Chemistry for update: Chirality II

Introduction

A large part of our introductory discussion of chirality and optical activity involved the definition of new concepts. The ideas we considered included

chirality
stereoisomers
enantiomers
Cahn-Ingold-Prelog rules
optical activity
specific rotation
polarimetry
racemic mixture
enantiomeric excess

Most of the examples we considered involved molecules which contained a single chiral atom. In this section we will look at structures which contain two or more chiral centers. We'll start with a structure of historical importance, tartaric acid. Over 100 years ago, Louis Pasteur noticed that a sample of sodium ammonium tartrate, a salt of tartaric acid used in wine making, contained two crystalline forms. Pasteur separated the two forms using a pair of tweezers. Careful investigation revealed the following facts:

One form was the mirror image of the other.
A solution of the two forms was optically inactive.
Solutions of the individual forms were optically active. Moreover, the specific rotations of teh two forms were equal in magnitude, but opposite in sign.

In essence, this was the birth of stereochemistry. The compound that Pasteur examined contained two chiral carbon atoms. In general, a compound that contains n chiral atoms can exist in 2ⁿ stereoisomeric forms. These stereosiomers may be sub-divided into two groups, enantiomers and diastereomers.

Diastereomers

If a compound contains two chiral atoms, it may exist in four stereoisomeric forms. Since the configuration at each chiral carbon may be either R or S, there are four stereochemical possibilities: RR, SS, RS, and SR. The RR and SS stereoisomers are enantiomers. The RS and SR stereoisomers are also enantiomers. The RR stereoisomer is a diastereomer of both the RS and the SR stereoisomers. The SS stereoisomer is a diastereomer of both the RS and SR stereoisomers. Confused? Figure 1 should make things a bit clearer. It shows sawhorse projections of the four stereoisomers of 2-chloro-3-fluorobutane.

Figure 1

Ride 'em Cowboy

The enantiomeric pairs are shown in matching colors in the figure. Notice that the configurations at C-2 and C-3 of one enantiomer are reversed in the other. For diastereomers the configurations are opposite at only one of the two chiral centers. So what is the definition of diastereomers? Diastereomers are stereosiomers that are not enantiomers.

Exercise 1 A compound that contains 3 chiral atoms may exist in eight stereoisomeric forms. If one of them is designated RRR, what are the designations for the other seven?

Exercise 2 The group attached to C-2 that has priority 2 in 2-chloro-3-fluorobutane is CH(F)CH₃. What are the other three groups ? Enter the group with priority 1 in the first box, priority 3 in the second box, and priority 4 in the third box.

Exercise 3 What are the four groups attached to C-3 in 2-chloro-3-fluorobutane? Enter the group with priority 1 in the first box, priority 2 in the second box, etc.

Unlike enantiomers, diastereomers have different physical properties. They have different melting points, boiling points, densities, etc. While the optical rotations of enantiomers are equal and opposite, there is no a priori relationship between the optical rotations of diastereomers. This should be apparent from the structures and optical rotations of the four stereoisomers of the amino acid threonine shown in Figure 2. The naturally occuring stereoisomer of threonine is enclosed in the box within the box.

Figure 3

More 'mers

Exercise 4 Of the four groups attached to C-2 in threonine, the CH(OH)CH₃ group has priority 2. Enter the group with priority 1 in the first box, priority 3 in the second box, and priority 4 in the third box.

Exercise 5 What are the four groups attached to C-3 in threonine? Enter the group with priority 1 in the first box, priority 2 in the second box, etc. Use the parenthetical format shown in Exercise 4 to enter groups with a branched structure.

Let's return to Pasteur's compound, tartaric acid. We mentioned earlier that this compound contains two chiral carbon atoms, and that, in general, a compound that contains n chiral atoms can exist in 2ⁿ stereoisomeric forms. Tartaric acid proves the exception to this rule. There are only three stereoisomeric forms of tartaric acid. They are shown in Figure 4.

Figure 4

Rules Are Made To Be Broken

It should be apparent that the structures shown in red are mirror images. Closer inspection, however, will reveal that they are not enantiomers. They are two molecules of the same compound. It is called DL-tartaric acid. Imagine an axis that lies half way between C₂and C₃ in the H-C₂-C₃-H plane of the left hand structure. If you rotate the structure by 180^o around that axis, you will generate a new orientation which is identical to the right hand structure. Furthermore, you should recognize that there is an internal symmetry plane that bisects the C₂-C₃bond in both representations of DL-tartaric acid. This situation arises from the fact that the H, OH, and CO₂H groups on C₂ occupy mirror image positions with respect to those same groups on C₃. Stereoisomers of molecules which contain two or more chiral centers and an internal plane of symmetry are called meso compounds. They are not optically active even though they contain chiral atoms. Remember, net optical rotation can occur only in solutions where one molecule cannot assume an orientation that is the mirror image of the orientation of another molecule.

DL-tartaric acid is sometimes called meso-tartaric acid. It is a diastereomer of D-tartaric acid and L-tartaric acid. Notice that the H, OH, and CO₂H groups on C₂ of D-tartaric acid do not occupy mirror image positions relative to the H, OH, and CO₂H groups on C₃, nor do they in the naturally occuring form, L-tartaric acid.

Exercise 6 Which of the following molecular formulas represents a compound that can exist as a meso structure?