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

Abstract

The Suzuki–Miyaura cross-coupling between polyfluorinated 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.

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

“…Notably, the strong mechanical agitation provided by ball milling enables efficient solid-state organic transformations. Thus far, mechanochemical palladiumcatalyzed cross-coupling reactions such as Suzuki-Miyaura [34][35][36][37][38][39][40][41][42][43][44][45][46][47], Buchwald-Hartwig [48][49][50][51][52], Sonogashira [53][54][55][56], Negishi [57], Mizoroki-Heck [58][59][60], and C-S bond-forming [61] reactions have been developed. Our group has also been interested in this class of mechanochemical transformations, particularly in the development of cross-coupling reactions that proceed in the solid state [43][44][45][46][47][48][49][50].…”

Mechanochemical C−X/C−H Functionalization: An Alternative Strategic Access to Pharmaceuticals

“…Based on this solid‐state cross‐coupling strategy, they discovered a new luminescent organic material with a strong red emission. This high‐temperature solid‐state ball‐milling technique could also significantly accelerate cross‐coupling of weakly nucleophilic polyfluorinated organoboron reagents and pinacol esters in the absence of any stoichiometric pinacol and Na 2 SO 4 ⋅ 10H 2 O additives [48k] …”

Insight into the Reactivity Profile of Solid-State Aryl Bromides in Suzuki–Miyaura Cross-Coupling Reactions Using Ball Milling

“…More recently, we discovered that such polyaromatic halides, including insoluble pigments and dyes, reacted smoothly under high-temperature ball-milling conditions in which ball milling reactions were carried out while applying a heat gun. 8,14 This protocol allows solid-state coupling reactions to be carried out at approximately 120 °C. Although these studies advanced the solid-state cross-coupling chemistry, 2d 5 8 , 12 13 14 15 insight into the unique reactivity of solid substrates and the effect of reaction temperature have not been fully investigated.…”

“…More recently, we discovered that such polyaromatic halides, including insoluble pigments and dyes, reacted smoothly under high-temperature ball-milling conditions in which ball milling reactions were carried out while applying a heat gun. 8,14…”

“…8,14 This protocol allows solid-state coupling reactions to be carried out at approximately 120 °C. Although these studies advanced the solid-state cross-coupling chemistry, 2d 5 8 , 12 13 14 15 insight into the unique reactivity of solid substrates and the effect of reaction temperature have not been fully investigated. To further expand the scope of solid-state cross-coupling, we realized that fundamental research is necessary to clarify the key factors that determine the reactivity of organic compounds under solid-state ball-milling conditions and the effect of temperature on a broad range of solid substrates with different physical properties (Scheme 1 ).…”