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

GRAPHICS 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 correspo nding N-oxides 3a-b followed by asymmetric hydrogenation using (RR)-[Rh(Et- DUPHOS)(COD)]BF4 [(RR)-6] catalyst and subsequent N-oxide reduction in 80-8 3% ee. This methodology was applied to the total synthesis of L-azatyrosine [(+)-12], an antitumor antibiotic, starting from (5-benzyloxy)-2-pyridylme thanol (7), in > 96% enantiomeric purity.