1. Optical activity arises in organic compounds that lack a plane of symmetry and exist as enantiomers, which are non-superimposable mirror images of each other. 2. Compounds with stereocenters, such as a carbon atom bonded to four different groups, can exist as distinct stereoisomers including enantiomers and diastereomers. 3. The maximum number of stereoisomers for a molecule with n stereocenters is 2n; however, some stereoisomers may be identical or achiral "meso" compounds lacking asymmetry.

1. Optical Activity - Chirality
A b t b d d t f diff t ld l d t ti l ti it d i
A carbon atom bonded to four different groups could lead to optical activity and is
called a stereogenic center.
CH3
CH2CH3
HO
H
In general organic compounds, which lack a plane of symmetry are optical active and
are called chiral compounds.
OH OH
OH OH
Achiral Chiral
Optically active compounds exist as enantiomers, which are mirror images of each
other

2. Optical Activity - Chirality
cis-1,2-dichlorocyclohexane
If enantiomers are in equilibrium with each other through ring flipping, one enantiomer
q g g pp g,
cannot be separated from the other.
Cl Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Ring flip 120°

3. Optical Activity - Chirality
Enantiomers
trans-1,2-dichlorocyclohexane
Cl Cl
Cl Cl
Cl Cl
Ring flip
Cl Cl
Cl
Cl

4. Absolute Configuration: Cahn-Inglod-Prelog Rule
Atom or Reason for Priority: First Point of Difference
Substituents on a chiral carbon are assigned priority, based primarily on the atomic
number of the atom directly bonded to the carbon atom
-I
-Br
-Cl
Atom or
Group
Reason for Priority: First Point of Difference
(Atomic numbers)
bromine (35)
chlorine (17)
iodine (53)
-OH
-NH2
-SH
O
Cl
oxygen (8)
nitrogen (7)
sulfur(16)
chlorine (17)
O
-COH
O
-CNH2
O
carbon to oxygen, oxygen, then oxygen (6 ->8, 8, 8)
carbon to oxygen, oxygen, then nitrogen (6 ->8, 8, 7)
-CH
-CH2 OH
-CH2 CH3
-CH2 NH2
carbon to oxygen, oxygen, then hydrogen (6 ->8, 8, 1)
carbon to oxygen (6 -> 8)
carbon to carbon (6 -> 6)
carbon to nitrogen (6 -> 7)
2 3
-CH2 H
-H
( )
carbon to hydrogen (6 -> 1)
hydrogen (1)

5. Absolute Configuration: R and S Notations
Each stereogenic center is assigned a configuration based on the following rules
Each stereogenic center is assigned a configuration, based on the following rules
1. Use the Cahn-Ingold-Prelog priority rules to assign priority (one through four) to the
four groups on the chiral carbon atom.
2. Orient the molecule so that the lowest priority atom is in the back (away from you).
Look at the remaining three groups of priority 1-3 If the remaining three groups are
Look at the remaining three groups of priority 1-3. If the remaining three groups are
arranged so that the priorities 1→2→3 are in a clockwise fashion, then assign the chiral
center as R (“rectus” or right). If the remaining three groups are arranged 1→2→3 in a
counterclockwise manner, then assign the chiral center as S (“sinister” or left)

6. Orienting a Tetrahedron – The Double Switch
Interchanging any two groups inverts the stereochemistry. So switch the lowest priority
group to the desired position. Then switch any other two groups. The “double-switch”
does not change the stereochemistry.

7. Fischer Projections
Representation of a three-dimensional molecule as a flat structure. A tetrahedral carbon
is represented using just two crossed lines:
Horizontal line is coming out of the plane of the page (towards you) and vertical line is
going back behind the plane of the paper (away from you)
F
I Cl
F
Br
I
Br
Br
Cl
H
H
HOOC
CH3
OH
COOH
H3C OH

8. Manipulation of Fischer Projections
Rotating a Fischer projection by 180° retains the configuration
Rotating a Fischer projection by 180 retains the configuration
Rotating a Fischer projection by 90° inverts the configuration
g p j y g
If one group of a Fischer projection is held steady, the other three groups can be rotated
g p p j y, g p
clockwise or counterclockwise without altering the configuration.

9. Assigning R and S Configurations to Fischer Projections
1. Assign priorities to the four substitutents according to the Cahn-Ingold-Prelog
rules
2. Perform the two allowed manipulations of the Fischer projection to place the
lowest priority group at the top (or bottom).
3 If the priority of the groups 1→2→3 are clockwise then assign the center as R if
3. If the priority of the groups 1→2→3 are clockwise then assign the center as R, if
1→2→3 are counterclockwise then assign the center as S.
CH2CH3
H OH1
2
4
place at
the top
H
HO CH CH
1 2
4
CH3
H OH1
3
4
hold steady
CH3
HO CH2CH3
1 2
3
clockwise - R
hold steady clockwise R

10. Molecules with more than one Stereocenter
If a molecule has one stereocenter it exists as R and S isomers, which are enantiomers.
If a molecule has two stereocenters, each of them can exist as R and S, independent of
the other center.
The maximum number of stereoisomers for a molecule having n stereocenters is 2n
2,3-dibromopentane has 2 chiral centers.
There can be 4 stereoisomers, which are
(2R,3R)
(2R 3S)
(2R,3S)
(2S,3R)
(2S,3S)
(2R,3R) and (2S,3S) isomers are enantiomers, so are (2R,3S) and (2S,3R) isomers
(2R,3R) isomer is a diastereomer of (2R,3S) and (2S,3R) isomers
Similarly, (2S,3S) isomer is a diastereomer of (2R,3S) and (2S,3R) isomers

11. Stereoisomers of 2,3-dibromopentane
H
Br
CH3
R
Br
H
CH3
S
H
Br
Br H
CH2CH3
S
Br
H
H Br
CH2CH3
R
ers
2 3 2 3
CH CH
iastereome
Br
H
CH3
Br H
S
S
H
Br
CH3
H Br
R
R
Di
CH2CH3 CH2CH3
E i
Enantiomers

12. Stereoisomers of 2,3-dibromobutane
CH3 CH3
H
Br
Br H
CH
S
R
Br
H
H Br
CH
R
S
Here the RS and SR isomers are
identical molecules.
This diastereomer is called ‘meso’ and
CH3 CH3
This diastereomer is called ‘meso’ and
is an achiral molecule
This results from the plane of
Br
H
CH3
B H
S
S
H
Br
CH3
H B
R
R
symmetry present in this isomer.
Thus, although the maximum number
of stereoisomers can never be more
Br H
CH3
S
H Br
CH3
of stereoisomers can never be more
than 2n, the actual number could be
lower.
Enantiomers

13. Meso diastereomers
HO OH
H H
HO OH
H H
HO OH
H H
HO H HOOC COOH
H H
HO OH
HO H HOOC COOH
Cl
Cl Cl
Cl

14. Chirality Without a Stereocenter - Biphenyls
If X is a small group the single bond connecting the two phenyl rings would undergo
If X-is a small group, the single bond connecting the two phenyl rings would undergo
easy rotation and result in racemization
Chirality resulting from restricted rotation about a single bond is called
Atropisomerism

15. Chi li Wi h S All
Chirality Without a Stereocenter - Allenes

16. Chi li Wi h S S i C d
Chirality Without a Stereocenter – Spiro Compounds