Temperature-Controlled Photoreactors and ChemBeads as Key Technologies for Robust and Practical Photochemical HTE
Paolo Piacentini, James M. Fordham, Eloísa Serrano, Luca Hepp, Marco Santagostino
Abstract
We report on our successful efforts to advance the robustness of screening photochemical reactions run in batch by using commercially available, temperature-controlled multiwell reactors in combination with ChemBead technology for precise solid dosing of the photoredox catalysts. The utility of this experimental setup was validated for five reaction classes, which were selected based on their varying sensitivity toward oxygen, temperature, and degree of homogeneity. The advantages and potential issues associated with the use of ChemBeads in high-throughput experimentation (HTE) photochemistry have been critically assessed. The presented multiarray photochemical setup was then applied to improve the scope of an Ir/Ni-co-catalyzed C–N visible-light cross-coupling reaction between aryl halides and fluorinated amines, which had remained limited until now. The optimal combination of categorical variables, the functional group compatibility, and the required structural elements in both the nucleophile and the electrophile partner for successful reactions were pinpointed. The reproducibility and transferability of the results to a larger-scale batch platform (PHIL photoreactor) was confirmed with a scale-up factor of 100. Finally, some suggestions for further improvements for temperature-controlled multiwell photoreactors compatible with HTE setups were listed.