synthesis - organic chemistry notes at examville.com

8/9/2019 Synthesis - Organic Chemistry Notes at Examville.com

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A N D T O T A L

S YN THESIS

12 3. 7 02

S T E R E O S E L E C T IV E

gar e t h j r ow la nds


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j

w h y d o w e n e e d T o ta l S y n th e s is ?

Wsiegmund@wikimedia commons

O

AcO

H

OH

OBzOH

O

O

OH

Ph

BzHN

AcO O

AcO

taxol


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Trois Ttes (TT)@Flickr

NH

H

O O

N

O

O

A s ym m e t ricS yn t he s is ?

w h y d o w e n e e d


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s yn thes is o f p u ree n a n t io m e r s im p or tant

NMe2

Me

P hO

Et O

n ov r adco ugh-s up pr e ss an t

Me2 NMe

P h O

Et

O

da r v onp a in k ille r


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natashalcd@Flickr

c ou r s e o u t lin e

6 lec turesa s ym m e t ric s yn the s is

6 lec turesto ta l s ynthe s is


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c o u r s e n o t e s


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recommended

books


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r

F EA T U R EA R T I C L E

Tos h i fum i Do h iand Yas

u yu k i K i ta

H yper va len t iod ine reag

en ts as a ne w

en trance to organoca ta

l ys ts I S S N1 35 9 - 7 3 4

5 C O MM U N I CA T I O N

Nor i fum i Fu j i ta, Se ij i S h i

n k a ie t a l.

An organoge ls ys tem ca

n con tro l t he

s tereoc hem ica l course o

f an t hracene

p ho tod imer i za t ion

1 35 9 - 7 3 45( 2 0 0 9 )1 6;1

- 0

w w w. rsc.o rg/c he mco

m m

Num ber 1 6 | 2 8 Apr i l 2

0 0 9 | Pages 2 05 3 2 2 2 4

C he m ica l Co m m u n ica

t io ns

, r .r

r .r ,

. . ,

, .

r r r

r r

r r

r r -r

r r

r r

r r

r

r r -

r r r

r r

r

F E T URE RT ICLE

Toshifumiohi and Yasu

yuki Kita

ypervalen tiod ine reage

nts a s a new

entr ance to organ ocatalyst

s ISS1 35 9-7 345 C MM UNIC

TI N

or i fum i Fuji ta, Se iji S hink

ai et a l.

n organogelsystem canco

ntro l the

stereochem icalcourse o

fant hracene

pho tod imer ization

1359 -73 45(2 00 9)16;1- 0

ww w.rsc.o rg/c hem com

m

umber 1 6 | 2 8 pril 2 009 | Pages

205 3 22 24

C he m ica lCo m m u n ic

a t io ns

w w w .r s c .o r g / o b c

V o l ume 7 | N umb e r 9 | 7 M ay 2 0 0 9 | P ag e s 17 37 19 8 8

C O M M U N I C AT I O N J e nni f e r R . H i s c o c k e t a l .F l u o r e s c e nt c ar b az o l y l u r e a ani o n r e c e p t o r s

14 7 7 - 0 5 2 0 ( 2 0 0 9 )7 : 9 ; 1- 6

journa ls


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lec ture oneterminology

s ub s t r a t e c o nt r o land


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chira l ob jec t

non-s upe r pos able


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chira l ob jec t



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OH

O

HS

NH 2H

HO

O

SH

H 2 N H

chira l com pounds



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OH

O

HS

NH 2H

HO

O

SH

H 2 N H

chira l com pounds

enant iom er s


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a c hir a l ob ject

s u p e rp o s a b le


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a c hir a l compounds

s u p e rp o s a b le

H OH


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a c hir a l compounds

s ym m e tr y

p la n e of Me Me

H OH


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na m ing:

123.202s

e e

CH 3HO

O

H NH 2


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CH 3HO

O

H NH 214

23

na m ing:

prio ritie s

groups CH 3 NH 2 H CO 2H

1st atom C N H C

2nd atom H, H, H O , O, O

priority 3 1 4 2


19/76

na m ing:low e s t pr ior ity

points aw ay

CH 3HO

O

H NH 2

H 3 COH

O

HH 2 N

14

2

3

1 4

2

3


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1

23

1

2 3

na m ing:

