The selective synthesis of diastereomers

Perhaps the most common case in which an asymmetric reaction leads to a pair of diastereomers is when one of the reactants is chiral. If we consider reduction of the carbonyl group in (55) for example, the two possible products are (-)-threonine (56) and (+)-a//o-threonine (57) which, as we have already seen, are diastereomeric with each other. 

Several different measures of the diastereoselectivity can be given. Just as for e.e., we can define the diastereomeric excess (d.e.) of a reaction as the proportion of the major diastereomer produced less that of the minor one. In examples such as the one here, where one new stereogenic unit is formed in a diastereoselective reaction, this is the preferred measure of selectivity. While it does not have the same correlation with optical purity as e.e., it does have the advantage that if the original stereogenic unit(s) are removed, as, for example, by removal of the chiral auxiliary in a second-generation method (see chapter 5), the e.e. of the final product correlates directly with the d.e. of the initial product. Thus if the mixture of (56) and (57) was decarboxylated, the e.e. of the resulting amino alcohol would be equal to the d.e. of (56)/(57). 

The most useful alternative measure of diastereoselectivity is the diastereomer ratio (d.r.) which, in contrast to d.e., is expressed not as a percentage but as a ratio. To take a simple example, if reduction of (55) gives (56) and (57) in a ratio of 90 10, the d.e. is 80% and the d.r. 9 1. For reactions in which two new stereogenic units are formed the diastereoselectivity is best expressed as the diastereomer ratio (see below). We do not favour the quantity % d.s. used by some authors.1 1 The terms diastereoselective and diastereospecific are used in an analogous way to enantioselective and enantiospecific. Note that a diastereomerically pure compound refers only to a pure enantiomeric pair of stereoisomers and gives no information on the ratio of the enantiomers present (see below). 

A slightly more complex case of diastereoselectivity arises in reactions in which two stereogenic units are formed simultaneously. Suppose, for example, the aldol reaction of benzaldehyde and ethyl 

If two atoms or groups in an achiral molecule differ in that reaction of one as opposed to the other leads to enantiomeric products, they are said to be enantiotopic and the whole molecule is described as being prochiral. By far the most common situation in which this applies is when two of the four groups joined to a tetrahedral centre are identical. Thus the benzylic hydrogen atoms in benzyl alcohol (62) are enantiotopic as are the two oxygens in an unsymmetrical sulphone (63), and the two methyls of an isopropyl group (64). 

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