Stereoretentive Regio- and Enantioselective Allylation of Isoxazolinones by a Planar Chiral Palladacycle Catalyst

Abstract

The catalytic allylic substitution is one of the most important tools in asymmetric synthesis to form C-C bonds in an enantioselective way. While high efficiency was previously accomplished in terms of enantio- and regiocontrol using different catalyst types, a strong general limitation is a very pronounced preference for the formation of allylic substitution products with (E)-configured C=C double bonds. Herein, we report that with a planar chiral palladacycle catalyst a diastereospecific reaction outcome is achieved using isoxazolinones and allylic imidates as substrates, thus maintaining the C=C double bond geometry of the allylic substrates in the highly enantioenriched products. DFT calculations show that the reactions proceed via an S_N 2 mechanism and not via π-allyl Pd complexes. Crucial for the high control is the stabilization of the allylic fragment in the S_N 2 transition state by π-interactions with the phenyl substituents of the pentaphenylferrocenyl catalyst core.

Keywords: Allylic Substitution; Asymmetric Catalysis; Diastereospecific; Palladium; Regioselective.