Organic Chemistry: Concepts and Applications - Headley Allan D. 2020

Stereochemistry
5.4 Nomenclature of the Absolute Configuration of Chiral Molecules

Since enantiomers are different molecules, they must have different names. The IUPAC nomenclature system that has been used so far gives exactly the same name for enantiomers. Since enantiomers are different compounds, they should have different names even if they are slightly different. Three chemists, R.S. Cahn, C. K. Ingold, and V. Prelog, were the first to devise a system to allow chemists to differentiate between enantiomers by using an absolute assignment. In the Cahn-Ingold-Prelog system, a set of rules were developed using the designations R (from the Latin rectus, which means right handed) and S (from the Latin sinister, which means left handed). The R, S system was developed to assign an absolute configuration for the stereogenic centers of chiral molecules.

Rules for R and S Assignments

1. Assign priority numbers to each atom bonded to the stereogenic carbon based on the atomic number of the atom that is directly bonded to the chiral carbon. This system of priority assignment has been mentioned before in the section on geometric isomers of alkenes (Section 4.5.1).

2. Orient the molecule in such a way that the group of lowest priority is away from view, i.e. in the back.

3. Trace the path from the group of highest priority to the group of lowest priority. That is, #1 to #2 then to #3, exclude #4 since it is away from view.

4. If that path traced is clockwise, assign the absolute configuration of R; and if the path is counterclockwise, assign the absolute configuration of S.

Some students find it much easier to use the Fischer projection and to orient the molecule such that the group of lowest priority is in one of the vertical positions. Remember that the groups of the vertical positions are in the back when using the Fischer projection. With the molecule in the Fischer projection and if the group (or atom) of lowest priority is in one of the vertical positions, trace the priority of the other groups from #1 to #2, then #3 and if that path traced is clockwise, assign the absolute configuration of R; and if the path is counterclockwise, assign the absolute configuration of S. If the group of lowest priority is not in one of the vertical positions, but in one of the horizontal positions, trace the priority of the other groups from #1 to #2, then #3 and if that path traced is clockwise assign the opposite configuration, S. The same is done if the counterclockwise is obtained. Since there are only two possibilities for the assignment, R or S, the orientation obtained is opposite to that if the group of lowest priority were in the back. Shown below is an illustration of this method.

Thus, the complete IUPAC names for stereogenic compounds should include the absolute configuration, R or S. The complete IUPAC names of the stereogenic molecules of 1-bromo-1-chloroethane are shown below.

Problem 5.5

Give the absolute configuration for each of the following molecules; that is, assign R or S absolute configuration.

It is important to know that enantiomers are really different compounds and that each plays important roles in biological systems. The discovery that there are enantiomers of thalidomide and that one enantiomer is the compound for desired biological activity and that the other enantiomer led to serious medical consequences led chemists to emphasize the importance of the purity of enantiomers, especially when used for drugs. A large percentage of the pharmaceutical drugs on the market today are chiral and are sold as single enantiomers since slight contamination of the enantiomer can cause serious medical consequences. Thus, it is imperative that the pharmaceutical industry exercise extreme care not to have contamination of enantiomers in drugs that can cause harmful side effects. Table 5.1 shows the structures of some popular drugs on the market today and the importance of specific enantiomers.

Table 5.1 Examples of different enantiomers of drugs having different physiological actions, the star indicates the chiral center.