Organocatalytic Oxidative Kinetic Resolution of Secondary Alcohols Using Chiral AZADO Derivatives

Abstract

Oxidative kinetic resolution (OKR) of secondary alcohols offers chemists a valuable opportunity for rapid preparation of chiral compounds. We present here a highly enantioselective organocatalytic OKR using chirally modified AZADO (2-azaadamantane N-oxyl) derivatives. AZADO is a highly active and stable nitroxyl radical type oxidation catalyst. On the basis of reaction mechanism of nitroxy-radical-catalyzed oxidation, we supposed that 2,4-substituted chiral AZADOs would be efficient for enantioselective oxidation of secondary alcohols. As the results, it was found that 4-Bn-2-Bu-AZADOH showed high catalytic activities for resolution of 2-aryl-1-cyclohexanols and 2-aryl-1-cyclopentanols with a K_rel value up to 82.2, although 4-Bn-2-Me-AZADO had a rather limited scope. This OKR was successfully applied to the total synthesis of (-)-idesolide which have a dimetic structure of hydroxyl cyclohexenone.