3861025 IR (ATR) 3422 1327 1151 1109 839 cm-1

[]28




N

HO

S O

O

Me

iPr

1m

H

NOE

NOE



= 100 Hz 1H) 690-696 (m 2H) 712-720 (m 3H) 732 (d J = 80 Hz 2H) 773 (d

J = 80 Hz 2H) 13

C NMR = 190 193 215 291 641 729 801 1247 1275


+

3461471 Found mz 3461466 IR (ATR) 3454 1331 1163 739 669 cm-1

[]27



Chapter 2

46


N

HO Ph

S O

O

1n

Me

SMe

1H NMR = 202 (s 3H) 218-258 (m 8H) 388-394 (m 2H) 427 (dd J = 84 48

Hz 1H) 688-693 (m 2H) 714-721 (m 3H) 740 (d J = 80 Hz 2H) 779 (d J = 80

Hz 2H) 13

C NMR = 154 216 290 297 634 725 733 1246 1277 1284


+

3781192 Found mz 3781188 IR (ATR) 3481 1339 1157 702 669 cm-1

[]28












N

HO

S O

O

Me

Me

1f

H

NOE

NOE


1H) 398 (q J = 64 Hz 1H) 424 (dd J = 84 08 Hz 1H) 732-744 (m 5H)

750-755 (m 2H) 774-778 (m 2H) 13

C NMR = 165 216 627 718 739 1257

Chapter 2

47



-1

[]25






HO2C Me

NHCbz

Me

NHCbz

O

N2N

O

Cbz

Me

6d5d

1) (COCl) 2 DMF

2) CH2N2 Rh2(OAc)4 (05 mol )

DCM rt 12 h4d

PhMgBr

THF rt 1 h

N

OH

Cbz

Me

7a

Ph

N

OH

H

Me

PhPd C (5 mol )

H2 (1atm)

MeOH rt 12 h

MeO SO2Cl

NEt3

DCM rt 12 h

N

HO Ph

S O

O

MeO

Me

1g









Me

NHCbz

O

N2

5d 1H NMR = 134 (d J = 68 Hz 3H) 420-436 (m 1H) 504-516 (m 2H) 534-564

(m 2H) 728-736 (m 5H) 13

C NMR = 184 535 (2C) 669 1280 1282 1285


+ 2481030 Found mz

2481028 IR (ATR) 2116 1717 1636 1533 1252 cm-1

[]28

D = -434 (c = 085 in CHCl3)


Chapter 2

48







N

O

Cbz

Me

6d


Hz 1H) 498-505 (m 1H) 513-521 (m 2H) 731-739 (m 5H) 13

C NMR = 153



696 cm-1

[]29

D = 390 (c = 068 in CHCl3)










N

OH

Cbz

Me

7a

Ph


= 96 Hz 1H) 458 (q J = 64 Hz 1H) 507-518 (m 2H) 729-746 (m 10H) 13

C

NMR = 142 623 667 689 730 1246 1278 1279 1280 1285 1287 1366

Chapter 2

49


+ 2981438 Found mz

2981433 IR (ATR) 1670 1423 1248 1016 702 cm-1

[]29

D = 46 (c = 089 in CHCl3)

N

OH

Cbz

Me

7b

MeO


1H) 432 (d J = 96 Hz 1H) 452-461 (m 1H) 506-518 (m 2H) 687-694 (m 2H)

726-739 (m 7H) 13

C NMR = 143 553 622 666 687 729 1140 1260 1278


+

3281543 Found mz 3281539 IR (ATR) 1682 1418 1352 1024 696 cm-1

[]29

D = 02 (c = 085 in CHCl3)








pressure







mmol 58 yield)

Chapter 2

50

N

HO

S O

O

MeO

Me

1g

H

NOE

NOE


390 (s 3H) 399 (d J = 92 Hz 1H) 419 (q J = 60 Hz 1H) 698-707 (m 4H)

720-727 (m 3H) 779-785 (m 2H) 13

C NMR = 143 557 627 701 731 1144



-1

[]28




N

HO

S O

O

F3C

Me

1h

H

NOE

NOE


406 (d J = 92 Hz 1H) 430 (qd J = 64 08 Hz 1H) 694-699 (m 2H) 721-727

(m 3H) 784 (d J = 80 Hz 2H) 801 (d J = 84 Hz 2H) 13

C NMR = 145 629

706 729 1232 (JC-F = 2711 Hz) 1245 1263 (JC-F = 37 Hz) 1283 12868 12871


+

3720876 Found mz 3720870 IR (ATR) 3503 1348 1323 1165 646 cm-1

[]28




Chapter 2

51

N

HO

S O

O

Me

1i

H

NOE

NOE


1H) 401 (d J = 88 Hz 1H) 422 (q J = 64 Hz 1H) 694-698 (m 2H) 720-724 (m

3H) 746-750 (m 2H) 767-772 (m 2H) 13

C NMR = 144 214 630 704 730

1247 1256 1279 1285 1286 1291 1341 1347 1395 1416 HRMS (ESI+)


1151 714 700 cm-1

[]29




N

HO

S O

O

Me

1j

H

NOE

NOE

S


Hz 1H) 425 (q J = 64 Hz 1H) 696-701 (m 2H) 720-728 (m 4H) 764-767 (m

1H) 769-772 (m 1H) 13

C NMR = 144 632 709 730 1246 1279 1281 1286


+ 3100566

Found mz 3100559 IR (ATR) 3508 1340 1151 756 669 cm-1

[]29




Chapter 2

52

N

HO

S O

O

Me

1k

H

NOE

NOE

OMe


1H) 394 (d J = 88 Hz 1H) 416 (q J = 64 Hz 1H) 670-675 (m 2H) 684-689 (m

2H) 756-762 (m 2H) 765-770 (m 1H) 786-790 (m 2H) 13

C NMR = 143 553

630 704 729 1138 1259 1283 1292 1332 1337 1348 1592 HRMS (ESI+)


1327 1155 606 cm-1

[]29





Screening







mmol 93 yield)

Chapter 2

53


rac -DM-BINAP

rac-BINAP

dppf

dppb

PPh3

dppe

46

trace

trace

yield

PCy3

Ligand

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

entry

1

2

3

4

5

6

7

8

nd

nd

nd

93

none nd

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a


entry Ligand yield

1

2

3

4

(R)-BINAP

(R)-DM-BINAP

(R)-SEGPHOS

(R)-DIFLUORPHOS

er

94

46

48

43

5

6

(R)-DM-SEGPHOS


3862

91

7

8

(R)-MeO-BIPHEP

(R)-MeO-DM-BIPHEP

64

91

892

3169

1288

1486

2476

2575

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a










Chapter 2

54

NS Me

HO PhMe

2a

O O


J = 148 Hz 1H) 683 (s 1H) 727-744 (m 6H) 781 (d J = 84 Hz 1H) 13

C NMR

= 216 361 626 732 1238 1263 1280 1284 1299 1301 1330 1412 1431


+ 3041002 Found mz 3040998 IR

(ATR) 3472 1325 1161 1142 735 cm-1

[]29




NS CH2D

HO Ph

D3C

2a-d

O O

D

D

D


J = 148 Hz 1H) 728-743 (m 5H) 13

C NMR = 201-210 (m) 358 (t JC-D = 212

Hz) 625 731 1234 (t JC-D = 249 Hz) 1262 1279 1283 1291-1300 (m 2C)


+ 3111441

Found mz 3111436 IR (ATR) 3524 1318 1290 1150 721 cm-1

NS Me

HO Ph

O O

S

2b


1H) 668 (d J = 52 z 1H) 730-738 (m 5H) 750 (d J = 52 Hz 1H) 13

C NMR =

378 630 722 1257 1264 1282 1286 1299 1338 1427 1467 HRMS (ESI+)


1150 1063 748 cm-1

[]29


Chapter 2

55



NS Me

HOMe

O O

OMe

2c


422 (d J = 148 Hz 1H) 684-690 (m 3H) 724-733 (m 3H) 774-779 (m 1H) 13

C

NMR = 216 360 553 626 729 1137 1237 1275 1299 1230 1328 1351


+ 3341108 Found mz

3341098 IR (ATR) 3441 1508 1250 1144 735 cm-1

[]29




NS Me

HOMe

O O

CF3



2H) 782 (d J = 80 Hz 1H) 13

C NMR = 216 360 625 731 12392 (q JC-F =

2708) 12395 1254 (q JC-F = 36 Hz) 1268 1298 1303 (q JC-F = 352) 1329


+ 3720876 Found

mz 3720869 IR (ATR) 3481 1323 1121 1067 733 cm-1

[]29




Chapter 2

56










SN

HO

Me

O OMe

Me

2e

H

NOE

NOE


= 68 Hz 1H) 675 (s 1H) 723-738 (m 6H) 777 (d J = 84 Hz 1H) 13

C NMR =

119 215 314 608 750 1242 1262 1275 1282 1298 1301 1316 1427


+ 3181158 Found mz

3181155 IR (ATR) 3481 1315 1163 1146 683 cm-1

[]28




SN

HO

Me

O OMe

MeO

2g

H

NOE

NOE

Chapter 2

57



5H) 782 (d J = 88 Hz 1H) 13

C NMR = 120 314 555 609 752 1144 1151



735 cm-1

[]29




SN

HO

Me

O OMe

F3C

2h

H

NOE

NOE



1H) 13

C NMR = 118 314 608 750 1228 (q JC-F = 2711 Hz) 1251 1258 (q



+ 3720876 Found

mz 3720872 IR (ATR) 3461 1325 1161 1142 739 cm-1

[]29




SN

HO

Me

O OMe

2i

H

NOE

NOE

Me

Chapter 2

58


J = 68 Hz 1H) 684 (d J = 80 Hz 1H) 718-736 (m 6H) 770 (s 1H) 13

C NMR

=119 211 314 607 748 1242 1262 1275 1282 1299 1338 1341 1395


+ 3181158 Found mz

3181155 IR (ATR) 3489 1448 1319 1148 735 cm-1

[]29




SN

HO

Me

O OMe

2j

H

NOE

NOES


1H) 656 (d J = 52 Hz 1H) 726-736 (m 5H) 743 (d J = 48 Hz 1H) 13

C NMR

= 114 319 619 742 1256 1266 1278 1284 1297 1334 1429 1480 HRMS


+ 3100566 Found mz 3100561 IR (ATR) 3524

1329 1151 1020 729 cm-1

[]29




SN

HO

Me

O OMe

2k

H

NOE

NOE

OMe


J = 68 Hz 1H) 685 (d J = 88 Hz 2H) 698-703 (m 1H) 722-730 (m 2H)

738-748 (m 2H) 785-790 (m 1H) 13

C NMR = 119 314 553 608 747 1136

Chapter 2

59



760 cm-1

[]26




SN

HO

Me

O OMe

2l

H

NOE

NOE

CF3

Me



= 84 Hz 2H) 778 (d J = 80 Hz 1H) 13

C NMR = 119 215 313 607 749




-1

[]26




SN

HO

iPr

O OMe

2m

H

NOE

NOE

Me


(m 1H) 264 (s 1H) 285 (s 3H) 441 (d J = 100 Hz 1H) 685 (s 1H) 714-735 (m

4H) 748 (d J = 76 Hz 2H) 772 (d J = 80 Hz 1H) 13

C NMR = 211 214 217

278 330 718 742 1244 1256 1270 1283 1292 1295 1300 1435 1442


+ 3461471 Found mz 3461466 IR

Chapter 2

60

(ATR) 3412 1315 1165 1146 683 cm-1

[]29




SN

HO

O OMe

2n

H

Me

NOE

SMe

1H NMR = 160-170 (m 1H) 184 (s 3H) 212-226 (m 4H) 230-242 (m 2H)

254-263 (m 1H) 294 (s 3H) 471 (dd J = 108 28 Hz 1H) 675 (s 1H) 722-738

(m 6H) 776 (d J = 80 Hz 1H) 13

C NMR = 150 215 242 301 321 643 748

1245 1262 1276 1283 12986 12993 1312 1429 1437 1441 HRMS (ESI+)


1165 1134 748 cm-1

[]28









was used as a


and


21 All



Chapter 2

61



2e

formula C17H19NO3S

fw 31739

T (K) 100(2)


space group P21c

a (Aring) 105967(5)


3) 152058(13)

Z 4 Dcalc (gcm

3) 1386

(mm-1

) 0225 F(000) 672



348500135

params 203 GOF on F

2 1069

R1 wR2 [Igt2(I)]

00322 00868

R1 wR2 (all data)

00335 00878

Chapter 2

62

























Med Chem 2003 46 1116








Chapter 2

63

































Chapter 2

64




2012 51 9160





11437-11439
























Chapter 2

65











2548-2551







11750









32 115



Chapter 2

66

Chapter 3

67

Chapter 3




Halides

Abstract






Chapter 3

68

Introduction
















2) are












several months


Et LiB

Ph

+B

Ph

Et

1a 74

(a)(b)[Me4N]


Chapter 3

69

















OMe

BrB

Ph

Et

OMe

3a

Ph

Et

OMe

H

4a

Pd-ligand AcOH

2a

+B

Ph

Et

1a

[Me4N]


EZ of 4ab

1 P(o-tol)3 69 397

2 P(t-Bu)3 47 1783

3 1-[(t-Bu)2P](biphenyl) 18 2872

4 2-[(t-Bu)2P](11-binaphthyl) 21 6733

5 DPEPhos 24 928



analysis



Chapter 3

70









Pd(0)

Pd

MeO

B

PdEt

OMe

Ph

B

Ph

Et

2a

BC

Pd

MeO

Br

A

1a

3a







dominates10
















Chapter 3

71










Chapter 3

72


BO

Ph

Et

OMe

5a 83

BO

Ph

Et

CF3

5b 85

BO

Ph

Et

NPhth

5c 82

BO

Ph

Et

5d 72b

BO

Ph

Et

5e 85

S

BO

n-Pr

Me

Cl

5f 74

BO

n-Pr

Ph

OMe

5g 82

BO

Ph

S

5h 83

BO

Ph

CO2Et

5i 81

BO

Ph

5j 82

Cl

BO

Ph

CF3

TBSO

BO

Cl

S

Ph

BO

Ph

Me

OMe

5n 71b

5m 925l 82

BO

Ph

5k 76

Me

+B

Ar

R

1

[Me4N]

2


BO

Ar

R

Ar

5







The reaction of 1a






Chapter 3

73








(E)-5o83 EZ = gt955

BO

Ph

Et

Ph

Ph

Et

PhO

NMe2

(Z)-685 EZ = lt595

Ph

Ph

EtO

NMe 2

(E)-675 EZ = 928

1a

(Z)-5o71 EZ = 793

+ PhBr

BO

Ph

Ph

Et

(a)

(c) (c)

(b)






Conclusions






Chapter 3

74




1H at 400 MHz and

11B at 128 MHz)



13C)

CD3CN ( = 194 for 1H =132 for


11B)









and Ph-9-BBN18


procedures


Et LiB

Ph

+B

Ph

Et

1a


2) Me4NCl MeOH

[Me4N]









74 yield)

Chapter 3

75

B

Ph

Et

1a

[Me4N]


136-207 (m 11H) 236-250 (m 2H) 303 (s 12 H) 679-686 (m 1H) 700-707 (m

2H) 735 (d J = 72 Hz 2H) 13

C NMR (CD3CN) = 149 166 266 (q JC-B = 379

Hz) 271 275 324 349 561 948 1221 1269 1339 11

B NMR = -133 HRMS




n-Pr LiB

Ar


2) Me4NCl MeOH B

n-Pr

1b

Cl

[Me4N]










Chapter 3

76

B

n-Pr

1b

Cl

[Me4N]

1H NMR (CD3CN) = 084-096 (m 5H) 111-121 (m 1H) 126-200 (m 13H)

235-250 (m 2H) 304 (s 12H) 700-705 (m 2H) 733 (d J = 84 Hz 2H) 13

C NMR

(CD3CN) = 139 234 249 266 (q JC-B = 393 Hz) 270 273 323 348 561

933 1265 1272 1355 11


[M-(NMe4)] 2991738 Found 2991730

B

n-Pr

1c

OMe

[Me4N]


128-201 (m 13H) 237-252 (m 2H) 303 (s 12H) 371 (s 3H) 663-668 (m 2H)

723 (d J = 81 Hz 2H) 13

C NMR (CD3CN) = 140 235 250 268 (q JC-B = 393

Hz) 272 275 324 349 554 561 929 1128 1344 1561 11

B NMR = -135


B

Ph

1d

[Me4N]


(m 2H) 134-196 (m 9H) 230-244 (m 2H) 304 (s 12H) 679-686 (m 1H)

699-706 (m 2H) 733 (d J = 72 Hz 2H) 13

C NMR (CD3CN) =23 87 266 (q

JC-B = 393 Hz) 271 274 323 349 562 1222 1269 1338 11

B NMR = -134


Chapter 3

77

B

Ph

1e

[Me4N]


(m 3H) 302 (s 12H) 679-686 (m 1H) 699-706 (m 2H) 734 (d J = 66 Hz 2H) 13

C NMR (CD3CN) = 253 268 (q JC-B = 379 Hz) 271 275 324 333 349 361

561 980 1221 1269 1339 11


[M-(NMe4)] 2912284 Found 2912278

B

1f

S

Ph

[Me4N]




09 Hz 1H) 712-730 (m 5H) 13

C NMR (CD3CN) = 240 268-290 (m) 325 347

380 562 928 1225 1261 1265 1271 1289 1297 1434 11

B NMR = -135


B

Ph

1g

TBSO

[Me4N]

1H NMR (CD3CN) = 005 (s 6H) 084-096 (m 11H) 110-120 (m 1H) 134-197

(m 9H) 216-233 (t J = 72 Hz 2H) 235-250 (m 2H) 301 (s 12H) 356 (t J = 78

Hz 2H) 680-687 (m 1H) 700-708 (m 2H) 735 (d J = 66 Hz 2H) 13

C NMR

(CD3CN) = -50 189 254-277 (m) 323 348 561 649 889 1222 1269

1339 11


Found 3812789

Chapter 3

78

B

Ph

1h

OMe

[Me4N]


(m 2H) 298 (s 12H) 373 (s 3H) 668-674 (m 2H) 701-718 (m 5H) 732 (d J =

87 Hz 2H) 13

C NMR (CD3CN) = 255-277 (m) 322 350 554 561 961 1129

1251 1287 1302 1312 1345 1564 11


C23H26BO [M-(NMe4)] 3292077 Found 3292081



Br

+

MeO


6 mol Ligand


2a

B

Ph

Et

OMe

(E)-3a

AcOH

Ph

Et

OMe

H

Ph

B

Et

OMe

+

+

(Z)-3a

(E)-4a

H

Et

OMe

Ph

(Z)-4a

B

Ph

Et

1a

[Me4N]









Chapter 3

79




B

Ph

Et

+


toluene 70 degC

Me3NO

Br

MeO

BO

Ph

Et

OMe

5a

1a

2a

[Me4N]









BO

Ph

Et

OMe


383 (s 3H) 438-444 (m 1H) 685-691 (m 2H) 714-736 (m 7H) 13

C NMR =

138 221 267 273 (br) 277 312 553 736 1132 1251 1278 1283 1298

1366 1436 1494 1586 11


3742417 Found 3742410

Chapter 3

80

BO

Ph

Et

CF3

5b


437-443 (m 1H) 718-726 (m 3H) 734-739 (m 2H) 745-748 (m 2H) 760-763

(m 2H) 13

C NMR = 135 220 266 271 (br) 276 312 738 12429 (q JC-F =

2701 Hz) 1247 (q JC-F = 36 Hz) 1280 1281 1289 (q JC-F = 320 Hz) 1291 1425

1476 1480 11


Found 4122186

BO

Ph

Et

NPhth

5c


440-450 (m 1H) 720-727 (m 3H) 734-739 (m 2H) 743-751 (m 4H) 777-783

(m 2H) 794-800 (m 2H) 13

C NMR = 137 221 266 274 (br) 275 312 738

1235 1254 1258 1279 1282 1294 1304 1317 1342 1429 1440 1482

1671 11

B NMR = 502 IR (KBr) = 2928 1742 1509 1381 714 cm-1

HRMS (EI)


BO

Ph

Et

5d

1H NMR = 021-034 (m 1H) 068-100 (m 8H) 120-150 (m 7H) 224-238 (m

1H) 244-258 (m 1H) 424-431 (m 1H) 722-754 (m 9H) 778 (d J = 78 Hz 1H)

783-788 (m 1H) 809-816 (m 1H) 13

C NMR = 137 216 219 259 262 264

(br) 282 309 314 734 1249 12537 12539 1255 1264 1270 1273 12795

Chapter 3

81

12799 1283 1321 1335 1413 1427 1467 11


for C28H31BO (M+) 3942468 Found 3942476

BO

Ph

Et

5e

S


448-456 (m 1H) 702 (dd J = 51 36 Hz 1H) 708 (dd J = 36 12 Hz 1H)

715-730 (m 4H) 732-738 (m 2H) 13

C NMR =141 221 271 289 312 739

1250 1255 1266 1269 1279 1281 1416 1427 1468 11

B NMR = 496


BO

n-Pr

Me

Cl

5f

1H NMR = 070 (t J = 75 Hz 3H) 096-133 (m 9H) 142-172 (m 6H) 220-228

(m 2H) 237 (s 3H) 439-446 (m 1H) 708-735 (m 8H) 13

C NMR = 140 212

219 221 267 274 (br) 313 363 737 1279 12846 12855 1298 1309 1365

1411 1420 1488 11


4062235 Found 4062237

BO

n-Pr

Ph

OMe

5g

Chapter 3

82


(s 3H) 435-450 (m 1H) 690 (d J = 81 Hz 2H) 711 (d J = 81 Hz 2H) 720-740

(m 5H) 13

C NMR = 140 219 221 267 274 (br) 312 362 551 736 1133

1267 1278 1287 1294 1354 1446 1475 1573 11




BO

Ph

S

5h

1H NMR = 027-032 (m 2H) 046-052 (m 2H) 098-130 (m 6H) 140-170 (m

8H) 430-445 (m 1H) 696-700 (m 1H) 704-707 (m 1H) 715-726 (m 2H)

729-738 (m 4H) 13

C NMR = 60 150 222 263 272 (br) 313 736 1241

1243 1253 1278 1290 1295 1410 1425 1431 11



BO

Ph

CO2Et

5i

1H NMR = 017-023 (m 2H) 045-053 (m 2H) 090-119 (m 6H) 132-173 (m

11H) 427-433 (m 1H) 438 (q J = 75 Hz 2H) 718-738 (m 7H) 798 (dt J = 78

15 Hz 2H) 13

C NMR = 56 144 151 220 263 269 (br) 312 609 735 1255

1279 1284 1287 1289 1303 1423 1453 1469 1665 11

B NMR = 496 IR

(KBr) = 2928 1717 1287 1100 cm-1


Found 4282526

BO

Ph

5j

Cl

Chapter 3

83

1H NMR = 023-029 (m 2H) 048-055 (m 2H) 094-123 (m 6H) 134-171 (m

8H) 432-439 (m 1H) 706-714 (m 1H) 718-726 (m 4H) 728-738 (m 4H) 13

C

NMR = 57 150 220 263 271 (br) 312 736 1255 1267 1279 1283 1284

1289 1304 1332 1423 1424 1461 11


C25H28BClO (M+) 3901922 Found 3901923

BO

Ph

5k

Me

1H NMR = 082-113 (m 6H) 126-164 (m 15H) 237 (s 3H) 268-280 (m 1H)

434-441 (m 1H) 704-709 (m 3H) 717-725 (m 4H) 730-737 (m 2H) 13

C NMR

= 215 219 248 263 273 (br) 312 315 433 735 1252 12689 12693 1275

1278 1283 1316 1365 1418 1424 1481 11


for C28H35BO (M+) 3982781 Found 3982780

BO

Cl

S

Ph

5l

1H NMR = 106-176 (m 13H) 250-260 (m 2H) 272-280 (m 2H) 441-449 (m

1H) 674 (dd J = 33 12 Hz 1H) 697-703 (m 3H) 709-738 (m 8H) 13

C

NMR(C6D6) =225 272 277 (br) 315 358 375 739 1247 1253 1261 1272

1285 12856 12861 1306 1335 1419 1427 1437 1491 11

B NMR = 495


BO

Ph

CF3

TBSO

5m

Chapter 3

84

1H NMR = -014 (s 6H) 079 (s 9H) 095-136 (m 6H) 142-168 (m 7H) 255 (t

J = 72 Hz 2H) 343 (t J = 72 Hz 2H) 435-442 (m 1H) 718-726 (m 3H)

731-737 (m 2H) 747 (d J = 81 Hz 2H) 759 (d J = 81 Hz 2H) 13

C NMR = -54

183 220 259 266 271 (br) 311 377 616 739 1242 (q JC-F = 2694 Hz) 1247

(q JC-F = 36 Hz) 1258 1280 1282 1290 (q JC-F = 320 Hz) 1291 1421 1422

1480 11



BO

Ph

Me

OMe

5n

1H NMR = 122-130 (m 4H) 138-162 (m 5H) 168-186 (m 4H) 237 (s 3H)

375 (s 3H) 443-450 (m 1H) 670 (dt J = 90 21 Hz 2H) 690-697 (m 4H)

702-708 (m 3H) 710-720 (m 4H) 13

C NMR = 213 222 269 312 550 738

1132 1260 1272 1285 1301 1307 1310 1362 1369 1423 1429 1483

1571 11


4362561


4-Bromobenzene

B

Ph

Et

+


toluene 70 degC

Me3NO BO

Ph

Ph

Et

(Z)-5o

1a

Ph Br

[Me4N]




Chapter 3

85






BO

Ph

Ph

Et


470-475 (m 1H) 685-710 (m 10H) 13

C NMR = 139 224 267 313 317 740

1248 1257 1272 127412938 12941 1421 1425 1275 11

B NMR = 512


BO

Ph

Et

Ph


438-443 (m 1H) 718-737 (m 10H) 13

C NMR = 137 221 266 274 (br) 277

312 737 1253 1268 1278 1279 1283 1288 1433 1442 1494 11

B NMR =



Bromide 2b

+

Br

ONMe2

Ph

Et

PhO

NMe2


THF K3PO4 60 degC

(Z)-Tamoxifen 6

2b

BO

Ph

Et

Ph

(E)-5o

Chapter 3

86









Chapter 3

87



2003 Vol 3








Rev 2006 250 1107









1976 108 281








74





Chapter 3

88





















2006 128 1828




Chapter 4

89

Chapter 4



Abstract






Chapter 4

90

Introduction





























Chapter 4

91


B

MOMO

[Me4N] +

MeO

Br

I

Br

MeO Br

B

MeO

MOMO MOMO

1a

2 3 87EZ = lt199

NaOH

50 degC

1 mol


toluene 50 degC
















procedure

Chapter 4

92



An











3

MeO

R

Br

4 92

R

MeO

R

Br

n = 2 5 87

n = 3 6 82n = 4 7 85

n

R

1 mol


toluene 50 degC

I

Br

NaOH

E

EE

R = OMOM








Chapter 4

93





Br

Br

R

R

Br

Br

8 86

R

R

Br

R

R

Br

9 92

E E

R = OMOM















Chapter 4

94


Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

Me3Si

Br

Ph

F

Me3Si

OMe

Br

Ph

F

S

Br

Me3Si

OMe

B

n-Pr

[Me4N]

Cl

B

Ph

[Me4N]

OMe

Br

S

Br

I

EtO2C

MOMO

MOMO

I

Br

F

1b

10 88

11 84

12 88

1a1c

cat Pd

NaOHcat Pd

cat Pd NaOH

Cs2CO3

Conclusions







Chapter 4

95




1H at 500 MHz and






13C) CD3CN ( = 194 for

1H =132 for

13C) and

BF3OEt2 ( = 000 for 11











11













Chapter 4

96

B

MOMO

[Me4N]

1a


202 (t J = 66 Hz 2H) 236-251 (m 2H) 304 (s 12H) 328 (s 3H) 346 (t J = 69

Hz 2H) 454 (s 2H) 678-685 (m 1H) 698-705 (m 2H) 734 (d J = 72 Hz 2H) 13

C NMR (CD3CN 75 MHz) = 210 267 (br) 271 275 282 297 324 349 551

561 681 928 968 1221 1269 1338 11



B

Ph

[Me4N]

1b

OMe


225 (t J = 72 Hz 2H) 234-249 (m 2H) 263 (t J = 72 Hz 2H) 303 (s 12H) 372

(s 3H) 663-669 (m 2H) 711-728 (m 7H) 13


272 275 324 349 381 554 560 1129 1266 1289 1298 1346 1434 1563 11


3572390 Found 3572383



B

MOMO

[Me4N]

+

MeO

Br

1 mol


toluene 50 degC

I

Br

MeO Br

NaOH

3

1a

MOMO

Chapter 4

97








MeO Br

3

MOMONOE

NOE




(t J = 66 Hz 2H) 376 (s 3H) 452 (s 2H) 667-675 (m 4H) 697-702 (m 2H)

709-736 (m 7H) 13

C NMR (75 MHz) = 255 298 356 5510 5514 676 964

1134 1196 1267 1282 1294 13046 13049 1323 1339 1376 1408 1420



spectroscopy

MeO

R

Br

4

R

R = OMOM




Chapter 4

98


2H) 325 (s 3H) 329 (s 3H) 331-341 (m 4H) 380 (s 3H) 451 (s 2H) 453 (s

2H) 662-678 (m 8H) 697-703 (m 2H) 706-738 (m 12H) 13

C NMR (150 MHz)

= 252 254 295 296 353 354 5502 5504 552 675 676 9629 9632 1131

1196 1265 1267 1281 1282 1285 12941 12942 1303 1304 1306 1324

1343 1377 1385 1390 1400 1413 1414 1418 1429 1435 1579 HRMS


7972818 Found

7972849

MeO

R

5

R

R = OMOM

R

Br




325 (s 3H) 327 (s 3H) 328 (s 3H) 330-342 (m 6H) 374 (s 3H) 450 (s 2H)

452 (s 2H) 454 (s 2H) 654-662 (m 4H) 666-678 (m 8H) 696-704 (m 4H)

712-737 (m 15H) 13

C NMR (75 MHz) = 254 256 296 297 298 3526 3534

355 551 675 676 963 1130 1196 1264 1267 1280 1281 1286 1294 1301

1302 1304 1306 1324 1344 1377 1384 1387 1392 1393 1398 1402 1409



10914437 Found 10914482

Chapter 4

99

MeO

R

6

R

R = OMOM

R

R

Br




330-341 (m 8H) 371 (s 3H) 448-454 (m 8H) 648-675 (m 16H) 695-703 (m

4H) 714-737 (m 20H) 13

C NMR (75 MHz) = 253 254 256 257 2969 2974

298 350 354 356 550 551 675 676 963 1131 1196 1264 1267 1279

1280 1281 1283 1288 1293 1294 1300 1301 1302 1305 1306 1323 1342

1377 1385 1387 1389 1391 1394 1396 1397 1401 1405 1409 1411 1413



13856057 Found 13856062

MeO

R

7

R

R = OMOM

R

R

R

Br




374 (s 3H) 447-452 (m 10 H) 649-679 (m 20 H) 690-695 (m 2H) 701-706 (m

2H) 710-736 (m 25H) 13

C NMR (75 MHz) = 2529 2535 256 257 2968

Chapter 4

100

2971 298 351 354 355 356 550 6746 6755 676 963 1131 1195 1264

1267 12795 1280 1281 1283 1285 1287 1293 12937 12944 1301 1302

1304 1306 1322 1343 1377 1384 1387 1389 1390 1391 1394 13976

13979 1401 1404 1408 1409 1412 1413 1416 1427 14318 14321 1434


16797677 Found 16797694

8

R

Br

R

Br

R = OMOM





(t J = 66 Hz 4H) 456 (s 4H) 668-673 (m 4H) 691 (s 4H) 710-721 (m 8H)

722-737 (m 6H) 13

C NMR (75 MHz) = 254 297 354 551 676 963 1198

1268 1282 1291 1293 1303 1323 1380 1400 1411 1417 1427 HRMS


8221905

9

R

R

R = OMOM

R

R

Br

Br



Chapter 4

101


6H) 330-340 (m 8H) 446 (s 4H) 453 (s 4H) 656-672 (m 12H) 688 (s 4H)

704-710 (m 4H) 714-718 (m 4H) 722-740 (m 16H) 13

C NMR (150 MHz) =

254 2962 2963 356 357 5501 5503 674 676 9629 9631 1197 1266

1268 1281 12818 12822 1290 1295 1296 1304 1308 1324 1379 1385

1394 1403 1405 1409 1416 1417 1427 1434 HRMS (MALDI-TOF-MS


14335057 Found 14335040

Ph

F

Me3Si

OMe

Br

10

NOE

NOE





3H) 676-686 (m 3H) 694-707 (m 6H) 709-728 (m 5H) 734 (d J = 84 Hz 2H) 13

C NMR (150 MHz) = -11 349 372 552 1135 1189 (d JC-F = 255 Hz)1202

(d JC-F = 92 Hz) 1258 1268 (d JC-F = 35 Hz) 1280 1283 1284 1300 1304 (d

JC-F = 159 Hz) 1326 1329 1332 (d JC-F = 45 Hz) 1339 1387 1417 1418 1430




Chapter 4

102

Ph

F

S

Br

Me3Si

OMe

11

MOMO




= 78 2H) 264-272 (m 2H) 282-289 (m 2H) 325 (s 3H) 328 (t J = 66 Hz 2H)

382 (s 3H) 448 (s 2H) 587 (d J = 39 Hz 1H) 660 (d J = 39 Hz 1H) 669-676

(m 2H) 684-696 (m 3H) 705-742 (m 16H) 13

C NMR (150 MHz) = -10 244

293 351 362 372 550 552 673 963 1127 1135 1161 (d JC-F = 225 Hz)

1244 (d JC-F = 32 Hz) 1258 1274 12827 12831 12837 12840 12856 12861

1295 1302 1307 (d JC-F = 155 Hz) 1324 1329 1330 (d JC-F = 45 Hz) 1333

1345 1385 1395 (d JC-F = 12 Hz) 1412 1416 (d JC-F = 80 Hz) 1419 1422



Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

12MOMO




mmol) t1 10 h t2 12 h

Chapter 4

103


210-224 (m 4H) 264-272 (m 2H) 279-287 (m 2H) 323-333 (m 5H) 373 (s


1H) 666-672 (m 2H) 679-694 (m 5H) 703-737 (m 20H) 773 (d J = 84 Hz

2H) 13

C NMR (150 MHz) = -11 141 143 225 244 293 350 359 370 385

550 551 607 674 963 1134 1159 (d JC-F = 224 Hz) 1243 (d JC-F = 29 Hz)

1258 1269 1271 12808 12811 12815 12820 12823 12838 12844 1290

1293 1300 1301 (d JC-F = 158 Hz) 1302 1307 1323 (d JC-F = 47 Hz) 13258

13261 1328 1336 1344 1356 1379 1382 1390 (d JC-F = 12 Hz) 1409 14190

14191 14216 (d JC-F = 80 Hz) 14219 14222 1438 1446 1476 1583 1600 (d

JC-F = 2448 Hz) 1664 IR (KBr) = 2955 1717 1509 1273 1248 1111 837 cm-1


11294440

Found 11294465

Chapter 4

104




Chem 1999 201 163




897















2404


2006 128 1828



Chapter 5

105

Chapter 5




Abstract






Chapter 5

106

Introduction





moiety1b


























Chapter 5

107


B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

OHMe

Ph

1a

3a 85

MeO

OMe

2a

B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

1b

OMe

2a

OHMe

Ph

OMe

3b 88

[Me4N]

[Me4N]




Oxidative









Chapter 5

108


O

I

O

PdI

Pd(0)

B

1a

C

Pd(0)3a

Ar = p-MeOC6H4-

Me Me

OMe

Ar

Ph

B

D

A

Pd

O

ArB

Me

Ph

B

O

ArPh

Me

Me4NI

2a







Chapter 5

109


R3

O

I

B

R2

R1

+1 mol Pd

toluene50 degC 1 h

OHR3

R1

R2

OHMe

Ph

S

OHMe

OMe

OHPh

Ph

OMe

3f 72

3h 763j 80

3g 84

3d 82

3c 83

OHMe

Ph

CF3

1 2 3

OHH

Ph

OMe

OHPh

Ph

OMe

O

O

OHPh

3e 92

F

OMe

OHPh

Ph

OMe

F3C

3i 62

R4R4

MeO

[Me4N]










Chapter 5

110

OHMe

t-Bu

S

3k 89

B +1 mol Pd

toluene

50 degC 1 h

2a

t-Bu

S

(1)

1c

[Me4N]

OHMe

n-Bu

Me

3l 80

B

n-Bu

+1 mol Pd

toluene50 degC 1 h

2a

Me

(2)

1d

[Me4N]










n-Hex

13 equiv

Ph

Li

065 equiv

(H-9-BBN) 2


1 mol Pd

toluene 50 degC 1 h

10 equiv 2aOH

Me

n-Oct

11 equiv

3m 91 (based on 2a)

B

n-Oct

PhLi

Ph




Chapter 5

111


in 59 yield11


OHH

Ph

OMe

MnO2

DCM rt

Ph

OMe

O

NH2NH2 KOHPh

OMe

4 96 5 59

3n 74

(CH2OH)2 150 C

1a +

CHO

I2b

1 mol Pd

Conclusions




Chapter 5

112



and 13


B at 128 MHz)



13C) CD3CN (δ = 194 for

1H δ = 132 for


11B) IR






(Merck)





and alkynylborate14




Li

BPh

+

B

Ph

1a


2) Me4NCl MeOH

[Me4N]

MeO

MeO










Chapter 5

113

B

Ph

1a

[Me4N]

MeO


(m 2H) 296 (s 12H) 372 (s 3H) 668-675 (m 2H) 685-691 (m 1H) 700-712 (m

4H) 743 (d J = 64 Hz 2H) 13

C NMR (CD3CN) δ = 256-272 (m) 270 274 322

350 557 560 955 1145 1227 (2C) 1273 1324 1341 1578 The boron-bound


11B NMR


3292079

B

Ph

1b

[Me4N]

OMe


(m 2H) 295 (s 12H) 374 (s 3H) 666-675 (m 2H) 702-718 (m 5H) 733 (d J =

84 Hz 2H) 13

C NMR (CD3CN) δ = 254-274 (m) 270 273 321 350 554 560





B

nBu

1d

[Me4N]

Me


(m 4H) 136-157 (m 6H) 170-196 (m 4H) 220-234 (m 5H) 304 (s 12H)

697-701 (m 2H) 704-709 (m 2H) 13

C NMR (CD3CN) δ = 152 212 270

271-290 (m) 282 288 318 324 357 561 1279 1296 1314 1344 The

Chapter 5

114




[M-(NMe4)]- 2932446 Found 2932454

B

Ph

1e

[Me4N]

F3C


(m 2H) 292 (s 12H) 690-696 (m 1H) 710-718 (m 2H) 728 (dd J = 88 08 Hz

2H) 744-752 (m 4H) 13

C NMR (CD3CN) δ = 252-270 (m) 269 273 321 351






B

Ph

1f

[Me4N]

