A new method for the enantioselective synthesis of N-Boc-α,α-disubstituted α-amino acids

A new method for the enantioselective synthesis of N-Boc-alpha,alpha -disubstituted alpha -amino acids has been developed. The starting materials are diastereomerically pure 3,3-disubstituted allyl alcohols, prepared by DIBAL-H reduction of the corresponding unsaturated esters derived from carbocupration of an acetylenic ester or from Wadsworth-Emmons olefination of a ketone. Sharpless epoxidation of the allylic alcohols provided enantiomerically enriched epoxy alcohols that were submitted to nucleophilic ring-opening under Crotti's conditions N3Na/LiClO4) to give 3-azido-1,2-diols. Hydrogenation and in situ protection provided the N-Boc-3-amino-1,2-diols that were oxidatively cleaved to the alpha,alpha -disubstituted N-Boc-alpha -amino acids. Protected alpha -methyl-alpha -phenylglycine and alpha -methylisoleucine have been prepared by this methodology. (C) 2001 Elsevier Science Ltd. All rights reserved.