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CAS No. : | 3857-83-8 | MDL No. : | MFCD00192341 |
Formula : | C11H7F3O3S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | MDWRQYBWVTXIIJ-UHFFFAOYSA-N |
M.W : | 276.23 | Pubchem ID : | 4546341 |
Synonyms : |
|
Num. heavy atoms : | 18 |
Num. arom. heavy atoms : | 10 |
Fraction Csp3 : | 0.09 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 6.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 59.6 |
TPSA : | 51.75 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.97 cm/s |
Log Po/w (iLOGP) : | 1.89 |
Log Po/w (XLOGP3) : | 4.25 |
Log Po/w (WLOGP) : | 5.41 |
Log Po/w (MLOGP) : | 2.91 |
Log Po/w (SILICOS-IT) : | 2.3 |
Consensus Log Po/w : | 3.35 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -4.44 |
Solubility : | 0.00995 mg/ml ; 0.000036 mol/l |
Class : | Moderately soluble |
Log S (Ali) : | -5.05 |
Solubility : | 0.00247 mg/ml ; 0.00000895 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -4.62 |
Solubility : | 0.00657 mg/ml ; 0.0000238 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.59 |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P280-P305+P351+P338-P310 | UN#: | 3261 |
Hazard Statements: | H314 | Packing Group: | Ⅱ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium acetate In dimethyl sulfoxide at 60℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With triphenyl-arsane In N,N-dimethyl-formamide at 60℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With triphenyl-arsane In N,N-dimethyl-formamide at 60℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With pyridine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; | |
99% | With pyridine In dichloromethane at 25℃; for 16h; Inert atmosphere; | |
99% | With pyridine In dichloromethane at 0 - 20℃; |
97% | With triethylamine In dichloromethane at -20℃; for 2h; | |
97% | With pyridine In dichloromethane at 20℃; Inert atmosphere; Cooling with ice; | General Procedure A: General synthesis of aryl triflates General procedure: To a flame-dried 25 mL round-bottom flask fitted with a rubber septum and equipped with a magnetic stir bar was added phenol (1.0 equiv). The contents were evacuated and backfilled three times with nitrogen. Anhydrous DCM (0.7 M) and distilled pyridine (4.2 equiv) were added via syringe and the stirred solution was cooled in an ice bath for 10 min. Triflic anhydride (1.4 equiv) was added dropwise over 5 min. The reaction was slowly warmed to room temperature. After 10-14 h, the reaction was diluted with Et2O (30 mL) and quenched with 1 M aqueous HCl (30 mL). The organic layer was extracted. The organic layer washed with water (2 x 25mL), then brine (25 mL), dried over MgSO4, filtered, and concentrated via rotary evaporation. The aryl triflate was purified by flash chromatography (gradient 2-20% EtOAc/hexanes over 45 column volumes. |
97% | With pyridine In dichloromethane at 0℃; for 2h; Inert atmosphere; | Procedure A. Preparation of Aryl Trifluoromethanesulfonates General procedure: Prepared following an adaptation of the published procedure.7 To a cooled (0 °C), stirred solution of the phenol (10 mmol) and pyridine (20 mmol) in CH2Cl2 (50 mL) under Ar or N2 was added via syringe trifluoromethanesulfonic anhydride (13 mmol). After stirring for 1-3 h, the reaction mixture was treated with aq satd NH4Cl. The CH2Cl2 phase was separated and washed sequentially with aqueous copper sulfate (2x) and H2O and dried (MgSO4). Filtration, concentration of the filtrate in vacuo and purification afforded the product. |
96% | With pyridine In dichloromethane at 0℃; for 0.25h; | |
96% | With pyridine In dichloromethane at 0 - 25℃; Inert atmosphere; | |
96% | With pyridine In dichloromethane at 0 - 25℃; for 5h; Inert atmosphere; | |
96% | With pyridine In dichloromethane at 0 - 20℃; for 5h; Schlenk technique; Inert atmosphere; | |
95% | With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere; | |
95% | With pyridine at 20℃; for 24h; | |
93% | With 4-dimethylaminopyridine; triethylamine In dichloromethane at 0℃; for 2h; Inert atmosphere; | |
92% | With pyridine Ambient temperature; | |
92% | With pyridine In dichloromethane at 20℃; for 1h; | |
91% | With pyridine In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere; | |
91% | With triethylamine In dichloromethane at 0 - 20℃; Schlenk technique; Inert atmosphere; | |
91% | With pyridine In dichloromethane at -78 - 20℃; for 16h; | |
88% | With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere; | |
88% | With pyridine In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere; | |
87% | With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere; | |
84% | With pyridine at 0 - 20℃; for 22h; | |
82% | With pyridine In dichloromethane at 0 - 20℃; | |
82% | With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere; | |
81% | With 2,6-di-tert-butyl-4-methylpyridine In dichloromethane for 4h; Ambient temperature; | |
78% | With pyridine In dichloromethane at 0 - 20℃; for 1.25h; Inert atmosphere; | General procedure: A solution of 2-naphthol(200 mg, 1.4 mmol) in 25 ml CH2Cl2 was cooled to 0 °C under an atmosphere of nitrogen. Pyridine (135 µl, 1.67 mmol)and subsequently trifluormethanesulfonic anhydride (0.33 ml, 1.95 mmol)was added dropwise in 15 min. The mixture was stirred for 1 h at 0 °C, before it was washed with saturated Na2CO3 solution and brine. The organic layer was dried over anhydrous MgSO4. Evaporation of the solvent and purification by flash chromatography on silica gel (petroleum ether) afforded 3c(299 mg, 1.09 mmol, 78 %) as colorless solid. |
76% | With pyridine In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere; | |
69% | Stage #1: β-naphthol With tripotassium phosphate tribasic In lithium hydroxide monohydrate; toluene at 0℃; for 0.5h; Stage #2: trifluoromethylsulfonic anhydride In lithium hydroxide monohydrate; toluene at 0℃; for 0.5h; | |
64% | With potassium carbonate In toluene at 0 - 20℃; | |
41% | With pyridine In dichloromethane at 20℃; for 2h; | |
35% | With pyridine; diethyl phenylmethanephosphonate In dichloromethane at 20℃; for 12h; | |
In dichloromethane at 0℃; for 3h; | ||
Stage #1: trifluoromethylsulfonic anhydride With pyridine; N-(4-methoxyphenyl)-2,2-dimethylpropanamide In dichloromethane at -78℃; for 0.0833333h; Inert atmosphere; Stage #2: β-naphthol In dichloromethane at 0 - 25℃; for 3h; Inert atmosphere; | ||
With triethylamine In toluene at 20℃; Flow reactor; | ||
With tripotassium phosphate tribasic In lithium hydroxide monohydrate; toluene at 0 - 20℃; for 0.5h; | ||
With pyridine In dichloromethane at 25℃; for 5h; Inert atmosphere; | ||
With triethylamine In dichloromethane at 0 - 20℃; | ||
With pyridine at 0 - 25℃; | ||
With pyridine In dichloromethane at 0 - 25℃; for 12h; Inert atmosphere; | 4.2. Synthesis of starting materials General procedure: After phenols and pyridine were dissolved in dry DCM, triflic anhydridewas added slowly by syringe over 5 min at 0 °C. Then the reaction mixture was allowed to bewarmed up to 25 °C and further stirred at 25 °C for 12 h. After the reaction mixture was quenche dwith water, the aqueous layer was extracted with CH2Cl2 and the combined organic layer was dried over Na2SO4 and then filtrated. The products were purified by regular flash chromatography (petroleumether/EtOAc mixtures) [10]. | |
With pyridine In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere; | ||
With triethylamine Inert atmosphere; | ||
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 3h; | ||
With triethylamine In dichloromethane at 0 - 20℃; Schlenk technique; Inert atmosphere; | ||
With pyridine In dichloromethane at 20℃; | ||
With pyridine In dichloromethane at 0 - 25℃; for 12h; Inert atmosphere; | 2. Synthesis of starting materials. General procedure: Under N2 atmosphere, phenols and pyridine were dissolved in dry CH2Cl2, then, triflic anhydride was added slowly by syringe over 5 min at 0°C. Then the reaction mixture was allowed to be warmed up to 25°C and further stirred at 25°C for 12 h. After the reaction mixture was quenched with water, the aqueous layer was extracted with CH2Cl2 and the combined organic layer was dried over Na2SO4 and then filtrated. The products were purified by regular flash chromatography (petroleum ether/EtOAc mixtures).1 | |
Stage #1: β-naphthol With pyridine In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: trifluoromethylsulfonic anhydride In dichloromethane at 20℃; Inert atmosphere; | ||
With pyridine In dichloromethane at 0 - 20℃; for 5h; Inert atmosphere; Schlenk technique; Sealed tube; | ||
With pyridine In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere; | ||
Stage #1: β-naphthol With pyridine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: trifluoromethylsulfonic anhydride In dichloromethane at 20℃; for 2h; | 1.1 (1) Synthesis of 8-aldehyde-2-naphthol Under a nitrogen atmosphere at 0° C., 2-naphthol (28.8 g, 200 mmol) and pyridine (24 mL, 300 mmol) were dissolved in dichloromethane (150 mL), and then the mixture was stirred at 0° C. for 0.5 h. Then trifluoromethanesulfonic anhydride (48 mL, 300 mmol) was slowly added dropwise to the solution. After the addition is complete, return to room temperature and stir for another 2 hours. After the completion of the reaction of the raw materials detected by TLC, a 2.0M hydrochloric acid solution (200 mL) was slowly added dropwise to the reaction solution at 0°C. The mixture was extracted with dichloromethane (3x 100mL), washed with saturated sodium bicarbonate (3x 200mL), washed with saturated brine (200mL), dried with sodium sulfate, filtered, and the solvent was rotary evaporated to obtain a red liquid as the crude product 4-1. After vacuum drying, it was directly used in the next step. | |
