A methylation reagent for compounds bearing NÀ H, OÀ H, and SÀ H functionalities was developed. Methyl trifluoroacetate (MTFA) was commonly considered as trifluoroacetylating reagent or trifluoromethylating reagent. In this work, we report the methylation behavior of MTFA under mild conditions with good functional group tolerance, allowing the transformation of a wide range of substrates, including N,H-heteroaromatic compounds, phenolic compounds, carboxylic acids, thiophenols, secondary amides and imides, in high yields. This method was preliminarily applied to the chemoselective methylation of bifunctionalized secondary amide.
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