An Automated Electrochemical Flow Platform to Accelerate Library Synthesis and Reaction Optimization
Eduardo Rial‐Rodríguez, Jason D. Williams, David Cantillo, Thomas Fuchß, Alena Sommer, Hans‐Michael Eggenweiler, C. Oliver Kappe, Gabriele Laudadio
Abstract
Automated batch and flow setups are well-established for high throughput experimentation in both thermal chemistry and photochemistry. However, the development of automated electrochemical platforms is hindered by cell miniaturization challenges in batch and difficulties in designing effective single-pass flow systems. In order to address these issues, we have designed and implemented a new, slug-based automated electrochemical flow platform. This platform was successfully demonstrated for electrochemical C-N cross-couplings of E3 ligase binders with diverse amines (44 examples), which were subsequently transferred to a continuous-flow mode for confirmation and isolation, showing its applicability for medicinal chemistry purposes. To further validate the versatility of the platform, Design of Experiments (DoE) optimization was performed for an unsuccessful library target. This optimization process, fully automated by the platform, resulted in a remarkable 6-fold increase in reaction yield.