Mechanistic Basis for Efficient, Site-Selective, Aerobic Catalytic Turnover in Pd-Catalyzed C-H Imidoylation of Heterocycle-Containing Molecules.

A recently reported Pd-catalyzed method for oxidative imidoylation of C-H bonds exhibits unique features that have important implications for Pd-catalyzed aerobic oxidation catalysis: (1) The reaction tolerates heterocycles that commonly poison Pd catalysts. (2) The site selectivity of C-H activation is controlled by an N-methoxyamide group rather than a suitably positioned heterocycle. (3) A Pd source, Pd(dba) (dba = dibenzylideneacetone), is superior to Pd(OAc) as a precatalyst, and other Pd sources are ineffective. (4) The reaction performs better with air, rather than pure O. The present study elucidates the origin of these features. Kinetic, mechanistic, and in situ spectroscopic studies establish that Pd-mediated C-H activation is the turnover-limiting step. The BuNC substrate is shown to coordinate more strongly to Pd than pyridine, thereby contributing to the lack of heterocycle catalyst poisoning. A well-defined Pd-peroxo complex is a competent intermediate that promotes substrate coordination via proton-coupled ligand exchange. The effectiveness of this substrate coordination step correlates with the basicity of the anionic ligands coordinated to Pd, and Pd catalyst precursors are most effective because they selectively afford the Pd-peroxo in situ. Finally, elevated O pressures are shown to contribute to background oxidation of the isonitrile, thereby explaining the improved performance of reactions conducted with air rather than 1 atm O. These collective results explain the unique features of the aerobic C-H imidoylation of N-methoxybenzamides and have important implications for other Pd-catalyzed aerobic C-H oxidation reactions.