Electrochemical Self-Optimization for the Synthesis of Densely Functionalized Molecules

The implementation of closed-loop automation in electrochemistry has been limited by engineering and chemical difficulties, especially when applied to the synthesis of densely functionalized molecules. To overcome these issues, we developed a modular autonomous platform integrating Bayesian optimization and on-line analysis. This flow electrochemical system leveraged a slug-based approach to minimize the material consumption while ensuring a fast workflow. The versatility of the platform was demonstrated in three different case studies, including a nickel-catalyzed C–N cross-coupling, an anodic modification of an amino acid, and a decarboxylative alkylation of a natural product. These reactions were optimized by considering a broad range of chemical inputs, translated into different continuous and categorical variables. Furthermore, the automation of anodic reactions was achieved by implementing a gas release module. Finally, the isolation of the desired products was achieved by translating the slug conditions into continuous flow.