Kinetic resolution of cyclic benzylic azides enabled by site- and enantioselective C(sp3)-H oxidation

Catalytic nonenzymatic kinetic resolution (KR) of racemates remains one of the most powerful tools to prepare enantiopure compounds, which dominantly relies on the manipulation of reactive functional groups. Moreover, catalytic KR of organic azides represents a formidable challenge due to the small size and instability of the azido group. Here, an effective KR of cyclic benzylic azides through site- and enantioselective C(sp(3))-H oxidation is described. The manganese catalyzed oxidative KR reaction exhibits good functional group tolerance, and is applicable to a range of tetrahydroquinoline- and indoline-based organic azides with excellent site- and enantio-discrimination. Computational studies elucidate that the effective chiral recognition is derived from hydrogen bonding interaction between substrate and catalyst. Catalytic kinetic resolution of racemates is among the best ways to prepare enantiopure compounds, but this process is difficult with organic azides given the small size of the azido group. Here, the authors show kinetic resolution of cyclic benzylic azides through site- and enantioselective C(sp3)-H oxidation.