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Electrochemical synthesis of biaryls by reductive extrusion from N,N’-diarylureas

The synthesis of biaryl compounds by the transition-metal free coupling of arenes is an important contemporary challenge, aiming to avoid the toxicity and cost profiles associated with the metal catalysts commonly used in the synthesis of these pharmaceutically relevant motifs. In this paper, we des...

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Autores principales: Stammers, Ellie, Parsons, Chris D., Clayden, Jonathan, Lennox, Alastair J. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10382484/
https://www.ncbi.nlm.nih.gov/pubmed/37507363
http://dx.doi.org/10.1038/s41467-023-40237-6
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author Stammers, Ellie
Parsons, Chris D.
Clayden, Jonathan
Lennox, Alastair J. J.
author_facet Stammers, Ellie
Parsons, Chris D.
Clayden, Jonathan
Lennox, Alastair J. J.
author_sort Stammers, Ellie
collection PubMed
description The synthesis of biaryl compounds by the transition-metal free coupling of arenes is an important contemporary challenge, aiming to avoid the toxicity and cost profiles associated with the metal catalysts commonly used in the synthesis of these pharmaceutically relevant motifs. In this paper, we describe an electrochemical approach to the synthesis of biaryls in which aniline derivatives are coupled through the formation and reduction of a temporary urea linkage. The conformational alignment of the arenes in the N,N’-diaryl urea intermediates promotes C-C bond formation following single-electron reduction. Our optimized conditions are suitable for the synthesis of a variety of biaryls, including sterically hindered examples carrying ortho-substituents, representing complementary reactivity to most metal catalysed methods.
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spelling pubmed-103824842023-07-30 Electrochemical synthesis of biaryls by reductive extrusion from N,N’-diarylureas Stammers, Ellie Parsons, Chris D. Clayden, Jonathan Lennox, Alastair J. J. Nat Commun Article The synthesis of biaryl compounds by the transition-metal free coupling of arenes is an important contemporary challenge, aiming to avoid the toxicity and cost profiles associated with the metal catalysts commonly used in the synthesis of these pharmaceutically relevant motifs. In this paper, we describe an electrochemical approach to the synthesis of biaryls in which aniline derivatives are coupled through the formation and reduction of a temporary urea linkage. The conformational alignment of the arenes in the N,N’-diaryl urea intermediates promotes C-C bond formation following single-electron reduction. Our optimized conditions are suitable for the synthesis of a variety of biaryls, including sterically hindered examples carrying ortho-substituents, representing complementary reactivity to most metal catalysed methods. Nature Publishing Group UK 2023-07-28 /pmc/articles/PMC10382484/ /pubmed/37507363 http://dx.doi.org/10.1038/s41467-023-40237-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Stammers, Ellie
Parsons, Chris D.
Clayden, Jonathan
Lennox, Alastair J. J.
Electrochemical synthesis of biaryls by reductive extrusion from N,N’-diarylureas
title Electrochemical synthesis of biaryls by reductive extrusion from N,N’-diarylureas
title_full Electrochemical synthesis of biaryls by reductive extrusion from N,N’-diarylureas
title_fullStr Electrochemical synthesis of biaryls by reductive extrusion from N,N’-diarylureas
title_full_unstemmed Electrochemical synthesis of biaryls by reductive extrusion from N,N’-diarylureas
title_short Electrochemical synthesis of biaryls by reductive extrusion from N,N’-diarylureas
title_sort electrochemical synthesis of biaryls by reductive extrusion from n,n’-diarylureas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10382484/
https://www.ncbi.nlm.nih.gov/pubmed/37507363
http://dx.doi.org/10.1038/s41467-023-40237-6
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