Aerobic Iron-Catalyzed Cross-Coupling with Polar Organometallic Reagents in Deep Eutectic Solvents

Over the past decades, iron-catalyzed Kumada-type cross-coupling reactions have undergone substantial development, particularly for transformations involving Csp³ alkyl halides and Csp² aryl Grignard reagents. These processes are conventionally carried out in anhydrous THF under inert atmosphere and commonly require additives such as TMEDA to ensure efficient catalyst performance. In light of the emerging potential of organolithium and Grignard reagents in deep eutectic solvents (DESs) and building upon our previous work on rapid palladium-catalyzed cross-couplings of organolithium and organozinc reagents in greener media, we undertook a comprehensive investigation into the reactivity of these organometallic species in DESs under iron catalysis, aerobic conditions, and at room temperature, with the aim of developing a more sustainable protocol for such transformations. A variety of DESs were evaluated as reaction media, and the behavior of organolithium compounds and Grignard reagents as nucleophiles was systematically compared. Our findings reveal that, within strongly hydrogen-bonded DES environments, traditional ligands such as TMEDA may lose their effectiveness. Notably, the DES medium itself plays a crucial role in suppressing homocoupling side reactions, while simultaneously favoring productive cross-coupling and preventing rapid quenching of the organometallic species.