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

Abstract

Electrochemical synthesis can provide more sustainable routes to industrial chemicals^1-3. Electrosynthetic oxidations may often be performed 'reagent-free', generating hydrogen (H₂) 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 applications⁴, but more sustainable options are needed at larger scale. Anodic water oxidation is an especially appealing option^1,5,6, but many reductions require anhydrous, air-free reaction conditions. In such cases, H₂ 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 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-catalysed cross-electrophile coupling (XEC), a reaction class gaining widespread adoption in 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 H₂ anode technology disclosed here offers a general strategy to support H₂-driven electrosynthetic reductions.