A Radical Strategy for the Synthesis of Polyfluorinated Biaromatic Hydrocarbons via Nickel-Catalyzed Reductive Cross-Coupling

The polyfluorinated biaromatic framework is a key structural motif in pharmaceutical chemistry and advanced functional materials. However, its synthesis is frequently hindered by multistep processes and stringent reaction conditions. In this study, we present a nickel-catalyzed reductive cross-coupling strategy between halogenated arenes, offering a streamlined and efficient route to polyfluorinated biaryl hydrocarbons via a radical mechanism. This method exhibits broad substrate scope and significantly reduces the complexity of synthetic routes to a range of fluorinated compounds, including liquid crystals, the nonsteroidal anti-inflammatory drug diflunisal, and aminopeptidase inhibitors, highlighting its practical relevance. Mechanistic investigations indicate that a nickel(0) species facilitates the activation of polyfluorinated aryl bromides, generating key polyfluoroaryl radicals that drive the cross-coupling process. Overall, this work introduces a practical and versatile approach to accessing polyfluorinated biaryl structures and broadens the applicability of reductive biaryl coupling methodologies.