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Nucleophilic Radiofluorination Using Tri-tert-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics

We present a quantum chemical analysis of the (18)F-fluorination of 1,3-ditosylpropane, promoted by a quaternary ammonium salt (tri-(tert-butanol)-methylammonium iodide (TBMA-I) with moderate to good radiochemical yields (RCYs), experimentally observed by Shinde et al. We obtained the mechanism of t...

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Detalles Bibliográficos
Autores principales: Oh, Young-Ho, Shinde, Sandip S., Lee, Sungyul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8838713/
https://www.ncbi.nlm.nih.gov/pubmed/35164308
http://dx.doi.org/10.3390/molecules27031044
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author Oh, Young-Ho
Shinde, Sandip S.
Lee, Sungyul
author_facet Oh, Young-Ho
Shinde, Sandip S.
Lee, Sungyul
author_sort Oh, Young-Ho
collection PubMed
description We present a quantum chemical analysis of the (18)F-fluorination of 1,3-ditosylpropane, promoted by a quaternary ammonium salt (tri-(tert-butanol)-methylammonium iodide (TBMA-I) with moderate to good radiochemical yields (RCYs), experimentally observed by Shinde et al. We obtained the mechanism of the S(N)2 process, focusing on the role of the –OH functional groups facilitating the reactions. We found that the counter-cation TBMA(+) acts as a bifunctional promoter: the –OH groups function as a bidentate ‘anchor’ bridging the nucleophile [(18)F]F(−) and the –OTs leaving group or the third –OH. These electrostatic interactions cooperate for the formation of the transition states of a very compact configuration for facile S(N)2 (18)F-fluorination.
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spelling pubmed-88387132022-02-13 Nucleophilic Radiofluorination Using Tri-tert-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics Oh, Young-Ho Shinde, Sandip S. Lee, Sungyul Molecules Article We present a quantum chemical analysis of the (18)F-fluorination of 1,3-ditosylpropane, promoted by a quaternary ammonium salt (tri-(tert-butanol)-methylammonium iodide (TBMA-I) with moderate to good radiochemical yields (RCYs), experimentally observed by Shinde et al. We obtained the mechanism of the S(N)2 process, focusing on the role of the –OH functional groups facilitating the reactions. We found that the counter-cation TBMA(+) acts as a bifunctional promoter: the –OH groups function as a bidentate ‘anchor’ bridging the nucleophile [(18)F]F(−) and the –OTs leaving group or the third –OH. These electrostatic interactions cooperate for the formation of the transition states of a very compact configuration for facile S(N)2 (18)F-fluorination. MDPI 2022-02-03 /pmc/articles/PMC8838713/ /pubmed/35164308 http://dx.doi.org/10.3390/molecules27031044 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oh, Young-Ho
Shinde, Sandip S.
Lee, Sungyul
Nucleophilic Radiofluorination Using Tri-tert-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics
title Nucleophilic Radiofluorination Using Tri-tert-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics
title_full Nucleophilic Radiofluorination Using Tri-tert-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics
title_fullStr Nucleophilic Radiofluorination Using Tri-tert-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics
title_full_unstemmed Nucleophilic Radiofluorination Using Tri-tert-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics
title_short Nucleophilic Radiofluorination Using Tri-tert-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics
title_sort nucleophilic radiofluorination using tri-tert-butanol ammonium as a bifunctional organocatalyst: mechanism and energetics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8838713/
https://www.ncbi.nlm.nih.gov/pubmed/35164308
http://dx.doi.org/10.3390/molecules27031044
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