discussed under the broad headings of either reactions that require a catalyst or
those that do not require a catalyst for their stereoselectivity. However, it is
emphasized that this and the subdivisions used are a simplification, and many
reactions can fall into more than one category.
Methods that use catalysts to obtain stereoselectivity
Both enzyme (Figure 10.7) and non-enzyme catalysts (Figure 10.8) may be
used.
A wide variety of enzyme controlled stereospecific transformations are
known. These transformations include oxidations, reductions, reductive amina-
tions, addition of ammonia, transaminations and hydrations. In each case the
configuration of the new asymmetric centre will depend on the structure of the
substrate. However, substrates whose reactive centres have similar structures
will often produce asymmetric centres with the same configuration. Enzyme
based methods are economical in their use of chiral material but suffer from the
disadvantage that they can require large quantities of the enzyme to produce
significant quantities of the drug.
A number of stereospecific non-enzyme catalysts have been developed
that convert achiral substrates into chiral products. These catalysts are
usually either complex organic (Figure 10.8(a) ) or organometallic com-
pounds (Figure 10.8(b) ). The organometallic catalysts are usually optically
active complexes whose structures usually contain one or more chiral ligands.
An exception is the Sharpless–Katsuki epoxidation, which uses a mixture
of an achiral titanium complex and an enantiomer of diethyl tartrate
(Figure 10.8(c) ).
R O RO
OO
OHR NHiPrP. oleovorans(S) (S)R = CH 3 OCH 2 CH 2 −−
Metoprolol 98% e.e.
OOOO
OxoisophoroneBakers yeastOxidation:
Reduction:
(R)80% e.e.Various routes to carotenoids and
other terpenoid compoundsFigure 10.7 Examples of enzyme controlled transformations210 AN INTRODUCTION TO LEAD AND ANALOGUE SYNTHESES