* 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.
Reference：
[1] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 11, p. 3527 - 3539
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[ 112-43-6 ]
[ 7766-50-9 ]
Yield
Reaction Conditions
Operation in experiment
100%
With carbon tetrabromide; triphenylphosphine In dichloromethane at 0℃; for 2 h;
A dichloromethane solution of 10-undecen-1-ol (30, 200 mg,1.17 mmol) was treated with CBr4(403 mg, 1.29 mmol,1.1 eq.) and Ph3P(340 mg, 1.29 mmol, 1.1 eq.) at 0 °C for2 h, and the reaction was quenched by addition of water. Thereaction mixture was extracted with dichloromethane andthe organic layer was dried over anhydrous Na2SO4powder.The organic solvent was evaporated in vacuo to obtain thecrude product. The crude product was used for the furtherreactions without chromatographic purification. The crudeproducts were purified by column chromatography on silicagel to obtain 1-bromo-10-undecene (31, 273 mg, quantitativeyield) [56] as colorless oil.
93%
With carbon tetrabromide; triphenylphosphine In dichloromethane at -5 - 20℃; for 14 h;
11-Undecen-1-ol (140 g, 0.82 mol) and CBr4 (300 g, 0.90 mol)were dissolved in CH2Cl2 (500 mL) in Schlenk flask and triphenylphosphine(237 g, 0.90 mol) was then added dropwise over 15 minat 5 C. The systemwas stirred at 5 C for 2 h, and raised to room temperature for 12 h. The solution was concentrated and a white precipitate formed which was removed by filtration. The resultantsolution was fractionally distilled under reduced pressure to get apurified and colorless liquid product (177 g).
82%
With N-Bromosuccinimide; triphenylphosphine In DMF (N,N-dimethyl-formamide) at 20℃; for 0.5 h;
To a solution of undec-10-en-1-ol (0.86 g, 5.0 mmol) in DMF (15 ML) was added triphenylphosphine (1.46 g, 5.6 mmol).The solution was cooled to 0° C. and NBS (0.96 g, 5.4 mmol) was added in portions.After stirring for 30 min at room temperature, the reaction was quenched with methanol (0.5 ML).The solution was diluted with ether (80 ML), washed with water, saturated aqueous NaHCO3 and brine successively.The organic layer was dried and concentrated.The residue was purified by flash chromatography on silica gel, eluding with hexane to afford 11-bromo-undec-1-ene (0.96 g, 82percent) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 5.79 (1H, m), 4.93 (2H, m), 3.38 (2H, t, J=6.9 Hz), 2.02 (2H, m), 1.83 (2H, m), 1.20-1.55 (12H, m); 13C NMR (75 MHz, CDCl3) δ 139.36, 114.33, 34.27, 33.99, 33.01, 29.57*2, 29.27, 29.09, 28.94, 28.35.
60%
With phosphorus tribromide In diethyl ether at -78 - 20℃; Inert atmosphere
Phosphorus tribromide (5.3 g, 19.6 mmol, 1.84 ml) was added dropwise to a solution of 10-Undecen-1-ol (10 g, 58.7 mmol) in diethyl ether (100 ml) at −78° C. over a period of 10 min and then the mixture was allowed to warm to room temperature and stirred under Ar overnight. The reaction mixture was quenched with water and the layers were separated. The aqueous layer was extracted with ether (5×30 ml) and the combined organic layers were washed with brine and dried over sodium sulfate. After evaporation of the solvent in vacuo, the crude product was purified by chromatography column on silica gel (hexane) to give pure product 8.2 g (yield: 60percent). 1H NMR (CDCl3) δ 5.85-5.75 (m, 1H), 5.01-4.91 (m, 2H), 3.37-3.41 (t, 2H, J=7.2 Hz), 2.06-1.99 (m, 2H), 1.88-1.81 (m, 2H), 1.39 (br, 2H), 1.29 (br, 10H). 13C NMR (CDCl3) δ 139.4, 114.3.3, 34.2, 34.1, 33.0, 31.8, 29.6, 29.3, 29.1, 29.0, 28.4.
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[ 112-43-6 ]
[ 74036-98-9 ]
[ 7766-50-9 ]
Reference：
[1] Helvetica Chimica Acta, 1926, vol. 9, p. 1086
4
[ 112-43-6 ]
[ 10035-10-6 ]
[ 74036-98-9 ]
[ 73641-91-5 ]
[ 7766-50-9 ]
Reference：
[1] Helvetica Chimica Acta, 1926, vol. 9, p. 1086
With ethanol; (BQ‑NCOP)IrHCl; sodium t-butanolate at 60℃; for 2h; Inert atmosphere; Schlenk technique; Sealed tube;
94%
With sodium tetrahydroborate; ruthenium(III) trichloride hydrate In 1-methyl-pyrrolidin-2-one; water at 0℃; for 1h; chemoselective reaction;
General procedure for alkene reduction
General procedure: To a 15-mL 1-neck reaction flask fitted with a glass stopper [Note: A larger-scale reaction may require the use of a pressure vessel and/or addition of NaBH4 in small portions.] were added a small spin bar, 0.18-0.20 mmol of substrate, 0.60 mL of 5:1 (v/v) [10:1 (v/v) in Table 1, entry 3] liquid amide(s)/H2O, and 7.0 mg (0.034 mmol) of ruthenium(III) chloride hydrate (Sigma-Aldrich Catalog No. 206229). After cooling the latter mixture to 0 C (external ice-H2O bath), 9.0 mg (0.24 mmol) of NaBH4 powder was added in one portion; and the mixture was subsequently stirred at 0 C for 60 min. The reaction was then quenched by addition of 2.0 mL of 2 M aqueous HCl to the reaction flask, followed by 1.0 mL of pentane and subsequent stirring of the mixture at 0 C for 15 min. The product was then isolated by dilution of the reaction mixture with 10 mL of 4:1 (v/v) pentane/dichloromethane; and solid material was removed by filtration through a small pad of Hyflo Super-Cel filtering aid. After dilution of the filtrate with 10 mL of pentane, removal of the liquid amide(s) was accomplished by washing the filtrate with 10% (w/v) aqueous NaCl (4 15 mL portions). The organic layer was subsequently dried over anhydrous MgSO4, filtered, and the volatile organic solvents were removed by evaporation at reduced pressure.
93%
With sodium tetrahydroborate; copper(ll) sulfate pentahydrate; cobalt(II) chloride hexahydrate In methanol at 20℃; for 0.333333h;
General hydrogenation procedure
General procedure: The catalyst precursor in form of a 0.04 M CuSO4 and 0.004 M CoCl2 solution was added to a solution of the alkene/alkyne compound in methanol. The reaction was started by adding an initial portion of NaBH4, resulting in a color change to black (in situ prepared catalyst) and vigorous gas evolution. Additional portions of NaBH4 were added in intervals of typically three or four minutes. The reaction itself was carried out at room temperature and normal atmosphere. However, generation of heat due to the exothermic character of the reaction usually heated the reaction mixture to 30-40 °C. Cooling is generally not necessary in small scale. For large scale reactions a reflux condenser was used. The higher reaction temperature did not influence the reaction yield. The reaction mixture was finally quenched by adding 2 M H2SO4. Work up was carried out by extracting the water/methanol phase with DCM. The catalyst in general stays within the water/methanol layer. Drying the DCM layer with MgSO4 followed by filtration removes all remaining catalyst particles. The drying agent was filtered of and the DCM was removed in vacuo.
87
To 10-undecenyl alcohol (10 g, 58.7 mmol), pyridine (0.08 mL, 2.53 mmol) was added, SOCl2 (4.7 mL) was slowly added thereto at 25° C. over about 5 minutes, and the mixture was then refluxed at 65° C. for 5 hours. The reaction mixture was extracted with methylene chloride and water and then distilled, yielding 11 g (98% yield) of pure 10-undecenyl chloride (15).15: 1H NMR (250 MHz, CDCl3) (ppm) 5.87-5.73 (m, 1H), 5.04-4.91 (t, 2H), 3.56-3.51 (t, J=6.78, 2H), 2.08-2.00 (q, Jab=6.7 Hz, Jbc=7.1, Jcd=6.9 2H), 1.82-1.71 (q, Jab=6.7 Hz, Jbc=6.8, Jcd=7.8, Jde=6.8, 2H), 1.29 (s, 12H).
94.6%
With tetrachloromethane; triphenylphosphine for 3h; Reflux;
94.6%
With tetrachloromethane; triphenylphosphine for 4h; Reflux;
1.1
The compound of compound ii is reacted with triphenylphosphine in a molar ratio1: 1.2The compound was prepared by refluxing in carbon tetrachloride for 4 hoursIii, 94.6%.
