Chen Ming-Yu, Charvet Sylvain, Payard Pierre-Adrien, Perrin Marie-Eve L, Vantourout Julien C
UMR 5246, ICBMS, Université de Lyon, Université Claude Bernard Lyon I, CNRS, INSA, CPE Lyon, 1 rue Victor Grignard, 69622, Villeurbanne cedex, France.
Angew Chem Int Ed Engl. 2024 Jan 8;63(2):e202311165. doi: 10.1002/anie.202311165. Epub 2023 Dec 4.
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 NiCl ⋅ 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.
报道了一种稳健的电化学驱动的镍催化不饱和卤化物和三氟甲磺酸酯（Br 到 Cl、I 到 Cl、I 到 Br 以及 OTf 到 Cl）的卤素交换反应。以 NiCl₂·甘醇二甲醚作为预催化剂、2,2'-联吡啶作为配体、N-甲基吡咯烷酮作为溶剂，并结合电化学方法，能够生成促进所需产物还原消除的镍物种。这种成对的电化学卤化反应与一系列不饱和卤化物和三氟甲磺酸酯兼容，包括杂环化合物、二卤代芳烃以及具有良好官能团耐受性的烯烃。联合实验和理论机理研究突出了三个催化过程：i）芳基卤化物向 Ni(0)物种的氧化加成，生成 Ni(II)中间体；ii）Ni(II)处的卤化物复分解；iii）Ni(II)电化学氧化为 Ni(III)，以便在还原消除时形成所需的芳基卤化物。该方法允许用相应更轻且亲脂性更强的 Cl 基团取代重卤素（I 或 Br）或极性原子（O），以阻断不期望的反应性或改变药物和农用化学品候选物的性质。
