Cargando…
Complementary Base Lowers the Barrier in SuFEx Click Chemistry for Primary Amine Nucleophiles
[Image: see text] The sulfur(VI) fluoride exchange (SuFEx) reaction is an emerging scheme for connecting molecular building blocks. Due to its broad functional group tolerance and rather stable resulting linkage, it is seeing rapid adoption in various fields of chemistry. Still, to date the reaction...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2020
|
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726939/ https://www.ncbi.nlm.nih.gov/pubmed/33324855 http://dx.doi.org/10.1021/acsomega.0c05049 |
_version_ | 1783620991070502912 |
---|---|
author | Luy, Jan-Niclas Tonner, Ralf |
author_facet | Luy, Jan-Niclas Tonner, Ralf |
author_sort | Luy, Jan-Niclas |
collection | PubMed |
description | [Image: see text] The sulfur(VI) fluoride exchange (SuFEx) reaction is an emerging scheme for connecting molecular building blocks. Due to its broad functional group tolerance and rather stable resulting linkage, it is seeing rapid adoption in various fields of chemistry. Still, to date the reaction mechanism is poorly understood, which hampers further development. Here, we show that the mechanism of the SuFEx reaction for the prototypical example of methanesulfonyl fluoride reacting with methylamine can be understood as an S(N)2-type reaction. By analyzing the reaction path with the help of density functional theory in vacuo and under consideration of solvent and co-reactant influence, we identify the often used complementary base as a crucial ingredient to lower the reaction barrier significantly by increasing the nucleophilicity of the primary amine. With the help of energy decomposition analysis at the transition state structures, we quantify the underlying stereoelectronic effects and propose new avenues for experimental exploration of the potential of SuFEx chemistry. |
format | Online Article Text |
id | pubmed-7726939 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-77269392020-12-14 Complementary Base Lowers the Barrier in SuFEx Click Chemistry for Primary Amine Nucleophiles Luy, Jan-Niclas Tonner, Ralf ACS Omega [Image: see text] The sulfur(VI) fluoride exchange (SuFEx) reaction is an emerging scheme for connecting molecular building blocks. Due to its broad functional group tolerance and rather stable resulting linkage, it is seeing rapid adoption in various fields of chemistry. Still, to date the reaction mechanism is poorly understood, which hampers further development. Here, we show that the mechanism of the SuFEx reaction for the prototypical example of methanesulfonyl fluoride reacting with methylamine can be understood as an S(N)2-type reaction. By analyzing the reaction path with the help of density functional theory in vacuo and under consideration of solvent and co-reactant influence, we identify the often used complementary base as a crucial ingredient to lower the reaction barrier significantly by increasing the nucleophilicity of the primary amine. With the help of energy decomposition analysis at the transition state structures, we quantify the underlying stereoelectronic effects and propose new avenues for experimental exploration of the potential of SuFEx chemistry. American Chemical Society 2020-11-23 /pmc/articles/PMC7726939/ /pubmed/33324855 http://dx.doi.org/10.1021/acsomega.0c05049 Text en © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Luy, Jan-Niclas Tonner, Ralf Complementary Base Lowers the Barrier in SuFEx Click Chemistry for Primary Amine Nucleophiles |
title | Complementary Base Lowers the Barrier in SuFEx Click
Chemistry for Primary Amine Nucleophiles |
title_full | Complementary Base Lowers the Barrier in SuFEx Click
Chemistry for Primary Amine Nucleophiles |
title_fullStr | Complementary Base Lowers the Barrier in SuFEx Click
Chemistry for Primary Amine Nucleophiles |
title_full_unstemmed | Complementary Base Lowers the Barrier in SuFEx Click
Chemistry for Primary Amine Nucleophiles |
title_short | Complementary Base Lowers the Barrier in SuFEx Click
Chemistry for Primary Amine Nucleophiles |
title_sort | complementary base lowers the barrier in sufex click
chemistry for primary amine nucleophiles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726939/ https://www.ncbi.nlm.nih.gov/pubmed/33324855 http://dx.doi.org/10.1021/acsomega.0c05049 |
work_keys_str_mv | AT luyjanniclas complementarybaselowersthebarrierinsufexclickchemistryforprimaryaminenucleophiles AT tonnerralf complementarybaselowersthebarrierinsufexclickchemistryforprimaryaminenucleophiles |