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Electrophotocatalytic Decoupled Radical Relay Enables Highly Efficient and Enantioselective Benzylic C–H Functionalization
journal contributionposted on 2022-11-17, 15:06 authored by Wenzheng Fan, Xueyao Zhao, Yunshun Deng, Pinhong Chen, Fei Wang, Guosheng Liu
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 diverse alkylarenes, many of which are much less reactive or even unreactive using the existing method relying on coupled radical relay. Moreover, the current protocol is also amenable to late-stage functionalization of bioactive molecules, including natural products and drugs.
transient radical intermediatemuch less reactiveincluding natural productseven unreactive usingcoupled radical relaybenzylic radical formationexisting method relying3 supsustainable methodunified approachtype photocatalyststage modificationstage functionalizationsimply modulatingmerging electrophotoindependently regulatehighly efficientfeedstocks upgradationelectronic propertyeffectively capturediverse alkylarenescurrent protocolcopper catalysiscomplex moleculesbioactive moleculesapplied currentalso amenable