High-throughput experimentation for photoredox cross-couplings using the automated photoredox optimization reactor

Abstract

High-throughput experimentation enables rapid reaction optimization by leveraging reaction miniaturization, automated processes, and advanced high-throughput analytical methods. To more effectively apply these principles to reactions mediated by photoredox catalysis, we developed the photoredox optimization (PRO) reactor. PRO is an automated platform that provides precise control over the delivered light irradiance to optically thin, temperature-controlled reaction volumes. Combined with high-intensity laser illumination, PRO facilitates accelerated photoredox reaction scouting using <10 μL of reaction material. Crude products from PRO reactions are automatically transferred to microplates for analysis by infrared matrix-assisted laser desorption electrospray ionization mass spectrometry (IR-MALDESI-MS) which can quantify 384 reactions in under 6 minutes. Validation of the PRO reactor was achieved through a series of challenging decarboxylative cross-coupling reactions, which resulted in improved isolated yields up to 58%. PRO then enabled the design and execution of higher throughput 384-reaction HTE arrays which achieved improved yields for two previously unsuccessful photoredox cross-couplings, ultimately identifying novel reaction conditions outside the scope of our traditional 96-reaction arrays.