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TCI Practical Example: Suzuki-Miyaura Cross Coupling Using an Alkenyl Boronic Acid Ester as a Substrate

We are proud to present the Suzuki-Miyaura cross coupling using Pd₂(dba)₃ and SPhos as catalysts.

Used Chemicals

• 4'-Chloroacetophenone [C0033]
• 1-Boc-1,2,3,6-tetrahydropyridine-4-boronic Acid Pinacol Ester [B4051]
• Tris(dibenzylideneacetone)dipalladium(0) (= Pd₂(dba)₃) [T2184]
• 2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl (= SPhos) [D5036]
• K₃PO₄
• Toluene
• Ethanol
• Water

Procedure

4'-Chloroacetophenone (200 mg, 1.29 mmol) and 1-Boc-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (440 mg, 1.42 mmol) were dissolved in degassed mixture of toluene (5.0 mL), EtOH (2.0 mL) and water (2.0 mL). To this solution was added K₃PO₄ (820 mg, 3.88 mmol), SPhos (21 mg, 0.052 mmol, 4 mol%) and Pd₂(dba)₃ (18 mg, 0.020 mmol, 1.5 mol%). The reaction mixture was refluxed for 21 h, allowed to cool to room temperature and quenched with water (5 mL). The organic phase was separated and washed with water (5 mL) and brine (5 mL), dried over Na₂SO₄ (10 g), concentrated under reduced pressure to afford the crude product as orange oil. It was purified by column chromatography on silica-gel (hexane:ethyl acetate = 100:0 - 70:30) to afford the product 1 as colorless crystalline solid (310 mg, 1.03 mmol, 80%).

Experimenter's Comments

Toluene was degassed by refluxing under nitrogen atmosphere.

Analytical Data

Compound 1

¹H NMR (400 MHz, benzene-d6); δ 7.90 (d, J = 8.7 Hz, 2H), 7.42 (d, J = 8.7 Hz, 2H), 6.15 (brs, 1H), 4.08 (m, 2H), 3.63 (m, 2H), 2.50 (s, 3H), 2.52 (m, 2H), 1.47 (s, 9H).

Lead Reference

• Catalysts for Suzuki−Miyaura Coupling Processes:  Scope and Studies of the Effect of Ligand Structure
• T. E. Barder, S. D. Walker, J. R. Martinelli, S. L. Buchwald, J. Am. Chem. Soc. 2005, 127, 4685.