Efficient strategy for the stereoselective synthesis of 2,3-disubstituted benzo[alpha]quinolizidine alkaloids: concise synthesis of (-)-protoemetinol

Abstract

The stereoselective synthesis of (-)-protoemetinol has been accomplished through nine steps from a known homoallylic amine. The key steps of the synthesis involve the efficient preparation of an aza-Claisen rearrangement (ACR) precursor using cross metathesis and amide enolate-induced ACR followed by acid-catalyzed transannulation for the elaboration of the benzo[alpha]quinolizine skeleton and three stereogenic centers. This unique synthetic route envisages a unified and versatile strategy for the synthesis of 2,3-disubstituted benzo[alpha]quinolizidine. (C) 2014 Elsevier Ltd. All rights reserved.