93%
With thionyl chloride for 1h; Heating;
91%
With tetra-(n-butyl)ammonium iodide; 1,2-dichloro-ethane; triphenylphosphine at 120℃; for 0.5h; Sealed tube; Inert atmosphere;
90%
With pyridine; thionyl chloride at 65℃; for 2h; Inert atmosphere;
82%
With thionyl chloride; triethylamine In dichloromethane at 0 - 20℃; for 6.5h;
11-chloroundec-1-ene (3)
6.33g (0,081mol) of thionyl chloride was added at 0°C to a solution of 11.50g (0.0675mol) of 10-undecen-1-ol and 8.18g (0.081mol) of triethylamine in a 100ml DCM solution over a period of 30min. After the addition was finished the reaction mixture was allowed to stir for 6h at room temperature and then poured into ice-cold water and extracted with DCM. The DCM solution was then dried over Na2SO4 and evaporated. The product as a colourless liquid was distilled under vacuum (1 mBar) at 65□C with the overall 82 % yield. 1H NMR (250MHz,) δ 5.81 (ddt, J=16.9, 10.1, 6.6Hz, 1H), 4.99 (m,3J=17Hz, 1H), 4.93(m, 3J=10Hz, 1H), 3.53 (t, 3J =6.7Hz, 2H), 2.04 (m, 2H), 1.77 (m, 2H), 1.51 - 1.23 (m, 12H).
70%
With pyridine; thionyl chloride at 50℃; for 2h;
54%
With toluene-4-sulfonic acid; 1-butyl-3-methylimidazolium chloride at 200℃; for 0.05h; microwave irradiation;
With thionyl chloride; 2,3-Dimethylaniline
With pyridine; thionyl chloride
With thionyl chloride
94 g
With pyridine; thionyl chloride at 65℃; for 5h;
With thionyl chloride
81 % Chromat.
With tetrachloromethane; diphenylphosphinated ethylene oligomer In toluene at 90℃; for 5h;
With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0℃; for 2h;
A dichloromethane solution of 10-undecen-1-ol (30, 200 mg,1.17 mmol) was treated with CBr4(403 mg, 1.29 mmol,1.1 eq.) and Ph3P(340 mg, 1.29 mmol, 1.1 eq.) at 0 C for2 h, and the reaction was quenched by addition of water. Thereaction mixture was extracted with dichloromethane andthe organic layer was dried over anhydrous Na2SO4powder.The organic solvent was evaporated in vacuo to obtain thecrude product. The crude product was used for the furtherreactions without chromatographic purification. The crudeproducts were purified by column chromatography on silicagel to obtain 1-bromo-10-undecene (31, 273 mg, quantitativeyield) [56] as colorless oil.
93%
With carbon tetrabromide; triphenylphosphine; In dichloromethane; at -5 - 20℃; for 14h;
11-Undecen-1-ol (140 g, 0.82 mol) and CBr4 (300 g, 0.90 mol)were dissolved in CH2Cl2 (500 mL) in Schlenk flask and triphenylphosphine(237 g, 0.90 mol) was then added dropwise over 15 minat 5 C. The systemwas stirred at 5 C for 2 h, and raised to room temperature for 12 h. The solution was concentrated and a white precipitate formed which was removed by filtration. The resultantsolution was fractionally distilled under reduced pressure to get apurified and colorless liquid product (177 g).
82%
With N-Bromosuccinimide; triphenylphosphine; In DMF (N,N-dimethyl-formamide); at 20℃; for 0.5h;
To a solution of undec-10-en-1-ol (0.86 g, 5.0 mmol) in DMF (15 ML) was added triphenylphosphine (1.46 g, 5.6 mmol).The solution was cooled to 0 C. and NBS (0.96 g, 5.4 mmol) was added in portions.After stirring for 30 min at room temperature, the reaction was quenched with methanol (0.5 ML).The solution was diluted with ether (80 ML), washed with water, saturated aqueous NaHCO3 and brine successively.The organic layer was dried and concentrated.The residue was purified by flash chromatography on silica gel, eluding with hexane to afford 11-bromo-undec-1-ene (0.96 g, 82%) as a colorless oil: 1H NMR (300 MHz, CDCl3) delta 5.79 (1H, m), 4.93 (2H, m), 3.38 (2H, t, J=6.9 Hz), 2.02 (2H, m), 1.83 (2H, m), 1.20-1.55 (12H, m); 13C NMR (75 MHz, CDCl3) delta 139.36, 114.33, 34.27, 33.99, 33.01, 29.57*2, 29.27, 29.09, 28.94, 28.35.
60%
With phosphorus tribromide; In diethyl ether; at -78 - 20℃;Inert atmosphere;
Phosphorus tribromide (5.3 g, 19.6 mmol, 1.84 ml) was added dropwise to a solution of 10-Undecen-1-ol (10 g, 58.7 mmol) in diethyl ether (100 ml) at -78 C. over a period of 10 min and then the mixture was allowed to warm to room temperature and stirred under Ar overnight. The reaction mixture was quenched with water and the layers were separated. The aqueous layer was extracted with ether (5×30 ml) and the combined organic layers were washed with brine and dried over sodium sulfate. After evaporation of the solvent in vacuo, the crude product was purified by chromatography column on silica gel (hexane) to give pure product 8.2 g (yield: 60%). 1H NMR (CDCl3) delta 5.85-5.75 (m, 1H), 5.01-4.91 (m, 2H), 3.37-3.41 (t, 2H, J=7.2 Hz), 2.06-1.99 (m, 2H), 1.88-1.81 (m, 2H), 1.39 (br, 2H), 1.29 (br, 10H). 13C NMR (CDCl3) delta 139.4, 114.3.3, 34.2, 34.1, 33.0, 31.8, 29.6, 29.3, 29.1, 29.0, 28.4.
With N-Bromosuccinimide; N2; triphenylphosphine; In dichloromethane;
Synthesis of omega-Undecenyl Bromide (2) In a flame-dried dual-necked 200 ml round bottomed flask equipped with a teflon-coated magnetic stir bar and a condenser and N2 inlet, were placed 8.5 g (50 mmol) of omega-undecenyl alcohol (1) and 100 ml of dry dichloromethane. The flask was covered with aluminum foil and mixture was stirred and cooled in a CCl4/dry ice bath (-23 C.). 15.7 g (60 mmol) of triphenylphosphine was added to the mixture and stirred until it dissolved. 9.8 g (55 mmol) of NBS was added all at once to the mixture and was stirred at -23 C. for 1 hour. The flask was removed from the cold bath and the mixture was allowed to stir at room temperature for 30 minutes. The solution was transfered to a separatory funnel and was washed with water saturated with sodium carbonate. The organic layer was dried with MgSO4, filtered, and concentrated on a rotary evaporator. The purple precipitate was extracted with 3*50 ml aliquots of hexanes using a combination of mechanical stirring, heat and sonication. The resulting suspension was filtered, and the hexanes removed on a rotary evaporator. The material was filtered through a short column of neutral alumina (5 cm height, 3 cm diameter) using hexanes under vacuum and the product was concentrated on a rotary evaporator to yield a clear liquid. Yield 10.64 g (91%); IR (neat) 3074, 2926, 1639, 1458, 999, 909 cm-1; 1H NMR (400 MHz, CDCl3) delta 5.79 (1H, dddd,J=17.2, 10.2, 7.0, 7.0 Hz), 4.93 (2H, m), 3.38 (2H, t), 2.02 (2H, dd, J=6.2, 1.1 Hz), 1.83 (2H, m), 1.24-1.44 (12H, m); 13C NMR(400 MHz, CDCl3) delta 139.03, 114.05, 33.93, 33.79, 32.86, 29.38, 29.08, 28.92, 28.76, 28.18.
With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0 - 20℃; for 2h;
General procedure: Triphenylphosphine (9.23 g, 35.2 mmol) was added in several portions to a cooled (0 C) solution of 9-decen-1-ol or 10-undecen-1-ol (32.0 mmol) and CBr4 (33.6 mmol, 11.1 g) in dichloromethane (50 ml). The reaction mixture was stirred for 1 h at 0 C and 1 h at room temperature and subsequently evaporated. The residue was filtered through a short silica gel column (5 × 10 cm) in hexane as a mobile phase. The eluate was evaporated and the crude bromide was dissolved in acetone (150 ml) and N-methyl-morpholine N-oxide (10 ml of 50% aqueous solution, 48.0 mmol) and osmium tetroxide (2.0 g of 4% aqueous solution) were added. The reaction mixture was stirred for 3 h at room temperature, then concentrated ( 50 ml) and partitioned between ether (100 ml) and an aqueous solution of sodium thiosulfate (100 ml). The aqueous layer was washed with ether again (50 ml). The combined ether portions were dried over MgSO4, filtered and evaporated. The residue was purified on a short silica gel column (5 × 10 cm) in ethyl acetate/hexane (3:2). The fractions were evaporated and the product was crystallized from toluene-hexane. Yield: 6.85 g of 10-bromo-1,2-decandiol or 7.31 g of 11-bromo-1,2-dodecanediol (85%).
