Bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II)

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

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.

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

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).

• 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.

• 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.

• 4-Bromobiphenyl [B1330]
• Bis(sulfur Dioxide)-1,4-diazabicyclo[2.2.2]octane Adduct (= DABSO) [B3960]
• Bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (= PdCl₂(Amphos)₂ [B6255]
• Triethylamine (=Et₃N) [T0424]
• N-Fluorobenzenesulfonimide (=NFSI) [F0335]
• Isopropyl Alcohol (= IPA)

To a solution of 4-bromobiphenyl (1.17 g, 5.00 mmol), DABSO (721 mg, 3.00 mmol), and PdCl₂(Amphos)₂ (177 mg, 0.25 mmol) in anhydrous isopropyl alcohol (20 mL) was added triethylamine (2.1 mL, 15 mmol) at room temperature and the mixture was stirred at 75 °C for 23 hours. The suspension was cooled at room temperature and NFSI (2.36 g, 7.5 mmol) was added and the reaction mixture stirred for 3 hours until completion. The solvent was removed under reduced pressure. The residue was diluted with ethyl acetate (20 mL) and filtrated through celite pad. The filtrate was washed with saturated aqueous Na₂S₂O₃ solution (20 mL) and brine (20 mL), dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by medium pressure preparative chromatography (ethyl acetate:hexane = 2:98 - 5:95 on silica gel) to give compound 1 as a white solid (928 mg, 79%).

The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:9, Rf = 0.57) and UPLC-MS.

Compound 1

¹H NMR (400 MHz, CDCl₃); δ 8.12–8.04 (m, 2H), 7.86–7.80 (m, 2H), 7.67–7.58 (m, 2H), 7.44-7.55 (m, 3H).

• One-pot palladium-catalyzed synthesis of sulfonyl fluorides from aryl bromides
• A. T. Davies, J. M. Curto, S. W. Bagley, M. C. Willis, Chem. Sci. 2017, 8, 1233.