Picolinamide Ligands: Nickel-Catalyzed Reductive Cross-Coupling of Aryl Bromides with Bromocyclopropane and Beyond

The arylcyclopropane motif as the combination of aryl and cyclopropyl ring systems can be found in an increasing amount of approved and investigational drugs. Herein, we have developed a mild, efficient nickel-catalyzed reductive cross-coupling protocol, featuring a simple Ni(II) precatalyst and a novel picolinamide NN₂ pincer ligand. A variety of (hetero)aryl bromides could successfully couple with cyclopropyl bromide to furnish the valued arylcyclopropanes in good to excellent yields. This method is applicable to other alkyl bromides as well. Notably, the reaction is tolerant of a broad range of functionalities including free amines. Furthermore, the synthesis of several significant intermediates of bioactive molecules was achieved in grams, proving the practicability of this method.