Problem: 2,5-dimethyl-1,1-cyclopentane dicarboxylic acid exist as two isomers

(A & B; differ in mp; A is optically inactive but B is not)),Upon heating (mono decarboxylation)
A yields two 2,5-dimethylcyclopentanecarboxylic acid (optically inactive) and
B yields one (optically active). Assign structures of A & B.

HO2C CO2H
 HO2C CO2H
Hint:
CO2H CO2H
heat
A + Me Me

CO2H CO2H
HO2C CO2H
heat
or

B
same
A & B are diastereomers
 Compounds with no stereogenic centres

The presence of chiral atom is neither a

necessary nor a sufficient condition to be
optically active

H3C H
Me H H Me C C C
C
C
H H H
Me Me achiral
H

These mirror images are not superimposable - enantiomers

O O
H H
N N
PPh2
rotation around the single
bond is restricted PPh2
N N
H H
O O
nonsuperimposable enantiomers
substituted allenes
biphenyls

has been resolved

half-life for racemization
is 78 min at 118oC
Biphenyl atropisomerism and absolute configuration

2
H
H

4 H H(Br) 3
Br
As+Me3 As+Me3
1
(R)

1
S CH2S
4 3
H CH2S
S
H
2
(S)
Optically active di- and mono-substituted biphenyls
Configurational nomenclature of alkylidenecycloalkanes, oximes and spiranes
 Helical and propellor Molecules

Left handed and Right Handed Hexahelicene

Cl

Cl Cl Rotation restricted

Cl Cl
Cl Cl
N
Cl Cl
Cl Cl
Cl Cl
Cl Cl
Propellor
perchlorotriphenylamine
 Biological importance of chirality

• Chirality is a phenomenon that pervades the universe

• Human body is structurally chiral
• Helical seashells are chiral
• Most plants show chirality in the way they wind around
supporting structures
• Most of the molecules that make up plants and animals
are chiral and usually one form of the chiral molecule
occurs in a given species
• All but one of the 20 amino acids are chiral and L-form
• Almost all natural sugars are chiral
• DNA itself has a helical structure and all naturally occurring
DNA turns to right.
• Chiral molecules can show different handedness in
many ways, including the way they affect human beings
Why the smells of Orange and lemons are different?

R- (+)-limonene S- (-)-limonene
smell of orange smell of lemons

Enantiomeric smell !!!

 Perfumery compounds from jasmine
O

Jasmone

Cis-jasmone is the main compound in jasmone perfume

O
O

S
R CO2Me
CO2Me

strong odour odourless

(+)-Z-methyl epijasmonate (-)-Z-methyl epijasmonate
 R
O
Z O
H
Japonilure

• pheromone released by Japanese beetles as a means of

communication
•Larva of the beetles are serious crop pests
•25 µg/trap catches thousands of beetles
• 1% of the other enantiomer destroys the activity
 Me
*
COOH

Ibuprofen
500 mg of one tablet contains only half of its as active drug

Me
Me
COOH
COOH

S is active R is inactive
 HO HO
Drug for the treatment of NH2
NH2
Parkinson’s disease
Only L-dopa can restore
HO CO2H
the nerve function. HO CO2H

L-dopa D-dopa
marketed as a toxic
single enantiomer

Me
Me
NMe2
Me2N C
C O
O
O
O

Novrad
Darvon
(anticough agent)
(Pain killer)
 Thalidomide tragedy

N
*

O
O N O
H
Thalidomide

•Drug sold in racemic mixture (approved in Canada & Europe but not in US)

• dexorotatory isomer  sedative

•levorotatory isomer  cause of birth defects
• even dextro isomers can cause mild defects because of
invivo racemization
Chemical Properties of Enantiomers
 Stereochemistry
Physical Properties of Stereoisomers
• Enantiomeric excess (optical purity) is a measurement of
how much one enantiomer is present in excess of the
racemic mixture. It is denoted by the symbol ee.

ee = % of one enantiomer - % of the other enantiomer.

• Consider the following example—If a mixture contains
75% of one enantiomer and 25% of the other, the
enantiomeric excess is 75% - 25% = 50%. Thus, there is a
50% excess of one enantiomer over the racemic mixture.
• The enantiomeric excess can also be calculated if the
specific rotation [] of a mixture and the specific rotation
[] of a pure enantiomer are known.
ee = ([] mixture/[] pure enantiomer) x 100.
 Enantiomeric Excess
When a mixture of enantiomers is neither
enantiomerically pure (all one enantiomer) nor
racemic (equal amounts of two enantiomers), the
relative amounts of the enantiomers in the mixture
can be expressed as the enantiomeric excess (optical
purity).

e.e.= d - l x 100
d + l
(excess of one over the other) x100
= (entire mixture)
 Resolution of Enantiomers

Enantiomers have the same physical properties so they can not be separated directly.

