Rago Alexander J, Vasilopoulos Aristidis, Dombrowski Amanda W, Wang Ying
Advanced Chemistry Technologies Group, AbbVie, Inc., 1 N Waukegan Road, North Chicago, Illinois 60064, United States.
Org Lett. 2022 Nov 25;24(46):8487-8492. doi: 10.1021/acs.orglett.2c03346. Epub 2022 Nov 15.
Ni-catalyzed aryl-alkyl coupling reactions are reliant on using a limited set of commercially available bidentate nitrogenous ligands to enable the reaction, because noncommercial analogues usually entail challenging syntheses. In this work, di(2-picolyl)amines (DPAs) are explored as an alternative modular ligand class for the nickel-catalyzed aryl-alkyl cross-electrophile coupling. Novel DPA ligands were synthesized directly from inexpensive amine and pyridine building blocks in a single step. This facile synthetic route enabled the parallel synthesis of DPA ligands with varied steric and electronic properties. From this collection of ligands, a few robust ligands for C(sp)-C(sp) cross-electrophile coupling were identified and tested in the cross-coupling of a range of diverse molecules, including model examples for late-stage functionalization.
镍催化的芳基-烷基偶联反应依赖于使用一组有限的市售双齿含氮配体来实现该反应，因为非商业类似物的合成通常具有挑战性。在这项工作中，二（2-吡啶基）胺（DPA）被探索作为镍催化的芳基-烷基交叉亲电试剂偶联的替代模块化配体类别。新型DPA配体可通过一步反应直接由廉价的胺和吡啶构建块合成。这种简便的合成路线能够平行合成具有不同空间和电子性质的DPA配体。从这组配体中，鉴定出了一些用于C(sp)-C(sp)交叉亲电试剂偶联的稳健配体，并在一系列不同分子的交叉偶联中进行了测试，包括后期功能化的模型示例。
