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

Angewandte Chemie - International Edition

4 years ago

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

Akira Saito, Masakatsu Shibasaki, Naoya Kumagai

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 α-CF3 amide and Pd0-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 CuI and Pd0 engage in distinct catalytic roles without ligand scrambling to render the dual catalysis operative to achieve asymmetric α-allylation of the amide. The stereoselective cyclization of the obtained α-CF3-γ,δ-unsaturated amides to give tetrahydropyran and γ-lactone-fused cyclopropane skeletons highlights the synthetic utility of the present catalytic method as a new entry to non-racemic CF3-containing compounds. A strategic merger of CuI/base-catalyzed enolization of an α-CF3 amide and Pd0-catalyzed allylic alkylation to give enantioselective α-allylation of the amide was developed. This method delivers chiral building blocks bearing a stereogenic carbon center connected to a CF3, an amide carbonyl, and an allylic group. Phosphine complexes of CuI and Pd0 engaged in distinct catalytic roles without ligand scrambling to produce cooperative dual catalysis.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201702113