C–N Coupling in Electrochemical Amino Acid Synthesis Occurs in Solution, not on the Catalyst Surface
Year: 2026
Type: preprint
Abstract: Amino acids are valuable targets for electrochemical synthesis, yet the mechanism of the central C–N bond-forming step remains unclear. Many studies assume that C–N coupling occurs on various electrocatalyst surface efficiently, an assumption that is difficult to reconcile with the strikingly diverse range of reported catalysts. Taking glycine synthesis from oxalic acid and hydroxylamine as a model reaction, we combine density functional theory with NMRbased experiments to investigate the origin of C–N coupling. The overall reaction can be described as three decoupled steps: (i) electrochemical reduction of oxalic acid to glyoxylic acid, (ii) a spontaneous solution-phase condensation that forms the C–N bond, and (iii) electrochemical reduction of glyoxylic acid oxime to glycine. For the C-N coupling step, calculations on model metal surfaces yield high barriers for this condensation, whereas a water-mediated proton-transfer pathway substantially lowers the calculated barrier in solution, consistent with the experimentally observed spontaneous oxime formation. We also observed this mechanism across a range of aldehydes and ketones, suggesting that effective electrocatalysts need to only drive reactant and oxime reduction rather than C–N coupling itself.
Source: ChemRxiv
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7204544140