Reconfigurable Flow Platform for Automated Reagent Screening and Autonomous Optimization for Bioinspired Lignans Synthesis

Abstract

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.

Direct C−H Arylation of Indole‐3‐Acetic Acid Derivatives Enabled by an Autonomous Self‐Optimizing Flow Reactor

“…These powerful automated devices combine flow reactors with process control instrumentations, in‐line/online analyses and optimization algorithms to assist the decision‐making process of chemists [27–34] . Our lab also recently contributed to this emerging field of research with the development of a reconfigurable flow platform for the screening of reagents and the autonomous optimization of chemical transformations including natural product synthesis [35–37] …”

Application of reactor engineering concepts in continuous flow chemistry: a review

“…It was implemented as an automated screening platform to evaluate a matrix of 4 catalysts and 5 oxidants (plus the blank) at two different temperatures, resulting in an array of 50 reactions. 164 7 In-line purification/downstream processing technologies in flow Downstream processing and purification under flow conditions is typically characterised by chemical differentiation between reagents, products and by-products, and today the use of scavengers and catch-and-release approaches are commonplace in the field. The translation of more traditional purification techniques such as extraction, recrystallisation, distillation, filtration and chromatography which are largely based on the physical properties of molecules in large continue to prove challenging under flow conditions.…”

“…Photographs reproduced with permission. 160,164 Reaction Chemistry & Engineering Review able to efficiently effect continuous on-the-fly solvent swapping.…”

Merging Gradient‐Based Methods to Improve Benchtop NMR Spectroscopy: A New Tool for Flow Reaction Optimization

“…Benchtop NMR already showed its potential in the context of flow chemistry as an essential element of self-optimizing autonomous flow reactors . [9,15,16] Thus, to enrich essential NMR developments on compact apparatus, we were interested in showing the potential of multi-suppression methods combined with TSE PSYCHE for analyzing complex chemical mixtures composed on bigger-sized molecules at low field. Regarding solvent suppression, we focused on m W5 methods that gave optimum results on the model samples.…”