With phosphorus tribromide; In toluene; at -10℃; for 1h;Inert atmosphere;
A five liter reaction flask was fitted with a mechanical stirring apparatus, a condenser, an addition funnel, and a thermocouple. The reaction flask was flame dried, and then cooled under a nitrogen atmosphere to room temperature. Under a static nitrogen blanket the reaction flask was charged with 10-undecen-1-ol (468 g, 3 mol) and toluene (1 L) while stirring. The contents were cooled to -10 C. and phosphorus tribromide (270 g, 1 mol) was added dropwise. The temperature was maintained at -10 C. with the aid of a Jack-o-matic, and the reaction mixture was aged for one hour. The reaction mixture was subsequently quenched and washed with brine (1 L). The organic layer was removed, and the product was distilled to provide 11-bromo-undec-1-ene (boiling point 95 C. at a pressure of 10 mm Hg).[0030]1H NMR: 5.77-5.86 ppm (m, 1H), 4.99 ppm (d, 1H, J=17.2 Hz), 4.93 ppm (d, 1H, J=10.2 Hz), 3.42 ppm (t, 2H, J=6.9 Hz), 2.01-2.07 ppm (m, 2H), 1.81-1.89 ppm (m, 2H), 1.36-1.43 ppm (m, 4H), 1.29 ppm (br, 8H)
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 0.5h; Inert atmosphere;
Synthesis of 10-undecene-1-ol (3):
To a stirred solution of LiAlH4 (1.50 g, 40.76 mmol) in dry THF (100 mL) was added dropwise 10-undecenoic acid (5.0 g, 27.17 mmol) in dry THF (10 mL) with vigorous stirring at 0 °C and the mixture was stirred for 30 min at room temperature. The reaction mixture was quenched with ethyl acetate. The solution was filtered and the organic layer was washed with H2O, brine and dried over Na2SO4. After removal of the solvent, the residue was purified by column chromatography (4% ethyl acetate in hexane) afforded (3) as a colorless oil (4.48 g, 97%). Spectroscopic data were consistent with the literature data.11 IR (neat) max: 3370, 3076, 2926, 1639, 1460, 1054, 908 cm-1; 1H NMR (300 MHz, CDCl3) : 1.24-1.41 (12H, m, H-3, H-4, H-5, H-6, H-7, H-8), 1.49-1.59 ( 2H, m, H-2), 1.98-2.07 (2H, m, H-9), 3.59 (2H, t, J = 6.79 Hz, H-1), 4.87-4.99 (2H, m, H-11), 5.68-5.83 (1H, m, H-10); m/z ( EI) 152 [M+-18].
96%
With lithium aluminium tetrahydride In diethyl ether for 3h; Heating;
95%
With lithium aluminium tetrahydride In tetrahydrofuran for 12h; Heating;
95%
With lithium aluminium tetrahydride In tetrahydrofuran for 12h; Heating;
93%
With lithium aluminium tetrahydride In tetrahydrofuran for 2h; Heating;
92%
With indium(III) bromide; 1,1,3,3-Tetramethyldisiloxane In chloroform at 60℃; for 1h; Inert atmosphere;
90%
With sodium bis(2-methoxyethoxy)aluminium dihydride In benzene for 1h; Heating;
90%
With samarium diiodide; water; triethylamine In tetrahydrofuran at 20℃; for 2h; Inert atmosphere;
88%
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 50℃;
79%
Stage #1: 10-undecenoic acid With trimethylphenylsilane; C69H55ClP3Ru In tetrahydrofuran at 60℃; for 16h; Glovebox;
Stage #2: With hydrogenchloride In tetrahydrofuran; water at 20℃; for 1h; Glovebox; chemoselective reaction;
77%
With lithium aluminium tetrahydride In diethyl ether for 16h; Ambient temperature;
65%
With lithium aluminium tetrahydride In tetrahydrofuran at -10 - 70℃; for 66h;
10-Undecen-1-ol (6)
LiAlH4 (1.04 g, 27.4 mmol, 3 eq) was added slowly in portions to a solution of 10-undecenoic acid (5) (1.70 g, 9.22 mmol, 1 eq) in dry THF (92 mL, 0.10 M) at -10°C. The reaction mixture was allowed to warm to rt and then stirred at 70°C for 66 h. The reaction mixture was cooled to 0 °C and then quenched by the slow addition of water (50 mL) followed by 1 M aqueous HCl (25 mL). The mixture was allowed to warm to rt and the separated aqueous layer was extracted twice with diethyl ether (100 mL). The combined organic extracts were dried over sodium sulphate, filtered and then concentrated in vaccuo. The crude residue was purified by flash column chromatography on silica using a gradient of 15-20% ethyl acetate in petroleum ether as eluent to give the alcohol 6 (1.02 g, 65%) as a colourless oil; δH (300 MHz, CDCl3) 5.80 (1H, ddt, J 17.0, 10.2 and 6.7, H2C=CH), 5.02-4.86 (2H, m, H2C=CH), 3.62 (2H, t, J 6.6, CH2OH), 2.07-1.97 (2H, m, H2C=CHCH2), 1.58-1.49 (3H, m, CH2 and OH), 1.39-1.23 (12H, m, 6x CH2). The 1H NMR data recorded for 6 was identical to the data reported in the literature [2].
49%
With sodium tetrahydroborate; benzene-1,2-diol; trifluoroacetic acid In tetrahydrofuran at 25℃; for 4h;
With lithium aluminium tetrahydride; diethyl ether
With sodium bis(2-methoxyethoxy)aluminium dihydride
Multi-step reaction with 2 steps
1: sulfuric acid / 24 h / Reflux
2: diisobutylaluminium hydride / tetrahydrofuran; hexane / 5 h / -78 °C
With hydrido(phosphonite)cobalt(I); 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In 2-methyltetrahydrofuran for 16h; Sealed tube; Darkness; Schlenk technique; chemoselective reaction;
With diisobutylaluminium hydride In tetrahydrofuran; dichloromethane at -78℃; for 3h;
91%
With C30H34Cl2N2P2Ru; potassium methanolate; hydrogen In tetrahydrofuran at 20℃; Glovebox; Autoclave; chemoselective reaction;
30 Example 30: Chemoselective hydrogenation of unsaturated ester compounds catalyzed by ruthenium complex Il at room temperature
General procedure: In a glove box, add a ruthenium complex Il (0.75 mg, 0.001 mmol),Potassium methoxide (7 mg, 0.1 mmol), tetrahydrofuran (2 mL), and ester compound (1 mmol).After sealing the autoclave, take it out of the glove box and fill it with 5atm of hydrogen.The reaction vessel was stirred at room temperature for 16 to 24 hours.After slowly releasing excess hydrogen, the reaction solution was depressurized to remove the solvent, and the residue was purified by a short column of silica gel to obtain an alcohol compound.The results are shown in Table 8.
90%
With ethanol; RuCl<SUB>2</SUB>(PPh<SUB>3</SUB>)(Ph<SUB>2</SUB>P(CH<SUB>2</SUB>)<SUB>2</SUB>NHCH<SUB>2</SUB>Py); potassium <i>tert</i>-butylate In toluene at 80℃; for 16h;
With tetrahydrofuran; potassium m-borate; lithium chloride
With lithium aluminium tetrahydride; diethyl ether
With [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; hydrogen; sodium methylate In toluene at 100℃; for 6h; Inert atmosphere; Autoclave; chemoselective reaction;
4
EXAMPLE 4 Under argon, RuCl2(PNNP) catalyst 4a (7.5 mg, 0.01 mol %) in toluene (5 ml) are treated 5 min with ultrasound to give a fine suspension which is added to a suspension of ethyl 10-undecenoate 1b (19.2 g, 90 mmol) and NaOMe (0.5 g, 9 mmol) in toluene (16 ml) in a 120 ml Premex autoclave under argon. The autoclave is flushed three times with hydrogen and then heated at 100° C. under 50 bar hydrogen and 1200 rpm with overhead stirring. After 6 hours the GC-analysis revealed 6% substrate 1b, 90% 10-undecenol 2a, 4% undecanol 2b. CO/DB selectivity: 96:4. After 20 h the autoclave is cooled, the pressure released and the content of the autoclave poured onto 2% H3PO4 (10 ml). After phase separation the organic phase is washed with water (2×30 ml), dried over MgSO4, filtered and evaporated. The residue of 15.6 g consisted of 80% 10-undecenol 2a, 15% undecanol 2b and 5% isomer 2d according to GCMS and NMR.
With pyridine at 0 - 20℃; for 19h; Inert atmosphere;
95%
With pyridine for 2h; Ambient temperature;
95%
With pyridine at 20℃; for 2h;
92%
With pyridine at 60℃; for 3h;
91%
With manganese(II) chloride tetrahydrate In neat (no solvent) at 25℃; for 4h;
General procedure for acetylation
General procedure: To a stirred mixture of alcohol/phenol/thiohenol/amine (1 mmol) and acetic anhydride(1.1 mmol), 0.01 mmol of MnCl24H2O was added at room temperature. The reaction mixture was stirred until alcohol/phenol/thiohenol/amine was consumed, the progress of the reaction was monitored by TLC. The reaction mixture was quenched with saturated aq. NaHCO3 and extracted with ethyl acetate (10mL 3). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude was passed through a small pad of silica gel (eluent: hexane: ethyl acetate) to obtain pure acetates (acetamides were precipitated out/crystallized direct from the reaction mixture) and characterized by 1H NMR and IR spectroscopy. The data was found to be in accord with previously reported acetates. Characterization data and 1H NMR spectra can be found via the “SupplementaryContent” section of this article’s webpage.
