Site- and enantioselective allylic and propargylic C-H oxidation enabled by copper-based biomimetic catalysis

Methods for direct, enantioselective oxidation of C(sp3)–H bonds in organic molecules will revolutionize the preparation of chiral alcohols and their derivatives, which are important moieties in natural products, pharmaceuticals and agrochemicals. Enzymatic catalysis, which employs key metal oxides to facilitate efficient hydrogen atom abstraction, has evolved as a highly selective approach for C-H oxidation in biological systems. Despite its effectiveness, reproducing this function and achieving high stereoselectivity in biomimetic catalysts has proven to be a daunting task. Here we present a copper-based mimetic catalytic system that achieves highly efficient asymmetric sp3 C-H oxidation with the C-H substrates as the limiting reagent. An unprecedent Cu(II)-bound tert-butoxy radical is responsible for the site-selective C–H bond cleavage, which resembles the active site of copper-based enzymes for C–H oxidation. The developed allylic and propargylic C-H oxidation reactions have been successfully accomplished with good functional group compatibility and exceptionally high site- and enantioselectivity, and this method is applicable for the late-stage oxidation of bioactive compounds.