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Asymmetric synthesis of monosubstituted and alpha alpha disubstituted alpha amino acids via diastereoselective glycine enolate alkylations



Asymmetric synthesis of monosubstituted and alpha alpha disubstituted alpha amino acids via diastereoselective glycine enolate alkylations



Journal of the American Chemical Society 113(24): 9276-9286



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.

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Accession: 007041307

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DOI: 10.1021/ja00024a038


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