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 online analysis. The versatility of the system 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, toward the optimization of single or multiple objectives. Furthermore, the automation of anodic reactions was achieved by implementing a gas release module. Finally, the desired products were isolated by translating the slug conditions into continuous flow.