Mechanism-Guided Design of Robust Palladium Catalysts for Selective Aerobic Oxidation of Polyols.

The palladium complex [()Pd(μ-OAc)][OTf] ( = neocuproine) is a selective catalyst for the aerobic oxidation of vicinal polyols to α-hydroxyketones, but competitive oxidation of the ligand methyl groups limits the turnover number and necessitates high Pd loadings. Replacement of the neocuproine ligand with 2,2'-biquinoline ligands was investigated as a strategy to improve catalyst performance and explore the relationship between ligand structure and reactivity. Evaluation of [()Pd(μ-OAc)][OTf] ( = 2,2'-biquinoline) as a catalyst for aerobic alcohol oxidation revealed a threefold enhancement in turnover number relative to the neocuproine congener, but a much slower rate. Mechanistic studies indicated that the slow rates observed with were a consequence of precipitation of an insoluble trinuclear palladium species─(Pd)(μ-O)─formed during catalysis and characterized by high-resolution electrospray ionization mass spectrometry. Density functional theory was used to predict that a sterically modified biquinoline ligand, = 7,7'-di--butyl-2,2'-biquinoline, would disfavor the formation of the trinuclear (LPd)(μ-O) species. This design strategy was validated as catalytic aerobic oxidation with [()Pd(μ-OAc)][OTf] is both robust and rapid, marrying the kinetics of the parent -supported system with the high aerobic turnover numbers of the -supported system. Changes in ligand structure were also found to modulate regioselectivity in the oxidation of complex glycoside substrates, providing new insights into structure-selectivity relationships with this class of catalysts.