programme - nus chemistry · highly enantioselective organic reactions promoted by primary amino...

1st Japan-Singapore Bilateral Symposium on Catalysis Singapore, 7th and 8th January 2008

1

PROGRAMME


2

Monday, 7 January 2008 __________________________________________________________________________________________ SYMPOSIUM SESSION 1 Time: 09:00 – 14:00 HRS Venue: Lecture Theatre 31, Blk S16, Level 3, Faculty of Science, NUS Chairperson: Yixin Lu, National University of Singapore 09:00 – 09:05 HRS Introductory remarks Yixin Lu (Symposium co-chair, NUS) 09:05 – 09:15 HRS Opening address Andrew T. S. Wee (Dean, Faculty of Science, NUS) 09:15 – 09:25 HRS Welcoming address T. S. Andy Hor (Head, Department of Chemistry, NUS) 09:25 – 09:55 HRS Catalytic Electron Transfer Reactions

Koichi Narasaka, Nanyang Technological University 09:55 – 10:25 HRS Carbon-Carbon Bond Forming Reactions via Cleavage of (sp3)C-F or

(sp3)C-Cl Bonds Nobuaki Kambe, Osaka University

10:25 – 10:55 HRS Adsorption-Induced Desorption of Benzene on Si(111)-7×7 by Substrate-Mediated Electronic Interactions Guo Qin Xu, National University of Singapore

10:55 – 11:20 HRS Tea/Coffee Break (Refreshments provided) 11:20 – 11:50 HRS Synthetic Utility of Diazoacetates with Chiral Metal and Non-Metal

Catalysts Keiji Maruoka, Kyoto University

11:50 – 12:20 HRS Aliphatic Polyketones from Palladium-Catalyzed Olefin-CO Copolymerization P K Wong, Institute of Chemical and Engineering Science

12:20 – 14:00 HRS Lunch Break (Buffet lunch provided) SYMPOSIUM SESSION 2 Time: 14:00 – 18:00 HRS Venue: Lecture Theatre 31, Blk S16, Level 3, Faculty of Science Chairperson: P K Wong, Institute of Chemical and Engineering Sciences 14:00 – 14:30 HRS Organotransition Metal Catalysis: Designing Active Catalysts at the

Molecular Root of Metal and Ligand Manipulations T. S. Andy Hor, National University of Singapore


3

14:30 – 15:00 HRS Development of N-methylimidazole (NMI)-catalyzed acylations directed towards process chemistry Yoo Tanabe, Kansei Gakuin University

15:00 – 15:30 HRS Catalytic Asymmetric Carbon-Carbon Bond Forming Reactions

Catalyzed by Chiral Schiff Base-Metal Complexes Masahiko Hayashi, Kobe University

15:30 – 15:50 HRS Tea/Coffee Break (Refreshments provided) 15:50 – 16:20 HRS The Asymmetric Aldol Reaction “In the Presence of Water” or “In

Water” Yujiro Hayashi, Science University of Tokyo

16:20 – 16:50 HRS Regio- and Stereoselective Formation of Oxetanes using Radical Ion Pairs and Triplet 1,4-Diradicals Manabu Abe, Hiroshima University

16:50 – 17:20 HRS Nitrogen-Directed Regioselective Arylation of Aromatic C-H Bond

catalyzed by Ruthenium Complexes Shuichi Oi, Tohoku University

17:20 – 17:50 HRS Pd-catalyzed Asymmetric Synthesis of Axially Chiral Allenes and their

Application in Organic Transformations Masamichi Ogasawara, Hokkaido University

Tuesday, 8 January 2008 __________________________________________________________________________________________ SYMPOSIUM SESSION 3 Time: 09:00 – 14:00 HRS Venue: Lecture Theatre 31, Blk S16, Level 3, Faculty of Science Chairperson: Koichi Narasaka, Nanyang Technological University 09:00 - 09:30 HRS Chiral Diene Ligands For Transition Metal-Catalyzed Asymmetric

Reactions Tamio Hayashi, Kyoto University

09:30 – 10:00 HRS Organic Superbase catalyzed Molecular Transformation

Yoshinori Kondo, Tohoku University 10:00 – 10:30 HRS Chiral Amine N-Oxides and Phosphine Oxides as Organocatalysts in

Enantioselective Reactions Makoto Nakajima, Kumamoto University

10:30 – 10:50 HRS Tea/Coffee Break (Refreshments provided)


4

10:50 – 11:20 HRS Iridium-Catalyzed Aromatic C-H Borylation Tatsuo Ishiyama, Hokkaido University

11:20 – 11:50 HRS Chiral Guanidine Catalysed Enantioselective Reactions

Choon Hong Tan, National University of Singapore 11:50 – 14:00 HRS Lunch Break SYMPOSIUM SESSION 4 Time: 14:00 – 18:00 HRS Venue: Lecture Theatre 31, Blk S16, Level 3, Faculty of Science Chairperson: Keiji Maruoka, Kyoto University 14:00 – 14:30 HRS Enantioselective Petasis-Type Reaction with Multi-Functional

Thiourea Yoshiji Takemoto, Kyoto University

14:30 – 15:00 HRS Molecular Design and Synthetic Applications of Chiral Tetraamino- phosphonium Salts Takashi Ooi, Nagoya University

15:00 – 15:30 HRS Development of Asymmetric Reactions based on Chiral Multimetallic Systems Yutaka Ukaji, Kanazawa University

15:30 – 15:50 HRS Tea/Coffee Break (Refreshments provided) 15:50 – 16:20 HRS Stereoselective Cascade Hydrogenation of 4-Tert-Butylphenol over

Bifunctional Zr-Zeolite Beta-Supported Metal Catalysts Gaik Khuan Chuah, National University of Singapore

16:20 – 16:50 HRS Palladium-Catalyzed CH Coupling Reactions of Heteroaromatic

Compounds Atsunori Mori, Kobe University

16:50 – 17:20 HRS Development of Enantioselective Fluoromethylations

Norio Shibata, Nagoya Institute of Technology 17:20 – 17:50 HRS Highly Enantioselective Organic Reactions promoted by Primary

Amino Acid-Derived Organocatalysts Yixin Lu, National University of Singapore

17:50 – 18:00 HRS Concluding remarks Keiji Maruoka (Symposium co-chair, Kyoto University)


5

ABSTRACTS


6

REGIO- AND STEREOSELECTIVE FORMATION OF OXETANES

USING RADICAL ION PAIRS AND TRIPLET 1,4-DIRADICALS Manabu ABE and Midori TERAZAWA

Department of Chemistry, Graduate School of Science, Hiroshima University,

1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan

[email protected]

ABSTRACT

Oxetanes possess a highly strain energy of 26 kcal/mol. Like epoxides, the ring-opening reaction accompanying bond-formation reactions would be very useful for synthetic purposes. Furthermore, since the oxetane ring is known to be an important part of biologically active compounds, such as Merrilactone A, Thromboxane A2, and Oxetanocin, the exploring of the efficient and selective methods for constructing the strained structure is challenging subject. Thus, the synthetic demand of the strained structure increases. The photochemical [2+2] cycloaddition of carbonyl compounds with alkenes, so-called the Paternò-Büchi (PB) Reaction, is a versatile method for synthesizing the oxetane ring systems. The reaction involves energetically high species, i.e. excited state of carbonyl compounds, thus, it seems to be quite difficult to control the region- and stereoselectivity of oxetanes formed in the photochemical process. However, our recent studies in this area have provided some methods to control the selectivities. In this presentation, our recent approach to construct the oxetane ring by using the photochemical reaction in the presence of photo-catalyst is summarized.

