Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

Metallaphotoredox catalysis is a powerful and versatile synthetic platform that enables cross-couplings under mild conditions with-out the need for noble metals. Its growing adoption in drug discovery has translated into an increased interest in sustainable and scalable reaction conditions. Here, we report a continuous-flow approach to metallaphotoredox catalysis using a heterogeneous catalyst that combines the function of a photo-and a nickel catalyst in a single material. The catalyst is embedded in a packed-bed reactor to combine reaction and (catalyst) separation in one step. The use of a packed bed simplifies the translation of optimized batch reaction conditions to continuous flow, as the only components present in the reaction mixture are the substrate and a base. The metallaphotoredox cross-coupling of sulfinates with aryl halides was used as a model system. The catalyst was shown to be stable, with a very low decrease of the yield (asymptotic to 1% per day) during a continuous experiment over seven days, and to be effective for C-O arylations when carboxylic acids are used as nucleophile instead of sulfinates.

Automated summary

Metallaphotoredox catalysis is a versatile synthetic platform that enables mild cross-couplings without the need for noble metals. In this study, a continuous-flow approach using a heterogeneous catalyst that combines both photo- and nickel-catalysts in one material is reported. The catalyst is embedded in a packed-bed reactor, simplifying the translation from batch to continuous flow reactions. The catalyst exhibited stability and effectiveness in the metallaphotoredox cross-coupling reactions.