Electrochemically Driven Nickel‐Catalyzed Halogenation of Unsaturated Halide and Triflate Derivatives

• Published in: Angewandte Chemie International Edition 2024-01, Vol.63 (2), p.e202311165-n/a
• Main Authors: Chen, Ming‐Yu, Charvet, Sylvain, Payard, Pierre‐Adrien, Perrin, Marie‐Eve L., Vantourout, Julien C.
• Format: Article
• Language: English
• Subjects: Agrochemicals; Alkenes; Aromatic compounds; Bromine; Catalysis; Chemical Sciences; Electrochemical oxidation; Electrochemistry; electrosynthesis; Halides; Halogenation; Halogens; Lipophilic; Metathesis; Nickel; nickel catalysis; Nickel chloride; or physical chemistry; reaction mechanisms; Theoretical and
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202311165

A robust electrochemically driven nickel‐catalyzed halogen exchange of unsaturated halides and triflates (Br to Cl, I to Cl, I to Br, and OTf to Cl) is reported. A combination of NiCl2 ⋅ glyme as the precatalyst, 2,2′‐bipyridine as a ligand, NMP as the solvent, and electrochemistry allowed the generation of a nickel species that promotes reductive elimination of the desired product. This paired electrochemical halogenation is compatible with a range of unsaturated halides and triflates, including heterocycles, dihaloarenes, and alkenes with good functional‐group tolerance. Joint experimental and theoretical mechanistic investigations highlighted three catalytic events: i) oxidative addition of the aryl halide to a Ni(0) species to deliver a Ni(II) intermediate; ii) halide metathesis at Ni(II); iii) electrochemical oxidation of Ni(II) to Ni(III) to enable the formation of the desired aryl halide upon reductive elimination. This methodology allows the replacement of heavy halogens (I or Br) or polar atoms (O) with the corresponding lighter and more lipophilic Cl group to block undesired reactivity or modify the properties of drug and agrochemical candidates. Joint experimental and theoretical techniques highlighted three main catalytic events in an electrochemically driven nickel‐catalyzed halogen exchange reaction of aryl halides: Oxidative addition of Ar−X to a Ni(0) species first delivers a Ni(II)ArX, which undergoes salt metathesis with chloride to afford Ni(II)ArCl. The latter is electrochemically oxidized to a Ni(III) species, enabling the formation of the product upon reductive elimination.