Geometric isomerism of alkenes, cyclic compounds: cis-trans and (E)-(Z) system of nomenclature b) Conformational isomers: Open chain and cyclic system c) Chirality of molecules: Enantiomers, diastereomers, racemic modification, Meso compound, R & S configuration, sequence rule, Optical rotation d) Asymmetric synthesis: Preparation of enantiomers by asymmetric synthesis & optical resolution method e) Stereo selective and stereo specific reaction f) Pharmaceutical importance of studding stereochemistry

2. Geometric Isomerism
Two possible configurations of 1,2-dichloroethane
These two models represent exactly the same molecule. These
molecules are not isomers
But what happens if you have a carbon-carbon double bond - as
in 1,2-dichloroethene?
These two molecules aren't the same.
In one, the two chlorine atoms are locked on opposite sides of the double bond.
This is known as the trans isomer. (trans : from latin meaning "across" - as in
transatlantic).
In the other, the two chlorine atoms are locked on the same side of the double
bond. This is know as the cis isomer. (cis : from latin meaning "on this side")

3. Definition
• The isomerism which occurs due to difference of the positions of the
substituents about a double bond or a ring is called geometric
isomerism.
It is also known as cis-trans isomerism.
Conditions for geometric isomerism
• There must be a carbon-carbon double bond in the compounds.
• Each of the carbon of the double bond must be attached to two
different substituents.
• Now…… Are these compounds below geometric isomers?
Geometric Isomerism
C C
H3C
C2H5
H
H
C C
C2H5
H3C
H
H
C C
H3C
H
C2H5
C2H5
H
CH3
C C
H3C
H
C2H5
H
C2H5
CH3

4. Why does geometric isomerism occur?
• Geometric isomerism occurs because there is no possibility of
free rotation about a double bond or a ring.
• As a result, the substituents are fixed in position. They can’t
change position without breaking bond.
• So, the two structures above are separate compounds, and
therefore isomers.
Types of geometric isomers
• There are two methods to denote geometric isomers. According
to these two methods there are:
C C
H3C
H
H
CH3
C C
H
H3C
H
CH3
can't rotate about
the double bond into
Cis or Trans isomers E or Z isomers
Geometric Isomerism Contd.

5. Cis/trans isomerism
• This method of denoting geometric isomerism works best when the
alkene is di-substituted. In fact, it will always work when the alkene is
di-substituted (and other conditions are fulfilled).
• But this method can fail with tri-substituted or tetra-substituted
alkenes.
Cis isomer
• The geometric isomer in which the identical groups on two carbons of
the double bond are on the same side of the double bond is called the
cis isomer.
Trans isomer
• The geometric isomer in which the identical groups on the two
carbons of the double bond are on the opposite sides of the double
bond is called the trans isomer.
• In cases of ring compounds, if the groups are on the same side of the
ring then it is cis and if on the opposite sides then it is trans.
Geometric Isomerism Contd.

6. • For this cis/trans method of denoting to work, there must be
at least one identical group on each carbon of the double
bond. For example:
C C
H3C
H
CH3
H
C C
C2H5
H
CH3
H
C C
C2H5
H3C
C2H5
H
C C
C2H5
H3C
CH3
C2H5
C C
C2H5
H3C
C3H7
H
Disubstituted Disubstituted Trisubstituted
Tetrasubstituted Trisubstituted
C C
C2H5
H3C
C4H9
C3H7
Tetrasubstituted
Geometric Isomerism Contd.

7. Cis isomer is less stable than trans isomer
• In cis isomer, two large groups on the separate carbons are always on
the same side. Thus, these two groups are closer to each other and repel
each other. This is called steric strain.
• On the other hand, in trans isomer the two large groups are on the
opposite sides. So they are far apart. Hence they don’t repel each other.
So, the steric strain is far less.
• This is why cis isomer is less stable than trans isomer.
Geometric Isomerism Contd.
C C
C2H5
H
CH3
H
cis-pentene-2
C C
C2H5
H
H
CH3
trans-pentene-2
large groups are close large groups are far

8. E/Z isomerism
• E/Z method of denoting geometric isomers is universal.
• This method will not fail even when cis/trans method has
failed.
• While this method can work on all compounds that have
geometric isomers, it is used for those compounds where
cis/trans method fails.
• According to this method, the groups attached to each carbon
of the double bond are analyzed and then given priorities
according to Cahn-Ingold-Prelog (CIP) rules.
• If the group of highest priority on both carbon are on the
same side, then it is Z (Z = Zusammen = Together) isomer, if
they are on opposite sides, then it is E (E = Entgegen =
Opposite) isomer.
Geometric Isomerism Contd.

