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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...

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Autores principales: Li, Bing-Yu, Voets, Lauren, Van Lommel, Ruben, Hoppenbrouwers, Fien, Alonso, Mercedes, Verhelst, Steven H. L., De Borggraeve, Wim M., Demaerel, Joachim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
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.
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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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