The Scripps Research Institute (TSRI), North Torrey Pines Road, La Jolla, CA, 92037, USA.
Asymchem Laboratories (Tianjin) Co., Ltd., TEDA, Tianjin, 300457, P. R. China.
Angew Chem Int Ed Engl. 2017 Oct 9;56(42):13088-13093. doi: 10.1002/anie.201707906. Epub 2017 Sep 14.
Along with amide bond formation, Suzuki cross-coupling, and reductive amination, the Buchwald-Hartwig-Ullmann-type amination of aryl halides stands as one of the most employed reactions in modern medicinal chemistry. The work herein demonstrates the potential of utilizing electrochemistry to provide a complementary avenue to access such critical bonds using an inexpensive nickel catalyst under mild reaction conditions. Of note is the scalability, functional-group tolerance, rapid rate, and the ability to employ a variety of aryl donors (Ar-Cl, Ar-Br, Ar-I, Ar-OTf), amine types (primary and secondary), and even alternative X-H donors (alcohols and amides).
与酰胺键形成、铃木交叉偶联和还原胺化反应一样，芳基卤化物的 Buchwald-Hartwig-Ullmann 型胺化反应是现代药物化学中最常用的反应之一。本文展示了利用电化学在温和的反应条件下使用廉价的镍催化剂为这些关键键提供补充途径的潜力。值得注意的是，该方法具有可扩展性、官能团耐受性、快速的反应速率，以及能够使用各种芳基供体（Ar-Cl、Ar-Br、Ar-I、Ar-Otf）、胺类（伯胺和仲胺），甚至是替代的 X-H 供体（醇和酰胺）。