86%
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 1h;
75%
With pyridine at 60℃; for 3h;
75%
With pyridine at 60℃; for 3h;
Undec-10-en-1-yl acetate (1w)
To a solution of 10-undecen-1-ol (0.50 g, 3.20 mmol, 1.00 equiv.) in pyridine (10 mL) was added acetic anhydride (0.91 mL, 9.60 mmol, 3.00 equiv.). After stirring for 3 h at 60 °C, the reaction mixture was diluted with ethyl acetate (25 mL) and washed sequentially with 1 N HCI (25 mL x 5) and brine (25 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated. The crude material was purified by flash column chromatography on silica gel (pentane/ethyl acetate) to afford the title compound. 75% yield; 1H NMR (600 MHz, CDCI3) d 5.83-5.78 (m, 1 H), 5.00-4.91 (m, 2H), 2.04 (s, 3H), 1.62-1.59 (m, 2H), 1.38-1.27 (m, 14H).
Stage #1: 10-Undecen-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 1h; Inert atmosphere;
Stage #2: With triethylamine In dichloromethane at -78 - 23℃; for 1h; Inert atmosphere;
94%
With molecular sieve; tetrapropylammonium perruthenate (VII); N-Methylmorpholine N-oxide In dichloromethane at 20℃; for 1h;
93%
With pyridine; oxygen In toluene at 80℃; for 8h;
91%
With pyridine; 4 A molecular sieve; oxygen for 17h;
90%
With pyridinium chlorochromate In dichloromethane for 2h; Molecular sieve;
Undec-10-enal (3)
In a 1 L flame-dried three-necked flask equipped with magnetic stirrer, were added dry dichloromethane (270 mL), pyridinium chlorochromate (85.44 g, 396.4 mmol), and finely crushed 3 Å molecular sieves (85 g). 10-undecen-1-ol (9spOH, available from commercialsource) was slowly added to the mixture (45 g, 264.2 mmol). After 2 hours, diethyl ether (270 mL)was added and the resulting heterogeneous mixture was poured in a 4 L beaker equipped with amagnetic stirrer containing diethyl ether (3 L). The remaining tar was triturated 3 times with diethyl ether (100 mL) and the resulting organic solutions were poured in the beaker. After the precipitated chromium byproduct and molecular sieves settled, the supernatant was purified by passing through a large silica plug. The solvents were removed in vacuo and the resulting dark oil was distilled over calcium hydride, affording a sweet-smelling clear liquid (40.1 g, 90%). The 1HNMR was consistent with the published spectrum.1
90%
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium carbonate; isocyanuric acid In ethyl acetate at 0 - 10℃; for 4h;
General Procedure for theoxidation of alcohols employing nitroxyl radical / imide / NaOCl in thepresence of K2CO3.
General procedure: To a mixture ofthe alcohol (3.839 mmol), K2CO3 (2.0 equiv, 7.678 mmol)and cyanuric acid (0.1 equiv, 0.384 mmol) in 20 mL of ethyl acetate were addedTEMPO or AZADO (3 mol%, 0.115 mmol) and 12% NaOCl (1.2 equiv, 4.607 mmol, Wako Pure Chemical Industries, Ltd.)at 0-10°C. The mixture was then stirred to complete. Thereaction mixture was extracted with ethyl acetate. The organic layer wasconcentrated under reduced pressure, and the residue was purified by silica gelcolumn chromatography to afford the corresponding product.
90%
With sodium chlorine monoxide; tetrabutylammonium bromide; Sodium hydrogenocarbonate; potassium bromide In dichloromethane; water monomer at 0℃; for 0.166667h; Schlenk technique;
89%
With pyridinium chlorochromate In dichloromethane at 20℃; for 5h;
88%
With pyridinium chlorochromate In dichloromethane at 23℃; for 16h; Inert atmosphere; Molecular sieve;
87%
With pyridine; air In toluene at 65℃; for 18h;
85%
With pyridinium chlorochromate In dichloromethane at -20℃; for 2h;
84%
With anhydrous Sodium acetate; pyridinium chlorochromate In dichloromethane
79%
Stage #1: 10-Undecen-1-ol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 0.25h; Inert atmosphere;
Stage #2: With triethylamine In dichloromethane for 0.5h; Inert atmosphere;
78%
With 2,2,6,6-tetramethyl-1-piperidinyloxy free radical; dimethylsulfane; oxygen In chlorobenzene at 90℃;
76%
With bis-trimethylsilanyl peroxide In dichloromethane at 25℃;
73%
With pyridinium chlorochromate In dichloromethane at 0℃; for 3h;
71%
With iodosylbenzene; ytterbium(III) nitrate In 1,2-dichloro-ethane at 80℃; for 4h;
70%
With N-Methylmorpholine N-oxide In dichloromethane for 3h; Ambient temperature;
70%
With NaBrO3; NaHCO3 buffer pH:10; anhydrous sodium carbonate In water monomer; 1,2-dichloro-ethane at 70℃; for 1.2h;
With hydrogen; copper(II) oxide
92 % Chromat.
With N-chloro-succinimide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetra-n-butyl-ammonium chloride; Sodium hydrogenocarbonate; potassium carbonate In dichloromethane for 24h; Ambient temperature; pH 8.6;
22 % Chromat.
With pyridine; 4 A molecular sieve; oxygen In toluene at 100℃; for 1h;
100 % Chromat.
With N-chloro-succinimide; 4 A molecular sieve; potassium carbonate In dichloromethane at 20℃; for 0.5h;
77 % Chromat.
With N-tert-butylbenzenesulfinimidoyl chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 0 - 20℃; for 1h;
99 % Chromat.
With N-chloro-succinimide; N-tert-butylbenzenesulfenamide; potassium carbonate In dichloromethane at 20℃; for 0.5h;
With poly[4-(diacetoxyiodo)styrene]; 2,2,6,6-tetramethyl-1-piperidinyloxy free radical In acetone at 20℃; for 4h;
Multi-step reaction with 4 steps
1: 73 percent / triethylamine / CH2Cl2 / 0.25 h / 0 °C
2: 93 percent / NaI / acetone / 2 h
3: 72 percent / AgNO2 / diethyl ether / a.) 0 deg C, 15 h, b.) room temperature, 8 h
4: 1.) NaH, tert-butyl alcohol, 2.)KMnO4, H3BO3 / 1.) pentane, 20 min, 2.) benzene, water, 2 min
Multi-step reaction with 2 steps
1: 1.) lead tetraacetate, Mn(OAc)2*4H2O / 1.) benzene, reflux
With pyridine-SO3 complex; dimethyl sulfoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.5h;
With tetrapropylammonium perruthenate (VII); N-Methylmorpholine N-oxide In dichloromethane at 20℃; for 1h; Molecular sieve; Inert atmosphere;
With Dess-Martin periodane In dichloromethane at 20℃; for 2h; Inert atmosphere;
50 mg
With hydrogenchloride; C18H38N2O(1+)*F6P(1-); 1-n-butyl-3-methylimidazolium bistrifluoromethylsulfonylamide; NaNO2 In water monomer at 60℃; for 5h;
With alcohol dehydrogenase from Escherichia coli; nicotinamide adenine dinucleotide In dimethyl sulfoxide at 25℃; Enzymatic reaction;
90 %Chromat.
With 3-(tert-butoxycarbonyl amino)-9-azabicyclo[3.3.1]nonane N-oxyl; oxygen; NaNO2 In acetic acid at 25℃; for 1.5h;
Typical procedure for the aerobic oxidation of p-methylbenzyl alcohol to p-methyl benzaldehyde (Table 2, entry 2):
General procedure: A 25-mL tube equipped with a magnetic stirrer bar was added p-methylbenzyl alcohol (0.122 g, 1 mmol), sodium nitrite (5.5 mg, 8 mol%) and 3-(tert-butoxycarbonyl amino)-9-azabicyclo[3.3.1]nonane N-oxyl (3-BocNH-ABNO) (7.7 mg, 3 mol%). After the air in the tube was replaced with O2, 1 mL of acetic acid was added with syringe. Then the mixture was stirred under dioxygen atmosphere (balloon) at room temperature until the reaction was completed. After the reaction was finished, to the reaction mixture was added 8 mL of diethyl ether. Then the mixture was transferred into a separation funnel, and washed with saturated sodium bicarbonate solution (10 mL×3). The aqueous phase was extracted with 8 mL of ether. The combined organic phases was concentrated on a rotary evaporator and the residue was purified by column chromatography on silica gel using petroleumether/diethyl ether as eluent to afford p-methyl benzaldehyde as a colorless liquid; yield: 0.108 g (90%).
