Novel bifunctional organocatalysts for enantioselective synthesis

Abstract

Inspired by the efficiency and selectivity achievable by hydrogen bonding in biological catalysis, the work in this thesis is concerned with the application of these principles to the development of small chiral organic molecules capable of asymmetric induction. To be responsible for both the design and testing of novel catalysts was for us a highly worthwhile and stimulating challenge. Preliminary investigations focused on (thio)urea catalysis of the Baylis-Hillman and Strecker reactions. Whilst enantioselectivity was poor in these test reactions, many instructive lessons with respect to bifunctional catalyst design were learned. With this knowledge in hand, a suite of cinchona alkaloid hybrid (thio)urea catalysts were prepared. Readily available pseudoenantiomers dihydroquinine and dihydroquinidine were modified, by means of a one-pot Mitsunobu inversion-Staudinger reduction, to include a (thio)urea moiety. Four diastereomeric catalysts were synthesised to probe the effect of C-8 and C-9 relative stereochemistry on catalyst performance.