Electrochemical Hydrogenation of Aza-Arenes Using H ₂ O as H Source

Electrochemical hydrogenation of aza-arenes is an appealing strategy to gain access to privileged saturated heterocycles for drug discovery, overcoming the limitations of classical hydrogenations that often suffer from energy-intensive conditions and safety hazards. Herein, we demonstrate an operationally simple, sustainable, and general electrochemical hydrogenation of aza-arenes with commercialized Ni foam electrodes and setup. With water as the hydrogen donor under acidic conditions, the reaction proceeds at ambient temperature and pressure to deliver broad substrate generality, excellent functional group tolerance, and excellent selectivity. The method tolerates a wide range of aza-arenes─including (iso)quinolines, quinoxalines, pyridines, and their nium salts─highlighting its generality and robustness. Synthetic utility was showcased through the preparation of bioactive molecules, while scalability was achieved up to 25 g of product, highlighting the method's technical applicability with stable 22 h operation without changes in the cell voltage or significant electrode degradation. Extensive mechanistic investigations using a combination of cyclic and RDE linear sweep voltammetry suggest two plausible routes based on the substrate's redox properties: hydrogenation by chemisorbed hydrogen (<i>H</i>_ads) or initial substrate reduction followed by <i>H</i>_ads transfer. This work sets a clean, practical, and versatile platform for aza-arene dearomatization, bridging academic interest with industrial targets in electrochemical hydrogenation.