2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

• 2-Chloro-m-xylene [C2164]
• 2-Methylphenylboronic Acid [M1313]
• Bis(dibenzylideneacetone)palladium (0) (Pd(dba)₂) [B1374]
• 2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos) [D5036]
• Tripotassium Phosphate (K₃PO₄)
• Toluene
• Ion-exchange water

To a 3-necked flask was charged with bis(dibenzylideneacetone)palladium (0) (66 mg, 0.115 mmol, 1.5 mol%), SPhos (94 mg, 0.229 mmol, 3.0 mol%), 2-methylphenylboronic acid (1.56 g, 11.5 mmol, 1.5 equiv.), tripotassium phosphate (4.87 g, 22.9 mmol, 3.0 equiv.) degassed toluene (15 mL), and ion-exchange water (1.5 mL) under nitrogen atmosphere. The mixture was stirred at room temperature for 5 min. 2-Chloro-m-xylene (1.0 mL, 7.64 mmol, 1.0 equiv.) was added one portion. The resulting mixture was stirred at reflux for 7 h. The reaction mixture was cooled to room temperature and quenched with water (10 mL). The organic layer was washed with water (10 mL), and brine (10 mL), dried with Na₂SO₄ (20 g) and then concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (hexane only) to afford the corresponding compound as a colorless oil (1.46 g, 97%).

i) Toluene was degassed by bubbling with nitrogen gas for 30 min.
ii) The reaction mixture was monitored by GC.

¹H NMR (400 MHz, CDCl₃); δ 7.23-7.33 (m, 3H), 7.22-7.10 (m, 3H), 7.00-7.06 (m, 1H), 1.99 (s, 3H), 1.97 (s, 6H).

¹³C NMR (101 MHz, CDCl₃); δ 141.0, 140.5, 135.8, 135.5, 129.9, 128.8, 127.2 127.0, 126.9, 126.0, 20.3, 19.4.

• 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.

• 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
• H₂O

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 H₂O (5 mL). The organic phase was separated and washed with H₂O (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 100% ~ hexane: EtOAc = 70: 30) to afford the product 1 as colorless crystalline solid (310 mg, 1.03 mmol, 80%).

Toluene was degassed by refluxing under nitrogen atmosphere.

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).