GRAPHIC ILLUSTRATION

O

oxetane

O

O

O

HO

O

H

HO

COOH

OH

ON

HO OHMerrilactone A Thromboxane A2 Oxetanocin

N

N

N

NH2

O +

The Paterno-Buechi Reaction

hν

BIOGRAPHY

Professor Abe, Manabu was born in Sakai City, Osaka Prefecture, Japan, in 1966. He received his Ph.D. from the Kyoto Institute of Technology (Professor Akira Oku), studying the oxidative ring-opening reaction of cyclopropanone acetals and its application to organic synthesis. In 1995, he became an assistant professor at Osaka University. In 2007, he became a Full Professor at the Department of Chemistry, Graduate School of Science, Hiroshima University. His research focuses on Reactive Intermediates Chemistry, especially on singlet as well as triplet diradicals.


7

STEREOSELECTIVE CASCADE HYDROGENATION OF 4-TERT-

BUTYLPHENOL OVER BIFUNCTIONAL ZR-ZEOLITE BETA-

SUPPORTED METAL CATALYSTS Yuntong NIE, Stephan JAENICKE, Herman van BEKKUMa and Gaik-Khuan CHUAH

Department of Chemistry, National University of Singapore, 3 Science Drive 3,

Singapore 117543 aCeramic Membrane Centre "The Pore" , TU Delft, Julianalaan 136, 2686 BL Delft, The

Netherlands

[email protected]

ABSTRACT

The hydrogenation of 4-tert-butylphenol was investigated over Zr-beta-supported rhodium catalysts. By designing a suitable bifunctional catalyst, the intermediate, 4-tert-butylcyclohexanone, formed by metal-catalysed hydrogenation of 4-tert-butylphenol, could be reduced via the highly stereoselective Meerwein-Ponndorf-Verley reduction over zirconium Lewis acid sites. Hence, in the presence of 2-propanol as solvent and MPV reductant, a high stereoselectivity to cis-4-tert-butylcyclohexanol was observed. Over 0.5 % Rh/Zr-beta, 4-tert-butylphenol was hydrogenated to the cis-alcohol with 95 % stereoselectivity. A higher metal loading or the use of solvents such as hexane or tert-butanol led to a lower stereoselectivity as metal-catalysed hydrogenation predominated. A two-step cascade reaction mechanism is proposed for the conversion of 4-alkylphenols to cis-4-alkylcyclohexanols..

GRAPHIC ILLUSTRATION OH

R

OH

R

O

R

OH

R

OH

R

2H2

enolads

ketoneR = tert-butyl or methyl trans-alcohol cis-alcohol

Rh+

iPrOH

Zr

Scheme 1 Designed cascade reaction for the conversion of 4-alkylphenols to cis-4-alkylcyclohexanols.

BIOGRAPHY Professor Chuah, Gaik Khuan received her B.Sc. in 1982 and her M.Sc. in 1983, both from National University of Singapore, and subsequently her Ph.D. from Texas A&M University in 1987. Currently, she is an Associate Professor in National University of Singapore. Her research interests focus on heterogeneous catalysis, synthesis of zeolites and mesoporous materials and green chemistry and applications of catalysis in areas of pollution abatement.


8

CATALYTIC ASYMMETRIC CARBON—CARBON BOND FORMING

REACTIONS CATALYZED BY CHIRAL SCHIFF BASE—METAL

COMPLEXES Masahiko HAYASHI

Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe 657-

8501, Japan

[email protected]

ABSTRACT

Catalytic asymmetric carbon—carbon bond forming reactions catalyzed by chiral Schiff base—metal complexes including 1) enantioselective alkylation using dialkylzinc of aldehydes (up to 97% ee), 2) enatioselective silylcyantion of aldehydes (up to 96% ee), 3) enantioselective addition of diketene to aldehydes (up to 92% ee) will be disclosed. Especially, in the case of the use of chiral Schiff bases containing oxazoline moieties derived from L-serine, the reaction of diketene with aldehydes afforded both enantiomers of 5-hydroxy-ketoesters were obtained at the same level of high enantioselectivity (up to 93% ee). New approach for complete reversal of enantioselection will be discussed.


R1CHO + R22Zn

1 mol% chiral Schiff base 1

R1 R2

OH

hexane, 0 °C97% ee

RCHO + Me3SiCN

20 mol% Ti(O-i-Pr)4__

chiral Schiff base 2

R CN

OSiMe3

CH2Cl2, -78 °C96% ee

RCHO +

100 mol% Ti(O-i-Pr)4__

20 mol% chiral Schiff base 3

R

OH

CH2Cl2, -40 °C92% ee

OO

CO2-i-Pr

O

OHN

OH

Ph

OHN

OH

Ph

OHN

OH

chiral Schiff base

1: 2: 3:

BIOGRAPHY

Professor Hayashi, Masahiko was born in Nagoya in 1960. He received his bachelor’s, masters’ and Ph. D degree from Nagoya University. After completion of his Ph. D work under the direction of Prof. Ryoji Noyori in 1988, he worked as a research associate in the Department of Chemistry Faculty of Science of Yamaguchi University in the group of Prof. Nobuki. Then he became Associate Professor in 1993. From 1995 to 1997 he was a visiting professor at the Max-Planck-Institut für Kohlenforschung. In 2001, He became a full professor of the Department of Chemistry, Graduate School of Science of Kobe University.


9

CHIRAL DIENE LIGANDS FOR TRANSITION METAL-CATALYZED

ASYMMETRIC REACTIONS Tamio HAYASHI

Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo

Kyoto 606-8502, Japan

[email protected]

ABSTRACT

One of the significant subjects for developing catalytic asymmetric reactions is the design and preparation of a chiral ligand which will fit in with a given reaction efficiently in catalytic activity and enantioselectivity. As conceptually new chiral ligands, we have recently prepared enantiomerically pure C2-symmetric chiral dienes, whose basic diene skeleton is bicyclo[2.2.1]hepta-2,5-diene (nbd*), bicyclo[2.2.2]octa-2,5-diene (bod*), or bicyclo[3.3.1]nona-2,6-diene (bnd*). They have two alkyl or aryl substituents on the double bonds, one on each of the two double bonds. The chiral diene ligands were found to be better than the conventional chiral ligands represented by chiral bisphosphines in terms of catalytic activity and enantioselectivity in some of the catalytic asymmetric reactions. Their high performance was observed in rhodium-catalyzed asymmetric addition of organoboron reagents to α,β-unsaturated ketones, N-sulfonylimines, and so on.


