Electrophoto-catalytic decoupled radical relay enables highly efficient and enantioselective benzylic C-H functionalization

Asymmetric sp3 C-H functionalization has been demonstrated to substantially expedite target molecule synthesis, spanning from feedstocks upgradation to late-stage modification of complex molecules. Herein, we report a highly efficient and sustainable method for enantioselective benzylic C-H cyanation by merging electrophoto- and copper-catalysis. A novel catalytic system allows one to independently regulate the hydrogen atom transfer step for benzylic radical formation and speciation of Cu(II)/Cu(I) to effectively capture the transient radical intermediate, through tuning the electronic property of anthraquinone-type photocatalyst and simply modulating the applied current, respectively. Such decoupled radical relay catalysis enables a unified approach for enantioselective benzylic C-H cyanation of alkylarenes with wide range electron property from E-poor to super E-rich, most of which are much less reactive or even unreactive using the existing method relied on coupled radical relay. Moreover, the current protocol is also amenable to late-stage functionalization of bioactive molecules, including natural products and drugs.