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 CF 3 CO 2 H without any racemization.