S



48 32 Hz 1H) 703-719 (m 6H) 13

C NMR (CD3CN) δ = 266 272 270-286 (m)

323 348 560 962 1231 1256 1266 1274 1290 1300 1314 The boron-bound

sp2 and sp


11B NMR


- 3051541 Found

3051541

Chapter 5

115


(H-9BBN) 2

H tBu

THF 0 degC

THF -78 degC to rt

2) Me4NCl MeOH

Li

1)S

B

1c

[Me4N]

S

tBu














B

1c

[Me4N]

S

tBu


4H) 222-235 (m 2H) 306 (s 12H) 552 (d J = 172 Hz 1H) 591 (d J = 176 Hz


Hz 1H) 13

C NMR (CD3CN) δ = 273 276 278-296 (m) 311 327 341 352 561





Chapter 5

116












OHMe

3aOMe

NOE

no NOE

IR (ATR) 3315 1508 1248 752 694 cm-1

1H NMR δ = 159 (s 3H) 204 (bs 1H)

382 (s 3H) 684-690 (m 2H) 721-730 (m 8H) 742-748 (m 2H) 751-755 (m

1H) 13

C NMR δ = 239 552 832 1139 1208 1218 1265 1268 1272 1280


C23H21O2 [M+H]+ 3291536 Found 3291556

OHMe

OMe

3b

NOE

no NOE

IR (ATR) 3319 1508 1248 760 702 cm-1

1H NMR δ = 160 (s 3H) 208 (s 1H)

378 (s 3H) 674-680 (m 2H) 718-723(m 1H) 724-744 (m 9H) 750-755 (m

1H) 13

C NMR δ = 241 551 833 1134 1205 1218 1263 1270 1274 1284


Chapter 5

117

C23H20O2Cl [M+Cl]- 3631146 Found 3631148

OHMe

Ph

3cCF3

IR (ATR) 3298 1319 1121 750 696 cm-1

1H NMR δ = 160 (s 3H) 210 (bs 1H)

716-722 (m 1H) 723-732 (m 5H) 737-747 (m 4H) 752-764 (m 3H) 13

C NMR

δ = 240 833 1205 1221 1241 (q JC-F = 2701 Hz) 1255 (q JC-F = 37 Hz) 1269

1277 1282 1286 1293 1295 (q JC-F = 322 Hz) 1296 1341 1373 1385 1414


- 3651159 Found 3651159

OHMe

Ph

3d

S

IR (ATR) 3319 1350 1088 752 694 cm-1

1H NMR δ = 177 (s 3H) 209 (bs 1H)

696-702 (m 2H) 718 (dd J = 52 Hz 12Hz 1H) 723-730 (m 2H) 735-740 (m

3H) 742-752 (m 3H) 753-758 (m 1H) 13

C NMR δ = 254 833 1207 1216

1259 1265 1266 1275 1282 1287 1290 1294 1347 1360 1374 1410 1426


+ 3050995 Found 3050992

OHMe

OMe

3e

IR (ATR) 3310 1508 1244 1034 758 cm-1

1H NMR δ = 144 (s 3H) 158-202 (m


5H) 747 (d J = 68 Hz 1H) 13

C NMR δ = 238 266 267 305 311 382 552

822 1136 1211 1219 1257 12789 12793 1304 1406 1409 1467 1499


+ 3382115 Found 3382104

Chapter 5

118

OHH

Ph

3fOMe

MeO

IR (ATR) 3472 1601 1508 1244 704 cm-1

1H NMR δ = 174 (d J = 88 Hz 1H)


= 80 Hz 24 Hz 1H) 692-697 (m 2H) 718-730 (m 5H) 732-736 (m 2H) 753 (d

J = 84 Hz 1H) 13

C NMR δ = 552 555 766 1072 1109 1143 1244 1267 1272

1283 1292 1303 1342 1363 1390 1445 1457 1592 1606 HRMS (ESI+)


OHPh

Ph

3gOMe

IR (ATR) 3422 1508 1244 1028 746 698 cm-1

1H NMR δ = 248 (s 1H) 385 (s

3H) 695 (d J = 88 Hz 2H) 704-714 (m 5H) 715-732 (m 7H) 736-740 (m 2H)

755 (d J = 88 Hz 2H) 13

C NMR δ = 552 868 1141 1210 1231 1250 1268

12698 12702 1271 1278 12836 12844 1294 1304 1340 1402 1417 1427


+ 3911693 Found

3911718

OHPh

Ph

3hOMe

O

O

IR (ATR) 3362 1470 1244 1034 696 cm-1

1H NMR δ = 239 (s 1H) 385 (s 3H)

591 (dd J = 164 16 Hz 2H) 673 (d J = 44 Hz 2H) 690-696 (m 2H) 702-708

(m 5H) 720-736 (m 5H) 749-754 (m 2H) 13

C NMR δ = 552 863 1012 1024

Chapter 5

119

1049 1142 1249 12690 12692 1270 1278 1285 1292 1304 1340 1367


+

4341518 Found 4341505

OHPh

Ph

3iOMe

F3C

IR (ATR) 3545 1508 1321 1115 696 cm-1

1H NMR δ = 249 (s 1H) 387 (s 3H)

694-700 (m 2H) 704-715 (m 5H) 723-738 (m 6H) 742-755 (m 4H) 13

C NMR

δ = 553 866 1145 1177 (q JC-F = 37 Hz) 1233 1241 (q JC-F = 36 Hz) 1242 (q

JC-F = 2702 Hz) 1249 1260 1275 1276 1280 1287 1295 1304 1308 (q JC-F =


C29H21F3O2Cl [M+Cl]- 4931177 Found 4931192

OHPh

3j

F

OMe

IR (ATR) 3356 1242 1028 741 696 cm-1

1H NMR δ = 164-178 (m 2H) 183-208


4H) 719-737 (m 6H) 13

C NMR δ = 2675 2681 308 310 383 551 862 1114


1268 1271 1283 1303 1371 (d JC-F = 29 Hz) 1410 1418 (d JC-F = 15 Hz)



+ 4001839 Found 4001835

OHMe

S

tBu

3k

Chapter 5

120

IR (ATR) 3298 1358 1078 756 689 cm-1

1H NMR δ = 111 (s 9H) 168 (s 3H)

188 (s 1H) 640 (d J = 164 Hz 1H) 656 (d J = 164 Hz 1H) 718-730 (m 4H)

739-751 (m 3H) 13

C NMR δ = 257 295 340 822 1169 1204 1215 1242

1255 1262 1283 1285 1324 1346 1415 1452 1462 1506 HRMS (ESI+)


OHMe

nBu

OMe3l

IR (ATR) 3335 1508 1084 918 758 cm-1

1H NMR δ = 085 (t J = 72 Hz 3H) 130

(tt J = 72 72 Hz 2H) 141-167 (m 6H) 229-250 (m 5H) 702-706 (m 1H)

716-728 (m 6H) 744-748 (m 1H) 13

C NMR δ = 138 213 232 237 252 314

829 1198 1215 1256 1282 1286 1291 1318 1370 1374 1430 1492 1496


+ 2931900 Found 2931890



nHex

(H-9BBN) 2


Li

Ph

B

nOct

Li

Ph

Me

O

I


toluene 50 degC 1 h

H2O2 aq

NaOH aq

OHMe

nOct

Ph3m

MeOH




Chapter 5

121













yield)

OHMe

nOct

Ph3m

IR (ATR) 3335 1456 1078 752 698 cm-1

1H NMR δ = 096 (t J = 68 Hz 3H)

129-156 (m 15H) 160 (s 1H) 208-227 (m 2H) 274-281 (m 2H) 287-294 (m

2H) 719-728 (m 5H) 729-736 (m 3H) 742 (d J = 72 Hz 1H) 13

C NMR δ = 141

226 234 247 277 293 294 295 304 319 345 825 1186 1213 1252 1260


[M]+ 3622610 Found 3622619

OHH

Ph

OMe

3n

IR (ATR) 3354 1508 1246 764 692 cm-1

1H NMR δ = 185 (bs 1H) 386 (s 3H)

567 (s 1H) 692-697 (m 2H) 718-738 (m 10H) 763-766 (m 1H) 13

C NMR δ =

552 773 1143 1206 1237 1263 1268 1272 1283 1287 1292 1303 1342


- 3131234

Found 3131237

Chapter 5

122

The 1H


15


OHH

Ph

OMe

3n

MnO2

DCM rt

Ph

OMe

4

O







The 1H


16

Ph

OMe

4

O

(CH 2OH)2

NH2NH2

KOH Ph

OMe

5








The 1H


5

Chapter 5

123






1395ndash1411



17638ndash17640





3201ndash3222



















Chapter 5

124












3283ndash3292









74








Chem 1989 54 1485ndash1491



2006 128 1828

Chapter 5

125



4781-4787


Chem 1989 54 1485

Chapter 5

126

127

List of Publication

Chapter 1



Angew Chem Int Ed 2012 51 11750-11752

Chapter 2


Benzosultams


J Am Chem Soc 2013 135 19103-19106

Chapter 3





Org Lett 2009 11 5434-5437

Chapter 4


Units


Org Lett 2010 12 3179-3181

Chapter 5




Eur J Org Chem 2013 1421-1424

Other Publication




Chem Lett 2013 42 1076


3






obtained

Et

Ph

Ph

B O+

PhBr LPd(-allyl)Cl

L = XANTPhos

LPd(-allyl)Cl

L = P(o-tol)3 Ph

Et

Ph

B O

B

Et

Ph

Et

Ph

B

Ph

Ph

Et

B

Ph

Me3NO

Me3NO

[Me4N]







MeO

Br

I

Br

NaOH

R Ph

MeO Br

B

R

Ph

RB

Ph

OMe

[Me4N]

R Ph

MeOR Ph

Br

R =OMOM

n

B

R

Ph

[Me4N] I

Br

NaOH

R Ph

MeOR Ph

Br

n = 2~4

Pd-XANTPhos

Pd-XANTPhos






4


regioselectively

I

Me

O+

MeOH

R2

R1Pd-XANTPhosB

R2

R1

[Me4N]


5

Reference





































6








10990




2003 Vol 3





Q Z J Med Chem 2009 52 4192



2006 250 1107



2419













7



17638ndash17640


8

Chapter 1

9

Chapter 1


Ketones

Abstract






Chapter 1

10

Introduction







2 One







starting substances


CO2

sun

CO2energy charge

high energy

intermediates











8






Chapter 1

11


Ph

O

NTs

Mesolar light

N

Ph OH

Ts

2a 91

1aDMA







over 04 kWm-2



in eight hours on


Figure





kWhm-2



Chapter 1

12


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

0

20

40

60

80

100

0 1 2 3 4 5 6











(56)

Chapter 1

13


40 equiv Cs2CO3

1 atm CO2

DMA 60 degC

OO

O

Ph

NHTs

3a 93

N

Ph OH

Ts

2a








N

Ph O

Ts

A

N

Ph O

Ts

B

O

O

OO

O

Ph

NTs

CO2

H

C

Cs2CO3

CsHCO 3

Cs

Cs

Cs

2

1

N

Ph OH

Ts

2a

OO

O

Ph

NHTs

3a












N

Ts

OHPh

4

Chapter 1

14




solar light

CO2Cs2CO3

60degCDMAPh

O

NTs

Me

1a

OO

O

Ph

NHTs

3a 83






chloro groups10





Ar

O

NR

Me OO

O

Ar

NHR3

1

OO

O

NHTs3b 80

MeO

OO

O

NHTs3c 57

F3C

OO

O

NHTs3d 73

Cl

OO

O

NHTs3e 85

Br

OO

O

Ph

NH

3f 87

O2S OMe

OO

O

Ph

NH

3g 85

O2S CF3

OO

O

Ph

NH

3h 87

O2S

N

solar lightCO2

Cs2CO3

60degCDMA




Chapter 1

15

Conclusions















Chapter 1

16












indicator (Merck)






Ph

O

NTs

MeTsClMeNH2 +

Et2OTsNHMe

CH3CN

K2CO3












Chapter 1

17


Ph

O

NTs

Me


745-751 (m 2H) 760 (tt J = 76 12 Hz 1H) 771-775 (m 2H) 795-799 (m 2H)

13C NMR δ = 215 356 560 1275 1282 1288 1297 1338 1347 1348 1436


+ 3041002 Found mz 3040994 IR

(ATR) 1693 1339 1227 1157 743 cm-1

O

NTs

Me

1bMeO


733 (d J = 80 Hz 2H) 770-774 (m 2H) 796-802 (m 2H) 13

C NMR δ = 215

355 555 558 1139 1275 1277 1296 1307 1346 1436 1640 1921 HRMS


+ 3341108 Found mz 3341101 IR (ATR) 1688

1601 1329 1180 1159 cm-1

O

NTs

Me

1cF3C


= 84 Hz 2H) 776 (d J = 84 Hz 2H) 812 (d J = 84 Hz 2H) 13

C NMR δ = 215

357 564 1234 (q JC-F = 2711 Hz) 1259 (q JC-F = 37 Hz) 1276 1288 1298



1121 1109 cm-1

Chapter 1

18

O

NTs

Me

1dCl


(m 2H) 771 (d J = 80 Hz 2H) 792-796 (m 2H) 13

C NMR δ = 216 356 561



1159 1088 cm-1

O

NTs

Me

1eBr


= 84 Hz 2H) 771 (d J = 84 Hz 2H) 786 (d J = 84 Hz 2H) 13

C NMR δ = 215

356 561 1275 1291 1297 1298 1321 1334 1344 1438 1930 HRMS (ESI+)


1223 1155 810cm-1

Ph

O

NS

Me

1f

OMe

OO

1H NMR δ = 282 (s 3H) 389 (s 3H) 456 (s 2H) 698-703 (m 2H) 746-751 (m

2H) 761 (tt J = 72 12 Hz 1H)776-781 (m 2H) 796-800 (m 2H) 13

C NMR δ =

356 556 561 1142 1283 1288 1294 1297 1338 1348 1630 1938 HRMS


+ 3200951 Found mz 3200943 IR (ATR) 1692

1342 1259 1155 741 cm-1

Chapter 1

19

Ph

O

NS

Me

1g

CF3

OO


780 (d J = 84 Hz 2H) 790-794 (m 2H) 798 (d J = 80 Hz 2H) 13

C NMR δ =

356 558 1233 (q JC-F = 2711 Hz) 1261 (q JC-F = 36 Hz) 12796 12799 1289



1059 748 cm-1

Ph

O

NS

Me

1h

N

OO

1H NMR δ = 302 (s 3H) 486 (s 2H) 744-753 (m 3H) 757-762 (m 1H)

788-798 (m 4H) 870 (ddd J = 48 16 08 Hz 1H)13

C NMR δ = 363 569 1224



752 cm-1


Ph

O

NTs

Mesolar light

N

Ph OH

TsDMA rt

1a

2a








Chapter 1

20


N

Ph OH

Ts


2H) 728-737 (m 5H) 740 (d J = 80 Hz 2H) 779 (d J = 80 Hz 2H) 13

C NMR δ

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS




N 458 O 1555 S 1058 IR (ATR) 3477 1333 1184 1148 671 cm-1


N

Ph OH

Ts

2a

40 equiv Cs2CO3

1 atm CO2

DMA 60 C

OO

O

Ph

NHTs

3a








mmol 93 yield)

Chapter 1

21



40 equiv Cs2CO3

60 CPh

O

NR

Me OO

O

Ph

NHR3a

1a

solar light

DMA rt

1 atm CO2











OO

O

Ph

NHTs



726-732 (m 4H) 734-743 (m 3H) 769-773 (m 2H) 13

C NMR δ = 215 503

724 850 1242 1269 1292 1299 1365 1381 1439 1542 HRMS (ESI+) Calcd

for C17H18NO5S M+H+


C 5878 H 493 N 403 O 2303 S 923 Found C 5871 H 496 N 389 O

2284 S 932 IR (ATR) 3261 1773 1435 1319 1045 cm-1

Chapter 1

22

OO

O

NHTs

3b

MeO



56 Hz 1H) 688-693 (m 2H) 719-724 (m 2H) 728 (d J = 80 Hz 2H) 770 (d J =

84 Hz 2H) 13

C NMR δ = 215 503 554 724 848 1145 1256 1269 1298


+

3781006 Found mz 3780996 IR (ATR) 3238 1794 1518 1329 1057 723 cm-1

OO

O

NHTs

3c

F3C



729 (d J = 84 Hz 2H) 746 (d J = 84 Hz 2H) 765-771 (m 4H) 13

C NMR δ =

215 501 722 846 1235 (q JC-F = 2704 Hz) 1249 1263 (q JC-F = 37 Hz) 1268



1067 cm-1

OO

O

NHTs

3d

Cl



722-727 (m 2H) 728 (d J = 84 Hz 2H) 735-739 (m 2H) 769 (d J = 84 Hz 2H)

13C NMR δ = 215 502 723 847 1257 1268 1294 1300 1353 1364 1365


+ 3820510 Found mz

Chapter 1

23

3820506 IR (ATR) 3250 1800 1325 1155 1069 cm-1

OO

O

NHTs

3e

Br



716-720 (m 2H) 728 (d J = 80 Hz 2H) 750-755 (m 2H) 766-770 (m 2H) 13

C

NMR δ = 215 501 723 847 1235 1260 1268 1300 1323 1364 1370 1441


+ 4260005 Found mz 4260003

IR (ATR) 3252 1800 1331 1175 1057 cm-1

OO

O

Ph

NH

SO

O

OMe



693-698 (m 2H) 727-732 (m 2H) 734-744 (m 3H) 773-778 (m 2H) 13

C NMR

δ = 503 556 724 849 1145 1242 1291 1292 1310 1381 1541 1632 HRMS


+ 3640849 Found mz 3640836 IR (ATR) 3246

1801 1325 1155 1067 cm-1

OO

O

Ph

NH

SO

O

CF3

3g

Chapter 1

24



2H) 735-744 (m 3H) 775 (d J = 88 Hz 2H) 796 (d J = 84 Hz 2H) 13

C NMR δ

= 505 725 851 1231 (q JC-F = 2711 Hz) 1241 1265 (q JC-F = 37 Hz) 1274



1161 1105 cm-1

OO

O

Ph

NH

SO

O

N




1H) 798 (d J = 76 Hz 1H) 866 (d J = 44 Hz 1H) 13

C NMR δ = 510 723 849



1175 1063 cm-1


N

Ts

OHPh

N

Ts

O CeCl 3

PhLi

THF -78 C to rt

4






Chapter 1

25






N

Ts

OHPh


351-364 (m 4H) 726-738 (m 7H) 773-777 (m 2H) 13

C NMR δ = 215 396

469 608 804 1250 1276 1280 1286 1297 1339 1418 1435 HRMS (ESI+)


1325 1159 1101 770 cm-1

Chapter 1

26











Soc 2011 133 12881

























25 312

Chapter 1

27








Chapter 1

28

Chapter 2

29

Chapter 2



Abstract







Chapter 2

30

Introduction














A



Indanones are


A rearrangement













Whereas







Chapter 2

31




N

HO Ph

S NS Me

HO PhMe

1a2a 96

Me

O

OO O


2) is





The generated








N

S O

O

O[Rh]

Ph

SN

[Rh]O Ph

O OMe

[Rh] OH

N

S O

O

O Ph

H

[Rh]

H

N

[Rh]O Ph

S O

O

Me Me

Me

Me

1a

H2O

2a

A B

CD

1a

A




Chapter 2

32








N

HO Ph

SN

S CH19D11

HO Ph

D3C

1a-d2a-d 96

D3C

O

O

O O

D

D

D

D

D

D

H01D09

8



D12




Application




1

2

SN

HO Ar

O OMe

N

HO Ar

S O

O


K2CO 3 (20 equiv)


NS Me

HO PhMe

2a

91 er = 928

O O

NS Me

HO Ph

2b

95 er = 937

O O

S

NS Me

HOMe

2c

90 er = 937

O O

OMe

NS Me

HOMe

2c

92 er = 919

O O

CF3



Chapter 2

33










HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6 84

5 56



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3


PhMgBr

THF rt 1 h N

HO

Ts

Me

1e 93

er gt 991 dr = 201

Ph

3







SN

HO PhMe

O OMe

MeN

HO Ph

S O

O

Me

Me

1e

er gt 991 dr = 201

2e 99

er gt 991 dr gt 201





Chapter 2

34









SN

PhRhOMe

O OMe

Me

SN

PhRhOMe

O OMe

Me

favored

disfavored

F

F

NSRh

Ph

Me

O

O

MeO

H

Me

E

E

NSRh

Ph

Me

O

O

MeO

Me

H














Chapter 2

35


1

er gt 991 dr gt 201

2

er gt 991 dr gt 201

SN

HO ArR

O OMe

N

HO Ar

S O

O





1 N

HO Ph

S O

O

Me

Me

1f

SN

HO PhMe

O OMe

Me

2e 99

6 N

HO

S O

O

Me

1k

OMe

SN

HOMe

O OMe

2k 97

OMe

2

N

HO Ph

S O

O

MeO

Me

1g

SN

HO PhMe

O OMe

MeO

2g 98

7 N

HO

S O

O

Me

Me

1l

CF3

SN

HOMe

O OMe

Me

2l 97

CF3

3 N

HO Ph

S O

O

F3C

Me

1h

SN

HO PhMe

O OMe

F3C

2h 99

8 N

HO Ph

S O

O

Me

i-Pr

1m

SN

HO Phi-Pr

O OMe

Me

2m 97

4

N

HO Ph

S O

O

Me

1iMe

SN

HO PhMe

O OMeMe

2i 99

9 N

HO Ph

S O

O

Me

SMe

SN

HO Ph

O OMe

Me

2n 97

SMe

5 N

HO Ph

S O

O

Me

S

1j

SN

HO PhMe

O OMeS

2j 99



Chapter 2

36

Conclusions






Chapter 2

37





13C NMR


13C at 10069












N

OHNEt3

DCM rt 12 h


2) PhMgBrTHF rt 3 h

N

HO Ph

1a

TsCl

N

OH

8a

H HCl

Ts Ts









Chapter 2

38

N

S

Me

O

O

OH

8a 1H NMR = 213 (bs 1H) 245 (s 3H) 350-361 (m 2H) 394-404 (m 2H)

442-452 (m 1H) 737 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR =



-1

N

S

D3C

O

O

OH

8a-d

D

D

D

D

1H NMR = 283 (bs 1H) 349-355 (m 2H) 389-396 (m 2H) 435-444 (m 1H)



+ 2351128 Found mz

2351125 IR (ATR) 3503 1333 1142 1059 638 cm-1

N

S O

O

OH

8b

S

1H NMR = 277 (bs 1H) 357-364 (m 2H) 400-407 (m 2H) 441-450 (m 1H)


1H) 13



1038 737 cm-1

Chapter 2

39














N

HO Ph

S

1a

Me

O

O


2H) 728-737 (m 5H) 739 (d J = 84 Hz 2H) 778 (d J = 80 Hz 2H) 13

C NMR

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS


+ 3041002 Found mz 3040995 IR (ATR) 3477

1333 1184 1148 671 cm-1


N

HO Ph

S

1a-d

D3C

O

O

D

D

D

D


(m 5H) 13

C NMR = 203-211 (m) 652 703 1244 1281 (t JC-D = 247 Hz)


Chapter 2

40


702 648 cm-1

N

HO Ph

S

S

O

O



1H) 13

C NMR = 656 702 1244 1280 1283 1288 1331 13387 13392 1417


+ 2960410 Found mz 2960404 IR

(ATR) 3524 1333 1161 1148 748 cm-1

N

HO

S

Me

O

O

OMe

1c



2H) 775 (d J = 80 Hz 2H) 13

C NMR =216 553 652 702 1139 1259 1285


+

3341108 Found mz 3341097 IR (ATR) 3460 1518 1331 1250 1146 cm-1

N

HO

S

Me

O

O

CF3



C NMR

Chapter 2

41

=216 654 697 1239 (q JC-F = 2704 Hz) 1249 1255 (q JC-F = 37 Hz) 1284



1109 1076 cm-1


1l-1n

HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6a

5a



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3

acetone H2O

rt 10 h 4a

PhMgBr

THF rt 1 h N

OH

Ts

Me

1e

Ph

3a



procedure16













Me

NHTs

O

N2


Chapter 2

42

2H) 730 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR = 194 215 539


+

2680750 Found mz 2680747 IR (ATR) 2112 1639 1337 1319 1161 cm-1

[]27

D = -1184 (c = 079 in CHCl3)


i-Pr

NHTs

O

N2



2H) 769 (d J = 84 Hz 2H) 13

C NMR =169 193 215 315 548 647 1273


+ 2961063

Found mz 2961060 IR (ATR) 2129 1622 1362 1329 1161 cm-1

[]28

D = -730 (c = 071 in CHCl3)

NHTs

O

N2

5c

SMe

1H NMR = 174-196 (m 2H) 204 (s 3H) 242 (s 3H) 244-252 (m 2H)

390-400 (m 1H) 541 (s 1H) 560-572 (m 1H) 730 (d J = 84 Hz 2H) 772 (d J =

84 Hz 2H) 13

C NMR = 153 215 297 323 545 585 1272 1297 1366 1439


+ 3280784 Found mz 3280779

IR (ATR) 2129 1618 1375 1339 1163 cm-1

[]29

D = -506 (c = 063 in CHCl3)









Chapter 2

43

N

O

Ts

Me

6a

1H NMR = 145 (d J = 68 Hz 3H) 246 (s 3H) 443-454 (m 2H) 473-480 (m

1H) 736-742 (m 2H) 776-781 (m 2H) 13

C NMR = 157 216 696 810 1284


+ 2400689

Found mz 2400688 IR (ATR) 1825 1339 1155 669 cm-1

[]28

D = 614 (c = 081 in CHCl3)


N

O

Ts

i-Pr

6b

1H NMR = 099-111 (m 6H) 206-218 (m 1H) 246 (s 3H) 441 (dd J = 164 36


2H) 777 (d J = 80 Hz 2H) 13

C NMR = 174 181 216 304 703 903 1284


+ 2681002

Found mz 2680998 IR (ATR) 1815 1340 1155 1007 671 cm-1

[]29

D = 567 (c = 095 in CHCl3)

N

O

Ts

6c

SMe

1H NMR = 204 (s 3H) 209-218 (m 2H) 247 (s 3H) 265-279 (m 2H) 446 (d


2H) 780 (d J = 80 Hz 2H) 13

C NMR = 147 216 291 293 705 832 1286


+ 3000723

Found mz 3000718 IR (ATR) 1813 1342 1308 1157 667 cm-1

[]29

D = 1183 (c = 036 in CHCl3)


Chapter 2

44










N

HO

S O

O

Me

Me

1e

H

NOE

NOE



(m 3H) 739 (d J = 84 Hz 2H) 777 (d J = 84 Hz 2H) 13

C NMR = 144 216

628 702 731 1247 1279 1284 1285 1298 1319 1415 1443 HRMS (ESI+)


1155 1092 667 cm-1

[]25




Chapter 2

45

N

HO

S O

O

Me

1l

H

NOE

NOE

CF3

Me



739-747 (m 4H) 777 (d J = 84 Hz 2H) 13

C NMR = 143 216 630 706 727

1238 (JC-F = 2704 Hz) 1253 1254 (JC-F = 36 Hz) 1285 1299 1301 (JC-F = 324


+ 3861032

Found mz 3861025 IR (ATR) 3422 1327 1151 1109 839 cm-1

[]28




N

HO

S O

O

Me

iPr

1m

H

NOE

NOE



= 100 Hz 1H) 690-696 (m 2H) 712-720 (m 3H) 732 (d J = 80 Hz 2H) 773 (d

J = 80 Hz 2H) 13

C NMR = 190 193 215 291 641 729 801 1247 1275


+

3461471 Found mz 3461466 IR (ATR) 3454 1331 1163 739 669 cm-1

[]27



Chapter 2

46


N

HO Ph

S O

O

1n

Me

SMe

1H NMR = 202 (s 3H) 218-258 (m 8H) 388-394 (m 2H) 427 (dd J = 84 48

Hz 1H) 688-693 (m 2H) 714-721 (m 3H) 740 (d J = 80 Hz 2H) 779 (d J = 80

Hz 2H) 13

C NMR = 154 216 290 297 634 725 733 1246 1277 1284


+

3781192 Found mz 3781188 IR (ATR) 3481 1339 1157 702 669 cm-1

[]28












N

HO

S O

O

Me

Me

1f

H

NOE

NOE


1H) 398 (q J = 64 Hz 1H) 424 (dd J = 84 08 Hz 1H) 732-744 (m 5H)

750-755 (m 2H) 774-778 (m 2H) 13

C NMR = 165 216 627 718 739 1257

Chapter 2

47



-1

[]25






HO2C Me

NHCbz

Me

NHCbz

O

N2N

O

Cbz

Me

6d5d

1) (COCl) 2 DMF

2) CH2N2 Rh2(OAc)4 (05 mol )

DCM rt 12 h4d

PhMgBr

THF rt 1 h

N

OH

Cbz

Me

7a

Ph

N

OH

H

Me

PhPd C (5 mol )

H2 (1atm)

MeOH rt 12 h

MeO SO2Cl

NEt3

DCM rt 12 h

N

HO Ph

S O

O

MeO

Me

1g









Me

NHCbz

O

N2

5d 1H NMR = 134 (d J = 68 Hz 3H) 420-436 (m 1H) 504-516 (m 2H) 534-564

(m 2H) 728-736 (m 5H) 13

C NMR = 184 535 (2C) 669 1280 1282 1285


+ 2481030 Found mz

2481028 IR (ATR) 2116 1717 1636 1533 1252 cm-1

[]28

D = -434 (c = 085 in CHCl3)


Chapter 2

48







N

O

Cbz

Me

6d


Hz 1H) 498-505 (m 1H) 513-521 (m 2H) 731-739 (m 5H) 13

C NMR = 153



696 cm-1

[]29

D = 390 (c = 068 in CHCl3)










N

OH

Cbz

Me

7a

Ph


= 96 Hz 1H) 458 (q J = 64 Hz 1H) 507-518 (m 2H) 729-746 (m 10H) 13

C

NMR = 142 623 667 689 730 1246 1278 1279 1280 1285 1287 1366

Chapter 2

49


+ 2981438 Found mz

2981433 IR (ATR) 1670 1423 1248 1016 702 cm-1

[]29

D = 46 (c = 089 in CHCl3)

N

OH

Cbz

Me

7b

MeO


1H) 432 (d J = 96 Hz 1H) 452-461 (m 1H) 506-518 (m 2H) 687-694 (m 2H)

726-739 (m 7H) 13

C NMR = 143 553 622 666 687 729 1140 1260 1278


+

3281543 Found mz 3281539 IR (ATR) 1682 1418 1352 1024 696 cm-1

[]29

D = 02 (c = 085 in CHCl3)








pressure







mmol 58 yield)

Chapter 2

50

N

HO

S O

O

MeO

Me

1g

H

NOE

NOE


390 (s 3H) 399 (d J = 92 Hz 1H) 419 (q J = 60 Hz 1H) 698-707 (m 4H)

720-727 (m 3H) 779-785 (m 2H) 13

C NMR = 143 557 627 701 731 1144



-1

[]28




N

HO

S O

O

F3C

Me

1h

H

NOE

NOE


406 (d J = 92 Hz 1H) 430 (qd J = 64 08 Hz 1H) 694-699 (m 2H) 721-727

(m 3H) 784 (d J = 80 Hz 2H) 801 (d J = 84 Hz 2H) 13

C NMR = 145 629

706 729 1232 (JC-F = 2711 Hz) 1245 1263 (JC-F = 37 Hz) 1283 12868 12871


+

3720876 Found mz 3720870 IR (ATR) 3503 1348 1323 1165 646 cm-1

[]28




Chapter 2

51

N

HO

S O

O

Me

1i

H

NOE

NOE


1H) 401 (d J = 88 Hz 1H) 422 (q J = 64 Hz 1H) 694-698 (m 2H) 720-724 (m

3H) 746-750 (m 2H) 767-772 (m 2H) 13

C NMR = 144 214 630 704 730

1247 1256 1279 1285 1286 1291 1341 1347 1395 1416 HRMS (ESI+)


1151 714 700 cm-1

[]29




N

HO

S O

O

Me

1j

H

NOE

NOE

S


Hz 1H) 425 (q J = 64 Hz 1H) 696-701 (m 2H) 720-728 (m 4H) 764-767 (m

1H) 769-772 (m 1H) 13

C NMR = 144 632 709 730 1246 1279 1281 1286


+ 3100566

Found mz 3100559 IR (ATR) 3508 1340 1151 756 669 cm-1

[]29




Chapter 2

52

N

HO

S O

O

Me

1k

H

NOE

NOE

OMe


1H) 394 (d J = 88 Hz 1H) 416 (q J = 64 Hz 1H) 670-675 (m 2H) 684-689 (m

2H) 756-762 (m 2H) 765-770 (m 1H) 786-790 (m 2H) 13

C NMR = 143 553

630 704 729 1138 1259 1283 1292 1332 1337 1348 1592 HRMS (ESI+)


1327 1155 606 cm-1

[]29





Screening







mmol 93 yield)

Chapter 2

53


rac -DM-BINAP

rac-BINAP

dppf

dppb

PPh3

dppe

46

trace

trace

yield

PCy3

Ligand

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

entry

1

2

3

4

5

6

7

8

nd

nd

nd

93

none nd

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a


entry Ligand yield

1

2

3

4

(R)-BINAP

(R)-DM-BINAP

(R)-SEGPHOS

(R)-DIFLUORPHOS

er

94

46

48

43

5

6

(R)-DM-SEGPHOS


3862

91

7

8

(R)-MeO-BIPHEP

(R)-MeO-DM-BIPHEP

64

91

892

3169

1288

1486

2476

2575

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a










Chapter 2

54

NS Me

HO PhMe

2a

O O


J = 148 Hz 1H) 683 (s 1H) 727-744 (m 6H) 781 (d J = 84 Hz 1H) 13

C NMR

= 216 361 626 732 1238 1263 1280 1284 1299 1301 1330 1412 1431


+ 3041002 Found mz 3040998 IR

(ATR) 3472 1325 1161 1142 735 cm-1

[]29




NS CH2D

HO Ph

D3C

2a-d

O O

D

D

D


J = 148 Hz 1H) 728-743 (m 5H) 13

C NMR = 201-210 (m) 358 (t JC-D = 212

Hz) 625 731 1234 (t JC-D = 249 Hz) 1262 1279 1283 1291-1300 (m 2C)


+ 3111441

Found mz 3111436 IR (ATR) 3524 1318 1290 1150 721 cm-1

NS Me

HO Ph

O O

S

2b


1H) 668 (d J = 52 z 1H) 730-738 (m 5H) 750 (d J = 52 Hz 1H) 13

C NMR =

378 630 722 1257 1264 1282 1286 1299 1338 1427 1467 HRMS (ESI+)


1150 1063 748 cm-1

[]29


Chapter 2

55



NS Me

HOMe

O O

OMe

2c


422 (d J = 148 Hz 1H) 684-690 (m 3H) 724-733 (m 3H) 774-779 (m 1H) 13

C

NMR = 216 360 553 626 729 1137 1237 1275 1299 1230 1328 1351


+ 3341108 Found mz

3341098 IR (ATR) 3441 1508 1250 1144 735 cm-1

[]29




NS Me

HOMe

O O

CF3



2H) 782 (d J = 80 Hz 1H) 13

C NMR = 216 360 625 731 12392 (q JC-F =

2708) 12395 1254 (q JC-F = 36 Hz) 1268 1298 1303 (q JC-F = 352) 1329


+ 3720876 Found

mz 3720869 IR (ATR) 3481 1323 1121 1067 733 cm-1

[]29




Chapter 2

56










SN

HO

Me

O OMe

Me

2e

H

NOE

NOE


= 68 Hz 1H) 675 (s 1H) 723-738 (m 6H) 777 (d J = 84 Hz 1H) 13

C NMR =

119 215 314 608 750 1242 1262 1275 1282 1298 1301 1316 1427


+ 3181158 Found mz

3181155 IR (ATR) 3481 1315 1163 1146 683 cm-1

[]28




SN

HO

Me

O OMe

MeO

2g

H

NOE

NOE

Chapter 2

57



5H) 782 (d J = 88 Hz 1H) 13

C NMR = 120 314 555 609 752 1144 1151



735 cm-1

[]29




SN

HO

Me

O OMe

F3C

2h

H

NOE

NOE



1H) 13

C NMR = 118 314 608 750 1228 (q JC-F = 2711 Hz) 1251 1258 (q



+ 3720876 Found

mz 3720872 IR (ATR) 3461 1325 1161 1142 739 cm-1

[]29




SN

HO

Me

O OMe

2i

H

NOE

NOE

Me

Chapter 2

58


J = 68 Hz 1H) 684 (d J = 80 Hz 1H) 718-736 (m 6H) 770 (s 1H) 13

C NMR

=119 211 314 607 748 1242 1262 1275 1282 1299 1338 1341 1395


+ 3181158 Found mz

3181155 IR (ATR) 3489 1448 1319 1148 735 cm-1

[]29




SN

HO

Me

O OMe

2j

H

NOE

NOES


1H) 656 (d J = 52 Hz 1H) 726-736 (m 5H) 743 (d J = 48 Hz 1H) 13

C NMR

= 114 319 619 742 1256 1266 1278 1284 1297 1334 1429 1480 HRMS


+ 3100566 Found mz 3100561 IR (ATR) 3524

1329 1151 1020 729 cm-1

[]29




SN

HO

Me

O OMe

2k

H

NOE

NOE

OMe


J = 68 Hz 1H) 685 (d J = 88 Hz 2H) 698-703 (m 1H) 722-730 (m 2H)

738-748 (m 2H) 785-790 (m 1H) 13

C NMR = 119 314 553 608 747 1136

Chapter 2

59



760 cm-1

[]26




SN

HO

Me

O OMe

2l

H

NOE

NOE

CF3

Me



= 84 Hz 2H) 778 (d J = 80 Hz 1H) 13

C NMR = 119 215 313 607 749




-1

[]26




SN

HO

iPr

O OMe

2m

H

NOE

NOE

Me


(m 1H) 264 (s 1H) 285 (s 3H) 441 (d J = 100 Hz 1H) 685 (s 1H) 714-735 (m

4H) 748 (d J = 76 Hz 2H) 772 (d J = 80 Hz 1H) 13

C NMR = 211 214 217

278 330 718 742 1244 1256 1270 1283 1292 1295 1300 1435 1442


+ 3461471 Found mz 3461466 IR

Chapter 2

60

(ATR) 3412 1315 1165 1146 683 cm-1

[]29




SN

HO

O OMe

2n

H

Me

NOE

SMe

1H NMR = 160-170 (m 1H) 184 (s 3H) 212-226 (m 4H) 230-242 (m 2H)

