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Published on: November 30, 2022
Regioselective ortho halogenation of N-aryl amides and ureas via oxidative halodeboronation: harnessing boron
Ganesh H Shinde1, Ganesh S Ghotekar1, Francoise M Amombo Noa2
1Department of Chemistry and Molecular Biology, University of Gothenburg SE-41296 Gothenburg Sweden henrik.sunden@chem.gu.se.
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.
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