Stereochemistry

The study of the three dimensional structure of molecules.

IsomersA review
Constitutional/Structural Isomers: differ in their bonding sequence; their atoms are connected differently. Stereoisomers: have the same bonding sequence, but differ in the orientation of their atoms in space. One special type of stereoisomerism that you have seen is geometric isomerism (e.g. cis/trans isomers).

Chirality
Chiral: a chiral object is one that has right and left handed forms, or a nonsuperimposable (nonidentical) mirror image. A chiral object has a mirror image that is different from the original object. An object that is not chiral is described as achiral. An atom is chiral only if it has four different groups attached to it. The mirror image of a chiral molecule is called its enantiomer.

Do problems 5-1, 5-2 and 5-3 in the text.

Chiral Molecules vs. Chiral Centers

A molecule with one chiral center is a chiral molecule. A molecule with more than one chiral center is achiral if it has a plane of symmetry. Enantiomers have identical physical properties (e.g. bp, mp, density) except that they rotate plane polarized light in equal but opposite directions. They are said to possess optical activity or to be optically active. Achiral molecules are not optically active!
Do problem 5-4 in the text.

Chiral: does not contain a plane of symmetry

Achiral: contains a plane of symmetry

Br H

H Br

Br H

Br H

chiral

achiral

Optical Activity
Optical Activity is measured with a polarimeter. A compound in a polarimeter can rotate plane polarized light to the right or left by a specific number of degrees that must be determined experimentally. Compounds that rotate plane polarized light to the right (clockwise) are called dextrorotatory (d), and compounds that rotate plane polarized light to the left (counterclockwise) are called levorotatory (l). In IUPAC notation, this is abbreviated by the signs (+) and (-) respectively.

Nomenclature of Chiral Carbon Atoms

The configuration about chiral carbons is named using the Cahn-Ingold-Prelog convention, which assigns to each chiral carbon atom a letter (R) or (S).

Cahn-Ingold-Prelog Rules:

Assign a priority to each group bonded to the chiral carbon. The higher the atomic number of the atom, the higher its priority. With different isotopes of the same element, the heavier isotopes have higher priority. When there is a tie, use the next atoms along the chain as tiebreakers. Treat double and triple bonds as if each were bonded to a separate atom.

Cahn-Ingold-Prelog Rules

Using a three dimensional drawing or a model, put the fourth priority group in the back and view the molecule along the bond from the chiral carbon to the fourth priority group. Draw an arrow from the first priority group, through the second, to the third. If the arrow points clockwise, the chiral atom is called (R). If the arrow points counterclockwise, the chiral atom is called (S).

Do problem 5-5 in the text.

Biological Discrimination of Enantiomers

Enantiomers can be distinguished through the use of chiral probes. A polarimeter is one example of a chiral probe. Enzymes are a type of chiral probe that are found in living systems. In general, just one out of a pair of enantiomers produces the characteristic effect; the other either has a no effect or has a totally different (and sometimes toxic) effect.
Do problem 5-10 in the text.

Racemic Mixtures
A mixture that contains equal amounts of a pair or enantiomers is called a racemic mixture or a racemate, a () pair, or a (d,l) pair. A racemic mixture is symbolized by placing () or (d,l) in front of the name of the compound. Racemic mixtures are optically inactive. Since the enantiomers rotate plane polarized light in equal but opposite directions, the net result is an optical rotation of zero.

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)

Chiral Compounds Without Chiral Atoms

There are some molecules that do not contain chiral carbons but are chiral.

Biphenyls: some ortho substituted biphenyls are locked into one of two chiral, enantiomeric staggered conformations.
Br Br Br Br

I I

I I

Staggered conformation (chiral)

Staggered conformation (chiral)

Chiral compounds without chiral atoms

Allenes: Compounds containing a C=C=C unit are

called allenes. In allene, the central C atom is sp hybridized, but the two outer carbons are sp2. The whole molecule does not lie in the same plane. An allene is

chiral if each end has two distinct substituents.

H3C C H C C H H CH3 H3C C C C H CH3

Enantiomers of 2,3-pentadiene Do problem 5-14 in the text.

Fischer Projections

Easiest to use when > 1 chiral center Sugars almost always drawn as FP The carbon chain is always drawn along the vertical line of the Fischer projection The rules for assignment of R,S configurations are the same.

C C

horizontal is always coming out at you

consider each chiral center separately

Do problems 5-15, 5-16, 5-17 and 5-18.

Diastereomers
Must have >1 chiral center Stereoisomers which are not enantiomers. i.e. stereoisomers that are not mirror images. Have different physical properties The maximum # of stereoisomers = 2n where n is the number of chiral centers. Examples of diastereometric relationships include cis/trans isomerism in rings and cis/ trans isomerism about double bonds.

Do problem 5-19 and 5-22 in the text.

Diastereomers

HO H CH3 CH3 H Br
(2R, 3S)-3-bromo-2-butanol

HO H CH3 Br CH3 H

(2R, 3R)-3-bromo-2-butanol

DIASTEREOMERS MIRROR IMAGES AT C3 BUT NOT AT C2

Meso Compounds
has >1 chiral center chiral centers are mirror images

has mirror plane through center of molecule

contains chiral centers, but compound is achiral

doesnt rotate light

no enantiomeric pair (mirror images superimposable)

Resolution of Enantiomers
The separation of enantiomers is called resolution. A chiral probe is necessary for the resolution of enantiomers. Such a probe is called a resolving agent. Enantiomers can be resolved chemically or chromatographically.