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Updated: Oct 21, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Tf2O/TTBP (2,4,6-Tri-tert-butylpyrimidine): An Alternative Amide Activation System for the Direct Transformations of
Qian He1, Jian-Liang Ye1, Fang-Fang Xu1
1Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. China.
Abstract:
Ten types of Tf2O/TTBP-mediated amide transformation reactions were investigated. The results showed that compared with pyridine derivatives 2,6-di-tert-butyl-4-methylpyridine (DTBMP) and 2-fluoropyridine (2-F-Pyr.), TTBP can serve as an alternative amide activation system for the direct transformation of both secondary and tertiary amides. For most surveyed examples, higher or comparable yields were generally obtained. In addition, Tf2O/TTBP combination was used to promote the condensation reactions of 2-(tert-butyldimethylsilyloxy)furan (TBSOF) with both tertiary and secondary amides, the one-pot reductive Bischler-Napieralski-type reaction of tertiary lactams, and Movassaghi and Hill's modern version of the Bischler-Napieralski reaction. The value of the Tf2O/TTBP-based methodology was further demonstrated by the concise and high-yielding syntheses of several natural products.
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