Tris(dibenzylideneacetone)dipalladium(0)

Used Chemicals

• 4-Chloroanisole [C0122]
• Diphenylamine
• Tris(dibenzylideneacetone)dipalladium(0) (= Pd₂(dba)₃) [T2184]
• Tri-tert-butylphosphonium Tetrafluoroborate (= tBu₃P・HBF₄) [T2584]
• Sodium tert-Butoxide (= NaOtBu) [S0450]
• Toluene

Procedure

To a 3-necked 300 mL round bottom flask was charged with diphenylamine (5.01 g, 29.6 mmol, 1.0 eq.), 4-chloroanisole (4.48 g, 31.4 mmol, 1.05 eq.) and degassed toluene (150 mL). To this solution was added Pd₂(dba)₃ (0.287 g, 0.131 mmol, 1 mol%), tri-tert-butylphosphonium tetrafluoroborate (0.198 g, 0.683 mmol, 2 mol%) and sodium tert-butoxide (6.34 g, 66.0 mmol, 2.2 eq.). The reaction mixture was refluxed for 16 hr under nitrogen atmosphere. After cooled to room temperature, the reaction was diluted with CH₂Cl₂ (300 mL). The suspension was filtered and the filtrate was dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude and brown solid. The crude product was purified by silica-gel column chromatography (hexane/EtOAc = 99/1 then 8/1) to afford the light brown solid (7.0 g) containing 10 mol% of diphenylamine. Removal of the residual diphenylamine by recrystallization from hexane (55 mL, 60 °C then 15 °C) gave 4-methoxytriphenylamine as a white solid (5.26 g, 65 %).

Experimenter’s Comments

The reaction mixture was monitored by TLC (EtOAc/hexane = 1/10. Starting materials: Rf = 0.36 (diphenylamine), 0.59 (4-chloroanisole); target product: Rf = 0.46).

Analytical Data（4-Methoxytriphenylamine）

¹H NMR (400 MHz, CD₂Cl₂); δ 7.26-7.17 (m, 4H), 7.10-6.98 (m, 6H), 6.98-6.91 (m, 2H), 6.89-6.82 (m, 2H), 3.79 (s, 3H).

¹³C NMR (101 MHz, CD₂Cl₂); δ 156.72, 148.56, 141.00, 129.39, 127.72, 123.12, 122.15, 115.05, 55.77.

Lead References

• Air-Stable Trialkylphosphonium Salts:  Simple, Practical, and Versatile Replacements for Air-Sensitive Trialkylphosphines. Applications in Stoichiometric and Catalytic Processes
  • M. R. Netherton, G. C. Fu, Org. Lett. 2001, 3, 4295.
• An Air and Thermally Stable One- Component Catalyst for the Amination of Aryl Chlorides
  • D. Zim, S. L. Buchwald, Org. Lett. 2003, 5, 2413.

Other References

• A Simple Catalytic Method for the Conversion of Aryl Bromides to Arylamines
  • A. Guram, R. Rennels, S. Buchwald, Angew. Chem. Int. Ed. 1995, 34, 1348.
• Palladium-catalyzed synthesis of arylamines from aryl halides. Mechanistic studies lead to coupling in the absence of tin reagents
  • J. Louie, J. F. Hartwig, Tetrahedron Lett. 1995, 36, 3609.

Used Chemicals

• 1,4-Dichlorobenzene [D0687]
• Piperidin
• Tris(dibenzylideneacetone)dipalladium(0) (= Pd₂(dba)₃) [T2184]
• 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (= XPhos) [D5038]
• Sodium tert-Butoxide [S0450]
• Toluene

Procedure

1,4-Dichlorobenzene (500 mg, 3.40 mmol) and piperidine (869 mg, 10.2 mmol) were dissolved in degassed toluene (15.0 mL). To this solution was added sodium tert-butoxide (817 mg, 8.50 mmol), XPhos (65 mg, 0.136 mmol, 4 mol%) and Pd₂(dba)₃ (47 mg, 0.051 mmol, 1.5 mol%). The reaction was refluxed for 16 h and quenched with H₂O (15 mL) after cooling to room temperature. The organic phase was separated and washed with H₂O (10 mL) and brine (10 mL), dried over Na₂SO₄ (30 g), concentrated under reduced pressure to afford the crude product as brown solid, which was purified by column chromatography on silica gel (CH₂Cl₂ 100% → CH₂Cl₂: EtOAc = 30: 70) to afford the product 1 as a pale yellow solid. The obtained solid was dissolved in hexane and decolorized by activated carbon. After removal of activated carbon by filtration, the filtrate was concentrated to afford the product 1 as a white powder (782 mg, 2.66 mmol, 78%).

Experimenter's Comments

Toluene was degassed by refluxing under nitrogen atmosphere.
Completion of the reaction was confirmed by HPLC.
Obtained product was colorized gradually by the exposure of air and light.

Analytical Data（Compound 1）

¹H NMR (400 MHz, CDCl₃); δ 6.92 (s, 4H), 2.92 (t, J = 5.9, 8H), 1.54 (m, 8H), 1.32 (m, 4H).

Other References

• A Simple Catalytic Method for the Conversion of Aryl Bromides to Arylamines
  • A. S. Guram, R. A. Rennels, S. L. Buchwald, Angew. Chem. Int. Ed. 1995, 34, 1348.

• Palladium-catalyzed synthesis of arylamines from aryl halides. Mechanistic studies lead to coupling in the absence of tin reagents
  • J. Louie, J. F. Hartwig, Tetrahedron Lett. 1995, 36, 3609.

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
• H₂O

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 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%).

Experimenter's Comments

Toluene was degassed by refluxing under nitrogen atmosphere.

Analytical Data（N-Phenylethyl-3-phenylpropaneamide）

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).

References

• Palladium-Catalyzed Intramolecular O-Arylation of Enolates:  Application to Benzo[b]furan Synthesis
  • M. C. Willis, D. Taylor, A. T. Gillmore, Org. Lett. 2004, 6, 4755.


Application
C-C Formation Reaction



References

• Highly Efficient and Accelerated Suzuki Aryl Couplings Mediated by Phosphine-Free Palladium Sources
  • T. I. Wallow, B. M. Novak, J. Org. Chem. 1994, 59, 5034.
• Palladium-catalyzed cross-coupling of allyl halides with organotins
  • F. K. Sheffy, J. K. Stille, J. Am. Chem. Soc. 1983, 105, 7173.
• Heck Reactions in the Presence of P(t-Bu)3:  Expanded Scope and Milder Reaction Conditions for the Coupling of Aryl Chlorides
  • A. F. Littke, G. C. Fu, J. Org. Chem. 1999, 64, 10.
• Scope and Limitations of the Pd/BINAP-Catalyzed Amination of Aryl Bromides
  • J. P. Wolfe, S. L. Buchwald, J. Org. Chem. 2000, 65, 1144.
• Synthesis of 7H-indolo[2,3-c]quinolines: study of the Pd-catalyzed intramolecular arylation of 3-(2-bromophenylamino)quinolines under microwave irradiation
  • S. Hostyn, B. U. W. Maes, G. Van Baelen, A. Gulevskaya, C. Meyers, K. Smits, Tetrahedron 2006, 62, 4676.


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