Cu/Pd Synergistic Dual Catalysis: Asymmetric α-Allylation of an α-CF3 Amide

Despite the burgeoning demand for fluorine-containing chemical entities, the construction of CF3-containing stereogenic centers has remained elusive. Herein, we report the strategic merger of CuI/base-catalyzed enolization of an alpha-CF3 amide and Pd-0-catalyzed allylic alkylation in an enantioselective manner to deliver chiral building blocks bearing a stereogenic carbon center connected to a CF3, an amide carbonyl, and a manipulable allylic group. The phosphine complexes of Cu-I and Pd-0 engage in distinct catalytic roles without ligand scrambling to render the dual catalysis operative to achieve asymmetric alpha-allylation of the amide. The stereoselective cyclization of the obtained alpha-CF3-gamma, delta-unsaturated amides to give tetrahydropyran and g-lactone-fused cyclopropane skeletons highlights the synthetic utility of the present catalytic method as a new entry to non-racemic CF3-containing compounds.