Work

Nickel-Catalyzed Cross-Coupling of Aryl Chlorides by Heated Mechanochemistry: Scalable Suzuki–Miyaura Reactions via Twin-Screw Extrusion

Year: 2025

Type: article

Abstract: The direct use of aryl chlorides in Suzuki-Miyaura cross-coupling remains a long-standing challenge due to the inert nature of the C-Cl bond. Herein, we report the first nickel-catalyzed Suzuki-Miyaura cross-coupling of aryl chlorides under solvent-minimized, heated mechanochemical conditions. Employing liquid-assisted grinding (LAG) and thermal input, a broad range of electron-deficient and electron-rich aryl chlorides were successfully coupled with aryl boronic acids in under 1 h. The methodology was translated to a twin-screw extrusion (TSE) process, enabling continuous production at scales up to 400 mmol and 65 g isolated product. This work demonstrates a sustainable, scalable strategy for C-C bond formation using readily available feedstocks, highlighting the synergy between nickel catalysis, mechanochemistry, and continuous flow processing.

Source: JACS Au

DOI: 10.1021/jacsau.5c00934

Authors: Sarah E. Raby-Buck, Renan R. Mattioli, Robert R. A. Bolt, Katharine Ingram, Julio C. Pastre, Duncan L. Browne