Control of N-Heterocyclic Carbene Catalyzed Reactions of Enals: Asymmetric Synthesis of Oxindole-γ-Amino Acid Derivatives

Abstract

A strategy to control the switch between a non-cycloaddition reaction and a cycloaddition reaction of enals, using N-heterocyclic carbene (NHC) catalyisis, has been developed. The new scalable protocol leads to γ-amino-acid esters bearing a tetrasubstituted stereocenter in good yields and high stereoselectivities by homo-Mannich reactions of enals and isatin-derived ketimines. By simply changing the N-ketimine substituent to an ortho-hydroxy phenyl group, the corresponding spirocyclic oxindolo-γ-lactams are obtained.

Keywords: asymmetric synthesis; carbenes; cycloaddition; lactams; oxindoles.