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Updated: May 12, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Metal-free fluorination of C(sp3)-H bonds using a catalytic N-oxyl radical
Yuuki Amaoka1, Masanori Nagatomo, Masayuki Inoue
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Abstract:
A direct conversion of C(sp(3))-H bonds to C(sp(3))-F bonds has been developed. In this process, a catalytic N-oxyl radical generated from N,N-dihydroxypyromellitimide abstracts hydrogen from the C(sp(3))-H bond and Selectfluor acts to trap the resulting carbon radical to form the C(sp(3))-F bond. This simple metal-free protocol enables the chemoselective introduction of a fluorine atom into various aromatic and aliphatic compounds and serves as a powerful tool for the efficient synthesis of fluorinated molecules.
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