Lecture 1 Stereochemistry

T. K. Sarkar

Enantiomers and Chirality

O CN R H
-

HO R

CN H

How many products are formed ?

O R H CN Approach from front face of the carbonyl O HO R R H CN Approach from back face of the carbonyl NC R H A (Mirror images) B OH R H HO CN A & B are enantiomers Structures that are not superimposable on their mirror images, and can thefore exist as enantiomers, are called chiral R H NC OH

CN H

Drawing Molecules
H H3C H HH HH HH H H linoleic acid linoleic acid H C H H C H H C H H C H C H C H H C C C H C H C H H C H H H C C H H H C H H C H CO2H HH HH H O HH H H H H HH HH HH H OH

or or
H H C H

CH3CH2CH2CH2CH2CH=CHCH2CH=CHCH2CH2CH2CH2CH2CH2CH2CO2H

H H H H linoleic acid

X-ray picture of linoleic acid

OH O

linoleic acid

What happens when cyanide is added to acetone

HO Me CN Me HO Me

CN
Me

Plane of symmetry runs through central carbon, OH, CN

Acetone Cyanohydrine

So, any structure that has no plane of symmetry can exist as two mirror-image forms (enantiomers)
Some examples of structures other than chemical structures which are chiral

Amusing ? The ancient Egyptians had less care for the chirality of hands

Stereogenic centres
If a molecule contains one carbon atom carrying four different groups it will not have a plane of symmetry and must therefore be chiral. A carbon atom carrying four different groups is a stereogenic or chiral centre Stereoisomers & Constitutional isomers
OH R CN R CN OH HO R CN H R HO CN H

Constitutional isomrs

Enantiomers NC

R CN

HO R

CN H R

HO

CN H

trans / cis isomers HO CN NC R R H

H OH

H R

OH CN

two configurations : going from one enantiomer to the other requires a bond to be broken

3 conformations of the same enantiomer: going from one to the other requires rotation about a bond

Racemic mixture A racemic mixture is a mixture of two enantiomers in equal proportion

MeMgCl

Consisting of CHO OH HO H 50 OH CHO Consisting of OH O O HO H

:
H : 50 OH

HO

H O 50

:
:

50

Cahn-Ingold-Prelog rules :
CH3 HO CH2 CH3 H H CH2 CH3 CH3 OH

Both are "2-butanol''

Absolute configuration : The R & S notation

1. Assign priority sequence to the four groups attached to a stereogenic carbon following sequence rule 2. Observe the stereogenic centre from a direction opposite to the group of lowest priority 3. Trace the path from 1 to 2 to 3. If clockwise R (rectus, right) If anti clockwise S (sinister, left)
1 1

4 2

3 2

Sequence rules:
1. Priority is first assigned on the basis of the atomic number of the atom that is directly attached to the stereo centre.
CH3 ? (a) HO H (d) CH2 ? CH3

2. When a priority cannot be assigned on the basis of AN, then the next set of atoms/groups are examined.
(c) (a) HO CH2 (b) CH3 CH3 H, H, H H (d) H, H

C
c CH3

3. Rotate the structure so that (d) is directed away from us.

CH3 HO CH2 CH3 H d H OH a CH2CH3 b

4. Groups containing double or triple bonds are assigned as if both atoms were duplicated and triplicated.
C Y C Y

(Y) (C) (Y) (C) C Y C Y

(Y) (C) CH CH2 CH2CH3

both CH So move to next carbon H C H C H

H C H

H C H H

(C) (C) H, C, C

H, H, C

Vinyl > ethyl

Diastereomers
Diastereomers are stereoisomers that are not mirror images. Two diastereomers are different compounds and have different relative stereochemistry. Diastereomers may be chiral (have no plane of symmetry):
Ar O CO2Me Ar O CO2Me

Diastereomers may be achiral

OH OH

plane of symmetry

Chiral compounds with no stereogenic centres

Me C H Me Me H H C H Me

These mirror images are not superimposable - enantiomers

O rotation around the single bond is restricted PPh2 PPh2 N H O H N

O H N

N H O

nonsuperimposable enantiomers

Tartaric acids
OH HO2C
R R

OH CO2H diastereomers HO2C

R S

CO2H

OH enantiomers OH HO2C

OH

?
HO2C
S

OH
R

CO2H OH

CO2H

OH 22 = 4 HO2C HO

stereoisomers ?
CO2H
S R

meso
OH

Recommended Books 1. Organic Chemistry (2nd Ed.) by P. Y. Bruice 2. Organic Chemistry by Clayden, Greeves, Warren and Wothers 3. A Guide Book to mechanism in Organic Chemistry by P. Sykes