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

Electrochemical synthesis can provide more sustainable routes to industrial chemicals 1-3 . Electrosynthetic oxidations often may be performed "reagent-free", generating hydrogen (H 2 ) 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 4 , but more sustainable options are needed at large scale. Anodic water oxidation is an especially appealing option 1,5,6 , but many reductions require anhydrous, air-free reaction conditions. In such cases, H 2 represents an ideal alternative, motivating the growing interest in the electrochemical hydrogen oxidation reaction (HOR) under non-aqueous conditions 7-12 . Here, we report a mediated H 2 anode that achieves indirect electrochemical oxidation of H 2 by pairing thermal catalytic hydrogenation of an anthraquinone mediator with electrochemical oxidation of the anthrahydroquinone. This quinone-mediated H 2 anode is used to support nickel-catalyzed cross-electrophile coupling (XEC), a reaction class gaining widespread adoption within the pharmaceutical industry 13-15 . 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 2 anode technology disclosed here offers a general strategy to support H 2 -driven electrosynthetic reductions.