Enantioselective Synthesis of Cyclic Nitrones by Chemoselective Intramolecular Allylic Alkylation of Oximes

Abstract

The enantio- and chemoselective iridium-catalyzed N-allylation of oximes is described for the first time. Intramolecular kinetic resolution provides access to cyclic nitrones and enantioenriched aliphatic allylic alcohols. Salient features of this transformation are its ability to employ E/Z-isomeric mixtures of oxime starting materials convergently and high functional group tolerance. The implementation of N-allylation/1,3-dipolar cycloaddition reaction sequences furnishes tricyclic isoxazolidines in highly enantio- and diastereoselective fashion. The synthetic utility of the approach is demonstrated by the efficient, formal synthesis of the marine natural product (+)-halichlorine.

Keywords: 1,3-dipolar cycloaddition; enantioselective catalysis; iridium; nitrones; oximes.