9. CIP rules for E/Z naming convention
• Substituents on any one of the two double-bonded carbon
atom is looked at.
• First, the atom which is directly attached to the double bond
carbon is looked at. This is the first atom. The group where
first atom has higher atomic number has higher priority.
Geometric Isomerism Contd.
C C
C
Br
C2H5
H
H3C
H H
Atomic number = 35
Atomic number = 12
Bromine gets
priority so
C C
C2H5
Br
C2H5
H
Priority 2
Priority 1

10. • If, both groups are attached by the same first atom,
then the atomic number of the second atom (atom
attached to first atom) is looked at.
• Similarly, if the second atoms are also same, third
atoms are looked at.
Geometric Isomerism Contd.
C C
C
C
C2H5
H
C
H H
Atomic number = 12
Atomic number = 16
Oxygen gets
priority so
C C
C2H5
HOH2C
C2H5
H
Priority 2
Priority 1
O
H H
H
H
H
H

11. • If the first atoms of two groups have the same higher atomic number
substituents, one with more such substituent is given higher priority.
Geometric Isomerism Contd.
C C
C
C
C2H5
H
C
H H
Atomic number = 12
Atomic number = 1
Carbon gets
priority so
C C
C3H7
C2H5
C2H5
H
Priority 1
Priority 2
C
H H
H
C
H H
H HH
H
H
C C
CH2
HC
C2H5
H
One higher atomic number substituent
Two gets
priority so
C C
ClH2C
Cl2HC
C2H5
H
Priority 2
Priority 1Cl Cl
Cl
Two higher atomic number substituent

12. • If there is any double bond or triple bond within the group, it is
considered at two or three single bonds respectively. So:
• Exemplary:
• If there is a phenyl group attached to first atom, then it is thought that
First atom is attached to three carbons.
Geometric Isomerism Contd.
C C
CH2
C
C2H5
H
first atom is attached to one O and two H
Two gets
priority so
C C
HOH2C
OHC
C2H5
H
Priority 2
Priority 1O H
HO
First atom is attached to two O and one H
C
O
H C
O O
Hmeans

13. • Example of E and Z isomers:
• Z isomer is not always cis and E isomer is not always trans
Geometric Isomerism Contd.
C C
C2H5
H3C
C2H5
H
Priority 1
Priority 2
Priority 1
Priority 2
Z-3-methylhexene-3
C C
C2H5
H3C
H
C2H5
Priority 1
Priority 2
Priority 2
Priority 1
E-3-methylhexene-3
C C
C2H5
Br
C2H5
H
Priority 1
Priority 2 Priority 1
Priority 2
E-3-bromohexene-3
[cis-bromohexene-3]
C C
C2H5
Br
H
C2H5
Priority 1
Priority 2 Priority 2
Priority 1
Z-3-bromohexene-3
[trans-bromohexene-3]

14. Representation of optical isomerism
• In general optical isomerism is represented
based on two criteria:
• Based on optical activity
– d/l method (old).
– (+)/(-) method (modern).
• Based on configuration around chiral carbon.
– D/L method (limited use).
– R/S method (universal).
Optical Isomerism Contd.

15. Optical isomers based on optical activity
• Based on the ability to rotate the plane of the
plane-polarized light, optical isomers are divided
into two types.
– Dextrorotatory: Rotates the plane to the right. It is
denoted by d- or (+).
– Levorotatory: Rotates the plane to the left. It is denoted by
l- or (-).
Optical Isomerism Contd.

