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

TL;DR

This paper introduces a cost-effective method to synthesize diarylmethane compounds using cobalt-based catalysts, offering a promising alternative to traditional palladium-based methods.

Contribution

The study presents a novel cobalt-based Negishi cross-coupling method without auxiliary ligands for diarylmethane synthesis.

Findings

Cobalt halides enabled efficient diarylmethane synthesis under mild conditions with yields comparable to palladium catalysts.

The CoBr2/DMAc system provided excellent selectivity (>99%) for the cross-coupling reactions.

Computational studies provided mechanistic insights into the cobalt-catalyzed process.

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.

The online version contains supplementary material available at 10.1038/s41598-025-10180-1.

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