Kim Seoyoung, Goldfogel Matthew J, Ahern Benjamin N, Salgueiro Daniel C, Guzei Ilia A, Weix Daniel J
Department of Chemistry, University of Wisconsin─Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
J Am Chem Soc. 2025 Jan 22;147(3):2616-2625. doi: 10.1021/jacs.4c14769. Epub 2025 Jan 10.
Aryl triflates make up a class of aryl electrophiles that are available in a single step from the corresponding phenol. Despite the known reactivity of nickel complexes for aryl C-O bond activation of phenol derivatives, nickel-catalyzed cross-electrophile coupling using aryl triflates has proven challenging. Herein, we report a method to form C(sp)-C(sp) bonds by coupling aryl triflates with alkyl bromides and chlorides using phenanthroline (phen) or pyridine-2,6-bis(-cyanocarboxamidine) (PyBCam)-ligated nickel catalysts. The scope of the reaction is demonstrated with 38 examples (61 ± 14% average yield). Mechanistic studies provide a rationale for the conditions used and a roadmap for further applications of cross-electrophile coupling. First, the rate of alkyl radical generation is controlled by maintaining the majority of alkyl halide as the alkyl chloride, which is unreactive, and utilizing a dynamic halide exchange process to adjust the concentration of reactive alkyl bromide or iodide. Second, the challenge of using electron-rich aryl triflates appears to be due to off-cycle transmetalation to form unproductive aryl zinc reagents. The optimal PyBCam ligand together with LiCl avoids this deleterious transmetalation step.
芳基三氟甲磺酸酯构成了一类可从相应苯酚一步制得的芳基亲电试剂。尽管已知镍配合物对苯酚衍生物的芳基碳 - 氧键具有活化作用，但使用芳基三氟甲磺酸酯进行镍催化的交叉亲电试剂偶联已被证明具有挑战性。在此，我们报道了一种使用菲咯啉（phen）或吡啶 - 2,6 - 双（- 氰基甲脒）（PyBCam）配体的镍催化剂，通过芳基三氟甲磺酸酯与烷基溴化物和氯化物偶联形成C(sp)-C(sp)键的方法。该反应的适用范围通过38个实例得以证明（平均产率为61 ± 14%）。机理研究为所用条件提供了理论依据，并为交叉亲电试剂偶联的进一步应用提供了路线图。首先，通过使大部分卤代烷保持为无反应性的烷基氯，并利用动态卤化物交换过程来调节活性烷基溴或碘化物的浓度，从而控制烷基自由基的生成速率。其次，使用富电子芳基三氟甲磺酸酯的挑战似乎源于环外转金属化形成无活性的芳基锌试剂。最佳的PyBCam配体与LiCl一起避免了这一有害的转金属化步骤。
