Asymmetric transformation of L-homoserine lactone to an optically active 2-substituted pyrrolidine for clemastine

Abstract

The asymmetric transformation of L-homoserine lactone to (R)-ethyl 2-(2-chloroethyl)pyrrolidine-1-carboxylate for clemastine has been accomplished by a combination of regioselective N-allylation and ring-closing metathesis. A key feature associated with the synthesis involved the racemization-minimized N-allylation of carbamate version of an amino ester by using P4-phosphazene as a base. This method might offer an alternative route to obtain optically active 2-substituted pyrrolidines from alpha-amino esters, not easily accessible from proline-based asymmetric transformations. (C) 2011 Elsevier Ltd. All rights reserved.