Ni-Catalyzed Electrochemical C(sp2)−C(sp3) Cross-Coupling Reactions

• Published in: ChemRxiv
• Main Authors: Luo, Jian, Hu, Bo, wu, wenda, hu, maowei, Liu, Tianbiao
• Format: Paper
• Language: English
• Edition: 2
• Subjects: Chemistry; Electrocatalysis; Homogeneous Catalysis; Redox Catalysis; electrosynthesis; cross coupling; Ni catalysis; post-stage functionalization; organic halide; organic borate; flow cell synthesis
• ISSN: 2573-2293
• DOI: 10.26434/chemrxiv.11813505.v2

Nickel (Ni) catalyzed carbon-carbon (C−C) cross-coupling has been considerably developed in last decades and has demonstrated unique reactivities compared to palladium. However, existing Ni catalyzed cross-coupling reactions, despite success in organic synthesis, are still subject to the use of air-sensitive nucleophiles (i.e. Grignard and organozinc reagents), or catalysts (i.e. Ni0 pre-catalysts), significantly limiting their academic and industrial adoption. Herein, we report that, through electrochemical voltammetry screening and optimization, the redox neutral C(sp2)‒C(sp3) cross-coupling can be accomplished in an undivided cell configuration using bench-stable aryl halide or β-bromostyrene (electrophiles) and benzylic trifluoroborate (nucleophiles) reactants, non-precious, bench stable catalysts consisting of NiCl2•glyme pre-catalyst and polypyridine ligands under ambient conditions. The broad reaction scope and good yields of the Ni-catalyzed electrochemical coupling reaction were confirmed by 48 examples of aryl/β-styrenyl chloride/bromide and benzylic trifluoroborates. Its potential applications were demonstrated by late-stage functionalization of pharmaceuticals and natural amino acid modification. Furthermore, this electrochemical C−C cross-coupling reaction was demonstrated at gram-scale in a flow-cell electrolyzer for practical industrial adoption. Finally, an array of chemical and electrochemical studies mechanistically indicates that electrochemical C−C cross-coupling reaction proceeds through an unconventional radical trans-metalation mechanism.