An Enantioselective Bidentate Auxiliary Directed Palladium-Catalyzed Benzylic C−H Arylation of Amines Using a BINOL Phosphate Ligand

A new enantioselective palladium(II)-catalyzed benzylic C−H arylation reaction of amines is enabled by the bidentate picolinamide (PA) directing group. This reaction provides the first example of enantioselective benzylic γ-C−H arylations of alkyl amines, and proceeds with up to 97 % ee. The 2,2′-dihydroxy-1,1′-binaphthyl (BINOL) phosphoric acid ligand, Cs2CO3, and solvent-free conditions are essential for high enantioselectivity. Mechanistic studies suggest that multiple BINOL ligands are involved in the stereodetermining C−H palladation step.