Interfacial Tuning of Electrocatalytic Ag Surfaces for Fragment-Based Electrophile Coupling

Construction of C‒C bonds in medicinal chemistry frequently draws on the reductive coupling of organic halides with ketones or aldehydes. Catalytic C(sp³)‒C(sp³) bond formation, however, is constrained by the competitive side reactivity of radical intermediates following sp³ organic halide activation. Here, an alternative paradigm deploys catalytic Ag surfaces for reductive fragment-based electrophile coupling compatible with sp³ organic halides. We use in-situ spectroscopy, electrochemical analyses, and simulation to uncover the catalytic interfacial structure and guide reaction development. Specifically, Mg(OAc)₂ outcompetes the interaction between Ag and the aldehyde, thereby tuning the Ag surface for selective product formation. Data are consistent with an increased population of Mg-bound aldehyde facilitating the addition of a carbon-centered radical (product of Ag-electrocatalyzed organic halide reduction) to the carbonyl. Electron transfer from Ag to the resultant alkoxy radical yields the desired alcohol. Molecular interfacial tuning at reusable catalytic electrodes will accelerate development of sustainable organic synthetic methods.