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Updated: Aug 27, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Direct Synthesis of α-Aryl-α-Trifluoromethyl Alcohols via Nickel Catalyzed Cross-Electrophile Coupling
Lorenzo Lombardi1,2, Alessandro Cerveri1, Riccardo Giovanelli1,2
1Dipartimento di Chimica "Giacomo Ciamician", Alma Mater Studiorum-, Università di Bologna, Via Selmi 2, 40126, Bologna, Italy.
Abstract:
A nickel-catalyzed reductive cross-electrophile coupling between the redox-active N-trifluoroethoxyphthalimide and iodoarenes is documented. The protocol reproduces a formal arylation of trifluoroacetaldehyde under mild conditions in high yields (up to 88 %) and with large functional group tolerance (30 examples). A combined computational and experimental investigation revealed a pivotal solvent assisted 1,2-Hydrogen Atom Transfer (HAT) process to generate a nucleophilic α-hydroxy-α-trifluoromethyl C-centered radical for the Csp2 -Csp3 bond forming process.
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