Palladium Catalyst for the Suzuki-Miyaura Coupling of Heteroaryl Chlorides

　Pd(Amphos)₂Cl₂ (1) is an air-stable divalent palladium complex that catalyzes Suzuki-Miyaura coupling with heteroaryl chlorides.^1,2) This reaction is characterized by high yields of coupling products even when heteroaryl chlorides, which are inexpensive but have low reactivity, are used as raw materials, and some reactions exceed catalytic turnover rates (TON) of 10000. In addition, the reaction is applicable to substrates having free amino group and sulfur functional groups that can be catalyst poisons. Since the obtained heterobiaryl skeletons are important structures in drug discovery research, it is expected that the coupling reaction with 1 will be widely used.

Practical Example: Synthesis of 2-(o-tolyl)-pyridineamine with 1

　To a 50 mL 3-neck flask under nitrogen atmosphere, 3-amino-2-chloropyridine (0.8 g, 6.2 mmol), 2-methylphenylboronic acid (1.0 g, 7.4 mmol, 1.2 eq), 1 (0.044 g, 0.062 mmol, 1 mol%), potassium carbonate (1.3 g, 9.4 mmol) were added, and the reaction mixture was refluxed at 90 °C for 5 hours. After confirming the disappearance of the raw material, the reaction solution was cooled to room temperature, and then water (20 mL) was added and extracted with ethyl acetate. The organic layer was washed with 1 mol/L sodium hydroxide solution and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The crude product obtained was purified by silica gel column chromatography (hexane : ethyl acetate=1 : 1), and 2-(o-tolyl)-3-pyridinamine (0.90 g, 79% yield) was obtained as a milky white powder.

References

• 1) New Air-Stable Catalysts for General and Efficient Suzuki−Miyaura Cross-Coupling Reactions of Heteroaryl Chlorides
  • A. S. Guram, A. O. King, J. G. Allen, X. Wang, L. B. Schenkel, J. Chan, E. E. Bunel, M. M. Faul, R. D. Larsen, M. J. Martinelli, P. J. Reider, Org. Lett. 2006, 8, 1787.
• 2) New Catalysts for Suzuki−Miyaura Coupling Reactions of Heteroatom-Substituted Heteroaryl Chlorides
  • A. S. Guram, X. Wang, E. E. Bunel, M. M. Faul, R. D. Larsen, M. J. Martinelli, J. Org. Chem. 2007, 72, 5104.

Related Products

A0836

3-Amino-2-chloropyridine

M1313

2-Methylphenylboronic Acid (contains varying amounts of Anhydride)

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