254-263 (m 1H) 294 (s 3H) 471 (dd J = 108 28 Hz 1H) 675 (s 1H) 722-738

(m 6H) 776 (d J = 80 Hz 1H) 13

C NMR = 150 215 242 301 321 643 748

1245 1262 1276 1283 12986 12993 1312 1429 1437 1441 HRMS (ESI+)


1165 1134 748 cm-1

[]28









was used as a


and


21 All



Chapter 2

61



2e

formula C17H19NO3S

fw 31739

T (K) 100(2)


space group P21c

a (Aring) 105967(5)


3) 152058(13)

Z 4 Dcalc (gcm

3) 1386

(mm-1

) 0225 F(000) 672



348500135

params 203 GOF on F

2 1069

R1 wR2 [Igt2(I)]

00322 00868

R1 wR2 (all data)

00335 00878

Chapter 2

62

























Med Chem 2003 46 1116








Chapter 2

63

































Chapter 2

64




2012 51 9160





11437-11439
























Chapter 2

65











2548-2551







11750









32 115



Chapter 2

66

Chapter 3

67

Chapter 3




Halides

Abstract






Chapter 3

68

Introduction
















2) are












several months


Et LiB

Ph

+B

Ph

Et

1a 74

(a)(b)[Me4N]


Chapter 3

69

















OMe

BrB

Ph

Et

OMe

3a

Ph

Et

OMe

H

4a

Pd-ligand AcOH

2a

+B

Ph

Et

1a

[Me4N]


EZ of 4ab

1 P(o-tol)3 69 397

2 P(t-Bu)3 47 1783

3 1-[(t-Bu)2P](biphenyl) 18 2872

4 2-[(t-Bu)2P](11-binaphthyl) 21 6733

5 DPEPhos 24 928



analysis



Chapter 3

70









Pd(0)

Pd

MeO

B

PdEt

OMe

Ph

B

Ph

Et

2a

BC

Pd

MeO

Br

A

1a

3a







dominates10
















Chapter 3

71










Chapter 3

72


BO

Ph

Et

OMe

5a 83

BO

Ph

Et

CF3

5b 85

BO

Ph

Et

NPhth

5c 82

BO

Ph

Et

5d 72b

BO

Ph

Et

5e 85

S

BO

n-Pr

Me

Cl

5f 74

BO

n-Pr

Ph

OMe

5g 82

BO

Ph

S

5h 83

BO

Ph

CO2Et

5i 81

BO

Ph

5j 82

Cl

BO

Ph

CF3

TBSO

BO

Cl

S

Ph

BO

Ph

Me

OMe

5n 71b

5m 925l 82

BO

Ph

5k 76

Me

+B

Ar

R

1

[Me4N]

2


BO

Ar

R

Ar

5







The reaction of 1a






Chapter 3

73








(E)-5o83 EZ = gt955

BO

Ph

Et

Ph

Ph

Et

PhO

NMe2

(Z)-685 EZ = lt595

Ph

Ph

EtO

NMe 2

(E)-675 EZ = 928

1a

(Z)-5o71 EZ = 793

+ PhBr

BO

Ph

Ph

Et

(a)

(c) (c)

(b)






Conclusions






Chapter 3

74




1H at 400 MHz and

11B at 128 MHz)



13C)

CD3CN ( = 194 for 1H =132 for


11B)









and Ph-9-BBN18


procedures


Et LiB

Ph

+B

Ph

Et

1a


2) Me4NCl MeOH

[Me4N]









74 yield)

Chapter 3

75

B

Ph

Et

1a

[Me4N]


136-207 (m 11H) 236-250 (m 2H) 303 (s 12 H) 679-686 (m 1H) 700-707 (m

2H) 735 (d J = 72 Hz 2H) 13

C NMR (CD3CN) = 149 166 266 (q JC-B = 379

Hz) 271 275 324 349 561 948 1221 1269 1339 11

B NMR = -133 HRMS




n-Pr LiB

Ar


2) Me4NCl MeOH B

n-Pr

1b

Cl

[Me4N]










Chapter 3

76

B

n-Pr

1b

Cl

[Me4N]

1H NMR (CD3CN) = 084-096 (m 5H) 111-121 (m 1H) 126-200 (m 13H)

235-250 (m 2H) 304 (s 12H) 700-705 (m 2H) 733 (d J = 84 Hz 2H) 13

C NMR

(CD3CN) = 139 234 249 266 (q JC-B = 393 Hz) 270 273 323 348 561

933 1265 1272 1355 11


[M-(NMe4)] 2991738 Found 2991730

B

n-Pr

1c

OMe

[Me4N]


128-201 (m 13H) 237-252 (m 2H) 303 (s 12H) 371 (s 3H) 663-668 (m 2H)

723 (d J = 81 Hz 2H) 13

C NMR (CD3CN) = 140 235 250 268 (q JC-B = 393

Hz) 272 275 324 349 554 561 929 1128 1344 1561 11

B NMR = -135


B

Ph

1d

[Me4N]


(m 2H) 134-196 (m 9H) 230-244 (m 2H) 304 (s 12H) 679-686 (m 1H)

699-706 (m 2H) 733 (d J = 72 Hz 2H) 13

C NMR (CD3CN) =23 87 266 (q

JC-B = 393 Hz) 271 274 323 349 562 1222 1269 1338 11

B NMR = -134


Chapter 3

77

B

Ph

1e

[Me4N]


(m 3H) 302 (s 12H) 679-686 (m 1H) 699-706 (m 2H) 734 (d J = 66 Hz 2H) 13

C NMR (CD3CN) = 253 268 (q JC-B = 379 Hz) 271 275 324 333 349 361

561 980 1221 1269 1339 11


[M-(NMe4)] 2912284 Found 2912278

B

1f

S

Ph

[Me4N]




09 Hz 1H) 712-730 (m 5H) 13

C NMR (CD3CN) = 240 268-290 (m) 325 347

380 562 928 1225 1261 1265 1271 1289 1297 1434 11

B NMR = -135


B

Ph

1g

TBSO

[Me4N]

1H NMR (CD3CN) = 005 (s 6H) 084-096 (m 11H) 110-120 (m 1H) 134-197

(m 9H) 216-233 (t J = 72 Hz 2H) 235-250 (m 2H) 301 (s 12H) 356 (t J = 78

Hz 2H) 680-687 (m 1H) 700-708 (m 2H) 735 (d J = 66 Hz 2H) 13

C NMR

(CD3CN) = -50 189 254-277 (m) 323 348 561 649 889 1222 1269

1339 11


Found 3812789

Chapter 3

78

B

Ph

1h

OMe

[Me4N]


(m 2H) 298 (s 12H) 373 (s 3H) 668-674 (m 2H) 701-718 (m 5H) 732 (d J =

87 Hz 2H) 13

C NMR (CD3CN) = 255-277 (m) 322 350 554 561 961 1129

1251 1287 1302 1312 1345 1564 11


C23H26BO [M-(NMe4)] 3292077 Found 3292081



Br

+

MeO


6 mol Ligand


2a

B

Ph

Et

OMe

(E)-3a

AcOH

Ph

Et

OMe

H

Ph

B

Et

OMe

+

+

(Z)-3a

(E)-4a

H

Et

OMe

Ph

(Z)-4a

B

Ph

Et

1a

[Me4N]









Chapter 3

79




B

Ph

Et

+


toluene 70 degC

Me3NO

Br

MeO

BO

Ph

Et

OMe

5a

1a

2a

[Me4N]









BO

Ph

Et

OMe


383 (s 3H) 438-444 (m 1H) 685-691 (m 2H) 714-736 (m 7H) 13

C NMR =

138 221 267 273 (br) 277 312 553 736 1132 1251 1278 1283 1298

1366 1436 1494 1586 11


3742417 Found 3742410

Chapter 3

80

BO

Ph

Et

CF3

5b


437-443 (m 1H) 718-726 (m 3H) 734-739 (m 2H) 745-748 (m 2H) 760-763

(m 2H) 13

C NMR = 135 220 266 271 (br) 276 312 738 12429 (q JC-F =

2701 Hz) 1247 (q JC-F = 36 Hz) 1280 1281 1289 (q JC-F = 320 Hz) 1291 1425

1476 1480 11


Found 4122186

BO

Ph

Et

NPhth

5c


440-450 (m 1H) 720-727 (m 3H) 734-739 (m 2H) 743-751 (m 4H) 777-783

(m 2H) 794-800 (m 2H) 13

C NMR = 137 221 266 274 (br) 275 312 738

1235 1254 1258 1279 1282 1294 1304 1317 1342 1429 1440 1482

1671 11

B NMR = 502 IR (KBr) = 2928 1742 1509 1381 714 cm-1

HRMS (EI)


BO

Ph

Et

5d

1H NMR = 021-034 (m 1H) 068-100 (m 8H) 120-150 (m 7H) 224-238 (m

1H) 244-258 (m 1H) 424-431 (m 1H) 722-754 (m 9H) 778 (d J = 78 Hz 1H)

783-788 (m 1H) 809-816 (m 1H) 13

C NMR = 137 216 219 259 262 264

(br) 282 309 314 734 1249 12537 12539 1255 1264 1270 1273 12795

Chapter 3

81

12799 1283 1321 1335 1413 1427 1467 11


for C28H31BO (M+) 3942468 Found 3942476

BO

Ph

Et

5e

S


448-456 (m 1H) 702 (dd J = 51 36 Hz 1H) 708 (dd J = 36 12 Hz 1H)

715-730 (m 4H) 732-738 (m 2H) 13

C NMR =141 221 271 289 312 739

1250 1255 1266 1269 1279 1281 1416 1427 1468 11

B NMR = 496


BO

n-Pr

Me

Cl

5f

1H NMR = 070 (t J = 75 Hz 3H) 096-133 (m 9H) 142-172 (m 6H) 220-228

(m 2H) 237 (s 3H) 439-446 (m 1H) 708-735 (m 8H) 13

C NMR = 140 212

219 221 267 274 (br) 313 363 737 1279 12846 12855 1298 1309 1365

1411 1420 1488 11


4062235 Found 4062237

BO

n-Pr

Ph

OMe

5g

Chapter 3

82


(s 3H) 435-450 (m 1H) 690 (d J = 81 Hz 2H) 711 (d J = 81 Hz 2H) 720-740

(m 5H) 13

C NMR = 140 219 221 267 274 (br) 312 362 551 736 1133

1267 1278 1287 1294 1354 1446 1475 1573 11




BO

Ph

S

5h

1H NMR = 027-032 (m 2H) 046-052 (m 2H) 098-130 (m 6H) 140-170 (m

8H) 430-445 (m 1H) 696-700 (m 1H) 704-707 (m 1H) 715-726 (m 2H)

729-738 (m 4H) 13

C NMR = 60 150 222 263 272 (br) 313 736 1241

1243 1253 1278 1290 1295 1410 1425 1431 11



BO

Ph

CO2Et

5i

1H NMR = 017-023 (m 2H) 045-053 (m 2H) 090-119 (m 6H) 132-173 (m

11H) 427-433 (m 1H) 438 (q J = 75 Hz 2H) 718-738 (m 7H) 798 (dt J = 78

15 Hz 2H) 13

C NMR = 56 144 151 220 263 269 (br) 312 609 735 1255

1279 1284 1287 1289 1303 1423 1453 1469 1665 11

B NMR = 496 IR

(KBr) = 2928 1717 1287 1100 cm-1


Found 4282526

BO

Ph

5j

Cl

Chapter 3

83

1H NMR = 023-029 (m 2H) 048-055 (m 2H) 094-123 (m 6H) 134-171 (m

8H) 432-439 (m 1H) 706-714 (m 1H) 718-726 (m 4H) 728-738 (m 4H) 13

C

NMR = 57 150 220 263 271 (br) 312 736 1255 1267 1279 1283 1284

1289 1304 1332 1423 1424 1461 11


C25H28BClO (M+) 3901922 Found 3901923

BO

Ph

5k

Me

1H NMR = 082-113 (m 6H) 126-164 (m 15H) 237 (s 3H) 268-280 (m 1H)

434-441 (m 1H) 704-709 (m 3H) 717-725 (m 4H) 730-737 (m 2H) 13

C NMR

= 215 219 248 263 273 (br) 312 315 433 735 1252 12689 12693 1275

1278 1283 1316 1365 1418 1424 1481 11


for C28H35BO (M+) 3982781 Found 3982780

BO

Cl

S

Ph

5l

1H NMR = 106-176 (m 13H) 250-260 (m 2H) 272-280 (m 2H) 441-449 (m

1H) 674 (dd J = 33 12 Hz 1H) 697-703 (m 3H) 709-738 (m 8H) 13

C

NMR(C6D6) =225 272 277 (br) 315 358 375 739 1247 1253 1261 1272

1285 12856 12861 1306 1335 1419 1427 1437 1491 11

B NMR = 495


BO

Ph

CF3

TBSO

5m

Chapter 3

84

1H NMR = -014 (s 6H) 079 (s 9H) 095-136 (m 6H) 142-168 (m 7H) 255 (t

J = 72 Hz 2H) 343 (t J = 72 Hz 2H) 435-442 (m 1H) 718-726 (m 3H)

731-737 (m 2H) 747 (d J = 81 Hz 2H) 759 (d J = 81 Hz 2H) 13

C NMR = -54

183 220 259 266 271 (br) 311 377 616 739 1242 (q JC-F = 2694 Hz) 1247

(q JC-F = 36 Hz) 1258 1280 1282 1290 (q JC-F = 320 Hz) 1291 1421 1422

1480 11



BO

Ph

Me

OMe

5n

1H NMR = 122-130 (m 4H) 138-162 (m 5H) 168-186 (m 4H) 237 (s 3H)

375 (s 3H) 443-450 (m 1H) 670 (dt J = 90 21 Hz 2H) 690-697 (m 4H)

702-708 (m 3H) 710-720 (m 4H) 13

C NMR = 213 222 269 312 550 738

1132 1260 1272 1285 1301 1307 1310 1362 1369 1423 1429 1483

1571 11


4362561


4-Bromobenzene

B

Ph

Et

+


toluene 70 degC

Me3NO BO

Ph

Ph

Et

(Z)-5o

1a

Ph Br

[Me4N]




Chapter 3

85






BO

Ph

Ph

Et


470-475 (m 1H) 685-710 (m 10H) 13

C NMR = 139 224 267 313 317 740

1248 1257 1272 127412938 12941 1421 1425 1275 11

B NMR = 512


BO

Ph

Et

Ph


438-443 (m 1H) 718-737 (m 10H) 13

C NMR = 137 221 266 274 (br) 277

312 737 1253 1268 1278 1279 1283 1288 1433 1442 1494 11

B NMR =



Bromide 2b

+

Br

ONMe2

Ph

Et

PhO

NMe2


THF K3PO4 60 degC

(Z)-Tamoxifen 6

2b

BO

Ph

Et

Ph

(E)-5o

Chapter 3

86









Chapter 3

87



2003 Vol 3








Rev 2006 250 1107









1976 108 281








74





Chapter 3

88





















2006 128 1828




Chapter 4

89

Chapter 4



Abstract






Chapter 4

90

Introduction





























Chapter 4

91


B

MOMO

[Me4N] +

MeO

Br

I

Br

MeO Br

B

MeO

MOMO MOMO

1a

2 3 87EZ = lt199

NaOH

50 degC

1 mol


toluene 50 degC
















procedure

Chapter 4

92



An











3

MeO

R

Br

4 92

R

MeO

R

Br

n = 2 5 87

n = 3 6 82n = 4 7 85

n

R

1 mol


toluene 50 degC

I

Br

NaOH

E

EE

R = OMOM








Chapter 4

93





Br

Br

R

R

Br

Br

8 86

R

R

Br

R

R

Br

9 92

E E

R = OMOM















Chapter 4

94


Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

Me3Si

Br

Ph

F

Me3Si

OMe

Br

Ph

F

S

Br

Me3Si

OMe

B

n-Pr

[Me4N]

Cl

B

Ph

[Me4N]

OMe

Br

S

Br

I

EtO2C

MOMO

MOMO

I

Br

F

1b

10 88

11 84

12 88

1a1c

cat Pd

NaOHcat Pd

cat Pd NaOH

Cs2CO3

Conclusions







Chapter 4

95




1H at 500 MHz and






13C) CD3CN ( = 194 for

1H =132 for

13C) and

BF3OEt2 ( = 000 for 11











11













Chapter 4

96

B

MOMO

[Me4N]

1a


202 (t J = 66 Hz 2H) 236-251 (m 2H) 304 (s 12H) 328 (s 3H) 346 (t J = 69

Hz 2H) 454 (s 2H) 678-685 (m 1H) 698-705 (m 2H) 734 (d J = 72 Hz 2H) 13

C NMR (CD3CN 75 MHz) = 210 267 (br) 271 275 282 297 324 349 551

561 681 928 968 1221 1269 1338 11



B

Ph

[Me4N]

1b

OMe


225 (t J = 72 Hz 2H) 234-249 (m 2H) 263 (t J = 72 Hz 2H) 303 (s 12H) 372

(s 3H) 663-669 (m 2H) 711-728 (m 7H) 13


272 275 324 349 381 554 560 1129 1266 1289 1298 1346 1434 1563 11


3572390 Found 3572383



B

MOMO

[Me4N]

+

MeO

Br

1 mol


toluene 50 degC

I

Br

MeO Br

NaOH

3

1a

MOMO

Chapter 4

97








MeO Br

3

MOMONOE

NOE




(t J = 66 Hz 2H) 376 (s 3H) 452 (s 2H) 667-675 (m 4H) 697-702 (m 2H)

709-736 (m 7H) 13

C NMR (75 MHz) = 255 298 356 5510 5514 676 964

1134 1196 1267 1282 1294 13046 13049 1323 1339 1376 1408 1420



spectroscopy

MeO

R

Br

4

R

R = OMOM




Chapter 4

98


2H) 325 (s 3H) 329 (s 3H) 331-341 (m 4H) 380 (s 3H) 451 (s 2H) 453 (s

2H) 662-678 (m 8H) 697-703 (m 2H) 706-738 (m 12H) 13

C NMR (150 MHz)

= 252 254 295 296 353 354 5502 5504 552 675 676 9629 9632 1131

1196 1265 1267 1281 1282 1285 12941 12942 1303 1304 1306 1324

1343 1377 1385 1390 1400 1413 1414 1418 1429 1435 1579 HRMS


7972818 Found

7972849

MeO

R

5

R

R = OMOM

R

Br




325 (s 3H) 327 (s 3H) 328 (s 3H) 330-342 (m 6H) 374 (s 3H) 450 (s 2H)

452 (s 2H) 454 (s 2H) 654-662 (m 4H) 666-678 (m 8H) 696-704 (m 4H)

712-737 (m 15H) 13

C NMR (75 MHz) = 254 256 296 297 298 3526 3534

355 551 675 676 963 1130 1196 1264 1267 1280 1281 1286 1294 1301

1302 1304 1306 1324 1344 1377 1384 1387 1392 1393 1398 1402 1409



10914437 Found 10914482

Chapter 4

99

MeO

R

6

R

R = OMOM

R

R

Br




330-341 (m 8H) 371 (s 3H) 448-454 (m 8H) 648-675 (m 16H) 695-703 (m

4H) 714-737 (m 20H) 13

C NMR (75 MHz) = 253 254 256 257 2969 2974

298 350 354 356 550 551 675 676 963 1131 1196 1264 1267 1279

1280 1281 1283 1288 1293 1294 1300 1301 1302 1305 1306 1323 1342

1377 1385 1387 1389 1391 1394 1396 1397 1401 1405 1409 1411 1413



13856057 Found 13856062

MeO

R

7

R

R = OMOM

R

R

R

Br




374 (s 3H) 447-452 (m 10 H) 649-679 (m 20 H) 690-695 (m 2H) 701-706 (m

2H) 710-736 (m 25H) 13

C NMR (75 MHz) = 2529 2535 256 257 2968

Chapter 4

100

2971 298 351 354 355 356 550 6746 6755 676 963 1131 1195 1264

1267 12795 1280 1281 1283 1285 1287 1293 12937 12944 1301 1302

1304 1306 1322 1343 1377 1384 1387 1389 1390 1391 1394 13976

13979 1401 1404 1408 1409 1412 1413 1416 1427 14318 14321 1434


16797677 Found 16797694

8

R

Br

R

Br

R = OMOM





(t J = 66 Hz 4H) 456 (s 4H) 668-673 (m 4H) 691 (s 4H) 710-721 (m 8H)

722-737 (m 6H) 13

C NMR (75 MHz) = 254 297 354 551 676 963 1198

1268 1282 1291 1293 1303 1323 1380 1400 1411 1417 1427 HRMS


8221905

9

R

R

R = OMOM

R

R

Br

Br



Chapter 4

101


6H) 330-340 (m 8H) 446 (s 4H) 453 (s 4H) 656-672 (m 12H) 688 (s 4H)

704-710 (m 4H) 714-718 (m 4H) 722-740 (m 16H) 13

C NMR (150 MHz) =

254 2962 2963 356 357 5501 5503 674 676 9629 9631 1197 1266

1268 1281 12818 12822 1290 1295 1296 1304 1308 1324 1379 1385

1394 1403 1405 1409 1416 1417 1427 1434 HRMS (MALDI-TOF-MS


14335057 Found 14335040

Ph

F

Me3Si

OMe

Br

10

NOE

NOE





3H) 676-686 (m 3H) 694-707 (m 6H) 709-728 (m 5H) 734 (d J = 84 Hz 2H) 13

C NMR (150 MHz) = -11 349 372 552 1135 1189 (d JC-F = 255 Hz)1202

(d JC-F = 92 Hz) 1258 1268 (d JC-F = 35 Hz) 1280 1283 1284 1300 1304 (d

JC-F = 159 Hz) 1326 1329 1332 (d JC-F = 45 Hz) 1339 1387 1417 1418 1430




Chapter 4

102

Ph

F

S

Br

Me3Si

OMe

11

MOMO




= 78 2H) 264-272 (m 2H) 282-289 (m 2H) 325 (s 3H) 328 (t J = 66 Hz 2H)

382 (s 3H) 448 (s 2H) 587 (d J = 39 Hz 1H) 660 (d J = 39 Hz 1H) 669-676

(m 2H) 684-696 (m 3H) 705-742 (m 16H) 13

C NMR (150 MHz) = -10 244

293 351 362 372 550 552 673 963 1127 1135 1161 (d JC-F = 225 Hz)

1244 (d JC-F = 32 Hz) 1258 1274 12827 12831 12837 12840 12856 12861

1295 1302 1307 (d JC-F = 155 Hz) 1324 1329 1330 (d JC-F = 45 Hz) 1333

1345 1385 1395 (d JC-F = 12 Hz) 1412 1416 (d JC-F = 80 Hz) 1419 1422



Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

12MOMO




mmol) t1 10 h t2 12 h

Chapter 4

103


210-224 (m 4H) 264-272 (m 2H) 279-287 (m 2H) 323-333 (m 5H) 373 (s


1H) 666-672 (m 2H) 679-694 (m 5H) 703-737 (m 20H) 773 (d J = 84 Hz

2H) 13

C NMR (150 MHz) = -11 141 143 225 244 293 350 359 370 385

550 551 607 674 963 1134 1159 (d JC-F = 224 Hz) 1243 (d JC-F = 29 Hz)

1258 1269 1271 12808 12811 12815 12820 12823 12838 12844 1290

1293 1300 1301 (d JC-F = 158 Hz) 1302 1307 1323 (d JC-F = 47 Hz) 13258

13261 1328 1336 1344 1356 1379 1382 1390 (d JC-F = 12 Hz) 1409 14190

14191 14216 (d JC-F = 80 Hz) 14219 14222 1438 1446 1476 1583 1600 (d

JC-F = 2448 Hz) 1664 IR (KBr) = 2955 1717 1509 1273 1248 1111 837 cm-1


11294440

Found 11294465

Chapter 4

104




Chem 1999 201 163




897















2404


2006 128 1828



Chapter 5

105

Chapter 5




Abstract






Chapter 5

106

Introduction





moiety1b


























Chapter 5

107


B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

OHMe

Ph

1a

3a 85

MeO

OMe

2a

B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

1b

OMe

2a

OHMe

Ph

OMe

3b 88

[Me4N]

[Me4N]




Oxidative









Chapter 5

108


O

I

O

PdI

Pd(0)

B

1a

C

Pd(0)3a

Ar = p-MeOC6H4-

Me Me

OMe

Ar

Ph

B

D

A

Pd

O

ArB

Me

Ph

B

O

ArPh

Me

Me4NI

2a







Chapter 5

109


R3

O

I

B

R2

R1

+1 mol Pd

toluene50 degC 1 h

OHR3

R1

R2

OHMe

Ph

S

OHMe

OMe

OHPh

Ph

OMe

3f 72

3h 763j 80

3g 84

3d 82

3c 83

OHMe

Ph

CF3

1 2 3

OHH

Ph

OMe

OHPh

Ph

OMe

O

O

OHPh

3e 92

F

OMe

OHPh

Ph

OMe

F3C

3i 62

R4R4

MeO

[Me4N]










Chapter 5

110

OHMe

t-Bu

S

3k 89

B +1 mol Pd

toluene

50 degC 1 h

2a

t-Bu

S

(1)

1c

[Me4N]

OHMe

n-Bu

Me

3l 80

B

n-Bu

+1 mol Pd

toluene50 degC 1 h

2a

Me

(2)

1d

[Me4N]










n-Hex

13 equiv

Ph

Li

065 equiv

(H-9-BBN) 2


1 mol Pd

toluene 50 degC 1 h

10 equiv 2aOH

Me

n-Oct

11 equiv

3m 91 (based on 2a)

B

n-Oct

PhLi

Ph




Chapter 5

111


in 59 yield11


OHH

Ph

OMe

MnO2

DCM rt

Ph

OMe

O

NH2NH2 KOHPh

OMe

4 96 5 59

3n 74

(CH2OH)2 150 C

1a +

CHO

I2b

1 mol Pd

Conclusions




Chapter 5

112



and 13


B at 128 MHz)



13C) CD3CN (δ = 194 for

1H δ = 132 for


11B) IR






(Merck)





and alkynylborate14




Li

BPh

+

B

Ph

1a


2) Me4NCl MeOH

[Me4N]

MeO

MeO










Chapter 5

113

B

Ph

1a

[Me4N]

MeO


(m 2H) 296 (s 12H) 372 (s 3H) 668-675 (m 2H) 685-691 (m 1H) 700-712 (m

4H) 743 (d J = 64 Hz 2H) 13

C NMR (CD3CN) δ = 256-272 (m) 270 274 322

350 557 560 955 1145 1227 (2C) 1273 1324 1341 1578 The boron-bound


11B NMR


3292079

B

Ph

1b

[Me4N]

OMe


(m 2H) 295 (s 12H) 374 (s 3H) 666-675 (m 2H) 702-718 (m 5H) 733 (d J =

84 Hz 2H) 13

C NMR (CD3CN) δ = 254-274 (m) 270 273 321 350 554 560





B

nBu

1d

[Me4N]

Me


(m 4H) 136-157 (m 6H) 170-196 (m 4H) 220-234 (m 5H) 304 (s 12H)

697-701 (m 2H) 704-709 (m 2H) 13

C NMR (CD3CN) δ = 152 212 270

271-290 (m) 282 288 318 324 357 561 1279 1296 1314 1344 The

Chapter 5

114




[M-(NMe4)]- 2932446 Found 2932454

B

Ph

1e

[Me4N]

F3C


(m 2H) 292 (s 12H) 690-696 (m 1H) 710-718 (m 2H) 728 (dd J = 88 08 Hz

2H) 744-752 (m 4H) 13

C NMR (CD3CN) δ = 252-270 (m) 269 273 321 351






B

Ph

1f

[Me4N]

S



48 32 Hz 1H) 703-719 (m 6H) 13

C NMR (CD3CN) δ = 266 272 270-286 (m)

323 348 560 962 1231 1256 1266 1274 1290 1300 1314 The boron-bound

sp2 and sp


11B NMR


- 3051541 Found

3051541

Chapter 5

115


(H-9BBN) 2

H tBu

THF 0 degC

THF -78 degC to rt

2) Me4NCl MeOH

Li

1)S

B

1c

[Me4N]

S

tBu














B

1c

[Me4N]

S

tBu


4H) 222-235 (m 2H) 306 (s 12H) 552 (d J = 172 Hz 1H) 591 (d J = 176 Hz


Hz 1H) 13

C NMR (CD3CN) δ = 273 276 278-296 (m) 311 327 341 352 561





Chapter 5

116












OHMe

3aOMe

NOE

no NOE

IR (ATR) 3315 1508 1248 752 694 cm-1

1H NMR δ = 159 (s 3H) 204 (bs 1H)

382 (s 3H) 684-690 (m 2H) 721-730 (m 8H) 742-748 (m 2H) 751-755 (m

1H) 13

C NMR δ = 239 552 832 1139 1208 1218 1265 1268 1272 1280


C23H21O2 [M+H]+ 3291536 Found 3291556

OHMe

OMe

3b

NOE

no NOE

IR (ATR) 3319 1508 1248 760 702 cm-1

1H NMR δ = 160 (s 3H) 208 (s 1H)

378 (s 3H) 674-680 (m 2H) 718-723(m 1H) 724-744 (m 9H) 750-755 (m

1H) 13

C NMR δ = 241 551 833 1134 1205 1218 1263 1270 1274 1284


Chapter 5

117

C23H20O2Cl [M+Cl]- 3631146 Found 3631148

OHMe

Ph

3cCF3

IR (ATR) 3298 1319 1121 750 696 cm-1

1H NMR δ = 160 (s 3H) 210 (bs 1H)

716-722 (m 1H) 723-732 (m 5H) 737-747 (m 4H) 752-764 (m 3H) 13

C NMR

δ = 240 833 1205 1221 1241 (q JC-F = 2701 Hz) 1255 (q JC-F = 37 Hz) 1269

1277 1282 1286 1293 1295 (q JC-F = 322 Hz) 1296 1341 1373 1385 1414


- 3651159 Found 3651159

OHMe

Ph

3d

S

IR (ATR) 3319 1350 1088 752 694 cm-1

1H NMR δ = 177 (s 3H) 209 (bs 1H)

696-702 (m 2H) 718 (dd J = 52 Hz 12Hz 1H) 723-730 (m 2H) 735-740 (m

3H) 742-752 (m 3H) 753-758 (m 1H) 13

C NMR δ = 254 833 1207 1216

1259 1265 1266 1275 1282 1287 1290 1294 1347 1360 1374 1410 1426


+ 3050995 Found 3050992

OHMe

OMe

3e

IR (ATR) 3310 1508 1244 1034 758 cm-1

1H NMR δ = 144 (s 3H) 158-202 (m


5H) 747 (d J = 68 Hz 1H) 13

C NMR δ = 238 266 267 305 311 382 552

822 1136 1211 1219 1257 12789 12793 1304 1406 1409 1467 1499


+ 3382115 Found 3382104

Chapter 5

118

OHH

Ph

3fOMe

MeO

IR (ATR) 3472 1601 1508 1244 704 cm-1

1H NMR δ = 174 (d J = 88 Hz 1H)


= 80 Hz 24 Hz 1H) 692-697 (m 2H) 718-730 (m 5H) 732-736 (m 2H) 753 (d

J = 84 Hz 1H) 13

C NMR δ = 552 555 766 1072 1109 1143 1244 1267 1272

1283 1292 1303 1342 1363 1390 1445 1457 1592 1606 HRMS (ESI+)


OHPh

Ph

3gOMe

IR (ATR) 3422 1508 1244 1028 746 698 cm-1

1H NMR δ = 248 (s 1H) 385 (s

3H) 695 (d J = 88 Hz 2H) 704-714 (m 5H) 715-732 (m 7H) 736-740 (m 2H)

755 (d J = 88 Hz 2H) 13

C NMR δ = 552 868 1141 1210 1231 1250 1268

12698 12702 1271 1278 12836 12844 1294 1304 1340 1402 1417 1427


+ 3911693 Found

3911718

OHPh

Ph

3hOMe

O

O

IR (ATR) 3362 1470 1244 1034 696 cm-1

1H NMR δ = 239 (s 1H) 385 (s 3H)

591 (dd J = 164 16 Hz 2H) 673 (d J = 44 Hz 2H) 690-696 (m 2H) 702-708

(m 5H) 720-736 (m 5H) 749-754 (m 2H) 13

C NMR δ = 552 863 1012 1024

Chapter 5

119

1049 1142 1249 12690 12692 1270 1278 1285 1292 1304 1340 1367


+

4341518 Found 4341505

OHPh

Ph

3iOMe

F3C

IR (ATR) 3545 1508 1321 1115 696 cm-1

1H NMR δ = 249 (s 1H) 387 (s 3H)

694-700 (m 2H) 704-715 (m 5H) 723-738 (m 6H) 742-755 (m 4H) 13

C NMR

δ = 553 866 1145 1177 (q JC-F = 37 Hz) 1233 1241 (q JC-F = 36 Hz) 1242 (q

JC-F = 2702 Hz) 1249 1260 1275 1276 1280 1287 1295 1304 1308 (q JC-F =


C29H21F3O2Cl [M+Cl]- 4931177 Found 4931192

OHPh

3j

F

OMe

IR (ATR) 3356 1242 1028 741 696 cm-1

1H NMR δ = 164-178 (m 2H) 183-208


4H) 719-737 (m 6H) 13

C NMR δ = 2675 2681 308 310 383 551 862 1114


1268 1271 1283 1303 1371 (d JC-F = 29 Hz) 1410 1418 (d JC-F = 15 Hz)



+ 4001839 Found 4001835

OHMe

S

tBu

3k

Chapter 5

120

IR (ATR) 3298 1358 1078 756 689 cm-1

1H NMR δ = 111 (s 9H) 168 (s 3H)

188 (s 1H) 640 (d J = 164 Hz 1H) 656 (d J = 164 Hz 1H) 718-730 (m 4H)

739-751 (m 3H) 13

C NMR δ = 257 295 340 822 1169 1204 1215 1242

1255 1262 1283 1285 1324 1346 1415 1452 1462 1506 HRMS (ESI+)


OHMe

nBu

OMe3l

IR (ATR) 3335 1508 1084 918 758 cm-1

1H NMR δ = 085 (t J = 72 Hz 3H) 130

(tt J = 72 72 Hz 2H) 141-167 (m 6H) 229-250 (m 5H) 702-706 (m 1H)

716-728 (m 6H) 744-748 (m 1H) 13

C NMR δ = 138 213 232 237 252 314

829 1198 1215 1256 1282 1286 1291 1318 1370 1374 1430 1492 1496


+ 2931900 Found 2931890



nHex

(H-9BBN) 2


Li

Ph

B

nOct

Li

Ph

Me

O

I


toluene 50 degC 1 h

H2O2 aq

NaOH aq

OHMe

nOct

Ph3m

MeOH




Chapter 5

121













yield)

OHMe

nOct

Ph3m

IR (ATR) 3335 1456 1078 752 698 cm-1

1H NMR δ = 096 (t J = 68 Hz 3H)

129-156 (m 15H) 160 (s 1H) 208-227 (m 2H) 274-281 (m 2H) 287-294 (m

2H) 719-728 (m 5H) 729-736 (m 3H) 742 (d J = 72 Hz 1H) 13

C NMR δ = 141

226 234 247 277 293 294 295 304 319 345 825 1186 1213 1252 1260


[M]+ 3622610 Found 3622619

OHH

Ph

OMe

3n

IR (ATR) 3354 1508 1246 764 692 cm-1

1H NMR δ = 185 (bs 1H) 386 (s 3H)

567 (s 1H) 692-697 (m 2H) 718-738 (m 10H) 763-766 (m 1H) 13

C NMR δ =

552 773 1143 1206 1237 1263 1268 1272 1283 1287 1292 1303 1342


- 3131234

Found 3131237

Chapter 5

122

The 1H


15


OHH

Ph

OMe

3n

MnO2

DCM rt

Ph

OMe

4

O







The 1H


16

Ph

OMe

4

O

(CH 2OH)2

NH2NH2

KOH Ph

OMe

5








The 1H


5

Chapter 5

123






1395ndash1411



17638ndash17640





3201ndash3222



















Chapter 5

124












3283ndash3292









74








Chem 1989 54 1485ndash1491



2006 128 1828

Chapter 5

125



4781-4787


Chem 1989 54 1485

Chapter 5

126

127

List of Publication

Chapter 1



Angew Chem Int Ed 2012 51 11750-11752

Chapter 2


Benzosultams


J Am Chem Soc 2013 135 19103-19106

Chapter 3





Org Lett 2009 11 5434-5437

Chapter 4


Units


Org Lett 2010 12 3179-3181

Chapter 5




Eur J Org Chem 2013 1421-1424

Other Publication




Chem Lett 2013 42 1076


4


regioselectively

I

Me

O+

MeOH

R2

R1Pd-XANTPhosB

R2

R1

[Me4N]


5

Reference





































6








10990




2003 Vol 3





Q Z J Med Chem 2009 52 4192



2006 250 1107



2419













7



17638ndash17640


8

Chapter 1

9

Chapter 1


Ketones

Abstract






Chapter 1

10

Introduction







2 One







starting substances


CO2

sun

CO2energy charge

high energy

intermediates











8






Chapter 1

11


Ph

O

NTs

Mesolar light

N

Ph OH

Ts

2a 91

1aDMA







over 04 kWm-2



in eight hours on


Figure





kWhm-2



Chapter 1

12


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

0

20

40

60

80

100

0 1 2 3 4 5 6











(56)

Chapter 1

13


40 equiv Cs2CO3

1 atm CO2

DMA 60 degC

OO

O

Ph

NHTs

3a 93

N

Ph OH

Ts

2a








N

Ph O

Ts

A

N

Ph O

Ts

B

O

O

OO

O

Ph

NTs

CO2

H

C

Cs2CO3

CsHCO 3

Cs

Cs

Cs

2

1

N

Ph OH

Ts

2a

OO

O

Ph

NHTs

3a












N

Ts

OHPh

4

Chapter 1

14




solar light

CO2Cs2CO3

60degCDMAPh

O

NTs

Me

1a

OO

O

Ph

NHTs

3a 83






chloro groups10





Ar

O

NR

Me OO

O

Ar

NHR3

1

OO

O

NHTs3b 80

MeO

OO

O

NHTs3c 57

F3C

OO

O

NHTs3d 73

Cl

OO

O

NHTs3e 85

Br

OO

O

Ph

NH

3f 87

O2S OMe

OO

O

Ph

NH

3g 85

O2S CF3

OO

O

Ph

NH

3h 87

O2S

N

solar lightCO2

Cs2CO3

60degCDMA




Chapter 1

15

Conclusions















Chapter 1

16












indicator (Merck)






Ph

O

NTs

MeTsClMeNH2 +

Et2OTsNHMe

CH3CN

K2CO3












Chapter 1

17


Ph

O

NTs

Me


745-751 (m 2H) 760 (tt J = 76 12 Hz 1H) 771-775 (m 2H) 795-799 (m 2H)

