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Updated: Jul 9, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Soft Fluorination of 4-Alkylpyridines
Faizan Rasheed1, Jiaqi Shi1, Tao Zeng1
1Department of Chemistry, York University, 4700 Keele Street, Toronto ON, M3J 1P3, Canada.
Abstract:
We report the mild and selective mono- and difluorination of 4-alkylpyridines. The process involves soft-dearomatization of pyridines to the corresponding alkylidene dihydropyridines and treatment with Selectfluor. The reaction tolerates a broad range of functional groups, including those bearing acidic and weak C-H bonds. In addition, selective fluorination of 4-alkylpyridines attached to 2-alkylpyridines and 2-alkylpyrimidines can be achieved in good yields, but a 4-alkylpyridine tethered to a 4-alkylpyrimidine is fluorinated at both heterobenzylic positions.
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