Inter- and Intra-Molecular Organocatalysis of S<sub>N</sub>2 Fluorination by Crown Ether: Kinetics and Quantum Chemical Analysis
We present the intra- and inter-molecular organocatalysis of S<sub>N</sub>2 fluorination using CsF by crown ether to estimate the efficacy of the promoter and to elucidate the reaction mechanism. The yields of intramolecular S<sub>N</sub>2 fluorination of the veratrole substr...
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2021-05-01
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| author | Young-Ho Oh Wonhyuck Yun Chul-Hee Kim Sung-Woo Jang Sung-Sik Lee Sungyul Lee Dong-Wook Kim |
| author_facet | Young-Ho Oh Wonhyuck Yun Chul-Hee Kim Sung-Woo Jang Sung-Sik Lee Sungyul Lee Dong-Wook Kim |
| author_sort | Young-Ho Oh |
| collection | DOAJ |
| description | We present the intra- and inter-molecular organocatalysis of S<sub>N</sub>2 fluorination using CsF by crown ether to estimate the efficacy of the promoter and to elucidate the reaction mechanism. The yields of intramolecular S<sub>N</sub>2 fluorination of the veratrole substrates are measured to be very small (<1% in 12 h) in the absence of crown ether promoters, whereas the S<sub>N</sub>2 fluorination of the substrate possessing a crown ether unit proceeds to near completion (~99%) in 12 h. We also studied the efficacy of intermolecular rate acceleration by an independent promoter 18-crown-6 for comparison. We find that the fluorinating yield of a veratrole substrate (leaving group = −OMs) in the presence of 18-crown-6 follows the almost identical kinetic course as that of intramolecular S<sub>N</sub>2 fluorination, indicating the mechanistic similarity of intra- and inter-molecular organocatalysis of the crown ether for S<sub>N</sub>2 fluorination. The calculated relative Gibbs free energies of activation for these reactions, in which the crown ether units act as Lewis base promoters for S<sub>N</sub>2 fluorination, are in excellent agreement with the experimentally measured yields of fluorination. The role of the metal salt CsF is briefly discussed in terms of whether it reacts as a contact ion pair or as a “free” nucleophile F<sup>−</sup>. |
| first_indexed | 2024-03-10T11:22:40Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T11:22:40Z |
| publishDate | 2021-05-01 |
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| series | Molecules |
| spelling | doaj.art-245486ad3a9544d08118d1fa78d341162023-11-21T19:54:09ZengMDPI AGMolecules1420-30492021-05-012610294710.3390/molecules26102947Inter- and Intra-Molecular Organocatalysis of S<sub>N</sub>2 Fluorination by Crown Ether: Kinetics and Quantum Chemical AnalysisYoung-Ho Oh0Wonhyuck Yun1Chul-Hee Kim2Sung-Woo Jang3Sung-Sik Lee4Sungyul Lee5Dong-Wook Kim6Department of Applied Chemistry, Kyung Hee University, Duckyoung-daero 1732, Yongin City 446-701, KoreaDepartment of Chemistry, Inha University, 100 Inha-ro, Nam-gu, Incheon 402-751, KoreaDepartment of Chemistry, Inha University, 100 Inha-ro, Nam-gu, Incheon 402-751, KoreaDepartment of Applied Chemistry, Kyung Hee University, Duckyoung-daero 1732, Yongin City 446-701, KoreaDepartment of Applied Chemistry, Kyung Hee University, Duckyoung-daero 1732, Yongin City 446-701, KoreaDepartment of Applied Chemistry, Kyung Hee University, Duckyoung-daero 1732, Yongin City 446-701, KoreaDepartment of Chemistry, Inha University, 100 Inha-ro, Nam-gu, Incheon 402-751, KoreaWe present the intra- and inter-molecular organocatalysis of S<sub>N</sub>2 fluorination using CsF by crown ether to estimate the efficacy of the promoter and to elucidate the reaction mechanism. The yields of intramolecular S<sub>N</sub>2 fluorination of the veratrole substrates are measured to be very small (<1% in 12 h) in the absence of crown ether promoters, whereas the S<sub>N</sub>2 fluorination of the substrate possessing a crown ether unit proceeds to near completion (~99%) in 12 h. We also studied the efficacy of intermolecular rate acceleration by an independent promoter 18-crown-6 for comparison. We find that the fluorinating yield of a veratrole substrate (leaving group = −OMs) in the presence of 18-crown-6 follows the almost identical kinetic course as that of intramolecular S<sub>N</sub>2 fluorination, indicating the mechanistic similarity of intra- and inter-molecular organocatalysis of the crown ether for S<sub>N</sub>2 fluorination. The calculated relative Gibbs free energies of activation for these reactions, in which the crown ether units act as Lewis base promoters for S<sub>N</sub>2 fluorination, are in excellent agreement with the experimentally measured yields of fluorination. The role of the metal salt CsF is briefly discussed in terms of whether it reacts as a contact ion pair or as a “free” nucleophile F<sup>−</sup>.https://www.mdpi.com/1420-3049/26/10/2947organocatalysisS<sub>N</sub>2 fluorinationcrown etherquantum chemistry |
| spellingShingle | Young-Ho Oh Wonhyuck Yun Chul-Hee Kim Sung-Woo Jang Sung-Sik Lee Sungyul Lee Dong-Wook Kim Inter- and Intra-Molecular Organocatalysis of S<sub>N</sub>2 Fluorination by Crown Ether: Kinetics and Quantum Chemical Analysis Molecules organocatalysis S<sub>N</sub>2 fluorination crown ether quantum chemistry |
| title | Inter- and Intra-Molecular Organocatalysis of S<sub>N</sub>2 Fluorination by Crown Ether: Kinetics and Quantum Chemical Analysis |
| title_full | Inter- and Intra-Molecular Organocatalysis of S<sub>N</sub>2 Fluorination by Crown Ether: Kinetics and Quantum Chemical Analysis |
| title_fullStr | Inter- and Intra-Molecular Organocatalysis of S<sub>N</sub>2 Fluorination by Crown Ether: Kinetics and Quantum Chemical Analysis |
| title_full_unstemmed | Inter- and Intra-Molecular Organocatalysis of S<sub>N</sub>2 Fluorination by Crown Ether: Kinetics and Quantum Chemical Analysis |
| title_short | Inter- and Intra-Molecular Organocatalysis of S<sub>N</sub>2 Fluorination by Crown Ether: Kinetics and Quantum Chemical Analysis |
| title_sort | inter and intra molecular organocatalysis of s sub n sub 2 fluorination by crown ether kinetics and quantum chemical analysis |
| topic | organocatalysis S<sub>N</sub>2 fluorination crown ether quantum chemistry |
| url | https://www.mdpi.com/1420-3049/26/10/2947 |
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