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

摘要

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 ~(31)P 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 MnO_(2) in one of the reactions slows phosphine oxidation by catalyzing disproportionation of H_(2)O_(2) and thereby supports productive catalytic turnover. Negligible oxidation of the chiral phosphine (S ,S )-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.