13C NMR δ = 215 356 560 1275 1282 1288 1297 1338 1347 1348 1436


+ 3041002 Found mz 3040994 IR

(ATR) 1693 1339 1227 1157 743 cm-1

O

NTs

Me

1bMeO


733 (d J = 80 Hz 2H) 770-774 (m 2H) 796-802 (m 2H) 13

C NMR δ = 215

355 555 558 1139 1275 1277 1296 1307 1346 1436 1640 1921 HRMS


+ 3341108 Found mz 3341101 IR (ATR) 1688

1601 1329 1180 1159 cm-1

O

NTs

Me

1cF3C


= 84 Hz 2H) 776 (d J = 84 Hz 2H) 812 (d J = 84 Hz 2H) 13

C NMR δ = 215

357 564 1234 (q JC-F = 2711 Hz) 1259 (q JC-F = 37 Hz) 1276 1288 1298



1121 1109 cm-1

Chapter 1

18

O

NTs

Me

1dCl


(m 2H) 771 (d J = 80 Hz 2H) 792-796 (m 2H) 13

C NMR δ = 216 356 561



1159 1088 cm-1

O

NTs

Me

1eBr


= 84 Hz 2H) 771 (d J = 84 Hz 2H) 786 (d J = 84 Hz 2H) 13

C NMR δ = 215

356 561 1275 1291 1297 1298 1321 1334 1344 1438 1930 HRMS (ESI+)


1223 1155 810cm-1

Ph

O

NS

Me

1f

OMe

OO

1H NMR δ = 282 (s 3H) 389 (s 3H) 456 (s 2H) 698-703 (m 2H) 746-751 (m

2H) 761 (tt J = 72 12 Hz 1H)776-781 (m 2H) 796-800 (m 2H) 13

C NMR δ =

356 556 561 1142 1283 1288 1294 1297 1338 1348 1630 1938 HRMS


+ 3200951 Found mz 3200943 IR (ATR) 1692

1342 1259 1155 741 cm-1

Chapter 1

19

Ph

O

NS

Me

1g

CF3

OO


780 (d J = 84 Hz 2H) 790-794 (m 2H) 798 (d J = 80 Hz 2H) 13

C NMR δ =

356 558 1233 (q JC-F = 2711 Hz) 1261 (q JC-F = 36 Hz) 12796 12799 1289



1059 748 cm-1

Ph

O

NS

Me

1h

N

OO

1H NMR δ = 302 (s 3H) 486 (s 2H) 744-753 (m 3H) 757-762 (m 1H)

788-798 (m 4H) 870 (ddd J = 48 16 08 Hz 1H)13

C NMR δ = 363 569 1224



752 cm-1


Ph

O

NTs

Mesolar light

N

Ph OH

TsDMA rt

1a

2a








Chapter 1

20


N

Ph OH

Ts


2H) 728-737 (m 5H) 740 (d J = 80 Hz 2H) 779 (d J = 80 Hz 2H) 13

C NMR δ

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS




N 458 O 1555 S 1058 IR (ATR) 3477 1333 1184 1148 671 cm-1


N

Ph OH

Ts

2a

40 equiv Cs2CO3

1 atm CO2

DMA 60 C

OO

O

Ph

NHTs

3a








mmol 93 yield)

Chapter 1

21



40 equiv Cs2CO3

60 CPh

O

NR

Me OO

O

Ph

NHR3a

1a

solar light

DMA rt

1 atm CO2











OO

O

Ph

NHTs



726-732 (m 4H) 734-743 (m 3H) 769-773 (m 2H) 13

C NMR δ = 215 503

724 850 1242 1269 1292 1299 1365 1381 1439 1542 HRMS (ESI+) Calcd

for C17H18NO5S M+H+


C 5878 H 493 N 403 O 2303 S 923 Found C 5871 H 496 N 389 O

2284 S 932 IR (ATR) 3261 1773 1435 1319 1045 cm-1

Chapter 1

22

OO

O

NHTs

3b

MeO



56 Hz 1H) 688-693 (m 2H) 719-724 (m 2H) 728 (d J = 80 Hz 2H) 770 (d J =

84 Hz 2H) 13

C NMR δ = 215 503 554 724 848 1145 1256 1269 1298


+

3781006 Found mz 3780996 IR (ATR) 3238 1794 1518 1329 1057 723 cm-1

OO

O

NHTs

3c

F3C



729 (d J = 84 Hz 2H) 746 (d J = 84 Hz 2H) 765-771 (m 4H) 13

C NMR δ =

215 501 722 846 1235 (q JC-F = 2704 Hz) 1249 1263 (q JC-F = 37 Hz) 1268



1067 cm-1

OO

O

NHTs

3d

Cl



722-727 (m 2H) 728 (d J = 84 Hz 2H) 735-739 (m 2H) 769 (d J = 84 Hz 2H)

13C NMR δ = 215 502 723 847 1257 1268 1294 1300 1353 1364 1365


+ 3820510 Found mz

Chapter 1

23

3820506 IR (ATR) 3250 1800 1325 1155 1069 cm-1

OO

O

NHTs

3e

Br



716-720 (m 2H) 728 (d J = 80 Hz 2H) 750-755 (m 2H) 766-770 (m 2H) 13

C

NMR δ = 215 501 723 847 1235 1260 1268 1300 1323 1364 1370 1441


+ 4260005 Found mz 4260003

IR (ATR) 3252 1800 1331 1175 1057 cm-1

OO

O

Ph

NH

SO

O

OMe



693-698 (m 2H) 727-732 (m 2H) 734-744 (m 3H) 773-778 (m 2H) 13

C NMR

δ = 503 556 724 849 1145 1242 1291 1292 1310 1381 1541 1632 HRMS


+ 3640849 Found mz 3640836 IR (ATR) 3246

1801 1325 1155 1067 cm-1

OO

O

Ph

NH

SO

O

CF3

3g

Chapter 1

24



2H) 735-744 (m 3H) 775 (d J = 88 Hz 2H) 796 (d J = 84 Hz 2H) 13

C NMR δ

= 505 725 851 1231 (q JC-F = 2711 Hz) 1241 1265 (q JC-F = 37 Hz) 1274



1161 1105 cm-1

OO

O

Ph

NH

SO

O

N




1H) 798 (d J = 76 Hz 1H) 866 (d J = 44 Hz 1H) 13

C NMR δ = 510 723 849



1175 1063 cm-1


N

Ts

OHPh

N

Ts

O CeCl 3

PhLi

THF -78 C to rt

4






Chapter 1

25






N

Ts

OHPh


351-364 (m 4H) 726-738 (m 7H) 773-777 (m 2H) 13

C NMR δ = 215 396

469 608 804 1250 1276 1280 1286 1297 1339 1418 1435 HRMS (ESI+)


1325 1159 1101 770 cm-1

Chapter 1

26











Soc 2011 133 12881

























25 312

Chapter 1

27








Chapter 1

28

Chapter 2

29

Chapter 2



Abstract







Chapter 2

30

Introduction














A



Indanones are


A rearrangement













Whereas







Chapter 2

31




N

HO Ph

S NS Me

HO PhMe

1a2a 96

Me

O

OO O


2) is





The generated








N

S O

O

O[Rh]

Ph

SN

[Rh]O Ph

O OMe

[Rh] OH

N

S O

O

O Ph

H

[Rh]

H

N

[Rh]O Ph

S O

O

Me Me

Me

Me

1a

H2O

2a

A B

CD

1a

A




Chapter 2

32








N

HO Ph

SN

S CH19D11

HO Ph

D3C

1a-d2a-d 96

D3C

O

O

O O

D

D

D

D

D

D

H01D09

8



D12




Application




1

2

SN

HO Ar

O OMe

N

HO Ar

S O

O


K2CO 3 (20 equiv)


NS Me

HO PhMe

2a

91 er = 928

O O

NS Me

HO Ph

2b

95 er = 937

O O

S

NS Me

HOMe

2c

90 er = 937

O O

OMe

NS Me

HOMe

2c

92 er = 919

O O

CF3



Chapter 2

33










HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6 84

5 56



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3


PhMgBr

THF rt 1 h N

HO

Ts

Me

1e 93

er gt 991 dr = 201

Ph

3







SN

HO PhMe

O OMe

MeN

HO Ph

S O

O

Me

Me

1e

er gt 991 dr = 201

2e 99

er gt 991 dr gt 201





Chapter 2

34









SN

PhRhOMe

O OMe

Me

SN

PhRhOMe

O OMe

Me

favored

disfavored

F

F

NSRh

Ph

Me

O

O

MeO

H

Me

E

E

NSRh

Ph

Me

O

O

MeO

Me

H














Chapter 2

35


1

er gt 991 dr gt 201

2

er gt 991 dr gt 201

SN

HO ArR

O OMe

N

HO Ar

S O

O





1 N

HO Ph

S O

O

Me

Me

1f

SN

HO PhMe

O OMe

Me

2e 99

6 N

HO

S O

O

Me

1k

OMe

SN

HOMe

O OMe

2k 97

OMe

2

N

HO Ph

S O

O

MeO

Me

1g

SN

HO PhMe

O OMe

MeO

2g 98

7 N

HO

S O

O

Me

Me

1l

CF3

SN

HOMe

O OMe

Me

2l 97

CF3

3 N

HO Ph

S O

O

F3C

Me

1h

SN

HO PhMe

O OMe

F3C

2h 99

8 N

HO Ph

S O

O

Me

i-Pr

1m

SN

HO Phi-Pr

O OMe

Me

2m 97

4

N

HO Ph

S O

O

Me

1iMe

SN

HO PhMe

O OMeMe

2i 99

9 N

HO Ph

S O

O

Me

SMe

SN

HO Ph

O OMe

Me

2n 97

SMe

5 N

HO Ph

S O

O

Me

S

1j

SN

HO PhMe

O OMeS

2j 99



Chapter 2

36

Conclusions






Chapter 2

37





13C NMR


13C at 10069












N

OHNEt3

DCM rt 12 h


2) PhMgBrTHF rt 3 h

N

HO Ph

1a

TsCl

N

OH

8a

H HCl

Ts Ts









Chapter 2

38

N

S

Me

O

O

OH

8a 1H NMR = 213 (bs 1H) 245 (s 3H) 350-361 (m 2H) 394-404 (m 2H)

442-452 (m 1H) 737 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR =



-1

N

S

D3C

O

O

OH

8a-d

D

D

D

D

1H NMR = 283 (bs 1H) 349-355 (m 2H) 389-396 (m 2H) 435-444 (m 1H)



+ 2351128 Found mz

2351125 IR (ATR) 3503 1333 1142 1059 638 cm-1

N

S O

O

OH

8b

S

1H NMR = 277 (bs 1H) 357-364 (m 2H) 400-407 (m 2H) 441-450 (m 1H)


1H) 13



1038 737 cm-1

Chapter 2

39














N

HO Ph

S

1a

Me

O

O


2H) 728-737 (m 5H) 739 (d J = 84 Hz 2H) 778 (d J = 80 Hz 2H) 13

C NMR

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS


+ 3041002 Found mz 3040995 IR (ATR) 3477

1333 1184 1148 671 cm-1


N

HO Ph

S

1a-d

D3C

O

O

D

D

D

D


(m 5H) 13

C NMR = 203-211 (m) 652 703 1244 1281 (t JC-D = 247 Hz)


Chapter 2

40


702 648 cm-1

N

HO Ph

S

S

O

O



1H) 13

C NMR = 656 702 1244 1280 1283 1288 1331 13387 13392 1417


+ 2960410 Found mz 2960404 IR

(ATR) 3524 1333 1161 1148 748 cm-1

N

HO

S

Me

O

O

OMe

1c



2H) 775 (d J = 80 Hz 2H) 13

C NMR =216 553 652 702 1139 1259 1285


+

3341108 Found mz 3341097 IR (ATR) 3460 1518 1331 1250 1146 cm-1

N

HO

S

Me

O

O

CF3



C NMR

Chapter 2

41

=216 654 697 1239 (q JC-F = 2704 Hz) 1249 1255 (q JC-F = 37 Hz) 1284



1109 1076 cm-1


1l-1n

HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6a

5a



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3

acetone H2O

rt 10 h 4a

PhMgBr

THF rt 1 h N

OH

Ts

Me

1e

Ph

3a



procedure16













Me

NHTs

O

N2


Chapter 2

42

2H) 730 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR = 194 215 539


+

2680750 Found mz 2680747 IR (ATR) 2112 1639 1337 1319 1161 cm-1

[]27

D = -1184 (c = 079 in CHCl3)


i-Pr

NHTs

O

N2



2H) 769 (d J = 84 Hz 2H) 13

C NMR =169 193 215 315 548 647 1273


+ 2961063

Found mz 2961060 IR (ATR) 2129 1622 1362 1329 1161 cm-1

[]28

D = -730 (c = 071 in CHCl3)

NHTs

O

N2

5c

SMe

1H NMR = 174-196 (m 2H) 204 (s 3H) 242 (s 3H) 244-252 (m 2H)

390-400 (m 1H) 541 (s 1H) 560-572 (m 1H) 730 (d J = 84 Hz 2H) 772 (d J =

84 Hz 2H) 13

C NMR = 153 215 297 323 545 585 1272 1297 1366 1439


+ 3280784 Found mz 3280779

IR (ATR) 2129 1618 1375 1339 1163 cm-1

[]29

D = -506 (c = 063 in CHCl3)









Chapter 2

43

N

O

Ts

Me

6a

1H NMR = 145 (d J = 68 Hz 3H) 246 (s 3H) 443-454 (m 2H) 473-480 (m

1H) 736-742 (m 2H) 776-781 (m 2H) 13

C NMR = 157 216 696 810 1284


+ 2400689

Found mz 2400688 IR (ATR) 1825 1339 1155 669 cm-1

[]28

D = 614 (c = 081 in CHCl3)


N

O

Ts

i-Pr

6b

1H NMR = 099-111 (m 6H) 206-218 (m 1H) 246 (s 3H) 441 (dd J = 164 36


2H) 777 (d J = 80 Hz 2H) 13

C NMR = 174 181 216 304 703 903 1284


+ 2681002

Found mz 2680998 IR (ATR) 1815 1340 1155 1007 671 cm-1

[]29

D = 567 (c = 095 in CHCl3)

N

O

Ts

6c

SMe

1H NMR = 204 (s 3H) 209-218 (m 2H) 247 (s 3H) 265-279 (m 2H) 446 (d


2H) 780 (d J = 80 Hz 2H) 13

C NMR = 147 216 291 293 705 832 1286


+ 3000723

Found mz 3000718 IR (ATR) 1813 1342 1308 1157 667 cm-1

[]29

D = 1183 (c = 036 in CHCl3)


Chapter 2

44










N

HO

S O

O

Me

Me

1e

H

NOE

NOE



(m 3H) 739 (d J = 84 Hz 2H) 777 (d J = 84 Hz 2H) 13

C NMR = 144 216

628 702 731 1247 1279 1284 1285 1298 1319 1415 1443 HRMS (ESI+)


1155 1092 667 cm-1

[]25




Chapter 2

45

N

HO

S O

O

Me

1l

H

NOE

NOE

CF3

Me



739-747 (m 4H) 777 (d J = 84 Hz 2H) 13

C NMR = 143 216 630 706 727

1238 (JC-F = 2704 Hz) 1253 1254 (JC-F = 36 Hz) 1285 1299 1301 (JC-F = 324


+ 3861032

Found mz 3861025 IR (ATR) 3422 1327 1151 1109 839 cm-1

[]28




N

HO

S O

O

Me

iPr

1m

H

NOE

NOE



= 100 Hz 1H) 690-696 (m 2H) 712-720 (m 3H) 732 (d J = 80 Hz 2H) 773 (d

J = 80 Hz 2H) 13

C NMR = 190 193 215 291 641 729 801 1247 1275


+

3461471 Found mz 3461466 IR (ATR) 3454 1331 1163 739 669 cm-1

[]27



Chapter 2

46


N

HO Ph

S O

O

1n

Me

SMe

1H NMR = 202 (s 3H) 218-258 (m 8H) 388-394 (m 2H) 427 (dd J = 84 48

Hz 1H) 688-693 (m 2H) 714-721 (m 3H) 740 (d J = 80 Hz 2H) 779 (d J = 80

Hz 2H) 13

C NMR = 154 216 290 297 634 725 733 1246 1277 1284


+

3781192 Found mz 3781188 IR (ATR) 3481 1339 1157 702 669 cm-1

[]28












N

HO

S O

O

Me

Me

1f

H

NOE

NOE


1H) 398 (q J = 64 Hz 1H) 424 (dd J = 84 08 Hz 1H) 732-744 (m 5H)

750-755 (m 2H) 774-778 (m 2H) 13

C NMR = 165 216 627 718 739 1257

Chapter 2

47



-1

[]25






HO2C Me

NHCbz

Me

NHCbz

O

N2N

O

Cbz

Me

6d5d

1) (COCl) 2 DMF

2) CH2N2 Rh2(OAc)4 (05 mol )

DCM rt 12 h4d

PhMgBr

THF rt 1 h

N

OH

Cbz

Me

7a

Ph

N

OH

H

Me

PhPd C (5 mol )

H2 (1atm)

MeOH rt 12 h

MeO SO2Cl

NEt3

DCM rt 12 h

N

HO Ph

S O

O

MeO

Me

1g









Me

NHCbz

O

N2

5d 1H NMR = 134 (d J = 68 Hz 3H) 420-436 (m 1H) 504-516 (m 2H) 534-564

(m 2H) 728-736 (m 5H) 13

C NMR = 184 535 (2C) 669 1280 1282 1285


+ 2481030 Found mz

2481028 IR (ATR) 2116 1717 1636 1533 1252 cm-1

[]28

D = -434 (c = 085 in CHCl3)


Chapter 2

48







N

O

Cbz

Me

6d


Hz 1H) 498-505 (m 1H) 513-521 (m 2H) 731-739 (m 5H) 13

C NMR = 153



696 cm-1

[]29

D = 390 (c = 068 in CHCl3)










N

OH

Cbz

Me

7a

Ph


= 96 Hz 1H) 458 (q J = 64 Hz 1H) 507-518 (m 2H) 729-746 (m 10H) 13

C

NMR = 142 623 667 689 730 1246 1278 1279 1280 1285 1287 1366

Chapter 2

49


+ 2981438 Found mz

2981433 IR (ATR) 1670 1423 1248 1016 702 cm-1

[]29

D = 46 (c = 089 in CHCl3)

N

OH

Cbz

Me

7b

MeO


1H) 432 (d J = 96 Hz 1H) 452-461 (m 1H) 506-518 (m 2H) 687-694 (m 2H)

726-739 (m 7H) 13

C NMR = 143 553 622 666 687 729 1140 1260 1278


+

3281543 Found mz 3281539 IR (ATR) 1682 1418 1352 1024 696 cm-1

[]29

D = 02 (c = 085 in CHCl3)








pressure







mmol 58 yield)

Chapter 2

50

N

HO

S O

O

MeO

Me

1g

H

NOE

NOE


390 (s 3H) 399 (d J = 92 Hz 1H) 419 (q J = 60 Hz 1H) 698-707 (m 4H)

720-727 (m 3H) 779-785 (m 2H) 13

C NMR = 143 557 627 701 731 1144



-1

[]28




N

HO

S O

O

F3C

Me

1h

H

NOE

NOE


406 (d J = 92 Hz 1H) 430 (qd J = 64 08 Hz 1H) 694-699 (m 2H) 721-727

(m 3H) 784 (d J = 80 Hz 2H) 801 (d J = 84 Hz 2H) 13

C NMR = 145 629

706 729 1232 (JC-F = 2711 Hz) 1245 1263 (JC-F = 37 Hz) 1283 12868 12871


+

3720876 Found mz 3720870 IR (ATR) 3503 1348 1323 1165 646 cm-1

[]28




Chapter 2

51

N

HO

S O

O

Me

1i

H

NOE

NOE


1H) 401 (d J = 88 Hz 1H) 422 (q J = 64 Hz 1H) 694-698 (m 2H) 720-724 (m

3H) 746-750 (m 2H) 767-772 (m 2H) 13

C NMR = 144 214 630 704 730

1247 1256 1279 1285 1286 1291 1341 1347 1395 1416 HRMS (ESI+)


1151 714 700 cm-1

[]29




N

HO

S O

O

Me

1j

H

NOE

NOE

S


Hz 1H) 425 (q J = 64 Hz 1H) 696-701 (m 2H) 720-728 (m 4H) 764-767 (m

1H) 769-772 (m 1H) 13

C NMR = 144 632 709 730 1246 1279 1281 1286


+ 3100566

Found mz 3100559 IR (ATR) 3508 1340 1151 756 669 cm-1

[]29




Chapter 2

52

N

HO

S O

O

Me

1k

H

NOE

NOE

OMe


1H) 394 (d J = 88 Hz 1H) 416 (q J = 64 Hz 1H) 670-675 (m 2H) 684-689 (m

2H) 756-762 (m 2H) 765-770 (m 1H) 786-790 (m 2H) 13

C NMR = 143 553

630 704 729 1138 1259 1283 1292 1332 1337 1348 1592 HRMS (ESI+)


1327 1155 606 cm-1

[]29





Screening







mmol 93 yield)

Chapter 2

53


rac -DM-BINAP

rac-BINAP

dppf

dppb

PPh3

dppe

46

trace

trace

yield

PCy3

Ligand

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

entry

1

2

3

4

5

6

7

8

nd

nd

nd

93

none nd

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a


entry Ligand yield

1

2

3

4

(R)-BINAP

(R)-DM-BINAP

(R)-SEGPHOS

(R)-DIFLUORPHOS

er

94

46

48

43

5

6

(R)-DM-SEGPHOS


3862

91

7

8

(R)-MeO-BIPHEP

(R)-MeO-DM-BIPHEP

64

91

892

3169

1288

1486

2476

2575

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a










Chapter 2

54

NS Me

HO PhMe

2a

O O


J = 148 Hz 1H) 683 (s 1H) 727-744 (m 6H) 781 (d J = 84 Hz 1H) 13

C NMR

= 216 361 626 732 1238 1263 1280 1284 1299 1301 1330 1412 1431


+ 3041002 Found mz 3040998 IR

(ATR) 3472 1325 1161 1142 735 cm-1

[]29




NS CH2D

HO Ph

D3C

2a-d

O O

D

D

D


J = 148 Hz 1H) 728-743 (m 5H) 13

C NMR = 201-210 (m) 358 (t JC-D = 212

Hz) 625 731 1234 (t JC-D = 249 Hz) 1262 1279 1283 1291-1300 (m 2C)


+ 3111441

Found mz 3111436 IR (ATR) 3524 1318 1290 1150 721 cm-1

NS Me

HO Ph

O O

S

2b


1H) 668 (d J = 52 z 1H) 730-738 (m 5H) 750 (d J = 52 Hz 1H) 13

C NMR =

378 630 722 1257 1264 1282 1286 1299 1338 1427 1467 HRMS (ESI+)


1150 1063 748 cm-1

[]29


Chapter 2

55



NS Me

HOMe

O O

OMe

2c


422 (d J = 148 Hz 1H) 684-690 (m 3H) 724-733 (m 3H) 774-779 (m 1H) 13

C

NMR = 216 360 553 626 729 1137 1237 1275 1299 1230 1328 1351


+ 3341108 Found mz

3341098 IR (ATR) 3441 1508 1250 1144 735 cm-1

[]29




NS Me

HOMe

O O

CF3



2H) 782 (d J = 80 Hz 1H) 13

C NMR = 216 360 625 731 12392 (q JC-F =

2708) 12395 1254 (q JC-F = 36 Hz) 1268 1298 1303 (q JC-F = 352) 1329


+ 3720876 Found

mz 3720869 IR (ATR) 3481 1323 1121 1067 733 cm-1

[]29




Chapter 2

56










SN

HO

Me

O OMe

Me

2e

H

NOE

NOE


= 68 Hz 1H) 675 (s 1H) 723-738 (m 6H) 777 (d J = 84 Hz 1H) 13

C NMR =

119 215 314 608 750 1242 1262 1275 1282 1298 1301 1316 1427


+ 3181158 Found mz

3181155 IR (ATR) 3481 1315 1163 1146 683 cm-1

[]28




SN

HO

Me

O OMe

MeO

2g

H

NOE

NOE

Chapter 2

57



5H) 782 (d J = 88 Hz 1H) 13

C NMR = 120 314 555 609 752 1144 1151



735 cm-1

[]29




SN

HO

Me

O OMe

F3C

2h

H

NOE

NOE



1H) 13

C NMR = 118 314 608 750 1228 (q JC-F = 2711 Hz) 1251 1258 (q



+ 3720876 Found

mz 3720872 IR (ATR) 3461 1325 1161 1142 739 cm-1

[]29




SN

HO

Me

O OMe

2i

H

NOE

NOE

Me

Chapter 2

58


J = 68 Hz 1H) 684 (d J = 80 Hz 1H) 718-736 (m 6H) 770 (s 1H) 13

C NMR

=119 211 314 607 748 1242 1262 1275 1282 1299 1338 1341 1395


+ 3181158 Found mz

3181155 IR (ATR) 3489 1448 1319 1148 735 cm-1

[]29




SN

HO

Me

O OMe

2j

H

NOE

NOES


1H) 656 (d J = 52 Hz 1H) 726-736 (m 5H) 743 (d J = 48 Hz 1H) 13

C NMR

= 114 319 619 742 1256 1266 1278 1284 1297 1334 1429 1480 HRMS


+ 3100566 Found mz 3100561 IR (ATR) 3524

1329 1151 1020 729 cm-1

[]29




SN

HO

Me

O OMe

2k

H

NOE

NOE

OMe


J = 68 Hz 1H) 685 (d J = 88 Hz 2H) 698-703 (m 1H) 722-730 (m 2H)

738-748 (m 2H) 785-790 (m 1H) 13

C NMR = 119 314 553 608 747 1136

Chapter 2

59



760 cm-1

[]26




SN

HO

Me

O OMe

2l

H

NOE

NOE

CF3

Me



= 84 Hz 2H) 778 (d J = 80 Hz 1H) 13

C NMR = 119 215 313 607 749




-1

[]26




SN

HO

iPr

O OMe

2m

H

NOE

NOE

Me


(m 1H) 264 (s 1H) 285 (s 3H) 441 (d J = 100 Hz 1H) 685 (s 1H) 714-735 (m

4H) 748 (d J = 76 Hz 2H) 772 (d J = 80 Hz 1H) 13

C NMR = 211 214 217

278 330 718 742 1244 1256 1270 1283 1292 1295 1300 1435 1442


+ 3461471 Found mz 3461466 IR

Chapter 2

60

(ATR) 3412 1315 1165 1146 683 cm-1

[]29




SN

HO

O OMe

2n

H

Me

NOE

SMe

1H NMR = 160-170 (m 1H) 184 (s 3H) 212-226 (m 4H) 230-242 (m 2H)

254-263 (m 1H) 294 (s 3H) 471 (dd J = 108 28 Hz 1H) 675 (s 1H) 722-738

(m 6H) 776 (d J = 80 Hz 1H) 13

C NMR = 150 215 242 301 321 643 748

1245 1262 1276 1283 12986 12993 1312 1429 1437 1441 HRMS (ESI+)


1165 1134 748 cm-1

[]28









was used as a


and


21 All



Chapter 2

61



2e

formula C17H19NO3S

fw 31739

T (K) 100(2)


space group P21c

a (Aring) 105967(5)


3) 152058(13)

Z 4 Dcalc (gcm

3) 1386

(mm-1

) 0225 F(000) 672



348500135

params 203 GOF on F

2 1069

R1 wR2 [Igt2(I)]

00322 00868

R1 wR2 (all data)

00335 00878

Chapter 2

62

























Med Chem 2003 46 1116








Chapter 2

63

































Chapter 2

64




2012 51 9160





11437-11439
























Chapter 2

65











2548-2551







11750









32 115



Chapter 2

66

Chapter 3

67

Chapter 3




Halides

Abstract






Chapter 3

68

Introduction
















2) are












several months


Et LiB

Ph

+B

Ph

Et

1a 74

(a)(b)[Me4N]


Chapter 3

69

















OMe

BrB

Ph

Et

OMe

3a

Ph

Et

OMe

H

4a

Pd-ligand AcOH

2a

+B

Ph

Et

1a

[Me4N]


EZ of 4ab

1 P(o-tol)3 69 397

2 P(t-Bu)3 47 1783

3 1-[(t-Bu)2P](biphenyl) 18 2872

4 2-[(t-Bu)2P](11-binaphthyl) 21 6733

5 DPEPhos 24 928



analysis



Chapter 3

70









Pd(0)

Pd

MeO

B

PdEt

OMe

Ph

B

Ph

Et

2a

BC

Pd

MeO

Br

A

1a

3a







dominates10
















Chapter 3

71










Chapter 3

72


BO

Ph

Et

OMe

5a 83

BO

Ph

Et

CF3

5b 85

BO

Ph

Et

NPhth

5c 82

BO

Ph

Et

5d 72b

BO

Ph

Et

5e 85

S

BO

n-Pr

Me

Cl

5f 74

BO

n-Pr

Ph

OMe

5g 82

BO

Ph

S

5h 83

BO

Ph

CO2Et

5i 81

BO

Ph

5j 82

Cl

BO

Ph

CF3

TBSO

BO

Cl

S

Ph

BO

Ph

Me

OMe

5n 71b

5m 925l 82

BO

Ph

5k 76

Me

+B

Ar

R

1

[Me4N]

2


BO

Ar

R

Ar

5







The reaction of 1a






Chapter 3

73








(E)-5o83 EZ = gt955

BO

Ph

Et

Ph

Ph

Et

PhO

NMe2

(Z)-685 EZ = lt595

Ph

Ph

EtO

NMe 2

(E)-675 EZ = 928

1a

(Z)-5o71 EZ = 793

+ PhBr

BO

Ph

Ph

Et

(a)

(c) (c)

(b)






Conclusions






Chapter 3

74




1H at 400 MHz and

11B at 128 MHz)



13C)

CD3CN ( = 194 for 1H =132 for


11B)









and Ph-9-BBN18


procedures


Et LiB

Ph

+B

Ph

Et

1a


2) Me4NCl MeOH

[Me4N]









74 yield)

Chapter 3

75

B

Ph

Et

1a

[Me4N]


136-207 (m 11H) 236-250 (m 2H) 303 (s 12 H) 679-686 (m 1H) 700-707 (m

2H) 735 (d J = 72 Hz 2H) 13

C NMR (CD3CN) = 149 166 266 (q JC-B = 379

Hz) 271 275 324 349 561 948 1221 1269 1339 11

B NMR = -133 HRMS




n-Pr LiB

Ar


2) Me4NCl MeOH B

n-Pr

1b

Cl

[Me4N]










Chapter 3

76

B

n-Pr

1b

Cl

[Me4N]

1H NMR (CD3CN) = 084-096 (m 5H) 111-121 (m 1H) 126-200 (m 13H)

235-250 (m 2H) 304 (s 12H) 700-705 (m 2H) 733 (d J = 84 Hz 2H) 13

C NMR

(CD3CN) = 139 234 249 266 (q JC-B = 393 Hz) 270 273 323 348 561

933 1265 1272 1355 11


[M-(NMe4)] 2991738 Found 2991730

B

n-Pr

1c

OMe

[Me4N]


128-201 (m 13H) 237-252 (m 2H) 303 (s 12H) 371 (s 3H) 663-668 (m 2H)

723 (d J = 81 Hz 2H) 13

C NMR (CD3CN) = 140 235 250 268 (q JC-B = 393

Hz) 272 275 324 349 554 561 929 1128 1344 1561 11

B NMR = -135


B

Ph

1d

[Me4N]


(m 2H) 134-196 (m 9H) 230-244 (m 2H) 304 (s 12H) 679-686 (m 1H)

699-706 (m 2H) 733 (d J = 72 Hz 2H) 13

C NMR (CD3CN) =23 87 266 (q

JC-B = 393 Hz) 271 274 323 349 562 1222 1269 1338 11

B NMR = -134


Chapter 3

77

B

Ph

1e

[Me4N]


(m 3H) 302 (s 12H) 679-686 (m 1H) 699-706 (m 2H) 734 (d J = 66 Hz 2H) 13

C NMR (CD3CN) = 253 268 (q JC-B = 379 Hz) 271 275 324 333 349 361

561 980 1221 1269 1339 11


[M-(NMe4)] 2912284 Found 2912278

B

1f

S

Ph

[Me4N]




09 Hz 1H) 712-730 (m 5H) 13

C NMR (CD3CN) = 240 268-290 (m) 325 347

380 562 928 1225 1261 1265 1271 1289 1297 1434 11

B NMR = -135


B

Ph

1g

TBSO

[Me4N]

1H NMR (CD3CN) = 005 (s 6H) 084-096 (m 11H) 110-120 (m 1H) 134-197

(m 9H) 216-233 (t J = 72 Hz 2H) 235-250 (m 2H) 301 (s 12H) 356 (t J = 78

Hz 2H) 680-687 (m 1H) 700-708 (m 2H) 735 (d J = 66 Hz 2H) 13

C NMR

(CD3CN) = -50 189 254-277 (m) 323 348 561 649 889 1222 1269

1339 11


Found 3812789

Chapter 3

78

B

Ph

1h

OMe

[Me4N]


(m 2H) 298 (s 12H) 373 (s 3H) 668-674 (m 2H) 701-718 (m 5H) 732 (d J =

87 Hz 2H) 13

C NMR (CD3CN) = 255-277 (m) 322 350 554 561 961 1129

1251 1287 1302 1312 1345 1564 11


C23H26BO [M-(NMe4)] 3292077 Found 3292081



Br

+

MeO


6 mol Ligand


2a

B

Ph

Et

OMe

(E)-3a

AcOH

Ph

Et

OMe

H

Ph

B

Et

OMe

+

+

(Z)-3a

(E)-4a

H

Et

OMe

Ph

(Z)-4a

B

Ph

Et

1a

[Me4N]









Chapter 3

79




B

Ph

Et

+


toluene 70 degC

Me3NO

Br

MeO

BO

Ph

Et

OMe

5a

1a

2a

[Me4N]









BO

Ph

Et

OMe


383 (s 3H) 438-444 (m 1H) 685-691 (m 2H) 714-736 (m 7H) 13

C NMR =

138 221 267 273 (br) 277 312 553 736 1132 1251 1278 1283 1298

1366 1436 1494 1586 11


3742417 Found 3742410

Chapter 3

80

BO

Ph

Et

CF3

5b


437-443 (m 1H) 718-726 (m 3H) 734-739 (m 2H) 745-748 (m 2H) 760-763

(m 2H) 13

C NMR = 135 220 266 271 (br) 276 312 738 12429 (q JC-F =

2701 Hz) 1247 (q JC-F = 36 Hz) 1280 1281 1289 (q JC-F = 320 Hz) 1291 1425

1476 1480 11


Found 4122186

BO

Ph

Et

NPhth

5c


440-450 (m 1H) 720-727 (m 3H) 734-739 (m 2H) 743-751 (m 4H) 777-783

(m 2H) 794-800 (m 2H) 13

C NMR = 137 221 266 274 (br) 275 312 738

1235 1254 1258 1279 1282 1294 1304 1317 1342 1429 1440 1482

1671 11

B NMR = 502 IR (KBr) = 2928 1742 1509 1381 714 cm-1

HRMS (EI)


BO

Ph

Et

5d

1H NMR = 021-034 (m 1H) 068-100 (m 8H) 120-150 (m 7H) 224-238 (m

1H) 244-258 (m 1H) 424-431 (m 1H) 722-754 (m 9H) 778 (d J = 78 Hz 1H)

783-788 (m 1H) 809-816 (m 1H) 13

C NMR = 137 216 219 259 262 264

(br) 282 309 314 734 1249 12537 12539 1255 1264 1270 1273 12795

Chapter 3

81

12799 1283 1321 1335 1413 1427 1467 11


for C28H31BO (M+) 3942468 Found 3942476

BO

Ph

Et

5e

S


448-456 (m 1H) 702 (dd J = 51 36 Hz 1H) 708 (dd J = 36 12 Hz 1H)

715-730 (m 4H) 732-738 (m 2H) 13

C NMR =141 221 271 289 312 739

1250 1255 1266 1269 1279 1281 1416 1427 1468 11

B NMR = 496


BO

n-Pr

Me

Cl

5f

1H NMR = 070 (t J = 75 Hz 3H) 096-133 (m 9H) 142-172 (m 6H) 220-228

(m 2H) 237 (s 3H) 439-446 (m 1H) 708-735 (m 8H) 13

C NMR = 140 212

219 221 267 274 (br) 313 363 737 1279 12846 12855 1298 1309 1365

1411 1420 1488 11


4062235 Found 4062237

BO

n-Pr

Ph

OMe

5g

Chapter 3

82


(s 3H) 435-450 (m 1H) 690 (d J = 81 Hz 2H) 711 (d J = 81 Hz 2H) 720-740

(m 5H) 13

C NMR = 140 219 221 267 274 (br) 312 362 551 736 1133

1267 1278 1287 1294 1354 1446 1475 1573 11




BO

Ph

S

5h

1H NMR = 027-032 (m 2H) 046-052 (m 2H) 098-130 (m 6H) 140-170 (m

8H) 430-445 (m 1H) 696-700 (m 1H) 704-707 (m 1H) 715-726 (m 2H)

729-738 (m 4H) 13

C NMR = 60 150 222 263 272 (br) 313 736 1241

1243 1253 1278 1290 1295 1410 1425 1431 11



BO

Ph

CO2Et

5i

1H NMR = 017-023 (m 2H) 045-053 (m 2H) 090-119 (m 6H) 132-173 (m

11H) 427-433 (m 1H) 438 (q J = 75 Hz 2H) 718-738 (m 7H) 798 (dt J = 78

15 Hz 2H) 13

C NMR = 56 144 151 220 263 269 (br) 312 609 735 1255

1279 1284 1287 1289 1303 1423 1453 1469 1665 11

B NMR = 496 IR

(KBr) = 2928 1717 1287 1100 cm-1


Found 4282526

BO

Ph

5j

Cl

Chapter 3

83

1H NMR = 023-029 (m 2H) 048-055 (m 2H) 094-123 (m 6H) 134-171 (m

8H) 432-439 (m 1H) 706-714 (m 1H) 718-726 (m 4H) 728-738 (m 4H) 13

C

NMR = 57 150 220 263 271 (br) 312 736 1255 1267 1279 1283 1284

1289 1304 1332 1423 1424 1461 11


C25H28BClO (M+) 3901922 Found 3901923

BO

Ph

5k

Me

1H NMR = 082-113 (m 6H) 126-164 (m 15H) 237 (s 3H) 268-280 (m 1H)

434-441 (m 1H) 704-709 (m 3H) 717-725 (m 4H) 730-737 (m 2H) 13

C NMR

= 215 219 248 263 273 (br) 312 315 433 735 1252 12689 12693 1275

1278 1283 1316 1365 1418 1424 1481 11


for C28H35BO (M+) 3982781 Found 3982780

BO

Cl

S

Ph

5l

1H NMR = 106-176 (m 13H) 250-260 (m 2H) 272-280 (m 2H) 441-449 (m

1H) 674 (dd J = 33 12 Hz 1H) 697-703 (m 3H) 709-738 (m 8H) 13

C

NMR(C6D6) =225 272 277 (br) 315 358 375 739 1247 1253 1261 1272

1285 12856 12861 1306 1335 1419 1427 1437 1491 11

B NMR = 495


BO

Ph

CF3

TBSO

5m

Chapter 3

84

1H NMR = -014 (s 6H) 079 (s 9H) 095-136 (m 6H) 142-168 (m 7H) 255 (t

J = 72 Hz 2H) 343 (t J = 72 Hz 2H) 435-442 (m 1H) 718-726 (m 3H)

