Photoredox Cyanomethylation of Indoles: Catalyst Modification and Mechanism

J Org Chem. 2018 Aug 17;83(16):8926-8935. doi: 10.1021/acs.joc.8b01146. Epub 2018 Jul 6.


The direct cyanomethylation of indoles at the 2- or 3-position was achieved via photoredox catalysis. The versatile nitrile synthon is introduced as a radical generated from bromoacetonitrile, a photocatalyst, and blue LED as a light source. The mechanism of the reaction is explored by determination of the Stern-Volmer quenching constants. By combining photophysical data and mass spectrometry to follow the catalyst decomposition, the catalyst ligands were tuned to enable synthetically useful yields of radical coupling products. A range of indole substrates with alkyl, aryl, halogen, ester, and ether functional groups participate in the reaction, affording products in 16-90% yields. The reaction allows the rapid construction of synthetically useful cyanomethylindoles, products that otherwise require several synthetic steps.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Indoles / chemistry*
  • Methylation
  • Nitriles / chemistry*
  • Oxidation-Reduction
  • Photochemical Processes*
  • Protons


  • Indoles
  • Nitriles
  • Protons