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TCI Practical Example: Palladium-Catalyzed Coupling Reaction of the Heterocyclic Sulfinate

We are proud to introduce the cross-coupling reaction using heterocyclic sulfinate salt as a substitute for unstable 2-pyridineboronic acid.

Used Chemicals

• Sodium Pyridine-2-sulfinate [O0533]
• 4-Bromotoluene [B0661]
• Palladium(II) Acetate (Purified) [P2161]
• Di-tert-butyl(methyl)phosphonium Tetrafluoroborate [D4731]
• Potassium Carbonate [P1748]
• 1,4-Dioxane

Procedure

Sodium pyridine-2-sulfinate (0.15 g，0.88 mmol), palladium(II) acetate (6.6 mg, 29 µmol), di-tert-butyl(methyl)phosphonium tetrafluoroborate (15 mg, 58 µmol), 4-bromotoluene (0.10 g, 0.58 mmol), potassium carbonate (0.16 g, 1.2 mmol), 1,4-dioxane (3 mL) were placed in a pressure vessel under nitrogen atmosphere at room temperature. The reaction mixture was stirred for 4 days at 120 °C, then palladium(II) acetate (6.6 mg, 29 µmol) and di-tert-butyl(methyl)phosphonium tetrafluoroborate (15 mg, 58 µmol) was added. The reaction mixture was stirred for another 4 days at 120 °C, then diluted with ethyl acetate and washed with water. The organic layer was dried by sodium sulfate, then concentrated under reduced pressure. The resulting crude product was purified by column chromatography (hexane:ethyl acetate = 5:1 on silica gel) to give 1 as a yellow oil (29 mg, 29% yield).

Experimenter’s Comments

The reaction mixtures were monitored by ¹H NMR.

Analytical Data

2-(p-Tolyl)pyridine (1)

¹H NMR (400 MHz, CDCl₃); δ 8.68 (d, 1H, J = 5.0 Hz), 7.89 (d, 2H, J = 8.3 Hz), 7.78-7.68 (m, 2H), 7.28 (d, 2H, J = 7.8 Hz), 7.23-7.18 (m, 1H), 2.41 (s, 3H).

¹³C NMR (101 MHz, CDCl₃); δ 157.8, 149.7, 139.1, 136.8, 136.7, 129.6, 126.9, 121.9, 120.4, 21.4. (2C are overlapped at aromatic area)

Lead Reference

• Catalyst Selection Facilitates the Use of Heterocyclic Sulfinates as General Nucleophilic Coupling Partners in Palladium-Catalyzed Coupling Reactions
• T. Markovic, B. N. Rocke, D. C. Blakemore, V. Mascitti, M. C. Willis, Org. Lett. 2017, 19, 6033.