RhCl

RhCl

RhCl

RhCl

PhPh

RhCl

RhCl

(R,R )-Ph-bod* (R,R )-Ph-bnd*(R,R )-Bn-nbd*

BIOGRAPHY Professor Hayashi, Tamio was born in Gifu, Japan, in 1948. He graduated from Kyoto University in 1970. He received his Ph.D. degree in 1975 from Kyoto University. Then he was appointed as a Research Associate in Faculty of Engineering, Kyoto University, before joining Colorado State University as a postdoctoral fellow during 1976-1977. He was promoted to Full Professor in 1989 in the Catalysis Research Center, Hokkaido University. Since 1994, he has been Full Professor in the Faculty of Science, Kyoto University. Awards won include the Award for Young Chemists of the Society of Synthetic Organic Chemistry, Japan (1983), the IBM (Japan) Prize (1991), The Chemical Society of Japan Award (2003), Thomson Scientific Research Front Award (2004), Molecular Chirality Award (2005), Ryoji Noyori Prize (2008), and Arthur C. Cope Scholor Awards (2008). He has been interested in the development of new reactions catalyzed by transition metal complexes, especially in catalytic asymmetric reactions.


10

THE ASYMMETRIC ALDOL REACTION “IN THE PRESENCE OF

WATER” OR “IN WATER” Yujiro HAYASHI

Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science,

Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan

[email protected]

ABSTRACT

Achieving a catalytic asymmetric reaction under environmentally benign conditions is a very important topic in current organic synthesis. Proline has been widely employed as a safe, inexpensive, asymmetric organocatalysis in the direct aldol reaction, and most of these reactions have been performed in polar organic solvents. We have found that highly enantioselective aldol reaction can proceed in the presence of highly lipophilic siloxyproline as an organocatalyst in aldehyde-ketone aldol reaction. In the aldol reaction of aldehyde-aldehyde, surfactant-proline-combined catalyst was found to be effective. Moreover, during our work to develop the asymmetric reactions in the presence of water, we have found that wet and dry proline catalyze the aldol reaction in a highly diastereo- and enantioselective manner in some cases. In the aldehyde-ketone aldol reaction, wet conditions are suitable, while in the aldehyde-aldehyde aldol reaction, dry conditions give good results. In some cases, we can isolate and purify the aldols without using any organic solvent.


H2O

Distillation

NH

CO2H

TBDPSO

10 g (70%)anti:syn=10:1>99%ee

OH

O

OH O

7.4 g (1 eq) 13.7 g (2 eq)

259 mg (1 mol%)

2.5 g silica gel

Filtration(60 ml AcOEt) 3.8 mL (3 equiv.)

2 days

BIOGRAPHY Professor Hayashi, Yujiro was born in 1962, and received his BSc in 1984 and MSc in 1986 from The University of Tokyo under the guidance of Professor Teruaki Mukaiyama. He received a Ph. D. degree from the same university under the supervision of Professor Koichi Narasaka. He was appointed as an assistant professor at The University of Tokyo in 1987. He moved to Tokyo University of Science as an associate professor in 1998 and was promoted to full professor in 2006. He undertook postdoctoral study at Harvard University (Prof. E. J. Corey) from 1994 to 1996. In 1998 he was honored with an Incentive Award in Synthetic Organic Chemistry, Japan.


11

ORGANOTRANSITION METAL CATALYSIS: DESIGNING ACTIVE

CATALYSTS AT THE MOLECULAR ROOT OF METAL AND

LIGAND MANIPULATIONS Zhiqiang WENG, Shihui TEO, Parag GUNARI and T. S. Andy HOR

Department of Chemistry, National University of Singapore, Kent Ridge, Singapore 117543

[email protected]

ABSTRACT

The future of organotransition metal catalysis lies very much in challenging molecular transformations that are scientifically exciting, technologically valuable, and economically viable. These formidable challenges have also presented an array of opportunities in the field of catalysis. We take a fundamental approach in believing that our best hope lies in clever catalyst design at its molecular roots, i.e. metal, ligands, and their synergistic relationship.1 In recent years, we have launched a series of projects in catalyst design using unsaturated metals, hemilabile and labile ligands. The model processes range from dehalogenative hydrogenation, reductive coupling, C-C hetero-coupling and very recently, to environmentally benign oxidation. We herein present some of our recent achievements, challenges and generally our thoughts. References (1) Z. Q. Weng, S. Teo and T. S. A. Hor, Acc. Chem. Res., 2007, 40, 676.


BIOGRAPHY

Professor Hor, Tzi Sum Andy [D.Sc.(Lond), D.Phil.(Oxford), B.Sc.(Hon) (Imperial College), Postdoc(Yale)] is Professor and Head of Chemistry in the National University of Singapore (NUS) http://www.chemistry.nus.edu.sg/ and President of Singapore National Institute of Chemistry (SNIC) http://snic.org.sg/ index.php He has published over 200 international papers in heterometallic syntheses and homogeneous catalysis with about 2,900 citations. He was conferred various fellowship such as Humboldt, Wilsmour, Anthony Mason, Frances Lion Memorial, Jackson Memorial and professorship at Sydney, Melbourne, Münster, Strasbourg, etc. Currently he is a member of the international advisory panel of Chem. Asian J.(VCH/Wiley) and Inorg. Chim. Acta.(Elsevier) He has delivered numerous invited/keynote lectures in different conferences and symposia, and will chair the 41st International Coordination Chemistry Conference (ICCC) in Singapore in 2014.

http://www.chemistry.nus.edu.sg/

http://snic.org.sg/%20index.php

http://snic.org.sg/%20index.php


12

IRIDIUM-CATALYZED AROMATIC C-H BORYLATION Tatsuo ISHIYAMA and Norio MIYAURA

Division of Chemical Process Engineering, Graduate School of Engineering,

Hokkaido University, Sapporo 060-8628, Japan

[email protected]

ABSTRACT

Aryl- and heteroarylboron derivatives are important class of compounds that have been applied to various fields of chemistry. Traditional methods for their synthesis are based on the reactions of trialkylborates with aryl- and heteroarylmagnesium or -lithium reagents. Pd-catalyzed cross-coupling of aryl and heteroaryl halides with tetra(alkoxo)diborons or di(alkoxo)boranes is a milder variant where the preparation of magnesium and lithium reagents is avoided. Alternatively, the catalytic C-H borylation of arenes and heteroarenes is highly attractive as a halide-free process for the synthesis of aryl- and heteroarylboron compounds. Among the catalyts developed to date, the combination of [Ir(OMe)(COD)]2 and dtbpy (4,4’-di-tert-butyl-2,2’-bipyridine) reported by us exhibits high activity, which allows the formation of aryl- and heteroarylboronates in high yields at room temperature from an equimolar eqivalent of bis(pinacolato)diboron or pinacolborane and arenes or heteroarenes.


BO

OH ArH B

O

OAr+

1/2[Ir(OMe)(COD)]2-dtbpy

hexane/r.t.(1.1 eq.) (1.0 eq.)

BO

OB

O

OArH B

O

OAr+

1/2[Ir(OMe)(COD)]2-dtbpy

hexane/r.t.2 2

(1.0 eq.) (2.0 eq.)

BIOGRAPHY Professor Ishimaya, Tatsuo was born in 1964 in Yamagata, Japan. He received his degrees of Bachelor in 1986, Masters in 1988 and Ph.D. in 1991 (under Prof. A. Suzuki and Prof. N. Miyaura), from Hokkaido University. He thereafter joined Hokkaido University as an Assistant Professor in 1991 and has been an Associate Professor in the university since 1994. He was also a postdoctoral fellow in Yale University. (New Haven, Prof. J. F. Hartwig, 1999-2000). His research interests are in the fields of organic chemistry and organometallic chemistry.


