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

Abstract

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.

Site‐Selective Palladium‐catalyzed Oxidation of Unprotected Aminoglycosides and Sugar Phosphates

“…[10][11][12] Mono-, di-and oligosaccharides have been functionalized with palladium-catalyzed oxidation reactions (Figure 1 A). [13][14][15][16][17][18] In particular, Waymouth's monocationic palladium neocuproine complex 1 (Figure 1B) in combination with terminal oxidants like benzoquinone or oxygen has proven to be a valuable tool, [19][20][21] as it selectively oxidizes the hydroxy group at the C3 position. [17,22,23] The resulting keto group opens routes for further modification of this important class of biomolecules.…”

Origin of site-selectivity of hydrogen atom transfer in carbohydrate C–H alkylations via photoredox catalysis

“…3 Because of multiple C–H bonds with similar reactivity in monosaccharide-based molecules, the control of selectivity in C–H modifications to access diverse sugar derivatives is challenging. By employing photoredox catalysis and transition metal catalysis, impressive selective C–H manipulations of carbohydrates, such as epimerization, 4 oxidation, 5 alkylation 6 and alkenylation, 7 have been realized. Recently, the Taylor group developed a site- and stereoselective C–H alkylation of carbohydrates aided by diarylborinic acid and photoredox catalysis (Scheme 1a).…”

A Predictive Model for the Pd‐Catalyzed Site‐Selective Oxidation of Diols

“…This renders C3 the most favored site for oxidation, [19] despite the fact that 1,3diaxial interactions impose steric hindrance on the C3À H. Recent work by the group of Waymouth revealed that the stereo-electronic factors that favor C3À OH oxidation can be overcome with sterically hindered ligands, leading to catalysts that have a reduced C3-selectivity. [20] The selective oxidation of oligomaltosides can be explained by sterics, as the glucose residue at the non-reducing end is the most accessible. [21] The results of these prior studies form an excellent starting point for the development of a model that predicts the siteselectivity of this catalytic oxidation.…”