16. Optical Isomerism Contd.
CH
COOH
OH
CHO H
COOH
This compound is denoted
()-tartaric acid because it's
specific optical rotation is 12o
On the other hand, it is denoted
L-tartaric acid because the OH group
on the carbon before terminal is on the left,
it has nothing to do with optical rotation
CHO
COOH
H
CH OH
COOH
This compound is denoted
()-tartaric acid because it's
specific optical rotation is 12o
On the other hand, it is denoted
D-tartaric acid because the OH group
on the carbon before terminal is on the right,
it has nothing to do with optical rotation
d/l or (+)/(-) denotation is placed on a compound after its optical
rotation is measured with a polarimeter. D/L or R/S denotion has
nothing to do with it.

17. D/L configuration
• D and L method is used to describe the position of the
atoms/groups around the chiral carbon. It doesn’t tell whether
the compound is dextrorotatory or levorotatory.
• This method was proposed by Rosanoff in 1906.
• This method uses the two enantiomers of Glyceraldehyde as
reference molecules.
• Any compound which looks like or degrades to D-glyceraldehyde
would be denoted by D- and any compound which looks like or
degrades to L-glceraldehyde would be denoted by L-.
Optical Isomerism Contd.
CHO
C
CH2OH
HO H
This enantiomer is dextrorotatory,
Rosanoff designated this molecule
as D-glyceraldehyde
CHO
C
CH2OH
H OH
This enantiomer is levorotatory,
Rosanoff designated this molecule
as L-glyceraldehyde

18. D/L naming method
• It can be applied to compounds which are similar to
glyceraldehyde or degrades to glyceraldehyde.
• This method is applied to:
– Carbohydrates
– Derivative of carbohydrates (e.g. some carboxylic acids, aldehydes)
– Amino acids
• For this method, first Fischer projection of the compound
must be drawn.
• For carbohydrates and its derivatives, the position of the
OH group on the highest numbered chiral carbon is
looked at. If the OH group is on the left it is termed L-
and if it on the right then it is termed D-.
Optical Isomerism Contd.

19. Optical Isomerism Contd.
CHO
C
CH2OH
HO H
CHO
C
CH2OH
H OH
L-glyceraldehyde D-glyceraldehyde
CHO
2
C
1
C
3
C
4
C
5
CH2OH
6
HO H
H OH
HO H
HO H
L-glucose
CHO
2
C
1
C
3
C
4
C
5
CH2OH
6
H OH
HO H
H OH
H OH
D-glucose
CH2OH
2
C
1
C
3
C
4
C
5
CH2OH
6
HO H
H OH
HO H
HO H
CH2OH
2
C
1
C
3
C
4
C
5
CH2OH
6
H OH
HO H
H OH
H OH
D-sorbitolL-sorbitol
CH2OH
2
C
1
C
3
C
4
C
5
COOH
6
HO H
H OH
HO H
HO H
CH2OH
2
C
1
C
3
C
4
C
5
COOH
6
H OH
HO H
H OH
H OH
D-glucoronic acidL-glucoronic acid

20. Optical Isomerism Contd.
L-lactic acid
CH3
C
COOH
HO H
CH3
C
COOH
H OH
D-lactic acid
L-erythrose D-erythrose
CHO
C
C
CH2OH
H OH
H OH
CHO
C
C
CH2OH
HO H
HO H
C
C
C
C
C
CH2OH
HO H
H OH
HO H
HO H
L-heptoglucose
C
C
C
C
C
CH2OH
H OH
HO H
H OH
H OH
D-heptoglucose
CHO CHO
HO H H OH

21. R/S configuration
• D/L method of expressing chiral carbon
configuration works on only a few types of
compounds.
• To express the configuration of chiral carbons in
other compounds, we need another method.
• This other method is the R/S method. This method
is universal, meaning that this method works on
any compound.
• In R/S method, the configuration of each chiral
carbon of the compound is described.
Optical Isomerism Contd.