13

CARBON-CARBON BOND FORMING REACTIONS VIA

CLEAVAGE OF (sp3)C-F OR (sp3)C-Cl BONDS Nobuaki KAMBE and Jun TERAO

Department of Applied Chemistry, Graduate School of Engineering, Osaka University

Suita, Osaka 565-0871, Japan

[email protected]

ABSTRACT

Carbon-fluoride bond is a strongest single bond in organic compounds. Especially alkyl fluorides have been recognized as stable and inert compounds towards a variety of chemical reagents and their synthetic application is very much limited. Alkyl chlorides, as well as alkyl fluorides, have not frequently been employed as reactants in transition metal chemistry. These are in large contrast to the chemistry of unsaturated compounds, where a considerable number of transformations involving (sp2)C-F or (sp2)C-Cl bond scission have been reported. We have found that cross-coupling reaction of alkyl fluorides and chlorides with Grignard reagents proceeds efficiently in the presence of Ni or Cu catalyst with cleavage of (sp3)C-F or (sp3)C-Cl bonds (Eq. 1). Ni also catalyzes alkylative dimerization of vinyl Grignard reagents with alkyl fluorides (Eq. 2). Corresponding alkyl chlorides, bromides and iodides do not give satisfactory results in this reaction. Alkylation of styrenes with alkyl fluorides takes place by the use of a Zr catalyst. We have also examined direct reaction of alkyl fluorides with aluminum and magnesium reagents and found that reaction proceeds with inversion of stereochemistry with respect to the α-carbon of primary alkyl fluorides, i. e., in a SN2 fashion.


BIOGRAPHY Professor Kambe, Nobuaki was born in Hyogo, Japan, in 1953. He received Ph.D. degree from Osaka University in and joined Department of Applied Chemistry, Faculty of Engineering, Osaka University in 1981 as an Assistant Professor. From 1982 to 1984, he stayed at Colorado State University as a postdoctoral fellow for Professor L.S. Hegedus. He was promoted to Associate Professor of Osaka University in 1989 and to Professor in 1999. He received the Chemical Society of Japan Award for Young Chemists in 1988 and the Japan Petroleum Institute Award for Encouragement of Research and Development in 1993. His research interests are in the areas of synthetic organic chemistry, organometallic chemistry, and physical organic chemistry.

Alkyl-X R-MgBr+ Alkyl RNiX2

or CuX2(1)

MgXNiX2(PPh3) MgX

Alkyl+ (2)Alkyl-F


14

ORGANIC SUPERBASE CATALYZED MOLECULAR

TRANSFORMATION Yoshinori KONDO and Hiroshi NAKA

Tohoku University, Aramaki Aza Aoba, Aoba-ku 6-3, Sendai 980-8578, Japan

[email protected]

ABSTRACT

Phosphazene bases are known to be strong organic superbases. Among them, t-Bu-P4 base shows extremely high basicity and has been used for various selective deprotonative transformations. The strong affinity of t-Bu-P4 base for protons is regarded as synthetically useful, however the ability of t-Bu-P4 base to activate organometallic compounds is undocumented largely. Control of the reactivities of various organometallic compounds is the key to the success of selective bond formation processes, and the development of organometallics reactions catalytically promoted by organic superbase is an important subject. We focused our initial interest on the catalytic activation of organosilicon compounds using phosphazene bases. A novel catalytic activation of various O, N, and C nucleophile-silicon bonds using t-Bu-P4 base was investigated to perform nucleophilic reactions with a variety of electrophiles. On the other hand, pyrrole ring architecture is one of the most ubiquitous functionality found in natural products, bioactive chemicals, and functional molecules. We also developed a phosphazene base catalyzed cyclization of multi-substituted N-aryl pyrroles from propargyl silyl ethers and imines. The reaction provides a new perspective in metal-free, catalytic pyrrole synthesis. Further investigation on the scopes and limitations are currently underway in our laboratory.


Ph

OSiMe3

Ph

N

Ar H

Ph

NPh

Ph Ar

Ph

+t-Bu-P4

toluene, r.t.

Ar= 4-ClC6H4 99%

NPN NN

t-Bu

PNMe2

NMe2

NMe2PMe2NNMe2

NMe2PNMe2

Me2N NMe2t-Bu-P4

BIOGRAPHY Professor Kondo, Yoshinori was born in 1958 in Ise city, Japan. He received his B.Sc. in 1980, M.Sc. in 1982 and Ph.D. in 1987, all from Tohoku University. He was a Postdoctoral Fellow in Stanford University (Palo Alto, Prof. B. M. Trost, 1989-1990) before joining Tohoku University as Associate Professor in 1994. He has been a Professor of Tohoku University since 1999. His research fields include organic chemistry, heterocyclic chemistry, organometallic chemistry, selective generation of carbanions using novel organic bases, high throughput methodologies for heterocyclic synthesis, design and preparation of novel organozinc species and the application to organic synthesis.


15

HIGHLY ENANTIOSELECTIVE ORGANIC REACTIONS PROMOTED

BY PRIMARY AMINO ACID-DERIVED ORGANOCATALYSTS Lili CHENG, Zhaoqin JIANG, Xiao HAN, Xiaoyu WU and Yixin LU

Department of Chemistry, 3 Science Drive 3, National University of Singapore, Singapore

117543, Republic of Singapore

[email protected]

ABSTRACT

In this talk, we will discuss our latest development on the primary amino acid derivative-promoted asymmetric organocatalytic reactions. In most cases, our reactions could be carried out in aqueous media. The hydrophobic organocatalysts we used could be easily derived from chiral pool, and had been shown to be efficient organocatalysts in many important organic reactions, including aldol reacions and Mannich reactions. Mechanistic insights of our reactions will also be discussed. The key feature of the organocatalysts described in this talk is that they do not contain a pyrrolidine moiety, yet, the catalytic efficiency of such catalysts is higher than that of proline in many occasions.


O

R1 + H

XOrganocatalyst

R

X

RR1

O

R2R2

up to 99% ee and 98% deX= O or N-PG

(2-10 mol%)

BIOGRAPHY

Assistant Professor Lu, Yixin studied chemistry and received his B.Sc. from Fudan University, Shanghai, China. He continued his graduate studies in Canada and obtained his Ph.D. in Organic Chemistry under the supervision of Prof. G. Just from McGill University in 2000. After his postdoctoral appointment with Prof. Peter W. Schiller in Clinical Research Institute of Montreal, Canada, and an RCMS fellow appointment with Prof. Ryoji Noyori at Nagoya University, Japan, Dr. Lu joined National University of Singapore (NUS) in September, 2003. His research mainly focuses on Organic Chemistry/Medicinal Chemistry. Current interests include the development of asymmetric organocatalytic synthetic methods, and development of analgesic and anti-cancer agents.


