2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl

• 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

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%).

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.

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).

• 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.

• 2-Chlorophenothiazine [C0248]
• Tributyl(2-thienyl)tin
• Palladium(II) Acetate (Purified) [P2161]
• 2-Dicyclohexylphosphino-2’,4’,6’-triisopropylbiphenyl (Xphos) [D5038]
• Cesium Fluoride [C2204]
• Toluene

To a solution of palladium(II) acetate (44.9 mg, 0.200 mmol, 4 mol%), XPhos (143 mg, 0.300 mmol, 6 mol%), cesium fluoride (2.28 g, 15.0 mmol) and 2-chlorophenothiazine (1.17 g, 5.00 mmol) in toluene (15.0 mL) was added tributyl(2-thienyl)tin (2.24 g, 1.90 mL, 6.00 mmol) and the reaction solution was stirred at 80 ºC for 24 h. After reaction mixture was cooled to room temperature, dichloromethane (15 mL) and H₂O (15 mL) were added. Separated water phase was extracted with dichloromethane (15 mL) for 3 times. Combined organic layer was dried over MgSO₄ (10 g) and concentrated under reduced pressure to afford the crude product as a brown solid. Crude was purified by column chromatography on silica-gel (hexane: EtOAc = 50 : 1 ~ 5 : 1 → dichloromethane) to afford 2-(thiophen-2-yl)-10H-phenothiazine as a yellow solid (990 mg, 3.51 mmol, 70%).

Completion of the reaction was confirmed by TLC (Hexane:EtOAc = 10:1, Rf: S.M.=0.28 T.M.=0.18) and GC.

¹H NMR (400 MHz, CDCl₃); δ 7.92 (brs, 1H), 7.42 (dd, J = 0.9, 5.0 Hz, 1H), 7.35 (dd, J = 0.9, 3.6 Hz, 1H), 7.08-7.13 (m, 2H), 6.94-7.03 (m, 4H), 6.73-6.82 (m, 2H).

• Rapid Access to New Angular Phenothiazine and Phenoxazine Dyes
  • E. A. Onoabedje, U. C. Okoro, D. W. Knight, J. Heterocycl. Chem. 2017, 54, 206.

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

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%).

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

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.

• 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.