Naturally occurring benzoxanthenones which belongs to the vast family of lignans, are promising biologically relevant targets. They are biosynthetically produced by the oxidative dimerization of 2-propenyl phenols. In this manuscript, we disclose a powerful automated flow-based strategy for identifying and optimizing a cobalt-catalyzed oxidizing system for the bio-inspired dimerization of 2-propenyl phenols. We designed a reconfigurable flow reactor associating on-line monitoring and process-control instrumentation. Our machine was first configured as an automated screening platform to evaluate a matrix of 4 catalysts (plus the blank) and 5 oxidant (plus the blank) at two different temperatures, resulting in an array of 50 reactions. The automated screening was conducted on micromole scale at a rate of one fully characterized reaction every 26 minutes. After having identified the most promising cobaltcatalyzed oxidizing system, the automated screening platform was straightforwardly reconfigured to an autonomous self-optimizing flow reactor by implementation of an optimization algorithm in the closed-loop system. The optimization campaign allowed the determination of very effective experimental conditions in a limited number of experiments which allowed to prepare natural products carpanone and polemannone B as well as synthetic analogues.

Continuous flow photo-thiol-ene reactions on cinchona alkaloids with a variety of organic thiols have been developed to deliver a series of unprecedented architectures. A self-optimizing flow photochemical reactor was deployed...