Ligand design enables Cu-catalyzed Ullmann-type C-N and C-O cross-coupling reactions in water

We developed a Cu-catalyzed Ullmann-type coupling in an aqueous medium for the efficient reaction of aryl bromides/iodides/chlorides and alcohols/amines using a newly developed ligand, L (C₂₃H₁₉N₃O₆). Under optimized reaction conditions, several classes of previously incompatible aryl bromides/chlorides were efficiently transformed, including base-sensitive heterocycles and those containing acidic functional groups. Using K₂CO₃ as the base, the methodology efficiently promotes C-N and C-O bond formation, enabling the synthesis of diarylamines, diaryl ethers, and nitrogen-containing heterocycles in good to excellent yields. The protocol exhibits a broad substrate scope, high functional group tolerance, and excellent compatibility with electron-rich and electron-deficient aryl halides and nucleophiles at 90 °C. Gram-scale synthesis is also reported.