Catalytic asymmetric synthesis of (S)-oxybutynin and a versatile intermediate for antimuscarinic agents

A practical synthesis of (S)-oxybutynin, a muscarinic receptor antagonist, using catalytic enantioselective cyanosilylation of cyclohexyl phenyl ketone (9a) as a key step is described. The key reaction proceeded with 94% ee using 1 mol% of Gd-1 catalyst, and was performed on a 100 g-scale. In addition, a short catalytic enantioselective synthesis of the versatile intermediate for Scios Nova analogues of antimuscarinic agents (7) is described. Application of the catalytic enantioselective cyanosilylation to ketones containing two sterically similar substituents on the carbonyl group is also discussed. (C) 2004 Elsevier Ltd. All rights reserved.