7 Dihydroxylation

Experiment 7, page 1

EXPERIMENT 7:
CATALYTIC ASYMMETRIC DIHYDROXYLATION OF OLEFINS

Aims of the experiment
To prepare an enantiomerically enriched 1,2-diol using Sharpless' catalytic asymmetric
dihydroxylation procedure, and to estimate the enantiomeric purity of the material you obtain.

Techniques used/learned:
Asymmetric catalysis; recrystallisation; measurement of optical rotations.

Introduction
The need to prepare compounds such as drug candidates in enantiomerically pure form means that
the organic chemist needs at his/her disposal a wide range of small chiral organic molecules from
which to construct their target molecules. One source of these chiral starting materials (sometimes
called 'chirons') is nature itself. However, such a 'chiral pool' supply is necessarily limited - the
pool may not contain a particular type of starting material, or it may only be available as the
opposite enantiomer to the one needed.
Thus, chemists have begun to devise methods for the synthesis of bothenantiomers of useful
small molecules from achiral starting materials.1This can be achieved through temporary
attachment of a chiral auxiliary to the achiral material (the synthesis is then diastereoselective,
rather than enantioselective); use of chiral reagents; or the use of chiral catalysts. The latter
approach,2though the less well developed of the three, is potentially the most interesting, since a
small amount of chiral catalyst can produce large amounts of enantiomerically enriched product.
One of the pioneers of this field has been Professor K Barry Sharpless of the Scripps Research
Institute. The eponymous epoxidation of allylic alcohols3was the first practical and reliable
catalytic asymmetric reaction, and more recently he has turned his attention to the asymmetric
osmium mediated dihydroxylation4(see scheme) and aminohydroxylation5of olefins, using
modified cinchona alkaloids as chiral ligands for osmium.