Enantioselective α-Arylation of Ketones with Aryl Triflates Catalyzed by Difluorphos Complexes of Palladium and Nickel

The asymmetric α-arylation of ketones with aryl triflates is described, and the use of this
electrophile with nickel and palladium catalysts containing a segphos derivative increases substantially
the scope of highly enantioselective arylations of ketone enolates. The combination of aryl triflates as
reactant, difluorphos as ligand, palladium catalysts for reactions of electron-neutral or electron-rich aryl
triflates, and nickel catalysts for reactions of electron-poor aryl triflates led to a series of α-arylations of
tetralone, indanone, cyclopentanone, and cyclohexanone derivatives. Enantioselectivities ranged from 70%
to 98% with 10 examples over 90%. Systematic studies on these α-arylations have revealed a number of
factors that affect enantioselectivity. Ligands containing biaryl backbones with smaller dihedral angles
generate catalysts that react with higher enantioselectivity than related ligands with larger dihedral angles.
In addition, faster rates for reactions of aryl triflates versus those for reactions of aryl bromides allow the
α-arylations of aryl triflates to be conducted at lower temperatures, and this lower temperature improves
enantioselectivity. Finally, studies that compare the enantioselectivities of catalytic reactions to those of
stoichiometric reactions of isolated [(segphos)Pd(Ar)(Br)], [(segphos)Pd(Ar)(I)], and [(segphos)Ni(C6H4-4-CN)Br] suggest that catalyst decomposition affects enantioselectivity.