With triethylamine In dichloromethane at 0 - 20℃; | 2. General Procedure for Synthesis of Aryl Triflates General procedure: To a solution of phenols (1.0 equiv, 0.5 M) in CH2Cl2 was added Et3N (2 equiv) at 0 °C. The mixture was allowed to stirred at 0 °C for 5 min followed by dropwise addition of Tf2O (1.5 equiv). The reaction mixture was warmed to room temperature and stirred until full consumption of starting materials (monitored by TLC). The resulting mixture was concentrated under reduced pressure and purified by flash column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With palladium diacetate; (C8H17)3SiH; 1,3-bis-(diphenylphosphino)propane; triethylamine In N,N-dimethyl-formamide at 70℃; for 3.5h; | |
69% | With pyridine; hydrogen In N,N-dimethyl-formamide at 80℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 1,1'-bis-(diphenylphosphino)ferrocene; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate In toluene at 100℃; for 5h; | |
93% | In 1-methyl-pyrrolidin-2-one at 198 - 206℃; for 0.75h; microwave irradiation; | |
77% | In toluene | 1 EXAMPLE 1 EXAMPLE 1 Representative example of Method A: N-(2-naphthyl)piperidine STR2 The method described in this example is representative of method "A". Into a screw-capped test tube were weighed 8.6 mg (0.015 mmol) Pd(dba)2, 12.8 mg (0.023 mmol) DPPF, and 44.3 mg (0.462 mmol) sodium t-butoxide (NaO-t-Bu). The solid materials were suspended in 8 ml of toluene. 2-Naphthyltriflate (85.0 mg, 0.308 mmol) was dissolved in 1 ml of toluene and added to the test tube. The test tube was sealed with a cap containing a polytetrafluoroethylene (PTFE) septum and removed from the dry box. Piperidine (40.0 μl, 0.462 mmol) was added to the test tube by syringe. The reaction mixture was heated at 105° C. for 5 hours. Thin layer chromatography (TLC) of the reaction mixture indicated complete consumption of the naphthyltriflate. The reaction mixture was cooled to room temperature, and the volatile materials were removed by rotary evaporation. Sublimation (120° C., 0.1 torr) of the resulting residue afforded N-(2-naphthyl)piperidine as a white solid (50.0 mg, 77% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene on polystyrene.HL In acetonitrile at 80℃; | |
92% | With potassium carbonate In N,N-dimethyl-formamide for 1h; Ambient temperature; | |
92% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With zinc In N,N-dimethyl-formamide at 100 - 110℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: tert-butyl 4-methylidenepiperidine-1-carboxylate With 9-borabicyclo[3.3.1]nonane dimer In tetrahydrofuran for 1h; Heating; Stage #2: 2-naphthyl triflate With potassium carbonate In tetrahydrofuran; water; N,N-dimethyl-formamide at 60℃; for 3h; | |
82% | Stage #1: tert-butyl 4-methylidenepiperidine-1-carboxylate With 9-borabicyclo[3.3.1]nonane dimer In tetrahydrofuran for 1h; Heating; Stage #2: 2-naphthyl triflate With triphenyl-arsane; caesium carbonate In tetrahydrofuran; water; N,N-dimethyl-formamide at 60℃; for 3h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With indium; triphenylphosphine; lithium chloride In N,N-dimethyl-formamide at 100℃; for 1h; | |
92% | With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; indium; triphenylphosphine; lithium chloride In N,N-dimethyl-formamide at 100℃; for 20h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With indium; triphenylphosphine; lithium chloride In N,N-dimethyl-formamide at 100℃; for 1h; | |
86% | With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; indium; triphenylphosphine; lithium chloride In N,N-dimethyl-formamide at 100℃; for 3h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With indium; triphenylphosphine; lithium chloride In N,N-dimethyl-formamide at 100℃; for 1h; | |
83% | With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; indium; triphenylphosphine; lithium chloride In N,N-dimethyl-formamide at 100℃; for 3h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | Stage #1: (2-methylpropyl)lithium With indium(III) chloride In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: carbon monoxide; 2-naphthyl triflate In tetrahydrofuran; hexane at 66℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98 % Chromat. | With triphenylphosphine In benzene at 78℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With palladium diacetate; triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In dimethyl sulfoxide at 70℃; for 17h; | |
94% | With palladium diacetate; triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In dimethyl sulfoxide at 70℃; for 17h; | [[0009]] The following is the general procedure used to make [N-SUCCINIMIDYL] 2- naphthoate (4) (Table 1, Entry [1)] : Scheme 2. 0 0 OSO2CF3 Pd (OAc) 2, ligand CO, Et3N, NHS da4o-N solvent 3 70 C 4 0/ DMSO and triethylamine were degassed by the way of three freeze-thaw cycles and N-hydroxysuccinimide was dried [OVER P205] in vacuum for 24 h. Under argon atmosphere, triethylamine (0.31 mL, 2.25 mmol) was added to a mixture of 2- naphthyl triflate (414.0 mg, 1.5 mmol), [prepared according to Echavarren et al. J. [AM.] [CHERRY.] Soc. 1987, [109,] 5478-5486], palladium acetate (16.8 mg. 0.075 mmol), Xantphos (43.4 mg, 0.075 mmol) and N-hydroxysuccinimide (241.5 mg, 2.1 mmol) in DMSO (2 mL). The solution was purged with carbon monoxide for 15 min and stirred under a CO balloon at [70C] for 17 hours. The reaction mixture was then cooled to room temperature, diluted with 20 mL of ethyl acetate and washed with saturated sodium bicarbonate solution and water. The organic phase was dried over sodium sulfate and evaporated to give crude product. Chromatography on silica gel using hexane: acetone (4: 1) provided [381.] 3 mg (94%) [N-HYDROXYSUCCINIMIDYL] 2- naphthoate as a white crystalline solid. |
90% | With palladium diacetate; triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 70℃; for 17h; | [[0009]] The following is the general procedure used to make [N-SUCCINIMIDYL] 2- naphthoate (4) (Table 1, Entry [1)] : Scheme 2. 0 0 OSO2CF3 Pd (OAc) 2, ligand CO, Et3N, NHS da4o-N solvent 3 70 C 4 0/ DMSO and triethylamine were degassed by the way of three freeze-thaw cycles and N-hydroxysuccinimide was dried [OVER P205] in vacuum for 24 h. Under argon atmosphere, triethylamine (0.31 mL, 2.25 mmol) was added to a mixture of 2- naphthyl triflate (414.0 mg, 1.5 mmol), [prepared according to Echavarren et al. J. [AM.] [CHERRY.] Soc. 1987, [109,] 5478-5486], palladium acetate (16.8 mg. 0.075 mmol), Xantphos (43.4 mg, 0.075 mmol) and N-hydroxysuccinimide (241.5 mg, 2.1 mmol) in DMSO (2 mL). The solution was purged with carbon monoxide for 15 min and stirred under a CO balloon at [70C] for 17 hours. The reaction mixture was then cooled to room temperature, diluted with 20 mL of ethyl acetate and washed with saturated sodium bicarbonate solution and water. The organic phase was dried over sodium sulfate and evaporated to give crude product. Chromatography on silica gel using hexane: acetone (4: 1) provided [381.] 3 mg (94%) [N-HYDROXYSUCCINIMIDYL] 2- naphthoate as a white crystalline solid. [[0010]] We explored the parameters for this conversion using 3, the triflate ester of 2-naphthol. The palladium source [Pd (OAc) 2] and the base [Et3N] were held constant. The temperature and pressure of the carbon monoxide were held at 1 atmosphere CO at 70 [C.] As shown in Scheme 2, we varied the Pd ligand (Xantphos, DPPF, DPPP, BINAP, DCPE, and [PPH3),] solvent (DMSO, DMF, toluene and dioxane), and stoichiometry. For the conversion of 3 to the corresponding active ester 4, we observed that an excellent yield of 94% could be realized using Xantphos (5 mol%) as Pd ligand with a 1: 1.4 : 1.5 molar ratio of 3: NHS [: ET3N] in DMSO for 17 hours. The success of this reaction was not highly dependent on time, in that tlc showed little starting material after 5 hours and little or no product decomposition after 24 hours. [[0011]] Using similar conditions, we found that when Xantphos was replaced with the following [WELL-KNOWN] Pd ligands, lower yields for this conversion were realized: BINAP (32%), DPPF (40%), DPPP (72%), [PPH3] (no reaction with triflate up to 10 mol%) or DCPE (no reaction with triflate up to 10 mol%). Besides the desired product 4 (when formed), the reaction mixtures for these examples contained either starting material or unknown by-products. We also found that the choice of solvent affected the yield. When 3 was subjected to the optimized conditions, replacing DMSO with other solvents known to be useful in Pd catalyzed reactions had the following effect on yield: DMF (59%), dioxane (90%), [THF] (63%), and toluene [(61%).] |
72% | With 1,3-bis-(diphenylphosphino)propane; palladium diacetate; triethylamine In dimethyl sulfoxide at 70℃; for 17h; | [[0009]] The following is the general procedure used to make [N-SUCCINIMIDYL] 2- naphthoate (4) (Table 1, Entry [1)] : Scheme 2. 0 0 OSO2CF3 Pd (OAc) 2, ligand CO, Et3N, NHS da4o-N solvent 3 70 C 4 0/ DMSO and triethylamine were degassed by the way of three freeze-thaw cycles and N-hydroxysuccinimide was dried [OVER P205] in vacuum for 24 h. Under argon atmosphere, triethylamine (0.31 mL, 2.25 mmol) was added to a mixture of 2- naphthyl triflate (414.0 mg, 1.5 mmol), [prepared according to Echavarren et al. J. [AM.] [CHERRY.] Soc. 1987, [109,] 5478-5486], palladium acetate (16.8 mg. 0.075 mmol), Xantphos (43.4 mg, 0.075 mmol) and N-hydroxysuccinimide (241.5 mg, 2.1 mmol) in DMSO (2 mL). The solution was purged with carbon monoxide for 15 min and stirred under a CO balloon at [70C] for 17 hours. The reaction mixture was then cooled to room temperature, diluted with 20 mL of ethyl acetate and washed with saturated sodium bicarbonate solution and water. The organic phase was dried over sodium sulfate and evaporated to give crude product. Chromatography on silica gel using hexane: acetone (4: 1) provided [381.] 3 mg (94%) [N-HYDROXYSUCCINIMIDYL] 2- naphthoate as a white crystalline solid. [[0010]] We explored the parameters for this conversion using 3, the triflate ester of 2-naphthol. The palladium source [Pd (OAc) 2] and the base [Et3N] were held constant. The temperature and pressure of the carbon monoxide were held at 1 atmosphere CO at 70 [C.] As shown in Scheme 2, we varied the Pd ligand (Xantphos, DPPF, DPPP, BINAP, DCPE, and [PPH3),] solvent (DMSO, DMF, toluene and dioxane), and stoichiometry. For the conversion of 3 to the corresponding active ester 4, we observed that an excellent yield of 94% could be realized using Xantphos (5 mol%) as Pd ligand with a 1: 1.4 : 1.5 molar ratio of 3: NHS [: ET3N] in DMSO for 17 hours. The success of this reaction was not highly dependent on time, in that tlc showed little starting material after 5 hours and little or no product decomposition after 24 hours. [[0011]] Using similar conditions, we found that when Xantphos was replaced with the following [WELL-KNOWN] Pd ligands, lower yields for this conversion were realized: BINAP (32%), DPPF (40%), DPPP (72%), [PPH3] (no reaction with triflate up to 10 mol%) or DCPE (no reaction with triflate up to 10 mol%). Besides the desired product 4 (when formed), the reaction mixtures for these examples contained either starting material or unknown by-products. We also found that the choice of solvent affected the yield. When 3 was subjected to the optimized conditions, replacing DMSO with other solvents known to be useful in Pd catalyzed reactions had the following effect on yield: DMF (59%), dioxane (90%), [THF] (63%), and toluene [(61%).] |
