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.