Issue 22, 2019

Radical cyanomethylation via vinyl azide cascade-fragmentation


Herein, a novel methodology for radical cyanomethylation is described. The process is initiated by radical addition to the vinyl azide reagent 3-azido-2-methylbut-3-en-2-ol which triggers a cascade-fragmentation mechanism driven by the loss of dinitrogen and the stabilised 2-hydroxypropyl radical, ultimately effecting cyanomethylation. Cyanomethyl groups can be efficiently introduced into a range of substrates via trapping of α-carbonyl, heterobenzylic, alkyl, sulfonyl and aryl radicals, generated from a variety of functional groups under both photoredox catalysis and non-catalytic conditions. The value of this approach is exemplified by the late-stage cyanomethylation of pharmaceuticals.

Graphical abstract: Radical cyanomethylation via vinyl azide cascade-fragmentation

Supplementary files

Article information

Article type
Edge Article
20 Mar 2019
04 May 2019
First published
07 May 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 5832-5836

Radical cyanomethylation via vinyl azide cascade-fragmentation

J. R. Donald and Sophie L. Berrell, Chem. Sci., 2019, 10, 5832 DOI: 10.1039/C9SC01370A

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