With dmap; [2,2]bipyridinyl; copper (I) iodide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In acetonitrile at 20℃; for 2h;
With potassium dioxotetrahydroxoosmate(VI); potassium carbonate; potassium hexacyanoferrate(III) In <i>tert</i>-butyl alcohol for 24h; Ambient temperature;
70%
With dihydrogen peroxide In formic acid at 30℃; for 2h;
With bromine In diethyl ether at -10 - 0℃; for 0.5h;
100%
With bromine In tetrachloromethane for 1h;
97%
With bis(1,3-dimethyl-2-imidazolidinone) hydrotribromide In dichloromethane at 20℃; for 1h;
4.2 Typical procedure for the bromination of olefins with 3a
General procedure: To a solution of 1-tetradecene (7a, 408mg, 2.08mmol) in CH2Cl2 (4mL) was added 44 3a (990mg, 2.11mmol), and the mixture was stirred at 20°C for 1h. The reaction mixture was then diluted with hexane (50mL) and washed with water (20mL×2). The organic layer was dried over Na2SO4 (15g) and concentrated in vacuo. The crude residue (690mg) was purified using silica gel column chromatography (eluent: hexane) to afford 1,2-dibromotetradecane (8a, 683mg, 92%) [23] as a colourless liquid;
92%
With bromine In dichloromethane at 4℃;
37%
With 1,1,1,3',3',3'-hexafluoro-propanol; N,N,N,N-tetraethylammonium tetrafluoroborate; ethylene dibromide In acetonitrile at 20℃; Inert atmosphere; Electrolysis;
With bromine
With bromine at -10 - 0℃; Yield given;
With bromine In dichloromethane 1.) -5 to 0 deg C, 4 h, addition of bromine; 2.) 0 deg C, 4 h; Yield given;
With bromine In tetrachloromethane for 4h; Ambient temperature; Yield given;
With diisobutylaluminium hydride In tetrahydrofuran; hexane at -78℃; for 5h;
98%
With C17H16BrMnNO3P; potassium <i>tert</i>-butylate; hydrogen In 1,4-dioxane at 100℃; for 6h; Autoclave; chemoselective reaction;
96%
With isopropyl alcohol In hexane at 0 - 20℃; for 0.25h; Inert atmosphere;
96%
Stage #1: Methyl 10-undecenoate With sodium triethylborohydride In diethyl ether; toluene at 20℃; for 8h; Inert atmosphere;
Stage #2: With sodium hydroxide In methanol; diethyl ether; toluene at 20℃; for 2h;
95%
With lithium aluminium tetrahydride In diethyl ether for 3h; Heating;
95.4%
With lithium aluminium tetrahydride In diethyl ether for 2h;
90%
With <i>tert</i>-butyl alcohol In tetrahydrofuran electrolysis (Mg electrodes, LiClO4);
85%
EXAMPLE 3 (REDUCTION OF METHYL 10-UNDECENOATE)
EXAMPLE 3 (REDUCTION OF METHYL 10-UNDECENOATE) General procedure I was followed to reduce methyl 10-undecenoate (594 mg, 3 mmol). The reduction took 9 hours at 40° C. Work-up yielded 431 mg (85% yield) of 10-undecen-1-ol as a clear oil.
80%
Stage #1: Methyl 10-undecenoate With phenylsilane; potassium hydroxide at 20℃; for 1h;
Stage #2: With hydrogenchloride; water In tetrahydrofuran at 20℃; for 1h;
71%
Stage #1: Methyl 10-undecenoate With phenylsilane; fac-[Mn-(xantphos)(CO)3Br] at 120℃; for 12h; Inert atmosphere;
Stage #2: With water; sodium hydroxide In methanol at 20℃; Inert atmosphere;
70%
With Triethoxysilane at 60℃; for 0.5h;
69%
With potassium <i>tert</i>-butylate; hydrogen; C27H23BrMnN2O2P In ethanol at 90℃; for 20h; chemoselective reaction;
65%
Stage #1: Methyl 10-undecenoate With [CpFe(CO)2(PCy3)][BF4]; phenylsilane at 100℃; for 24h; Irradiation; Neat (no solvent); Inert atmosphere;
Stage #2: With hydrogenchloride; water In tetrahydrofuran at 20℃; for 1h;
With lithium aluminium tetrahydride In diethyl ether
With OsHCl(CO)[(iPr)2PNH(CH2)2NHCH2Py]; potassium <i>tert</i>-butylate; hydrogen In tetrahydrofuran at 100℃; for 1h; Autoclave; regioselective reaction;
15
EXAMPLE 15. TYPICAL PROCEDURE FOR HYDROGENATION OF ESTERS USINGCOMPLEXES (la), AND (3).A solution of catalyst 1 (5.2 mg/mL) and a base (0.2 mmol) in THF was mixed with 0.02 mol of the ester substrate in 6 mL of THF. The mixture was then transferred into a 75 mL stainless-steel reactor (Parr 4740) equipped with a magnetic stir bar. The reactor was purged by two cycles of pressurization/venting with H2 (150 psi, 10 Bar), pressurized with H2 (725 psi, 50 Bar), and was disconnected from the H2 source. The hydrogenation was conducted at 40-100 °C. At the end of the required reaction time, the reactor was placed into a cold-water bath and depressurized afier cooling to the ambient temperature.
100 %Chromat.
With diisobutylaluminium hydride In toluene at 50℃; for 1h; Inert atmosphere;
Reaction procedure
General procedure: The reaction of UnCOOMe with alkylaluminum and MAO was carried out as following procedure: To the 0.2 M solution of UnCOOMe diluted with toluene (50 C) in N2 atmosphere,1.0-1.4 M of alkylaluminium (or MAO)/ n-decane solution (aluminum concentration was exactly determined by ion chromatography) was injected by syringe to start reaction. 1.0 ml of reaction mixture was treated with 3.0 ml of 1N HCl, and then the organic layer was analyzed by GC to determine the resulting products. Dried solvents (toluene and n-decane) used for the reaction were purchased from Wako Pure Chemical Industries, Ltd., and used without further purification. Alkylaluminum was purchased from Nippon Aluminum Alkyls, Ltd., MAO was purchased from TosohFinechem Corporation, and the remaining trimethylaluminum was evaporated in vacuo prior to use.
96 %Chromat.
With C36H62N2OP2Ru; hydrogen In isopropyl alcohol at 25℃; for 16h; Autoclave; chemoselective reaction;
With C22H14MnN2O4(1+)*BF4(1-); potassium hydride In tetrahydrofuran at 50℃; Inert atmosphere; Glovebox; Sealed tube;
With toluene-4-sulfonic acid In dichloromethane for 4h; Ambient temperature;
90%
With hydrogenchloride 1) 0 deg C, 4h 2) r.t., 24h;
90%
With hydrogenchloride 1) 0 deg C, 4h, 2) r.t., 24h;
90%
With ammonium chloride In tetrahydrofuran for 3h; Heating;
89%
With toluene-4-sulfonic acid In dichloromethane for 3h; Inert atmosphere; Cooling with ice;
3 Synthesis of 11-(9-decenyldimethylsilyl)undecan-1-ol
10-undecen-1-ol (85 g, 0.5 mol) and p-toluenesulfonic acid monohydrate (0.38 g, 2 mmol) were dissolved in dichloromethane (150 mL) and cooled in ice/water bath under nitrogen. To this solution was then added 3,4-dihydro-2H-pyran (50.4 g, 0.6 mol) dropwise over an hour. After the addition, the solution was stirred for additional two hours in ice/water bath and turned into purple. The solution was then diluted with hexanes (300 mL), washed with aqueous sodium bicarbonate (150 mL*2), and dried over MgSO4. After removal of solvents by rotary evaporation, the residual light brown oil was distilled under vacuum and the distillate at 75-79° C. (300 mTorr) was collected to give THP-protected 10-undecen-1-ol (1) as colorless oil (113 g, 89%). To Compound 1 (6.35 g, 25 mmol) was added Karstedt catalyst (2.1% Pt in xylene, 22 mg) and this mixture was then added into a ice/water bath cooled solution of 1,1,3,3-tetramethydisiloxane (6.7 g, 50 mmol) in hexanes dropwise over 30 min. After the addition, the mixture was stirred for additional three hours in ice/water bath. Solvent and excess 1,1,3,3-tetramethydisiloxane were then removed under vacuum to give the crude intermediate compound 2 as a light brown oil which was then added to a solution of 1,9-decadiene (5.2 g, 37.6 mmol) in hexanes (5 mL) dropwise over 30 min at room temperature. After the addition, the mixture was stirred at room temperature for additional two hours and volatiles were then removed under vacuum to give the residual crude intermediate compound 3 as light brown oil. To this brown oil was then added methanol (50 mL) and p-toluenesulfonic acid monohydrate (0.2 g) and the mixture was stirred at room temperature overnight. After removal of volatiles under reduced pressure, the residual brown oil was purified on silica gel using hexanes/ethyl acetate (85/15, v/v) as eluent to give 2.8 g 11-(9-decenyldimethylsilyl)undecan-1-ol as colorless oil (26.3% over three steps). 1H NMR δ 5.75-5.90 (m, 1H), 4.90-5.05 (m, 2H), 3.60-3.68 (t, 2H), 2.00-2.10 (m, 2H), 1.50-1.62 (m, 2H), 1.20-1.45 (br, 28H), 0.45-0.55 (m, 4H), 0.02 (s, 12H).
