Efficient Microwave-Assisted Palladium-Catalyzed Selective N-Arylation of Anilines with 2,3-Dihalopyridines in Water

Under aqueous conditions, transition-metal catalysis offers an attractive platform for greener C–N bond formation by reducing reliance on hazardous organic solvents. Herein, we report a microwave-assisted palladium-catalyzed selective N-arylation of anilines with 2,3-dihalopyridines in water. Systematic optimization revealed that a catalyst system comprising PdCl2(1,10-phenanthroline)2 and (±)-BINAP in the presence of K3PO4 enables efficient coupling under microwave irradiation. Under the optimized conditions (PdCl2(1,10-Phenanthroline)2, 2 mol%; (±)-BINAP, 3 mol%; K3PO4, 3.5 equiv; H2O, 2.5 mL; 150 °C; 30 min), the coupling of aniline with 2,3-dichloropyridine afforded the corresponding aminopyridine product in up to 91% isolated yield. The method was extended to various 2,3-dihalopyridines and substituted anilines, providing moderate to excellent yields with good regioselectivity. Mechanistically, the transformation is consistent with a Pd(0)/Pd(II) catalytic cycle involving oxidative addition, amido complex formation, and reductive elimination.