e:e:or d:e:¼
( yield of the major stereoisomeryield of the minor stereoisomer)
yield of the major stereoisomerþyield of the minor stereoisomer100 (10:1)
that is:
e:e:or d:e:¼% major stereoisomer% minor isomer (10:2)
The values of e.e. and d.e. are obtained by measuring the yields of the
individual stereoisomers. An e.e. or d.e. value of 0 per cent means that the
stereoisomers are produced in equal amounts. In the case of enantiomeric
mixtures the product is likely to be in the form of a racemic modification.
Conversely, an e.e. or d.e. value of 100%indicates that only one product is
formed. This rarely occurs in practice since most reactions yield a mixture of
isomers.
The stereochemistry of the product of a reaction will be influenced by the
structures of the reagent and substrate and the mechanisms by which they react.
For example, the hydroxylation of but-2-ene by osmium tetroxide and water
yields a racemate whilst bromination of the same compound with bromine
produces a meso compound (Figure 10.5). However, a stereoselective reaction
is most likely to occur when steric hindrance at the reaction centre restricts the
approach of the reagent to one direction (Figure 10.6). Furthermore, the action
of both enzyme and non-enzyme catalysts may also be used to introduce specific
stereochemical centres into a molecule.
In reactions that produce diastereoisomers the relative proportions of the
diastereoisomers produced will depend on the relative values of the acti-
vation energies of the pathways producing the stereoisomers. The greater the
difference in these activation energies, the higher the possibility of the reaction
being diastereoselective with respect to the product formed by the lowest acti-
vation energy pathway. Consequently, lowering the reaction temperature will
often favour the formation of the diastereoisomer with the lowest activation
energy.
10.2.3 General methods of asymmetric synthesis
There is no set method for designing an asymmetric synthesis. Each synthesis
must be treated on its merits and in all cases success will depend on the skill and
ingenuity of the research worker.
The range and scope of the reactions used in asymmetric synthesis is
extremely large and consequently difficult to classify. In this text they are
208 AN INTRODUCTION TO LEAD AND ANALOGUE SYNTHESES