Enantioselective synthesis of (2-pyridyl)alanines via catalytic hydrogenation and application to the synthesis of L-azatyrosine

reaction: see text] A novel method for the synthesis of (2-pyridyl)alanines 2a-b was developed by converting (2-pyridyl)dehydroamino acid derivatives 1a-b to the corresponding N-oxides 3a-b followed by asymmetric hydrogenation using (R,R)-Rh(Et-DUPHOS)(COD)]BF(4) (R,R)-6] catalyst and subsequent N-oxide reduction in 80-83% ee. This methodology was applied to the total synthesis of L-azatyrosine (+)-12], an antitumor antibiotic, starting from (5-benzyloxy)-2-pyridylmethanol (7), in >96% enantiomeric purity.