Selective Ni-Catalyzed\nCross-Electrophile Coupling\nof Heteroaryl Chlorides and Aryl Bromides at 1:1 Substrate Ratio

Nickel-catalyzed cross-electrophile\ncoupling (XEC) reactions\nof\n(hetero)aryl electrophiles represent appealing alternatives to palladium-catalyzed\nmethods for biaryl synthesis, but they often generate significant\nquantities of homocoupling and/or proto-dehalogenation side products.\nIn this study, an informer library of heteroaryl chloride and aryl\nbromide coupling partners is used to identify Ni-catalyzed XEC conditions\nthat access high selectivity for the cross-product when using equimolar\nquantities of the two substrates. Two different catalyst systems are\nidentified that show complementary scope and broad functional-group\ntolerance, and time-course data suggest that the two methods follow\ndifferent mechanisms. A NiBr<sub>2</sub>/terpyridine catalyst system\nwith Zn as the reductant converts the aryl bromide into an arylzinc\nintermediate that undergoes <i>in situ</i> coupling with\n2-chloropyridines, while a NiBr<sub>2</sub>/bipyridine catalyst system\nwith tetrakis(dimethylamino)ethylene as the reductant uses FeBr<sub>2</sub> and NaI as additives to achieve selective cross-coupling.