Olefin-accelerated solid-state C–N cross-coupling reactions using mechanochemistry

Palladium-catalyzed cross-coupling reactions are one of the most powerful and versatile methods to synthesize a wide range of complex functionalized molecules. However, the development of solid-state cross-coupling reactions remains extremely limited. Here, we report a rational strategy that provides a general entry to palladium-catalyzed Buchwald-Hartwig cross-coupling reactions in the solid state. The key finding of this study is that olefin additives can act as efficient molecular dispersants for the palladium-based catalyst in solid-state media to facilitate the challenging solid-state cross-coupling. Beyond the immediate utility of this protocol, our strategy could inspire the development of industrially attractive solvent-free palladium-catalyzed cross-coupling processes for other valuable synthetic targets. Cross-coupling reactions have been achieved in solution, yet tend to be inefficient in a solid state. Here, the authors report a solid-state palladium-catalyzed Buchwald-Hartwig cross-coupling using olefins as molecular dispersants, enabling reduction of solvent waste.