Enantioselective Synthesis of Cyclic Nitrones and Oxime Ethers by Chemoselective Allylic Alkylation of Oximes

The enantio- and chemoselective iridium-catalyzed N- and O-allylation of oximes is described for the first time. Kinetic resolution in an intramolecular setting provides access to cyclic nitrones, oxime ethers and enantioenriched aliphatic allylic alcohols. Salient features of this transformation are its ability to employ E/Z-isomeric mixtures of oxime starting materials convergently, high functional group tolerance, and divergent N- or O-allylation by choice of the reaction conditions. The implementation of N-allylation/1,3-dipolar cycloaddition reaction cascades furnish tricyclic isoxazolidines in highly enantio- and diastereoselective fashion. Expansion of this approach to the selective allylation of hydrazones allows enantioselective preparation of azomethine imines. The synthetic utility of the approach is demonstrated by the efficient, formal syntheses of glycoprotein GP IIb‐IIIa receptor antagonist (–)-roxifiban and marine natural product (+)-halichlorine.