Persistent organonickel complexes as general platforms for Csp²-Csp³ coupling reactions

The importance of constructing Csp²-Csp³ bonds has motivated the development of electrochemical, photochemical and thermal activation methods to reductively couple abundant aryl and alkyl electrophiles. However, these methodologies are limited to couplings of very specific substrate classes and require specialized sets of catalysts and reaction set-ups. Here we show a consolidation of these myriad strategies into a single set of conditions that enable reliable alkyl-aryl couplings, including those that were previously unknown. These reactions rely on the discovery of unusually persistent organonickel complexes that serve as stoichiometric platforms for C(sp²)-C(sp³) coupling. Aryl, heteroaryl or vinyl complexes of Ni can be inexpensively prepared on a multigram scale by mild electroreduction from the corresponding C(sp²) electrophile. Organonickel complexes can be isolated and stored or telescoped directly to reliably diversify drug-like molecules. Finally, the procedure was miniaturized to micromole scales by integrating soluble battery chemistries as redox initiators, enabling a high-throughput exploration of substrate diversity.