88.7%
With pyridinium p-toluenesulfonate In dichloromethane for 4h; Ambient temperature;
84%
With K-10 Montmorillonite clay In diethyl ether at 30℃; for 2h;
68%
With toluene-4-sulfonic acid In dichloromethane for 2h;
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 8 - 20℃;
5.1
Example 5 10- (1, 3-DIOXO-1, 3-DIHYDRO-ISOINDOL-2-YL)-DECANOIC ACID. Step 1 : 2-UNDEC-10-ENYL-1, 3-DIOXO-1, 3-DIHYDROISOINDOLE [00104] To a mixture of 10-UNDECEN-1-OL (4.23 g, 24.8 mmol), phthalimide (3.65 g, 24.8 mmol) and triphenylphosphine (6.51 g, 24.8 mmol) in anhydrous tetrahydrofuran (30 ml), a solution of DEAD (3.9 ml, 24.8 mmol) in anhydrous tetrahydrofuran (10 ml) was slowly added while keeping the temperature below 8-10°C. After 2 hours further DEAD (1.0 ml, 6.37 mmol) and triphenylphosphine (1.3 g, 4.96 mmol) were added and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the residue was triturated with diethyl ether (50 ml). The solid was removed by filtration and washed with diethyl ether (2 x 50 ml). The combined filtrates were concentrated and the residue was triturated with hexane (50 ml) at 40°C. The resulting solid was removed by filtration and washed with hexane (2 x 50 ml). The combined filtrates were concentrated and the residue was purified by column chromatography eluting with 10: 2 hexane: ethyl acetate mixture. The product was obtained as a low-melting white solid (4.9 g, 66% yield). M. p. 25-30°C. H NMR (DMSO-d6) 7.83 (4H, M) ; 5.76 (1H, m); 4.96 (1H, dq, J= 17.2, 1.6 Hz); 4.90 (1H, ddt, J= 10.2, 2.2, 1.1) ; 3.54 (2H, t, J=7.1), 1.97 (2H, q, J= 6. 7); 1.56 (2H, M) ; 1.35-1. 15 (14H, M).
66%
Stage #1: phthalimide; 10-Undecen-1-ol With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 8 - 10℃; for 2h;
Stage #2: With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃;
G.1.1
To a mixture of 10-UNDECEN-1-OL (4.23 g, 24.8 mmol), phthalimide (3.65 g, 24.8 mmol) and triphenylphosphine (6.51 g, 24.8 mmol) in anhydrous tetrahydrofuran (30 ml), a solution of DEAD (3.9 ml, 24.8 mmol) in anhydrous tetrahydrofuran (10 ml) was slowly added while keeping the temperature below 8-10°C. After 2 hours further DEAD (1.0 ml, 6. 37 mmol) and triphenylphosphine (1.3 g, 4.96 mmol) were added and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the residue was triturated with diethyl ether (50 ml). The solid was removed by filtration and washed with diethyl ether (2 x 50 ml). The combined filtrates were concentrated and the residue was triturated with hexane (50 ml) at 40°C. The resulting solid was removed by filtration and washed with hexane (2 x 50 ml). The combined filtrates were concentrated and the residue was purified by column chromatography eluting with 10: 2 hexane: ethyl acetate mixture. The product was obtained as a low-melting white solid (4.9 g, 66% yield). M. p. 25-30°C 'H NMR (DMSO-d6) 7.83 (4H, M) ; 5.76 (1H, M) ; 4.96 (1H, dq, J= 17.2, 1.6 Hz); 4.90 (1H, ddt, J= 10.2, 2.2, 1. 1); 3.54 (2H, t, J=7.1), 1.97 (2H, q, J= 6.7) ; 1.56 (2H, M) ; 1.35- 1.15 (14H, M).
38%
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran Ambient temperature;
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran for 4h; Ambient temperature;
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 4h;
2 1-Aminoundec-10-ene
A mixture of 10-undecene-1-ol (5.00 g, 29.36 mmol, 1 equiv), triphenylphosphine (7.70 g, 29.36 mmol, 1 equiv) and phthalimide (4.32 g, 29.36 mmol, 1 equiv) in dry tetrahydrofuran (THF, 30 ML) was stirred vigorously under argon.. diethyl azodicarboxylate (DEAD, 5.11 g, 29.36 mmol, 1 equiv) was diluted with THF (12 ML) and added dropwise by syringe.. After the addition, the reaction was stirred at room temperature for 4 hours.. The solvent was evaporated under vacuum and ether (30 ML) was added to precipitate the triphenylphosphine oxide and hydrazine dicarboxylate which were removed by filtration.. The precipitate was rinsed with ether (2*30 ML) and the combined filtrates were evaporated to afford a yellow solid.. The yellow solid was triturated with warm hexanes (3*50 ML) and filtered.. The combined hexanes were evaporated to give 1-phthalimidylundec-10-ene as a yellow wax.
With N,N-diethyl-α,α-difluoro(meta-methylbenzyl)amine In n-heptane for 0.166667h; microwave irradiation;
81%
With 4 A molecular sieve; 4‐methylbenzenesulfonyl fluoride; N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran for 17h; Heating;
70%
With 18-crown-6 ether; 1,2-Diiodoethane; triphenylphosphine; caesium fluoride In N,N-dimethyl-formamide at 120℃; for 2h; Sealed tube; Inert atmosphere;
69%
With potassium fluoride; N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran; N,N-dimethyl-formamide at 60℃; for 1h; Sealed tube;
Multi-step reaction with 2 steps
1: Et3N / CH2Cl2 / 0.5 h / -10 - 0 °C
2: 48 percent / KF; 18-crown-6 / acetonitrile / 40 h / Heating
Multi-step reaction with 2 steps
1: 85 percent / KF / diethyl ether / 0 °C
2: 83 percent / HBGF / 2 h / 125 °C
Stage #1: 10-Undecen-1-ol With t-butyl ammonium iodide In tetrahydrofuran at 0 - 20℃;
Stage #2: benzyl bromide In tetrahydrofuran at 20℃; for 3.5h;
94%
With tetra(tert-butyl)ammonium iodide; sodium hydride In tetrahydrofuran at 0℃;
86%
Stage #1: 10-Undecen-1-ol With tetra-(n-butyl)ammonium iodide; sodium hydride In hexane; N,N-dimethyl-formamide; mineral oil at 0 - 25℃; for 3h; Inert atmosphere;
Stage #2: benzyl bromide In hexane; N,N-dimethyl-formamide; mineral oil at 21 - 25℃; for 96h; Inert atmosphere;
78%
With sodium hydride In N,N-dimethyl-formamide
70%
With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃;
66%
With potassium <i>tert</i>-butylate In tetrahydrofuran for 15h; Heating;
With sodium hydride 1) in THF, 60 deg C, 1h, 2) reflux; Yield given. Multistep reaction;
With 1H-imidazole In dichloromethane at 20℃; for 3h;
4.1 TBS protection of undecenol to afford 6
Imidazole (1.02 g, 14.98 mmol) and TBSCl (2.26 g, 14.99 mmol) were added in turn to a solution of undecenol (2 mL, 9.98 mmol) in dry CH2Cl2 (30 mL) stirred in an ice-water bath. Stirring was continued at ambient temperature for 3h. Water (20 mL) was added. The mixture was extracted with CH2Cl2 (3×30 mL). The combined organic layers were washed with brine (20 mL) and dried over anhydrous Na2SO4. Removal of the drying agent by filtration and concentration on a rotary evaporator gave a crude oil, which on purification by column chromatography on silica gel (30:1 PE/EtOAc) afforded the known 6 as a colorless oil (2.87 g, 10.09 mmol, 100%). 1H NMR (500MHz, CDCl3) δ 5.82 (ddt, J=17.0, 10.2, 6.7Hz, 1H), 5.00 (ddd, J=17.1, 3.6, 1.6Hz, 1H), 4.93 (ddt, J=10.2, 2.1, 1.2Hz, 1H), 3.61 (t, J=6.6Hz, 2H), 2.07-2.02 (m, 2H), 1.55-1.48 (m, 2H), 1.42-1.35 (m, 2H), 1.32-1.28 (m, 10H), 0.90 (s, 9H), 0.06 (s, 6H).
98%
With 1H-imidazole at 20℃; Neat (no solvent);
97%
With 1H-imidazole; dmap In dichloromethane at 0 - 20℃; Inert atmosphere;
92%
With 1H-imidazole In N,N-dimethyl-formamide
92%
With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃;
92%
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 1h;
83%
Stage #1: 10-Undecen-1-ol With 1H-imidazole In dichloromethane for 0.0833333h;
Stage #2: tert-butyldimethylsilyl chloride In dichloromethane at 20℃; for 1h;
General Procedure for the formation of silyl ethers (1a).
General procedure: The starting material, 2-(3,4-dimethoxyphenyl)-ethan-1-ol (521 mg, 2.86 mmol, 1.0 equiv) was dissolved in dichloromethane (20 mL) and imidazole (583 mg, 8.58 mmol, 3.0 equiv) was added. The mixture was stirred for 5 minutes. tert-Butyldimethylsilyl chloride (518 mg, 3.43 mmol, 1.2 equiv) was added and the reaction mixture was stirred at room temperature for 1 hr. Water (20 mL) and dichloromethane (20 mL) were added and the mixture was shaken in a separating funnel. The aqueous layer was separated and washed with dichloromethane (2 x 5 mL). The combined organic layers were washed with water (20 mL), brine (20 mL) and dried over MgSO4. Following filtration, the solvent was removed under reduced pressure. The crude material was purified by column chromatography on silica gel (eluting with a gradient from petroleum ether to 1:1 petroleum ether : ether) to afford 820mg of 1a (97%).