731-737 (m 2H) 747 (d J = 81 Hz 2H) 759 (d J = 81 Hz 2H) 13

C NMR = -54

183 220 259 266 271 (br) 311 377 616 739 1242 (q JC-F = 2694 Hz) 1247

(q JC-F = 36 Hz) 1258 1280 1282 1290 (q JC-F = 320 Hz) 1291 1421 1422

1480 11



BO

Ph

Me

OMe

5n

1H NMR = 122-130 (m 4H) 138-162 (m 5H) 168-186 (m 4H) 237 (s 3H)

375 (s 3H) 443-450 (m 1H) 670 (dt J = 90 21 Hz 2H) 690-697 (m 4H)

702-708 (m 3H) 710-720 (m 4H) 13

C NMR = 213 222 269 312 550 738

1132 1260 1272 1285 1301 1307 1310 1362 1369 1423 1429 1483

1571 11


4362561


4-Bromobenzene

B

Ph

Et

+


toluene 70 degC

Me3NO BO

Ph

Ph

Et

(Z)-5o

1a

Ph Br

[Me4N]




Chapter 3

85






BO

Ph

Ph

Et


470-475 (m 1H) 685-710 (m 10H) 13

C NMR = 139 224 267 313 317 740

1248 1257 1272 127412938 12941 1421 1425 1275 11

B NMR = 512


BO

Ph

Et

Ph


438-443 (m 1H) 718-737 (m 10H) 13

C NMR = 137 221 266 274 (br) 277

312 737 1253 1268 1278 1279 1283 1288 1433 1442 1494 11

B NMR =



Bromide 2b

+

Br

ONMe2

Ph

Et

PhO

NMe2


THF K3PO4 60 degC

(Z)-Tamoxifen 6

2b

BO

Ph

Et

Ph

(E)-5o

Chapter 3

86









Chapter 3

87



2003 Vol 3








Rev 2006 250 1107









1976 108 281








74





Chapter 3

88





















2006 128 1828




Chapter 4

89

Chapter 4



Abstract






Chapter 4

90

Introduction





























Chapter 4

91


B

MOMO

[Me4N] +

MeO

Br

I

Br

MeO Br

B

MeO

MOMO MOMO

1a

2 3 87EZ = lt199

NaOH

50 degC

1 mol


toluene 50 degC
















procedure

Chapter 4

92



An











3

MeO

R

Br

4 92

R

MeO

R

Br

n = 2 5 87

n = 3 6 82n = 4 7 85

n

R

1 mol


toluene 50 degC

I

Br

NaOH

E

EE

R = OMOM








Chapter 4

93





Br

Br

R

R

Br

Br

8 86

R

R

Br

R

R

Br

9 92

E E

R = OMOM















Chapter 4

94


Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

Me3Si

Br

Ph

F

Me3Si

OMe

Br

Ph

F

S

Br

Me3Si

OMe

B

n-Pr

[Me4N]

Cl

B

Ph

[Me4N]

OMe

Br

S

Br

I

EtO2C

MOMO

MOMO

I

Br

F

1b

10 88

11 84

12 88

1a1c

cat Pd

NaOHcat Pd

cat Pd NaOH

Cs2CO3

Conclusions







Chapter 4

95




1H at 500 MHz and






13C) CD3CN ( = 194 for

1H =132 for

13C) and

BF3OEt2 ( = 000 for 11











11













Chapter 4

96

B

MOMO

[Me4N]

1a


202 (t J = 66 Hz 2H) 236-251 (m 2H) 304 (s 12H) 328 (s 3H) 346 (t J = 69

Hz 2H) 454 (s 2H) 678-685 (m 1H) 698-705 (m 2H) 734 (d J = 72 Hz 2H) 13

C NMR (CD3CN 75 MHz) = 210 267 (br) 271 275 282 297 324 349 551

561 681 928 968 1221 1269 1338 11



B

Ph

[Me4N]

1b

OMe


225 (t J = 72 Hz 2H) 234-249 (m 2H) 263 (t J = 72 Hz 2H) 303 (s 12H) 372

(s 3H) 663-669 (m 2H) 711-728 (m 7H) 13


272 275 324 349 381 554 560 1129 1266 1289 1298 1346 1434 1563 11


3572390 Found 3572383



B

MOMO

[Me4N]

+

MeO

Br

1 mol


toluene 50 degC

I

Br

MeO Br

NaOH

3

1a

MOMO

Chapter 4

97








MeO Br

3

MOMONOE

NOE




(t J = 66 Hz 2H) 376 (s 3H) 452 (s 2H) 667-675 (m 4H) 697-702 (m 2H)

709-736 (m 7H) 13

C NMR (75 MHz) = 255 298 356 5510 5514 676 964

1134 1196 1267 1282 1294 13046 13049 1323 1339 1376 1408 1420



spectroscopy

MeO

R

Br

4

R

R = OMOM




Chapter 4

98


2H) 325 (s 3H) 329 (s 3H) 331-341 (m 4H) 380 (s 3H) 451 (s 2H) 453 (s

2H) 662-678 (m 8H) 697-703 (m 2H) 706-738 (m 12H) 13

C NMR (150 MHz)

= 252 254 295 296 353 354 5502 5504 552 675 676 9629 9632 1131

1196 1265 1267 1281 1282 1285 12941 12942 1303 1304 1306 1324

1343 1377 1385 1390 1400 1413 1414 1418 1429 1435 1579 HRMS


7972818 Found

7972849

MeO

R

5

R

R = OMOM

R

Br




325 (s 3H) 327 (s 3H) 328 (s 3H) 330-342 (m 6H) 374 (s 3H) 450 (s 2H)

452 (s 2H) 454 (s 2H) 654-662 (m 4H) 666-678 (m 8H) 696-704 (m 4H)

712-737 (m 15H) 13

C NMR (75 MHz) = 254 256 296 297 298 3526 3534

355 551 675 676 963 1130 1196 1264 1267 1280 1281 1286 1294 1301

1302 1304 1306 1324 1344 1377 1384 1387 1392 1393 1398 1402 1409



10914437 Found 10914482

Chapter 4

99

MeO

R

6

R

R = OMOM

R

R

Br




330-341 (m 8H) 371 (s 3H) 448-454 (m 8H) 648-675 (m 16H) 695-703 (m

4H) 714-737 (m 20H) 13

C NMR (75 MHz) = 253 254 256 257 2969 2974

298 350 354 356 550 551 675 676 963 1131 1196 1264 1267 1279

1280 1281 1283 1288 1293 1294 1300 1301 1302 1305 1306 1323 1342

1377 1385 1387 1389 1391 1394 1396 1397 1401 1405 1409 1411 1413



13856057 Found 13856062

MeO

R

7

R

R = OMOM

R

R

R

Br




374 (s 3H) 447-452 (m 10 H) 649-679 (m 20 H) 690-695 (m 2H) 701-706 (m

2H) 710-736 (m 25H) 13

C NMR (75 MHz) = 2529 2535 256 257 2968

Chapter 4

100

2971 298 351 354 355 356 550 6746 6755 676 963 1131 1195 1264

1267 12795 1280 1281 1283 1285 1287 1293 12937 12944 1301 1302

1304 1306 1322 1343 1377 1384 1387 1389 1390 1391 1394 13976

13979 1401 1404 1408 1409 1412 1413 1416 1427 14318 14321 1434


16797677 Found 16797694

8

R

Br

R

Br

R = OMOM





(t J = 66 Hz 4H) 456 (s 4H) 668-673 (m 4H) 691 (s 4H) 710-721 (m 8H)

722-737 (m 6H) 13

C NMR (75 MHz) = 254 297 354 551 676 963 1198

1268 1282 1291 1293 1303 1323 1380 1400 1411 1417 1427 HRMS


8221905

9

R

R

R = OMOM

R

R

Br

Br



Chapter 4

101


6H) 330-340 (m 8H) 446 (s 4H) 453 (s 4H) 656-672 (m 12H) 688 (s 4H)

704-710 (m 4H) 714-718 (m 4H) 722-740 (m 16H) 13

C NMR (150 MHz) =

254 2962 2963 356 357 5501 5503 674 676 9629 9631 1197 1266

1268 1281 12818 12822 1290 1295 1296 1304 1308 1324 1379 1385

1394 1403 1405 1409 1416 1417 1427 1434 HRMS (MALDI-TOF-MS


14335057 Found 14335040

Ph

F

Me3Si

OMe

Br

10

NOE

NOE





3H) 676-686 (m 3H) 694-707 (m 6H) 709-728 (m 5H) 734 (d J = 84 Hz 2H) 13

C NMR (150 MHz) = -11 349 372 552 1135 1189 (d JC-F = 255 Hz)1202

(d JC-F = 92 Hz) 1258 1268 (d JC-F = 35 Hz) 1280 1283 1284 1300 1304 (d

JC-F = 159 Hz) 1326 1329 1332 (d JC-F = 45 Hz) 1339 1387 1417 1418 1430




Chapter 4

102

Ph

F

S

Br

Me3Si

OMe

11

MOMO




= 78 2H) 264-272 (m 2H) 282-289 (m 2H) 325 (s 3H) 328 (t J = 66 Hz 2H)

382 (s 3H) 448 (s 2H) 587 (d J = 39 Hz 1H) 660 (d J = 39 Hz 1H) 669-676

(m 2H) 684-696 (m 3H) 705-742 (m 16H) 13

C NMR (150 MHz) = -10 244

293 351 362 372 550 552 673 963 1127 1135 1161 (d JC-F = 225 Hz)

1244 (d JC-F = 32 Hz) 1258 1274 12827 12831 12837 12840 12856 12861

1295 1302 1307 (d JC-F = 155 Hz) 1324 1329 1330 (d JC-F = 45 Hz) 1333

1345 1385 1395 (d JC-F = 12 Hz) 1412 1416 (d JC-F = 80 Hz) 1419 1422



Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

12MOMO




mmol) t1 10 h t2 12 h

Chapter 4

103


210-224 (m 4H) 264-272 (m 2H) 279-287 (m 2H) 323-333 (m 5H) 373 (s


1H) 666-672 (m 2H) 679-694 (m 5H) 703-737 (m 20H) 773 (d J = 84 Hz

2H) 13

C NMR (150 MHz) = -11 141 143 225 244 293 350 359 370 385

550 551 607 674 963 1134 1159 (d JC-F = 224 Hz) 1243 (d JC-F = 29 Hz)

1258 1269 1271 12808 12811 12815 12820 12823 12838 12844 1290

1293 1300 1301 (d JC-F = 158 Hz) 1302 1307 1323 (d JC-F = 47 Hz) 13258

13261 1328 1336 1344 1356 1379 1382 1390 (d JC-F = 12 Hz) 1409 14190

14191 14216 (d JC-F = 80 Hz) 14219 14222 1438 1446 1476 1583 1600 (d

JC-F = 2448 Hz) 1664 IR (KBr) = 2955 1717 1509 1273 1248 1111 837 cm-1


11294440

Found 11294465

Chapter 4

104




Chem 1999 201 163




897















2404


2006 128 1828



Chapter 5

105

Chapter 5




Abstract






Chapter 5

106

Introduction





moiety1b


























Chapter 5

107


B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

OHMe

Ph

1a

3a 85

MeO

OMe

2a

B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

1b

OMe

2a

OHMe

Ph

OMe

3b 88

[Me4N]

[Me4N]




Oxidative









Chapter 5

108


O

I

O

PdI

Pd(0)

B

1a

C

Pd(0)3a

Ar = p-MeOC6H4-

Me Me

OMe

Ar

Ph

B

D

A

Pd

O

ArB

Me

Ph

B

O

ArPh

Me

Me4NI

2a







Chapter 5

109


R3

O

I

B

R2

R1

+1 mol Pd

toluene50 degC 1 h

OHR3

R1

R2

OHMe

Ph

S

OHMe

OMe

OHPh

Ph

OMe

3f 72

3h 763j 80

3g 84

3d 82

3c 83

OHMe

Ph

CF3

1 2 3

OHH

Ph

OMe

OHPh

Ph

OMe

O

O

OHPh

3e 92

F

OMe

OHPh

Ph

OMe

F3C

3i 62

R4R4

MeO

[Me4N]










Chapter 5

110

OHMe

t-Bu

S

3k 89

B +1 mol Pd

toluene

50 degC 1 h

2a

t-Bu

S

(1)

1c

[Me4N]

OHMe

n-Bu

Me

3l 80

B

n-Bu

+1 mol Pd

toluene50 degC 1 h

2a

Me

(2)

1d

[Me4N]










n-Hex

13 equiv

Ph

Li

065 equiv

(H-9-BBN) 2


1 mol Pd

toluene 50 degC 1 h

10 equiv 2aOH

Me

n-Oct

11 equiv

3m 91 (based on 2a)

B

n-Oct

PhLi

Ph




Chapter 5

111


in 59 yield11


OHH

Ph

OMe

MnO2

DCM rt

Ph

OMe

O

NH2NH2 KOHPh

OMe

4 96 5 59

3n 74

(CH2OH)2 150 C

1a +

CHO

I2b

1 mol Pd

Conclusions




Chapter 5

112



and 13


B at 128 MHz)



13C) CD3CN (δ = 194 for

1H δ = 132 for


11B) IR






(Merck)





and alkynylborate14




Li

BPh

+

B

Ph

1a


2) Me4NCl MeOH

[Me4N]

MeO

MeO










Chapter 5

113

B

Ph

1a

[Me4N]

MeO


(m 2H) 296 (s 12H) 372 (s 3H) 668-675 (m 2H) 685-691 (m 1H) 700-712 (m

4H) 743 (d J = 64 Hz 2H) 13

C NMR (CD3CN) δ = 256-272 (m) 270 274 322

350 557 560 955 1145 1227 (2C) 1273 1324 1341 1578 The boron-bound


11B NMR


3292079

B

Ph

1b

[Me4N]

OMe


(m 2H) 295 (s 12H) 374 (s 3H) 666-675 (m 2H) 702-718 (m 5H) 733 (d J =

84 Hz 2H) 13

C NMR (CD3CN) δ = 254-274 (m) 270 273 321 350 554 560





B

nBu

1d

[Me4N]

Me


(m 4H) 136-157 (m 6H) 170-196 (m 4H) 220-234 (m 5H) 304 (s 12H)

697-701 (m 2H) 704-709 (m 2H) 13

C NMR (CD3CN) δ = 152 212 270

271-290 (m) 282 288 318 324 357 561 1279 1296 1314 1344 The

Chapter 5

114




[M-(NMe4)]- 2932446 Found 2932454

B

Ph

1e

[Me4N]

F3C


(m 2H) 292 (s 12H) 690-696 (m 1H) 710-718 (m 2H) 728 (dd J = 88 08 Hz

2H) 744-752 (m 4H) 13

C NMR (CD3CN) δ = 252-270 (m) 269 273 321 351






B

Ph

1f

[Me4N]

S



48 32 Hz 1H) 703-719 (m 6H) 13

C NMR (CD3CN) δ = 266 272 270-286 (m)

323 348 560 962 1231 1256 1266 1274 1290 1300 1314 The boron-bound

sp2 and sp


11B NMR


- 3051541 Found

3051541

Chapter 5

115


(H-9BBN) 2

H tBu

THF 0 degC

THF -78 degC to rt

2) Me4NCl MeOH

Li

1)S

B

1c

[Me4N]

S

tBu














B

1c

[Me4N]

S

tBu


4H) 222-235 (m 2H) 306 (s 12H) 552 (d J = 172 Hz 1H) 591 (d J = 176 Hz


Hz 1H) 13

C NMR (CD3CN) δ = 273 276 278-296 (m) 311 327 341 352 561





Chapter 5

116












OHMe

3aOMe

NOE

no NOE

IR (ATR) 3315 1508 1248 752 694 cm-1

1H NMR δ = 159 (s 3H) 204 (bs 1H)

382 (s 3H) 684-690 (m 2H) 721-730 (m 8H) 742-748 (m 2H) 751-755 (m

1H) 13

C NMR δ = 239 552 832 1139 1208 1218 1265 1268 1272 1280


C23H21O2 [M+H]+ 3291536 Found 3291556

OHMe

OMe

3b

NOE

no NOE

IR (ATR) 3319 1508 1248 760 702 cm-1

1H NMR δ = 160 (s 3H) 208 (s 1H)

378 (s 3H) 674-680 (m 2H) 718-723(m 1H) 724-744 (m 9H) 750-755 (m

1H) 13

C NMR δ = 241 551 833 1134 1205 1218 1263 1270 1274 1284


Chapter 5

117

C23H20O2Cl [M+Cl]- 3631146 Found 3631148

OHMe

Ph

3cCF3

IR (ATR) 3298 1319 1121 750 696 cm-1

1H NMR δ = 160 (s 3H) 210 (bs 1H)

716-722 (m 1H) 723-732 (m 5H) 737-747 (m 4H) 752-764 (m 3H) 13

C NMR

δ = 240 833 1205 1221 1241 (q JC-F = 2701 Hz) 1255 (q JC-F = 37 Hz) 1269

1277 1282 1286 1293 1295 (q JC-F = 322 Hz) 1296 1341 1373 1385 1414


- 3651159 Found 3651159

OHMe

Ph

3d

S

IR (ATR) 3319 1350 1088 752 694 cm-1

1H NMR δ = 177 (s 3H) 209 (bs 1H)

696-702 (m 2H) 718 (dd J = 52 Hz 12Hz 1H) 723-730 (m 2H) 735-740 (m

3H) 742-752 (m 3H) 753-758 (m 1H) 13

C NMR δ = 254 833 1207 1216

1259 1265 1266 1275 1282 1287 1290 1294 1347 1360 1374 1410 1426


+ 3050995 Found 3050992

OHMe

OMe

3e

IR (ATR) 3310 1508 1244 1034 758 cm-1

1H NMR δ = 144 (s 3H) 158-202 (m


5H) 747 (d J = 68 Hz 1H) 13

C NMR δ = 238 266 267 305 311 382 552

822 1136 1211 1219 1257 12789 12793 1304 1406 1409 1467 1499


+ 3382115 Found 3382104

Chapter 5

118

OHH

Ph

3fOMe

MeO

IR (ATR) 3472 1601 1508 1244 704 cm-1

1H NMR δ = 174 (d J = 88 Hz 1H)


= 80 Hz 24 Hz 1H) 692-697 (m 2H) 718-730 (m 5H) 732-736 (m 2H) 753 (d

J = 84 Hz 1H) 13

C NMR δ = 552 555 766 1072 1109 1143 1244 1267 1272

1283 1292 1303 1342 1363 1390 1445 1457 1592 1606 HRMS (ESI+)


OHPh

Ph

3gOMe

IR (ATR) 3422 1508 1244 1028 746 698 cm-1

1H NMR δ = 248 (s 1H) 385 (s

3H) 695 (d J = 88 Hz 2H) 704-714 (m 5H) 715-732 (m 7H) 736-740 (m 2H)

755 (d J = 88 Hz 2H) 13

C NMR δ = 552 868 1141 1210 1231 1250 1268

12698 12702 1271 1278 12836 12844 1294 1304 1340 1402 1417 1427


+ 3911693 Found

3911718

OHPh

Ph

3hOMe

O

O

IR (ATR) 3362 1470 1244 1034 696 cm-1

1H NMR δ = 239 (s 1H) 385 (s 3H)

591 (dd J = 164 16 Hz 2H) 673 (d J = 44 Hz 2H) 690-696 (m 2H) 702-708

(m 5H) 720-736 (m 5H) 749-754 (m 2H) 13

C NMR δ = 552 863 1012 1024

Chapter 5

119

1049 1142 1249 12690 12692 1270 1278 1285 1292 1304 1340 1367


+

4341518 Found 4341505

OHPh

Ph

3iOMe

F3C

IR (ATR) 3545 1508 1321 1115 696 cm-1

1H NMR δ = 249 (s 1H) 387 (s 3H)

694-700 (m 2H) 704-715 (m 5H) 723-738 (m 6H) 742-755 (m 4H) 13

C NMR

δ = 553 866 1145 1177 (q JC-F = 37 Hz) 1233 1241 (q JC-F = 36 Hz) 1242 (q

JC-F = 2702 Hz) 1249 1260 1275 1276 1280 1287 1295 1304 1308 (q JC-F =


C29H21F3O2Cl [M+Cl]- 4931177 Found 4931192

OHPh

3j

F

OMe

IR (ATR) 3356 1242 1028 741 696 cm-1

1H NMR δ = 164-178 (m 2H) 183-208


4H) 719-737 (m 6H) 13

C NMR δ = 2675 2681 308 310 383 551 862 1114


1268 1271 1283 1303 1371 (d JC-F = 29 Hz) 1410 1418 (d JC-F = 15 Hz)



+ 4001839 Found 4001835

OHMe

S

tBu

3k

Chapter 5

120

IR (ATR) 3298 1358 1078 756 689 cm-1

1H NMR δ = 111 (s 9H) 168 (s 3H)

188 (s 1H) 640 (d J = 164 Hz 1H) 656 (d J = 164 Hz 1H) 718-730 (m 4H)

739-751 (m 3H) 13

C NMR δ = 257 295 340 822 1169 1204 1215 1242

1255 1262 1283 1285 1324 1346 1415 1452 1462 1506 HRMS (ESI+)


OHMe

nBu

OMe3l

IR (ATR) 3335 1508 1084 918 758 cm-1

1H NMR δ = 085 (t J = 72 Hz 3H) 130

(tt J = 72 72 Hz 2H) 141-167 (m 6H) 229-250 (m 5H) 702-706 (m 1H)

716-728 (m 6H) 744-748 (m 1H) 13

C NMR δ = 138 213 232 237 252 314

829 1198 1215 1256 1282 1286 1291 1318 1370 1374 1430 1492 1496


+ 2931900 Found 2931890



nHex

(H-9BBN) 2


Li

Ph

B

nOct

Li

Ph

Me

O

I


toluene 50 degC 1 h

H2O2 aq

NaOH aq

OHMe

nOct

Ph3m

MeOH




Chapter 5

121













yield)

OHMe

nOct

Ph3m

IR (ATR) 3335 1456 1078 752 698 cm-1

1H NMR δ = 096 (t J = 68 Hz 3H)

129-156 (m 15H) 160 (s 1H) 208-227 (m 2H) 274-281 (m 2H) 287-294 (m

2H) 719-728 (m 5H) 729-736 (m 3H) 742 (d J = 72 Hz 1H) 13

C NMR δ = 141

226 234 247 277 293 294 295 304 319 345 825 1186 1213 1252 1260


[M]+ 3622610 Found 3622619

OHH

Ph

OMe

3n

IR (ATR) 3354 1508 1246 764 692 cm-1

1H NMR δ = 185 (bs 1H) 386 (s 3H)

567 (s 1H) 692-697 (m 2H) 718-738 (m 10H) 763-766 (m 1H) 13

C NMR δ =

552 773 1143 1206 1237 1263 1268 1272 1283 1287 1292 1303 1342


- 3131234

Found 3131237

Chapter 5

122

The 1H


15


OHH

Ph

OMe

3n

MnO2

DCM rt

Ph

OMe

4

O







The 1H


16

Ph

OMe

4

O

(CH 2OH)2

NH2NH2

KOH Ph

OMe

5








The 1H


5

Chapter 5

123






1395ndash1411



17638ndash17640





3201ndash3222



















Chapter 5

124












3283ndash3292









74








Chem 1989 54 1485ndash1491



2006 128 1828

Chapter 5

125



4781-4787


Chem 1989 54 1485

Chapter 5

126

127

List of Publication

Chapter 1



Angew Chem Int Ed 2012 51 11750-11752

Chapter 2


Benzosultams


J Am Chem Soc 2013 135 19103-19106

Chapter 3





Org Lett 2009 11 5434-5437

Chapter 4


Units


Org Lett 2010 12 3179-3181

Chapter 5




Eur J Org Chem 2013 1421-1424

Other Publication




Chem Lett 2013 42 1076


5

Reference





































6








10990




2003 Vol 3





Q Z J Med Chem 2009 52 4192



2006 250 1107



2419













7



17638ndash17640


8

Chapter 1

9

Chapter 1


Ketones

Abstract






Chapter 1

10

Introduction







2 One







starting substances


CO2

sun

CO2energy charge

high energy

intermediates











8






Chapter 1

11


Ph

O

NTs

Mesolar light

N

Ph OH

Ts

2a 91

1aDMA







over 04 kWm-2



in eight hours on


Figure





kWhm-2



Chapter 1

12


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

0

20

40

60

80

100

0 1 2 3 4 5 6











(56)

Chapter 1

13


40 equiv Cs2CO3

1 atm CO2

DMA 60 degC

OO

O

Ph

NHTs

3a 93

N

Ph OH

Ts

2a








N

Ph O

Ts

A

N

Ph O

Ts

B

O

O

OO

O

Ph

NTs

CO2

H

C

Cs2CO3

CsHCO 3

Cs

Cs

Cs

2

1

N

Ph OH

Ts

2a

OO

O

Ph

NHTs

3a












N

Ts

OHPh

4

Chapter 1

14




solar light

CO2Cs2CO3

60degCDMAPh

O

NTs

Me

1a

OO

O

Ph

NHTs

3a 83






chloro groups10





Ar

O

NR

Me OO

O

Ar

NHR3

1

OO

O

NHTs3b 80

MeO

OO

O

NHTs3c 57

F3C

OO

O

NHTs3d 73

Cl

OO

O

NHTs3e 85

Br

OO

O

Ph

NH

3f 87

O2S OMe

OO

O

Ph

NH

3g 85

O2S CF3

OO

O

Ph

NH

3h 87

O2S

N

solar lightCO2

Cs2CO3

60degCDMA




Chapter 1

15

Conclusions















Chapter 1

16












indicator (Merck)






Ph

O

NTs

MeTsClMeNH2 +

Et2OTsNHMe

CH3CN

K2CO3












Chapter 1

17


Ph

O

NTs

Me


745-751 (m 2H) 760 (tt J = 76 12 Hz 1H) 771-775 (m 2H) 795-799 (m 2H)

13C NMR δ = 215 356 560 1275 1282 1288 1297 1338 1347 1348 1436


+ 3041002 Found mz 3040994 IR

(ATR) 1693 1339 1227 1157 743 cm-1

O

NTs

Me

1bMeO


733 (d J = 80 Hz 2H) 770-774 (m 2H) 796-802 (m 2H) 13

C NMR δ = 215

355 555 558 1139 1275 1277 1296 1307 1346 1436 1640 1921 HRMS


+ 3341108 Found mz 3341101 IR (ATR) 1688

1601 1329 1180 1159 cm-1

O

NTs

Me

1cF3C


= 84 Hz 2H) 776 (d J = 84 Hz 2H) 812 (d J = 84 Hz 2H) 13

C NMR δ = 215

357 564 1234 (q JC-F = 2711 Hz) 1259 (q JC-F = 37 Hz) 1276 1288 1298



1121 1109 cm-1

Chapter 1

18

O

NTs

Me

1dCl


(m 2H) 771 (d J = 80 Hz 2H) 792-796 (m 2H) 13

C NMR δ = 216 356 561



1159 1088 cm-1

O

NTs

Me

1eBr


= 84 Hz 2H) 771 (d J = 84 Hz 2H) 786 (d J = 84 Hz 2H) 13

C NMR δ = 215

356 561 1275 1291 1297 1298 1321 1334 1344 1438 1930 HRMS (ESI+)


1223 1155 810cm-1

Ph

O

NS

Me

1f

OMe

OO

1H NMR δ = 282 (s 3H) 389 (s 3H) 456 (s 2H) 698-703 (m 2H) 746-751 (m

2H) 761 (tt J = 72 12 Hz 1H)776-781 (m 2H) 796-800 (m 2H) 13

C NMR δ =

356 556 561 1142 1283 1288 1294 1297 1338 1348 1630 1938 HRMS


+ 3200951 Found mz 3200943 IR (ATR) 1692

1342 1259 1155 741 cm-1

Chapter 1

19

Ph

O

NS

Me

1g

CF3

OO


780 (d J = 84 Hz 2H) 790-794 (m 2H) 798 (d J = 80 Hz 2H) 13

C NMR δ =

356 558 1233 (q JC-F = 2711 Hz) 1261 (q JC-F = 36 Hz) 12796 12799 1289



1059 748 cm-1

Ph

O

NS

Me

1h

N

OO

1H NMR δ = 302 (s 3H) 486 (s 2H) 744-753 (m 3H) 757-762 (m 1H)

788-798 (m 4H) 870 (ddd J = 48 16 08 Hz 1H)13

C NMR δ = 363 569 1224



752 cm-1


Ph

O

NTs

Mesolar light

N

Ph OH

TsDMA rt

1a

2a








Chapter 1

20


N

Ph OH

Ts


2H) 728-737 (m 5H) 740 (d J = 80 Hz 2H) 779 (d J = 80 Hz 2H) 13

C NMR δ

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS




N 458 O 1555 S 1058 IR (ATR) 3477 1333 1184 1148 671 cm-1


N

Ph OH

Ts

2a

40 equiv Cs2CO3

1 atm CO2

DMA 60 C

OO

O

Ph

NHTs

3a








mmol 93 yield)

Chapter 1

21



40 equiv Cs2CO3

60 CPh

O

NR

Me OO

O

Ph

NHR3a

1a

solar light

DMA rt

1 atm CO2











OO

O

Ph

NHTs



726-732 (m 4H) 734-743 (m 3H) 769-773 (m 2H) 13

C NMR δ = 215 503

724 850 1242 1269 1292 1299 1365 1381 1439 1542 HRMS (ESI+) Calcd

for C17H18NO5S M+H+


C 5878 H 493 N 403 O 2303 S 923 Found C 5871 H 496 N 389 O

2284 S 932 IR (ATR) 3261 1773 1435 1319 1045 cm-1

Chapter 1

22

OO

O

NHTs

3b

MeO



56 Hz 1H) 688-693 (m 2H) 719-724 (m 2H) 728 (d J = 80 Hz 2H) 770 (d J =

84 Hz 2H) 13

C NMR δ = 215 503 554 724 848 1145 1256 1269 1298


+

3781006 Found mz 3780996 IR (ATR) 3238 1794 1518 1329 1057 723 cm-1

OO

O

NHTs

3c

F3C



729 (d J = 84 Hz 2H) 746 (d J = 84 Hz 2H) 765-771 (m 4H) 13

C NMR δ =

215 501 722 846 1235 (q JC-F = 2704 Hz) 1249 1263 (q JC-F = 37 Hz) 1268



1067 cm-1

OO

O

NHTs

3d

Cl



722-727 (m 2H) 728 (d J = 84 Hz 2H) 735-739 (m 2H) 769 (d J = 84 Hz 2H)

13C NMR δ = 215 502 723 847 1257 1268 1294 1300 1353 1364 1365


+ 3820510 Found mz

Chapter 1

23

3820506 IR (ATR) 3250 1800 1325 1155 1069 cm-1

OO

O

NHTs

3e

Br



716-720 (m 2H) 728 (d J = 80 Hz 2H) 750-755 (m 2H) 766-770 (m 2H) 13

C

NMR δ = 215 501 723 847 1235 1260 1268 1300 1323 1364 1370 1441


+ 4260005 Found mz 4260003

IR (ATR) 3252 1800 1331 1175 1057 cm-1

OO

O

Ph

NH

SO

O

OMe



693-698 (m 2H) 727-732 (m 2H) 734-744 (m 3H) 773-778 (m 2H) 13

C NMR

δ = 503 556 724 849 1145 1242 1291 1292 1310 1381 1541 1632 HRMS


+ 3640849 Found mz 3640836 IR (ATR) 3246

1801 1325 1155 1067 cm-1

OO

O

Ph

NH

SO

O

CF3

3g

Chapter 1

24



2H) 735-744 (m 3H) 775 (d J = 88 Hz 2H) 796 (d J = 84 Hz 2H) 13

C NMR δ

= 505 725 851 1231 (q JC-F = 2711 Hz) 1241 1265 (q JC-F = 37 Hz) 1274



1161 1105 cm-1

OO

O

Ph

NH

SO

O

N




1H) 798 (d J = 76 Hz 1H) 866 (d J = 44 Hz 1H) 13

C NMR δ = 510 723 849



1175 1063 cm-1


N

Ts

OHPh

N

Ts

O CeCl 3

PhLi

THF -78 C to rt

4






Chapter 1

25






N

Ts

OHPh


351-364 (m 4H) 726-738 (m 7H) 773-777 (m 2H) 13

C NMR δ = 215 396

469 608 804 1250 1276 1280 1286 1297 1339 1418 1435 HRMS (ESI+)


1325 1159 1101 770 cm-1

Chapter 1

26











Soc 2011 133 12881

























25 312

Chapter 1

27








Chapter 1

28

Chapter 2

29

Chapter 2



Abstract







Chapter 2

30

Introduction














A



Indanones are


A rearrangement













Whereas







Chapter 2

31




N

HO Ph

S NS Me

HO PhMe

1a2a 96

Me

O

OO O


2) is





The generated








N

S O

O

O[Rh]

Ph

SN

[Rh]O Ph

O OMe

[Rh] OH

N

S O

O

O Ph

H

[Rh]

H

N

[Rh]O Ph

S O

O

Me Me

Me

Me

1a

H2O

2a

A B

CD

1a

A




Chapter 2

32








N

HO Ph

SN

S CH19D11

HO Ph

D3C

1a-d2a-d 96

D3C

O

O

O O

D

D

D

D

D

D

H01D09

8



D12




Application




1

2

SN

HO Ar

O OMe

N

HO Ar

S O

O


K2CO 3 (20 equiv)


NS Me

HO PhMe

2a

91 er = 928

O O

NS Me

HO Ph

2b

95 er = 937

O O

S

NS Me

HOMe

2c

90 er = 937

O O

OMe

NS Me

HOMe

2c

92 er = 919

O O

CF3



Chapter 2

33










HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6 84

5 56



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3


PhMgBr

THF rt 1 h N

HO

Ts

Me

1e 93

er gt 991 dr = 201

Ph

3







SN

HO PhMe

O OMe

MeN

HO Ph

S O

O

Me

Me

1e

er gt 991 dr = 201

2e 99

er gt 991 dr gt 201





Chapter 2

34









SN

PhRhOMe

O OMe

Me

SN

PhRhOMe

O OMe

Me

favored

disfavored

F

F

NSRh

Ph

Me

O

O

MeO

H

Me

E

E

NSRh

Ph

Me

O

O

MeO

Me

H














Chapter 2

35


1

er gt 991 dr gt 201

2

er gt 991 dr gt 201

SN

HO ArR

O OMe

N

HO Ar

S O

O





1 N

HO Ph

S O

O

Me

Me

1f

SN

HO PhMe

O OMe

Me

2e 99

6 N

HO

S O

O

Me

1k

OMe

SN

HOMe

O OMe

2k 97

OMe

2

N

HO Ph

S O

O

MeO

Me

1g

SN

HO PhMe

O OMe

MeO

2g 98

7 N

HO

S O

O

Me

Me

1l

CF3

SN

HOMe

O OMe

Me

2l 97

CF3

3 N

HO Ph

S O

O

F3C

Me

1h

SN

HO PhMe

O OMe

F3C

2h 99

8 N

HO Ph

S O

O

Me

i-Pr

1m

SN

HO Phi-Pr

O OMe

Me

2m 97

4

N

HO Ph

S O

O

Me

1iMe

SN

HO PhMe

O OMeMe

2i 99

9 N

HO Ph

S O

O

Me

SMe

SN

HO Ph

O OMe

Me

2n 97

SMe

5 N

HO Ph

S O

O

Me

S

1j

SN

HO PhMe

O OMeS

2j 99



Chapter 2

36

Conclusions






Chapter 2

37





13C NMR


13C at 10069












N

OHNEt3

DCM rt 12 h


2) PhMgBrTHF rt 3 h

N

HO Ph

1a

TsCl

N

OH

8a

H HCl

Ts Ts









Chapter 2

38

N

S

Me

O

O

OH

8a 1H NMR = 213 (bs 1H) 245 (s 3H) 350-361 (m 2H) 394-404 (m 2H)

442-452 (m 1H) 737 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR =



-1

N

S

D3C

O

O

OH

8a-d

D

D

D

D

1H NMR = 283 (bs 1H) 349-355 (m 2H) 389-396 (m 2H) 435-444 (m 1H)



+ 2351128 Found mz

2351125 IR (ATR) 3503 1333 1142 1059 638 cm-1

N

S O

O

OH

8b

S

1H NMR = 277 (bs 1H) 357-364 (m 2H) 400-407 (m 2H) 441-450 (m 1H)


1H) 13



1038 737 cm-1

Chapter 2

39














N

HO Ph

S

1a

Me

O

O


2H) 728-737 (m 5H) 739 (d J = 84 Hz 2H) 778 (d J = 80 Hz 2H) 13

C NMR

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS


+ 3041002 Found mz 3040995 IR (ATR) 3477

1333 1184 1148 671 cm-1


N

HO Ph

S

1a-d

D3C

O

O

D

D

D

D


(m 5H) 13

C NMR = 203-211 (m) 652 703 1244 1281 (t JC-D = 247 Hz)


Chapter 2

40


702 648 cm-1

N

HO Ph

S

S

O

O



1H) 13

C NMR = 656 702 1244 1280 1283 1288 1331 13387 13392 1417


+ 2960410 Found mz 2960404 IR

(ATR) 3524 1333 1161 1148 748 cm-1

N

HO

S

Me

O

O

OMe

1c



2H) 775 (d J = 80 Hz 2H) 13

C NMR =216 553 652 702 1139 1259 1285


+

3341108 Found mz 3341097 IR (ATR) 3460 1518 1331 1250 1146 cm-1

N

HO

S

Me

O

O

CF3



C NMR

Chapter 2

41

=216 654 697 1239 (q JC-F = 2704 Hz) 1249 1255 (q JC-F = 37 Hz) 1284



1109 1076 cm-1


1l-1n

HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6a

5a



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3

acetone H2O

rt 10 h 4a

PhMgBr

THF rt 1 h N

OH

Ts

Me

1e

Ph

3a



procedure16













Me

NHTs

O

N2


Chapter 2

42

2H) 730 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR = 194 215 539


+

2680750 Found mz 2680747 IR (ATR) 2112 1639 1337 1319 1161 cm-1

[]27

D = -1184 (c = 079 in CHCl3)


i-Pr

NHTs

O

N2



2H) 769 (d J = 84 Hz 2H) 13

C NMR =169 193 215 315 548 647 1273


+ 2961063

Found mz 2961060 IR (ATR) 2129 1622 1362 1329 1161 cm-1

[]28

D = -730 (c = 071 in CHCl3)

