Photoredox Cyanomethylation of Indoles: Catalyst Modification and Mechanism

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...

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Bibliographic Details
Published in:Journal of organic chemistry 2018-08, Vol.83 (16), p.8926-8935
Main Authors: O’Brien, Connor J, Droege, Daniel G, Jiu, Alexander Y, Gandhi, Shivaani S, Paras, Nick A, Olson, Steven H, Conrad, Jay
Format: Article
Language:English
Subjects:
Catalysis
Indoles - chemistry
Methylation
Nitriles - chemistry
Oxidation-Reduction
Photochemical Processes
Protons
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Summary: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.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.8b01146