Optical Activity - Chirality
A carbon
b atom t b d d to
bonded t four
f diff
different
t groups could
ld lead
l d to
t optical
ti l activity
ti it andd is
i
called a stereogenic center.
CH3
H
CH2CH3
HO
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
Optical Activity - Chirality
cis-1,2-dichlorocyclohexane
If enantiomers are in equilibrium
q with each other through
g ringg flipping,
pp g, one enantiomer
cannot be separated from the other.
Cl Cl Cl
Cl
Ring flip 120°
Cl Cl
Optical Activity - Chirality
trans-1,2-dichlorocyclohexane
Enantiomers
Cl Cl
Cl Cl
Ring f lip
Cl Cl
Cl Cl
Absolute Configuration: Cahn-Inglod-Prelog Rule
Substituents on a chiral carbon are assigned priority, based primarily on the atomic
number of the atom directly bonded to the carbon atom
Atom or Reason for Priority: First Point of D ifferen ce
Grou p (Atomic numbers)
-I iodine (53)
-Br bromin e (35)
-Cl
Cl ch lorine (17)
-SH su lfu r (16)
-OH oxygen (8)
-NH2 nitrogen (7)
O
-COH carbon to oxygen, oxygen, th en oxygen (6 ->8, 8, 8)
O
-CNH2 carbon to oxygen, oxygen, th en nitrogen (6 ->8, 8, 7)
O
-CH carbon to oxygen, oxygen, th en hydrogen (6 ->8, 8, 1)
-CH2 OH carbon to oxygen (6 -> 8)
-CH2 NH2 carbon to nitrogen (6 -> 7)
-CH2 CH3 carbon to carbon ((6 -> 6))
-CH2 H carbon to hydrogen (6 -> 1)
-H hydrogen (1)
Absolute Configuration: R and S Notations
Each stereogenic center is assigned a configuration,
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.
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)
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.
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 F
I Cl
I
Br Br
Cl
H
H
H3C OH
OH
HOOC
CH3 COOH
Manipulation of Fischer Projections
Rotating a Fischer projection by 180
180° retains the configuration
Rotatingg a Fischer pprojection
j byy 90° inverts the configuration
g
If one ggroupp of a Fischer pprojection
j is held steady,
y, the other three ggroups
p can be rotated
clockwise or counterclockwise without altering the configuration.
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
3. If the priority of the groups 1→2→3 are clockwise then assign the center as R,
R if
1→2→3 are counterclockwise then assign the center as S.
place at
the top
2 CH2CH3 4H
4H OH 1 1HO CH2CH3 2
3 CH3 3 CH3
hold steady clockwise - R
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
Stereoisomers of 2,3-dibromopentane
CH3 CH3
R S
Br H H Br
S R
Diiastereomeers Br H H Br
CH2CH3 CH2CH3
CH3 CH3
S R
H Br Br H
S R
Br H H Br
CH2CH3 CH2CH3
E
Enantiomers
i
Stereoisomers of 2,3-dibromobutane
CH3 CH3
R S
Br H H Br Here the RS and SR isomers are
S R identical molecules.
Br H H Br
CH3 CH3 This diastereomer is called ‘meso’ and
is an achiral molecule
This results from the plane of
CH3 CH3 symmetry present in this isomer.
S R
H Br Br H Thus, although the maximum number
S R of stereoisomers can never be more
B
Br H H B
Br
than 2n, the actual number could be
CH3 CH3 lower.
Enantiomers
Meso diastereomers
HO H H OH HO OH
HO H H OH H H
HO H HOOC COOH
Cl Cl Cl
Cl
Chirality Without a Stereocenter - Biphenyls
If X-is
X is a small group,
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
Chi li Without
Chirality Wi h a Stereocenter
S - Allenes
All
Chi li Without
Chirality Wi h a Stereocenter
S – Spiro
S i Compounds
C d
