Tunable Noncovalent Interactions for Stereodivergent Organo/Metal Dual Catalysis: Asymmetric Allenylation of Both 3-Alkyl and 3-Aryl Oxindoles

Abstract The development of advanced catalytic paradigms for the precise synthesis of all stereoisomers of chiral molecules has long been an important yet challenging pursuit. Organo/metal dual catalysis represents a powerful platform for stereodivergent construction of vicinal stereocenters. However, stereodivergent synthesis targeting nonadjacent stereoelements remains challenging due to the lack of robust remote chiral induction models. Herein, we report a switchable noncovalent organo/palladium dual-catalytic strategy enabling the stereodivergent asymmetric allenylation of both 3-alkyl and 3-aryl oxindoles with racemic allenyl esters. Tuning noncovalent interaction modes alongside ligand and organocatalyst configurations accessed all four stereoisomers bearing nonadjacent axial chirality and all-carbon quaternary stereocenters with high selectivity (up to 97% yield, 99% ee, and >20:1 dr). Synthetic utility is demonstrated through the stereodivergent construction of 1,5,5′- and 1,3-centrally chiral oxindoles and formal asymmetric total syntheses of three bioactive alkaloids. Furthermore, mechanistic investigations enable the isolation and structural elucidation of the active α-alkynylidene π-allyl metal species, providing direct experimental validation of the proposed catalytic cycle.