SYNTHESIS OF ENANTIOMERICALLY PURE D-(HETEROARYL)ALANINES AND L-(HETEROARYL)ALANINES BY ASYMMETRIC HYDROGENATION OF (Z)-ALPHA-AMINO-ALPHA,BETA-DIDEHYDRO ESTERS
T. Masquelin et al., SYNTHESIS OF ENANTIOMERICALLY PURE D-(HETEROARYL)ALANINES AND L-(HETEROARYL)ALANINES BY ASYMMETRIC HYDROGENATION OF (Z)-ALPHA-AMINO-ALPHA,BETA-DIDEHYDRO ESTERS, Helvetica Chimica Acta, 77(5), 1994, pp. 1395-1411
Homogeneous asymmetric hydrogenation of a wide range of methyl and ter
t-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-py
rrolylalanines (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 p
repared in high yields using the phosphosylglycine-ester method (Schem
e 1), Isomerically pure (Z)-alpha-amino-alpha,beta-didehydro esters we
re required to obtain the highest enantiomeric excesses (ee's) in the
asymmetric hydrogenation, and the tert- butyl-ester strategy was benef
icial in terms of both getting pure (Z)-alpha-amino-alpha,beta-didehyd
ro esters and obtaining high ee's in the hydrogenation. Finally, in co
ntrast to the methyl-ester series, deprotection of the tert- butyl est
ers 4a-d, g was easily performed using CF3CO2H without any racemizatio
n.