78%
With dmap; triethylamine In dichloromethane at 20℃; for 24h; Inert atmosphere;
74%
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 72h;
65%
With 1H-imidazole In dichloromethane at 0 - 20℃; for 4h;
With 1H-imidazole In dichloromethane at 20℃; for 1h;
With trimethylamine In diethyl ether at 0 - 20℃; for 3h;
99%
With trimethylamine In dichloromethane at 0℃; for 1h; Inert atmosphere; Sealed tube;
98%
With triethylamine In dichloromethane
98%
Stage #1: undec-10-en-1-ol With triethylamine In dichloromethane at 0℃; for 0.25h; Inert atmosphere;
Stage #2: methanesulfonyl chloride In dichloromethane at 0 - 20℃; for 1.5h; Inert atmosphere;
88%
With pyridine at 0℃; for 15h;
81%
With triethylamine In dichloromethane at 0℃; for 3h;
73%
With triethylamine In dichloromethane at 0℃; for 0.25h;
142 g
With triethylamine In dichloromethane at 0℃;
With triethylamine In dichloromethane for 2h;
With triethylamine In dichloromethane at -10 - 0℃; for 0.5h;
With triethylamine In dichloromethane at 20℃; for 2h;
With triethylamine In dichloromethane
Stage #1: undec-10-en-1-ol With triethylamine In toluene at 20℃; for 0.5h;
Stage #2: methanesulfonyl chloride In toluene at 0℃;
With 4-dimethylaminopyridine; triethylamine In dichloromethane at 0 - 20℃;
With aluminum oxide In hexane for 20h; Ambient temperature; other tert-butyldimethylsilyl ethers;
95%
With toluene-4-sulfonic acid In methanol; dichloromethane at 20 - 25℃; for 0.333333h; Flow reactor;
General Procedure for the flow deprotection of silyl ethers (3a-j).
General procedure: The system (Figure 4) was primed with solvent (DCM and 0.3 M aqueous NaOH) prior to the introduction of the substrates. Substrates were present as 0.034 M solutions (20 mL) in glass vials. These were placed in a square 4 x 4 rack. Following initiation of the computer-vision system (and checking to make sure the aqueous-out tap was opening/closing properly), activation of the autosampler/liquid-handling schedule was initiated by pressing ‘s’ on the computer keyboard. The outlet of the flow stream for each product was then collected until the autosampler moved to the waste position between each run. 5 mL of substrate was taken up during each run, 4 mL of which entered the holding loop (the line between the autosampler and 3-way-valve 1 was 1 mL in volume). Outlet collection flasks were changed manually. The products were isolated by removing solvent under reduced pressure.
94%
With water; aluminium In hexane for 24h; change in substrate concentration in time, comparison other silyl groups;
With LACTIC ACID; triethylamine In dichloromethane at 0℃;
94%
With pyridine at 0 - 20℃; for 2h; Inert atmosphere;
92%
With pyridine
92%
With pyridine In chloroform for 2.5h;
91%
With pyridine at 15 - 20℃; for 2h;
89.7%
With triethylamine; trimethylamine In dichloromethane at 0℃; for 1.5h;
89.6%
With dmap; triethylamine In dichloromethane at 0℃; for 2h; Inert atmosphere;
Synthesis of undec-10-enyl- 4-methylbenzenesulfonate (4):
Triethyl amine (2.78 mL, 20 mmol), p-tosylchloride (2.28 g, 12 mmol) and a catalytic amount of DMAP in 10 mL dry CH2Cl2 were added to 10-undecene-1-ol (1.7 g, 10 mmol) in dry CH2Cl2 solution at 0 °C. The reaction mixture was stirred for 2 h at 0 °C under N2 atmosphere. The resulting mixture was washed with 50 mL of H2O, brine and dried over Na2SO4. After concentrated in vacuo, the residue was purified by column chromatography (1% ethyl acetate in hexane) afforded (4) (2.90 g, 89.6%) as a clear syrup. Spectroscopic data were consistent with the literature data.12 IR (neat) max: 3072, 2926, 2854, 1638, 1598, 1365, 1186, 911, 822, 661 cm-1; 1H NMR (300 MHz, CDCl3) : 1.17-1.43 (12H, m, H-3, H-4, H-5, H-6, H-7, H-8), 1.57-1.69 ( 2H, m, H-2), 1.98-2.05 (2H, q, J = 6.6 Hz, H-9), 2.46 (3H, s, ArCH3), 3.98 (2H, t, J = 6.4 Hz, H-1), 4.88-5.00 (2H, br m, H-11), 5.68-5.81 (1H, br m, H-10), 7.31 (2H, d, J = 8.1 Hz, ArH), 7.76 (2H, d, J = 8.1 Hz, ArH); m/z (ESI) 347 [M+Na] +.
79%
With trimethylamine hydrochloride; triethylamine In dichloromethane at 0 - 20℃;
78%
With pyridine at 0℃; for 16h;
77%
With dmap; triethylamine In dichloromethane at 0℃; Glovebox;
75%
With triethylamine In dichloromethane for 4h;
65%
With triethylamine In dichloromethane at 20℃;
58%
With triethylamine In tetrahydrofuran at 70℃; for 8h;
29%
With pyridine In water Inert atmosphere;
In pyridine
With pyridine at 0℃; for 12h;
With pyridine
With potassium hydroxide In tetrahydrofuran 1.) 0 deg C, 4 h, 2.) RT, 6 h;
4-oxo-4-(undec-10-en-1-yloxy)butanoicacid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
89%
With dmap In dichloromethane at 45℃; for 56h;
4-Oxo-4-(undec-10-en-1-yloxy)butanoic acid (7)
4-(Dimethylamino)pyridine (DMAP) (6.4 mg, 52 μmol, 0.05 eq) was added to a solution of undec-10-en-1-ol (6) (220 mg, 1.29 mmol, 1.22 eq) and succinic anhydride (106 mg, 1.06 mmol, 1 eq) in dry CH2Cl2 (23 mL, 0.05 M) and stirred at 45 °C for 56 h. The reaction mixture was cooled to rt and then concentrated in vaccuo The crude residue was purified by flash column chromatography on silica using a gradient of 15-20% ethyl acetate in petroleum ether as eluent to give the mono-ester 7 (256 mg, 89%) as an off-white solid; mp 39-38 °C (ethyl acetate/petroleum ether); νmax (CDCl3/cm-1) 3547, 3075, 2829, 2856, 1723 and 1176; δH (300 MHz, CDCl3) 10.79 (1H, br. s, COOH), 5.81 (1H, ddt, J 17.0, 10.2 and 6.7, H2C=CH), 5.03-4.90 (2H, m, H2C=CH), 4.08 (2H, t, J 6.7, CH2OCO), 2.71-2.59 (4H, m, OCOCH2CH2COOH), 2.08-1.99 (2H, m, H2C=CHCH2), 1.67-1.56 (2H, m, CH2), 1.42-1.24 (12H, m, 6x CH2); δC (100 MHz, CDCl3) 178.2, 172.6, 139.6, 114.5, 65.5, 34.2, 29.84, 29.79, 29.6, 29.5, 29.3, 28.9, 26.2; m/z (ES) 293.1720 (M++Na, 75%, C15H26O4Na requires 293.1723).
With dmap; triethylamine In dichloromethane for 1h; Ambient temperature;
Stage #1: 10-Undecenal With [CpFe(IMes)(CO)2]I; phenylsilane In tetrahydrofuran at 70℃; for 1h; Inert atmosphere; Irradiation;
Stage #2: With methanol; sodium hydroxide In tetrahydrofuran; water at 20℃; for 1h; Inert atmosphere;
96%
Stage #1: 10-Undecenal With (dppe)2Fe(H)2*(C7H8)2; Na-tetrakis(ethoxy)borate In toluene at 100℃; for 1h; visible light irradiation; Inert atmosphere;
Stage #2: With water; sodium hydroxide In methanol; toluene at 20℃; for 16h;
94%
With diisopropoxytitanium(III) tetrahydroborate In dichloromethane at -20℃; for 0.133333h;
93%
Stage #1: 10-Undecenal With polymethylhydrosiloxane; P(MeNCH2CH2)3N In tetrahydrofuran at 20℃; for 1h;
Stage #2: In tetrahydrofuran at 20℃; for 1h;
85%
With (ethylenediamine)[1,2-bis(diphenylphosphino)ethane]ruthenium(II)[bis(adamantane-1-carboxylate)]; hydrogen; benzoic acid In n-heptane at 70℃; Autoclave; Inert atmosphere;
6 Undec-10-en-1-ol synthesis
Undec-10-enal (84 g, 0.5 mol.), heptane (84 g, 100 wt. %, technical grade), and (ethylenediamine)[1,2-bis(diphenylphosphino)ethane]ruthenium[bis((adamantane-1-carboxylate)] (45.9 mg, 0.05 mmol, 0.01 mol.%) were loaded altogether in a 300 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 10 bars hydrogen. It was then heated to 70° C. and hydrogen pressure was maintained to 10 bars during all the reaction to afford desired product with 90% selectivity. After complete reaction conversion (checked by both hydrogen consumption and GC), autoclave was cooled down to 25° C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After initial flash distillation and further fractional distillation, undec-10-en-1-ol was obtained in 85% yield.
