Su Zhi-Ming, Zhu Jieru, Poole Darren L, Rafiee Mohammad, Paton Robert S, Weix Daniel J, Stahl Shannon S
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Molecular Modalities Capabilities, GSK Medicines Research Centre, Gunnels Wood Rd., Stevenage SG1 2NY, U.K.
J Am Chem Soc. 2025 Jan 8;147(1):353-361. doi: 10.1021/jacs.4c10776. Epub 2024 Dec 23.
Nickel-catalyzed cross-electrophile coupling (XEC) reactions of (hetero)aryl electrophiles represent appealing alternatives to palladium-catalyzed methods for biaryl synthesis, but they often generate significant quantities of homocoupling and/or proto-dehalogenation side products. In this study, an informer library of heteroaryl chloride and aryl bromide coupling partners is used to identify Ni-catalyzed XEC conditions that access high selectivity for the cross-product when using equimolar quantities of the two substrates. Two different catalyst systems are identified that show complementary scope and broad functional-group tolerance, and time-course data suggest that the two methods follow different mechanisms. A NiBr/terpyridine catalyst system with Zn as the reductant converts the aryl bromide into an arylzinc intermediate that undergoes coupling with 2-chloropyridines, while a NiBr/bipyridine catalyst system with tetrakis(dimethylamino)ethylene as the reductant uses FeBr and NaI as additives to achieve selective cross-coupling.
镍催化的（杂）芳基亲电试剂的交叉亲电偶联（XEC）反应是钯催化的联芳基合成方法的有吸引力的替代方法，但它们通常会产生大量的同偶联和/或原脱卤副产物。在本研究中，使用杂芳基氯和芳基溴偶联伙伴的信息库来确定镍催化的XEC条件，该条件在使用等摩尔量的两种底物时对交叉产物具有高选择性。确定了两种不同的催化剂体系，它们显示出互补的范围和广泛的官能团耐受性，并且时间进程数据表明这两种方法遵循不同的机制。以锌作为还原剂的NiBr/三联吡啶催化剂体系将芳基溴转化为芳基锌中间体，该中间体与2-氯吡啶发生偶联，而以四（二甲氨基）乙烯作为还原剂的NiBr/联吡啶催化剂体系使用FeBr和NaI作为添加剂来实现选择性交叉偶联。
