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HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes

In the present work, the employment of fluorinated alcohols, specifically 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), as solvent and promoter of the catalyst-free synthesis of substituted tetrahydrofuranes through the addition of electron-rich alkenes to epoxydes is described. The unique properties of...

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Autores principales: Llopis, Natalia, Baeza, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435839/
https://www.ncbi.nlm.nih.gov/pubmed/32751509
http://dx.doi.org/10.3390/molecules25153464
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author Llopis, Natalia
Baeza, Alejandro
author_facet Llopis, Natalia
Baeza, Alejandro
author_sort Llopis, Natalia
collection PubMed
description In the present work, the employment of fluorinated alcohols, specifically 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), as solvent and promoter of the catalyst-free synthesis of substituted tetrahydrofuranes through the addition of electron-rich alkenes to epoxydes is described. The unique properties of this fluorinated alcohol, which is very different from their non-fluorinated analogs, allows carrying out this new straightforward protocol under smooth reaction conditions affording the corresponding adducts in moderate yields in the majority of cases. Remarkably, this methodology has allowed the synthesis of new tetrahydrofuran-based spiro compounds as well as tetrahydrofurobenzofuran derivatives. The scope and limitations of the process are also discussed. Mechanistic studies were also performed pointing towards a purely ionic or a S(N)2-type process depending on the nucleophilicity of the alkene employed.
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spelling pubmed-74358392020-08-25 HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes Llopis, Natalia Baeza, Alejandro Molecules Article In the present work, the employment of fluorinated alcohols, specifically 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), as solvent and promoter of the catalyst-free synthesis of substituted tetrahydrofuranes through the addition of electron-rich alkenes to epoxydes is described. The unique properties of this fluorinated alcohol, which is very different from their non-fluorinated analogs, allows carrying out this new straightforward protocol under smooth reaction conditions affording the corresponding adducts in moderate yields in the majority of cases. Remarkably, this methodology has allowed the synthesis of new tetrahydrofuran-based spiro compounds as well as tetrahydrofurobenzofuran derivatives. The scope and limitations of the process are also discussed. Mechanistic studies were also performed pointing towards a purely ionic or a S(N)2-type process depending on the nucleophilicity of the alkene employed. MDPI 2020-07-30 /pmc/articles/PMC7435839/ /pubmed/32751509 http://dx.doi.org/10.3390/molecules25153464 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Llopis, Natalia
Baeza, Alejandro
HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes
title HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes
title_full HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes
title_fullStr HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes
title_full_unstemmed HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes
title_short HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes
title_sort hfip-promoted synthesis of substituted tetrahydrofurans by reaction of epoxides with electron-rich alkenes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435839/
https://www.ncbi.nlm.nih.gov/pubmed/32751509
http://dx.doi.org/10.3390/molecules25153464
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