The selective synthesis of enantiomers

An asymmetric synthesis may be defined as a synthesis in which an achiral unit in an ensemble of substrate molecules is converted to a chiral unit such that the possible stereoisomers are formed in unequal amounts. 

In the simplest case an achiral substrate is converted to an unequal mixture of the two enantiomers of a chiral product containing only one stereogenic unit. The aim is obviously to achieve the highest possible proportion of the desired enantiomer to maximise the enantioselectivity. The most commonly used measure of the degree of enantioselectivity achieved is the enantiomeric excess (e.e.). This is defined as the proportion of the major enantiomer less that of the minor enantiomer and is cornmonly expressed as a percentage. Thus, for example, if the reduction of acetophenone is carried out asymmetrically to give the enantiomeric alcohols (14) and (15) in a ratio of 90 10, then the e.e. of the process is 80%. Similarly an e.e. of 90% would correspond to an enantiomer ratio of 95 5. The reason for using the enantiomeric excess rather than the enantiomer ratio is that in almost all casesl l it corresponds directly with the optical purity. Thus in the example above (14) has an optical rotation of-120 and (15) of+120°. A sample of 80% e.e. which contains 90% of (14) and 10% of (15) will have a net optical rotation of (0.9 x -120°) +(0.1 x +120°)=-96° which is 80% of the value for the pure major enantiomer. 

Thus for any sample of a compound for which the optical rotation of the pure enantiomer is known, the e.e. can be determined directly from the observed rotation. 

Special mention should be made of the two extreme values of e.e. An e.e. of 100% corresponds to an enantiomerically pure compound (thetermhomochiral which is also sometimes used is not favoured). A reaction which gives a product of 100% e.e. is enantiospedflc. Since this represents an ideal situation which is rarely attainable in practice, the term enantioselective should generally be used. An e.e. of 0% corresponds to a 1 1 mixture of enantiomers known as a racemic mixture or racemate (this is denoted by the prefix ( )-). The process by which the stereogenic unit in a chiral compound is destroyed and then reformed with random stereochemistry leading to a fall in the e.e., eventually to zero, is 

Finally in this section it should be noted that the solubility of a pure enantiomer and the racemate are not necessarily equal. For a racemic solid compound recrystallisation can give racemic crystals (containing equal proportions of both enantiomers) or individual crystals of each enantiomer which can sometimes be separated. In rare cases there can even be spontaneous crystallisation of one pure enantiomer although this should theoretically happen equally often to give the opposite enantiomer. As soon as we move to solid compounds with a significant e.e. however, it is quite common for the major enantiomer and the racemate to be separable by crystallisation. This phenomenon of enantiomeric enrichment is extremely useful since in many cases solid products of 60-80% e.e. from asymmetric synthesis can be enriched to over 95% e.e. by one or two recrystallisations. 

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