63% | With palladium diacetate; triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In tetrahydrofuran at 70℃; for 17h; | [[0009]] The following is the general procedure used to make [N-SUCCINIMIDYL] 2- naphthoate (4) (Table 1, Entry [1)] : Scheme 2. 0 0 OSO2CF3 Pd (OAc) 2, ligand CO, Et3N, NHS da4o-N solvent 3 70 C 4 0/ DMSO and triethylamine were degassed by the way of three freeze-thaw cycles and N-hydroxysuccinimide was dried [OVER P205] in vacuum for 24 h. Under argon atmosphere, triethylamine (0.31 mL, 2.25 mmol) was added to a mixture of 2- naphthyl triflate (414.0 mg, 1.5 mmol), [prepared according to Echavarren et al. J. [AM.] [CHERRY.] Soc. 1987, [109,] 5478-5486], palladium acetate (16.8 mg. 0.075 mmol), Xantphos (43.4 mg, 0.075 mmol) and N-hydroxysuccinimide (241.5 mg, 2.1 mmol) in DMSO (2 mL). The solution was purged with carbon monoxide for 15 min and stirred under a CO balloon at [70C] for 17 hours. The reaction mixture was then cooled to room temperature, diluted with 20 mL of ethyl acetate and washed with saturated sodium bicarbonate solution and water. The organic phase was dried over sodium sulfate and evaporated to give crude product. Chromatography on silica gel using hexane: acetone (4: 1) provided [381.] 3 mg (94%) [N-HYDROXYSUCCINIMIDYL] 2- naphthoate as a white crystalline solid. [[0010]] We explored the parameters for this conversion using 3, the triflate ester of 2-naphthol. The palladium source [Pd (OAc) 2] and the base [Et3N] were held constant. The temperature and pressure of the carbon monoxide were held at 1 atmosphere CO at 70 [C.] As shown in Scheme 2, we varied the Pd ligand (Xantphos, DPPF, DPPP, BINAP, DCPE, and [PPH3),] solvent (DMSO, DMF, toluene and dioxane), and stoichiometry. For the conversion of 3 to the corresponding active ester 4, we observed that an excellent yield of 94% could be realized using Xantphos (5 mol%) as Pd ligand with a 1: 1.4 : 1.5 molar ratio of 3: NHS [: ET3N] in DMSO for 17 hours. The success of this reaction was not highly dependent on time, in that tlc showed little starting material after 5 hours and little or no product decomposition after 24 hours. [[0011]] Using similar conditions, we found that when Xantphos was replaced with the following [WELL-KNOWN] Pd ligands, lower yields for this conversion were realized: BINAP (32%), DPPF (40%), DPPP (72%), [PPH3] (no reaction with triflate up to 10 mol%) or DCPE (no reaction with triflate up to 10 mol%). Besides the desired product 4 (when formed), the reaction mixtures for these examples contained either starting material or unknown by-products. We also found that the choice of solvent affected the yield. When 3 was subjected to the optimized conditions, replacing DMSO with other solvents known to be useful in Pd catalyzed reactions had the following effect on yield: DMF (59%), dioxane (90%), [THF] (63%), and toluene [(61%).] |
61% | With palladium diacetate; triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 70℃; for 17h; | [[0009]] The following is the general procedure used to make [N-SUCCINIMIDYL] 2- naphthoate (4) (Table 1, Entry [1)] : Scheme 2. 0 0 OSO2CF3 Pd (OAc) 2, ligand CO, Et3N, NHS da4o-N solvent 3 70 C 4 0/ DMSO and triethylamine were degassed by the way of three freeze-thaw cycles and N-hydroxysuccinimide was dried [OVER P205] in vacuum for 24 h. Under argon atmosphere, triethylamine (0.31 mL, 2.25 mmol) was added to a mixture of 2- naphthyl triflate (414.0 mg, 1.5 mmol), [prepared according to Echavarren et al. J. [AM.] [CHERRY.] Soc. 1987, [109,] 5478-5486], palladium acetate (16.8 mg. 0.075 mmol), Xantphos (43.4 mg, 0.075 mmol) and N-hydroxysuccinimide (241.5 mg, 2.1 mmol) in DMSO (2 mL). The solution was purged with carbon monoxide for 15 min and stirred under a CO balloon at [70C] for 17 hours. The reaction mixture was then cooled to room temperature, diluted with 20 mL of ethyl acetate and washed with saturated sodium bicarbonate solution and water. The organic phase was dried over sodium sulfate and evaporated to give crude product. Chromatography on silica gel using hexane: acetone (4: 1) provided [381.] 3 mg (94%) [N-HYDROXYSUCCINIMIDYL] 2- naphthoate as a white crystalline solid. [[0010]] We explored the parameters for this conversion using 3, the triflate ester of 2-naphthol. The palladium source [Pd (OAc) 2] and the base [Et3N] were held constant. The temperature and pressure of the carbon monoxide were held at 1 atmosphere CO at 70 [C.] As shown in Scheme 2, we varied the Pd ligand (Xantphos, DPPF, DPPP, BINAP, DCPE, and [PPH3),] solvent (DMSO, DMF, toluene and dioxane), and stoichiometry. For the conversion of 3 to the corresponding active ester 4, we observed that an excellent yield of 94% could be realized using Xantphos (5 mol%) as Pd ligand with a 1: 1.4 : 1.5 molar ratio of 3: NHS [: ET3N] in DMSO for 17 hours. The success of this reaction was not highly dependent on time, in that tlc showed little starting material after 5 hours and little or no product decomposition after 24 hours. [[0011]] Using similar conditions, we found that when Xantphos was replaced with the following [WELL-KNOWN] Pd ligands, lower yields for this conversion were realized: BINAP (32%), DPPF (40%), DPPP (72%), [PPH3] (no reaction with triflate up to 10 mol%) or DCPE (no reaction with triflate up to 10 mol%). Besides the desired product 4 (when formed), the reaction mixtures for these examples contained either starting material or unknown by-products. We also found that the choice of solvent affected the yield. When 3 was subjected to the optimized conditions, replacing DMSO with other solvents known to be useful in Pd catalyzed reactions had the following effect on yield: DMF (59%), dioxane (90%), [THF] (63%), and toluene [(61%).] |
59% | With palladium diacetate; triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In DMF (N,N-dimethyl-formamide) at 70℃; for 17h; | [[0009]] The following is the general procedure used to make [N-SUCCINIMIDYL] 2- naphthoate (4) (Table 1, Entry [1)] : Scheme 2. 0 0 OSO2CF3 Pd (OAc) 2, ligand CO, Et3N, NHS da4o-N solvent 3 70 C 4 0/ DMSO and triethylamine were degassed by the way of three freeze-thaw cycles and N-hydroxysuccinimide was dried [OVER P205] in vacuum for 24 h. Under argon atmosphere, triethylamine (0.31 mL, 2.25 mmol) was added to a mixture of 2- naphthyl triflate (414.0 mg, 1.5 mmol), [prepared according to Echavarren et al. J. [AM.] [CHERRY.] Soc. 1987, [109,] 5478-5486], palladium acetate (16.8 mg. 0.075 mmol), Xantphos (43.4 mg, 0.075 mmol) and N-hydroxysuccinimide (241.5 mg, 2.1 mmol) in DMSO (2 mL). The solution was purged with carbon monoxide for 15 min and stirred under a CO balloon at [70C] for 17 hours. The reaction mixture was then cooled to room temperature, diluted with 20 mL of ethyl acetate and washed with saturated sodium bicarbonate solution and water. The organic phase was dried over sodium sulfate and evaporated to give crude product. Chromatography on silica gel using hexane: acetone (4: 1) provided [381.] 3 mg (94%) [N-HYDROXYSUCCINIMIDYL] 2- naphthoate as a white crystalline solid. [[0010]] We explored the parameters for this conversion using 3, the triflate ester of 2-naphthol. The palladium source [Pd (OAc) 2] and the base [Et3N] were held constant. The temperature and pressure of the carbon monoxide were held at 1 atmosphere CO at 70 [C.] As shown in Scheme 2, we varied the Pd ligand (Xantphos, DPPF, DPPP, BINAP, DCPE, and [PPH3),] solvent (DMSO, DMF, toluene and dioxane), and stoichiometry. For the conversion of 3 to the corresponding active ester 4, we observed that an excellent yield of 94% could be realized using Xantphos (5 mol%) as Pd ligand with a 1: 1.4 : 1.5 molar ratio of 3: NHS [: ET3N] in DMSO for 17 hours. The success of this reaction was not highly dependent on time, in that tlc showed little starting material after 5 hours and little or no product decomposition after 24 hours. [[0011]] Using similar conditions, we found that when Xantphos was replaced with the following [WELL-KNOWN] Pd ligands, lower yields for this conversion were realized: BINAP (32%), DPPF (40%), DPPP (72%), [PPH3] (no reaction with triflate up to 10 mol%) or DCPE (no reaction with triflate up to 10 mol%). Besides the desired product 4 (when formed), the reaction mixtures for these examples contained either starting material or unknown by-products. We also found that the choice of solvent affected the yield. When 3 was subjected to the optimized conditions, replacing DMSO with other solvents known to be useful in Pd catalyzed reactions had the following effect on yield: DMF (59%), dioxane (90%), [THF] (63%), and toluene [(61%).] |
