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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.
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%).
Experimenter's Comments
Completion of the reaction was confirmed by TLC (Hexane:EtOAc = 10:1, Rf: S.M.=0.28 T.M.=0.18) and GC.
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.
Expanding Pd-Catalyzed C−N Bond-Forming Processes: The First Amidation of Aryl Sulfonates, Aqueous Amination, and Complementarity with Cu-Catalyzed Reactions
