Acceleration of Pd-Catalyzed Amide N-Arylations Using Cocatalytic Metal Triflates: Substrate Scope and Mechanistic Study

The Pd/xantphos-catalyzed cross-coupling of amides and aryl halides is accelerated by cocatalytic metal triflate additives. A survey of nitrogen nucleophiles reveals improved yields for a variety of N-aryl amide products when Al(OTf)(3) is employed as a catalytic additive, with some exceptions. Initial rates of catalysis indicate that the Lewis acid acceleration is more pronounced when bromobenzene (PhBr) is used in comparison with iodobenzene (PhI). The observation of an aryl halide dependence on rate and various qualitative kinetic experiments are consistent with a mechanism in which ligand exchange of halide for amide (transmetalation) is turnover limiting. The mechanism may be different depending on whether PhBr or PhI is used as a coupling partner. Oxidative addition complexes (xantphos)Pd(Ph)(X) (X = Br, I; xantphos = 4,S-bis(diphenylphosphino)-9,9-dimethylxanthene), likely intermediates in catalysis, have been prepared; their differing interactions with Yb(OTf)(3) in solution resemble the halide dependence of the catalytic mechanism, which we propose originates from a reversible Lewis acid mediated halide abstraction during catalysis.