40% | With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine In dimethyl sulfoxide at 70℃; for 17h; | [[0009]] The following is the general procedure used to make [N-SUCCINIMIDYL] 2- naphthoate (4) (Table 1, Entry [1)] : Scheme 2. 0 0 OSO2CF3 Pd (OAc) 2, ligand CO, Et3N, NHS da4o-N solvent 3 70 C 4 0/ DMSO and triethylamine were degassed by the way of three freeze-thaw cycles and N-hydroxysuccinimide was dried [OVER P205] in vacuum for 24 h. Under argon atmosphere, triethylamine (0.31 mL, 2.25 mmol) was added to a mixture of 2- naphthyl triflate (414.0 mg, 1.5 mmol), [prepared according to Echavarren et al. J. [AM.] [CHERRY.] Soc. 1987, [109,] 5478-5486], palladium acetate (16.8 mg. 0.075 mmol), Xantphos (43.4 mg, 0.075 mmol) and N-hydroxysuccinimide (241.5 mg, 2.1 mmol) in DMSO (2 mL). The solution was purged with carbon monoxide for 15 min and stirred under a CO balloon at [70C] for 17 hours. The reaction mixture was then cooled to room temperature, diluted with 20 mL of ethyl acetate and washed with saturated sodium bicarbonate solution and water. The organic phase was dried over sodium sulfate and evaporated to give crude product. Chromatography on silica gel using hexane: acetone (4: 1) provided [381.] 3 mg (94%) [N-HYDROXYSUCCINIMIDYL] 2- naphthoate as a white crystalline solid. [[0010]] We explored the parameters for this conversion using 3, the triflate ester of 2-naphthol. The palladium source [Pd (OAc) 2] and the base [Et3N] were held constant. The temperature and pressure of the carbon monoxide were held at 1 atmosphere CO at 70 [C.] As shown in Scheme 2, we varied the Pd ligand (Xantphos, DPPF, DPPP, BINAP, DCPE, and [PPH3),] solvent (DMSO, DMF, toluene and dioxane), and stoichiometry. For the conversion of 3 to the corresponding active ester 4, we observed that an excellent yield of 94% could be realized using Xantphos (5 mol%) as Pd ligand with a 1: 1.4 : 1.5 molar ratio of 3: NHS [: ET3N] in DMSO for 17 hours. The success of this reaction was not highly dependent on time, in that tlc showed little starting material after 5 hours and little or no product decomposition after 24 hours. [[0011]] Using similar conditions, we found that when Xantphos was replaced with the following [WELL-KNOWN] Pd ligands, lower yields for this conversion were realized: BINAP (32%), DPPF (40%), DPPP (72%), [PPH3] (no reaction with triflate up to 10 mol%) or DCPE (no reaction with triflate up to 10 mol%). Besides the desired product 4 (when formed), the reaction mixtures for these examples contained either starting material or unknown by-products. We also found that the choice of solvent affected the yield. When 3 was subjected to the optimized conditions, replacing DMSO with other solvents known to be useful in Pd catalyzed reactions had the following effect on yield: DMF (59%), dioxane (90%), [THF] (63%), and toluene [(61%).] |
32% | With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; triethylamine In dimethyl sulfoxide at 70℃; for 17h; | [[0009]] The following is the general procedure used to make [N-SUCCINIMIDYL] 2- naphthoate (4) (Table 1, Entry [1)] : Scheme 2. 0 0 OSO2CF3 Pd (OAc) 2, ligand CO, Et3N, NHS da4o-N solvent 3 70 C 4 0/ DMSO and triethylamine were degassed by the way of three freeze-thaw cycles and N-hydroxysuccinimide was dried [OVER P205] in vacuum for 24 h. Under argon atmosphere, triethylamine (0.31 mL, 2.25 mmol) was added to a mixture of 2- naphthyl triflate (414.0 mg, 1.5 mmol), [prepared according to Echavarren et al. J. [AM.] [CHERRY.] Soc. 1987, [109,] 5478-5486], palladium acetate (16.8 mg. 0.075 mmol), Xantphos (43.4 mg, 0.075 mmol) and N-hydroxysuccinimide (241.5 mg, 2.1 mmol) in DMSO (2 mL). The solution was purged with carbon monoxide for 15 min and stirred under a CO balloon at [70C] for 17 hours. The reaction mixture was then cooled to room temperature, diluted with 20 mL of ethyl acetate and washed with saturated sodium bicarbonate solution and water. The organic phase was dried over sodium sulfate and evaporated to give crude product. Chromatography on silica gel using hexane: acetone (4: 1) provided [381.] 3 mg (94%) [N-HYDROXYSUCCINIMIDYL] 2- naphthoate as a white crystalline solid. [[0010]] We explored the parameters for this conversion using 3, the triflate ester of 2-naphthol. The palladium source [Pd (OAc) 2] and the base [Et3N] were held constant. The temperature and pressure of the carbon monoxide were held at 1 atmosphere CO at 70 [C.] As shown in Scheme 2, we varied the Pd ligand (Xantphos, DPPF, DPPP, BINAP, DCPE, and [PPH3),] solvent (DMSO, DMF, toluene and dioxane), and stoichiometry. For the conversion of 3 to the corresponding active ester 4, we observed that an excellent yield of 94% could be realized using Xantphos (5 mol%) as Pd ligand with a 1: 1.4 : 1.5 molar ratio of 3: NHS [: ET3N] in DMSO for 17 hours. The success of this reaction was not highly dependent on time, in that tlc showed little starting material after 5 hours and little or no product decomposition after 24 hours. [[0011]] Using similar conditions, we found that when Xantphos was replaced with the following [WELL-KNOWN] Pd ligands, lower yields for this conversion were realized: BINAP (32%), DPPF (40%), DPPP (72%), [PPH3] (no reaction with triflate up to 10 mol%) or DCPE (no reaction with triflate up to 10 mol%). Besides the desired product 4 (when formed), the reaction mixtures for these examples contained either starting material or unknown by-products. We also found that the choice of solvent affected the yield. When 3 was subjected to the optimized conditions, replacing DMSO with other solvents known to be useful in Pd catalyzed reactions had the following effect on yield: DMF (59%), dioxane (90%), [THF] (63%), and toluene [(61%).] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 85℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: 2-naphthyl triflate With bis(bis(trimethylsilyl)amido)zinc(II); tri-tert-butyl phosphine; tetrabutylammomium bromide In tetrahydrofuran at 50℃; for 9h; Stage #2: With hydrogenchloride In tetrahydrofuran; diethyl ether |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73.3% | With palladium diacetate; N-ethyl-N,N-diisopropylamine; 1,4-di(diphenylphosphino)-butane In dimethyl sulfoxide at 95℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With tris(2,4-pentanedionato)ruthenium(III); 3,4,7,8-Tetramethyl-o-phenanthrolin; ethylmagnesium bromide; lithium bromide In 1,4-dioxane at 120℃; for 48h; | |
91% | With [Cp*Ru(CH3CN)3]OTf; lithium bromide at 100℃; for 6h; Inert atmosphere; | |
81% | With potassium fluoride; tris-(dibenzylideneacetone)dipalladium(0); t-BuBrettPhos; potassium bromide In 1,4-dioxane at 130℃; for 16h; Inert atmosphere; |
Multi-step reaction with 2 steps 1: 98 percent / Et3N / PdCl2(dppf) / dioxane / Heating 2: 79 percent / aq. CuBr2 / methanol / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 84% 2: 3% | With indium(III) chloride; indium; lithium chloride In N,N-dimethyl-formamide at 100℃; for 2h; | |
1: 68 % Chromat. 2: 10 % Chromat. | With indium(III) chloride; indium; lithium chloride In N,N-dimethyl-formamide at 100℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With potassium acetate; triphenylphosphine In N,N-dimethyl-formamide at 150℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With bis(1,5-cyclooctadiene)nickel(0); caesium carbonate; 1,2-bis-(dicyclohexylphosphino)ethane In 1,4-dioxane at 120℃; for 12h; Inert atmosphere; Sealed tube; | 29 Example 29 [0115] 2-(Naphthalen-2-yl)benzoxazole was obtained in the same manner as in Example 1, except using naphthalen-2-yl triflate instead of naphthalen-2-yl pivalate. The yield thereof was about 100%. |
86% | With caesium carbonate; triphenylphosphine In N,N-dimethyl-formamide at 150℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With tol-BINAP; copper(I) oxide; 1,10-Phenanthroline; palladium(II) bromide In 1-methyl-pyrrolidin-2-one at 50 - 190℃; Microwave irradiation; Inert atmosphere; | |
62% | With tol-BINAP; copper(I) oxide; 1,10-Phenanthroline; palladium(II) iodide In 1-methyl-pyrrolidin-2-one at 170℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With tol-BINAP; copper(I) oxide; 1,10-Phenanthroline; palladium(II) acetylacetonate In 1-methyl-pyrrolidin-2-one at 50 - 190℃; Inert atmosphere; Microwave irradiation; | |
98% | With copper(I) oxide; 1,10-Phenanthroline; Tri(p-tolyl)phosphine; palladium(II) iodide In 1-methyl-pyrrolidin-2-one at 170℃; for 1h; | |
72% | With 2,6-dimethylpyridine; triphenylphosphine; silver carbonate; palladium dichloride In 1-methyl-pyrrolidin-2-one at 130℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With tris-(dibenzylideneacetone)dipalladium(0); t-BuBrettPhos; tris(3,5-dioxaheptyl)amine; sodium nitrite In <i>tert</i>-butyl alcohol at 130℃; Schlenk technique; Inert atmosphere; | |
87% | With tris-(dibenzylideneacetone)dipalladium(0); t-BuBrettPhos; tris(3,5-dioxaheptyl)amine; sodium nitrite In <i>tert</i>-butyl alcohol at 130℃; for 24h; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With trans-chloro(1-naphthyl)bis-(triphenylphosphine)nickel(II); potassium carbonate; triphenylphosphine In toluene at 100℃; for 5h; Inert atmosphere; | |
55% | With tripotassium phosphate monohydrate; [{C4H2N-2,5-(CH2PPh2)2-κ3PNP}NiCl] In toluene at 130℃; for 16h; Inert atmosphere; | 4.4. General procedure for Suzuki-Miyaura reactions General procedure: A Schlenk flask was charged with catalyst (1-5mol%), electrophile (1.0 equiv.), boronic acid (1.4 equiv.), K3PO4·H2O (2.5 equiv.) and 15mL of toluene. The mixture was heated to 130°C and allowed to stir for 16h under an atmosphere of nitrogen. After this time, the reaction was allowed to cool and quenched with 10mL of a saturated aqueous oxalic acid solution. The resulting biphasic mixture was diluted with 20mL of diethyl ether and the organic layer separated and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated to dryness. Cross-coupled products were then purified by silica gel chromatography using 5-10% ethyl acetate in hexanes. 1H NMR spectroscopy of the isolated products in CDCl3 was used to confirm identity. |
