The palladium complex [(L 1 )Pd(μ-OAc)]2[OTf]2 (L 1 = 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 [(L 2 )Pd(μ-OAc)]2[OTf]2 (L 2 = 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 L 2 were a consequence of precipitation of an insoluble trinuclear palladium species(L 2 Pd)3(μ-O)2 2+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, L 3 = 7,7′-di-tert-butyl-2,2′-biquinoline, would disfavor the formation of the trinuclear (LPd)3(μ-O)2 2+ species. This design strategy was validated as catalytic aerobic oxidation with [(L 3 )Pd(μ-OAc)]2[OTf]2 is both robust and rapid, marrying the kinetics of the parent L 1 -supported system with the high aerobic turnover numbers of the L 2 -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.