Palladium-catalyzed oxidation and kinetic resolution of alcohols under aerobic conditions

The development of reactions using practical reagents and conditions is of exceptional importance in organic synthesis. Consequently, metal-catalyzed aerobic oxidations have recently gained significant attention due to the inherent practical advantages associated with use of molecular oxygen as an atom efficient, environmentally benign, and inexpensive oxidant. The research described here focuses on developing Pd-catalyzed aerobic oxidations of alcohols.; A catalyst for the Pd-catalyzed aerobic oxidative kinetic resolution of secondary alcohols was developed using Pd(II) salts and (-)-sparteine. In general, this reaction is effective for a variety of secondary alcohols and can be applied to the desymmetrization of meso diols. Through the mechanistic insight developed for this reaction, both a second-generation approach for enantioselective alcohol oxidation and an improved catalyst for the simple oxidation of alcohols were designed. The second-generation approach to enantioselective alcohol oxidation relies on modular catalyst development and is highlighted by the use of a chiral ligand and a chiral base with "matched" interactions providing a more selective oxidative kinetic resolution. The improved catalyst for general alcohol oxidation relies on a well-defined complex using a N-heterocyclic carbene ligand and acetate as both ligand and base. This general alcohol oxidation is effective at low catalyst loading and mild conditions for an aerobic alcohol oxidation.