Cation-Controlled eFluorination: Engineering Reactive Intermediates for Selective C–F Bond Formation

Conspectus Selective C–F bond formation remains a fundamental challenge in synthetic chemistry as fluorination reactions often involve highly reactive intermediates, competing decomposition pathways, and fluoride sources whose effective reactivity depends strongly on their chemical environment. Although conventional fluorination methods have enabled broad applications in medicinal chemistry and agrochemical science, many approaches rely on stoichiometric oxidants or electrophilic fluorinating reagents, which limit selectivity, functional-group tolerance, and operational simplicity. Electrochemical synthesis offers a complementary strategy in which electrons function as traceless redox reagents, enabling controlled generation of reactive intermediates under comparatively mild conditions. A central theme emerging from modern electrochemical fluorination is that selective C–F bond formation depends less on the intrinsic nucleophilicity of fluoride and more on the controlled generation, stabilization, and interception of cationic intermediates. Across diverse reaction classes, productive fluorination occurs when electrochemical conditions, substrate structure, solvent environment, and fluoride speciation are collectively matched to prolong intermediate lifetime while suppressing overoxidation, elimination, rearrangement, or fragmentation pathways. In this context, fluoride availability is not a fixed property but is governed by hydrogen bonding, ion pairing, solvation, and the identity of the fluoride source itself, including poly(HF) salts, tetrafluoroborate systems, and metal fluoride complexes. In this Account, we summarize recent advances in electrochemical fluorination mediated by stabilized radical cation and carbocation intermediates with an emphasis on contributions from our group. We discuss how heteroatom substitution, π-system delocalization, neighboring-group participation, and control of electrochemical parameters can be leveraged to direct selective fluoride capture. Representative systems include sulfur-, oxygen-, and nitrogen-assisted fluorination manifolds, radical-polar crossover fluorination of benzylic and tertiary substrates, fluorination involving vinyl and arene radical cations, and electrogenerated hypervalent iodine mediators that enable fluorination through related oxidative pathways. Attention is devoted to mechanistic principles that unify these transformations. Collectively, the studies show that electrochemistry provides additional tunability; however, oxidation mode, medium, fluoride speciation, mass transport, and intermediate lifetime remain interdependent. Cyclic voltammetry, radical-trapping, isotope-labeling, and reaction-environment studies increasingly frame electrochemical fluorination as a parameter-matching problem rather than a collection of isolated reaction classes. Beyond reaction development, these advances establish broader conceptual foundations for electrosynthetic fluorination. Continued progress will require a better understanding of fluoride speciation, ion-pairing effects, and reactive intermediate lifetimes under operating electrochemical conditions. We anticipate that integrating mechanistic analysis and reaction engineering will enable increasingly predictable and selective fluorination strategies, including applications in late-stage functionalization, radiochemistry, and sustainable fluorine incorporation.