Ion-Pair Breakers and Anionic Brønsted Acids for Helmholtz-Layer Catalysis with External Electric Fields in Microfluidic Capacitors.

Despite strong support from theory and biological systems, catalysis with externally applied electric fields remains difficult to implement for practical organic synthesis purposes. We approached this central challenge last year with catalytic Helmholtz layers in microfluidic capacitors: in response to applied electric fields (AEFs), specifically designed ion pairs were found to separate and assemble into Helmholtz layers, generating strong, effective electric fields (EEFs) that catalyze reactions. The objective of this study was to identify fundamental principles to construct catalytic Helmholtz layers, focusing on ion-pair separation and the integration of functional motifs. Epoxide-opening polyether cascade cyclizations are used as benchmark reactions because they work in apolar solvents and offer mechanistic diversity and thus a wide responsive product space. With tight ion pairs like tetrabutylammonium bisulfate in apolar solvents, reaction yields Y increase nonlinearly with applied voltage V, starting from 0%. We attributed these nonlinear YV curves to the formation of catalytic Helmholtz layers with high EEFs above a critical voltage required for ion-pair separation. Electric-field catalysis (EFC) then proceeds through stabilization of the transition state by the EEFs, assisted by anionic Brønsted acids that are acidified by the EEFs of their own Helmholtz layers. Inactivity with nonfunctional ion pairs, the absence of detectable currents ≥1 mA up to 20 V, and insensitivity to radical scavengers support this mechanism. To facilitate ion-pair separation and integrate molecular recognition motifs into the catalytic Helmholtz layers, anion-binding ion-pair breakers are introduced. Centered around Schreiner thioureas, these breakers lower the critical voltage, increase maximal yields at saturation to completion, and influence selectivity. With the concepts of voltage-gated EFC, ion-pair breakers, and anionic Brønsted acids in functional Helmholtz layers, the general understanding reached in this study provides the conceptual mechanistic framework for the development of practical electric-field organic synthesis at high voltage.