N-Heterocyclic carbene-catalyzed remote C(sp3)-H acylation of amides

An N-heterocyclic carbene catalyzed benzylic C-H acylation of o-alkyl benzamides and cascade cycliza-tion is developed through a radical-mediated 1,5-hydrogen atom transfer (HAT) mechanism. Different from photoredox catalysis, this light-free approach enables the generation of amidyl radicals through sin-gle-electron transfer (SET) with Breslow enolates. The mild process tolerates most common functional groups and delivers a variety of dihydroisoquinolinones in moderate to high yields. The electrochemical character of the aryloxyamide is consistent with the hypothesis of ground-state SET and a plausible mechanism for the organocatalytic transformation is proposed.(c) 2023 Elsevier Ltd. All rights reserved.

Automated summary

A light-free approach using N-heterocyclic carbene catalysis and a radical-mediated 1,5-hydrogen atom transfer (HAT) mechanism is developed for the benzylic C-H acylation and cascade cyclization of o-alkyl benzamides. Different from photoredox catalysis, this method generates amidyl radicals through single-electron transfer (SET) with Breslow enolates. The mild process tolerates various functional groups and provides a variety of dihydroisoquinolinones in moderate to high yields. The electrochemical properties of the aryloxyamide support the hypothesis of ground-state SET, and a plausible mechanism for the organocatalytic transformation is proposed.