Mechanistic studies of palladium-catalyzed aerobic alcohol oxidation

Several palladium catalysts for aerobic substrate oxidation have appeared in the last 12 years. Two successful catalyst systems, the Pd(OAc)2/DMSO system and the Pd(OAc)2/pyridine system, were reported in 1998 for alcohol oxidation. At the time there was very little mechanistic understanding of aerobic palladium-catalyzed oxidations. This report focuses on kinetic studies of these two palladium catalysts to gain insight into the mechanism.; Studies of the Pd(OAc)2/DMSO system revealed that dioxygen is solely responsible for catalyst oxidation. Incomplete alcohol oxidation indicates catalyst decomposition. Both unimolecular and bimolecular phenomenological pathways describe catalyst decomposition. Catalyst decomposition is exacerbated by mass-transfer-limited conditions. Kinetic studies revealed that alcohol oxidation is turnover-limiting. The rate also depends on [acetic acid] and is inhibited by both acetophenone and water. The rate does not depend on oxygen pressure, but higher turnovers are observed at elevated oxygen pressures.; Investigation of the Pd(OAc)2/pyridine system revealed both pyridine and acetate promote catalyst reoxidation and prevent catalyst decomposition; however, when pyridine is present in excess of palladium, the rate is inhibited. A mechanism supported by kinetic studies and in situ NMR spectroscopy described by the following steps: The catalyst exists in equilibrium between (py)2Pd(OAc)2 and a hydrogen-bonded alcohol adduct, (py)2Pd(OAc)2(alcohol). An alkoxide intermediate is formed via proton-coupled ligand substitution. Pyridine dissociation followed by turnover-limiting beta-hydride elimination completes the mechanism of alcohol oxidation. The catalyst is sensitive to electronic variations of both the pyridine and the carboxylate ligands.; The effect of molecular sieves on reaction rates and catalyst stability was investigated. Kinetic studies of both catalyst systems revealed that molecular sieves do scavenge water. They inhibit hydrogen peroxide disproportionation. In the Pd(OAc)2/pyridine system, the principal benefit of molecular sieves is most consistent with acting as a Bronsted base. In the Pd(OAc) 2/DMSO system, molecular sieves have no effect on the rate, but instead they extend the catalyst lifetime.; The insights gained from the kinetic studies have provided understanding of major influences on the catalyst. This work has laid the groundwork for the rational development of new catalysts with the hopes that high turnover numbers and fast rates can be achieved.