Neighbouring group effects promote substitution reactions over elimination and provide a stereocontrolled route to chloramphenicol

In reactions of beta-brominated valine and p-nitrophenylalamine derivatives to give beta-hydroxy amino acid derivatives the carboxyl group, when protected as an amide, exerts a neighbouring group effect to facilitate the substitution process, and reduce competing elimination reactions. As a consequence of the effect, the (2R,3R)- and (2R,3S)-stereoisomers of 3-bromo-N-tert-butyl-N-alpha-phthaloyl-p-nitrophenylalaninamide both react to give (2S,3R)-3-hydroxy-N-tert-butyl-N(alpha)phthaloyl-p-nitrophenylalaninamide, providing a stereoconvergent route to chloramphenicol. Copyright (C) 1996 Elsevier Science Ltd