Synthesis of Enantiomerically Pure D‐ and L‐(Heteroaryl)alanines by asymmetric hydrogenation of (Z)‐α‐amino‐αβ‐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)-α-amino-α,β-didehydro esters 1a–f and 2a–d, f, g were prepared in high yields using the phosphorylglycine-ester method (Scheme 1). Isomerically pure (Z)-α-amino-α,β-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)-α-amino-α,β-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.