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SuFEx-enabled, chemoselective synthesis of triflates, triflamides and triflimidates
Sulfur(vi) Fluoride Exchange (SuFEx) chemistry has emerged as a next-generation click reaction, designed to assemble functional molecules quickly and modularly. Here, we report the ex situ generation of trifluoromethanesulfonyl fluoride (CF(3)SO(2)F) gas in a two chamber system, and its use as a new...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864708/ https://www.ncbi.nlm.nih.gov/pubmed/35310484 http://dx.doi.org/10.1039/d1sc06267k |
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author | Li, Bing-Yu Voets, Lauren Van Lommel, Ruben Hoppenbrouwers, Fien Alonso, Mercedes Verhelst, Steven H. L. De Borggraeve, Wim M. Demaerel, Joachim |
author_facet | Li, Bing-Yu Voets, Lauren Van Lommel, Ruben Hoppenbrouwers, Fien Alonso, Mercedes Verhelst, Steven H. L. De Borggraeve, Wim M. Demaerel, Joachim |
author_sort | Li, Bing-Yu |
collection | PubMed |
description | Sulfur(vi) Fluoride Exchange (SuFEx) chemistry has emerged as a next-generation click reaction, designed to assemble functional molecules quickly and modularly. Here, we report the ex situ generation of trifluoromethanesulfonyl fluoride (CF(3)SO(2)F) gas in a two chamber system, and its use as a new SuFEx handle to efficiently synthesize triflates and triflamides. This broadly tolerated protocol lends itself to peptide modification or to telescoping into coupling reactions. Moreover, redesigning the S(VI)–F connector with a S[double bond, length as m-dash]O → S[double bond, length as m-dash]NR replacement furnished the analogous triflimidoyl fluorides as SuFEx electrophiles, which were engaged in the synthesis of rarely reported triflimidate esters. Notably, experiments showed H(2)O to be the key towards achieving chemoselective trifluoromethanesulfonation of phenols vs. amine groups, a phenomenon best explained—using ab initio metadynamics simulations—by a hydrogen bonded termolecular transition state for the CF(3)SO(2)F triflylation of amines. |
format | Online Article Text |
id | pubmed-8864708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-88647082022-03-17 SuFEx-enabled, chemoselective synthesis of triflates, triflamides and triflimidates Li, Bing-Yu Voets, Lauren Van Lommel, Ruben Hoppenbrouwers, Fien Alonso, Mercedes Verhelst, Steven H. L. De Borggraeve, Wim M. Demaerel, Joachim Chem Sci Chemistry Sulfur(vi) Fluoride Exchange (SuFEx) chemistry has emerged as a next-generation click reaction, designed to assemble functional molecules quickly and modularly. Here, we report the ex situ generation of trifluoromethanesulfonyl fluoride (CF(3)SO(2)F) gas in a two chamber system, and its use as a new SuFEx handle to efficiently synthesize triflates and triflamides. This broadly tolerated protocol lends itself to peptide modification or to telescoping into coupling reactions. Moreover, redesigning the S(VI)–F connector with a S[double bond, length as m-dash]O → S[double bond, length as m-dash]NR replacement furnished the analogous triflimidoyl fluorides as SuFEx electrophiles, which were engaged in the synthesis of rarely reported triflimidate esters. Notably, experiments showed H(2)O to be the key towards achieving chemoselective trifluoromethanesulfonation of phenols vs. amine groups, a phenomenon best explained—using ab initio metadynamics simulations—by a hydrogen bonded termolecular transition state for the CF(3)SO(2)F triflylation of amines. The Royal Society of Chemistry 2022-01-05 /pmc/articles/PMC8864708/ /pubmed/35310484 http://dx.doi.org/10.1039/d1sc06267k Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Li, Bing-Yu Voets, Lauren Van Lommel, Ruben Hoppenbrouwers, Fien Alonso, Mercedes Verhelst, Steven H. L. De Borggraeve, Wim M. Demaerel, Joachim SuFEx-enabled, chemoselective synthesis of triflates, triflamides and triflimidates |
title | SuFEx-enabled, chemoselective synthesis of triflates, triflamides and triflimidates |
title_full | SuFEx-enabled, chemoselective synthesis of triflates, triflamides and triflimidates |
title_fullStr | SuFEx-enabled, chemoselective synthesis of triflates, triflamides and triflimidates |
title_full_unstemmed | SuFEx-enabled, chemoselective synthesis of triflates, triflamides and triflimidates |
title_short | SuFEx-enabled, chemoselective synthesis of triflates, triflamides and triflimidates |
title_sort | sufex-enabled, chemoselective synthesis of triflates, triflamides and triflimidates |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864708/ https://www.ncbi.nlm.nih.gov/pubmed/35310484 http://dx.doi.org/10.1039/d1sc06267k |
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