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Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines

2-Fluoroindoles as an important structural scaffold are widely existing in many bioactive or therapeutic agents. Despite their potential usefulness, efficient constructions of 2-fluoroindole derivatives are very sparce. The development of straightforward synthetic approaches to access 2-fluoroindole...

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Autores principales: Su, Jianke, Hu, Xinyuan, Huang, Hua, Guo, Yu, Song, Qiuling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371155/
https://www.ncbi.nlm.nih.gov/pubmed/34404806
http://dx.doi.org/10.1038/s41467-021-25313-z
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author Su, Jianke
Hu, Xinyuan
Huang, Hua
Guo, Yu
Song, Qiuling
author_facet Su, Jianke
Hu, Xinyuan
Huang, Hua
Guo, Yu
Song, Qiuling
author_sort Su, Jianke
collection PubMed
description 2-Fluoroindoles as an important structural scaffold are widely existing in many bioactive or therapeutic agents. Despite their potential usefulness, efficient constructions of 2-fluoroindole derivatives are very sparce. The development of straightforward synthetic approaches to access 2-fluoroindoles is highly desirable for studying their fundamental properties and applications. Herein, we report an efficient and general strategy for the construction of 2-fluoroindoles in which a wide variety of 2-fluoroindoles were accessed with high efficiency and chemoselectivity. Instead of starting from indole skeletons, our strategy constructs indole scaffolds alongside the incorporation of fluorine atom on C2 position in a formal [4+1] cyclization from readily accessible ortho-vinylanilines and difluorocarbene. In our protocol, commercially accessible halodifluoroalkylative reagents provide one carbon and one fluorine atom by cleaving one C-N tertiary bond and forming one C-N bond and one C-C double bond with ortho-vinylanilines. Downstream transformations on 2-fluoroindoles lead to various valuable bioactive molecules which demonstrated significant synthetic advantages over previous reports. And mechanistic studies suggest that the reaction undergoes a cascade difluorocarbene-trapping and intramolecular Michael addition reaction followed by Csp(3)-F bond cleavage.
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spelling pubmed-83711552021-09-02 Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines Su, Jianke Hu, Xinyuan Huang, Hua Guo, Yu Song, Qiuling Nat Commun Article 2-Fluoroindoles as an important structural scaffold are widely existing in many bioactive or therapeutic agents. Despite their potential usefulness, efficient constructions of 2-fluoroindole derivatives are very sparce. The development of straightforward synthetic approaches to access 2-fluoroindoles is highly desirable for studying their fundamental properties and applications. Herein, we report an efficient and general strategy for the construction of 2-fluoroindoles in which a wide variety of 2-fluoroindoles were accessed with high efficiency and chemoselectivity. Instead of starting from indole skeletons, our strategy constructs indole scaffolds alongside the incorporation of fluorine atom on C2 position in a formal [4+1] cyclization from readily accessible ortho-vinylanilines and difluorocarbene. In our protocol, commercially accessible halodifluoroalkylative reagents provide one carbon and one fluorine atom by cleaving one C-N tertiary bond and forming one C-N bond and one C-C double bond with ortho-vinylanilines. Downstream transformations on 2-fluoroindoles lead to various valuable bioactive molecules which demonstrated significant synthetic advantages over previous reports. And mechanistic studies suggest that the reaction undergoes a cascade difluorocarbene-trapping and intramolecular Michael addition reaction followed by Csp(3)-F bond cleavage. Nature Publishing Group UK 2021-08-17 /pmc/articles/PMC8371155/ /pubmed/34404806 http://dx.doi.org/10.1038/s41467-021-25313-z Text en © The Author(s) 2021 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
Su, Jianke
Hu, Xinyuan
Huang, Hua
Guo, Yu
Song, Qiuling
Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines
title Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines
title_full Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines
title_fullStr Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines
title_full_unstemmed Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines
title_short Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines
title_sort difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371155/
https://www.ncbi.nlm.nih.gov/pubmed/34404806
http://dx.doi.org/10.1038/s41467-021-25313-z
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