Issue 46, 2023

Regioselective ortho halogenation of N-aryl amides and ureas via oxidative halodeboronation: harnessing boron reactivity for efficient C–halogen bond installation

Abstract

The installation of the C–halogen bond at the ortho position of N-aryl amides and ureas represents a tool to prepare motifs that are ubiquitous in biologically active compounds. To construct such prevalent bonds, most methods require the use of precious metals and a multistep process. Here we report a novel protocol for the long-standing challenge of regioselective ortho halogenation of N-aryl amides and ureas using an oxidative halodeboronation. By harnessing the reactivity of boron over nitrogen, we merge carbonyl-directed borylation with consecutive halodeboronation, enabling the precise introduction of the C–X bond at the desired ortho position of N-aryl amides and ureas. This method offers an efficient, practical, and scalable solution for synthesizing halogenated N-heteroarenes under mild conditions, highlighting the superiority of boron reactivity in directing the regioselectivity of the reaction.

Graphical abstract: Regioselective ortho halogenation of N-aryl amides and ureas via oxidative halodeboronation: harnessing boron reactivity for efficient C–halogen bond installation

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Article information

Article type
Edge Article
Submitted
01 Sep 2023
Accepted
23 Oct 2023
First published
23 Oct 2023
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., 2023,14, 13429-13436

Regioselective ortho halogenation of N-aryl amides and ureas via oxidative halodeboronation: harnessing boron reactivity for efficient C–halogen bond installation

G. H. Shinde, G. S. Ghotekar, F. M. Amombo Noa, L. Öhrström, P. Norrby and H. Sundén, Chem. Sci., 2023, 14, 13429 DOI: 10.1039/D3SC04628A

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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