16

SYNTHETIC UTILITY OF DIAZOACETATES WITH CHIRAL METAL

AND NON-METAL CATALYSTS Keiji MARUOKA

Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto, Japan

[email protected]

ABSTRACT

The design of new catalysts and new organic transformations in an environmentally benign manner is increasingly important in recent years for the construction of new and useful chiral molecules from simple organic resources. In this context, diazoacetates have unique chemical properties due to their rich functionality in the molecules. Accordingly, we have developed several new, catalytic asymmetric transformations of diazoacetates with certain chiral metal and non-metal catalysts. For example, asymmetric 1,3-dipolar cycloaddition has been effected by designing conceptually new chiral bis-titanium catalysts possessing (R)- or (S)-binaphthol as a chiral auxiliary. In addition, asymmetric Mannich reaction has been realized by using binaphthyl-modified chiral Brønsted acid catalysts as efficient organocatalysts.


O

OTi

OPri

O

O

OTi

PriO

CO2H

CO2H

Ar

Ar

Ar

NHBoc

N2

CO2R

N NH

RO2C CHOMe

N2CHCO2R

*

BIOGRAPHY Professor Maruoka, Keiji graduated from Kyoto University (1976) and received his Ph.D. (1980) from University of Hawaii. He became an assistant professor (1980), promoted to a lecturer (1985) and an associate professor (1990) of Nagoya University. He moved to Hokkaido University as a full professor (1995-2001), and currently is a professor of chemistry in Kyoto University since 2000. He published his work in over 270 scientific papers. His current research interests include bidentate Lewis acids in organic synthesis and practical asymmetric synthesis with chiral C2-symmetric phase-transfer catalysts and chiral bifunctional organocatalysts. He is now a leader of the group research project, “Advanced Molecular Transformations of Carbon Resources” consisting 100 university professors. Recently, he was awarded Synthetic Organic Chemistry Award of Japan (2003), Nagoya Silver Medal (2004), the Award by the Minister of Education, Culture, Sports, Science and Technology (2006), the Japan Chemical Society Award (2007) and Novartis Lectureship Award (2007/2008).


17

PALLADIUM-CATALYZED CH COUPLING REACTIONS OF

HETEROAROMATIC COMPOUNDS Atsunori MORI

Department of Chemical Science and Engineering, Kobe University, Rokkodai, Nada, Kobe

657-8501, Japan

[email protected]

ABSTRACT

Palladium-catalyzed CH arylation reactions of thiazole and thiophene derivatives are described. The reaction of 5-membered heteroaromatic compounds such as thiazole and thiophene with aryl halides takes place in the presence of a palladium catalyst and an activator. Optimization of reaction conditions and the catalyst system is studied. Properties on the obtained arylated heteroaromatic molecules will also be discussed.


Z

SH ArylX

catalyst

+Z

SAryl

additive

Z = CH (thiophene); N (thiazole)

BIOGRAPHY

Professor Mori, Atsunori was born in 1959, in Japan, and obtained BS 1982; PhD 1987 both from Nagoya University under the direction of Prof. Hisashi Yamamoto. After postdoctral research in USA, he was appointed as a Research Associate of the Univeristy of Tokyo in 1988 and of JAIST (Japan Advanced Institute of Science and Technology) in 1993. In 1995, he moved to Tokyo Institute of Technology as an Associate Professor of Chemical Resources Laboratory. Since 2005, he has been a Professor of the Department of Chemical Science and Engineering, Kobe University.


18

CHIRAL AMINE N-OXIDES AND PHOSPHINE OXIDES AS

ORGANOCATALYSTS IN ENANTIOSELECTIVE REACTIONS Makoto NAKAJIMA

Faculty of Medical and Pharmaceutical Sciences, Kumamoto University

[email protected]

ABSTRACT

Numerous chiral base-catalyzed reactions have been developed, but most base catalysts are Brønsted bases, such as amines or metal alkoxides. Recently Lewis base-catalyzed reactions, utilizing the nucleophilicity toward a silicon atom, have attracted considerable attention. Amine N-oxides or phosphine oxides possess a high nucleophilicity derived from the polarization between oxygen-hetero atom bonds. This nucleophilicity allows amine N-oxides and phosphine oxides to act like other Lewis bases and produces hypervalent silicates with trichlorosilyl compounds. We have designed and synthesized novel chiral amine N-oxides and phosphine oxides and found that these Lewis base catalysts exhibited high enantioselectivities in several asymmetric reactions. For example, BQNO is an excellent catalyst for the allylation of aldehydes with allyltrichlorosilanes. BINAPO catalyzed the aldol reaction of trichlorosilyl enol ethers to afford the adducts in high enantio- and diastereoselectivities. These results provide the first successful examples that employ chiral amine N-oxides or phosphine oxides as organocatalysts in the enantioselective reactions.


N+ N+

O–O–CH3O

CHOSiCl3

iPr2NEt, CH2Cl2 CH3O

OH

BQNO (10 mol %)

91% yield, 92% ee

+

BQNO

OSiCl3

90% yield, 96% ee

iPr2NEt, CH2Cl2

BINAPO (3 mol %)

BINAPO

P

P

O

O

PhPhPhPh

OOH

O2NO2N

CHO

+

BIOGRAPHY Professor Nakajima, Makoto received his Ph.D. from the University of Tokyo in 1988 under the direction of Prof. K. Koga. He joined the faculty as a Research Associate at the University of Tokyo in 1988. In 1990-1992 he worked as a postdoctoral fellow with Prof. W. C. Still at Columbia University. In 1993, he moved to the Department of Pharmaceutical Sciences, Hokkaido University as an Assistant Professor in Prof. S. Hashimoto’s group and was promoted to Associate Professor in 1998. In 2004, he joined Kumamoto University as a Professor of Medical and Pharmaceutical Sciences.


19

CATALYTIC ELECTRON TRANSFER REACTIONS CATALYTIC ELECTRON TRANSFER REACTIONS Koichi NARASAKA Koichi NARASAKA

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical

Sciences, Nanyang Technological University, Singapore 637371, Singapore

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical

Sciences, Nanyang Technological University, Singapore 637371, Singapore

[email protected] [email protected]

ABSTRACT ABSTRACT

A single electron transfer process is one of the key methods for the activation of organic molecules. In this lecture would be introduced some catalytic electron transfer processes, which are applied for carbon-nitrogen bond formation.

A single electron transfer process is one of the key methods for the activation of organic molecules. In this lecture would be introduced some catalytic electron transfer processes, which are applied for carbon-nitrogen bond formation. One electron reduction of O-substituted oximes generates their anion radicals, which act as the corresponding alkylideneaminyl radical equivalents. By employing γ,δ-unsaturated oximes, intramolecular nitrogen-radical addition reactions proceed in a catalytic manner by using photosensitizers, arenediols, or copper(I) species for the electron transfer mediators. Various dihydropyrroles are prepared by these catalytic processes, and these proceeses are applied in the synthesis of an alkaloid, peduncularine.

One electron reduction of O-substituted oximes generates their anion radicals, which act as the corresponding alkylideneaminyl radical equivalents. By employing γ,δ-unsaturated oximes, intramolecular nitrogen-radical addition reactions proceed in a catalytic manner by using photosensitizers, arenediols, or copper(I) species for the electron transfer mediators. Various dihydropyrroles are prepared by these catalytic processes, and these proceeses are applied in the synthesis of an alkaloid, peduncularine. β-Indolyl oximes are converted to α-carbolines in a radical pathway by the treatment with a catalytic amount of Cu(I). In contrast, nucleophilic cyclization of β-indolyl oxime derivatives affords indoline derivatives.

