1,1,1,3,3,3-Hexafluoro-2-Propanol-Promoted Friedel–Crafts Reaction: Metal-Free Synthesis of C3-Difluoromethyl Carbinol-Containing Imidazo[1,2-<i>a</i>]pyridines at Room Temperature
A facile and efficient method has been developed for the synthesis of C3-difluoromethyl carbinol-containing imidazo[1,2-<i>a</i>]pyridines at room temperature via the HFIP-promoted Friedel–Crafts reaction of difluoroacetaldehyde ethyl hemiacetal and imidazo[1,2-<i>a</i>]pyrid...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/22/7522 |
| _version_ | 1797458265274056704 |
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| author | Juanjuan Gao Zhaowen Liu Xiaohua Guo Longhui Wu Zhixi Chen Kai Yang |
| author_facet | Juanjuan Gao Zhaowen Liu Xiaohua Guo Longhui Wu Zhixi Chen Kai Yang |
| author_sort | Juanjuan Gao |
| collection | DOAJ |
| description | A facile and efficient method has been developed for the synthesis of C3-difluoromethyl carbinol-containing imidazo[1,2-<i>a</i>]pyridines at room temperature via the HFIP-promoted Friedel–Crafts reaction of difluoroacetaldehyde ethyl hemiacetal and imidazo[1,2-<i>a</i>]pyridines. This strategy could be applied to the direct C(sp<sup>2</sup>)-H hydroxydifluoromethylation of imidazo[1,2-<i>a</i>]pyridines and afford a series of novel difluoromethylated carbinols in good to satisfactory yields with 29 examples. Furthermore, gram-scale and synthetic transformation experiments have also been achieved, demonstrating its potential applicable value in organic synthesis. This green protocol has several advantages, including being transition metal- and oxidant-free, being carried out at room temperature, having high efficiency, and having a wide substrate scope. |
| first_indexed | 2024-03-09T16:34:36Z |
| format | Article |
| id | doaj.art-b6b867a4e0d042178e74a769eff329ee |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T16:34:36Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b6b867a4e0d042178e74a769eff329ee2023-11-24T14:58:06ZengMDPI AGMolecules1420-30492023-11-012822752210.3390/molecules282275221,1,1,3,3,3-Hexafluoro-2-Propanol-Promoted Friedel–Crafts Reaction: Metal-Free Synthesis of C3-Difluoromethyl Carbinol-Containing Imidazo[1,2-<i>a</i>]pyridines at Room TemperatureJuanjuan Gao0Zhaowen Liu1Xiaohua Guo2Longhui Wu3Zhixi Chen4Kai Yang5College of Pharmacy, Gannan Medical University, Ganzhou 341000, ChinaCollege of Pharmacy, Gannan Medical University, Ganzhou 341000, ChinaCollege of Pharmacy, Gannan Medical University, Ganzhou 341000, ChinaCollege of Pharmacy, Gannan Medical University, Ganzhou 341000, ChinaCollege of Pharmacy, Gannan Medical University, Ganzhou 341000, ChinaCollege of Pharmacy, Gannan Medical University, Ganzhou 341000, ChinaA facile and efficient method has been developed for the synthesis of C3-difluoromethyl carbinol-containing imidazo[1,2-<i>a</i>]pyridines at room temperature via the HFIP-promoted Friedel–Crafts reaction of difluoroacetaldehyde ethyl hemiacetal and imidazo[1,2-<i>a</i>]pyridines. This strategy could be applied to the direct C(sp<sup>2</sup>)-H hydroxydifluoromethylation of imidazo[1,2-<i>a</i>]pyridines and afford a series of novel difluoromethylated carbinols in good to satisfactory yields with 29 examples. Furthermore, gram-scale and synthetic transformation experiments have also been achieved, demonstrating its potential applicable value in organic synthesis. This green protocol has several advantages, including being transition metal- and oxidant-free, being carried out at room temperature, having high efficiency, and having a wide substrate scope.https://www.mdpi.com/1420-3049/28/22/7522hydroxydifluoromethylationFriedel–Crafts reactionimidazo[1,2-<i>a</i>]pyridineHFIP |
| spellingShingle | Juanjuan Gao Zhaowen Liu Xiaohua Guo Longhui Wu Zhixi Chen Kai Yang 1,1,1,3,3,3-Hexafluoro-2-Propanol-Promoted Friedel–Crafts Reaction: Metal-Free Synthesis of C3-Difluoromethyl Carbinol-Containing Imidazo[1,2-<i>a</i>]pyridines at Room Temperature Molecules hydroxydifluoromethylation Friedel–Crafts reaction imidazo[1,2-<i>a</i>]pyridine HFIP |
| title | 1,1,1,3,3,3-Hexafluoro-2-Propanol-Promoted Friedel–Crafts Reaction: Metal-Free Synthesis of C3-Difluoromethyl Carbinol-Containing Imidazo[1,2-<i>a</i>]pyridines at Room Temperature |
| title_full | 1,1,1,3,3,3-Hexafluoro-2-Propanol-Promoted Friedel–Crafts Reaction: Metal-Free Synthesis of C3-Difluoromethyl Carbinol-Containing Imidazo[1,2-<i>a</i>]pyridines at Room Temperature |
| title_fullStr | 1,1,1,3,3,3-Hexafluoro-2-Propanol-Promoted Friedel–Crafts Reaction: Metal-Free Synthesis of C3-Difluoromethyl Carbinol-Containing Imidazo[1,2-<i>a</i>]pyridines at Room Temperature |
| title_full_unstemmed | 1,1,1,3,3,3-Hexafluoro-2-Propanol-Promoted Friedel–Crafts Reaction: Metal-Free Synthesis of C3-Difluoromethyl Carbinol-Containing Imidazo[1,2-<i>a</i>]pyridines at Room Temperature |
| title_short | 1,1,1,3,3,3-Hexafluoro-2-Propanol-Promoted Friedel–Crafts Reaction: Metal-Free Synthesis of C3-Difluoromethyl Carbinol-Containing Imidazo[1,2-<i>a</i>]pyridines at Room Temperature |
| title_sort | 1 1 1 3 3 3 hexafluoro 2 propanol promoted friedel crafts reaction metal free synthesis of c3 difluoromethyl carbinol containing imidazo 1 2 i a i pyridines at room temperature |
| topic | hydroxydifluoromethylation Friedel–Crafts reaction imidazo[1,2-<i>a</i>]pyridine HFIP |
| url | https://www.mdpi.com/1420-3049/28/22/7522 |
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