Development of Kilogram-Scale Electrochemical Ni-Catalyzed Cross Electrophile Coupling in Flow
Year: 2026
Type: article
Abstract: Organic electrosynthesis opens novel routes for pharmaceutical production; however, limited knowledge and experience with the scale up of this technique have hindered its industrial implementation. In this work, we report a kilogram-scale flow electrochemical Ni-catalyzed cross-electrophile coupling (XEC) to prepare a key intermediate in the synthesis of the toll-like receptor (TLR) 7/8 inhibitor afimetoran. We successfully demonstrate scalability across 2 orders of magnitude while maintaining reaction performance. We also conduct a continuous 120 h reaction, highlighting compatibility with industrially relevant time scales. Key design aspects of our custom parallel-plate reactor are discussed that enabled kilogram-scale synthesis with a single electrode stack. This report showcases that with proper reaction engineering, electrochemical Ni-catalyzed XEC is a viable alternative to existing Pd-catalyzed cross-coupling methods.
Authors: Megan Kelly, Luana Cardinale, Karrin V. Sackett, Suqi Zhang, Gregory L. Beutner, Benjamin Cohen, Shannon S. Stahl, Marcel Schreier
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: G2449006768, G6204066990
OpenAlex ID: W7164940223