Optical Activity - Chirality

A carbon atom bddbonded to four different groups could ldlead tooptical activit yand is 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 with each other throughring flipping, 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 flip

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 Difference Group (Atomic numbers) -I iodine (53) -Br bromine (35) -Cl chlorine (17) -SH sulfur (16) -OH oxygen (8)

-NH2 nitrogen (7) O -COH carbon to oxygen, oxygen, then oxygen (6 ->8, 8, 8) O

-CNH2 carbon to oxygen, oxygen, then nitrogen (6 ->8, 8, 7) O -CH carbon to oxygen, oxygen, then 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 , 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 arranged so that the priorities 1→2→3areinaclockwise fashion, then assign the chiral center as R (“rectus” or right). If the remaining three groups are arranged 1→2→3ina 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 Cl Br

H H H C OH OH 3 HOOC COOH CH3 Manipulation of Fischer Projections Rotating a Fischer projection by 180° retains the configuration

Rotating aFischer ppjrojection byy 90° inverts the configuration

If one ggproup of aFischer ppjrojection is held steady, the other three ggproups 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. 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.

place at the top 2CH2CH3 4H

4H OH1 1HO CH2CH32

3CH3 3CH3

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) (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 Br H H Br

rs CH CH CH CH ee 2 3 2 3 astereom ii CH3 CH3 D S R H Br Br H S R Br H H Br

CH2CH3 CH2CH3

Enantiomers 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 This diastereomer is called ‘meso’ and CH3 CH3 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 Br H H Br of stereoisomers can never be more 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 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 Chira lity Wi th out a S tereocenter - Allenes Chira lity Wi th out a S tereocenter – SiSpiro Compoun ds