Negishi Cross-Coupling Reactions Catalyzed by an Aminophosphine-Based Nickel System: A Reliable and General Applicable Reaction Protocol for the High-Yielding Synthesis of Biaryls

Treatment of NMP solutions of NiCl2 with 1,1',1 ''-(phosphanetriyl)tripiperidine (approximate to 2.05 equiv), dissolved in THF, in air at 25 degrees C forms a highly active catalytic system for the cross-coupling of a large variety of electronically activated, non-activated, deactivated, and ortho-substituted, heterocyclic, and functionalized aryl bromides and aryl chlorides with diarylzinc reagents. Very high levels of conversion and yields were obtained within 2 h at 60 degrees C in the presence of only 0.1 mol% of catalyst (based on nickel) and thus at catalyst loadings far lower than typically reported for nickel-catalyzed versions of the Negishi reaction. Various aryl halides-which may contain trifluoromethyl groups, fluorides, or other functional groups such as acetals, ketones, ethers, esters, lactones, amides, imines, anilines, alkenes, pyridines, quinolines, and pyrimidines-were successfully converted into the corresponding biaryls. Electronic and steric variations are tolerated in both reaction partners. Experimental observations indicate that a molecular (Ni-I/Ni-III) mechanism is operative.