ASYMMETRIC-SYNTHESIS OF MONOSUBSTITUTED AND ALPHA,ALPHA-DISUBSTITUTED ALPHA-AMINO-ACIDS VIA DIASTEREOSELECTIVE GLYCINE ENOLATE ALKYLATIONS

The enolates derived from the optically active (5S,6R)- and (5R,6S)-4(tert-butyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one (1a,b) and (5S,6R)- and (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-ones (2a,b) efficiently couple with alkyl halides to afford the corresponding anti-alpha-monosubstituted oxazinones (3 and 4). The enolate alkylation of the alpha-monosubstituted oxazinones (3 and 4) provides the corresponding alpha,alpha-disubstituted oxazinones (7 and 8). Dissolving-metal reduction of the homologated oxazinones allows the direct preparation of t-BOC-protected alpha-amino acids. In the case of a dissolving-metal-reducible functionality, hydrogenation over a Pd0 catalyst furnishes the zwitterionic amino acids. By employing this protocol several amino acids or their corresponding N-t-BOC derivatives, such as allylglycine, alanine, phenylalanine, beta-ethylaspartic acid, alpha-methylphenylalanine, N-(tert-butyloxycarbonyl)dimethallylglycine, N-(tert-butyloxycarbonyl)-2-(2'-propenyl)norvaline, N-(tert-butyloxycarbonyl)-2-(3'-methyl-2'-butenyl)alanine, N-(tert-butyloxycarbonyl)-2-(2'-propenyl)alanine, 2-(3'-phenylpropyl)alanine, 2-amino-6-(acetyloxy)hexanoic acid, and 2(tert-butyloxycarbonyl)amino-6-[(p-methoxybenzyl)thio]hexanoic acid, are prepared in high enantiomeric excess.