Setting Cyclohexane Stereochemistry with Oxidation

Thanks to its atomand step-economy, C–H bond oxidation represents a “hot topic” in synthetic chemistry. However, due to the ubiquity of such bonds in organic molecules, regioand enantioselective C–H bond oxidation turns out to be extremely challenging, and efficient direct methods are in high demand. Compared to the success of aliphatic sp C–H oxidation by enzymes (such as cytochrome P450, Figure 1), enantioselective oxidation of sp C–H bonds by nonenzymatic systems is quite rare, and the few examples are limited to relatively weak C–H bonds such as those in benzylic and allylic positions. In these reactions, chiral ligand coordinated high-valent metal–oxo species abstract a hydride atom from an sp C–H bond, followed by enantiomeric-determining radical rebound to the chiral metal hydroxide through a-face (or b-face) to provide enantiomerically enriched alcohol (Scheme 1a). However, the reported catalytic systems only provide moderate levels of efficiency and enantioselectivity. Until recently, the alternative strategies have used radical relays for the enantioselective cyanation of benzylic C–H bonds, which provides excellent enantioselectivity in high efficiency. For nonactivated aliphatic C–H bonds, however, despite decades of past research, enantioselective reactions remain elusive.