ASYMMETRIC-SYNTHESIS OF ALPHA,ALPHA-DISUBSTITUTED ALPHA-AMINO-ACIDS VIA AN INTRAMOLECULAR STRECKER SYNTHESIS

A series of optically active alpha,alpha-disubstituted alpha-amino aci ds have been synthesized starring with an achiral or a racemic 2-hydro xy ketone. The key transformation to the present synthesis is an intra molecular version of Strecker synthesis. An alpha-keto ester having a chiral amino acid as the ester group afforded cyclic amino nitrile, in a highly stereoselective manner, in which the amino group and the chi rality were diastereoselectively transplanted into the internal ketone group via an imine-enamine equilibrium of the cyclic ketimine interme diate. Oxidation of the amino group followed by removal of the resulti ng imino group and hydrolysis of the nitrile group afforded alpha-hydr oxymethyl alpha-amino acid. The use of L-amino acid as the chirality t ransferring group gave R enantiomer, and its S enantiomer was obtained when D-amino acid was employed The syntheses of optically active alph a-substituted serines, alpha-methylthreonines, and 1-amino-2-hydroxycy cloalkanecarboxylic acids are described.