Issue 35, 2022

Investigations into mechanism and origin of regioselectivity in the metallaphotoredox-catalyzed α-arylation of N-alkylbenzamides

Abstract

A mechanistic study on the α-arylation of N-alkylbenzamides catalyzed by a dual nickel/photoredox system using aryl bromides is reported herein. This study elucidates the origins of site-selectivity of the transformation, which is controlled by the generation of a hydrogen atom transfer (HAT) agent by a photocatalyst and bromide ions in solution. Tetrabutylammonium bromide was identified as a crucial additive and source of a potent HAT agent, which led to increases in yields and a lowering of the stoichiometries of the aryl bromide coupling partner. NMR titration experiments and Stern–Volmer quenching studies provide evidence for complexation to and oxidation of bromide by the photocatalyst, while elementary steps involving deprotonation of the N-alkylbenzamide or 1,5-HAT were ruled out through mechanistic probes and kinetic isotope effect analysis. This study serves as a valuable tool to better understand the α-arylation of N-alkylbenzamides, and has broader implications in halide-mediated C–H functionalization reactions.

Graphical abstract: Investigations into mechanism and origin of regioselectivity in the metallaphotoredox-catalyzed α-arylation of N-alkylbenzamides

Supplementary files

Article information

Article type
Edge Article
Submitted
05 Apr 2022
Accepted
19 Aug 2022
First published
19 Aug 2022
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., 2022,13, 10566-10573

Investigations into mechanism and origin of regioselectivity in the metallaphotoredox-catalyzed α-arylation of N-alkylbenzamides

A. W. Rand, M. Chen and J. Montgomery, Chem. Sci., 2022, 13, 10566 DOI: 10.1039/D2SC01962K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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