Sequential Dual Catalysis Merging Enantioselective Cu-Catalyzed Conjugate Addition with Intramolecular Pd/Ir-Catalyzed Allylic Alkylation.

The combination of asymmetric conjugate addition and allylic alkylation has emerged as a powerful strategy for the stereocontrolled construction of complex molecules. However, such transformations have been largely limited to intermolecular processes and have not been explored on β-substituted enones. Herein, we report a sequential one-pot dual catalytic approach that merges Cu-catalyzed enantioselective conjugate addition of trialkylaluminum reagents with intramolecular Pd- or Ir-catalyzed allylic alkylation. The methodology enables the synthesis of fused and bridged bicyclic frameworks bearing all-carbon quaternary stereocenters in good yields and high enantioselectivities. In addition, catalyst-controlled stereodivergent synthesis was achieved through the combination of enantiomeric Cu and Ir catalysts, providing selective access to all four stereoisomers of a representative bicyclic product. This work provides a versatile strategy for the synthesis of enantioenriched bicyclic architectures, and its synthetic utility was further demonstrated through a gram-scale synthesis and application to the formal syntheses of (+)-β-gorgonene and (+)-8,9-epi-β-gorgonene.