Organocatalytic 1,6-hydrophosphination of para-quinone methides: enantioselective access to chiral 3-phosphoxindoles bearing phosphorus-substituted quaternary carbon stereocenters

Abstract

An efficient organocatalytic enantioselective 1,6-hydrophosphonylation of para-quinone methides derived from isatins with H-phosphorus oxides has been achieved in the presence of bifunctional cinchona alkaloid-based urea. This methodology provides a straightforward approach for accessing a variety of chiral 3-phosphoxindoles bearing phosphorus-substituted quaternary carbon stereocenters with a high level of chemoselectivity and remote stereocontrol (up to 99% yield, 99 : 1 er). This environmentally benign protocol represents a unique example of the asymmetric organocatalytic 1,6-conjugate addition reaction of phosphorus nucleophiles in an atom-economical manner.