Continuous-Flow Electrosynthesis beyond Scaleup

Organic electrosynthesis has emerged as a powerful platform for sustainable molecular synthesis, while continuous-flow electrochemistry is often viewed primarily as a technology for process intensification and scaleup. In our studies, however, we have found that the significance of continuous-flow electrochemistry extends far beyond improved productivity. The unique reaction environments created by single-pass flow electrolysis─including short residence times, spatially evolving electrochemical conditions, efficient mass transfer, and distinctive electrode interfacial microenvironments─can fundamentally alter reaction outcomes and facilitate transformations that are difficult to achieve in conventional batch reactors. In this Account, we summarize our efforts in developing continuous-flow electrosynthesis as a synthetic platform for challenging oxidative molecular transformations. We first show how single-pass flow electrolysis suppresses undesired secondary electrode reactions, enabling selective oxidative cyclizations, C-H oxygenation, and C-H amination reactions. We then discuss how continuous-flow electrolysis expands the accessible reactivity space of electro-oxidation by promoting productive utilization of highly reactive intermediates, exemplified by sulfur-centered radical chemistry and phosphorus radical cation chemistry. Particular emphasis is placed on electrochemical microenvironment engineering, where local ion distributions and acid-base properties within the electric double layer can be exploited to control reactivity. We further demonstrate how these concepts culminate in electro-oxidative asymmetric catalysis, where continuous-flow electrolysis provides an expanded operational window for simultaneously optimizing electrochemical and stereochemical parameters. Finally, we describe the translation of these transformations from laboratory-scale reactions to continuous production through reactor number-up and process integration. We anticipate that the next phase of development in flow electrosynthesis will be driven as much by advances in reactor engineering as by advances in synthetic methodology, ultimately enabling increasingly sophisticated continuous and electrified manufacturing platforms.