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.
Highlights
The recent renaissance of synthetic organic radical chemistry has seen the development of several approaches for the introduction of nitrile functionality into molecules through the trapping of radical intermediates with a variety of closed-shell reagents
Cyanomethyl groups can be efficiently introduced into a range of substrates via trapping of a-carbonyl, heterobenzylic, alkyl, sulfonyl and aryl radicals, generated from a variety of functional groups under both photoredox catalysis and non-catalytic conditions
The direct C–H cyanation of arenes has been performed under photoredox catalysis, using cyanide generated from TMSCN to trap an aryl radical cation.5g
Summary
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 cascadefragmentation mechanism driven by the loss of dinitrogen and the stabilised 2-hydroxypropyl radical, effecting cyanomethylation. Cyanomethyl groups can be efficiently introduced into a range of substrates via trapping of a-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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