22. R/S naming method
1. First, every chiral carbons in the molecule are identified.
2. Then the configuration in each chiral carbon is
determined.
3. To determine the configuration, the groups attached to
the chiral carbons are assigned priority 1, 2, 3, and 4
according to Cahn-Ingold-Prelog (CIP) rules.
4. The group with priority 4 (lowest priority) is sent to the
back. Then it is identified which direction follows if one
goes from 1 → 2 → 3.
5. If the direction is right (clockwise), the chiral carbon is at
R (R = rectus, meaning right) configuration.
6. If the direction is left (anticlockwise), the chiral carbon is
at S (S = sinister, meaning left) configuration.
Optical Isomerism Contd.

23. CIP rules with examples
• The group whose first atom (atom connected to the chiral
carbon) has highest atomic number is given priority 1 and so
on.
Optical Isomerism Contd.
Br C
F
I
H
Priority 3
(atomic number = 9)
Priority 1
(atomic number = 53)
Priority 2
(atomic number = 35)
Priority 4
(atomic number = 1)
Anticlockwise direction, steering wheel to the right
So, it is at R configuration
R-Bromo-fluoro-iodo-methane

24. • If first atoms are identical, then second atom will be
looked at. If the second atoms are also identical, third
atom will be looked at and so on.
• If the first atoms are identical, second atoms are also
identical, then the group with greater number of high
atomic number second atoms is given higher priority.
Optical Isomerism Contd.
The number of the chiral
carbon is written before
the configuration is
written
NC C
CH2OH
C2H5
CH3
Priority 1
Priority 2
Priority 3
Priority 4
(2S)-2-Hydroxymethyl-2-methyl-butyronitrile

25. • If there is any double or triple bond, then it is considered as
two single bonds or three single bonds respectively.
Optical Isomerism Contd.
NC C
CH2OH
CHCl2
CH2Cl
Priority 1
Priority 2 Priority 3
Priority 4
(2S)-3,3-Dichloro-2-chloromethyl-2-hydroxymethyl-propionitrile
HOOC C
CH2OH
CHCl2
CH2Cl
Priority 2
Priority 1
Priority 3
Priority 4
(2R)-3,3-Dichloro-2-chloromethyl-2-hydroxymethyl-propionic acid

26. • It is important to note however that Fischer projection is not always
reliable, and one should convert the Fischer projection into wedge
and dash projection.
Optical Isomerism Contd.
C
Br
H F
CH3
C
Br
H F
CH3
Br
H3C
H
F
If the configuration is determined from Fischer projection,
then this compound is (S)-1-Bromo-1-fluoro-ethane
But actually the configuration is R
C
Br
H F
CH3
CH3
Br
F
H
Now the configuration is R
Br
H3C
H
FWhen is looked with the H (4th priority)
away from the viewer, it looks like
Fischer projection in wedge and dash projection looks like following

27. A Simple trick
• If the lowest priority group (priority 4 group) is bonded by vertical bonds,
then we can use the Fischer projection to determine R/S configuration
directly.
• If the lowest priority group is bonded by horizontal group, then
determine the R/S configuration directly. The correct configuration is
the opposite of the configuration determined.
Optical Isomerism Contd.
Br C
F
I
Cl
Lowest priority group is vertically bonded,
just figure out the configuration
Br
C F
I
Cl
Lowest priority group is vertically bonded,
figure out the configuration. The opposite of
that configuration is the correct one
S configuration From Fischer projection: S configuration
Actual: R configuration

28. • Find the configuration of following structures
Optical Isomerism Contd.
H3C C
CH2OH
OH
C
Br
Cl
CH3
(2R, 3S)-3-Bromo-3-chloro-2-methyl-butane-1,2-diol
Cl
CHOOC CH3
H
(2S)-2-Chloro-propionic acid
COOH
CH OH
CH3
(R)-Lactic acid
CHO
C
C
C
C
CH2OH
H OH
HO H
H OH
H OH
(2R, 3S, 4R, 5R)-Pentahydroxyhexanal
CHO
C
C
C
C
CH2OH
HO H
H OH
HO H
HO H
(2S, 3R, 4S, 5S)-Pentahydroxyhexanal

