Other Sources of Chirality and Stereoisomerism

Although less common, it is possible for chirality in small molecules to arise not from a point or center but from a chirality axis. Take, for example, the case of substituted allenes, functional groups formed when two sp²hybridized carbon centers are joined by a single sp hybridized carbon atom. The central carbon atom in allenes is often represented by a solid dot, as illustrated in Figure 1.1. The two π bonds in an allene are orthogonal, meaning that the substituents at either end of an allene are not in the same plane, but rather are related by a 90° twist. This arrangement is illustrated in the drawing of a pair of allene-containing enantiomers below (Figure 1.1). These molecules may not look like enantiomers at first glance but more careful inspection will reveal that they are not superimposable. These enantiomeric allenes do not have a chirality center but rather possess a chirality axis that can be imagined as a line running through the three carbon atoms of the allene. A chirality axis is also present in some molecules wherein free rotation about a single bond is not possible or is slow on human time scales. This is illustrated for a pair of enantiomers that contain no sp³ hybridized carbon atoms at all, but do possess bulky bromine atoms that restrict rotation about a central C–C bond (Figure 1.1). These molecules are rendered chiral by the presence of a chirality axis running through the C–C bond that connects the two aryl rings.

Figure 1.1 Compounds that are chiral by virtue of a chirality axis. The compounds at left are examples of allenes in which a central sp hybridized carbon is joined via orthogonal π bonds to two sp² hybridized carbon atoms. The compounds at right are enantiomers in which the large bromine atoms prevent free rotation about the C–C bond connecting the aryl rings.

An example of an important antibiotic that possesses multiple chirality axes of this type is detailedas follow: Isomerism that results from hindered rotation about single bonds is referred to as atropisomerism. Usually this occurs when large groups are present in close proximity to a C–C single bond, thus hindering its rotation. Stereoisomers that result from atropisomerism will be either enantiomers or diastereomers, so the term atropisomer does not replace the normal terms we use to describe stereoisomers. Rather atropisomerism describes a mechanism by which isomerism can occur (hindered rotation about a bond). A notable example of atropisomerism is found in the remarkable chemical structure of vancomycin, illustrated at right. This “antibiotic of last resort” contains multiple chirality axes stemming from hindered rotations about both C–C and C–O bonds where the various aryl rings are joined.