A general protocol for cross-coupling reactions can be made using nickel salt and visible light, according to a paper in Nature.

A cross-coupling reaction is the coupling of C atoms having a double bond [C(sp2)] to other atoms and usually occurs with transition metals. Well-known examples are the Suzuki-Miyaura coupling, the Heck reaction and the Negishi coupling. With all these different reactions you have a lot of possibilities, but the disadvantage is that the reaction conditions vary just as much. A Russian-German team has now developed a method that makes it much easier to perform different couplings, which should save a lot of optimisation steps.

The method, which the researchers call adaptive dynamic homogeneous catalysis (AD-HoC), uses nickel under visible light-driven redox reactions. The adaptive part is that you add a nickel salt that creates different nickel complexes. Under the influence of light, one of these complexes will then have the right properties to coordinate the coupling reaction.

Also, you keep the photocatalyst, the nickel salt and the electrophile (to which you want to couple the nucleophile) constant, so all you have to do is vary the nucleophile and sometimes add a little base. With this method you can couple C(sp2) atoms to S, Se, N, P, B, O, C(sp3, sp2, sp), Si and Cl. In the paper, they show nearly three hundred examples with different classes of electrophiles and nucleophiles, including some drug-like compounds. Unleash machine learning and artificial intelligence on this and vary the transition metal salt and the gates of variation will open wide, the authors suggest.

Ghosh, I. et al. (2023) Nature, DOI: 10.1038/s41586-023-06087-4