NHTs

O

N2

5c

SMe

1H NMR = 174-196 (m 2H) 204 (s 3H) 242 (s 3H) 244-252 (m 2H)

390-400 (m 1H) 541 (s 1H) 560-572 (m 1H) 730 (d J = 84 Hz 2H) 772 (d J =

84 Hz 2H) 13

C NMR = 153 215 297 323 545 585 1272 1297 1366 1439


+ 3280784 Found mz 3280779

IR (ATR) 2129 1618 1375 1339 1163 cm-1

[]29

D = -506 (c = 063 in CHCl3)









Chapter 2

43

N

O

Ts

Me

6a

1H NMR = 145 (d J = 68 Hz 3H) 246 (s 3H) 443-454 (m 2H) 473-480 (m

1H) 736-742 (m 2H) 776-781 (m 2H) 13

C NMR = 157 216 696 810 1284


+ 2400689

Found mz 2400688 IR (ATR) 1825 1339 1155 669 cm-1

[]28

D = 614 (c = 081 in CHCl3)


N

O

Ts

i-Pr

6b

1H NMR = 099-111 (m 6H) 206-218 (m 1H) 246 (s 3H) 441 (dd J = 164 36


2H) 777 (d J = 80 Hz 2H) 13

C NMR = 174 181 216 304 703 903 1284


+ 2681002

Found mz 2680998 IR (ATR) 1815 1340 1155 1007 671 cm-1

[]29

D = 567 (c = 095 in CHCl3)

N

O

Ts

6c

SMe

1H NMR = 204 (s 3H) 209-218 (m 2H) 247 (s 3H) 265-279 (m 2H) 446 (d


2H) 780 (d J = 80 Hz 2H) 13

C NMR = 147 216 291 293 705 832 1286


+ 3000723

Found mz 3000718 IR (ATR) 1813 1342 1308 1157 667 cm-1

[]29

D = 1183 (c = 036 in CHCl3)


Chapter 2

44










N

HO

S O

O

Me

Me

1e

H

NOE

NOE



(m 3H) 739 (d J = 84 Hz 2H) 777 (d J = 84 Hz 2H) 13

C NMR = 144 216

628 702 731 1247 1279 1284 1285 1298 1319 1415 1443 HRMS (ESI+)


1155 1092 667 cm-1

[]25




Chapter 2

45

N

HO

S O

O

Me

1l

H

NOE

NOE

CF3

Me



739-747 (m 4H) 777 (d J = 84 Hz 2H) 13

C NMR = 143 216 630 706 727

1238 (JC-F = 2704 Hz) 1253 1254 (JC-F = 36 Hz) 1285 1299 1301 (JC-F = 324


+ 3861032

Found mz 3861025 IR (ATR) 3422 1327 1151 1109 839 cm-1

[]28




N

HO

S O

O

Me

iPr

1m

H

NOE

NOE



= 100 Hz 1H) 690-696 (m 2H) 712-720 (m 3H) 732 (d J = 80 Hz 2H) 773 (d

J = 80 Hz 2H) 13

C NMR = 190 193 215 291 641 729 801 1247 1275


+

3461471 Found mz 3461466 IR (ATR) 3454 1331 1163 739 669 cm-1

[]27



Chapter 2

46


N

HO Ph

S O

O

1n

Me

SMe

1H NMR = 202 (s 3H) 218-258 (m 8H) 388-394 (m 2H) 427 (dd J = 84 48

Hz 1H) 688-693 (m 2H) 714-721 (m 3H) 740 (d J = 80 Hz 2H) 779 (d J = 80

Hz 2H) 13

C NMR = 154 216 290 297 634 725 733 1246 1277 1284


+

3781192 Found mz 3781188 IR (ATR) 3481 1339 1157 702 669 cm-1

[]28












N

HO

S O

O

Me

Me

1f

H

NOE

NOE


1H) 398 (q J = 64 Hz 1H) 424 (dd J = 84 08 Hz 1H) 732-744 (m 5H)

750-755 (m 2H) 774-778 (m 2H) 13

C NMR = 165 216 627 718 739 1257

Chapter 2

47



-1

[]25






HO2C Me

NHCbz

Me

NHCbz

O

N2N

O

Cbz

Me

6d5d

1) (COCl) 2 DMF

2) CH2N2 Rh2(OAc)4 (05 mol )

DCM rt 12 h4d

PhMgBr

THF rt 1 h

N

OH

Cbz

Me

7a

Ph

N

OH

H

Me

PhPd C (5 mol )

H2 (1atm)

MeOH rt 12 h

MeO SO2Cl

NEt3

DCM rt 12 h

N

HO Ph

S O

O

MeO

Me

1g









Me

NHCbz

O

N2

5d 1H NMR = 134 (d J = 68 Hz 3H) 420-436 (m 1H) 504-516 (m 2H) 534-564

(m 2H) 728-736 (m 5H) 13

C NMR = 184 535 (2C) 669 1280 1282 1285


+ 2481030 Found mz

2481028 IR (ATR) 2116 1717 1636 1533 1252 cm-1

[]28

D = -434 (c = 085 in CHCl3)


Chapter 2

48







N

O

Cbz

Me

6d


Hz 1H) 498-505 (m 1H) 513-521 (m 2H) 731-739 (m 5H) 13

C NMR = 153



696 cm-1

[]29

D = 390 (c = 068 in CHCl3)










N

OH

Cbz

Me

7a

Ph


= 96 Hz 1H) 458 (q J = 64 Hz 1H) 507-518 (m 2H) 729-746 (m 10H) 13

C

NMR = 142 623 667 689 730 1246 1278 1279 1280 1285 1287 1366

Chapter 2

49


+ 2981438 Found mz

2981433 IR (ATR) 1670 1423 1248 1016 702 cm-1

[]29

D = 46 (c = 089 in CHCl3)

N

OH

Cbz

Me

7b

MeO


1H) 432 (d J = 96 Hz 1H) 452-461 (m 1H) 506-518 (m 2H) 687-694 (m 2H)

726-739 (m 7H) 13

C NMR = 143 553 622 666 687 729 1140 1260 1278


+

3281543 Found mz 3281539 IR (ATR) 1682 1418 1352 1024 696 cm-1

[]29

D = 02 (c = 085 in CHCl3)








pressure







mmol 58 yield)

Chapter 2

50

N

HO

S O

O

MeO

Me

1g

H

NOE

NOE


390 (s 3H) 399 (d J = 92 Hz 1H) 419 (q J = 60 Hz 1H) 698-707 (m 4H)

720-727 (m 3H) 779-785 (m 2H) 13

C NMR = 143 557 627 701 731 1144



-1

[]28




N

HO

S O

O

F3C

Me

1h

H

NOE

NOE


406 (d J = 92 Hz 1H) 430 (qd J = 64 08 Hz 1H) 694-699 (m 2H) 721-727

(m 3H) 784 (d J = 80 Hz 2H) 801 (d J = 84 Hz 2H) 13

C NMR = 145 629

706 729 1232 (JC-F = 2711 Hz) 1245 1263 (JC-F = 37 Hz) 1283 12868 12871


+

3720876 Found mz 3720870 IR (ATR) 3503 1348 1323 1165 646 cm-1

[]28




Chapter 2

51

N

HO

S O

O

Me

1i

H

NOE

NOE


1H) 401 (d J = 88 Hz 1H) 422 (q J = 64 Hz 1H) 694-698 (m 2H) 720-724 (m

3H) 746-750 (m 2H) 767-772 (m 2H) 13

C NMR = 144 214 630 704 730

1247 1256 1279 1285 1286 1291 1341 1347 1395 1416 HRMS (ESI+)


1151 714 700 cm-1

[]29




N

HO

S O

O

Me

1j

H

NOE

NOE

S


Hz 1H) 425 (q J = 64 Hz 1H) 696-701 (m 2H) 720-728 (m 4H) 764-767 (m

1H) 769-772 (m 1H) 13

C NMR = 144 632 709 730 1246 1279 1281 1286


+ 3100566

Found mz 3100559 IR (ATR) 3508 1340 1151 756 669 cm-1

[]29




Chapter 2

52

N

HO

S O

O

Me

1k

H

NOE

NOE

OMe


1H) 394 (d J = 88 Hz 1H) 416 (q J = 64 Hz 1H) 670-675 (m 2H) 684-689 (m

2H) 756-762 (m 2H) 765-770 (m 1H) 786-790 (m 2H) 13

C NMR = 143 553

630 704 729 1138 1259 1283 1292 1332 1337 1348 1592 HRMS (ESI+)


1327 1155 606 cm-1

[]29





Screening







mmol 93 yield)

Chapter 2

53


rac -DM-BINAP

rac-BINAP

dppf

dppb

PPh3

dppe

46

trace

trace

yield

PCy3

Ligand

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

entry

1

2

3

4

5

6

7

8

nd

nd

nd

93

none nd

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a


entry Ligand yield

1

2

3

4

(R)-BINAP

(R)-DM-BINAP

(R)-SEGPHOS

(R)-DIFLUORPHOS

er

94

46

48

43

5

6

(R)-DM-SEGPHOS


3862

91

7

8

(R)-MeO-BIPHEP

(R)-MeO-DM-BIPHEP

64

91

892

3169

1288

1486

2476

2575

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a










Chapter 2

54

NS Me

HO PhMe

2a

O O


J = 148 Hz 1H) 683 (s 1H) 727-744 (m 6H) 781 (d J = 84 Hz 1H) 13

C NMR

= 216 361 626 732 1238 1263 1280 1284 1299 1301 1330 1412 1431


+ 3041002 Found mz 3040998 IR

(ATR) 3472 1325 1161 1142 735 cm-1

[]29




NS CH2D

HO Ph

D3C

2a-d

O O

D

D

D


J = 148 Hz 1H) 728-743 (m 5H) 13

C NMR = 201-210 (m) 358 (t JC-D = 212

Hz) 625 731 1234 (t JC-D = 249 Hz) 1262 1279 1283 1291-1300 (m 2C)


+ 3111441

Found mz 3111436 IR (ATR) 3524 1318 1290 1150 721 cm-1

NS Me

HO Ph

O O

S

2b


1H) 668 (d J = 52 z 1H) 730-738 (m 5H) 750 (d J = 52 Hz 1H) 13

C NMR =

378 630 722 1257 1264 1282 1286 1299 1338 1427 1467 HRMS (ESI+)


1150 1063 748 cm-1

[]29


Chapter 2

55



NS Me

HOMe

O O

OMe

2c


422 (d J = 148 Hz 1H) 684-690 (m 3H) 724-733 (m 3H) 774-779 (m 1H) 13

C

NMR = 216 360 553 626 729 1137 1237 1275 1299 1230 1328 1351


+ 3341108 Found mz

3341098 IR (ATR) 3441 1508 1250 1144 735 cm-1

[]29




NS Me

HOMe

O O

CF3



2H) 782 (d J = 80 Hz 1H) 13

C NMR = 216 360 625 731 12392 (q JC-F =

2708) 12395 1254 (q JC-F = 36 Hz) 1268 1298 1303 (q JC-F = 352) 1329


+ 3720876 Found

mz 3720869 IR (ATR) 3481 1323 1121 1067 733 cm-1

[]29




Chapter 2

56










SN

HO

Me

O OMe

Me

2e

H

NOE

NOE


= 68 Hz 1H) 675 (s 1H) 723-738 (m 6H) 777 (d J = 84 Hz 1H) 13

C NMR =

119 215 314 608 750 1242 1262 1275 1282 1298 1301 1316 1427


+ 3181158 Found mz

3181155 IR (ATR) 3481 1315 1163 1146 683 cm-1

[]28




SN

HO

Me

O OMe

MeO

2g

H

NOE

NOE

Chapter 2

57



5H) 782 (d J = 88 Hz 1H) 13

C NMR = 120 314 555 609 752 1144 1151



735 cm-1

[]29




SN

HO

Me

O OMe

F3C

2h

H

NOE

NOE



1H) 13

C NMR = 118 314 608 750 1228 (q JC-F = 2711 Hz) 1251 1258 (q



+ 3720876 Found

mz 3720872 IR (ATR) 3461 1325 1161 1142 739 cm-1

[]29




SN

HO

Me

O OMe

2i

H

NOE

NOE

Me

Chapter 2

58


J = 68 Hz 1H) 684 (d J = 80 Hz 1H) 718-736 (m 6H) 770 (s 1H) 13

C NMR

=119 211 314 607 748 1242 1262 1275 1282 1299 1338 1341 1395


+ 3181158 Found mz

3181155 IR (ATR) 3489 1448 1319 1148 735 cm-1

[]29




SN

HO

Me

O OMe

2j

H

NOE

NOES


1H) 656 (d J = 52 Hz 1H) 726-736 (m 5H) 743 (d J = 48 Hz 1H) 13

C NMR

= 114 319 619 742 1256 1266 1278 1284 1297 1334 1429 1480 HRMS


+ 3100566 Found mz 3100561 IR (ATR) 3524

1329 1151 1020 729 cm-1

[]29




SN

HO

Me

O OMe

2k

H

NOE

NOE

OMe


J = 68 Hz 1H) 685 (d J = 88 Hz 2H) 698-703 (m 1H) 722-730 (m 2H)

738-748 (m 2H) 785-790 (m 1H) 13

C NMR = 119 314 553 608 747 1136

Chapter 2

59



760 cm-1

[]26




SN

HO

Me

O OMe

2l

H

NOE

NOE

CF3

Me



= 84 Hz 2H) 778 (d J = 80 Hz 1H) 13

C NMR = 119 215 313 607 749




-1

[]26




SN

HO

iPr

O OMe

2m

H

NOE

NOE

Me


(m 1H) 264 (s 1H) 285 (s 3H) 441 (d J = 100 Hz 1H) 685 (s 1H) 714-735 (m

4H) 748 (d J = 76 Hz 2H) 772 (d J = 80 Hz 1H) 13

C NMR = 211 214 217

278 330 718 742 1244 1256 1270 1283 1292 1295 1300 1435 1442


+ 3461471 Found mz 3461466 IR

Chapter 2

60

(ATR) 3412 1315 1165 1146 683 cm-1

[]29




SN

HO

O OMe

2n

H

Me

NOE

SMe

1H NMR = 160-170 (m 1H) 184 (s 3H) 212-226 (m 4H) 230-242 (m 2H)

254-263 (m 1H) 294 (s 3H) 471 (dd J = 108 28 Hz 1H) 675 (s 1H) 722-738

(m 6H) 776 (d J = 80 Hz 1H) 13

C NMR = 150 215 242 301 321 643 748

1245 1262 1276 1283 12986 12993 1312 1429 1437 1441 HRMS (ESI+)


1165 1134 748 cm-1

[]28









was used as a


and


21 All



Chapter 2

61



2e

formula C17H19NO3S

fw 31739

T (K) 100(2)


space group P21c

a (Aring) 105967(5)


3) 152058(13)

Z 4 Dcalc (gcm

3) 1386

(mm-1

) 0225 F(000) 672



348500135

params 203 GOF on F

2 1069

R1 wR2 [Igt2(I)]

00322 00868

R1 wR2 (all data)

00335 00878

Chapter 2

62

























Med Chem 2003 46 1116








Chapter 2

63

































Chapter 2

64




2012 51 9160





11437-11439
























Chapter 2

65











2548-2551







11750









32 115



Chapter 2

66

Chapter 3

67

Chapter 3




Halides

Abstract






Chapter 3

68

Introduction
















2) are












several months


Et LiB

Ph

+B

Ph

Et

1a 74

(a)(b)[Me4N]


Chapter 3

69

















OMe

BrB

Ph

Et

OMe

3a

Ph

Et

OMe

H

4a

Pd-ligand AcOH

2a

+B

Ph

Et

1a

[Me4N]


EZ of 4ab

1 P(o-tol)3 69 397

2 P(t-Bu)3 47 1783

3 1-[(t-Bu)2P](biphenyl) 18 2872

4 2-[(t-Bu)2P](11-binaphthyl) 21 6733

5 DPEPhos 24 928



analysis



Chapter 3

70









Pd(0)

Pd

MeO

B

PdEt

OMe

Ph

B

Ph

Et

2a

BC

Pd

MeO

Br

A

1a

3a







dominates10
















Chapter 3

71










Chapter 3

72


BO

Ph

Et

OMe

5a 83

BO

Ph

Et

CF3

5b 85

BO

Ph

Et

NPhth

5c 82

BO

Ph

Et

5d 72b

BO

Ph

Et

5e 85

S

BO

n-Pr

Me

Cl

5f 74

BO

n-Pr

Ph

OMe

5g 82

BO

Ph

S

5h 83

BO

Ph

CO2Et

5i 81

BO

Ph

5j 82

Cl

BO

Ph

CF3

TBSO

BO

Cl

S

Ph

BO

Ph

Me

OMe

5n 71b

5m 925l 82

BO

Ph

5k 76

Me

+B

Ar

R

1

[Me4N]

2


BO

Ar

R

Ar

5







The reaction of 1a






Chapter 3

73








(E)-5o83 EZ = gt955

BO

Ph

Et

Ph

Ph

Et

PhO

NMe2

(Z)-685 EZ = lt595

Ph

Ph

EtO

NMe 2

(E)-675 EZ = 928

1a

(Z)-5o71 EZ = 793

+ PhBr

BO

Ph

Ph

Et

(a)

(c) (c)

(b)






Conclusions






Chapter 3

74




1H at 400 MHz and

11B at 128 MHz)



13C)

CD3CN ( = 194 for 1H =132 for


11B)









and Ph-9-BBN18


procedures


Et LiB

Ph

+B

Ph

Et

1a


2) Me4NCl MeOH

[Me4N]









74 yield)

Chapter 3

75

B

Ph

Et

1a

[Me4N]


136-207 (m 11H) 236-250 (m 2H) 303 (s 12 H) 679-686 (m 1H) 700-707 (m

2H) 735 (d J = 72 Hz 2H) 13

C NMR (CD3CN) = 149 166 266 (q JC-B = 379

Hz) 271 275 324 349 561 948 1221 1269 1339 11

B NMR = -133 HRMS




n-Pr LiB

Ar


2) Me4NCl MeOH B

n-Pr

1b

Cl

[Me4N]










Chapter 3

76

B

n-Pr

1b

Cl

[Me4N]

1H NMR (CD3CN) = 084-096 (m 5H) 111-121 (m 1H) 126-200 (m 13H)

235-250 (m 2H) 304 (s 12H) 700-705 (m 2H) 733 (d J = 84 Hz 2H) 13

C NMR

(CD3CN) = 139 234 249 266 (q JC-B = 393 Hz) 270 273 323 348 561

933 1265 1272 1355 11


[M-(NMe4)] 2991738 Found 2991730

B

n-Pr

1c

OMe

[Me4N]


128-201 (m 13H) 237-252 (m 2H) 303 (s 12H) 371 (s 3H) 663-668 (m 2H)

723 (d J = 81 Hz 2H) 13

C NMR (CD3CN) = 140 235 250 268 (q JC-B = 393

Hz) 272 275 324 349 554 561 929 1128 1344 1561 11

B NMR = -135


B

Ph

1d

[Me4N]


(m 2H) 134-196 (m 9H) 230-244 (m 2H) 304 (s 12H) 679-686 (m 1H)

699-706 (m 2H) 733 (d J = 72 Hz 2H) 13

C NMR (CD3CN) =23 87 266 (q

JC-B = 393 Hz) 271 274 323 349 562 1222 1269 1338 11

B NMR = -134


Chapter 3

77

B

Ph

1e

[Me4N]


(m 3H) 302 (s 12H) 679-686 (m 1H) 699-706 (m 2H) 734 (d J = 66 Hz 2H) 13

C NMR (CD3CN) = 253 268 (q JC-B = 379 Hz) 271 275 324 333 349 361

561 980 1221 1269 1339 11


[M-(NMe4)] 2912284 Found 2912278

B

1f

S

Ph

[Me4N]




09 Hz 1H) 712-730 (m 5H) 13

C NMR (CD3CN) = 240 268-290 (m) 325 347

380 562 928 1225 1261 1265 1271 1289 1297 1434 11

B NMR = -135


B

Ph

1g

TBSO

[Me4N]

1H NMR (CD3CN) = 005 (s 6H) 084-096 (m 11H) 110-120 (m 1H) 134-197

(m 9H) 216-233 (t J = 72 Hz 2H) 235-250 (m 2H) 301 (s 12H) 356 (t J = 78

Hz 2H) 680-687 (m 1H) 700-708 (m 2H) 735 (d J = 66 Hz 2H) 13

C NMR

(CD3CN) = -50 189 254-277 (m) 323 348 561 649 889 1222 1269

1339 11


Found 3812789

Chapter 3

78

B

Ph

1h

OMe

[Me4N]


(m 2H) 298 (s 12H) 373 (s 3H) 668-674 (m 2H) 701-718 (m 5H) 732 (d J =

87 Hz 2H) 13

C NMR (CD3CN) = 255-277 (m) 322 350 554 561 961 1129

1251 1287 1302 1312 1345 1564 11


C23H26BO [M-(NMe4)] 3292077 Found 3292081



Br

+

MeO


6 mol Ligand


2a

B

Ph

Et

OMe

(E)-3a

AcOH

Ph

Et

OMe

H

Ph

B

Et

OMe

+

+

(Z)-3a

(E)-4a

H

Et

OMe

Ph

(Z)-4a

B

Ph

Et

1a

[Me4N]









Chapter 3

79




B

Ph

Et

+


toluene 70 degC

Me3NO

Br

MeO

BO

Ph

Et

OMe

5a

1a

2a

[Me4N]









BO

Ph

Et

OMe


383 (s 3H) 438-444 (m 1H) 685-691 (m 2H) 714-736 (m 7H) 13

C NMR =

138 221 267 273 (br) 277 312 553 736 1132 1251 1278 1283 1298

1366 1436 1494 1586 11


3742417 Found 3742410

Chapter 3

80

BO

Ph

Et

CF3

5b


437-443 (m 1H) 718-726 (m 3H) 734-739 (m 2H) 745-748 (m 2H) 760-763

(m 2H) 13

C NMR = 135 220 266 271 (br) 276 312 738 12429 (q JC-F =

2701 Hz) 1247 (q JC-F = 36 Hz) 1280 1281 1289 (q JC-F = 320 Hz) 1291 1425

1476 1480 11


Found 4122186

BO

Ph

Et

NPhth

5c


440-450 (m 1H) 720-727 (m 3H) 734-739 (m 2H) 743-751 (m 4H) 777-783

(m 2H) 794-800 (m 2H) 13

C NMR = 137 221 266 274 (br) 275 312 738

1235 1254 1258 1279 1282 1294 1304 1317 1342 1429 1440 1482

1671 11

B NMR = 502 IR (KBr) = 2928 1742 1509 1381 714 cm-1

HRMS (EI)


BO

Ph

Et

5d

1H NMR = 021-034 (m 1H) 068-100 (m 8H) 120-150 (m 7H) 224-238 (m

1H) 244-258 (m 1H) 424-431 (m 1H) 722-754 (m 9H) 778 (d J = 78 Hz 1H)

783-788 (m 1H) 809-816 (m 1H) 13

C NMR = 137 216 219 259 262 264

(br) 282 309 314 734 1249 12537 12539 1255 1264 1270 1273 12795

Chapter 3

81

12799 1283 1321 1335 1413 1427 1467 11


for C28H31BO (M+) 3942468 Found 3942476

BO

Ph

Et

5e

S


448-456 (m 1H) 702 (dd J = 51 36 Hz 1H) 708 (dd J = 36 12 Hz 1H)

715-730 (m 4H) 732-738 (m 2H) 13

C NMR =141 221 271 289 312 739

1250 1255 1266 1269 1279 1281 1416 1427 1468 11

B NMR = 496


BO

n-Pr

Me

Cl

5f

1H NMR = 070 (t J = 75 Hz 3H) 096-133 (m 9H) 142-172 (m 6H) 220-228

(m 2H) 237 (s 3H) 439-446 (m 1H) 708-735 (m 8H) 13

C NMR = 140 212

219 221 267 274 (br) 313 363 737 1279 12846 12855 1298 1309 1365

1411 1420 1488 11


4062235 Found 4062237

BO

n-Pr

Ph

OMe

5g

Chapter 3

82


(s 3H) 435-450 (m 1H) 690 (d J = 81 Hz 2H) 711 (d J = 81 Hz 2H) 720-740

(m 5H) 13

C NMR = 140 219 221 267 274 (br) 312 362 551 736 1133

1267 1278 1287 1294 1354 1446 1475 1573 11




BO

Ph

S

5h

1H NMR = 027-032 (m 2H) 046-052 (m 2H) 098-130 (m 6H) 140-170 (m

8H) 430-445 (m 1H) 696-700 (m 1H) 704-707 (m 1H) 715-726 (m 2H)

729-738 (m 4H) 13

C NMR = 60 150 222 263 272 (br) 313 736 1241

1243 1253 1278 1290 1295 1410 1425 1431 11



BO

Ph

CO2Et

5i

1H NMR = 017-023 (m 2H) 045-053 (m 2H) 090-119 (m 6H) 132-173 (m

11H) 427-433 (m 1H) 438 (q J = 75 Hz 2H) 718-738 (m 7H) 798 (dt J = 78

15 Hz 2H) 13

C NMR = 56 144 151 220 263 269 (br) 312 609 735 1255

1279 1284 1287 1289 1303 1423 1453 1469 1665 11

B NMR = 496 IR

(KBr) = 2928 1717 1287 1100 cm-1


Found 4282526

BO

Ph

5j

Cl

Chapter 3

83

1H NMR = 023-029 (m 2H) 048-055 (m 2H) 094-123 (m 6H) 134-171 (m

8H) 432-439 (m 1H) 706-714 (m 1H) 718-726 (m 4H) 728-738 (m 4H) 13

C

NMR = 57 150 220 263 271 (br) 312 736 1255 1267 1279 1283 1284

1289 1304 1332 1423 1424 1461 11


C25H28BClO (M+) 3901922 Found 3901923

BO

Ph

5k

Me

1H NMR = 082-113 (m 6H) 126-164 (m 15H) 237 (s 3H) 268-280 (m 1H)

434-441 (m 1H) 704-709 (m 3H) 717-725 (m 4H) 730-737 (m 2H) 13

C NMR

= 215 219 248 263 273 (br) 312 315 433 735 1252 12689 12693 1275

1278 1283 1316 1365 1418 1424 1481 11


for C28H35BO (M+) 3982781 Found 3982780

BO

Cl

S

Ph

5l

1H NMR = 106-176 (m 13H) 250-260 (m 2H) 272-280 (m 2H) 441-449 (m

1H) 674 (dd J = 33 12 Hz 1H) 697-703 (m 3H) 709-738 (m 8H) 13

C

NMR(C6D6) =225 272 277 (br) 315 358 375 739 1247 1253 1261 1272

1285 12856 12861 1306 1335 1419 1427 1437 1491 11

B NMR = 495


BO

Ph

CF3

TBSO

5m

Chapter 3

84

1H NMR = -014 (s 6H) 079 (s 9H) 095-136 (m 6H) 142-168 (m 7H) 255 (t

J = 72 Hz 2H) 343 (t J = 72 Hz 2H) 435-442 (m 1H) 718-726 (m 3H)

731-737 (m 2H) 747 (d J = 81 Hz 2H) 759 (d J = 81 Hz 2H) 13

C NMR = -54

183 220 259 266 271 (br) 311 377 616 739 1242 (q JC-F = 2694 Hz) 1247

(q JC-F = 36 Hz) 1258 1280 1282 1290 (q JC-F = 320 Hz) 1291 1421 1422

1480 11



BO

Ph

Me

OMe

5n

1H NMR = 122-130 (m 4H) 138-162 (m 5H) 168-186 (m 4H) 237 (s 3H)

375 (s 3H) 443-450 (m 1H) 670 (dt J = 90 21 Hz 2H) 690-697 (m 4H)

702-708 (m 3H) 710-720 (m 4H) 13

C NMR = 213 222 269 312 550 738

1132 1260 1272 1285 1301 1307 1310 1362 1369 1423 1429 1483

1571 11


4362561


4-Bromobenzene

B

Ph

Et

+


toluene 70 degC

Me3NO BO

Ph

Ph

Et

(Z)-5o

1a

Ph Br

[Me4N]




Chapter 3

85






BO

Ph

Ph

Et


470-475 (m 1H) 685-710 (m 10H) 13

C NMR = 139 224 267 313 317 740

1248 1257 1272 127412938 12941 1421 1425 1275 11

B NMR = 512


BO

Ph

Et

Ph


438-443 (m 1H) 718-737 (m 10H) 13

C NMR = 137 221 266 274 (br) 277

312 737 1253 1268 1278 1279 1283 1288 1433 1442 1494 11

B NMR =



Bromide 2b

+

Br

ONMe2

Ph

Et

PhO

NMe2


THF K3PO4 60 degC

(Z)-Tamoxifen 6

2b

BO

Ph

Et

Ph

(E)-5o

Chapter 3

86









Chapter 3

87



2003 Vol 3








Rev 2006 250 1107









1976 108 281








74





Chapter 3

88





















2006 128 1828




Chapter 4

89

Chapter 4



Abstract






Chapter 4

90

Introduction





























Chapter 4

91


B

MOMO

[Me4N] +

MeO

Br

I

Br

MeO Br

B

MeO

MOMO MOMO

1a

2 3 87EZ = lt199

NaOH

50 degC

1 mol


toluene 50 degC
















procedure

Chapter 4

92



An











3

MeO

R

Br

4 92

R

MeO

R

Br

n = 2 5 87

n = 3 6 82n = 4 7 85

n

R

1 mol


toluene 50 degC

I

Br

NaOH

E

EE

R = OMOM








Chapter 4

93





Br

Br

R

R

Br

Br

8 86

R

R

Br

R

R

Br

9 92

E E

R = OMOM















Chapter 4

94


Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

Me3Si

Br

Ph

F

Me3Si

OMe

Br

Ph

F

S

Br

Me3Si

OMe

B

n-Pr

[Me4N]

Cl

B

Ph

[Me4N]

OMe

Br

S

Br

I

EtO2C

MOMO

MOMO

I

Br

F

1b

10 88

11 84

12 88

1a1c

cat Pd

NaOHcat Pd

cat Pd NaOH

Cs2CO3

Conclusions







Chapter 4

95




1H at 500 MHz and






13C) CD3CN ( = 194 for

1H =132 for

13C) and

BF3OEt2 ( = 000 for 11











11













Chapter 4

96

B

MOMO

[Me4N]

1a


202 (t J = 66 Hz 2H) 236-251 (m 2H) 304 (s 12H) 328 (s 3H) 346 (t J = 69

Hz 2H) 454 (s 2H) 678-685 (m 1H) 698-705 (m 2H) 734 (d J = 72 Hz 2H) 13

C NMR (CD3CN 75 MHz) = 210 267 (br) 271 275 282 297 324 349 551

561 681 928 968 1221 1269 1338 11



B

Ph

[Me4N]

1b

OMe


225 (t J = 72 Hz 2H) 234-249 (m 2H) 263 (t J = 72 Hz 2H) 303 (s 12H) 372

(s 3H) 663-669 (m 2H) 711-728 (m 7H) 13


272 275 324 349 381 554 560 1129 1266 1289 1298 1346 1434 1563 11


3572390 Found 3572383



B

MOMO

[Me4N]

+

MeO

Br

1 mol


toluene 50 degC

I

Br

MeO Br

NaOH

3

1a

MOMO

Chapter 4

97








MeO Br

3

MOMONOE

NOE




(t J = 66 Hz 2H) 376 (s 3H) 452 (s 2H) 667-675 (m 4H) 697-702 (m 2H)

709-736 (m 7H) 13

C NMR (75 MHz) = 255 298 356 5510 5514 676 964

1134 1196 1267 1282 1294 13046 13049 1323 1339 1376 1408 1420



spectroscopy

MeO

R

Br

4

R

R = OMOM




Chapter 4

98


2H) 325 (s 3H) 329 (s 3H) 331-341 (m 4H) 380 (s 3H) 451 (s 2H) 453 (s

2H) 662-678 (m 8H) 697-703 (m 2H) 706-738 (m 12H) 13

C NMR (150 MHz)

= 252 254 295 296 353 354 5502 5504 552 675 676 9629 9632 1131

1196 1265 1267 1281 1282 1285 12941 12942 1303 1304 1306 1324

1343 1377 1385 1390 1400 1413 1414 1418 1429 1435 1579 HRMS


7972818 Found

7972849

MeO

R

5

R

R = OMOM

R

Br




325 (s 3H) 327 (s 3H) 328 (s 3H) 330-342 (m 6H) 374 (s 3H) 450 (s 2H)

452 (s 2H) 454 (s 2H) 654-662 (m 4H) 666-678 (m 8H) 696-704 (m 4H)

712-737 (m 15H) 13

C NMR (75 MHz) = 254 256 296 297 298 3526 3534

355 551 675 676 963 1130 1196 1264 1267 1280 1281 1286 1294 1301

1302 1304 1306 1324 1344 1377 1384 1387 1392 1393 1398 1402 1409



10914437 Found 10914482

Chapter 4

99

MeO

R

6

R

R = OMOM

R

R

Br




330-341 (m 8H) 371 (s 3H) 448-454 (m 8H) 648-675 (m 16H) 695-703 (m

4H) 714-737 (m 20H) 13

C NMR (75 MHz) = 253 254 256 257 2969 2974

298 350 354 356 550 551 675 676 963 1131 1196 1264 1267 1279

1280 1281 1283 1288 1293 1294 1300 1301 1302 1305 1306 1323 1342

1377 1385 1387 1389 1391 1394 1396 1397 1401 1405 1409 1411 1413



13856057 Found 13856062

MeO

R

7

R

R = OMOM

R

R

R

Br




374 (s 3H) 447-452 (m 10 H) 649-679 (m 20 H) 690-695 (m 2H) 701-706 (m

2H) 710-736 (m 25H) 13

C NMR (75 MHz) = 2529 2535 256 257 2968

Chapter 4

100

2971 298 351 354 355 356 550 6746 6755 676 963 1131 1195 1264

1267 12795 1280 1281 1283 1285 1287 1293 12937 12944 1301 1302

1304 1306 1322 1343 1377 1384 1387 1389 1390 1391 1394 13976

13979 1401 1404 1408 1409 1412 1413 1416 1427 14318 14321 1434


16797677 Found 16797694

8

R

Br

R

Br

R = OMOM





(t J = 66 Hz 4H) 456 (s 4H) 668-673 (m 4H) 691 (s 4H) 710-721 (m 8H)

722-737 (m 6H) 13

C NMR (75 MHz) = 254 297 354 551 676 963 1198

1268 1282 1291 1293 1303 1323 1380 1400 1411 1417 1427 HRMS


8221905

9

R

R

R = OMOM

R

R

Br

Br



Chapter 4

101


6H) 330-340 (m 8H) 446 (s 4H) 453 (s 4H) 656-672 (m 12H) 688 (s 4H)

704-710 (m 4H) 714-718 (m 4H) 722-740 (m 16H) 13

C NMR (150 MHz) =

254 2962 2963 356 357 5501 5503 674 676 9629 9631 1197 1266

1268 1281 12818 12822 1290 1295 1296 1304 1308 1324 1379 1385

1394 1403 1405 1409 1416 1417 1427 1434 HRMS (MALDI-TOF-MS


14335057 Found 14335040

Ph

F

Me3Si

OMe

Br

10

NOE

NOE





3H) 676-686 (m 3H) 694-707 (m 6H) 709-728 (m 5H) 734 (d J = 84 Hz 2H) 13

C NMR (150 MHz) = -11 349 372 552 1135 1189 (d JC-F = 255 Hz)1202

(d JC-F = 92 Hz) 1258 1268 (d JC-F = 35 Hz) 1280 1283 1284 1300 1304 (d

JC-F = 159 Hz) 1326 1329 1332 (d JC-F = 45 Hz) 1339 1387 1417 1418 1430




Chapter 4

102

Ph

F

S

Br

Me3Si

OMe

11

MOMO




= 78 2H) 264-272 (m 2H) 282-289 (m 2H) 325 (s 3H) 328 (t J = 66 Hz 2H)

382 (s 3H) 448 (s 2H) 587 (d J = 39 Hz 1H) 660 (d J = 39 Hz 1H) 669-676

(m 2H) 684-696 (m 3H) 705-742 (m 16H) 13

C NMR (150 MHz) = -10 244

293 351 362 372 550 552 673 963 1127 1135 1161 (d JC-F = 225 Hz)

1244 (d JC-F = 32 Hz) 1258 1274 12827 12831 12837 12840 12856 12861

1295 1302 1307 (d JC-F = 155 Hz) 1324 1329 1330 (d JC-F = 45 Hz) 1333

1345 1385 1395 (d JC-F = 12 Hz) 1412 1416 (d JC-F = 80 Hz) 1419 1422



Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

12MOMO




mmol) t1 10 h t2 12 h

Chapter 4

103


210-224 (m 4H) 264-272 (m 2H) 279-287 (m 2H) 323-333 (m 5H) 373 (s


1H) 666-672 (m 2H) 679-694 (m 5H) 703-737 (m 20H) 773 (d J = 84 Hz

2H) 13

C NMR (150 MHz) = -11 141 143 225 244 293 350 359 370 385

550 551 607 674 963 1134 1159 (d JC-F = 224 Hz) 1243 (d JC-F = 29 Hz)

1258 1269 1271 12808 12811 12815 12820 12823 12838 12844 1290

1293 1300 1301 (d JC-F = 158 Hz) 1302 1307 1323 (d JC-F = 47 Hz) 13258

13261 1328 1336 1344 1356 1379 1382 1390 (d JC-F = 12 Hz) 1409 14190

14191 14216 (d JC-F = 80 Hz) 14219 14222 1438 1446 1476 1583 1600 (d

JC-F = 2448 Hz) 1664 IR (KBr) = 2955 1717 1509 1273 1248 1111 837 cm-1


11294440

Found 11294465

Chapter 4

104




Chem 1999 201 163




897















2404


2006 128 1828



Chapter 5

105

Chapter 5




Abstract






Chapter 5

106

Introduction





moiety1b


























Chapter 5

107


B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

OHMe

Ph

1a

3a 85

MeO

OMe

2a

B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

1b

OMe

2a

OHMe

Ph

OMe

3b 88

[Me4N]

[Me4N]




Oxidative









Chapter 5

108


O

I

O

PdI

Pd(0)

B

1a

C

Pd(0)3a

Ar = p-MeOC6H4-

Me Me

OMe

Ar

Ph

B

D

A

Pd

O

ArB

Me

Ph

B

O

ArPh

Me

Me4NI

2a







Chapter 5

109


R3

O

I

B

R2

R1

+1 mol Pd

toluene50 degC 1 h

OHR3

R1

R2

OHMe

Ph

S

OHMe

OMe

OHPh

Ph

OMe

3f 72

3h 763j 80

3g 84

3d 82

3c 83

OHMe

Ph

CF3

1 2 3

OHH

Ph

OMe

OHPh

Ph

OMe

O

O

OHPh

3e 92

F

OMe

OHPh

Ph

OMe

F3C

3i 62

R4R4

MeO

[Me4N]










