Electrophotocatalytic Decoupled Radical Relay Enables Highly Efficient and Enantioselective Benzylic C-H Functionalization

J Am Chem Soc. 2022 Nov 30;144(47):21674-21682. doi: 10.1021/jacs.2c09366. Epub 2022 Nov 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products*
  • Catalysis
  • Copper
  • Electronics
  • Stereoisomerism

Substances

  • Biological Products
  • Copper