Bioinspired Site-Selective Hydroperoxidation of Unactivated C(sp3)–H Bonds Useful for Late-Stage Functionalization

Organic hydroperoxides are a class of important compounds existing ubiquitously in natural products and biologically significant molecules. The ideal preparation method towards this compound class is direct hydroperoxidation of C(sp3)–H bonds. Despite significant advances in C(sp3)–H functionalization, the site-selective hydroperoxidation of unactivated C(sp3)–H bonds remains a substantial challenge. Inspired by the biosynthetic catalysis of cyclooxygenase, we developed a general and practical method for the direct and site-selective hydroperoxidation of unactivated C(sp3)–H bonds enabled by a hydrogen atom transfer (HAT) strategy involving O2 as the oxidant and bromine radical as the HAT catalyst under mild photochemical conditions. The reaction results of diverse substrates, such as alkanes, alcohols, ketones, terpenoids, and derivatives of amino acids, peptides, glucose, ribofuranose, phosphonates, and drugs, showed that this method is robust and efficient, and is useful for the late-stage C–H functionalization of drugs and natural products.