Electrochemical synthesis of biaryls by reductive extrusion from N,N’-diarylureas
Abstract 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 pape...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40237-6 |
| _version_ | 1797769453116588032 |
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| author | Ellie Stammers Chris D. Parsons Jonathan Clayden Alastair J. J. Lennox |
| author_facet | Ellie Stammers Chris D. Parsons Jonathan Clayden Alastair J. J. Lennox |
| author_sort | Ellie Stammers |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T21:09:10Z |
| format | Article |
| id | doaj.art-9ccdf55698314fa8ba454d9fe1651fe1 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-12T21:09:10Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-9ccdf55698314fa8ba454d9fe1651fe12023-07-30T11:18:56ZengNature PortfolioNature Communications2041-17232023-07-011411610.1038/s41467-023-40237-6Electrochemical synthesis of biaryls by reductive extrusion from N,N’-diarylureasEllie Stammers0Chris D. Parsons1Jonathan Clayden2Alastair J. J. Lennox3School of Chemistry, University of Bristol, Cantock’s CloseEarly Chemical Development, Pharmaceutical Sciences, R&D, AstraZenecaSchool of Chemistry, University of Bristol, Cantock’s CloseSchool of Chemistry, University of Bristol, Cantock’s CloseAbstract 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.https://doi.org/10.1038/s41467-023-40237-6 |
| spellingShingle | Ellie Stammers Chris D. Parsons Jonathan Clayden Alastair J. J. Lennox Electrochemical synthesis of biaryls by reductive extrusion from N,N’-diarylureas Nature Communications |
| 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 |
| url | https://doi.org/10.1038/s41467-023-40237-6 |
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