Highly Enantioselective Control of Dynamic Cascade Transformations by Dual Catalysis: Asymmetric Synthesis of Polysubstituted Spirocyclic Oxindoles

Abstract

The highly enantioselective (up to >99.5:0.5 er) synthesis of polysubstituted spirocyclic oxindoles with four new contiguous stereocenters, including the spiro all-carbon quaternary center, is disclosed. It is accomplished by the highly stereoselective control of a dynamic conjugate/intramolecular allylic alkylation relay sequence based on the synergistic cooperation of metal and chiral amine catalysts in which the careful selection of organic ligand, metal complex, and chiral amine is essential. The intramolecular C–C bond-forming step occurred only when both the metal and chiral amine catalysts were present.