Pd-Catalyzed Aerobic Oxidation Reactions: Strategies To Increase Catalyst Lifetimes

The palladium complex [(neocuproine)Pd(mu-OAc)](2) [OTf](2) (1; neocuproine = 2,9-dimethyl-1,10-phenanthroline) is an effective catalyst precursor for the selective oxidation of primary and secondary alcohols, vicinal diols, polyols, and carbohydrates. Both air and benzoquinone can be used as terminal oxidants, but aerobic oxidations are accompanied by oxidative degradation of the neocuproine ligand, thus necessitating, high Pd loadings. Several strategies to improve aerobic catalyst lifetimes were devised, guided by mechanistic studies of catalyst deactivation. These studies implicate a radical autoxidation mechanism initiated by H atom abstraction from the neocuproine ligand. Ligand modifications designed to retard H atom abstractions as well as the addition of sacrificial H atom donors increase catalyst lifetimes and lead to higher turnover numbers (TON) under aerobic conditions. Additional investigations revealed that the addition of benzylic hydroperoxides or styrene leads to significant increases in TON as well. Mechanistic studies suggest that benzylic hydroperoxides function as H atom donors and that styrene is effective at intercepting Pd hydrides. These strategies enabled the selective aerobic oxidation of polyols on preparative scales using as little as 0.25 mol % of Pd, a major improvement over previous work.