Improved Catalyst Design for the Palladium-Catalyzed Enantioselective Oxidation of Chiral Secondary Alcohols: Access to Both Enantiomeric Series

Enantioenriched alcohols are ubiquitous in the structures and syntheses of natural products and pharmaceuticals. Catalytic, asymmetric alcohol oxidation can be a useful method to access these molecules.[1] Previously, we reported the development of an aerobic kinetic resolution of alcohols by catalytic [Pd(nbd)Cl2] (1, nbd = norbornadiene) and the naturally occurring alkaloid (−)-sparteine (sp, (−)-2) in the presence of molecular oxygen.[2-6] Although this system successfully resolves a wide range of secondary alcohols to high enantiomeric excess, the rates of oxidation for certain substrates are prohibitively slow. Furthermore, the use of 2 as a ligand, which is only commercially available as the (−)-antipode, restricts access to alcohols in one enantiomeric series. [7] Herein, we disclose the development of a catalyst based on an understanding of reaction mechanism that effects dramatic rate increases, thereby