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

The palladium complex [(L1)Pd(mu-OAc)]2[OTf]2 (L1 = neocuproine) is a selective catalyst for the aerobic oxidation of vicinal polyols to a-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 [(L2)Pd(mu- OAc)]2[OTf]2 (L2 = 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 L2 were a consequence of precipitation of an insoluble trinuclear palladium species-(L2Pd)3(mu-O)22+-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, L3 = 7,7 '-di-tert-butyl-2,2 '-biquinoline, would disfavor the formation of the trinuclear (LPd)3(mu-O)22+ species. This design strategy was validated as catalytic aerobic oxidation with [(L3)Pd(mu-OAc)]2[OTf]2 is both robust and rapid, marrying the kinetics of the parent L1-supported system with the high aerobic turnover numbers of the L2 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.

Automated summary

The strategy of improving catalyst performance is achieved by replacing ligands. Experimental results show that using 7,7'-di-tert-butyl-2,2'-biquinoline (L3) as the ligand can enhance the catalyst's effectiveness. Furthermore, changes in ligand structure can also modulate the regioselectivity of the substrate.