Desymmetrization of cyclohexanes by site- and stereoselective C–H functionalization

Carbon–hydrogen (C–H) bonds have long been considered unreactive and are inert to traditional chemical reagents, yet new methods for the transformation of these bonds are continually being developed1–9. However, it is challenging to achieve such transformations in a highly selective manner, especially if the C–H bonds are unactivated10 or not adjacent to a directing group11–13. Catalyst-controlled site-selectivity—in which the inherent reactivities of the substrates14 can be overcome by choosing an appropriate catalyst—is an appealing concept, and substantial effort has been made towards catalyst-controlled C–H functionalization6,15–17, in particular methylene C–H bond functionalization. However, although several new methods have targeted these bonds in cyclic alkanes, the selectivity has been relatively poor18–20. Here we illustrate an additional level of sophistication in catalyst-controlled C–H functionalization, whereby unactivated cyclohexane derivatives can be desymmetrized in a highly site- and stereoselective manner through donor/acceptor carbene insertion. These studies demonstrate the potential of catalyst-controlled site-selectivity to govern which C–H bond will react, which could enable new strategies for the production of fine chemicals.