With potassium fluoride; palladium diacetate; tricyclohexylphosphine In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 18h; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: 2-naphthyl triflate With water; palladium diacetate; caesium carbonate; sodium thiosulfate; XPhos In toluene; <i>tert</i>-butyl alcohol at 80℃; for 24h; Inert atmosphere; Stage #2: With hydrogenchloride; zinc In water for 1h; Cooling with ice; | 2.2. General procedure for Table 3 An oven-dried Schlenk tube was charged with Pd(OAc)2 (11.2 mg) and Xphos (71.5 mg), equipped with a magnetic stir bar. The tube was evacuated and backfilled with argon three times before tBuOH (4 mL)/toluene (6 mL) and H2O (180 μL) was added. The solution was heated to 110 °C for 1.5 min. One millilitre of the solution was transferred to another oven-dried Schlenk tube, which was charged with aryl halides 1 (0.5 mmol), sodium thiosulfate 2 (100 mg), Cs2CO3 (1 mmol, 325 mg) equipped with a magnetic stir bar. Then the tube was stirred at 80 °C for 24 h. The solid substance was separated from the reaction mixture and washed with ether. Zn dust (0.5 g) and HCl (10%, 5 mL) were added to the solid substance with cooling by ice-water. After stirred for 1 h, the mixture was extracted with ethyl acetate. The organic layer was washed with H2O and brine and dried over Na2SO4. Removal of solvent in vacuo provided the desired product with satisfactory purity. Some relatively stable products were purified via column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With cesium fluoride;bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; t-BuBrettPhos; In toluene; at 110℃;Sealed tube; | General Procedure 3. In a nitrogen-filled glovebox, [(cinammyl)PdCl]2 (2.5 mg, 5.0 mummol, 2.5 mol %), tBuBrettPhos, MeBuBrettPhos or iPrtBuBrettPhos (15 mummol, 7.5 mol %) and cesium fluoride (76 mg, 0.5 mmol, 2 eq) were added to a screw-cap vial. Then, solvent (1 mL) and aryl triflate (0.25 mmol) were added. The vial was capped, taken out of the glovebox and stirred for 12-15 h at T C. After the mixture cooled to RT, 4-fluorotoluene (28 muL, 0.25 mmol, 1 eq.) was added and the yield and regioselectivity was determined by 19F-NMR. 2-Fluoronaphthelene. According to procedure 3,2-naphthyl trifluoromethanesulfonate (69 mg) was transformed (T=110 C., L=tBuBrettPhos, solvent=toluene, NMR yield=77%, no regioisomers). 19F-NMR: delta=-114.9 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran; diethyl ether for 6h; Reflux; | |
90% | With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran; diethyl ether for 6h; Reflux; Inert atmosphere; | 4.3.1. Typical procedure for the synthesis of β,β-difluorostyrenes 4 General procedure: To the solution of 2 (0.125 M in THF and diethyl ether, 7.6 mL,0.95 mmol) were added a solution of 4-iodoanisole (3b, 189 mg, 0.81 mmol) in THF (1.5 mL) and Pd(PPh3)4 (17 mg, 15 mmol). After being refluxed for 6 h, the reaction mixture was filtered through a pad of silica gel (diethyl ether). The filtrate was concentrated under reduced pressure and purified by preparative thin layer chromatography on silica gel (pentane/diethyl ether = 20:1) to give 4b (119 mg, 87%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With potassium carbonate; ruphos In water; toluene at 100℃; for 6h; Inert atmosphere; Sealed vial; | 8 In an open vial with pressure-release top, a stirred mixture of 2- naphthyltrifluoromethanesulfonate (Aldrich, St. Louis, MO) (69 mg, 0.25 mmol), palladium(II) acetate (5.5 mg, 0.025 mmol), 2-dicyclohexylphosphino-2',6'- diisopropoxybiphenyl (23 mg, 0.05 mmol), K2C03 (138 mg, 1.0 mmol) and trans-2- (trifluoromethyl)cyclopropylboronic acid MIDA ester (99 mg, 0.38 mmol) in toluene (2.5 mL) and H20 (0.5 mL) was de-gassed with N2 for 15 minutes, then the reaction mixture placed under nitrogen, sealed and heated to 100 °C and stirred for 6 hours. After allowing to cool, the reaction mixture was diluted with H20 (15 mL) and EtOAc (20 mL), filtered through Celite and the filter cake washed with EtOAc (2 x 20 mL). The filtrate was partitioned and the aqueous layer extracted with EtOAc (2 x 15 mL). The combined organic extracts were dried (Na2S04), filtered and concentrated under vacuum to leave a crude residue. The residue was purified by preparative thin-layer chromatography (2 prep TLC plates used) using EtOAc / hexane (1:99) as eluent to give the product (45.9 mg, 78%) as a solid.[00217] Data identical to above in Example 5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 1h; Inert atmosphere; | General procedure: The utilized base (0.5mmol,2equivalents) was suspended in 1ml solvent under an atmosphere of nitrogen. Nucleophile (0.3mmol, 1.2equivalents) and subsequently triflate(0.25mmol, 1equivalent) dissolved in 1ml solvent were added.The mixture was stirred at 100°C for 1h and subsequently cooled to room temperature, before it was diluted with water. The aqueous layer was extracted four times with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous MgSO4 and the solvents were removed under reduced pressure. The products were obtained by flash chromatography on silica gel (CH2Cl2/methanol 99.5/0.5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With tetrabutylammonium acetate; palladium diacetate at 35℃; for 4h; Green chemistry; | General procedure for the preparation of N-aryl sulfonamides General procedure: A mixture of Pd(OAc)2 (5 mg, 0.02 mmol), aryl source (1 mmol), sulfonamide source (1.0 mmol), Cu(OAc)2 (9 mg, 0.05 mmol; in the presence of sulfonyl azides), and TBAA (2.0 mmol) in PEG-400 (3 g) was stirred for the appropriate time at 35-50°C under air. The crude reaction mixture was diluted with EtOAc (5 mL) and a saturated NH4Cl solution (5 mL). The mixture was stirred for an additional 30 min and the layers were separated. The aqueous layer was extracted with EtOAc (6 mL × 3). The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuo. The residue was purified by column chromatography (silica gel, hexane:EtOAc 1:3) to give the desired product. Spectral data for all compounds except 6c, 6f, and 6n have been reported in previous reports.[19,30,31] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With palladium diacetate; caesium carbonate In toluene at 100℃; for 12h; Sealed tube; Inert atmosphere; | General procedure D for preparation of 3h and 3y with naphthyl bromides and triflates as substrates in Table 3 General procedure: In a sealed vial, under nitrogen, p-methylbenzoyldiphenylphosphine (61 mg, 0.20 mmol, 1.0 equiv), Pd(OAc)2 (1.4 mg, 0.006 mmol), naphthyl bromides or triflates (0.21 mmol, 1.05 equiv), Cs2CO3 (72 mg, 0.22 mmol, 1.1 equiv) and toluene (0.5 mL) were mixed and stirred at 100 oC for 12 h. When reaction completed, the reaction mixture was directly purified by flash column chromatography on silica gel to give pure product. |
85% | With dichloro [1,1'-bis(diphenylphosphino)propane]palladium(II); caesium carbonate In toluene at 100℃; for 12h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With 1,1'-bis-(diphenylphosphino)ferrocene; bis(1,5-cyclooctadiene)nickel (0); sodium carbonate In 1,4-dioxane at 80℃; for 20h; Inert atmosphere; | h 4.3. Typical procedure for the nickel-catalyzed phosphorylation of aryl triflates with P(O)-H compounds General procedure: Under a N2 atmosphere, 0.2 mmol aryl triflate 1a, 0.2 mmol Ph2P(O)H 2a,10 mol% Ni(COD)2, 10 mol% dppf,1.0 equiv Na2CO3 and 2 mL dioxane were charged into a 10 mL schlenck tube. The mixturewas stirred at 80 °C for 20 h. After removal of the volatile, the residues were passed through a short silica chromatography (particlesize 37-54 mm, petroleum ether/ethyl acetate as eluent) toafford analytically pure organophosphorus compounds 3. Purification by chromatography (petroleum ether/EtOAc = 1:1) afforded 3j (57.7 mg, 88%) as a white solid. Rf = 0.29 (petroleum ether/EtOAc = 1:1); 1H NMR (400 MHz CDCl3): δ 8.29 (d, J = 14.0 Hz, 1H), 7.91-7.85 (m, 3H), 7.74-7.44 (m, 13H). 13C NMR (100 MHz CDCl3): δ 134.74 (d, JC-P = 2.2 Hz), 134.05 (d, JC-P = 9.3 Hz), 132.45 (d, JC-P = 103.7 Hz), 132.43 (d, JC-P = 13.2 Hz), 132.17 (d, JC-P = 9.9 Hz), 132.07 (d, JC-P = 2.8 Hz), 129.47 (d, JC-P = 103.8 Hz), 128.99, 128.60 (d, JC-P = 12.1 Hz), 128.37 (d, JC-P = 10.6 Hz), 128.32, 127.86 (d, JC-P = 0.6 Hz), 127.01, 126.84 (d, JC-P = 10.7 Hz). 31P NMR (162 MHz CDCl3): δ 29.51 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In dichloromethane for 2h; | 4. General Procedure for Sulfonation. 3-phenylpropyl methanesulfonate General procedure: In a 50 mL round-bottomed flask, 3-phenylpropan-1-ol (0.136 ml 1 mmol) and triethylamine (0.140 ml, 3 mmol) were added to DCM (25 ml). The methanesulfonyl chloride (0.090 ml, 1.2 mmol) was added slowly and allowed to stir for 2 hours, After the completion of reaction, Add water and reaction mixture was extracted with DCM. Organic layer washed with brine and dried over Na2SO4 and concentrated in vacuo. The title compound was isolated using column chromatography (0-20% EtOAc: hexane) gave 0.192 mg 90% colorless oil. | |
