Quinone-mediated hydrogen anode for non-aqueous reductive electrosynthesis.

Electrochemical synthesis can provide more sustainable routes to industrial chemicals. Electrosynthetic oxidations may often be performed 'reagent-free', generating hydrogen (H) derived from the substrate as the sole by-product at the counter electrode. Electrosynthetic reductions, however, require an external source of electrons. Sacrificial metal anodes are commonly used for small-scale applications, but more sustainable options are needed at larger scale. Anodic water oxidation is an especially appealing option, but many reductions require anhydrous, air-free reaction conditions. In such cases, H represents an ideal alternative, motivating the growing interest in the electrochemical hydrogen oxidation reaction (HOR) under non-aqueous conditions. Here we report a mediated H anode that achieves indirect electrochemical oxidation of H by pairing thermal catalytic hydrogenation of an anthraquinone mediator with electrochemical oxidation of the anthrahydroquinone. This quinone-mediated H anode is used to support nickel-catalysed cross-electrophile coupling (XEC), a reaction class gaining widespread adoption in the pharmaceutical industry. Initial validation of this method in small-scale batch reactions is followed by adaptation to a recirculating flow reactor that enables hectogram-scale synthesis of a pharmaceutical intermediate. The mediated H anode technology disclosed here offers a general strategy to support H-driven electrosynthetic reductions.