Boron-Mediated Regiospecific Ortho Halogenation of N-Aryl Am-ides and Ureas: Harnessing Boron Reactivity for Efficient C-X Bond Formation

16 August 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

The installation of the C-halogen bond to 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 demand 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 halodeborylation, 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 regiospecificity of the reaction.

Keywords

boron
ortho-functionalization
ipso-addition
metal-free
Regioselective
Selectfluor

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