Highly enantioselective enzymatic resolution of aromatic beta-amino acid amides with Pd-catalyzed racemization

Abstract

The kinetic resolution of an aromatic beta-amino acid amide 3a-d via N-acylation was explored with two lipases, Candida antarctica lipase A (CALA) and Pseudomonas stutzeri lipase (PSL). The PSL-catalyzed resolution proceeded with excellent enantioselectivity (E = >400) to give both acylated products and unreacted substrates in enantiopure forms. Three additional aromatic beta-amino acid amides 3b-d were also resolved by PSL with a high level of enantioselectivity (E = >200). The PSL-catalyzed resolution of 3a was coupled with a Pd-catalyzed racemization to obtain enantiopure N-acylated product (R)-4a (>99% ee) in high yield (90%). (C) 2013 Elsevier Ltd. All rights reserved.