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Updated: Mar 15, 2026

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Efficient Microwave-Assisted Palladium-Catalyzed Selective N-Arylation of Anilines with 2,3-Dihalopyridines in Water
Hao-Chun Hu1, Cheng-Yi Chen2, Shyh-Chyun Yang1,2,3,4
1Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
Abstract:
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.
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