β-Indolyl oximes are converted to α-carbolines in a radical pathway by the treatment with a catalytic amount of Cu(I). In contrast, nucleophilic cyclization of β-indolyl oxime derivatives affords indoline derivatives.

GRAPHIC ILLUSTRATION GRAPHIC ILLUSTRATION

O

NO

O

O

N(CH2)2

H

Br

O

O

OCOC6F5

CuBr·SMe2 LiBr

O

N

OCOC6F5


19

O

NO

O

O

N(CH2)2

H

Br

O

O

OCOC6F5

CuBr·SMe2 LiBr

O

N

OCOC6F5

Cu-Br

(CH2)2O

O

BIOGRAPHY Professor Narasaka, Koichi received his Ph.D. from the Tokyo Institute of Technology in 1972. Professor Narasaka held several positions in the University of Tokyo, namely Research Associate, Lecturer, Associate Professor and thereafter Professor, during the period between 1972 and 2007. Currently, he is the Nanyang Professor of Nanyang Technological University. He has won many awards which include the Chemical Society of Japan Award (2000), Louis Pasteur Medal (France (2001), Merck-Schuhardt Lectureship Award (Germany) (2002) and Toray Science and Technology Prize (2005).


20

PD-CATALYZED ASYMMETRIC SYNTHESIS OF AXIALLY CHIRAL

ALLENES AND THEIR APPLICATION IN ORGANIC

TRANSFORMATIONS Masamichi OGASAWARA

Catalysis Research Center, Hokkaido University, Kita-ku, Sapporo 001-0021, Japan

[email protected]

ABSTRACT

Recently, our group developed a novel Pd-catalyzed reaction of 2-bromo-1,3-dienes with a soft nucleophile giving substituted allenes. The reaction was extended to an asymmetric counterpart by the use of a chiral Pd-catalyst and axially chiral allenes could be prepared with high enantioselectivity. The reaction is tolerant to a variety of functional groups, and thus we have an opportunity to prepare enantiomerically enriched axially chiral allenes which are capable of functioning as chiral synthons in subsequent organic transformations. The scheme shown below represents interesting application of our protocol: catalytic asymmetric synthesis of allenylsilanes. The allenylsilanes react with electrophiles in a stereospecific fashion to transfer their axial chirality to newly formed stereogenic centers. The reaction sequence allows us to construct "quaternary chiral carbons substituted with four carbon atoms" by the indirect catalytic asymmetric process. Additional application of the Pd-catalyzed reaction will be presented..


Me3SiBr

R

E

E

OMeMeO •

HMe3Si

E E

OMe

OMe

R

88% ee (R = H)76% ee (R = Me)

Pd/(R)-segphosdba TiCl4+

CsOtBu

R = H, Me; E = COOMe

MeO

REE*

*

88% ee; cis/trans = 1/2 (R = H)76% ee; cis/trans = 1/1 (R = Me)

BIOGRAPHY

Professor Ogasawara, Masamichi was born in Funabashi-city, Japan, in 1966. He obtained a B.E. degree in 1989, and his Ph.D. degree in 1994 from the University of Tokyo. He became a postdoctoral fellow at Indiana University from 1994 to 1996, then at Northwestern University from 1996 to 1997. In 1997, he was appointed as a Research Associate at Department of Chemistry, Graduate School of Science in Kyoto University. Since 2002, he has been working as an Associate Professor at the Catalysis Research Center in Hokkaido University. He is a recipient of Daicel Award in Synthetic Organic Chemistry (2003) and the Incentive Award in Synthetic Organic Chemistry, Japan (2006). His research interests lie in organometallic chemistry of phosphole derivatives and development of transition-metal-catalyzed reactions for enantioselective organic synthesis.


21

NITROGEN-DIRECTED REGIOSELECTIVE ARYLATION OF

AROMATIC C-H BOND CATALYZED BY RUTHENIUM COMPLEXES Shuichi OI

Department of Biomolecular Engineering, Graduate School of Engineering,

Tohoku University, Sendai 980-8579, Japan

[email protected]

ABSTRACT

There has been much interest in direct transition metal-catalyzed C-C bond formation of aromatic compounds involving activation of normally unreactive aromatic C-H bonds, particularly in terms of synthetic and atom efficiency. We report here nitrogen-directed ortho-selective direct cross-coupling reaction of aromatic C-H bonds with aryl halides and direct homo-coupling reaction of two aromatic C-H bonds, catalyzed by ruthenium complexes. References (1) Oi, S.; Fukita, S.; Hirata, N.; Watanuki, N.; Miyano, S.; Inoue, Y. Org. Lett. 2001, 3, 2579. (2) Oi, S.; Ogino, Y.; Fukita, S.; Inoue, Y. Org. Lett. 2002, 4, 1783. (3) Oi, S.; Aizawa, E.; Ogino, Y.; Inoue, Y. J. Org. Chem. 2005, 70, 3113.(4) Oi, S.; Sakai, K.; Inoue, Y. Org. Lett. 2005, 7, 4009. (5) Oi, S.; Tanaka, Y.; Inoue, Y. Organometallics 2006, 25, 4773.


N

H

XR

+

N

Rcat. [RuCl2(η6-C6H6)]2, PPh3

K2CO3, NMP

N

NH

N+

cat. [RuCl2(cod)]n, PPh3

methallyl acetateK2CO3, xylene

C-H + C-X cross

C-H + C-H homo

BIOGRAPHY

Professor Oi, Shuichi was born in Aomori, Japan in 1964. He graduated from Tohoku University in 1987. He received his Ph. D. degree in 1992 from Tohoku University. He was appointed as a Research Associate (1992) then Lecturer (1993) in Faculty of Engineering, Tohoku University. He was an Overseas Research Scholars administered by MEXT at Stanford University during 1999-2000. He has been an Associate Professor in Graduate School of Engineering, Tohoku University since 2001. Awards won include the Tokin Foundation Award (1996), Sankyo Award in Synthetic Organic Chemistry, Japan (1997), and Konica Award in Synthetic Organic Chemistry, Japan (2001). His research interest is in development of new reaction catalyzed by transition metal complexes.


22

MOLECULAR DESIGN AND SYNTHETIC APPLICATIONS OF

CHIRAL TETRAAMINOPHOSPHONIUM SALTS Takashi OOI

Department of Applied Chemistry, Graduate School of Engineering, Nagoya University

Chikusa, Nagoya 464-8603, Japan

[email protected]

ABSTRACT

In this presentation, I would like to show the details of the molecular design of a chiral tetraaminophosphonium salt 1 possessing the phosphorus-centered [5.5]-spirocyclic core, which can be synthesized in a single step from L-valine-derived diamine. The three-dimensional molecular structure was successfully verified by the single-crystal X-ray diffraction analysis, which also identified a secondary interaction between the phosphonium cation and chloride ion via double hydrogen-bonding. The potential of this novel onium salt as a chiral organic molecular catalyst has been demonstrated in an application to asymmetric direct Henry reaction.