Chapter 5

110

OHMe

t-Bu

S

3k 89

B +1 mol Pd

toluene

50 degC 1 h

2a

t-Bu

S

(1)

1c

[Me4N]

OHMe

n-Bu

Me

3l 80

B

n-Bu

+1 mol Pd

toluene50 degC 1 h

2a

Me

(2)

1d

[Me4N]










n-Hex

13 equiv

Ph

Li

065 equiv

(H-9-BBN) 2


1 mol Pd

toluene 50 degC 1 h

10 equiv 2aOH

Me

n-Oct

11 equiv

3m 91 (based on 2a)

B

n-Oct

PhLi

Ph




Chapter 5

111


in 59 yield11


OHH

Ph

OMe

MnO2

DCM rt

Ph

OMe

O

NH2NH2 KOHPh

OMe

4 96 5 59

3n 74

(CH2OH)2 150 C

1a +

CHO

I2b

1 mol Pd

Conclusions




Chapter 5

112



and 13


B at 128 MHz)



13C) CD3CN (δ = 194 for

1H δ = 132 for


11B) IR






(Merck)





and alkynylborate14




Li

BPh

+

B

Ph

1a


2) Me4NCl MeOH

[Me4N]

MeO

MeO










Chapter 5

113

B

Ph

1a

[Me4N]

MeO


(m 2H) 296 (s 12H) 372 (s 3H) 668-675 (m 2H) 685-691 (m 1H) 700-712 (m

4H) 743 (d J = 64 Hz 2H) 13

C NMR (CD3CN) δ = 256-272 (m) 270 274 322

350 557 560 955 1145 1227 (2C) 1273 1324 1341 1578 The boron-bound


11B NMR


3292079

B

Ph

1b

[Me4N]

OMe


(m 2H) 295 (s 12H) 374 (s 3H) 666-675 (m 2H) 702-718 (m 5H) 733 (d J =

84 Hz 2H) 13

C NMR (CD3CN) δ = 254-274 (m) 270 273 321 350 554 560





B

nBu

1d

[Me4N]

Me


(m 4H) 136-157 (m 6H) 170-196 (m 4H) 220-234 (m 5H) 304 (s 12H)

697-701 (m 2H) 704-709 (m 2H) 13

C NMR (CD3CN) δ = 152 212 270

271-290 (m) 282 288 318 324 357 561 1279 1296 1314 1344 The

Chapter 5

114




[M-(NMe4)]- 2932446 Found 2932454

B

Ph

1e

[Me4N]

F3C


(m 2H) 292 (s 12H) 690-696 (m 1H) 710-718 (m 2H) 728 (dd J = 88 08 Hz

2H) 744-752 (m 4H) 13

C NMR (CD3CN) δ = 252-270 (m) 269 273 321 351






B

Ph

1f

[Me4N]

S



48 32 Hz 1H) 703-719 (m 6H) 13

C NMR (CD3CN) δ = 266 272 270-286 (m)

323 348 560 962 1231 1256 1266 1274 1290 1300 1314 The boron-bound

sp2 and sp


11B NMR


- 3051541 Found

3051541

Chapter 5

115


(H-9BBN) 2

H tBu

THF 0 degC

THF -78 degC to rt

2) Me4NCl MeOH

Li

1)S

B

1c

[Me4N]

S

tBu














B

1c

[Me4N]

S

tBu


4H) 222-235 (m 2H) 306 (s 12H) 552 (d J = 172 Hz 1H) 591 (d J = 176 Hz


Hz 1H) 13

C NMR (CD3CN) δ = 273 276 278-296 (m) 311 327 341 352 561





Chapter 5

116












OHMe

3aOMe

NOE

no NOE

IR (ATR) 3315 1508 1248 752 694 cm-1

1H NMR δ = 159 (s 3H) 204 (bs 1H)

382 (s 3H) 684-690 (m 2H) 721-730 (m 8H) 742-748 (m 2H) 751-755 (m

1H) 13

C NMR δ = 239 552 832 1139 1208 1218 1265 1268 1272 1280


C23H21O2 [M+H]+ 3291536 Found 3291556

OHMe

OMe

3b

NOE

no NOE

IR (ATR) 3319 1508 1248 760 702 cm-1

1H NMR δ = 160 (s 3H) 208 (s 1H)

378 (s 3H) 674-680 (m 2H) 718-723(m 1H) 724-744 (m 9H) 750-755 (m

1H) 13

C NMR δ = 241 551 833 1134 1205 1218 1263 1270 1274 1284


Chapter 5

117

C23H20O2Cl [M+Cl]- 3631146 Found 3631148

OHMe

Ph

3cCF3

IR (ATR) 3298 1319 1121 750 696 cm-1

1H NMR δ = 160 (s 3H) 210 (bs 1H)

716-722 (m 1H) 723-732 (m 5H) 737-747 (m 4H) 752-764 (m 3H) 13

C NMR

δ = 240 833 1205 1221 1241 (q JC-F = 2701 Hz) 1255 (q JC-F = 37 Hz) 1269

1277 1282 1286 1293 1295 (q JC-F = 322 Hz) 1296 1341 1373 1385 1414


- 3651159 Found 3651159

OHMe

Ph

3d

S

IR (ATR) 3319 1350 1088 752 694 cm-1

1H NMR δ = 177 (s 3H) 209 (bs 1H)

696-702 (m 2H) 718 (dd J = 52 Hz 12Hz 1H) 723-730 (m 2H) 735-740 (m

3H) 742-752 (m 3H) 753-758 (m 1H) 13

C NMR δ = 254 833 1207 1216

1259 1265 1266 1275 1282 1287 1290 1294 1347 1360 1374 1410 1426


+ 3050995 Found 3050992

OHMe

OMe

3e

IR (ATR) 3310 1508 1244 1034 758 cm-1

1H NMR δ = 144 (s 3H) 158-202 (m


5H) 747 (d J = 68 Hz 1H) 13

C NMR δ = 238 266 267 305 311 382 552

822 1136 1211 1219 1257 12789 12793 1304 1406 1409 1467 1499


+ 3382115 Found 3382104

Chapter 5

118

OHH

Ph

3fOMe

MeO

IR (ATR) 3472 1601 1508 1244 704 cm-1

1H NMR δ = 174 (d J = 88 Hz 1H)


= 80 Hz 24 Hz 1H) 692-697 (m 2H) 718-730 (m 5H) 732-736 (m 2H) 753 (d

J = 84 Hz 1H) 13

C NMR δ = 552 555 766 1072 1109 1143 1244 1267 1272

1283 1292 1303 1342 1363 1390 1445 1457 1592 1606 HRMS (ESI+)


OHPh

Ph

3gOMe

IR (ATR) 3422 1508 1244 1028 746 698 cm-1

1H NMR δ = 248 (s 1H) 385 (s

3H) 695 (d J = 88 Hz 2H) 704-714 (m 5H) 715-732 (m 7H) 736-740 (m 2H)

755 (d J = 88 Hz 2H) 13

C NMR δ = 552 868 1141 1210 1231 1250 1268

12698 12702 1271 1278 12836 12844 1294 1304 1340 1402 1417 1427


+ 3911693 Found

3911718

OHPh

Ph

3hOMe

O

O

IR (ATR) 3362 1470 1244 1034 696 cm-1

1H NMR δ = 239 (s 1H) 385 (s 3H)

591 (dd J = 164 16 Hz 2H) 673 (d J = 44 Hz 2H) 690-696 (m 2H) 702-708

(m 5H) 720-736 (m 5H) 749-754 (m 2H) 13

C NMR δ = 552 863 1012 1024

Chapter 5

119

1049 1142 1249 12690 12692 1270 1278 1285 1292 1304 1340 1367


+

4341518 Found 4341505

OHPh

Ph

3iOMe

F3C

IR (ATR) 3545 1508 1321 1115 696 cm-1

1H NMR δ = 249 (s 1H) 387 (s 3H)

694-700 (m 2H) 704-715 (m 5H) 723-738 (m 6H) 742-755 (m 4H) 13

C NMR

δ = 553 866 1145 1177 (q JC-F = 37 Hz) 1233 1241 (q JC-F = 36 Hz) 1242 (q

JC-F = 2702 Hz) 1249 1260 1275 1276 1280 1287 1295 1304 1308 (q JC-F =


C29H21F3O2Cl [M+Cl]- 4931177 Found 4931192

OHPh

3j

F

OMe

IR (ATR) 3356 1242 1028 741 696 cm-1

1H NMR δ = 164-178 (m 2H) 183-208


4H) 719-737 (m 6H) 13

C NMR δ = 2675 2681 308 310 383 551 862 1114


1268 1271 1283 1303 1371 (d JC-F = 29 Hz) 1410 1418 (d JC-F = 15 Hz)



+ 4001839 Found 4001835

OHMe

S

tBu

3k

Chapter 5

120

IR (ATR) 3298 1358 1078 756 689 cm-1

1H NMR δ = 111 (s 9H) 168 (s 3H)

188 (s 1H) 640 (d J = 164 Hz 1H) 656 (d J = 164 Hz 1H) 718-730 (m 4H)

739-751 (m 3H) 13

C NMR δ = 257 295 340 822 1169 1204 1215 1242

1255 1262 1283 1285 1324 1346 1415 1452 1462 1506 HRMS (ESI+)


OHMe

nBu

OMe3l

IR (ATR) 3335 1508 1084 918 758 cm-1

1H NMR δ = 085 (t J = 72 Hz 3H) 130

(tt J = 72 72 Hz 2H) 141-167 (m 6H) 229-250 (m 5H) 702-706 (m 1H)

716-728 (m 6H) 744-748 (m 1H) 13

C NMR δ = 138 213 232 237 252 314

829 1198 1215 1256 1282 1286 1291 1318 1370 1374 1430 1492 1496


+ 2931900 Found 2931890



nHex

(H-9BBN) 2


Li

Ph

B

nOct

Li

Ph

Me

O

I


toluene 50 degC 1 h

H2O2 aq

NaOH aq

OHMe

nOct

Ph3m

MeOH




Chapter 5

121













yield)

OHMe

nOct

Ph3m

IR (ATR) 3335 1456 1078 752 698 cm-1

1H NMR δ = 096 (t J = 68 Hz 3H)

129-156 (m 15H) 160 (s 1H) 208-227 (m 2H) 274-281 (m 2H) 287-294 (m

2H) 719-728 (m 5H) 729-736 (m 3H) 742 (d J = 72 Hz 1H) 13

C NMR δ = 141

226 234 247 277 293 294 295 304 319 345 825 1186 1213 1252 1260


[M]+ 3622610 Found 3622619

OHH

Ph

OMe

3n

IR (ATR) 3354 1508 1246 764 692 cm-1

1H NMR δ = 185 (bs 1H) 386 (s 3H)

567 (s 1H) 692-697 (m 2H) 718-738 (m 10H) 763-766 (m 1H) 13

C NMR δ =

552 773 1143 1206 1237 1263 1268 1272 1283 1287 1292 1303 1342


- 3131234

Found 3131237

Chapter 5

122

The 1H


15


OHH

Ph

OMe

3n

MnO2

DCM rt

Ph

OMe

4

O







The 1H


16

Ph

OMe

4

O

(CH 2OH)2

NH2NH2

KOH Ph

OMe

5








The 1H


5

Chapter 5

123






1395ndash1411



17638ndash17640





3201ndash3222



















Chapter 5

124












3283ndash3292









74








Chem 1989 54 1485ndash1491



2006 128 1828

Chapter 5

125



4781-4787


Chem 1989 54 1485

Chapter 5

126

127

List of Publication

Chapter 1



Angew Chem Int Ed 2012 51 11750-11752

Chapter 2


Benzosultams


J Am Chem Soc 2013 135 19103-19106

Chapter 3





Org Lett 2009 11 5434-5437

Chapter 4


Units


Org Lett 2010 12 3179-3181

Chapter 5




Eur J Org Chem 2013 1421-1424

Other Publication




Chem Lett 2013 42 1076


6








10990




2003 Vol 3





Q Z J Med Chem 2009 52 4192



2006 250 1107



2419













7



17638ndash17640


8

Chapter 1

9

Chapter 1


Ketones

Abstract






Chapter 1

10

Introduction







2 One







starting substances


CO2

sun

CO2energy charge

high energy

intermediates











8






Chapter 1

11


Ph

O

NTs

Mesolar light

N

Ph OH

Ts

2a 91

1aDMA







over 04 kWm-2



in eight hours on


Figure





kWhm-2



Chapter 1

12


0

20

40

60

80

100

0 1 2 3 4 5 6 7 8

0

20

40

60

80

100

0 1 2 3 4 5 6











(56)

Chapter 1

13


40 equiv Cs2CO3

1 atm CO2

DMA 60 degC

OO

O

Ph

NHTs

3a 93

N

Ph OH

Ts

2a








N

Ph O

Ts

A

N

Ph O

Ts

B

O

O

OO

O

Ph

NTs

CO2

H

C

Cs2CO3

CsHCO 3

Cs

Cs

Cs

2

1

N

Ph OH

Ts

2a

OO

O

Ph

NHTs

3a












N

Ts

OHPh

4

Chapter 1

14




solar light

CO2Cs2CO3

60degCDMAPh

O

NTs

Me

1a

OO

O

Ph

NHTs

3a 83






chloro groups10





Ar

O

NR

Me OO

O

Ar

NHR3

1

OO

O

NHTs3b 80

MeO

OO

O

NHTs3c 57

F3C

OO

O

NHTs3d 73

Cl

OO

O

NHTs3e 85

Br

OO

O

Ph

NH

3f 87

O2S OMe

OO

O

Ph

NH

3g 85

O2S CF3

OO

O

Ph

NH

3h 87

O2S

N

solar lightCO2

Cs2CO3

60degCDMA




Chapter 1

15

Conclusions















Chapter 1

16












indicator (Merck)






Ph

O

NTs

MeTsClMeNH2 +

Et2OTsNHMe

CH3CN

K2CO3












Chapter 1

17


Ph

O

NTs

Me


745-751 (m 2H) 760 (tt J = 76 12 Hz 1H) 771-775 (m 2H) 795-799 (m 2H)

13C NMR δ = 215 356 560 1275 1282 1288 1297 1338 1347 1348 1436


+ 3041002 Found mz 3040994 IR

(ATR) 1693 1339 1227 1157 743 cm-1

O

NTs

Me

1bMeO


733 (d J = 80 Hz 2H) 770-774 (m 2H) 796-802 (m 2H) 13

C NMR δ = 215

355 555 558 1139 1275 1277 1296 1307 1346 1436 1640 1921 HRMS


+ 3341108 Found mz 3341101 IR (ATR) 1688

1601 1329 1180 1159 cm-1

O

NTs

Me

1cF3C


= 84 Hz 2H) 776 (d J = 84 Hz 2H) 812 (d J = 84 Hz 2H) 13

C NMR δ = 215

357 564 1234 (q JC-F = 2711 Hz) 1259 (q JC-F = 37 Hz) 1276 1288 1298



1121 1109 cm-1

Chapter 1

18

O

NTs

Me

1dCl


(m 2H) 771 (d J = 80 Hz 2H) 792-796 (m 2H) 13

C NMR δ = 216 356 561



1159 1088 cm-1

O

NTs

Me

1eBr


= 84 Hz 2H) 771 (d J = 84 Hz 2H) 786 (d J = 84 Hz 2H) 13

C NMR δ = 215

356 561 1275 1291 1297 1298 1321 1334 1344 1438 1930 HRMS (ESI+)


1223 1155 810cm-1

Ph

O

NS

Me

1f

OMe

OO

1H NMR δ = 282 (s 3H) 389 (s 3H) 456 (s 2H) 698-703 (m 2H) 746-751 (m

2H) 761 (tt J = 72 12 Hz 1H)776-781 (m 2H) 796-800 (m 2H) 13

C NMR δ =

356 556 561 1142 1283 1288 1294 1297 1338 1348 1630 1938 HRMS


+ 3200951 Found mz 3200943 IR (ATR) 1692

1342 1259 1155 741 cm-1

Chapter 1

19

Ph

O

NS

Me

1g

CF3

OO


780 (d J = 84 Hz 2H) 790-794 (m 2H) 798 (d J = 80 Hz 2H) 13

C NMR δ =

356 558 1233 (q JC-F = 2711 Hz) 1261 (q JC-F = 36 Hz) 12796 12799 1289



1059 748 cm-1

Ph

O

NS

Me

1h

N

OO

1H NMR δ = 302 (s 3H) 486 (s 2H) 744-753 (m 3H) 757-762 (m 1H)

788-798 (m 4H) 870 (ddd J = 48 16 08 Hz 1H)13

C NMR δ = 363 569 1224



752 cm-1


Ph

O

NTs

Mesolar light

N

Ph OH

TsDMA rt

1a

2a








Chapter 1

20


N

Ph OH

Ts


2H) 728-737 (m 5H) 740 (d J = 80 Hz 2H) 779 (d J = 80 Hz 2H) 13

C NMR δ

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS




N 458 O 1555 S 1058 IR (ATR) 3477 1333 1184 1148 671 cm-1


N

Ph OH

Ts

2a

40 equiv Cs2CO3

1 atm CO2

DMA 60 C

OO

O

Ph

NHTs

3a








mmol 93 yield)

Chapter 1

21



40 equiv Cs2CO3

60 CPh

O

NR

Me OO

O

Ph

NHR3a

1a

solar light

DMA rt

1 atm CO2











OO

O

Ph

NHTs



726-732 (m 4H) 734-743 (m 3H) 769-773 (m 2H) 13

C NMR δ = 215 503

724 850 1242 1269 1292 1299 1365 1381 1439 1542 HRMS (ESI+) Calcd

for C17H18NO5S M+H+


C 5878 H 493 N 403 O 2303 S 923 Found C 5871 H 496 N 389 O

2284 S 932 IR (ATR) 3261 1773 1435 1319 1045 cm-1

Chapter 1

22

OO

O

NHTs

3b

MeO



56 Hz 1H) 688-693 (m 2H) 719-724 (m 2H) 728 (d J = 80 Hz 2H) 770 (d J =

84 Hz 2H) 13

C NMR δ = 215 503 554 724 848 1145 1256 1269 1298


+

3781006 Found mz 3780996 IR (ATR) 3238 1794 1518 1329 1057 723 cm-1

OO

O

NHTs

3c

F3C



729 (d J = 84 Hz 2H) 746 (d J = 84 Hz 2H) 765-771 (m 4H) 13

C NMR δ =

215 501 722 846 1235 (q JC-F = 2704 Hz) 1249 1263 (q JC-F = 37 Hz) 1268



1067 cm-1

OO

O

NHTs

3d

Cl



722-727 (m 2H) 728 (d J = 84 Hz 2H) 735-739 (m 2H) 769 (d J = 84 Hz 2H)

13C NMR δ = 215 502 723 847 1257 1268 1294 1300 1353 1364 1365


+ 3820510 Found mz

Chapter 1

23

3820506 IR (ATR) 3250 1800 1325 1155 1069 cm-1

OO

O

NHTs

3e

Br



716-720 (m 2H) 728 (d J = 80 Hz 2H) 750-755 (m 2H) 766-770 (m 2H) 13

C

NMR δ = 215 501 723 847 1235 1260 1268 1300 1323 1364 1370 1441


+ 4260005 Found mz 4260003

IR (ATR) 3252 1800 1331 1175 1057 cm-1

OO

O

Ph

NH

SO

O

OMe



693-698 (m 2H) 727-732 (m 2H) 734-744 (m 3H) 773-778 (m 2H) 13

C NMR

δ = 503 556 724 849 1145 1242 1291 1292 1310 1381 1541 1632 HRMS


+ 3640849 Found mz 3640836 IR (ATR) 3246

1801 1325 1155 1067 cm-1

OO

O

Ph

NH

SO

O

CF3

3g

Chapter 1

24



2H) 735-744 (m 3H) 775 (d J = 88 Hz 2H) 796 (d J = 84 Hz 2H) 13

C NMR δ

= 505 725 851 1231 (q JC-F = 2711 Hz) 1241 1265 (q JC-F = 37 Hz) 1274



1161 1105 cm-1

OO

O

Ph

NH

SO

O

N




1H) 798 (d J = 76 Hz 1H) 866 (d J = 44 Hz 1H) 13

C NMR δ = 510 723 849



1175 1063 cm-1


N

Ts

OHPh

N

Ts

O CeCl 3

PhLi

THF -78 C to rt

4






Chapter 1

25






N

Ts

OHPh


351-364 (m 4H) 726-738 (m 7H) 773-777 (m 2H) 13

C NMR δ = 215 396

469 608 804 1250 1276 1280 1286 1297 1339 1418 1435 HRMS (ESI+)


1325 1159 1101 770 cm-1

Chapter 1

26











Soc 2011 133 12881

























25 312

Chapter 1

27








Chapter 1

28

Chapter 2

29

Chapter 2



Abstract







Chapter 2

30

Introduction














A



Indanones are


A rearrangement













Whereas







Chapter 2

31




N

HO Ph

S NS Me

HO PhMe

1a2a 96

Me

O

OO O


2) is





The generated








N

S O

O

O[Rh]

Ph

SN

[Rh]O Ph

O OMe

[Rh] OH

N

S O

O

O Ph

H

[Rh]

H

N

[Rh]O Ph

S O

O

Me Me

Me

Me

1a

H2O

2a

A B

CD

1a

A




Chapter 2

32








N

HO Ph

SN

S CH19D11

HO Ph

D3C

1a-d2a-d 96

D3C

O

O

O O

D

D

D

D

D

D

H01D09

8



D12




Application




1

2

SN

HO Ar

O OMe

N

HO Ar

S O

O


K2CO 3 (20 equiv)


NS Me

HO PhMe

2a

91 er = 928

O O

NS Me

HO Ph

2b

95 er = 937

O O

S

NS Me

HOMe

2c

90 er = 937

O O

OMe

NS Me

HOMe

2c

92 er = 919

O O

CF3



Chapter 2

33










HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6 84

5 56



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3


PhMgBr

THF rt 1 h N

HO

Ts

Me

1e 93

er gt 991 dr = 201

Ph

3







SN

HO PhMe

O OMe

MeN

HO Ph

S O

O

Me

Me

1e

er gt 991 dr = 201

2e 99

er gt 991 dr gt 201





Chapter 2

34









SN

PhRhOMe

O OMe

Me

SN

PhRhOMe

O OMe

Me

favored

disfavored

F

F

NSRh

Ph

Me

O

O

MeO

H

Me

E

E

NSRh

Ph

Me

O

O

MeO

Me

H














Chapter 2

35


1

er gt 991 dr gt 201

2

er gt 991 dr gt 201

SN

HO ArR

O OMe

N

HO Ar

S O

O





1 N

HO Ph

S O

O

Me

Me

1f

SN

HO PhMe

O OMe

Me

2e 99

6 N

HO

S O

O

Me

1k

OMe

SN

HOMe

O OMe

2k 97

OMe

2

N

HO Ph

S O

O

MeO

Me

1g

SN

HO PhMe

O OMe

MeO

2g 98

7 N

HO

S O

O

Me

Me

1l

CF3

SN

HOMe

O OMe

Me

2l 97

CF3

3 N

HO Ph

S O

O

F3C

Me

1h

SN

HO PhMe

O OMe

F3C

2h 99

8 N

HO Ph

S O

O

Me

i-Pr

1m

SN

HO Phi-Pr

O OMe

Me

2m 97

4

N

HO Ph

S O

O

Me

1iMe

SN

HO PhMe

O OMeMe

2i 99

9 N

HO Ph

S O

O

Me

SMe

SN

HO Ph

O OMe

Me

2n 97

SMe

5 N

HO Ph

S O

O

Me

S

1j

SN

HO PhMe

O OMeS

2j 99



Chapter 2

36

Conclusions






Chapter 2

37





13C NMR


13C at 10069












N

OHNEt3

DCM rt 12 h


2) PhMgBrTHF rt 3 h

N

HO Ph

1a

TsCl

N

OH

8a

H HCl

Ts Ts









Chapter 2

38

N

S

Me

O

O

OH

8a 1H NMR = 213 (bs 1H) 245 (s 3H) 350-361 (m 2H) 394-404 (m 2H)

442-452 (m 1H) 737 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR =



-1

N

S

D3C

O

O

OH

8a-d

D

D

D

D

1H NMR = 283 (bs 1H) 349-355 (m 2H) 389-396 (m 2H) 435-444 (m 1H)



+ 2351128 Found mz

2351125 IR (ATR) 3503 1333 1142 1059 638 cm-1

N

S O

O

OH

8b

S

1H NMR = 277 (bs 1H) 357-364 (m 2H) 400-407 (m 2H) 441-450 (m 1H)


1H) 13



1038 737 cm-1

Chapter 2

39














N

HO Ph

S

1a

Me

O

O


2H) 728-737 (m 5H) 739 (d J = 84 Hz 2H) 778 (d J = 80 Hz 2H) 13

C NMR

= 216 652 703 1244 1281 1284 1286 1299 1312 1420 1444 HRMS


+ 3041002 Found mz 3040995 IR (ATR) 3477

1333 1184 1148 671 cm-1


N

HO Ph

S

1a-d

D3C

O

O

D

D

D

D


(m 5H) 13

C NMR = 203-211 (m) 652 703 1244 1281 (t JC-D = 247 Hz)


Chapter 2

40


702 648 cm-1

N

HO Ph

S

S

O

O



1H) 13

C NMR = 656 702 1244 1280 1283 1288 1331 13387 13392 1417


+ 2960410 Found mz 2960404 IR

(ATR) 3524 1333 1161 1148 748 cm-1

N

HO

S

Me

O

O

OMe

1c



2H) 775 (d J = 80 Hz 2H) 13

C NMR =216 553 652 702 1139 1259 1285


+

3341108 Found mz 3341097 IR (ATR) 3460 1518 1331 1250 1146 cm-1

N

HO

S

Me

O

O

CF3



C NMR

Chapter 2

41

=216 654 697 1239 (q JC-F = 2704 Hz) 1249 1255 (q JC-F = 37 Hz) 1284



1109 1076 cm-1


1l-1n

HO2C Me

NHTs

Me

NHTs

O

N2

N

O

Ts

Me

6a

5a



benzene 90 C 1 min

HO2C Me

NH2

TsCl NEt3

acetone H2O

rt 10 h 4a

PhMgBr

THF rt 1 h N

OH

Ts

Me

1e

Ph

3a



procedure16













Me

NHTs

O

N2


Chapter 2

42

2H) 730 (d J = 84 Hz 2H) 772 (d J = 84 Hz 2H) 13

C NMR = 194 215 539


+

2680750 Found mz 2680747 IR (ATR) 2112 1639 1337 1319 1161 cm-1

[]27

D = -1184 (c = 079 in CHCl3)


i-Pr

NHTs

O

N2



2H) 769 (d J = 84 Hz 2H) 13

C NMR =169 193 215 315 548 647 1273


+ 2961063

Found mz 2961060 IR (ATR) 2129 1622 1362 1329 1161 cm-1

[]28

D = -730 (c = 071 in CHCl3)

NHTs

O

N2

5c

SMe

1H NMR = 174-196 (m 2H) 204 (s 3H) 242 (s 3H) 244-252 (m 2H)

390-400 (m 1H) 541 (s 1H) 560-572 (m 1H) 730 (d J = 84 Hz 2H) 772 (d J =

84 Hz 2H) 13

C NMR = 153 215 297 323 545 585 1272 1297 1366 1439


+ 3280784 Found mz 3280779

IR (ATR) 2129 1618 1375 1339 1163 cm-1

[]29

D = -506 (c = 063 in CHCl3)









Chapter 2

43

N

O

Ts

Me

6a

1H NMR = 145 (d J = 68 Hz 3H) 246 (s 3H) 443-454 (m 2H) 473-480 (m

1H) 736-742 (m 2H) 776-781 (m 2H) 13

C NMR = 157 216 696 810 1284


+ 2400689

Found mz 2400688 IR (ATR) 1825 1339 1155 669 cm-1

[]28

D = 614 (c = 081 in CHCl3)


N

O

Ts

i-Pr

6b

1H NMR = 099-111 (m 6H) 206-218 (m 1H) 246 (s 3H) 441 (dd J = 164 36


2H) 777 (d J = 80 Hz 2H) 13

C NMR = 174 181 216 304 703 903 1284


+ 2681002

Found mz 2680998 IR (ATR) 1815 1340 1155 1007 671 cm-1

[]29

D = 567 (c = 095 in CHCl3)

N

O

Ts

6c

SMe

1H NMR = 204 (s 3H) 209-218 (m 2H) 247 (s 3H) 265-279 (m 2H) 446 (d


2H) 780 (d J = 80 Hz 2H) 13

C NMR = 147 216 291 293 705 832 1286


+ 3000723

Found mz 3000718 IR (ATR) 1813 1342 1308 1157 667 cm-1

[]29

D = 1183 (c = 036 in CHCl3)


Chapter 2

44










N

HO

S O

O

Me

Me

1e

H

NOE

NOE



(m 3H) 739 (d J = 84 Hz 2H) 777 (d J = 84 Hz 2H) 13

C NMR = 144 216

628 702 731 1247 1279 1284 1285 1298 1319 1415 1443 HRMS (ESI+)


1155 1092 667 cm-1

[]25




Chapter 2

45

N

HO

S O

O

Me

1l

H

NOE

NOE

CF3

Me



739-747 (m 4H) 777 (d J = 84 Hz 2H) 13

C NMR = 143 216 630 706 727

1238 (JC-F = 2704 Hz) 1253 1254 (JC-F = 36 Hz) 1285 1299 1301 (JC-F = 324


+ 3861032

Found mz 3861025 IR (ATR) 3422 1327 1151 1109 839 cm-1

[]28




N

HO

S O

O

Me

iPr

1m

H

NOE

NOE



= 100 Hz 1H) 690-696 (m 2H) 712-720 (m 3H) 732 (d J = 80 Hz 2H) 773 (d

J = 80 Hz 2H) 13

C NMR = 190 193 215 291 641 729 801 1247 1275


+

3461471 Found mz 3461466 IR (ATR) 3454 1331 1163 739 669 cm-1

[]27



Chapter 2

46


N

HO Ph

S O

O

1n

Me

SMe

1H NMR = 202 (s 3H) 218-258 (m 8H) 388-394 (m 2H) 427 (dd J = 84 48

Hz 1H) 688-693 (m 2H) 714-721 (m 3H) 740 (d J = 80 Hz 2H) 779 (d J = 80

Hz 2H) 13

C NMR = 154 216 290 297 634 725 733 1246 1277 1284


+

3781192 Found mz 3781188 IR (ATR) 3481 1339 1157 702 669 cm-1

[]28












N

HO

S O

O

Me

Me

1f

H

NOE

NOE


1H) 398 (q J = 64 Hz 1H) 424 (dd J = 84 08 Hz 1H) 732-744 (m 5H)

750-755 (m 2H) 774-778 (m 2H) 13

C NMR = 165 216 627 718 739 1257

Chapter 2

47



-1

[]25






HO2C Me

NHCbz

Me

NHCbz

O

N2N

O

Cbz

Me

6d5d

1) (COCl) 2 DMF

2) CH2N2 Rh2(OAc)4 (05 mol )

DCM rt 12 h4d

PhMgBr

THF rt 1 h

N

OH

Cbz

Me

7a

Ph

N

OH

H

Me

PhPd C (5 mol )

H2 (1atm)

MeOH rt 12 h

MeO SO2Cl

NEt3

DCM rt 12 h

N

HO Ph

S O

O

MeO

Me

1g









Me

NHCbz

O

N2

5d 1H NMR = 134 (d J = 68 Hz 3H) 420-436 (m 1H) 504-516 (m 2H) 534-564

(m 2H) 728-736 (m 5H) 13

C NMR = 184 535 (2C) 669 1280 1282 1285


+ 2481030 Found mz

2481028 IR (ATR) 2116 1717 1636 1533 1252 cm-1

[]28

D = -434 (c = 085 in CHCl3)


Chapter 2

48







N

O

Cbz

Me

6d


Hz 1H) 498-505 (m 1H) 513-521 (m 2H) 731-739 (m 5H) 13

C NMR = 153



696 cm-1

[]29

D = 390 (c = 068 in CHCl3)










N

OH

Cbz

Me

7a

Ph


= 96 Hz 1H) 458 (q J = 64 Hz 1H) 507-518 (m 2H) 729-746 (m 10H) 13

C

NMR = 142 623 667 689 730 1246 1278 1279 1280 1285 1287 1366

Chapter 2

49


+ 2981438 Found mz

2981433 IR (ATR) 1670 1423 1248 1016 702 cm-1

[]29

D = 46 (c = 089 in CHCl3)

N

OH

Cbz

Me

7b

MeO


1H) 432 (d J = 96 Hz 1H) 452-461 (m 1H) 506-518 (m 2H) 687-694 (m 2H)

726-739 (m 7H) 13

C NMR = 143 553 622 666 687 729 1140 1260 1278


+

3281543 Found mz 3281539 IR (ATR) 1682 1418 1352 1024 696 cm-1

[]29

D = 02 (c = 085 in CHCl3)








pressure







mmol 58 yield)

Chapter 2

50

N

HO

S O

O

MeO

Me

1g

H

NOE

NOE


390 (s 3H) 399 (d J = 92 Hz 1H) 419 (q J = 60 Hz 1H) 698-707 (m 4H)

720-727 (m 3H) 779-785 (m 2H) 13

C NMR = 143 557 627 701 731 1144



-1

[]28




N

HO

S O

O

F3C

Me

1h

H

NOE

NOE


406 (d J = 92 Hz 1H) 430 (qd J = 64 08 Hz 1H) 694-699 (m 2H) 721-727

(m 3H) 784 (d J = 80 Hz 2H) 801 (d J = 84 Hz 2H) 13

C NMR = 145 629

706 729 1232 (JC-F = 2711 Hz) 1245 1263 (JC-F = 37 Hz) 1283 12868 12871


+

3720876 Found mz 3720870 IR (ATR) 3503 1348 1323 1165 646 cm-1

[]28




Chapter 2

51

N

HO

S O

O

Me

1i

H

NOE

NOE


1H) 401 (d J = 88 Hz 1H) 422 (q J = 64 Hz 1H) 694-698 (m 2H) 720-724 (m

3H) 746-750 (m 2H) 767-772 (m 2H) 13

C NMR = 144 214 630 704 730

1247 1256 1279 1285 1286 1291 1341 1347 1395 1416 HRMS (ESI+)


1151 714 700 cm-1

[]29




N

HO

S O

O

Me

1j

H

NOE

NOE

S


Hz 1H) 425 (q J = 64 Hz 1H) 696-701 (m 2H) 720-728 (m 4H) 764-767 (m

1H) 769-772 (m 1H) 13

C NMR = 144 632 709 730 1246 1279 1281 1286


+ 3100566

Found mz 3100559 IR (ATR) 3508 1340 1151 756 669 cm-1

[]29




Chapter 2

52

N

HO

S O

O

Me

1k

H

NOE

NOE

OMe


1H) 394 (d J = 88 Hz 1H) 416 (q J = 64 Hz 1H) 670-675 (m 2H) 684-689 (m

2H) 756-762 (m 2H) 765-770 (m 1H) 786-790 (m 2H) 13

C NMR = 143 553

630 704 729 1138 1259 1283 1292 1332 1337 1348 1592 HRMS (ESI+)


1327 1155 606 cm-1

[]29





Screening







mmol 93 yield)

Chapter 2

53


rac -DM-BINAP

rac-BINAP

dppf

dppb

PPh3

dppe

46

trace

trace

yield

PCy3

Ligand

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

entry

1

2

3

4

5

6

7

8

nd

nd

nd

93

none nd

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a


entry Ligand yield

1

2

3

4

(R)-BINAP

(R)-DM-BINAP

(R)-SEGPHOS

(R)-DIFLUORPHOS

er

94

46

48

43

5

6

(R)-DM-SEGPHOS


3862

91

7

8

(R)-MeO-BIPHEP

(R)-MeO-DM-BIPHEP

64

91

892

3169

1288

1486

2476

2575

2 mol [Rh(OH)cod]2

Ligand (10mol P)

toluene 60 C 12 h

20 eq K2CO3

NS Me

HO PhMe

2a

O O

N

HO Ph

Ts

1a










Chapter 2

54

NS Me

HO PhMe

2a

O O


J = 148 Hz 1H) 683 (s 1H) 727-744 (m 6H) 781 (d J = 84 Hz 1H) 13

C NMR

= 216 361 626 732 1238 1263 1280 1284 1299 1301 1330 1412 1431


+ 3041002 Found mz 3040998 IR

(ATR) 3472 1325 1161 1142 735 cm-1

[]29




NS CH2D

HO Ph

D3C

2a-d

O O

D

D

D


J = 148 Hz 1H) 728-743 (m 5H) 13

C NMR = 201-210 (m) 358 (t JC-D = 212

Hz) 625 731 1234 (t JC-D = 249 Hz) 1262 1279 1283 1291-1300 (m 2C)


+ 3111441

Found mz 3111436 IR (ATR) 3524 1318 1290 1150 721 cm-1

NS Me

HO Ph

O O

S

2b


1H) 668 (d J = 52 z 1H) 730-738 (m 5H) 750 (d J = 52 Hz 1H) 13

C NMR =

378 630 722 1257 1264 1282 1286 1299 1338 1427 1467 HRMS (ESI+)


1150 1063 748 cm-1

[]29


Chapter 2

55



NS Me

HOMe

O O

OMe

2c


422 (d J = 148 Hz 1H) 684-690 (m 3H) 724-733 (m 3H) 774-779 (m 1H) 13

C

NMR = 216 360 553 626 729 1137 1237 1275 1299 1230 1328 1351


+ 3341108 Found mz

3341098 IR (ATR) 3441 1508 1250 1144 735 cm-1

[]29




NS Me

HOMe

O O

CF3



2H) 782 (d J = 80 Hz 1H) 13

C NMR = 216 360 625 731 12392 (q JC-F =

2708) 12395 1254 (q JC-F = 36 Hz) 1268 1298 1303 (q JC-F = 352) 1329


+ 3720876 Found

mz 3720869 IR (ATR) 3481 1323 1121 1067 733 cm-1

[]29




Chapter 2

56










SN

HO

Me

O OMe

Me

2e

H

NOE

NOE


= 68 Hz 1H) 675 (s 1H) 723-738 (m 6H) 777 (d J = 84 Hz 1H) 13

C NMR =

119 215 314 608 750 1242 1262 1275 1282 1298 1301 1316 1427


+ 3181158 Found mz

3181155 IR (ATR) 3481 1315 1163 1146 683 cm-1

[]28




SN

HO

Me

O OMe

MeO

2g

H

NOE

NOE

Chapter 2

57



5H) 782 (d J = 88 Hz 1H) 13

C NMR = 120 314 555 609 752 1144 1151



735 cm-1

[]29




SN

HO

Me

O OMe

F3C

2h

H

NOE

NOE



1H) 13

C NMR = 118 314 608 750 1228 (q JC-F = 2711 Hz) 1251 1258 (q



+ 3720876 Found

mz 3720872 IR (ATR) 3461 1325 1161 1142 739 cm-1

[]29




SN

HO

Me

O OMe

2i

H

NOE

NOE

Me

Chapter 2

58


J = 68 Hz 1H) 684 (d J = 80 Hz 1H) 718-736 (m 6H) 770 (s 1H) 13

C NMR

=119 211 314 607 748 1242 1262 1275 1282 1299 1338 1341 1395


+ 3181158 Found mz

3181155 IR (ATR) 3489 1448 1319 1148 735 cm-1

[]29




SN

HO

Me

O OMe

2j

H

NOE

NOES


1H) 656 (d J = 52 Hz 1H) 726-736 (m 5H) 743 (d J = 48 Hz 1H) 13

C NMR

= 114 319 619 742 1256 1266 1278 1284 1297 1334 1429 1480 HRMS


+ 3100566 Found mz 3100561 IR (ATR) 3524

1329 1151 1020 729 cm-1

[]29




SN

HO

Me

O OMe

2k

H

NOE

NOE

OMe


J = 68 Hz 1H) 685 (d J = 88 Hz 2H) 698-703 (m 1H) 722-730 (m 2H)

