Bis(dibenzylideneacetone)palladium(0)

Used Chemicals

• 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

Procedure

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%).

Experimenter's Comments

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

Analytical Data（2,2',6-Trimethyl-1,1'-biphenyl）

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.

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.

Used Chemicals

• 4-Chlorotoluene [C0297]
• Morpholine [M0465]
• Bis(dibenzylideneacetone)palladium (0) [B1374]
• 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (XPhos) [D5038]
• Sodium tert-Butoxide [S0450]
• Toluene

Procedure

To a 2-necked flask was charged with bis(dibenzylideneacetone)palladium (0) (36 mg, 0.0633 mmol, 1.5 mol%), XPhos (60 mg, 0.127 mmol, 3.0 mol%), sodium tert-butoxide (811 mg, 8.44 mmol, 2.0 equiv.) and toluene (5 mL) under nitrogen atmosphere. The mixture was stirred at room temperature for 5 min. 4-chlorotoluene (0.5 mL, 4.22 mmol, 1.0 equiv.), and morpholine (0.55 mL, 6.33 mmol, 1.5 equiv.) were added in one portion. The resulting mixture was stirred at reflux for 6 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 : ethyl acetate = 9 : 1) to afford the corresponding compound as an orange solid (700 mg, 94%).

Experimenter's Comments

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

Analytical Data（Compound 1）

¹H NMR (400 MHz, CDCl₃); δ 7.10 (d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.7 Hz, 2H), 3.87 (t, J = 4.8 Hz, 4H), 3.11 (t, J = 4.8 Hz, 4H), 2.28 (s, 3H).

¹³C NMR (101 MHz, CDCl₃); δ 149.1, 129.7, 129.5, 116.0, 66.9, 49.9, 20.4.

Lead Reference

• Expanding Pd-Catalyzed C−N Bond-Forming Processes:  The First Amidation of Aryl Sulfonates, Aqueous Amination, and Complementarity with Cu-Catalyzed Reactions
  • H. Huang, K. W. Anderson, D. Zim, L. Jiang, A. Klapars, S. L. Buchwald, J. Am. Chem. Soc. 2003, 125, 6653.

References

• Pd-Catalyzed Kumada－Corriu Cross-Coupling Reactions at Low Temperatures Allow the Use of Knochel-type Grignard Reagents
  • R. Martin, S. L. Buchwald, J. Am. Chem. Soc. 2007, 129, 3844.