NO2

R2+

R1 = aromatic, aliphaticR2 = H, Me, Et

(M ,S)-1/KOtBu(1~5 mol%)

THF, -78 oC P

HN

NH

ArAr

Cl

(M,S)-1 (Ar = p-CF3-C6H4)

HNH

HN

Ar

ArH

R1

O

HR1 R2

OH

NO2

anti /syn = 4:1~>19:174~96% yield, 93~99% ee

BIOGRAPHY

Professor Ooi, Takashi was born in Nagoya in 1965. He received his Ph.D. (1994) from Nagoya University under the direction of Professor Hisashi Yamamoto, and joined the group of Professor Julius Rebek, Jr. at MIT as a postdoctoral fellow (1994-1995). He was appointed as an assistant professor at Hokkaido University in 1995 and promoted to a lecturer (1998). He moved to Kyoto University as an associate professor (2001), and became a full professor of Nagoya University in 2006. He was awarded the Chugai Award in Synthetic Organic Chemistry, Japan (1997), the Japan Chemical Society Award for Young Chemist (1999) and the Thieme Journal Award (2006). His current research interests are focused on the development of new and useful synthetic methodologies by designing organic molecular catalysts including chiral quaternary onium salts.


23

DEVELOPMENT OF ENANTIOSELECTIVE

FLUOROMETHYLATIONS Norio SHIBATA

Department of Applied Chemistry, Graduate School of Engineering, Nagoya Institute of

Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan

[email protected]

ABSTRACT

Enantiocontrolled synthesis of fluorine-containing organic molecules is extremely important in the field of medicinal chemistry and material science. Enantioselective fluorination and fluoromethylation reactions are especially attractive for this purpose because non-fluorinated prochiral substrates can be directly transformed to chiral fluoro-organic compounds with controlled absolute configuration by these methods. Significant progress has been made in the development of asymmetric fluorination reactions in recent years; however, direct enantioselective fluoromethylation remains a challenge. We recently found 1-fluorobis(phenylsulfonyl)methane, FBSM, to be a synthetic equivalent of a fluoromethide species under the Tsuji-Trost allylic alkylation conditions, which provided the palladium-catalyzed asymmetric allylic monofluoromethylation reaction with high enantiocontrol. We also disclosed an unprecedented catalytic enantioselective monofluoromethylation reaction of in situ-generated prochiral imines with FBSM in the presence of a chiral phase transfer catalyst under the combination of Mannich-type reaction with reductive desulfonylation. In this lecture, we show our recent progress of the development of enantioselective monofluoromethylation reactions based on FBSM chemistry. Development of enantioselective trifluoromethylation reaction using Ruppert reagent is also disclosed.


FPhO2S SO2Ph

FBSM

Me3Si-CF3

Ruppert Reagent

HR1 R2

R3 CFxHy

CFxHy=CFH2, CF3

*

BIOGRAPHY Professor Shibata, Norio received his Ph.D. in 1993 from Osaka University. Subsequently, he was a Postdoctoral Fellow in Osaka Unviersity (1993-1994), University of Oxford (1994-1996), and Sagami Chemical Research Institute (1996), before becoming a lecturer in Toyama Medical & Pharmaceutical University in 1997. He joined Nagoya Institute of Technology as an associate professor and has stayed on since. Professor Shibata was the winner of Fluorine Prize in 2005.


24

ENANTIOSELECTIVE PETASIS-TYPE REACTION WITH MULTI-

FUNCTIONAL THIOUREA Yousuke YAMAOKA, Hideto MIYABE and Yoshiji TAKEMOTO

Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto

606-8501, JAPAN

[email protected]

ABSTRACT

We have already developed bifunctional aminothiourea catalysts bearing a tertiary amino group with expecting the synchronous activation of a nucleophile and an electrophile. From the study, it was revealed that their weak acidity compared with metallic Lewis acids could be overcome by this modification and these bifunctional catalysts could be used efficiently for a wide range of diastereo- and enantioselective nucleophilic reactions such as Michael addition of 1,3-diketones to nitroolefines, aza-Henry reaction of nitroalkanes to N-Boc imines, and hydrazination of cyclic β-keto esters.1-3) We recently discovered that new thiourea catalyst 1, bearing an 1,2-amino alcohol moiety, significantly accelerated the Petasis-type reaction of alkenylboronic acids 3 to N-phenoxycarbonyl quinolinium salts, prepared from quinolines 2, to afford 1,2-addition products 4 with high enantioselectivity (up to 97% ee).


BIOGRAPHY

Professor Takemoto, Yoshiji was born in Osaka in 1960 and received his B.Sc (1983) and Ph.D. degree (1988) from Osaka University. After working as a postdoctoral fellow with Prof. R. A. Holton at Florida State University from 1988 and with Dr. S. Terashima at Sagami Chemical Research Center from 1989, he joined the Faculty of Pharmaceutical Sciences, Osaka University, as an Assistant Professor in 1990. He moved to the Graduate School of Pharmaceutical Sciences, Kyoto University, as an Associate Professor in 1998 and was promoted to Professor in 2000. His research interests are in the areas of transition-metal chemistry, organocatalyst chemistry, and total synthesis of natural products.


25

CHIRAL GUANIDINE CATALYSED ENANTIOSELECTIVE

REACTIONS Choon-Hong TAN

Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore

[email protected]

ABSTRACT

Several chiral bicyclic guanidines were prepared and found to be excellent enantioselective catalysts for Michael, Phospha-Michael and Diels-Alder reactions. One of these guanidines catalysed the reaction between anthrones and various dienophiles. The catalyst can tolerate a range of substituted anthrones. Excellent yields, high regioselectivities and high enantioselectivities can be obtained. Asymmetric Michael reactions can also be achieved using these catalysts. A variety of 1,3-dicarbonyl compounds, including S,S’-dialkyl dithiomalonates, dialkyl malonates, 1,3-diketones and benzoylacetate, can function as the Michael donors giving high enantioselectivities and yields. Asymmetric catalytic Phospha-Michael reaction was also achieved using diaryl phosphine oxide and nitroalkenes. These reactions will be presented in the seminar. References J. Shen, T. T. Nguyen, Y.-P. Goh, W. Ye, X. Fu, J. Xu, C.-H. Tan, Chiral Bicyclic Guanidine Catalyzed Enantioselective Reactions of Anthrones. Journal of the American Chemical Society, 2006, 128, 13692-13693.


SN

O

OPh

Cl

OH

S

CH2Cl2, -20 oC, 4 hrs92% yield, 99% ee

(10 mol%)NH

N

NBn BnO

Cl

N

O

O

Ph+

Cl

Cl

BIOGRAPHY Assistant Professor Tan, Choon-Hong received his B.Sc.(Hons) in 1995 and his Ph.D. in 1999, both from the National University of Singapore. He was a Postdoctoral Fellow in Harvard University (2000-2002) and in Harvard Medical School (2002-2003), before joining the National University of Singapore as an Assistant Professor.


26

DEVELOPMENT OF N-METHYLIMIDAZOLE (NMI)-CATALYZED

ACYLATIONS DIRECTED TOWARDS PROCESS CHEMISTRY Ryohei NAGASE, Hidefumi NAKATSUJI, Tomonori MISAKI, and Yoo TANABE

Department of Chemistry, School of Science and Technology, Kwansei Gakuin University,

2-1 Gakuen, Sanda, Hyogo 669-1337, Japan Address of University

[email protected]

ABSTRACT

Acylation reaction is a frequently-used reaction in organic synthesis and process chemistry. During our ongoing study on the development of process chemistry, we present here efficient acylations promoted by N-methylimidazole (NMI) as a key catalysts; (i) Esterifucations and amide-formations and (ii) Ti-crossed Claisen condensations.

