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Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates

An expansion of the solvent‐free synthetic toolbox is essential for advances in the sustainable chemical industry. Mechanochemical reactions offer a superior safety profile and reduced amount of waste compared to conventional solvent‐based synthesis. Herein a new mechanochemical method was developed...

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Autores principales: Dalidovich, Tatsiana, Nallaparaju, Jagadeesh Varma, Shalima, Tatsiana, Aav, Riina, Kananovich, Dzmitry G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303792/
https://www.ncbi.nlm.nih.gov/pubmed/34932893
http://dx.doi.org/10.1002/cssc.202102286
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author Dalidovich, Tatsiana
Nallaparaju, Jagadeesh Varma
Shalima, Tatsiana
Aav, Riina
Kananovich, Dzmitry G.
author_facet Dalidovich, Tatsiana
Nallaparaju, Jagadeesh Varma
Shalima, Tatsiana
Aav, Riina
Kananovich, Dzmitry G.
author_sort Dalidovich, Tatsiana
collection PubMed
description An expansion of the solvent‐free synthetic toolbox is essential for advances in the sustainable chemical industry. Mechanochemical reactions offer a superior safety profile and reduced amount of waste compared to conventional solvent‐based synthesis. Herein a new mechanochemical method was developed for nucleophilic substitution of alcohols using fluoro‐N,N,N′,N′‐tetramethylformamidinium hexafluorophosphate (TFFH) and K(2)HPO(4) as an alcohol‐activating reagent and a base, respectively. Alcohol activation and reaction with a nucleophile were performed in one milling jar via reactive isouronium intermediates. Nucleophilic substitution with amines afforded alkylated amines in 31–91 % yields. The complete stereoinversion occurred for the S(N)2 reaction of (R)‐ and (S)‐ethyl lactates. Substitution with halide anions (F(−), Br(−), I(−)) and oxygen‐centered (CH(3)OH, PhO(−)) nucleophiles was also tested. Application of the method to the synthesis of active pharmaceutical ingredients has been demonstrated.
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spelling pubmed-93037922022-07-28 Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates Dalidovich, Tatsiana Nallaparaju, Jagadeesh Varma Shalima, Tatsiana Aav, Riina Kananovich, Dzmitry G. ChemSusChem Research Articles An expansion of the solvent‐free synthetic toolbox is essential for advances in the sustainable chemical industry. Mechanochemical reactions offer a superior safety profile and reduced amount of waste compared to conventional solvent‐based synthesis. Herein a new mechanochemical method was developed for nucleophilic substitution of alcohols using fluoro‐N,N,N′,N′‐tetramethylformamidinium hexafluorophosphate (TFFH) and K(2)HPO(4) as an alcohol‐activating reagent and a base, respectively. Alcohol activation and reaction with a nucleophile were performed in one milling jar via reactive isouronium intermediates. Nucleophilic substitution with amines afforded alkylated amines in 31–91 % yields. The complete stereoinversion occurred for the S(N)2 reaction of (R)‐ and (S)‐ethyl lactates. Substitution with halide anions (F(−), Br(−), I(−)) and oxygen‐centered (CH(3)OH, PhO(−)) nucleophiles was also tested. Application of the method to the synthesis of active pharmaceutical ingredients has been demonstrated. John Wiley and Sons Inc. 2022-01-20 2022-02-08 /pmc/articles/PMC9303792/ /pubmed/34932893 http://dx.doi.org/10.1002/cssc.202102286 Text en © 2021 The Authors. ChemSusChem published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Dalidovich, Tatsiana
Nallaparaju, Jagadeesh Varma
Shalima, Tatsiana
Aav, Riina
Kananovich, Dzmitry G.
Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates
title Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates
title_full Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates
title_fullStr Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates
title_full_unstemmed Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates
title_short Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates
title_sort mechanochemical nucleophilic substitution of alcohols via isouronium intermediates
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303792/
https://www.ncbi.nlm.nih.gov/pubmed/34932893
http://dx.doi.org/10.1002/cssc.202102286
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