CATALYTIC ASYMMETRIC DIHYDROXYLATION OF OLEFINS

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Experiment 7, page 1

Department ofChemistry, Imperial College
Third YearAdvanced Practical Organic Chemistry

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.

Ligands for the AD reaction...........are derived from cinchona alkaloids:Catalytic cycle for the AD reaction
Ligand
+
OsO₄^{Os (VI)}dihydroquinine^co-oxidant^b^-facedihydroquinidine
"HO" "OH"
a -face