Direct Synthesis of α-Aryl-α-Trifluoromethyl Alcohols via Nickel Catalyzed Cross-Electrophile Coupling

Lorenzo Lombardi; Alessandro Cerveri; Riccardo Giovanelli; Marta Castiñeira Reis; Carlos Silva López; Giulio Bertuzzi; Marco Bandini

doi:10.1002/anie.202211732

Direct Synthesis of α-Aryl-α-Trifluoromethyl Alcohols via Nickel Catalyzed Cross-Electrophile Coupling

Angew Chem Int Ed Engl. 2022 Nov 21;61(47):e202211732. doi: 10.1002/anie.202211732. Epub 2022 Oct 18.

Authors

Lorenzo Lombardi^{1

2}, Alessandro Cerveri¹, Riccardo Giovanelli^{1

2}, Marta Castiñeira Reis³, Carlos Silva López³, Giulio Bertuzzi^{1

2}, Marco Bandini^{1

2}

Affiliations

¹ Dipartimento di Chimica "Giacomo Ciamician", Alma Mater Studiorum-, Università di Bologna, Via Selmi 2, 40126, Bologna, Italy.
² Center for Chemical Catalysis-C3, Alma Mater Studiorum-, Università di Bologna, Via Selmi 2, 40126, Bologna, Italy.
³ Universidade de Vigo, AS Lagoas (Marcosende) s/n, 36310, Vigo, Spain.

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.

Keywords: Cross-Electrophile Coupling; DFT Calculation; Hydrogen Atom Transfer; Nickel Catalysis; Trifluoromethylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alcohols*
Catalysis
Nickel* / chemistry
Oxidation-Reduction

Substances

Nickel
Alcohols