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Updated: Apr 23, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
A chelating nucleophile plays a starring role: 1,8-naphthyridine-catalyzed polycomponent α,α-difluorination of acid
Andrew Griswold1, Steven Bloom, Thomas Lectka
1Department of Chemistry, Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
Abstract:
A dually activated ketene enolate, generated from an acid chloride, the unusual chelating nucleophile (1,8-naphthyridine), and a Lewis acid, reacts to afford a host of α,α-difluorinated products in the presence of a benchtop-stable fluorinating agent (Selectfluor). The use of this method to synthesize otherwise difficult to make products is highlighted along with computational and spectroscopic support for the proposed chelate.
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