2.1. Overview of Chirality
The word chirality is derived from the ancient Greek word for "hand" and means handedness, reflecting the left and right-handedness of the molecules that are chiral in nature. In fact, the left and right hands are perfect examples for demonstrating the non-superimposable property of chiral objects. The left and right hands are mirror images of each other, and no matter how the two are arranged, one cannot be placed directly over the top of the other in the exact same orientation. Chiral molecules are molecules whose mirror images are not superimposable upon each other. Likewise, achiral compounds have superimposable mirror images.

Compounds that have the same atoms connected in the same order but differ from each other in the way the atoms are oriented in space are called stereoisomers. Enantiomers are chiral molecules that are structurally different from each other only in the left and right-handedness of their orientations (Exhibit 2.1) i.e. no matter how the two are arranged, one cannot be superimposed on the other in exactly the same orientation. Enantiomers have the same physical properties, but behave differently under certain conditions. They react in different ways and at different rates with other chiral compounds and may react at different rates in the presence of chiral catalysts and optically active solvents. A useful way to think of this phenomenon is that it is analogous to putting your right hand into a left-handed glove--the "fit" isn't the same as if you were to put your right hand into a right-handed glove.

Exhibit 2.1 Chirality--Handed/Mirror-Image Relationship

When polarized light is passed through a pure sample of each enantiomer, the plane of the polarized light is rotated in opposite directions, in equal amounts, by the two enantiomers. The material is considered to be optically active if rotation of the plane of the polarized light occurs. Isomers are referred to as levo-, and indicated with the notation (-) if they rotate polarized light to the left, and dextro-, notated as (+) if they rotate polarized light to the right.

A racemic mixture, or racemate, is the term used to describe a mixture of equal amounts of enantiomers. A racemate is optically inactive because the opposite rotations of the two enantiomers cancel each other out. Any chemical reaction that comprises solely of achiral or racemic starting materials, reagents, and solvents will result in a racemic mixture or optically inactive products.

The absolute configuration of a molecule indicates the actual arrangement of the substituents in the chiral compound. The direction of rotation of plane polarized light bears no relationship to the absolute configuration of a chiral molecule. Originally, the absolute configuration of all compounds was related back to the isomers of compounds called glyceraldehydes, which were assigned as D- (rotates plane polarized light to the right) and L- (rotates plane polarized light to the left).

Today, the Cahn-Ingold-Prelog system is the accepted method for assigning absolute configuration of chiral molecules. Only the amino acids and carbohydrates and their derivatives are still commonly assigned with the D- and L- descriptors. The Cahn-Ingold-Prelog system consists of a set of rules for prioritizing the substituents on a chiral carbon atom. If the substituents increase in priority going clockwise around the carbon atom, the configuration is assigned as (R)-. Likewise, if the substituents increase in priority going counter-clockwise around the carbon atom, the configuration is assigned as (S)-.

Absolute configurations still must be determined either by x-ray crystallography or through relationships with compounds of known configuration. The relationship can be established through several means including:

• conversion to a known compound without loss of chirality;
• conversion at the chiral center if the mechanism of the reaction is understood; and
• biochemical methods with enzymes specific for certain configurations, where the enzyme reacts selectively with either the (R)- or (S)- isomer and leaves the other enantiomer unconverted.

Many compounds contain more than one chiral center. In these cases, the maximum number of stereoisomers is 2ⁿ where n is the number of chiral centers. Thus, in the case of a compound with two chiral carbon atoms, there are a total of four possible stereoisomers. Two of the isomers will be mirror images that are not superimposable on each other, and therefore enantiomers. The other two isomers are called diastereomers--they are stereoisomers that are not enantiomers but rather are non-superimposable, non-mirror images (Exhibit 2.2).

Exhibit 2.2 Diastereomers and Enantiomers

Exhibit 2.2 illustrates the relationship between enantiomers and diastereomers. Compounds (a) and (b) are non-superimposable mirror images of each other and are therefore enantiomers. The same is the case for compounds (c) and (d). However, if we take for example, compound (a) and compound (c), they are stereoisomers of each other, but do not have a mirror image relationship. These are therefore said to be diastereomers.

A meso compound is a diastereomer with two chiral centers, where the substituent groups on both of the chiral carbon atoms are the same. Meso compounds contain a plane of symmetry within the molecule, making them achiral and therefore optically inactive (Exhibit 2.3)

Exhibit 2.3 Meso Structures

Unlike enantiomers, diastereomers have different physical and chemical properties, and these differences in chemical and physical properties often make the diastereomers easy to separate from one another. In addition, generally speaking, diastereomers can be distinguished from one another using normal analytical techniques such as nuclear magnetic resonance (NMR).