A possible technique for separation is chemical modification into diastereomers, which

possess different physical properties. Once in hand, diastereomers can be separated
by physical means, such as boiling point or recrystallization and then converted back
into enantiomers.

Two key requirements:

1. The reaction must be reversible so that the enantiomers can be released.
2. The reagent that reacts with the enantiomers must be stereochemically pure.

Example: The resolution of (S) and (R)-2-butanol via esterification with

enantiomerically pure (R,R)-tartaric acid.

Key reaction: Esterification

O + O
H
R-C-O-H + H-O-R' R-C-O-R' + H2O
acid alcohol ester
 Reaction Scheme

CH2CH3
S
O H separate
CH2CH3 O C CH3 then H+
H R OH CH2CH3
HO H
H2O
CH3 HO RH HO H
CO2H + CO2H CH3
(S)-2-butanol H CO2H
H OH (S)-2-butanol
+ H OH
HO H +
HO H
CO2H CH2CH3
CH2CH3 CO2H
(R,R)-tartaric acid H R O separate CH2CH3
H OH (R,R)-tartaric acid
CH3 CH3C O then H+ H OH
H R OH
CH3
(R)-2-butanol H2O
HO RH (R)-2-butanol
CO2H

The initial product esters are diastereomers of each other and can be separated by
selective recrystallization (i.e. different solubilities in a solvent). The alcohols are
recovered by hydrolysis of the esters (reversible reaction).
Q. Identical, enantiomeric, or diastereomeric?

O
&

CHO CH2OH
O
H NH2 H OH
&
HO H H NH2
CH2OH CHO

& O
S S

H H Cl CH3
H H
Cl Ph & H Ph
CH3 H
Q. Give structures (with R/S specification) of the products
in the following reaction?

cold alkaline
(R)-HOCH2CHOHCH=CH2 A (opt active) + B (opt. inactive)
KMnO4

Q. The following compound racemises in base, why?

O
O
O O HO
-
B O O
O
R S
HO
H
H
H

Q. Mosher’s Acid
MeO CF3
R or S ?
COOH
1.
KMnO4
HO
A (chiral) + B (achiral)
OH

(R) Identify A & B

2.
H2/Ni
C (chiral) + D (achiral)

Both C & D are C8H18, identify them.

(R)

3. Two stereoisomers are obtained from the reaction of HBr with (3S, 4S)-4-bromo-3-methyl-1-pentene.
one of the stereoisomer is optically active and the other is not. Explain?

Me H
+ HBr
Br H
Me
 O
NaOH
Predict the product with stereochemistry
D2O

(S)-2-Methyl-1-phenyl-butan-1-one

O
H2 O
OMe S O
S ?
O
O

1-((S)-1-Benzenesulfonyl-ethanesulf
onyl)-4-methoxy-benzene
1. When lactic acid is heated two diastereomeric compounds are formed.
one exhibits enantiomerism and the other is meso compound. Identify
the compounds and explain the reactions?

2.
O
NaOMe
HO2C S ?
O SPh

O
NaOMe
HO2C S ?
O SPh
 Consider a hydrocarbon, X (molecular formula C5H8) which
is optically active. This substance manifests all three
hybridization states of carbon (sp, sp2, and sp3). Reaction of
X with H2 over Pd metal catalyst forms n-pentane. Such
reactions do not break carbon-carbon bonds.

A. How many sites of unsaturation are in X?

B. Draw three dimensional structural formulas for X and for

any stereoisomers of X. Can you distinguish between the
stereoisomers using the information given here?

C. Are there any chiral carbon centers in X?

Cis-2,4-dimethylcyclobutanone on LAH reduction provides two alcohols, write down their
structures and comment on their chirality. The trans isomer on the other side yields only
one alcohol. Explain the phenomena?

Me O

Me
Hint:

OH OH
O
LAH
+

Both are achiral (meso)

OH OH
O
LAH
=

chiral
In the following reaction predict the final stereochemistry of the product acid?

a)SOCl2
b) Et3N
CO2H CO2H

c) H2O

(R)
Assign absolute configuration for each of these following molecules

OH

NH2 O
CN
SH
OH
CF3 OH
Br
CN
S
OH
State with explanations whether the following molecules are chiral or achiral?

O O
S

OH
CF3
N
CO2H CF3 F
HO O