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 will revolutionize the preparation of chiral alcohols and their derivatives. Enzymatic catalysis, which uses key metal-oxo species 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 biomimetic catalytic system that achieves highly efficient asymmetric sp3 C–H oxidation with C–H substrates as the limiting reagent. A 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 method has been successfully accomplished with good functional group compatibility and exceptionally high site- and enantioselectivity, which is applicable for the late-stage oxidation of bioactive compounds. The efficiency of enantioselective sp3 C–H bond oxidation using small synthetic catalysts is usually limited. Now a catalytic system involving a Cu(II)-bound tert-butoxy radical for site-selective C–H bond cleavage achieves allylic and propargylic sp3 C–H oxidation with the C–H substrates as the limiting reagent.