Mechanistic Characterization of Aerobic Alcohol Oxidation Catalyzed by Pd(OAc)₂/Pyridine Including Identification of the Catalyst Resting State and the Origin of Nonlinear [Catalyst] Dependence

The Pd(OAc)₂/pyridine catalyst system is one of the most convenient and versatile catalyst systems for selective aerobic oxidation of organic substrates. This report describes the catalytic mechanism of Pd(OAc)₂/pyridine-mediated oxidation of benzyl alcohol, which has been studied by gas-uptake kinetic methods and ¹H NMR spectroscopy. The data reveal that turnover-limiting substrate oxidation by palladium(II) proceeds by a four-step pathway involving (1) formation of an adduct between the alcohol substrate and the square-planar palladium(II) complex, (2) proton-coupled ligand substitution to generate a palladium-alkoxide species, (3) reversible dissociation of pyridine from palladium(II) to create a three-coordinate intermediate, and (4) irreversible β-hydride elimination to produce benzaldehyde. The catalyst resting state, characterized by ¹H NMR spectroscopy, consists of an equilibrium mixture of (py)₂Pd(OAc)₂, 1, and the alcohol adduct of this complex, 1·RCH₂OH. These in situ spectroscopic data provide direct support for the mechanism proposed from kinetic studies. The catalyst displays higher turnover frequency at lower catalyst loading, as revealed by a nonlinear dependence of the rate on [catalyst]. This phenomenon arises from a competition between forward and reverse reaction steps that exhibit unimolecular and bimolecular dependences on [catalyst]. Finally, overoxidation of benzyl alcohol to benzoic acid, even at low levels, contributes to catalyst deactivation by formation of a less active palladium benzoate complex.