Synthesis of diarylmethanes by means of Negishi cross-coupling enabled by cobalt-solvent coordination

Abstract

Abstract The diarylmethane backbone is a base of molecules relevant for various industrial and especially pharmaceutical applications where they serve as a platform for the discovery of new drugs. One of the most versatile methods of their synthesis are cross-coupling reactions that have served synthetic chemistry for nearly five decades and offer diverse opportunities for the synthesis of complex organic compounds. Although palladium catalysts have traditionally dominated this field, the emergence of first-row transition-metal (pre)catalysts presents promising alternatives because of their cost-effectiveness and the possibility of new reactivities. In this context, Negishi cross-coupling of benzylzinc bromide and its congeners with aryl, alkyl, alkenyl, alkynyl iodides and bromides, facilitated by simple cobalt halides without the addition of an auxiliary ligand, is presented. The optimisation of reaction conditions, including solvent selection, is discussed alongside the mechanistic insights gained through computational studies. A variety of diarylmethanes were synthesised under mild conditions, with yields comparable to those obtained with Pd catalysts, with excellent selectivity (> 99%) provided by commercially available anhydrous CoBr2 / DMAc catalytic system.