Santiclockwise Rclockwise right


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NH 2

H 3 C CO 2 HH 3 COH

O

HH 2 N1

4

23

1

23

SSna m ing:

fina lly... ( S )-2-a m inopropanoic a c id


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P

O

OMeMe

H Ph

NS

O

t -Bu

N

N

Ru

N

N

N

Nnon-car bon-based

chir a l compounds

princ ipa lss am e


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chira li t yo fother f or m s a x i a l

O

O

O

O

O

O

O

O

MonkeyBoy69@ickr


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chira li t yo fother f or m s

mugley@ickr

PPh 2

PPh 2

Ph 2 P

Ph 2 P

a x i a l

h


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chira li t yo fother f or m s h e l i c a l

P [8]helicene M [8]helicene


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chira li t yo fother f or m s

plan a r

Fe PPh 2

Ph

FePh 2 P

Ph

ore


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compounds w i t h

enantiom ers

s te r eocentr e s2or more

OH

NH 2

OH

NH 2

ore


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compounds w i t h

dia s te reois om ers

s te r eocentr e s2or more

OH

NH 2

OH

NH 2

OH

NH 2

OH

NH 2

more


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compounds w i t hs te r eocentr e s2or more

enantiom ers

OH

NH 2

OH

NH 2


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s te r eocentr e s2

com pounds

4

OH

NH 2

OH

NH 2

OH

NH 2

OH

NH 2


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s te r eocentr e s3

com pounds

8

HOCHO

OH OH

OH

HOCHO

OH OH

OH

HOCHO

OH OH

OH

HOCHO

OH OH

OH

HOCHO

OH OH

OH

HOCHO

OH OH

OH

HOCHO

OH OH

OH

HOCHO

OH OH

OH


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s te r eocentr e sn

com pounds

2 n


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generalisation !thisis a !


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HO 2 CCO 2 H

OH

OH

HO 2 CCO 2 H

OH

OH

HO 2 C

CO 2 HOH

OH

HO 2 C

CO 2 HOH

OH

s te r eocentr e s2

com pounds

3


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HO 2 CCO 2 H

OH

OH

HO 2 CCO 2 H

OH

OH

HO 2 C

CO 2 H

OH

OH

HO 2 C

CO 2 H

OH

OH

s te r eocentr e s2

com pounds

3 dia ste re ois om ers


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HO 2 CCO 2 H

OH

OH

HO 2 CCO 2 H

OH

OH

HO 2 C

CO 2 HOH

OH

HO 2 C

CO 2 HOH

OH

s te r eocentr e s2

com pounds

3 enantiom ers


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s te r eocentr e s2

com pounds

3 ide nt ic a lm es o

HO 2 CCO 2 H

OH

OH

HO 2 CCO 2 H

OH

OH

HO 2 C

CO 2 HOH

OH

HO 2 C

CO 2 HOH

OH

o


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com poundsm es o

HO 2 C

OH

CO 2 H

HO

HO 2 C CO 2 H

OH

OH

o


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s ym m e try

com poundsm es o

achir a lp lane o f

HO

HO 2 C

OH

CO 2 H

i NH NH


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properties

enantiom er side n t ic a lha ve

NH2NH2

NH2H2N

mp = 41-45Cmp = 40-43C

di t o is om ers NH NH


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propertiesdi f fe re n tha ve

dia s te reo is om ers NH2NH2

mp = 41-45Cbp = 221C

NH2NH2

diff c e betw e e n


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di f fe re nc e be t w e e n

dia s te reo is om e rs

synthesisa s ym m e t ric to

ke y

re


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brittanyculver@ickr

h o w do w e m eas ure

pur ity ?


45/76

NH 2

NH 2

NH 2

H 2 N

NH 2

NH 2

=

80 % 20 % 60 %eeenantiom eric exces s ee


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NH 2

NH 2

NH 2

H 2 N

=

80 % 20 %

4 : 1

e na nt iom e ric rat io (e r)


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NH 2

NH 2

NH 2

NH 2

80 % 20 %

diastereoisomeric excess 60 % dediastereoisomeric ratio 4 : 1 dr

ure


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brittanyculver@ickr

h o w do w e m eas ure

ee?

f righta n d


49/76

ha nde d g lo ve s le f t r ig h ta n d

ide ntic a l

ar e

un tilyou dd h d


50/76

un til you a dd a ha nd

hemis try


51/76

s am et he

David Reeves from Flickr

c h e m i s t r y

dia ste re ois om e rs

n e ed

hemis try


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s am et hec h e m i s t r y

dia ste re ois om e rs

n e ed.

