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Construction of sterically congested oxindole derivatives via visible-light-induced radical-coupling
The oxindole scaffold represents an important structural feature in many natural products and pharmaceutically relevant molecules. Herein, we report a visible-light-induced modular methodology for the synthesis of complex 3,3′-disubstituted oxindole derivatives. A library of valuable fluoroalkyl-con...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635216/ https://www.ncbi.nlm.nih.gov/pubmed/34976361 http://dx.doi.org/10.1039/d1sc05273j |
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author | Shen, Yanling Lei, Ning Lu, Cong Xi, Dailin Geng, Xinxin Tao, Pan Su, Zhishan Zheng, Ke |
author_facet | Shen, Yanling Lei, Ning Lu, Cong Xi, Dailin Geng, Xinxin Tao, Pan Su, Zhishan Zheng, Ke |
author_sort | Shen, Yanling |
collection | PubMed |
description | The oxindole scaffold represents an important structural feature in many natural products and pharmaceutically relevant molecules. Herein, we report a visible-light-induced modular methodology for the synthesis of complex 3,3′-disubstituted oxindole derivatives. A library of valuable fluoroalkyl-containing highly sterically congested oxindole derivatives can be synthesized by a catalytic three-component radical coupling reaction under mild conditions (metal & photocatalyst free, >80 examples). This strategy shows high functional group tolerance and broad substrate compatibility (including a wide variety of terminal or non-terminal alkenes, conjugated dienes and enynes, and a broad array of polyfluoroalkyl iodide and oxindoles), which enables modular modification of complex drug-like compounds in one chemical step. The success of solar-driven transformation, large-scale synthesis, and the late-stage functionalization of bioactive molecules, as well as promising tumor-suppressing biological activities, highlights the potential for practical applications of this strategy. Mechanistic investigations, including a series of control experiments, UV-vis spectroscopy and DFT calculations, suggest that the reaction underwent a sequential two-step radical-coupling process and the photosensitive perfluoroalkyl benzyl iodides are key intermediates in the transformation. |
format | Online Article Text |
id | pubmed-8635216 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-86352162021-12-30 Construction of sterically congested oxindole derivatives via visible-light-induced radical-coupling Shen, Yanling Lei, Ning Lu, Cong Xi, Dailin Geng, Xinxin Tao, Pan Su, Zhishan Zheng, Ke Chem Sci Chemistry The oxindole scaffold represents an important structural feature in many natural products and pharmaceutically relevant molecules. Herein, we report a visible-light-induced modular methodology for the synthesis of complex 3,3′-disubstituted oxindole derivatives. A library of valuable fluoroalkyl-containing highly sterically congested oxindole derivatives can be synthesized by a catalytic three-component radical coupling reaction under mild conditions (metal & photocatalyst free, >80 examples). This strategy shows high functional group tolerance and broad substrate compatibility (including a wide variety of terminal or non-terminal alkenes, conjugated dienes and enynes, and a broad array of polyfluoroalkyl iodide and oxindoles), which enables modular modification of complex drug-like compounds in one chemical step. The success of solar-driven transformation, large-scale synthesis, and the late-stage functionalization of bioactive molecules, as well as promising tumor-suppressing biological activities, highlights the potential for practical applications of this strategy. Mechanistic investigations, including a series of control experiments, UV-vis spectroscopy and DFT calculations, suggest that the reaction underwent a sequential two-step radical-coupling process and the photosensitive perfluoroalkyl benzyl iodides are key intermediates in the transformation. The Royal Society of Chemistry 2021-11-17 /pmc/articles/PMC8635216/ /pubmed/34976361 http://dx.doi.org/10.1039/d1sc05273j Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Shen, Yanling Lei, Ning Lu, Cong Xi, Dailin Geng, Xinxin Tao, Pan Su, Zhishan Zheng, Ke Construction of sterically congested oxindole derivatives via visible-light-induced radical-coupling |
title | Construction of sterically congested oxindole derivatives via visible-light-induced radical-coupling |
title_full | Construction of sterically congested oxindole derivatives via visible-light-induced radical-coupling |
title_fullStr | Construction of sterically congested oxindole derivatives via visible-light-induced radical-coupling |
title_full_unstemmed | Construction of sterically congested oxindole derivatives via visible-light-induced radical-coupling |
title_short | Construction of sterically congested oxindole derivatives via visible-light-induced radical-coupling |
title_sort | construction of sterically congested oxindole derivatives via visible-light-induced radical-coupling |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635216/ https://www.ncbi.nlm.nih.gov/pubmed/34976361 http://dx.doi.org/10.1039/d1sc05273j |
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