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Updated: Nov 30, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Nickel-Catalyzed N-Arylation of Fluoroalkylamines
Ryan T McGuire1, Arun A Yadav2, Mark Stradiotto1
1Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada.
Abstract:
The Ni-catalyzed N-arylation of β-fluoroalkylamines with broad scope is reported for the first time. Use of the air-stable pre-catalyst (PAd2-DalPhos)Ni(o-tol)Cl allows for reactions to be conducted at room temperature (25 °C, NaOtBu), or by use of a commercially available dual-base system (100 °C, DBU/NaOTf), to circumvent decomposition of the N-(β-fluoroalkyl)aniline product. The mild protocols disclosed herein feature broad (hetero)aryl (pseudo)halide scope (X=Cl, Br, I, and for the first time phenol-derived electrophiles), encompassing base-sensitive substrates and enantioretentive transformations, in a manner that is unmatched by any previously reported catalyst system.
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