A Glove-Box- and Schlenk-Line-Free Protocol for Solid-State C–N Cross-Coupling Reactions Using Mechanochemistry
Koji Kubota, Rikuro Takahashi, Minami Uesugi, Hajime Ito
Abstract
Carbon–nitrogen (C–N) bond-forming cross-coupling reactions catalyzed by palladium-based catalysts, the so-called Buchwald–Hartwig aminations, have been widely employed for the synthesis of pharmaceuticals and aryl-amine-based organic materials in academic and industrial settings. However, in solution, these reactions usually require glovebox and Schlenk line techniques, which greatly reduces their practical utility. Here, we report the development of operationally simple mechanochemical C–N cross-coupling reactions in the solid-state. Intensive investigations of various ball milling parameters revealed that the air-stable ligand tri(1-adamantyl)phosphine can be used to achieve solid-state coupling reactions between aryl halides and diarylamines with high efficiency. Notably, all experimental operations of the developed protocol can be carried out in air, thus providing a more convenient, industrially attractive, and sustainable alternative to conventional solution-based palladium-catalyzed C–N coupling reactions.