Palladium-Catalyzed Solid-State Polyfluoroarylation of Aryl Halides Using Mechanochemistry

The Suzuki-Miyaura cross-coupling between poly-fluorinated arylboron nucleophiles and aryl halides enables the efficient construction of polyfluorinated structural motifs frequently found in organic materials and catalysts. A key challenge associated with this transformation involves the slow transmetalation with weakly nucleophilic polyfluorinated organoboron reagents, which often reduces the yield of the coupling products. Here, we show that solid-state high-temperature ball-milling conditions facilitate a palladium-catalyzed cross-coupling with polyfluorinated arylboronic acids and pinacol esters employing a simple catalytic system in the absence of any stoichiometric additives. This reaction exhibits a broad substrate scope and can be carried out in air, and the use of large amounts of dry and degassed organic solvents is not required. The successful cross-coupling of weakly nucleophilic polyfluorinated organoboron reagents was ascribed to the extremely high concentrations of the substrates and the catalyst under solid-state conditions.

Automated summary

The palladium-catalyzed cross-coupling under solid-state high temperature ball-milling conditions enables efficient construction of polyfluorinated structural motifs without the need for stoichiometric additives, large amounts of organic solvents, and exhibits a broad substrate scope.