R S

R

R R S R

R S


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OH

Ph CO 2H

DCC,

DMAPOMeF3C i Pr

O H

O

Ph

F3C OMe

i Pr

O H

O

Ph

F3C OMe

c ov a le nt

Mos he r s a c id73J A CS512, 73J OC2143 & 91J A CS4092

de r iv a tis a tion


54/76

HO 2CCO 2H

OTol

OTol

O2CCO 2H

OTol

OTol

S diastereoisomer is insoluble

NaOH

()-propranolol-blocker

OOH

NH

OOH

NH2

OOH

NHionic ( s a lt )de r iv a tis a tion

te m pora ry


55/76

Pere Tubert Juh@ickr

t e m por a r y in te r a c tions

chir a l chrom atography

Si

N H

ONO 2

NO 2

Si

OSi

Si O

O

O

O

OSi

OSi

O

O

O

O

O

Me

Me

silica chiral amine


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as y m m e tr ic

synthesis


57/76

simpologist@ickr

c a na de ns o lide Te tra h de ron, 2 0 0 6 , 6 2 , 9 7 1 3

O

O

O

On -C 4 H 9

H H

s ubs tra te OO


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n -C 4 H 9H

O

OBnOMe

OSiMe 3

n -C 4 H 9

OH

OBn

OMe

O

TiCl 4

77%n -C 4 H 9

OH

OBnOMe

O

100%

0%100% de

s ubs t r a t e c ontr o l

O

O On -C 4 H 9

H H


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SarahWynne@ickr

C

ram


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Cont r o lhe la tionram

n -C 4 H 9

H

BnO O

H

Cl n

Ti

MeO

Me 3 SiO

angleBrghi-Dunitz


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angle

R

R

R

O

R

C OR

R

Nu

C OR

R

NuNu

*

repulsion

Br ghi-Dunitz

C

ram


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LR

O

Z S

M

R

O

Z

M

S L

Nu

LR

Nu OH

Z S


C

ram


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L

SZ

LR

O

Z S

M

R

O

Z

M

S L

Nu

LR

Nu OH

Z S

O

R

Z

LS

O

RNu

L

SZ

R

Nu OHZ

LSNu

OH

R

Me

HO


64/76

Ed Bierman@ickr this isnt the right sponge!

pr e s winholide T

e tra h de ron, 1 9 9 5 , 5 1 , 9 4 3 7

OMe

OMe

Me

HO

HOMe

Me

OH OH

Me

MeO

OOHO

s ubs tra te


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OMe

OMe

Me

OSi

OMe

Me

H

O

t -Bu

t -Bu

Me 3 Si Me

TiCl 4

94%95% de

OMe

OMe

Me

OSi

OMe

Me

OH

t -Bu

t -Bu

Me

s ubs t r a t e c ontr o l


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Fe lkin Ahn


67/76

modelFe lkin- A hn

L

M

SH

O

Nu

L

S

M H

O

NuNu

Fe lkin Ahn


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modelFe lkin- A hn

Ph H

O

Me H

Et MgBr

PhEt

Me H

Ph

EtMe H

H OH

HO H

25%

75% ( 50% de )

Fe lkin-Ahn


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modelFe lkin- A hn

Ph H

O

Me H

Ph

HMe

O

H

first ...

Ne wm a n pr o ject iondra w

Fe lkin-Ahn


70/76

modelFe lkin- A hn

Ph

HMe

O

H

H

Ph

Me

O

H

Ph

H

Me

O

H

Ph

Me

H

O

H

p e rp e nd ic u la r

r o ta tela rge group

Fe lkin-Ahn model


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Fe lkin- A hn

Ph

Me

H

O

HEt

Ph

Me

H

OH

Et H

PhMe

H

OHEt

H

PhEt

Me H

HO H

mode

not the w hole


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Ph

O

SMeLiEt 3BH

Phi Pr

SMe

HO H

Phi Pr

SMe

H OH

Zn (BH4)2

t s to r y

che la tion


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i Pr

MeS

H Ph

O

Zn

HH 3 B

a t ionc on tro l

no


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per pendicula r elemen te le c tr one ga tiv e

MeS

i Pr

HPh

O

H BEt 3

ca rbonyl

che la t ion


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Capt Kodak@ickr

sterics electronics

s ubs t r a te


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a t ec on tro l

n -C 4 H 9H

O

OBn

OMe

OSiMe 3

n -C 4 H 9

OH

OBn

OMe

O

TiCl 4

synthesis - organic chemistry notes at examville.com

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