Inspired by the intrinsic internal electric field present in enzymes, externally applied electric fields (AEFs) have long been predicted to accelerate and direct electron movement. [1]  However, the practical implementation of AEFs under standardized conditions for organic synthesis has yet to be realised. To face this challenge, we implemented catalytic Helmholtz layers in microfluidic capacitors. [2] In response to an AEF, tetrabutylammonium bisulfate in apolar solvents was found to dissociate and assemble into Helmholtz layers, generating strong effective electric fields (EEFs) that enhance the acidity of the bisulfate Bronsted acid anion, thereby catalyzing epoxide-opening polyether cascade cyclizations. To boost catalytic activity and enable unique AEF-driven reactivity, anion-binding ion-pair breakers are introduced. These amplifiers facilitate ion-pair separation and incorporate molecular recognition motifs into the catalytic Helmholtz layers. The insights gained in this study provide a conceptual mechanistic framework for the development of practical AEF catalysis for applications in organic synthesis.

1] Sason Shaik, David Donovich, Jyothish Joy, Zhanfeng Wang, Thijs Stuyver, J. Am. Chem. Soc, 2020, 142, 12551-12562.

[2] Shen-Yi Guo, Miguel Paraja, Augustina Jozeliunaite, Manuel Gallardo-Villagran, Quing-Xia Zhang, Alenka Marsalek, Naomi Sakai, Stefan Matile, Angew. Chem. Int. Ed, 2025, 64, e202517078