Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
J Org Chem. 2020 Mar 6;85(5):3234-3244. doi: 10.1021/acs.joc.9b03107. Epub 2020 Jan 14.
We report a visible light-mediated flow process for C-N cross-coupling of (hetero)aryl halides with a variety of amine coupling partners through the use of a photoredox/nickel dual catalyst system. Compared to the method in batch, this flow process enables a broader substrate scope, including less-activated (hetero)aryl bromides and electron-deficient (hetero)aryl chlorides, and significantly reduced reaction times (10 to 100 min). Furthermore, scale up of the reaction, demonstrated through the synthesis of tetracaine, is easily achieved, delivering the C-N cross-coupled products in consistently high yield of 84% on up to a 10 mmol scale.
我们报告了一种可见光介导的流动过程，通过使用光氧化还原/镍双催化剂体系，使各种胺偶联伙伴的（杂）芳基卤化物进行 C-N 交叉偶联。与分批法相比，这种流动过程能够实现更广泛的底物范围，包括活性较低的（杂）芳基溴化物和缺电子（杂）芳基氯化物，并且显著缩短了反应时间（10 至 100 分钟）。此外，通过合成特卡因，很容易实现反应的放大，在高达 10 mmol 的规模上，C-N 交叉偶联产物的收率始终保持在 84%的高水平。