With triethylamine In dichloromethane at 0℃; for 24h; | Phenyl Trifluoromethanesulfonate; Typical Procedure General procedure: A mixture of phenol (0.45 g, 5 mmol), trifluoromethanesulfonyl chloride (0.8 mL, 7.5 mmol) and Et3N (1.4 mL, 10 mmol) in THF (30 mL) was stirred at 0 °C for 24 h. The solvent was evaporated and to the resulting residue were added H2O (20 mL) and EtOAc (20 mL). The organic phase was decanted and dried (anhyd Na2SO4). Evaporation of the solvent and purification by column chromatography on silica gel (hexane/EtOAc, 4:1) gave the pure triflate in 85% yield (191 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.5% | Stage #1: 2,3,5,6-tetrafluorotoluene With isopropylmagnesium chloride In tetrahydrofuran at 20℃; for 12h; Stage #2: With 18-crown-6 ether In 1,4-dioxane; 1,2-dimethoxyethane at 20℃; for 0.5h; Stage #3: 2-naphthyl triflate With bis(1,5-cyclooctadiene)nickel (0); bis[2-(di(2-naphthyl)phosphino)phenyl]ether In tetrahydrofuran; 1,4-dioxane at 40℃; for 6h; | 16 2,3,5,6-tetrafluoro-1,1'-biphenyl 1,In the absence of anaerobic conditions,360 mg (2.4 mmol) of 1,2,4,5-tetrafluorobenzene was dissolved in 1 mL of tetrahydrofuran,Then, 1 mL of a 2 mol / L solution of isopropylmagnesium chloride in tetrahydrofuran was added,The reaction was stirred at room temperature for 12 hours,To the reaction solution was added 3 mL of 1,4-dioxane,0.6 mL of ethylene glycol dimethyl ether and 26.4 mg (0.10 mmol) of 18-crown ether-6,Stir for 30 minutes at room temperature.2, in the anhydrous anaerobic conditions,To 0.4 mL of tetrahydrofuran and 0.6 mL of 1,4-dioxane was added 20.6 g(0.08 mmol)Bis (1,5-cyclooctadiene) nickel,77 mg (0.1 mmol) of bis (2-bis (3,5-dimethyl-4-methoxyphenyl)phosphine)Phenyl ether,Stir for 30 minutes at room temperature.3, in the anhydrous anaerobic conditions,The reaction solution obtained in Step 1 and Step 2 was mixed,And 224 mg (1.0 mmol) of 2-methyl-5-iodothiophene was added,Stirring at room temperature for 6 hours,TLC detection reaction is complete,Add 0.5 mL of methanol for 10 min,After the reaction is quenched completely,The reaction solution was washed with 0.1 mol / L hydrochloric acid,And extracted with ethyl acetate,The ethyl acetate extract was dried over anhydrous sodium sulfate,Evaporated under reduced pressure,And then separated by silica gel column chromatography,To give the product 2-methyl-5- (2 ', 3', 5 ', 6'-tetrafluorophenyl) thiophene,Its yield was 91%.In step 1 of Example 1, 2.4 mmol of 1,2,4,5-tetrafluorobenzene was equimolar3-methyl-1,2,4,5-tetrafluorobenzene; in step 2,Bis (2-bis (3,5-dimethyl-4-methoxyphenyl) phosphine) phenylene ether was equimolarBis (2-bis (2-naphthyl) phosphine) phenyl ether;In step 3,2-methyl-5-iodothiophene was replaced with equimolar 2-naphthyl trifluoromethanesulfonate,The reaction temperature was raised to 40 ° C,The other steps were the same as in Example 1,To give 2- (4'-methyl-2 ', 3', 5 ', 6'-tetrafluorophenyl) naphthalene in a yield of 98.5% |
98% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: 1,3,5-trifluorobenzene With isopropylmagnesium chloride In tetrahydrofuran at 50℃; for 12h; Stage #2: With 18-crown-6 ether In 1,4-dioxane; 1,2-dimethoxyethane at 20℃; for 0.5h; Stage #3: 2-naphthyl triflate With bis(1,5-cyclooctadiene)nickel (0); bis[2-(di(2-naphthyl)phosphino)phenyl]ether In tetrahydrofuran; 1,4-dioxane at 40℃; for 6h; | 19 2,3,5,6-tetrafluoro-1,1'-biphenyl General procedure: 1,In the absence of anaerobic conditions,360 mg (2.4 mmol) of 1,2,4,5-tetrafluorobenzene was dissolved in 1 mL of tetrahydrofuran,Then, 1 mL of a 2 mol / L solution of isopropylmagnesium chloride in tetrahydrofuran was added,The reaction was stirred at room temperature for 12 hours,To the reaction solution was added 3 mL of 1,4-dioxane,0.6 mL of ethylene glycol dimethyl ether and 26.4 mg (0.10 mmol) of 18-crown ether-6,Stir for 30 minutes at room temperature.2, in the anhydrous anaerobic conditions,To 0.4 mL of tetrahydrofuran and 0.6 mL of 1,4-dioxane was added 20.6 g(0.08 mmol)Bis (1,5-cyclooctadiene) nickel,77 mg (0.1 mmol) of bis (2-bis (3,5-dimethyl-4-methoxyphenyl)phosphine)Phenyl ether,Stir for 30 minutes at room temperature.3, in the anhydrous anaerobic conditions,The reaction solution obtained in Step 1 and Step 2 was mixed,And 224 mg (1.0 mmol) of 2-methyl-5-iodothiophene was added,Stirring at room temperature for 6 hours,TLC detection reaction is complete,Add 0.5 mL of methanol for 10 min,After the reaction is quenched completely,The reaction solution was washed with 0.1 mol / L hydrochloric acid,And extracted with ethyl acetate,The ethyl acetate extract was dried over anhydrous sodium sulfate,Evaporated under reduced pressure,And then separated by silica gel column chromatography,To give the product 2-methyl-5- (2 ', 3', 5 ', 6'-tetrafluorophenyl) thiophene,Its yield was 91%. In step 1 of Example 1,A mixture of 2.4 mmol of 1,2,4,5-tetrafluorobenzene Using 3.0 mmol of 1,3,5_ tetrafluorobenzene is substituted,2. Ommol of isopropylmagnesium chloride is replaced with equimolar ethyl magnesium chloride,The reaction temperature was raised to 50 ° C; in step 2,(2-bis (3,5-dimethyl-4-methoxyphenyl) phosphine) phenylene ether was replaced with equimolar bis (2-phenyl) phosphine)In Step 3,2-methyl-5-iodothiophene was replaced with equimolar 2-naphthyl trifluoromethanesulfonate,The reaction temperature rose to 40 ° C,The other steps were the same as in Example 1, The yield of 2- (2',4',5'-trifluorophenyl) naphthalene was 91% |
91% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With nickel(II) bromide dimethoxyethane; manganese; bathophenanthroline; lithium bromide In N,N-dimethyl-formamide at 20 - 40℃; for 14h; Inert atmosphere; | 2-Butyl Naphthalene (2a); Typical Procedure for Nickel-Catalyzed Reductive Alkylation of Aryl Sulfonates with Alkyl Iodides General procedure: To a suspension of NiBr2·glyme (3.1 mg, 10 μmol), bathophenanthroline (3.9 mg, 12 μmol), manganese (22 mg, 0.40 mmol), and LiBr (26mg, 0.30 mmol) in DMF (0.4 mL) were added 2-naphthyl nonaflate (3a; 85.3 mg, 0.200 mmol) and 1-iodobutane (34.2 μL, 0.300 mmol) at r.t. After stirring for 14 h at 40 °C, the mixture was cooled to r.t. and to this was added aqueous phosphate buffer (pH 7.4, ca. 2 mL). The mixturewas extracted with Et2O (3 × ca. 2 mL) and the combined organic extracts were dried (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by chromatography (silica gel, n-hexane) to give 2a as a colorless oil; yield from 1a: 28.5 mg (0.155 mmol, 77%); yield from 3a: 34.8 mg (0.189 mmol, 94%); Rf = 0.60 (n-hexane). IR (ZnSe): 743, 783, 814, 851, 885, 947, 1125, 1269, 1377, 1454, 1464, 1508, 1601, 2857, 2928, 2955, 3051 cm-1. 1H NMR (CDCl3, 400 MHz): δ = 0.94 (t, J = 7.6 Hz, 3 H, CH3), 1.39 (tq, J =7.6, 7.6 Hz, 2 H, CH2), 1.69 (tt, J = 7.6, 7.6 Hz, 2 H, CH2), 2.77 (t, J = 7.6Hz, 2 H, CH2), 7.32 (d, J = 8.4 Hz, 1 H, Harom), 7.37-7.46 (m, 2 H, Harom), 7.60 (s, 1 H, Harom), 7.72-7.81 (m, 3 H, Harom). 13C{1H} NMR (CDCl3, 100 MHz): δ = 14.0 (CH3), 22.4 (CH2), 33.5 (CH2), 35.8 (CH2), 124.9 (CH), 125.8 (CH), 126.3 (CH), 127.36 (CH), 127.44 (CH), 127.6 (CH), 127.7 (CH), 131.9 (C), 133.6 (C), 140.4 (C). HRMS (ESI+): m/z [M]+ calcd for C14H16+: 184.1247; found: 184.1245. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; | trans-Bromo(naphthalen-2-yl)bis(tricyclohexylphosphine)nickel(II) (6) To a solution of 2-naphthyl triflate (1a; 1.38 g, 5.00 mmol) and LiBr(478 mg, 5.50 mmol) in THF (20 mL) were added PCy3 (4.21 g, 15.0mmol) and Ni(cod)2 (1.38 g, 5.02 mmol) at r.t. After stirring for 2 h at this temperature, the solution was concentrated under reduced pressure. The residue was washed with n-hexane and MeOH to give 6 as ayellow solid; yield: 3.50 g (4.23 mmol, 85%); mp 122 °C (dec.). IR (ZnSe): 731, 818, 849, 935, 1003, 1026, 1173, 1202, 1445, 1572,1748, 2845, 2924 cm-1. 1H NMR (C6D6, 400 MHz): δ = 0.85-1.30 (m, 18 H, Haliph), 1.47-1.57(m, 6 H, Haliph), 1.60-1.88 (m, 24 H, Haliph), 2.05-2.23 (m, 18 H, Haliph), 7.13-7.19 (m, 1 H, Harom), 7.29 (dd, J = 8.0, 8.0 Hz, 1 H, Harom), 7.40 (d, J = 8.0 Hz, 1 H, Harom), 7.59 (d, J = 8.0 Hz, 1 H, Harom), 7.65 (d, J = 8.0 Hz,1 H, Harom), 8.05 (s, 1 H, Harom), 8.15 (d, J = 8.0 Hz, 1 H, Harom). 13C{1H} NMR (C6D6, 100 MHz): δ = 27.5 (6 C, 6 CH2), 28.67 (6 C, 6 CH2), 28.71 (6 C, 6 CH2), 31.0 (6 C, 6 CH2), 31.1 (6 C, 6 CH2), 35.4 (t, 1JC-P = 8.7Hz, 6 C, 6 PCH), 123.9 (CH), 124.3 (CH), 126.1 (2 C, 2 CH), 131.3 (C), 133.6 (C), 138.2 (CH), 138.6 (CH), 150.1 (t, 2JC-P = 33.5 Hz, NiC). One signal for aromatic CH carbon overlapped with the solvent peak. 31P{1H} NMR (C6D6, 160 MHz): δ = 11.6 (s). HRMS (ESI+): m/z [M - Br]+ calcd for C46H73NiP2+: 745.4535; found: 745.4520. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With bis(1,5-cyclooctadiene)nickel (0); 18-crown-6 ether; 2-[bis((3,5-dimethyl-4-methoxyphenyl)phosphino)phenyl]ether; isopropylmagnesium chloride In tetrahydrofuran; 1,4-dioxane; 1,2-dimethoxyethane at 40℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With copper(l) iodide; sulfur; sodium t-butanolate In N,N-dimethyl-formamide at 120℃; for 8h; Inert atmosphere; | Symmetrical Diaryl Sulfides via Homocoupling Reaction Phenolic Esters; General Procedure General procedure: A one-necked flask was charged with CuI (10 mg, 0.05 mmol), NaOt-Bu (376 mg, 4.0 mmol), S8 (16 mg, 0.5 mmol), phenolic ester (1 mmol), anhyd DMF (2 mL) under an inert atmosphere. The mixture was magnetically stirred and heated at 120 °C for the appropriate reaction time (Table 6). After completion of the reaction, the mixture was cooled to r.t. H2O (4 mL) was added and the product was extracted with EtOAc (3 × 4 mL) and dried (anhyd Na2SO4). Evaporation of the solvent and purification by column chromatography on silica gel (n-hexane/EtOAc) gave the desired symmetrical diaryl sulfides in 75-93% yields. |
87 %Chromat. | With sulfur; nickel(II) ferrite; sodium t-butanolate In N,N-dimethyl-formamide at 120℃; for 9h; Inert atmosphere; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With copper(l) iodide; sulfur; sodium t-butanolate at 60 - 80℃; for 7h; | Unsymmetrical Diaryl Sulfides from Arylboronic Acid and Phenolic Esters; General Procedure General procedure: A one-necked flask was charged with CuI (30 mg, 0.15 mmol), NaOt-Bu (376 mg, 4.0 mmol), S8 (47 mg, 1.5 mmol), phenolic ester (1 mmol), arylboronic acid (1.1 mmol), and PEG200 (2 mL). The mixture was magnetically stirred and heated at 60-80 °C for the appropriate reaction time (Table 2). After completion of the reaction, the reaction mixture was cooled to r.t. H2O (4 mL) was added and the product was extracted with EtOAc (3 × 4 mL) and dried (anhyd Na2SO4). Evaporation of the solvent and purification by column chromatography on silicagel (n-hexane/EtOAc) gave the desired unsymmetrical diaryl sulfides in 74-95% yields. |
88 %Chromat. | With sulfur; nickel(II) ferrite; sodium t-butanolate at 90℃; for 10h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With copper(l) iodide; sulfur; sodium t-butanolate at 60 - 80℃; for 10h; | Unsymmetrical Diaryl Sulfides from Arylboronic Acid and Phenolic Esters; General Procedure General procedure: A one-necked flask was charged with CuI (30 mg, 0.15 mmol), NaOt-Bu (376 mg, 4.0 mmol), S8 (47 mg, 1.5 mmol), phenolic ester (1 mmol), arylboronic acid (1.1 mmol), and PEG200 (2 mL). The mixture was magnetically stirred and heated at 60-80 °C for the appropriate reaction time (Table 2). After completion of the reaction, the reaction mixture was cooled to r.t. H2O (4 mL) was added and the product was extracted with EtOAc (3 × 4 mL) and dried (anhyd Na2SO4). Evaporation of the solvent and purification by column chromatography on silicagel (n-hexane/EtOAc) gave the desired unsymmetrical diaryl sulfides in 74-95% yields. |
