Radical cyanomethylation via vinyl azide cascade-fragmentation

James Robert Donald; Sophie Berrell

doi:10.1039/C9SC01370A

Radical cyanomethylation via vinyl azide cascade-fragmentation

James Robert Donald^*, Sophie Berrell

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	5832-5836
Journal	Chemical Science
Volume	10
Issue number	22
Early online date	7 May 2019
DOIs	https://doi.org/10.1039/C9SC01370A
Publication status	Published - 14 Jun 2019

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10.1039/C9SC01370ALicence: CC BY

c9sc01370aFinal published version, 854 KBLicence: CC BY

Cite this

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title = "Radical cyanomethylation via vinyl azide cascade-fragmentation",

abstract = "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.",

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AU - Berrell, Sophie

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AB - 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.

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