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-α,α-disubstituted α-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 Crottiʹs 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 α,α-disubstituted N-Boc-α-amino acids. Protected α-methyl-α-phenylglycine and α-methylisoleucine have been prepared by this methodology.