84 %Chromat. | With sulfur; nickel(II) ferrite; sodium t-butanolate at 90℃; for 12h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With copper(l) iodide; sulfur; sodium t-butanolate at 60 - 80℃; for 5h; | Unsymmetrical Diaryl Sulfides from Arylboronic Acid and Phenolic Esters; General Procedure General procedure: A one-necked flask was charged with CuI (30 mg, 0.15 mmol), NaOt-Bu (376 mg, 4.0 mmol), S8 (47 mg, 1.5 mmol), phenolic ester (1 mmol), arylboronic acid (1.1 mmol), and PEG200 (2 mL). The mixture was magnetically stirred and heated at 60-80 °C for the appropriate reaction time (Table 2). After completion of the reaction, the reaction mixture was cooled to r.t. H2O (4 mL) was added and the product was extracted with EtOAc (3 × 4 mL) and dried (anhyd Na2SO4). Evaporation of the solvent and purification by column chromatography on silicagel (n-hexane/EtOAc) gave the desired unsymmetrical diaryl sulfides in 74-95% yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With potassium fluoride; copper diacetate; potassium carbonate; sulfur at 80℃; for 5h; | C-S Bond Formation by the Reaction of Triphenyltin Chloride with Phenolic Esters; General Procedure General procedure: A one-necked flask was charged with Cu(OAc)2 (30 mg, 0.15 mmol), K2CO3 (414 mg, 3.0 mmol), S8 (48 mg, 1.5 mmol), KF (180 mg, 3 mmol), phenolic ester (1 mmol), triphenyltin chloride (0.35 mmol), and PEG200 (1.5 mL). The mixture was magnetically stirred and heatedat 80 °C for the appropriate reaction time (Table 4). After completion of the reaction, the reaction mixture was cooled to r.t. H2O (4 mL) was added and the product was extracted with EtOAc (3 × 4 mL) and dried (anhyd Na2SO4). Evaporation of the solvent and purification by column chromatography on silica gel (n-hexane/EtOAc) gave the desired phenyl aryl sulfides in 79-94% yields. |
81 %Chromat. | With sulfur; potassium fluoride; nickel(II) ferrite; potassium carbonate at 85℃; for 6h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With bis(tricyclohexylphosphine)nickel(II) dichloride In toluene at 20℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With (o-hydroxyphenyl)diphenylphosphine; tetraethylammonium bromide; palladium diacetate; caesium carbonate In toluene at 120℃; for 24h; Inert atmosphere; Glovebox; | Germylation of Aryl Bromides 1 and Triflates 2 General procedure: Conditions B: To a dried screw capped vial were added aryl bromide 1 or aryl triflate 2 (0.50 mmol), Pd(OAc)2 (11.2 mg, 0.05 mmol, 10 mol %), ligand 5 (27.8 mg, 0.10 mmol, 20 mol %), Cs2CO3 (195.5 mg, 0.60 mmol, 1.2 equiv), Et4NBr (105.1 mg, 0.5 mmol, 1.0 equiv), hexamethyldigermane (3; 120 μL, 0.60 mmol, 1.2 equiv), and toluene (2.5 mL) under argon atmosphere in a glove box. The vial was capped and heated at 120 °C for 24 h with stirring. After cooling to r.t., H2O (2 mL) was added. After dilution with EtOAc, the organic layer was separated, and the aqueous layer was extracted with EtOAc (3 × 3 mL). The combined organic layers were washed with brine (3 mL) and dried (Na2SO4). After filtration and evaporation, purification of the crude product by silica gel column chromatography afforded the corresponding product 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With tris-(dibenzylideneacetone)dipalladium(0); tetrabutyl-ammonium chloride; sodium formate In N,N-dimethyl-formamide at 20℃; for 14h; Inert atmosphere; chemoselective reaction; | 4.1. 2-(Naphthalen-2-yl)tetrahydrofuran (2a) To a flame-dried, 0.5-dram vial fitted with a rubber septum and equipped with a magnetic stir bar was added 2-naphthalen-2-yl trifluoromethanesulfonate 1a (0.4 mmol, 1.0 equiv), Pd2dba3 (10 mol %), TBAC (1.5 equiv) and NaHCO2 (1.2 equiv). The contents were evacuated and backfilled three times with argon. 2,3-Dihydrofuran (DHF) (5.2 equiv) and DMF (0.7 M) was added via syringe and the reaction vial was sealed with a screw-top cap. The reaction mixture was stirred at room temperature for 14 h. The reaction was diluted with Et2O (3 mL) and filtered through a 3 cm pad of silica, flushing with 35 mL of Et2O. The solution was concentrated via rotary evaporation. The reductive-Heck product was isolated by flash chromatography (gradient 2-20% EtOAc/hexanes over 400 mL), to give desired product 2-(naphthalen-2-yl)tetrahydrofuran 2a (44 mg, 56% yield) as a colorless oil. 1H NMR: (400 MHz, chloroform-d) δ 7.85-7.78 (m, 4H), 7.49-7.41 (m, 3H), 5.07 (t, J = 7.2 Hz, 1H), 4.22-4.12 (m, 1H), 4.06-3.95 (m, 1H), 2.47-2.32 (m, 1H), 2.12-1.99 (m, 2H), 1.96-1.82 (m, 1H). 13C NMR: (126 MHz, chloroform-d): δ 141.05, 133.45, 132.93, 129.10, 128.22, 128.04, 127.79, 126.15, 125.72, 124.18, 80.93, 68.98, 34.76, 26.23. TLC: Rf = 0.22 (10% Et2O in hexanes). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With palladium diacetate; caesium carbonate; DavePhos In N,N-dimethyl acetamide at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: 3-Sulfolene With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 1h; Stage #2: With o-phenylenebis(diphenylphosphine); palladium diacetate In tetrahydrofuran at 20℃; for 0.25h; Inert atmosphere; Stage #3: 2-naphthyl triflate With potassium hydrogencarbonate In tetrahydrofuran at 20 - 100℃; Sealed tube; Inert atmosphere; stereoselective reaction; | General procedure for the desulfitative cross-coupling reaction of aryl sulfonates with 3-sulfolenes (GP1) General procedure: To a 25 mL flask, 3-sulfolene (2.2 mmol) and potassium tert-butoxide (224 mg, 2 mmol) were added freshly-distilled tetrahydrofuran (4 mL), and the reaction mixture (sulfinate suspension) was stirred for 1 h at rt. An oven-dried 35 mL glass pressure tube containing an elliptical rare-earth stir bar was purged with argon through a glass pipet for 5 min. Palladium acetate (11 mg, 0.05 mmol, 5 mol%) and dppbz (36 mg, 0.08 mmol, 8 mol%, 1,2-bis(diphenylphosphino)benzene) were added, followed by freshly-distilled tetrahydrofuran (4 mL). The pressure tube was capped with a septum that was connected to an argon line and a gas-bubbler, and the reaction mixture was stirred for 15 min at rt. Potassium bicarbonate (200 mg, 2 mmol) was added. Then, the sulfinate suspension mixture was added by means of a pipette. The reaction mixture was stirred for 5 min at rt, and an aryl sulfonate (1 mmol) was added. The pressure tube was sealed with a PTFE screw cap, and the reaction mixture was stirred for 1 h at rt. The temperature was then allowed to gradually reach 100 °C over 20 min, and the reaction mixture was vigorously stirred for 14-36 h at 100 °C. For work-up, the reaction mixture was cooled to rt, and a saturated solution of ammonium chloride (4 mL) was added, followed by ethyl acetate (20 mL). The reaction mixture was then extracted with ethyl acetate (4 × 10 mL). The organic phases were combined, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (ethyl acetate/hexane or diethyl ether/pentane) to give the 1,3-diene product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Stage #1: 2-cyclohexyl-4-methyl-2,5-dihydrothiophene 1,1-dioxide With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 1h; Stage #2: With o-phenylenebis(diphenylphosphine); palladium diacetate In tetrahydrofuran at 20℃; for 0.25h; Inert atmosphere; Stage #3: 2-naphthyl triflate With potassium hydrogencarbonate In tetrahydrofuran at 20 - 100℃; Sealed tube; Inert atmosphere; stereoselective reaction; | General procedure for the desulfitative cross-coupling reaction of aryl sulfonates with 3-sulfolenes (GP1) General procedure: To a 25 mL flask, 3-sulfolene (2.2 mmol) and potassium tert-butoxide (224 mg, 2 mmol) were added freshly-distilled tetrahydrofuran (4 mL), and the reaction mixture (sulfinate suspension) was stirred for 1 h at rt. An oven-dried 35 mL glass pressure tube containing an elliptical rare-earth stir bar was purged with argon through a glass pipet for 5 min. Palladium acetate (11 mg, 0.05 mmol, 5 mol%) and dppbz (36 mg, 0.08 mmol, 8 mol%, 1,2-bis(diphenylphosphino)benzene) were added, followed by freshly-distilled tetrahydrofuran (4 mL). The pressure tube was capped with a septum that was connected to an argon line and a gas-bubbler, and the reaction mixture was stirred for 15 min at rt. Potassium bicarbonate (200 mg, 2 mmol) was added. Then, the sulfinate suspension mixture was added by means of a pipette. The reaction mixture was stirred for 5 min at rt, and an aryl sulfonate (1 mmol) was added. The pressure tube was sealed with a PTFE screw cap, and the reaction mixture was stirred for 1 h at rt. The temperature was then allowed to gradually reach 100 °C over 20 min, and the reaction mixture was vigorously stirred for 14-36 h at 100 °C. For work-up, the reaction mixture was cooled to rt, and a saturated solution of ammonium chloride (4 mL) was added, followed by ethyl acetate (20 mL). The reaction mixture was then extracted with ethyl acetate (4 × 10 mL). The organic phases were combined, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (ethyl acetate/hexane or diethyl ether/pentane) to give the 1,3-diene product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: 2,2,4-trimethyl-2,5-dihydrothiophene-1,1-dioxide With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 1h; Stage #2: With o-phenylenebis(diphenylphosphine); palladium diacetate In tetrahydrofuran at 20℃; for 0.25h; Inert atmosphere; Stage #3: 2-naphthyl triflate With potassium hydrogencarbonate In tetrahydrofuran at 20 - 100℃; Sealed tube; Inert atmosphere; stereoselective reaction; | General procedure for the desulfitative cross-coupling reaction of aryl sulfonates with 3-sulfolenes (GP1) General procedure: To a 25 mL flask, 3-sulfolene (2.2 mmol) and potassium tert-butoxide (224 mg, 2 mmol) were added freshly-distilled tetrahydrofuran (4 mL), and the reaction mixture (sulfinate suspension) was stirred for 1 h at rt. An oven-dried 35 mL