Biphasic Electrosynthesis for Efficient Organic Reductions via Hydrogen-Atom Transfer

Reduction and oxidation are cornerstone transformations in organic synthesis. While reagents have traditionally been used to effect organic redox reactions, recent advances in electrochemical methodology have offered an attractive alternative approach. In principle, the electrification of these processes could minimize stoichiometric waste, supply arbitrarily tunable potentials, and leverage sustainable energy. However, the practical realization of these advantages is hampered by the need to use organic solvents, which originates from the insolubility of typical substrates in water. As a result, many electrosynthetic reactions require superstoichiometric organic supporting electrolytes, operate under constant current conditions with limited potential control at each electrode, and function under high Ohmic resistance and therefore low efficiencies. Here, we demonstrate a biphasic aqueous-organic approach to electrosynthesis enables the efficient, metal-free, and selective reduction of nitrogen centers. This hybrid format combines the highly optimized performance of aqueous electrochemical platforms with the synthetic versatility of organic media. By integrating reaction and separation into a single process, we minimize byproduct formation, bypass chromatographic purification, and recycle the metal-free redox mediator – either in sequential batch experiments or in continuous flow – with minimal loss (<1% per cycle). Mechanistic experiments demonstrate that reduction proceeds through hydrogen atom transfer in a thin zone near the phase boundary, with the overall process achieving near-perfect Faradaic efficiency and high current density. The concept of biphasic electrosynthesis readily generalizes to other redox transformations, offering more sustainable and more ideal options for both discovery and manufacturing