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Trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes
Vicinal trifluoromethyl azides have widespread applications in organic synthesis and drug development. However, their preparation is generally limited to transition-metal-catalyzed three-component reactions. We report here a simple and metal-free method that rapidly provides these building blocks fr...
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/PMC8179360/ https://www.ncbi.nlm.nih.gov/pubmed/34164089 http://dx.doi.org/10.1039/d0sc06473d |
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author | Huang, Hong-Gui Li, Weishuang Zhong, Dayou Wang, Hu-Chong Zhao, Jing Liu, Wen-Bo |
author_facet | Huang, Hong-Gui Li, Weishuang Zhong, Dayou Wang, Hu-Chong Zhao, Jing Liu, Wen-Bo |
author_sort | Huang, Hong-Gui |
collection | PubMed |
description | Vicinal trifluoromethyl azides have widespread applications in organic synthesis and drug development. However, their preparation is generally limited to transition-metal-catalyzed three-component reactions. We report here a simple and metal-free method that rapidly provides these building blocks from abundant alkenes and trifluoromethanesulfonyl azide (N(3)SO(2)CF(3)). This unprecedented two-component reaction employs readily available N(3)SO(2)CF(3) as a bifunctional reagent to concurrently incorporate both CF(3) and N(3) groups, which avoids the use of their expensive and low atom economic precursors. A wide range of functional groups, including bio-relevant heterocycles and amino acids, were tolerated. Application of this method was further demonstrated by scale-up synthesis (5 mmol), product derivatization to CF(3)-containing medicinal chemistry motifs, as well as late-stage modification of natural product and drug derivatives. |
format | Online Article Text |
id | pubmed-8179360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-81793602021-06-22 Trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes Huang, Hong-Gui Li, Weishuang Zhong, Dayou Wang, Hu-Chong Zhao, Jing Liu, Wen-Bo Chem Sci Chemistry Vicinal trifluoromethyl azides have widespread applications in organic synthesis and drug development. However, their preparation is generally limited to transition-metal-catalyzed three-component reactions. We report here a simple and metal-free method that rapidly provides these building blocks from abundant alkenes and trifluoromethanesulfonyl azide (N(3)SO(2)CF(3)). This unprecedented two-component reaction employs readily available N(3)SO(2)CF(3) as a bifunctional reagent to concurrently incorporate both CF(3) and N(3) groups, which avoids the use of their expensive and low atom economic precursors. A wide range of functional groups, including bio-relevant heterocycles and amino acids, were tolerated. Application of this method was further demonstrated by scale-up synthesis (5 mmol), product derivatization to CF(3)-containing medicinal chemistry motifs, as well as late-stage modification of natural product and drug derivatives. The Royal Society of Chemistry 2021-01-07 /pmc/articles/PMC8179360/ /pubmed/34164089 http://dx.doi.org/10.1039/d0sc06473d Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Huang, Hong-Gui Li, Weishuang Zhong, Dayou Wang, Hu-Chong Zhao, Jing Liu, Wen-Bo Trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes |
title | Trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes |
title_full | Trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes |
title_fullStr | Trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes |
title_full_unstemmed | Trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes |
title_short | Trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes |
title_sort | trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179360/ https://www.ncbi.nlm.nih.gov/pubmed/34164089 http://dx.doi.org/10.1039/d0sc06473d |
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