glass pressure tube containing an elliptical rare-earth stir bar was purged with argon through a glass pipet for 5 min. Palladium acetate (11 mg, 0.05 mmol, 5 mol%) and dppbz (36 mg, 0.08 mmol, 8 mol%, 1,2-bis(diphenylphosphino)benzene) were added, followed by freshly-distilled tetrahydrofuran (4 mL). The pressure tube was capped with a septum that was connected to an argon line and a gas-bubbler, and the reaction mixture was stirred for 15 min at rt. Potassium bicarbonate (200 mg, 2 mmol) was added. Then, the sulfinate suspension mixture was added by means of a pipette. The reaction mixture was stirred for 5 min at rt, and an aryl sulfonate (1 mmol) was added. The pressure tube was sealed with a PTFE screw cap, and the reaction mixture was stirred for 1 h at rt. The temperature was then allowed to gradually reach 100 °C over 20 min, and the reaction mixture was vigorously stirred for 14-36 h at 100 °C. For work-up, the reaction mixture was cooled to rt, and a saturated solution of ammonium chloride (4 mL) was added, followed by ethyl acetate (20 mL). The reaction mixture was then extracted with ethyl acetate (4 × 10 mL). The organic phases were combined, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (ethyl acetate/hexane or diethyl ether/pentane) to give the 1,3-diene product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: 3-(4-methylpent-3-en-1-yl)-2,5-dihydrothiophene-1,1-dioxide With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 1h; Stage #2: With o-phenylenebis(diphenylphosphine); palladium diacetate In tetrahydrofuran at 20℃; for 0.25h; Inert atmosphere; Stage #3: 2-naphthyl triflate With potassium hydrogencarbonate In tetrahydrofuran at 20 - 80℃; Sealed tube; Inert atmosphere; stereoselective reaction; | General procedure for the desulfitative cross-coupling reaction of aryl sulfonates with 3-sulfolenes (GP1) General procedure: To a 25 mL flask, 3-sulfolene (2.2 mmol) and potassium tert-butoxide (224 mg, 2 mmol) were added freshly-distilled tetrahydrofuran (4 mL), and the reaction mixture (sulfinate suspension) was stirred for 1 h at rt. An oven-dried 35 mL glass pressure tube containing an elliptical rare-earth stir bar was purged with argon through a glass pipet for 5 min. Palladium acetate (11 mg, 0.05 mmol, 5 mol%) and dppbz (36 mg, 0.08 mmol, 8 mol%, 1,2-bis(diphenylphosphino)benzene) were added, followed by freshly-distilled tetrahydrofuran (4 mL). The pressure tube was capped with a septum that was connected to an argon line and a gas-bubbler, and the reaction mixture was stirred for 15 min at rt. Potassium bicarbonate (200 mg, 2 mmol) was added. Then, the sulfinate suspension mixture was added by means of a pipette. The reaction mixture was stirred for 5 min at rt, and an aryl sulfonate (1 mmol) was added. The pressure tube was sealed with a PTFE screw cap, and the reaction mixture was stirred for 1 h at rt. The temperature was then allowed to gradually reach 100 °C over 20 min, and the reaction mixture was vigorously stirred for 14-36 h at 100 °C. For work-up, the reaction mixture was cooled to rt, and a saturated solution of ammonium chloride (4 mL) was added, followed by ethyl acetate (20 mL). The reaction mixture was then extracted with ethyl acetate (4 × 10 mL). The organic phases were combined, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (ethyl acetate/hexane or diethyl ether/pentane) to give the 1,3-diene product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With potassium phosphate In toluene at 110℃; for 20h; Inert atmosphere; Sealed tube; | 14 Example 14 This embodiment provides a method for preparing 2-naphthyl diphenylphosphinate, as follows: Under a nitrogen atmosphere, 0.30 mmol of diphenylphosphine oxide was added to the reactor, 0.20mmol 2-naphthyl trifluoromethanesulfonate, 0.50mmol potassium phosphate, 1.5mL toluene solvent, after sealing the tube, heated to 110 °C, continued stirring for 20 h, Stop the reaction, cool to room temperature, wash with water to remove excess alkali and generated salts, The aqueous phase was extracted with dichloromethane to obtain an organic phase, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The crude product was separated by column chromatography to obtain the target product, and the separation yield was 61% |
52% | With potassium phosphate In toluene at 100℃; for 20h; Inert atmosphere; Schlenk technique; | 3.General procedure for O-phosphorylation of aryl triflates. General procedure: Under N2 atmosphere, 0.2 mmol phenyl triflate 1a, 0.3 mmol Ph2P(O)H 2a, 2.5 equiv K3PO4 and 2 mL toluene were charged into a 10 mL schlenk tube. The mixture was stirred at 100°C for 20 h. After removal of the volatile, the residues were passed through a short silica chromatography (particle size 37~54 mm, petroleum ether/ethyl acetate as eluent) to afford analytically pure organophosphorus compounds 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water at 80℃; for 8h; Inert atmosphere; | 2.2-1 (2-1) Synthesis of BH-2 Under an argon atmosphere, a mixture of 4.0 g of BH-1-4, 3.5 g of BH-2-1, 0.260 g of tetrakistriphenylphosphine palladium, 10 mL of a 2M sodium carbonate aqueous solution, and 70 mL of DME was stirred at 80° C. for 8 hours. The resultant reaction liquid was cooled to room temperature, and extracted with ethyl acetate. Then, the organic phase was washed with water, dried over anhydrous magnesium sulfate, followed by distillation of the solvent under reduced pressure. The obtained residue was purified by silica gel column chromatography and recycllization to give 2.9 g of BH-2 in an yield of 59%. The compound was identified by molecular weight determination with FD/MS. It was confirmed that m/e=438 for the molecular weight of 438. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With manganese; 5,5'-dimethyl-2,2'-bipyridine; nickel dichloride In N,N-dimethyl-formamide at 20℃; for 24h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With chloro-trimethyl-silane; NiCl2 * 4 pyridine; zinc; [C(CH3)=N-(2-(t-Bu)C6H4)]2 In N,N-dimethyl acetamide at 30℃; for 24h; Inert atmosphere; Sealed tube; Glovebox; regioselective reaction; | 2.1 General procedure of arylalkylation reaction General procedure: An oven-dried 10 mL reaction tube equipped with a magneticstir bar was introduced to an argon-filled glove box. NiCl2·Py4 (11.3 mg, 0.025 mmol, 5 mol%), L1 (8.8 mg,0.025 mmol, 5 mol%), zinc (97.5 mg, 1.5 mmol, 3.0 equiv.)and anhydrous N,N-dimethylaniline (DMA) (2 mL) wereadded in this order. Then acrylate (0.5 mmol, 1.0 equiv.), aryliodide (0.75 mmol, 1.5 equiv.), acetal (0.5 mmol, 1.0 equiv.)and chlorotrimethylsilane (TMSCl) (190 μL, 1.5 mmol, 3.0equiv.) were added to the resulting mixture. The tube wassealed with a rubber stopper, and stirred at 30 °C for 24 h.After the reaction was complete, water (10 mL) was added,and then extracted with ethyl acetate (10 mL×3). The combinedorganic layers were dried over Na2SO4 and concentratedunder reduced pressure. The residue was purifiedby column chromatography using petroleum ether and ethylacetate as eluent, to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With 1,3-bis-(diphenylphosphino)propane; palladium diacetate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 80℃; for 2.5h; Inert atmosphere; Schlenk technique; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium hexafluoridophosphate; nickel(II) chloride ethylene glycol dimethyl ether complex; [(2,6-bispyrazolylpyridine)MnCl2]; diphenyl(1-(2-isopropyl-quinazolin-4-yl)-2-naphthyl)phosphine In N,N-dimethyl-formamide at 20℃; Electrolysis; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With bis(acetonitrile)palladium(II) chloride; tripotassium phosphate tribasic; dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane at 80℃; for 10h; Schlenk technique; Sealed tube; Inert atmosphere; stereoselective reaction; | 3. General Procedure for Synthesis of 2,3-Disubstituted Norbornene. General procedure: An oven-dried 10 mL Schlenk-type tube equipped with a magnetic stir bar was charged with aryl triflate (0.4 mmol), bicyclic alkene (0.72 mmol, 1.8 equiv), terminal alkyne (0.48 mmol, 1.2 equiv), Pd(MeCN)2Cl2 (0.02 mmol, 5 mol%), X-Phos (0.04 mmol, 10 mol%), K3PO4 (0.48 mmol, 1.2 equiv) and PhOMe (1.0 mL). The reaction tube was backfilled with nitrogen three times and well sealed. After the reaction mixture was stirred at 80 °C for 10 h, it was cooled down to ambient temperature. The resulting mixture was diluted with CH2Cl2 (5 mL), dried over Na2SO4, and concentrated in vacuo. Products were obtained by preparative thin-layer chromatography (petroleum ether/ethyl acetate). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With 1,3-DIOXOLANE; di-μ-chlorobis-[(η6-p-cymene)chlororuthenium(II)]; caesium fluoride at 20℃; for 16h; Glovebox; Inert atmosphere; Sealed tube; Irradiation; | General Procedure for Ru(II)-Catalyzed Direct Arylation General procedure: In an argon-filled glovebox, [Ru(p-cymene)Cl2]2 (0.005 mmol, 2.5mol%), CsF (0.4 mmol, 2 equiv), 1-arylpyrazole (1, 0.2 mmol, 1 equiv) and 1,3-dioxolane (1 mL) were added in a 10 mL test tube equipped with a magnetic stir bar. The reaction vessel was sealed with a rubber septum, transferred outside of the glovebox,then placed inside a blue LEDs reactor equipped with a ventilator and a magnetic stir plate. The reaction mixture was stirred for 30 min with blue light irradiation and transferred back into glovebox. In glovebox, arylhalide (2, 0.2 mmol, 1 equiv) was added to the reaction mixture. The reaction vessel was sealed and stirred at ambient temperature for 16 hours. After reaction, all volatile materials were removed under reduced pressure. The residue was purified by flash-column chromatography (SiO2, 5-15% EtOAc/petroleum ether) toyield the corresponding product 3. |
Tags: 3857-83-8 synthesis path| 3857-83-8 SDS| 3857-83-8 COA| 3857-83-8 purity| 3857-83-8 application| 3857-83-8 NMR| 3857-83-8 COA| 3857-83-8 structure
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P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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