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 <i>N</i>-methoxyamide group rather than a suitably positioned heterocycle. (3) A Pd⁰ source, Pd₂(dba)₃ (dba = dibenzylideneacetone), is superior to Pd­(OAc)₂ as a precatalyst, and other Pd^II sources are ineffective. (4) The reaction performs better with air, rather than pure O₂. The present study elucidates the origin of these features. Kinetic, mechanistic, and in situ spectroscopic studies establish that Pd^II-mediated C–H activation is the turnover-limiting step. The ^tBuNC substrate is shown to coordinate more strongly to Pd^II than pyridine, thereby contributing to the lack of heterocycle catalyst poisoning. A well-defined Pd^II–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^II, and Pd⁰ catalyst precursors are most effective because they selectively afford the Pd^II–peroxo in situ. Finally, elevated O₂ 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 O₂. These collective results explain the unique features of the aerobic C–H imidoylation of <i>N</i>-methoxybenzamides and have important implications for other Pd-catalyzed aerobic C–H oxidation reactions

Are Phosphines Viable Ligands for Pd-Catalyzed Aerobic Oxidation Reactions? Contrasting Insights from a Survey of Six Reactions

Phosphines are the broadest and most important class of ligands in homogeneous catalysis, but they are typically avoided in Pd-catalyzed aerobic oxidation reactions because of their susceptibility to oxidative degradation. Recent empirical reaction-development efforts have led to a growing number of Pd/phosphine catalyst systems for aerobic oxidative coupling reactions, but few of these studies have assessed the fate of the phosphine ligand. Here, we assess six different oxidative coupling reactions, including the homocoupling of boronic acids, amino- and alkoxycarbonylation reactions, intramolecular C–H annulation, and enantioselective Fujiwara–Moritani C–C coupling. The fate and role of the phosphine, analyzed by ³¹P NMR spectroscopy throughout the reaction time course in each case, varies in different reactions. In one case, the phosphine has an inhibitory effect and leads to lower selectivity relative to ligand-free conditions. In other cases, the phosphine ligands have a beneficial effect on the reaction but undergo oxidative decomposition in parallel with productive catalytic turnover. Inclusion of MnO₂ in one of the reactions slows phosphine oxidation by catalyzing disproportionation of H₂O₂ and thereby supports productive catalytic turnover. Negligible oxidation of the chiral phosphine (<i>S</i>,<i>S</i>)-chiraphos is observed during the enantioselective C–C coupling reaction, due to strong chelation of the ligand to Pd^II. The results of this study suggest that phosphines warrant broader attention as ligands for Pd-catalyzed aerobic oxidation reactions, particularly by implementing strategies identified for ligand stabilization

Spin adapted versus broken symmetry approaches in the description of magnetic coupling in heterodinuclear complexes

The performance of a series of wave function and density functional theory based methods in predicting the magnetic coupling constant of a family of heterodinuclear magnetic complexes has been studied. For the former, the accuracy is similar to other simple cases involving homodinuclear complexes, the main limitation being a sufficient inclusion of dynamical correlation effects. Nevertheless, these series of calculations provide an appropriate benchmark for density functional theory based methods. Here, the usual broken symmetry approach provides a convenient framework to predict the magnetic coupling constants but requires deriving the appropriate mapping. At variance with simple dinuclear complexes, spin projection based techniques cannot recover the corresponding (approximate) spin adapted solution. Present results also show that current implementation of spin flip techniques leads to unphysical results.close2