34. The stereoisomers of
aldohexoses• Monosaccharides which contain six carbons and a aldehyde group are called
aldohexoses.
• Aldohexose contains 4 chiral carbons, so a total of 24=16 stereoisomers are
there.
CHO
C
C
C
C
CH2OH
HO H
H OH
HO H
HO H
CHO
C
C
C
C
CH2OH
H OH
HO H
H OH
H OH
CHO
C
C
C
C
CH2OH
H OH
H OH
H OH
H OH
CHO
C
C
C
C
CH2OH
HO H
HO H
HO H
HO H
CHO
C
C
C
C
CH2OH
HO H
H OH
H OH
H OH
CHO
C
C
C
C
CH2OH
H OH
HO H
HO H
HO H
CHO
C
C
C
C
CH2OH
H OH
H OH
HO H
HO H
CHO
C
C
C
C
CH2OH
HO H
HO H
H OH
H OH
CHO
C
C
C
C
CH2OH
HO H
HO H
H OH
HO H
CHO
C
C
C
C
CH2OH
H OH
H OH
HO H
H OH
CHO
C
C
C
C
CH2OH
HO H
H OH
HO H
H OH
CHO
C
C
C
C
CH2OH
H OH
HO H
H OH
HO H
CHO
C
C
C
C
CH2OH
HO H
H OH
H OH
HO H
CHO
C
C
C
C
CH2OH
H OH
HO H
HO H
H OH
CHO
C
C
C
C
CH2OH
H OH
H OH
H OH
HO H
CHO
C
C
C
C
CH2OH
HO H
HO H
HO H
H OH
D-glucose
(+53o
)
L-glucose
(-53o
)
D-mannose
(+14o
)
L-mannose
(-14o
)
D-allose
(+14o
)
L-allose
(-14o
)
D-altrose
(+33o
)
L-altrose
(-33o
)
D-gulose
(-20o
)
L-gulose
(+20o
)
D-iodose
(+15o
)
L-iodose
(-15o
)
D-galactose
(+80o
)
L-galactose
(-80o
)
D-talose
(+21o
)
L-talose
(-21o
)

35. The stereoisomers of
aldohexoses Contd.
CHO
C
C
C
C
CH2OH
HO H
H OH
HO H
HO H
CHO
C
C
C
C
CH2OH
H OH
HO H
H OH
H OH
CHO
C
C
C
C
CH2OH
H OH
H OH
H OH
H OH
CHO
C
C
C
C
CH2OH
HO H
HO H
HO H
HO H
CHO
C
C
C
C
CH2OH
HO H
H OH
H OH
H OH
CHO
C
C
C
C
CH2OH
H OH
HO H
HO H
HO H
CHO
C
C
C
C
CH2OH
H OH
H OH
HO H
HO H
CHO
C
C
C
C
CH2OH
HO H
HO H
H OH
H OH
CHO
C
C
C
C
CH2OH
HO H
HO H
H OH
HO H
CHO
C
C
C
C
CH2OH
H OH
H OH
HO H
H OH
CHO
C
C
C
C
CH2OH
HO H
H OH
HO H
H OH
CHO
C
C
C
C
CH2OH
H OH
HO H
H OH
HO H
CHO
C
C
C
C
CH2OH
HO H
H OH
H OH
HO H
CHO
C
C
C
C
CH2OH
H OH
HO H
HO H
H OH
CHO
C
C
C
C
CH2OH
H OH
H OH
H OH
HO H
CHO
C
C
C
C
CH2OH
HO H
HO H
HO H
H OH
D-glucose
(+53o
)
L-glucose
(-53o
)
D-mannose
(+14o
)
L-mannose
(-14o
)
D-allose
(+14o
)
L-allose
(-14o
)
D-altrose
(+33o
)
L-altrose
(-33o
)
D-gulose
(-20o
)
L-gulose
(+20o
)
D-iodose
(+15o
)
L-iodose
(-15o
)
D-galactose
(+80o
)
L-galactose
(-80o
)
D-talose
(+21o
)
L-talose
(-21o
)