Organic Chemistry: Enantiomers and Diastereomers: Enantiomers

Stereogenic Centers

What makes a molecule chiral? It turns out that in the majority of cases chiral molecules result from carbon atoms that are bonded to four different groups. For example, C₂ in 2-butanol is attached to the four distinct groups -H, -Me, -Et, and -OH. There are two different ways to arrange four groups about tetrahedr al carbon, giving rise to chirality. (In fact, chiral molecules gave chemists evidence that carbon is indeed tetrahedral.) Such a carbon atom is called an asymmetric carbon because it lacks a plane of symmetry. Asymmetric carbons are also called "chiral carbons". Because asymmetric carbons give rise to stereoisomerism, they are stereogenic centers or stereocenters. Technica lly, there are other structural motifs that are stereocenters beside asymmetric carbons, but in practice the term "stereocenter" is used in place of "asymmetric carbon" to denote a carbon bonded to four different substituents.

Figure %: General description of asymmetric carbon atoms that are bonded to four different groups.

(R)/(S) Nomenclature

The goal of nomenclature is to allow chemists to unambiguously identify the structure of any molecule given its name. The presence of stereoisomers presents a special problem in this regard. For example, given a particular molecule of 2-butanol, how can we name it so that the name conveys its handedness? How can we convey exactly which enantiomer of 2-butanol we're talking about? Furthermore, what about molecules that contain several stereocenters? What is needed is a nomenclature system to designate the absolute configuration at each stereocenter.

The term "configuration" refers to the fixed spatial positioning of bonds at a particular stereogenic carbon atom. Do not confuse "configuration" with "conformation". Unlike conformations, which are constantly equilibrating back and forth between forms, configurations are fixed and do not change unless bonds are broken. The configurational designation is absolute in the sense that the exact three-dimensional structure of the molecule can be reconstructed using the name alone.

In order to specify the absolute configuration at any stereogenic carbon, first identify the four groups attached to it and assign priorities to them using the Cahn-Ingold-Prelog convention:

Examine the atoms directly attached to the stereogenic carbon. Groups attached with atoms of higher atomic number receive higher priority.
In the case of isotopes, assign higher priority to the group containing the atom of higher atomic mass.
When the attached atoms are identical, move down the next branching bond of the highest priority, and repeat until a difference is found.

Figure %: Assigning priorities to groups on 2-butanol according to the Cahn-Ingold-Prelog convention

After assigning priorities, look at the molecule so that the group of lowest priority is facing away from you. Now trace a circular path from the group of highest priority to the group of second priority to the group of third priority. If this path is c lockwise, the stereocenter has an (R) configuration. If the path is counterclockwise, the stereocenter has an (S) designation.