Designing of Bifunctional Ligand for Effective Cu(I)-Catalyzed C–N Cross-Coupling in Aqueous Micellar Conditions

We designed a hydrophobic, bifunctional ligand derived from 6-hydroxypicolinamide and harnessed its synergy with micelles to enable effective Cu-catalyzed C–N cross-coupling in water. A comprehensive investigation was conducted to elucidate the cooperative role of the micellar environment and the ligand to promote reaction efficiently. Micellar size and morphological evolution in the presence of a catalyst and substrate were analyzed using dynamic light scattering (DLS) and confocal laser scanning microscopy (CLSM). The formation and stabilization of the Cu catalyst in aqueous CNSL-1000-M were confirmed by UV–visible spectroscopy, transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). Notably, the micellar system outperformed conventional organic solvents─including DMF, 1,4-dioxane, DMSO, and toluene─in both catalytic activity and selectivity. Additionally, the aqueous CNSL-1000-M can be used as a recyclable reaction medium, and the broad applicability of this method was demonstrated across 33 substrates and further validated in a gram-scale reaction.