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TCI Practical Example: Suzuki-Miyaura Cross Coupling with PdCl₂(Amphos)₂

We are proud to introduce the Suzuki-Miyaura cross coupling of heteroaryl chloride and arylboronic acid by using PdCl₂(Amphos)₂ as a catalyst. This reaction proceeds even if the substrate has an unprotected amino group.

Used Chemicals

• 3-Amino-2-chloropyridine [A0836]
• 2-Methylphenylboronic Acid [M1313]
• Bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (= PdCl₂(Amphos)₂) [B6255]
• Potassium Carbonate [P1748]
• Toluene
• Ion-Exchange Water

Procedure

To a reaction vessel, 3-amino-2-chloropyridine (0.8 g, 6.2 mmol), 2-methylphenylboronic acid (1.0 g, 7.4 mmol, 1.2 eq.), PdCl₂(Amphos)₂ (0.044 g, 0.062 mmol, 1 mol%), potassium carbonate (1.3 g, 9.4 mmol, 1.5 eq.), toluene (20 mL), and ion-exchange water (2 mL) were sequentially added. Under N₂ atmosphere, the reaction mixture was refluxed at 90 °C for 5 hours. The reaction was monitored by TLC and after the reaction mixture was cooled at room temperature, water (20 mL) was added and extracted with ethyl acetate. The organic layer was washed with 1 mol/L NaOH aq and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduce pressure and the given crude product was purified by silica gel column chromatography (hexane:ethyl acetate = 1:1) to obtain 2-(o-tolyl)-3-pyridinamine (0.90 g, 79% yield) as a milky white powder.

Experimenter’s Comments

The reaction mixture was monitored by TLC (hexane:ethyl acetate = 1:1, Rf = 0.4).

Analytical Data

2-(o-tolyl)-3-pyridinamine

¹H NMR (400 MHz, CDCl₃); δ 8.06 (d, 1H, J = 2.7 Hz), 8.05 (d, 1H, J = 2.7 Hz), 7.34-7.27 (m, 4H), 7.13-7.10 (m, 2H), 3.70 (brs, 2H), 2.18 (s, 3H).

Lead Reference

• 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.

Other References

• Single-Molecule Spin Switch Based on Voltage-Triggered Distortion of the Coordination Sphere
• G. D. Harzmann, R. Frisenda, H. S. J. van der Zant, M. Mayor, Angew. Chem. Int. Ed. 2015, 54, 13425.