(i) Using TsCl – NMI, carboxylic acids (using NMI, acid chlorides) are converted to acylimidazolium intermediates, which condense with alcohols and primary or secondary amines to give the corresponding esters and amides (total ca. 100 examples).

(ii) Using Bu3N – NMI, carboxylic acids or acid chlorides are converted to acylimidazolium intermediates, which condense with methyl esters to give crossed β-ketoesters (total 25 examples).

1H NMR monitoring study supported the existence of these acylimidazolium intermediates. We applied these methods to short and efficient syntheses of useful compounds and natural products such as R-muscone, Z-civetone, cis-jasmone and its lactone analogue, 1β-methylcarbapenems, (+)-alternalic acid, and (-)-azapirene.


N NMe

R4

R1

Cl-O

activated acylammonium intermediate

R1CO2HTsCl - NMI

R1 CO2Me

R2OH or R3R4NH

R5

OCO2Me

R5

R1CO2R2

R1CONR3R4

R1COClNMI

or

NH

OO

OHOPh

OH

O

O OH

OCO2HHO

OH

(-)-Azaspirene

(+)-Alternaric acid

BIOGRAPHY

Professor Tanabe, Yoo received his Bachelor’s Degree from The University of Tokyo in 1978 and his Masters’ Degree from Kyoto Universitt in 1979. During his stay in Sumitomo Chemical Co. Ltd between 1980-1991, he joined The University of Tokyo as a Research Fellow for the period of 1983-1985. In 1991, he became an Associate Professor in Kwansei Gakuin University and since 1997, he was a Full Professor in the university. In addition, he was a Visiting Research Fellow of Groningen University (the Netherlands, Prof. Richard M. KELLOGG) during 1996-1997.



27

DEVELOPMENT OF ASYMMETRIC REACTIONS BASED ON

CHIRAL MULTIMETALLIC SYSTEMS Yutaka UKAJI

Graduate School of Natural Science and Technology, Kanazawa University, Kakuma,

Kanazawa 920-1192, JAPAN

[email protected]

ABSTRACT

A practical method for the construction of chiral molecules has been designed using a strategy based on the systems possessing multiple metal centers with a tartaric acid ester as a chiral auxiliary.1 The catalytic asymmetric addition of alkynylzinc reagents to nitrones was achieved by utilizing di(t-butyl) (R,R)-tartrate as a chiral auxiliary to afford the corresponding optically active (R)-N-(α-substituted)propargylic hydroxylamines. By the addition of methylzinc salt of a product-like racemic hydroxylamine, enantioselectivity of the N-propargylic hydroxylamines was enhanced up to 96% ee (eq. 1).2 The asymmetric 1,3-dipolar cycloaddition of azomethine imines to allyl alcohol was also achieved. When 3 equivalents of Grignard reagent were added to a mixture of allyl alcohol and (R,R)-DIPT, followed by adding azomethine imines, the corresponding optically active trans-pyrazolidines were obtained with excellent regio-, diastereo-, and enantioselectivities.3 References 1) Synlett 2003, 1075-1087. 2) Chem. Lett. 2007, 36, 44-45. 3) Submitted.


BIOGRAPHY Professor Ukaji, Yutaka was born in 1960 and received his B.S. in 1982 and Ph.D. in 1987 from the University of Tokyo under the direction of the Professor T. Mukaiyama. In 1987, he was appointed as Assistant at Mie University. In 1991, he moved to Professor K. Inomata's group at Kanazawa University, where he is currently Professor of Natural Science and Technology. He joined Professor R. L. Danheiser's group at MIT in 1995 and Professor C. P. Casey's group at University of Wisconsin-Madison from 2002 to 2003.


28

ALIPHATIC POLYKETONES FROM PALLADIUM-CATALYZED

OLEFIN-CO COPOLYMERIZATION PK WONG

Institute of Chemical and Engineering Sciences, Agency of Science, Technology, and

Research, Singapore

[email protected]

ABSTRACT

Perfectly alternating ethylene-CO copolymer is a high performance engineering plastic derived from the lowest-cost monomers, ethylene and carbon monoxide. It is also one of the rare examples of totally new backbone polymers commercialized by the chemical industry recently. This presentation will highlight the contributions of catalysis in the development of an economically viable manufacturing process of ethylene-CO copolymer as well as the challenges in propylene-CO copolymerization..


CH2=CH2 + CO

O

n

Pd catalyst

BIOGRAPHY Dr Wong, PK received his PhD in organic chemistry from the University of Iowa under the supervision of Professor John Stille. He began his industrial career at the Central Research Laboratories of Dow Chemicals in 1976. He joined Shell Chemicals in 1980 where he has worked in Houston and Amsterdam. While at Shell, he has carried out a variety of exploratory research projects in homogeneous catalysis and polymers, and participated in several development projects including the commercialization of aliphatic polyketones. In 2000, he joined Resolution Performance Products (formerly Shell Epoxy). He has been a principal scientist and program manager for the Applied Catalysis group at the Institute of Chemical and Engineering Sciences (ICES) in Singapore since November 2003.


ADSORPTION-INDUCED DESORPTION OF BENZENE ON SI(111)-7×7

BY SUBSTRATE-MEDIATED ELECTRONIC INTERACTIONS Guo Qin XU

Department of Chemistry, National University of Singapore, 3 Science Drive 3,

Singapore 117543

[email protected]

ABSTRACT

The process of benzene adsorption on an adjacent adatom-rest atom pair on Si(111)-7×7 at room temperature was studied using in-situ scanning tunneling microscopy (STM). Both adsorption and desorption of benzene were observed to take place mostly at adjacent sites during the process. DFT calculation results show that the bond length between the rest atom and the carbon atom in a pre-adsorbed benzene molecule increases due to the charge transfer from a neighboring rest atom in response to an approaching benzene molecule. Such increase in the bond length, when coupled resonantly to the C-Si thermal vibration, could result in bond breakage and desorption of the adsorbate. The studies provide strong evidences for the desorption of pre-adsorbed benzene caused by an adsorbing benzene at a neighboring site through a substrate-mediated electronic interaction.


Re1

B1B2Ce1

Ce2

Re2

Re1

B1B1B2Ce1

Ce2

Re2

BIOGRAPHY Professor Xu, Guo Qin received his B.Sc. degree in 1982 from Fudan University and Ph.D. degree in 1987 from Princeton University. He thereafter served postdoctoral fellowships in Brookhaven National Laboratory (1987-1989) and then University of Toronto (1989-1991), before joining the National University of Singapore as a Lecturer in 1991. He was promoted to Associate Professor in 1998 and was subsequently a full Professor since 2004. His research interests focus on surface chemistry and nano-materials and molecular conductivity. He was awarded the National Youth Award for Excellence in Science and Technology, Singapore National Youth Council (1997).

29

programme - nus chemistry · highly enantioselective organic reactions promoted by primary amino...

Documents