1,1,1,3,3,3-Hexafluoro-2-Propanol-Promoted Friedel–Crafts Reaction: Metal-Free Synthesis of C3-Difluoromethyl Carbinol-Containing Imidazo[1,2-a]pyridines at Room Temperature
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Published:2023-11-10
Issue:22
Volume:28
Page:7522
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Gao Juanjuan1,
Liu Zhaowen1,
Guo Xiaohua1,
Wu Longhui1,
Chen Zhixi1ORCID,
Yang Kai1ORCID
Affiliation:
1. College of Pharmacy, Gannan Medical University, Ganzhou 341000, China
Abstract
A facile and efficient method has been developed for the synthesis of C3-difluoromethyl carbinol-containing imidazo[1,2-a]pyridines at room temperature via the HFIP-promoted Friedel–Crafts reaction of difluoroacetaldehyde ethyl hemiacetal and imidazo[1,2-a]pyridines. This strategy could be applied to the direct C(sp2)-H hydroxydifluoromethylation of imidazo[1,2-a]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.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangxi Province
Scientific Research Fund of Jiangxi Provincial Education Department
Scientific Research Project of Gannan Medical University
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science