Asymmetric synthesis of alpha,alpha-disubstituted alpha-amino acids

A new method for the synthesis of each optically active alpha-methylserine (1a,1b) and alpha-methylthreonine (2a-2d) is described. Intramolecular Strecker synthesis of L-valine acetol ester 3 gave stereoselectively SS-ketimine 5, which upon oxidative removal of the L-valyl group furnished (R)-2-methylserine (2b). The use of D-valine afforded (S)-1a. The treatment of phenylalanine-dl-acetoin ester 7 gave a 4/1 mixture of 5S-ketimines, 9a and 9b. The mixture in the presence of trifluoroacetic acid was equilibrated to give 9b as the major product (9:1). Deuterium exchange experiments using 2-propanol-D clearly indicated the presence of equilibrium between the ketimines 8a and 8b via an enamine 8c. Removal of the phenylalanyl moiety from 9a and 9b afforded 2c and 2d, respectively, in 44-50% overall yields. The use of D-phenylalanine gave 2a and 2b.