738-748 (m 2H) 785-790 (m 1H) 13

C NMR = 119 314 553 608 747 1136

Chapter 2

59



760 cm-1

[]26




SN

HO

Me

O OMe

2l

H

NOE

NOE

CF3

Me



= 84 Hz 2H) 778 (d J = 80 Hz 1H) 13

C NMR = 119 215 313 607 749




-1

[]26




SN

HO

iPr

O OMe

2m

H

NOE

NOE

Me


(m 1H) 264 (s 1H) 285 (s 3H) 441 (d J = 100 Hz 1H) 685 (s 1H) 714-735 (m

4H) 748 (d J = 76 Hz 2H) 772 (d J = 80 Hz 1H) 13

C NMR = 211 214 217

278 330 718 742 1244 1256 1270 1283 1292 1295 1300 1435 1442


+ 3461471 Found mz 3461466 IR

Chapter 2

60

(ATR) 3412 1315 1165 1146 683 cm-1

[]29




SN

HO

O OMe

2n

H

Me

NOE

SMe

1H NMR = 160-170 (m 1H) 184 (s 3H) 212-226 (m 4H) 230-242 (m 2H)

254-263 (m 1H) 294 (s 3H) 471 (dd J = 108 28 Hz 1H) 675 (s 1H) 722-738

(m 6H) 776 (d J = 80 Hz 1H) 13

C NMR = 150 215 242 301 321 643 748

1245 1262 1276 1283 12986 12993 1312 1429 1437 1441 HRMS (ESI+)


1165 1134 748 cm-1

[]28









was used as a


and


21 All



Chapter 2

61



2e

formula C17H19NO3S

fw 31739

T (K) 100(2)


space group P21c

a (Aring) 105967(5)


3) 152058(13)

Z 4 Dcalc (gcm

3) 1386

(mm-1

) 0225 F(000) 672



348500135

params 203 GOF on F

2 1069

R1 wR2 [Igt2(I)]

00322 00868

R1 wR2 (all data)

00335 00878

Chapter 2

62

























Med Chem 2003 46 1116








Chapter 2

63

































Chapter 2

64




2012 51 9160





11437-11439
























Chapter 2

65











2548-2551







11750









32 115



Chapter 2

66

Chapter 3

67

Chapter 3




Halides

Abstract






Chapter 3

68

Introduction
















2) are












several months


Et LiB

Ph

+B

Ph

Et

1a 74

(a)(b)[Me4N]


Chapter 3

69

















OMe

BrB

Ph

Et

OMe

3a

Ph

Et

OMe

H

4a

Pd-ligand AcOH

2a

+B

Ph

Et

1a

[Me4N]


EZ of 4ab

1 P(o-tol)3 69 397

2 P(t-Bu)3 47 1783

3 1-[(t-Bu)2P](biphenyl) 18 2872

4 2-[(t-Bu)2P](11-binaphthyl) 21 6733

5 DPEPhos 24 928



analysis



Chapter 3

70









Pd(0)

Pd

MeO

B

PdEt

OMe

Ph

B

Ph

Et

2a

BC

Pd

MeO

Br

A

1a

3a







dominates10
















Chapter 3

71










Chapter 3

72


BO

Ph

Et

OMe

5a 83

BO

Ph

Et

CF3

5b 85

BO

Ph

Et

NPhth

5c 82

BO

Ph

Et

5d 72b

BO

Ph

Et

5e 85

S

BO

n-Pr

Me

Cl

5f 74

BO

n-Pr

Ph

OMe

5g 82

BO

Ph

S

5h 83

BO

Ph

CO2Et

5i 81

BO

Ph

5j 82

Cl

BO

Ph

CF3

TBSO

BO

Cl

S

Ph

BO

Ph

Me

OMe

5n 71b

5m 925l 82

BO

Ph

5k 76

Me

+B

Ar

R

1

[Me4N]

2


BO

Ar

R

Ar

5







The reaction of 1a






Chapter 3

73








(E)-5o83 EZ = gt955

BO

Ph

Et

Ph

Ph

Et

PhO

NMe2

(Z)-685 EZ = lt595

Ph

Ph

EtO

NMe 2

(E)-675 EZ = 928

1a

(Z)-5o71 EZ = 793

+ PhBr

BO

Ph

Ph

Et

(a)

(c) (c)

(b)






Conclusions






Chapter 3

74




1H at 400 MHz and

11B at 128 MHz)



13C)

CD3CN ( = 194 for 1H =132 for


11B)









and Ph-9-BBN18


procedures


Et LiB

Ph

+B

Ph

Et

1a


2) Me4NCl MeOH

[Me4N]









74 yield)

Chapter 3

75

B

Ph

Et

1a

[Me4N]


136-207 (m 11H) 236-250 (m 2H) 303 (s 12 H) 679-686 (m 1H) 700-707 (m

2H) 735 (d J = 72 Hz 2H) 13

C NMR (CD3CN) = 149 166 266 (q JC-B = 379

Hz) 271 275 324 349 561 948 1221 1269 1339 11

B NMR = -133 HRMS




n-Pr LiB

Ar


2) Me4NCl MeOH B

n-Pr

1b

Cl

[Me4N]










Chapter 3

76

B

n-Pr

1b

Cl

[Me4N]

1H NMR (CD3CN) = 084-096 (m 5H) 111-121 (m 1H) 126-200 (m 13H)

235-250 (m 2H) 304 (s 12H) 700-705 (m 2H) 733 (d J = 84 Hz 2H) 13

C NMR

(CD3CN) = 139 234 249 266 (q JC-B = 393 Hz) 270 273 323 348 561

933 1265 1272 1355 11


[M-(NMe4)] 2991738 Found 2991730

B

n-Pr

1c

OMe

[Me4N]


128-201 (m 13H) 237-252 (m 2H) 303 (s 12H) 371 (s 3H) 663-668 (m 2H)

723 (d J = 81 Hz 2H) 13

C NMR (CD3CN) = 140 235 250 268 (q JC-B = 393

Hz) 272 275 324 349 554 561 929 1128 1344 1561 11

B NMR = -135


B

Ph

1d

[Me4N]


(m 2H) 134-196 (m 9H) 230-244 (m 2H) 304 (s 12H) 679-686 (m 1H)

699-706 (m 2H) 733 (d J = 72 Hz 2H) 13

C NMR (CD3CN) =23 87 266 (q

JC-B = 393 Hz) 271 274 323 349 562 1222 1269 1338 11

B NMR = -134


Chapter 3

77

B

Ph

1e

[Me4N]


(m 3H) 302 (s 12H) 679-686 (m 1H) 699-706 (m 2H) 734 (d J = 66 Hz 2H) 13

C NMR (CD3CN) = 253 268 (q JC-B = 379 Hz) 271 275 324 333 349 361

561 980 1221 1269 1339 11


[M-(NMe4)] 2912284 Found 2912278

B

1f

S

Ph

[Me4N]




09 Hz 1H) 712-730 (m 5H) 13

C NMR (CD3CN) = 240 268-290 (m) 325 347

380 562 928 1225 1261 1265 1271 1289 1297 1434 11

B NMR = -135


B

Ph

1g

TBSO

[Me4N]

1H NMR (CD3CN) = 005 (s 6H) 084-096 (m 11H) 110-120 (m 1H) 134-197

(m 9H) 216-233 (t J = 72 Hz 2H) 235-250 (m 2H) 301 (s 12H) 356 (t J = 78

Hz 2H) 680-687 (m 1H) 700-708 (m 2H) 735 (d J = 66 Hz 2H) 13

C NMR

(CD3CN) = -50 189 254-277 (m) 323 348 561 649 889 1222 1269

1339 11


Found 3812789

Chapter 3

78

B

Ph

1h

OMe

[Me4N]


(m 2H) 298 (s 12H) 373 (s 3H) 668-674 (m 2H) 701-718 (m 5H) 732 (d J =

87 Hz 2H) 13

C NMR (CD3CN) = 255-277 (m) 322 350 554 561 961 1129

1251 1287 1302 1312 1345 1564 11


C23H26BO [M-(NMe4)] 3292077 Found 3292081



Br

+

MeO


6 mol Ligand


2a

B

Ph

Et

OMe

(E)-3a

AcOH

Ph

Et

OMe

H

Ph

B

Et

OMe

+

+

(Z)-3a

(E)-4a

H

Et

OMe

Ph

(Z)-4a

B

Ph

Et

1a

[Me4N]









Chapter 3

79




B

Ph

Et

+


toluene 70 degC

Me3NO

Br

MeO

BO

Ph

Et

OMe

5a

1a

2a

[Me4N]









BO

Ph

Et

OMe


383 (s 3H) 438-444 (m 1H) 685-691 (m 2H) 714-736 (m 7H) 13

C NMR =

138 221 267 273 (br) 277 312 553 736 1132 1251 1278 1283 1298

1366 1436 1494 1586 11


3742417 Found 3742410

Chapter 3

80

BO

Ph

Et

CF3

5b


437-443 (m 1H) 718-726 (m 3H) 734-739 (m 2H) 745-748 (m 2H) 760-763

(m 2H) 13

C NMR = 135 220 266 271 (br) 276 312 738 12429 (q JC-F =

2701 Hz) 1247 (q JC-F = 36 Hz) 1280 1281 1289 (q JC-F = 320 Hz) 1291 1425

1476 1480 11


Found 4122186

BO

Ph

Et

NPhth

5c


440-450 (m 1H) 720-727 (m 3H) 734-739 (m 2H) 743-751 (m 4H) 777-783

(m 2H) 794-800 (m 2H) 13

C NMR = 137 221 266 274 (br) 275 312 738

1235 1254 1258 1279 1282 1294 1304 1317 1342 1429 1440 1482

1671 11

B NMR = 502 IR (KBr) = 2928 1742 1509 1381 714 cm-1

HRMS (EI)


BO

Ph

Et

5d

1H NMR = 021-034 (m 1H) 068-100 (m 8H) 120-150 (m 7H) 224-238 (m

1H) 244-258 (m 1H) 424-431 (m 1H) 722-754 (m 9H) 778 (d J = 78 Hz 1H)

783-788 (m 1H) 809-816 (m 1H) 13

C NMR = 137 216 219 259 262 264

(br) 282 309 314 734 1249 12537 12539 1255 1264 1270 1273 12795

Chapter 3

81

12799 1283 1321 1335 1413 1427 1467 11


for C28H31BO (M+) 3942468 Found 3942476

BO

Ph

Et

5e

S


448-456 (m 1H) 702 (dd J = 51 36 Hz 1H) 708 (dd J = 36 12 Hz 1H)

715-730 (m 4H) 732-738 (m 2H) 13

C NMR =141 221 271 289 312 739

1250 1255 1266 1269 1279 1281 1416 1427 1468 11

B NMR = 496


BO

n-Pr

Me

Cl

5f

1H NMR = 070 (t J = 75 Hz 3H) 096-133 (m 9H) 142-172 (m 6H) 220-228

(m 2H) 237 (s 3H) 439-446 (m 1H) 708-735 (m 8H) 13

C NMR = 140 212

219 221 267 274 (br) 313 363 737 1279 12846 12855 1298 1309 1365

1411 1420 1488 11


4062235 Found 4062237

BO

n-Pr

Ph

OMe

5g

Chapter 3

82


(s 3H) 435-450 (m 1H) 690 (d J = 81 Hz 2H) 711 (d J = 81 Hz 2H) 720-740

(m 5H) 13

C NMR = 140 219 221 267 274 (br) 312 362 551 736 1133

1267 1278 1287 1294 1354 1446 1475 1573 11




BO

Ph

S

5h

1H NMR = 027-032 (m 2H) 046-052 (m 2H) 098-130 (m 6H) 140-170 (m

8H) 430-445 (m 1H) 696-700 (m 1H) 704-707 (m 1H) 715-726 (m 2H)

729-738 (m 4H) 13

C NMR = 60 150 222 263 272 (br) 313 736 1241

1243 1253 1278 1290 1295 1410 1425 1431 11



BO

Ph

CO2Et

5i

1H NMR = 017-023 (m 2H) 045-053 (m 2H) 090-119 (m 6H) 132-173 (m

11H) 427-433 (m 1H) 438 (q J = 75 Hz 2H) 718-738 (m 7H) 798 (dt J = 78

15 Hz 2H) 13

C NMR = 56 144 151 220 263 269 (br) 312 609 735 1255

1279 1284 1287 1289 1303 1423 1453 1469 1665 11

B NMR = 496 IR

(KBr) = 2928 1717 1287 1100 cm-1


Found 4282526

BO

Ph

5j

Cl

Chapter 3

83

1H NMR = 023-029 (m 2H) 048-055 (m 2H) 094-123 (m 6H) 134-171 (m

8H) 432-439 (m 1H) 706-714 (m 1H) 718-726 (m 4H) 728-738 (m 4H) 13

C

NMR = 57 150 220 263 271 (br) 312 736 1255 1267 1279 1283 1284

1289 1304 1332 1423 1424 1461 11


C25H28BClO (M+) 3901922 Found 3901923

BO

Ph

5k

Me

1H NMR = 082-113 (m 6H) 126-164 (m 15H) 237 (s 3H) 268-280 (m 1H)

434-441 (m 1H) 704-709 (m 3H) 717-725 (m 4H) 730-737 (m 2H) 13

C NMR

= 215 219 248 263 273 (br) 312 315 433 735 1252 12689 12693 1275

1278 1283 1316 1365 1418 1424 1481 11


for C28H35BO (M+) 3982781 Found 3982780

BO

Cl

S

Ph

5l

1H NMR = 106-176 (m 13H) 250-260 (m 2H) 272-280 (m 2H) 441-449 (m

1H) 674 (dd J = 33 12 Hz 1H) 697-703 (m 3H) 709-738 (m 8H) 13

C

NMR(C6D6) =225 272 277 (br) 315 358 375 739 1247 1253 1261 1272

1285 12856 12861 1306 1335 1419 1427 1437 1491 11

B NMR = 495


BO

Ph

CF3

TBSO

5m

Chapter 3

84

1H NMR = -014 (s 6H) 079 (s 9H) 095-136 (m 6H) 142-168 (m 7H) 255 (t

J = 72 Hz 2H) 343 (t J = 72 Hz 2H) 435-442 (m 1H) 718-726 (m 3H)

731-737 (m 2H) 747 (d J = 81 Hz 2H) 759 (d J = 81 Hz 2H) 13

C NMR = -54

183 220 259 266 271 (br) 311 377 616 739 1242 (q JC-F = 2694 Hz) 1247

(q JC-F = 36 Hz) 1258 1280 1282 1290 (q JC-F = 320 Hz) 1291 1421 1422

1480 11



BO

Ph

Me

OMe

5n

1H NMR = 122-130 (m 4H) 138-162 (m 5H) 168-186 (m 4H) 237 (s 3H)

375 (s 3H) 443-450 (m 1H) 670 (dt J = 90 21 Hz 2H) 690-697 (m 4H)

702-708 (m 3H) 710-720 (m 4H) 13

C NMR = 213 222 269 312 550 738

1132 1260 1272 1285 1301 1307 1310 1362 1369 1423 1429 1483

1571 11


4362561


4-Bromobenzene

B

Ph

Et

+


toluene 70 degC

Me3NO BO

Ph

Ph

Et

(Z)-5o

1a

Ph Br

[Me4N]




Chapter 3

85






BO

Ph

Ph

Et


470-475 (m 1H) 685-710 (m 10H) 13

C NMR = 139 224 267 313 317 740

1248 1257 1272 127412938 12941 1421 1425 1275 11

B NMR = 512


BO

Ph

Et

Ph


438-443 (m 1H) 718-737 (m 10H) 13

C NMR = 137 221 266 274 (br) 277

312 737 1253 1268 1278 1279 1283 1288 1433 1442 1494 11

B NMR =



Bromide 2b

+

Br

ONMe2

Ph

Et

PhO

NMe2


THF K3PO4 60 degC

(Z)-Tamoxifen 6

2b

BO

Ph

Et

Ph

(E)-5o

Chapter 3

86









Chapter 3

87



2003 Vol 3








Rev 2006 250 1107









1976 108 281








74





Chapter 3

88





















2006 128 1828




Chapter 4

89

Chapter 4



Abstract






Chapter 4

90

Introduction





























Chapter 4

91


B

MOMO

[Me4N] +

MeO

Br

I

Br

MeO Br

B

MeO

MOMO MOMO

1a

2 3 87EZ = lt199

NaOH

50 degC

1 mol


toluene 50 degC
















procedure

Chapter 4

92



An











3

MeO

R

Br

4 92

R

MeO

R

Br

n = 2 5 87

n = 3 6 82n = 4 7 85

n

R

1 mol


toluene 50 degC

I

Br

NaOH

E

EE

R = OMOM








Chapter 4

93





Br

Br

R

R

Br

Br

8 86

R

R

Br

R

R

Br

9 92

E E

R = OMOM















Chapter 4

94


Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

Me3Si

Br

Ph

F

Me3Si

OMe

Br

Ph

F

S

Br

Me3Si

OMe

B

n-Pr

[Me4N]

Cl

B

Ph

[Me4N]

OMe

Br

S

Br

I

EtO2C

MOMO

MOMO

I

Br

F

1b

10 88

11 84

12 88

1a1c

cat Pd

NaOHcat Pd

cat Pd NaOH

Cs2CO3

Conclusions







Chapter 4

95




1H at 500 MHz and






13C) CD3CN ( = 194 for

1H =132 for

13C) and

BF3OEt2 ( = 000 for 11











11













Chapter 4

96

B

MOMO

[Me4N]

1a


202 (t J = 66 Hz 2H) 236-251 (m 2H) 304 (s 12H) 328 (s 3H) 346 (t J = 69

Hz 2H) 454 (s 2H) 678-685 (m 1H) 698-705 (m 2H) 734 (d J = 72 Hz 2H) 13

C NMR (CD3CN 75 MHz) = 210 267 (br) 271 275 282 297 324 349 551

561 681 928 968 1221 1269 1338 11



B

Ph

[Me4N]

1b

OMe


225 (t J = 72 Hz 2H) 234-249 (m 2H) 263 (t J = 72 Hz 2H) 303 (s 12H) 372

(s 3H) 663-669 (m 2H) 711-728 (m 7H) 13


272 275 324 349 381 554 560 1129 1266 1289 1298 1346 1434 1563 11


3572390 Found 3572383



B

MOMO

[Me4N]

+

MeO

Br

1 mol


toluene 50 degC

I

Br

MeO Br

NaOH

3

1a

MOMO

Chapter 4

97








MeO Br

3

MOMONOE

NOE




(t J = 66 Hz 2H) 376 (s 3H) 452 (s 2H) 667-675 (m 4H) 697-702 (m 2H)

709-736 (m 7H) 13

C NMR (75 MHz) = 255 298 356 5510 5514 676 964

1134 1196 1267 1282 1294 13046 13049 1323 1339 1376 1408 1420



spectroscopy

MeO

R

Br

4

R

R = OMOM




Chapter 4

98


2H) 325 (s 3H) 329 (s 3H) 331-341 (m 4H) 380 (s 3H) 451 (s 2H) 453 (s

2H) 662-678 (m 8H) 697-703 (m 2H) 706-738 (m 12H) 13

C NMR (150 MHz)

= 252 254 295 296 353 354 5502 5504 552 675 676 9629 9632 1131

1196 1265 1267 1281 1282 1285 12941 12942 1303 1304 1306 1324

1343 1377 1385 1390 1400 1413 1414 1418 1429 1435 1579 HRMS


7972818 Found

7972849

MeO

R

5

R

R = OMOM

R

Br




325 (s 3H) 327 (s 3H) 328 (s 3H) 330-342 (m 6H) 374 (s 3H) 450 (s 2H)

452 (s 2H) 454 (s 2H) 654-662 (m 4H) 666-678 (m 8H) 696-704 (m 4H)

712-737 (m 15H) 13

C NMR (75 MHz) = 254 256 296 297 298 3526 3534

355 551 675 676 963 1130 1196 1264 1267 1280 1281 1286 1294 1301

1302 1304 1306 1324 1344 1377 1384 1387 1392 1393 1398 1402 1409



10914437 Found 10914482

Chapter 4

99

MeO

R

6

R

R = OMOM

R

R

Br




330-341 (m 8H) 371 (s 3H) 448-454 (m 8H) 648-675 (m 16H) 695-703 (m

4H) 714-737 (m 20H) 13

C NMR (75 MHz) = 253 254 256 257 2969 2974

298 350 354 356 550 551 675 676 963 1131 1196 1264 1267 1279

1280 1281 1283 1288 1293 1294 1300 1301 1302 1305 1306 1323 1342

1377 1385 1387 1389 1391 1394 1396 1397 1401 1405 1409 1411 1413



13856057 Found 13856062

MeO

R

7

R

R = OMOM

R

R

R

Br




374 (s 3H) 447-452 (m 10 H) 649-679 (m 20 H) 690-695 (m 2H) 701-706 (m

2H) 710-736 (m 25H) 13

C NMR (75 MHz) = 2529 2535 256 257 2968

Chapter 4

100

2971 298 351 354 355 356 550 6746 6755 676 963 1131 1195 1264

1267 12795 1280 1281 1283 1285 1287 1293 12937 12944 1301 1302

1304 1306 1322 1343 1377 1384 1387 1389 1390 1391 1394 13976

13979 1401 1404 1408 1409 1412 1413 1416 1427 14318 14321 1434


16797677 Found 16797694

8

R

Br

R

Br

R = OMOM





(t J = 66 Hz 4H) 456 (s 4H) 668-673 (m 4H) 691 (s 4H) 710-721 (m 8H)

722-737 (m 6H) 13

C NMR (75 MHz) = 254 297 354 551 676 963 1198

1268 1282 1291 1293 1303 1323 1380 1400 1411 1417 1427 HRMS


8221905

9

R

R

R = OMOM

R

R

Br

Br



Chapter 4

101


6H) 330-340 (m 8H) 446 (s 4H) 453 (s 4H) 656-672 (m 12H) 688 (s 4H)

704-710 (m 4H) 714-718 (m 4H) 722-740 (m 16H) 13

C NMR (150 MHz) =

254 2962 2963 356 357 5501 5503 674 676 9629 9631 1197 1266

1268 1281 12818 12822 1290 1295 1296 1304 1308 1324 1379 1385

1394 1403 1405 1409 1416 1417 1427 1434 HRMS (MALDI-TOF-MS


14335057 Found 14335040

Ph

F

Me3Si

OMe

Br

10

NOE

NOE





3H) 676-686 (m 3H) 694-707 (m 6H) 709-728 (m 5H) 734 (d J = 84 Hz 2H) 13

C NMR (150 MHz) = -11 349 372 552 1135 1189 (d JC-F = 255 Hz)1202

(d JC-F = 92 Hz) 1258 1268 (d JC-F = 35 Hz) 1280 1283 1284 1300 1304 (d

JC-F = 159 Hz) 1326 1329 1332 (d JC-F = 45 Hz) 1339 1387 1417 1418 1430




Chapter 4

102

Ph

F

S

Br

Me3Si

OMe

11

MOMO




= 78 2H) 264-272 (m 2H) 282-289 (m 2H) 325 (s 3H) 328 (t J = 66 Hz 2H)

382 (s 3H) 448 (s 2H) 587 (d J = 39 Hz 1H) 660 (d J = 39 Hz 1H) 669-676

(m 2H) 684-696 (m 3H) 705-742 (m 16H) 13

C NMR (150 MHz) = -10 244

293 351 362 372 550 552 673 963 1127 1135 1161 (d JC-F = 225 Hz)

1244 (d JC-F = 32 Hz) 1258 1274 12827 12831 12837 12840 12856 12861

1295 1302 1307 (d JC-F = 155 Hz) 1324 1329 1330 (d JC-F = 45 Hz) 1333

1345 1385 1395 (d JC-F = 12 Hz) 1412 1416 (d JC-F = 80 Hz) 1419 1422



Ph

F

S

n-Pr

Me3Si

OMe

Cl

CO2Et

12MOMO




mmol) t1 10 h t2 12 h

Chapter 4

103


210-224 (m 4H) 264-272 (m 2H) 279-287 (m 2H) 323-333 (m 5H) 373 (s


1H) 666-672 (m 2H) 679-694 (m 5H) 703-737 (m 20H) 773 (d J = 84 Hz

2H) 13

C NMR (150 MHz) = -11 141 143 225 244 293 350 359 370 385

550 551 607 674 963 1134 1159 (d JC-F = 224 Hz) 1243 (d JC-F = 29 Hz)

1258 1269 1271 12808 12811 12815 12820 12823 12838 12844 1290

1293 1300 1301 (d JC-F = 158 Hz) 1302 1307 1323 (d JC-F = 47 Hz) 13258

13261 1328 1336 1344 1356 1379 1382 1390 (d JC-F = 12 Hz) 1409 14190

14191 14216 (d JC-F = 80 Hz) 14219 14222 1438 1446 1476 1583 1600 (d

JC-F = 2448 Hz) 1664 IR (KBr) = 2955 1717 1509 1273 1248 1111 837 cm-1


11294440

Found 11294465

Chapter 4

104




Chem 1999 201 163




897















2404


2006 128 1828



Chapter 5

105

Chapter 5




Abstract






Chapter 5

106

Introduction





moiety1b


























Chapter 5

107


B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

OHMe

Ph

1a

3a 85

MeO

OMe

2a

B

Ph

Me

O

I

+

1 mol


toluene 50 degC 1 h

1b

OMe

2a

OHMe

Ph

OMe

3b 88

[Me4N]

[Me4N]




Oxidative









Chapter 5

108


O

I

O

PdI

Pd(0)

B

1a

C

Pd(0)3a

Ar = p-MeOC6H4-

Me Me

OMe

Ar

Ph

B

D

A

Pd

O

ArB

Me

Ph

B

O

ArPh

Me

Me4NI

2a







Chapter 5

109


R3

O

I

B

R2

R1

+1 mol Pd

toluene50 degC 1 h

OHR3

R1

R2

OHMe

Ph

S

OHMe

OMe

OHPh

Ph

OMe

3f 72

3h 763j 80

3g 84

3d 82

3c 83

OHMe

Ph

CF3

1 2 3

OHH

Ph

OMe

OHPh

Ph

OMe

O

O

OHPh

3e 92

F

OMe

OHPh

Ph

OMe

F3C

3i 62

R4R4

MeO

[Me4N]










Chapter 5

110

OHMe

t-Bu

S

3k 89

B +1 mol Pd

toluene

50 degC 1 h

2a

t-Bu

S

(1)

1c

[Me4N]

OHMe

n-Bu

Me

3l 80

B

n-Bu

+1 mol Pd

toluene50 degC 1 h

2a

Me

(2)

1d

[Me4N]










n-Hex

13 equiv

Ph

Li

065 equiv

(H-9-BBN) 2


1 mol Pd

toluene 50 degC 1 h

10 equiv 2aOH

Me

n-Oct

11 equiv

3m 91 (based on 2a)

B

n-Oct

PhLi

Ph




Chapter 5

111


in 59 yield11


OHH

Ph

OMe

MnO2

DCM rt

Ph

OMe

O

NH2NH2 KOHPh

OMe

4 96 5 59

3n 74

(CH2OH)2 150 C

1a +

CHO

I2b

1 mol Pd

Conclusions




Chapter 5

112



and 13


B at 128 MHz)



13C) CD3CN (δ = 194 for

1H δ = 132 for


11B) IR






(Merck)





and alkynylborate14




Li

BPh

+

B

Ph

1a


2) Me4NCl MeOH

[Me4N]

MeO

MeO










Chapter 5

113

B

Ph

1a

[Me4N]

MeO


(m 2H) 296 (s 12H) 372 (s 3H) 668-675 (m 2H) 685-691 (m 1H) 700-712 (m

4H) 743 (d J = 64 Hz 2H) 13

C NMR (CD3CN) δ = 256-272 (m) 270 274 322

350 557 560 955 1145 1227 (2C) 1273 1324 1341 1578 The boron-bound


11B NMR


3292079

B

Ph

1b

[Me4N]

OMe


(m 2H) 295 (s 12H) 374 (s 3H) 666-675 (m 2H) 702-718 (m 5H) 733 (d J =

84 Hz 2H) 13

C NMR (CD3CN) δ = 254-274 (m) 270 273 321 350 554 560





B

nBu

1d

[Me4N]

Me


(m 4H) 136-157 (m 6H) 170-196 (m 4H) 220-234 (m 5H) 304 (s 12H)

697-701 (m 2H) 704-709 (m 2H) 13

C NMR (CD3CN) δ = 152 212 270

271-290 (m) 282 288 318 324 357 561 1279 1296 1314 1344 The

Chapter 5

114




[M-(NMe4)]- 2932446 Found 2932454

B

Ph

1e

[Me4N]

F3C


(m 2H) 292 (s 12H) 690-696 (m 1H) 710-718 (m 2H) 728 (dd J = 88 08 Hz

2H) 744-752 (m 4H) 13

C NMR (CD3CN) δ = 252-270 (m) 269 273 321 351






B

Ph

1f

[Me4N]

S



48 32 Hz 1H) 703-719 (m 6H) 13

C NMR (CD3CN) δ = 266 272 270-286 (m)

323 348 560 962 1231 1256 1266 1274 1290 1300 1314 The boron-bound

sp2 and sp


11B NMR


- 3051541 Found

3051541

Chapter 5

115


(H-9BBN) 2

H tBu

THF 0 degC

THF -78 degC to rt

2) Me4NCl MeOH

Li

1)S

B

1c

[Me4N]

S

tBu














B

1c

[Me4N]

S

tBu


4H) 222-235 (m 2H) 306 (s 12H) 552 (d J = 172 Hz 1H) 591 (d J = 176 Hz


Hz 1H) 13

C NMR (CD3CN) δ = 273 276 278-296 (m) 311 327 341 352 561





Chapter 5

116












OHMe

3aOMe

NOE

no NOE

IR (ATR) 3315 1508 1248 752 694 cm-1

1H NMR δ = 159 (s 3H) 204 (bs 1H)

382 (s 3H) 684-690 (m 2H) 721-730 (m 8H) 742-748 (m 2H) 751-755 (m

1H) 13

C NMR δ = 239 552 832 1139 1208 1218 1265 1268 1272 1280


C23H21O2 [M+H]+ 3291536 Found 3291556

OHMe

OMe

3b

NOE

no NOE

IR (ATR) 3319 1508 1248 760 702 cm-1

1H NMR δ = 160 (s 3H) 208 (s 1H)

378 (s 3H) 674-680 (m 2H) 718-723(m 1H) 724-744 (m 9H) 750-755 (m

1H) 13

C NMR δ = 241 551 833 1134 1205 1218 1263 1270 1274 1284


Chapter 5

117

C23H20O2Cl [M+Cl]- 3631146 Found 3631148

OHMe

Ph

3cCF3

IR (ATR) 3298 1319 1121 750 696 cm-1

1H NMR δ = 160 (s 3H) 210 (bs 1H)

716-722 (m 1H) 723-732 (m 5H) 737-747 (m 4H) 752-764 (m 3H) 13

C NMR

δ = 240 833 1205 1221 1241 (q JC-F = 2701 Hz) 1255 (q JC-F = 37 Hz) 1269

1277 1282 1286 1293 1295 (q JC-F = 322 Hz) 1296 1341 1373 1385 1414


- 3651159 Found 3651159

OHMe

Ph

3d

S

IR (ATR) 3319 1350 1088 752 694 cm-1

1H NMR δ = 177 (s 3H) 209 (bs 1H)

696-702 (m 2H) 718 (dd J = 52 Hz 12Hz 1H) 723-730 (m 2H) 735-740 (m

3H) 742-752 (m 3H) 753-758 (m 1H) 13

C NMR δ = 254 833 1207 1216

1259 1265 1266 1275 1282 1287 1290 1294 1347 1360 1374 1410 1426


+ 3050995 Found 3050992

OHMe

OMe

3e

IR (ATR) 3310 1508 1244 1034 758 cm-1

1H NMR δ = 144 (s 3H) 158-202 (m


5H) 747 (d J = 68 Hz 1H) 13

C NMR δ = 238 266 267 305 311 382 552

822 1136 1211 1219 1257 12789 12793 1304 1406 1409 1467 1499


+ 3382115 Found 3382104

Chapter 5

118

OHH

Ph

3fOMe

MeO

IR (ATR) 3472 1601 1508 1244 704 cm-1

1H NMR δ = 174 (d J = 88 Hz 1H)


= 80 Hz 24 Hz 1H) 692-697 (m 2H) 718-730 (m 5H) 732-736 (m 2H) 753 (d

J = 84 Hz 1H) 13

C NMR δ = 552 555 766 1072 1109 1143 1244 1267 1272

1283 1292 1303 1342 1363 1390 1445 1457 1592 1606 HRMS (ESI+)


OHPh

Ph

3gOMe

IR (ATR) 3422 1508 1244 1028 746 698 cm-1

1H NMR δ = 248 (s 1H) 385 (s

3H) 695 (d J = 88 Hz 2H) 704-714 (m 5H) 715-732 (m 7H) 736-740 (m 2H)

755 (d J = 88 Hz 2H) 13

C NMR δ = 552 868 1141 1210 1231 1250 1268

12698 12702 1271 1278 12836 12844 1294 1304 1340 1402 1417 1427


+ 3911693 Found

3911718

OHPh

Ph

3hOMe

O

O

IR (ATR) 3362 1470 1244 1034 696 cm-1

1H NMR δ = 239 (s 1H) 385 (s 3H)

591 (dd J = 164 16 Hz 2H) 673 (d J = 44 Hz 2H) 690-696 (m 2H) 702-708

(m 5H) 720-736 (m 5H) 749-754 (m 2H) 13

C NMR δ = 552 863 1012 1024

Chapter 5

119

1049 1142 1249 12690 12692 1270 1278 1285 1292 1304 1340 1367


+

4341518 Found 4341505

OHPh

Ph

3iOMe

F3C

IR (ATR) 3545 1508 1321 1115 696 cm-1

1H NMR δ = 249 (s 1H) 387 (s 3H)

694-700 (m 2H) 704-715 (m 5H) 723-738 (m 6H) 742-755 (m 4H) 13

C NMR

δ = 553 866 1145 1177 (q JC-F = 37 Hz) 1233 1241 (q JC-F = 36 Hz) 1242 (q

JC-F = 2702 Hz) 1249 1260 1275 1276 1280 1287 1295 1304 1308 (q JC-F =


C29H21F3O2Cl [M+Cl]- 4931177 Found 4931192

OHPh

3j

F

OMe

IR (ATR) 3356 1242 1028 741 696 cm-1

1H NMR δ = 164-178 (m 2H) 183-208


4H) 719-737 (m 6H) 13

C NMR δ = 2675 2681 308 310 383 551 862 1114


1268 1271 1283 1303 1371 (d JC-F = 29 Hz) 1410 1418 (d JC-F = 15 Hz)



+ 4001839 Found 4001835

OHMe

S

tBu

3k

Chapter 5

120

IR (ATR) 3298 1358 1078 756 689 cm-1

1H NMR δ = 111 (s 9H) 168 (s 3H)

188 (s 1H) 640 (d J = 164 Hz 1H) 656 (d J = 164 Hz 1H) 718-730 (m 4H)

739-751 (m 3H) 13

C NMR δ = 257 295 340 822 1169 1204 1215 1242

1255 1262 1283 1285 1324 1346 1415 1452 1462 1506 HRMS (ESI+)


OHMe

nBu

OMe3l

IR (ATR) 3335 1508 1084 918 758 cm-1

1H NMR δ = 085 (t J = 72 Hz 3H) 130

(tt J = 72 72 Hz 2H) 141-167 (m 6H) 229-250 (m 5H) 702-706 (m 1H)

716-728 (m 6H) 744-748 (m 1H) 13

C NMR δ = 138 213 232 237 252 314

829 1198 1215 1256 1282 1286 1291 1318 1370 1374 1430 1492 1496


+ 2931900 Found 2931890



nHex

(H-9BBN) 2


Li

Ph

B

nOct

Li

Ph

Me

O

I


toluene 50 degC 1 h

H2O2 aq

NaOH aq

OHMe

nOct

Ph3m

MeOH




Chapter 5

121













yield)

OHMe

nOct

Ph3m

IR (ATR) 3335 1456 1078 752 698 cm-1

1H NMR δ = 096 (t J = 68 Hz 3H)

129-156 (m 15H) 160 (s 1H) 208-227 (m 2H) 274-281 (m 2H) 287-294 (m

2H) 719-728 (m 5H) 729-736 (m 3H) 742 (d J = 72 Hz 1H) 13

C NMR δ = 141

226 234 247 277 293 294 295 304 319 345 825 1186 1213 1252 1260


[M]+ 3622610 Found 3622619

OHH

Ph

OMe

3n

IR (ATR) 3354 1508 1246 764 692 cm-1

1H NMR δ = 185 (bs 1H) 386 (s 3H)

567 (s 1H) 692-697 (m 2H) 718-738 (m 10H) 763-766 (m 1H) 13

C NMR δ =

552 773 1143 1206 1237 1263 1268 1272 1283 1287 1292 1303 1342


- 3131234

Found 3131237

Chapter 5

122

The 1H


15


OHH

Ph

OMe

3n

MnO2

DCM rt

Ph

OMe

4

O







The 1H


16

Ph

OMe

4

O

(CH 2OH)2

NH2NH2

KOH Ph

OMe

5








The 1H


5

Chapter 5

123






1395ndash1411



17638ndash17640





3201ndash3222



















Chapter 5

124












3283ndash3292









74








Chem 1989 54 1485ndash1491



2006 128 1828

Chapter 5

125



4781-4787


Chem 1989 54 1485

Chapter 5

126

127

List of Publication

Chapter 1



Angew Chem Int Ed 2012 51 11750-11752

Chapter 2


Benzosultams


J Am Chem Soc 2013 135 19103-19106

Chapter 3





Org Lett 2009 11 5434-5437

Chapter 4


Units


Org Lett 2010 12 3179-3181

Chapter 5




Eur J Org Chem 2013 1421-1424

Other Publication




Chem Lett 2013 42 1076

title exploration of new reactivities of azetidinols and

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