Electrophilic asymmetric synthesis of a-hydroxy acids and a-hydroxy acid derivatives

Abstract

The formation of a new carbon-carbon bond is perhaps the most fundamental reaction in organic chemistry. Certainly one of the most challenging reactions is the formation of new carbon-carbon bonds in an asymmetric fashion to produce compounds containing new chiral centers. One method of inducing asymmetry in carbon-carbon bond forming reactions which has become increasing popular involves the use of chiral nucleophiles in electrophilic syntheses. In the past ten years the preparation of chiral nucleophiles from carbonyl derivatives and their use in electrophilic syntheses has been especially rapid growth and the application of this methodology to asymmetric synthesis has met with some success. This dissertation deals with attempts to form new carbon-carbon bonds via electrophilic reactions of chiral nucleophiles as a general route optically to active (alpha)-hydroxy acids. The preparation of chiral O-protected (alpha)-hydroxy esters and carboxamides from optically active alcohols and (beta)-amino alcohols and the subsequent generation of chiral enolates from these substrates were carried out. These chiral enolates were allowed to undergo electrophilic substitution reactions with a variety of alkyl halides to afford (alpha)-hydroxy acid derivatives containing new chiral centers at the (alpha)-carbon with diastereo-selectivities varying from 10% to 94%.