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Updated: Dec 23, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Synthesis of meta-Substituted Anilines via Copper-Catalyzed [1,3]-Methoxy Rearrangement
Itaru Nakamura1, Hiroki Tashiro2, Yasuhiro Ishida2
1Research and Analytical Center for Giant Molecules, Graduate School of Science, Tohoku University, 6-3 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8578, Japan.
Abstract:
meta-Substituted anilines were efficiently synthesized via copper-catalyzed [1,3]-methoxy rearrangement of N-methoxyanilines followed by Michael addition of nucleophiles to the in situ generated ortho-quinol imine. The present reaction exhibits excellent applicability of para-substituents, such as vinyl, methylthio, ester, and bromo, and carbon nucleophiles, such as 1,3,5-trimethoxybenzene, N-methylindole, and dimethyl malonate. Thus, the present rearrangement can resolve problems stemming from oxidation reactions, such as the use of stoichiometric amounts of oxidants and low compatibility of electron-withdrawing groups.
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