Quinone-mediated hydrogen anode for non-aqueous reductive electrosynthesis

Electrochemical synthesis can provide more sustainable routes to industrial chemicals. Electrosynthetic oxidations often may be performed "reagent-free", generating H2 derived from the substrate as the sole byproduct 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 large scale. Anodic water oxidation is an especially appealing option, but many reductions require anhydrous, air-free reaction conditions. This constraint motivates the growing interest in the electrochemical hydrogen oxidation reaction (HOR) under non-aqueous conditions. Here, we report a mediated H2 anode that achieves indirect electrochemical oxidation of H2 by pairing thermal catalytic hydrogenation of an anthraquinone mediator with electrochemical oxidation of the anthrahydroquinone. This quinone-mediated H2 anode is used to support nickel-catalyzed cross-electrophile coupling (XEC), a reaction class gaining widespread adoption within 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 H2 anode technology disclosed here offers a general strategy to support H2-driven electrosynthetic reductions.