ASYMMETRIC-SYNTHESIS OF ALPHA,ALPHA-DISUBSTITUTED ALPHA-AMINO-ACIDS

A new method for the synthesis of each optically active alpha-methylse rine (1a,1b) and alpha-methylthreonine (2a-2d) is described. Intramole cular Strecker synthesis of L-valine acetol ester 3 gave stereoselecti vely 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 trifluoroa cetic acid was equilibrated to give 9b as the major product (9:1). Deu terium exchange experiments using 2-propanol-D clearly indicated the p resence 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.