SYNTHESIS OF ENANTIOMERICALLY PURE D-(HETEROARYL)ALANINES AND L-(HETEROARYL)ALANINES BY ASYMMETRIC HYDROGENATION OF (Z)-ALPHA-AMINO-ALPHA,BETA-DIDEHYDRO ESTERS

Homogeneous asymmetric hydrogenation of a wide range of methyl and tert-butyl (Z)-2-(acylamino)-3-(heteroaryl)acrylates (see 1a-f and 2a-d, f, g, resp.) catalyzed by diphosphinerhodium catalysts was studied for the synthesis of enantiomerically pure 3-furyl-, 3-thienyl-, and 3-pyrrolylalanines (see 3a-f, and 4a-d, g; Scheme 1). The precursors, the (Z)-alpha-amino-alpha,beta-didehydro esters 1a-f and 2a-d, f, g were prepared in high yields using the phosphosylglycine-ester method (Scheme 1), Isomerically pure (Z)-alpha-amino-alpha,beta-didehydro esters were required to obtain the highest enantiomeric excesses (ee's) in the asymmetric hydrogenation, and the tert- butyl-ester strategy was beneficial in terms of both getting pure (Z)-alpha-amino-alpha,beta-didehydro esters and obtaining high ee's in the hydrogenation. Finally, in contrast to the methyl-ester series, deprotection of the tert- butyl esters 4a-d, g was easily performed using CF3CO2H without any racemization.