Iodomethane as an organocatalyst for the aerobic ortho-selective trifluoromethylation of pyridines

作     者：Jianjin Yu Renqin Zhan Chao-Jun Li Huiying Zeng 

作者机构：State Key Laboratory of Applied Organic ChemistryCollege of Chemistry and Chemical EngineeringLanzhou University.Lanzhou 730000China Department of ChemistryFQRNT Centre for Green Chemistry and CatalysisMcGll UniversityMontrealOuebec H3A OB8Canada 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2023年第66卷第1期

页      面：133-138页

核心收录：

学科分类：081705[工学-工业催化] 08[工学] 0817[工学-化学工程与技术] 0703[理学-化学] 

基　　金：supported by the National Natural Science Foundation of China(21971093) the Fundamental Research Funds for the Central Universities(lzujbky-2021-sp53) the International Joint Research Centre for Green Catalysis and Synthesis(2016B01017) the 111 Project。 

主　　题：iodomethane-catalysis trifluoromethylation pyridines transition-metal-free trifluoroacetic acid 

摘      要：Iodomethane is usually used as an electrophilic methylation reagent.Herein,we report its use as a C1 organocatalyst for the aerobic ortho-selective trifluoromethylation of pyridines in the absence of a transition metal.Trifluoroacetic acid(TFA)was employed as an inexpensive,readily available trifluoromethyl source.The reaction efficiently produced a variety of trifluoromethylation products,with good functional group compatibility.Pyridine-containing drug molecules could also be selectively trifluoromethylated for late-stage functionalizations.Mechanistic studies showed that iodomethane selectively reacted with the pyridine starting material,rather than the pyridine product,to generate the corresponding N-methylpyridinium iodide.The decarboxylation of trifluoroacetic acid produced a trifluoromethyl anion,which added to the methylpyridinium iodide,and the subsequent aerobic rearomatization led to the generation of the ortho-trifluoromethylated product.