82%
With indium isopropoxide; isopropyl alcohol at 25℃; for 3h; Inert atmosphere;
80%
With trichlorosilane; N,N-dimethyl-formamide In dichloromethane at 0℃; for 6h;
77%
Stage #1: 10-Undecenal With nickel(II) acetate tetrahydrate; tricyclohexylphosphine In tetrahydrofuran at 70℃; for 16h;
Stage #2: With sodium hydroxide In methanol
71%
Stage #1: 10-Undecenal With Cp(CO)2Mn(IMes); diphenylsilane In toluene at 25℃; for 8h; Schlenk technique; Inert atmosphere; UV-irradiation;
Stage #2: With sodium hydroxide In methanol; toluene at 20℃; for 2h; Schlenk technique; Inert atmosphere;
68%
With [Ni(1,3-dimesitylimidazol-2-ylidene)Clcyclopentadienyl]; sodium triethylborohydride; diphenylsilane In tetrahydrofuran at 25℃; for 1h; Inert atmosphere; Schlenk technique; chemoselective reaction;
58%
With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; tris[3,5-bis(trifluoromethyl)phenyl]-borane In 1,4-dioxane at 100℃; for 12h; Glovebox;
General procedure for the hydrogenation reaction
General procedure: In a glovebox, aldehydes (0.25 mmol) and the Hantzsch ester 1 (95 mg, 0.38 mmol) were added to asolution of tris[3,5-bis(trifluoromethy)phenyl]borane (9) (8.1 mg, 12.5 μmol) in 1 mL of anhydrous1,4-dioxane. The reaction mixture was stirred at 25 or 100 C for 12 h. An internal standard (biphenylor mesitylene) was added to the reaction mixture and filtrated through a cotton plug. The resultingsolution was analyzed with gas chromatography.
Multi-step reaction with 2 steps
1: [CpFe(IMes)(CO2)]I / 3 h / 30 °C / Inert atmosphere; Neat (no solvent); visible light irradiation
2: sodium hydroxide / methanol; water / 1 h / 20 °C
With (ethylenediamine)[1,2-bis(diphenylphosphino)ethane]ruthenium(II)[bis(adamantane-1-carboxylate)]; hydrogen In n-heptane at 80℃; for 16h; Autoclave; chemoselective reaction;
95 %Chromat.
With C18H32BrFeNO3P2; sodium formate In methanol; dodecane at 40℃; for 6h; Inert atmosphere; chemoselective reaction;
With hydrogen In isopropyl alcohol at 149.84℃; for 0.5h; Autoclave; chemoselective reaction;
With dichloro(3-phenyl-1H-inden-1-ylidene)bis(tricyclohexylphosphine)ruthenium(II); sodium formate; trimethyldodecylammonium chloride In water at 85℃; Schlenk technique;
With sodium tetrahydroborate In methanol at 0℃; for 1h;
With 2,2'-azobis(isobutyronitrile) at 65℃; for 12h; Inert atmosphere; Sealed tube;
44.1 Step-1: 12, 12, 13, 13, 14, 14, 15, 15, 15-Nonafluoro-10-iodopentadecan-1-ol
A mixture of 1,1,1,2,2,3,3,4,4-nonafluoro-4-iodobutane (40 g, 116 mmol), undec-10-en-1- ol (21.66 g, 127 mmol) and AIBN (1.899 g, 11.56 mmol) was heated at 65 °C In a sealed glass tube filled with nitrogen gas while gentle stirring. After 12 b, the resulting mixture was distilled under vacuum to give 12,12,13, 13, 14, 14, 15,15, 15-nonafluoro-10- iodopentadecan-1-ol (50 g, 97 mmol, 84 % yleld). 1H N R (400 MHz, CDCh): d 4.35 (m, 1H), 3.53 (t, J= 16.0, 6.4 Hz, 2H), 2.97-2.86 (m, 2H), 1.88-1.73 (m, 2H), 1.49-1.42 (m, 2H), 1.33 (s, 14H).
84%
With 2,2'-azobis(isobutyronitrile) at 65℃; for 12h; Inert atmosphere; Sealed tube;
44.1 Step-1: 12, 12, 13, 13, 14, 14, 15, 15, 15-Nonafluoro-10-iodopentadecan-1-ol
A mixture of 1,1,1,2,2,3,3,4,4-nonafluoro-4-iodobutane (40 g, 116 mmol), undec-10-en-1- ol (21.66 g, 127 mmol) and AIBN (1.899 g, 11.56 mmol) was heated at 65 °C In a sealed glass tube filled with nitrogen gas while gentle stirring. After 12 b, the resulting mixture was distilled under vacuum to give 12,12,13, 13, 14, 14, 15,15, 15-nonafluoro-10- iodopentadecan-1-ol (50 g, 97 mmol, 84 % yleld). 1H N R (400 MHz, CDCh): d 4.35 (m, 1H), 3.53 (t, J= 16.0, 6.4 Hz, 2H), 2.97-2.86 (m, 2H), 1.88-1.73 (m, 2H), 1.49-1.42 (m, 2H), 1.33 (s, 14H).
With 2,2'-azobis(isobutyronitrile) at 90℃;
With 2,2'-azobis(isobutyronitrile) at 80℃; for 4h;
With sodium dithionite; sodium hydrogencarbonate In water; acetonitrile at 20℃;
1
Example 1 Synthesis of 12,12,13,13,14,14,15,15,15-Nonafluoro-1-pentadecyl Benzotriazole-5-carboxylate [C4F9-(CH2)11-O2C-C6H4N3]. To a solution of 199.7 grams (0.577 mol) of perfluorobutyl iodide and 93.7 grams (0.550 mol) of 10-undecen-1-ol in a mixture of 700 milliliters of acetonitrile and 300 milliliters of water was added a mixture of 53.8 grams (0.640 mol) of NaHCO3 and 106.2 grams (0.610 mol) of Na2S2O4 in small portions with stirring. The reaction mixture was stirred at room temperature overnight and acidified with 1 N hydrochloric acid. The mixture was extracted with diethyl ether, and the combined organic phases were washed with saturated aqueous NaHCO3 and saturated aqueous NaCl and dried over MgSO4. Concentration afforded 234.4 grams of crude 12,12,13,13,14,14,15,15,15-nonafluoro-10-iodo-1-pentadecanol as a viscous, light amber liquid, which was used in the next step without further purification.
With sodium dithionite; sodium hydrogencarbonate In water; acetonitrile at 20 - 24℃; for 14 - 16h;
CF3 (CF2) 3 (CH2) [LOCH20H] was prepared according to the following method: To a mixture of 199.7 grams (g) of perfluoro-n-butyl iodide and 93.7 g of [10-UNDECEN-1-OL] in a mixture of 700 mL of acetonitrile and 300 mL of water was added a mixture of 53.8 g of sodium bicarbonate and 106.2 g of sodium dithionite in small portions with stirring. The reaction mixture was stirred at room temperature overnight and acidified with 1 N hydrochloric acid. The mixture was extracted with diethyl ether, and the combined organic phases were washed sequentially with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, then dried over anhydrous magnesium sulfate. Concentration afforded 234.4 g of crude CF3 (CF2) 3CH2CHI (CH2) [GCH20H] as a viscous, light amber liquid, which was used without further purification. To a slurry of 130.0 g of zinc powder in 500 mL of ethanol was added 5.0 g of acetic acid. A solution of 230.0 g [OF CF3] (CF2) 3CH2CHI (CH2) [GCH20H] in 100 mL of ethanol was added dropwise with stirring over 1 hr, and the reaction mixture was heated at [50 °C] for 4 hr. The mixture was filtered, the filtrate was concentrated to a viscous, light yellow liquid, and bulb-to- bulb distillation in several portions provided 97.3 g [OF CF3] (CF2) 3 [(CH2)] [LOCH20H] as a colorless solid, b. p. [160-200 °C] at 0.05 torr (7 Pa).
With sodium dithionite; sodium hydrogencarbonate In water; acetonitrile
With tert.-butylhydroperoxide In dichloromethane; water at 0 - 20℃; for 0.583333h; Protection from light;
General TBHP Mediated Wacker Reaction:Table 1 reports individual examples while the following description provides a common reaction scheme used in each example with deviations noted. In the dark, AgSbF6 (51.5 mg, 0.15 mmol), Pd(quinox)Cl2 complex (22.5 mg, 0.06 mmol), and a magnetic stir bar were added to a 100 mL round bottomed flask. DCM (4.8 mL) was added to the flask and the mixture was stirred for 15 min. The mixture was then diluted with DCM (20 mL) and 70 wt % TBHP(aq) (5.2 mL, 36 mmol) was added. The resulting mixture was stirred for an additional 10 min, before being cooled in an ice bath. Once the solution had cooled, the substrate (3.0 mmol) was added with stirring. After 5 min, the ice bath was removed and the reaction mixture was allowed to slowly warm to room temperature. Once TLC indicated complete consumption of starting material, the reaction was quenched with a saturated aqueous solution of Na2SO3 (50 mL) to consume excess TBHP. The mixture was transferred to a separatory funnel and diluted with hexanes (50 mL). The aqueous layer was separated and back extracted with hexanes (25 mL). The combined organics were washed with water (4×25 mL) and brine (50 mL). The combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel flash chromatography if necessary; the product containing fractions were combined and concentrated under reduced pressure. The general reaction scheme was as follows:; Several common protecting groups for allylic alcohols were shown to be compatible with these conditions, providing the methyl ketone products in high yields (Table 1, entries 1-4). No aldehyde product was detected in any of these cases by GC or 1H NMR analysis. Thus, the above approach can be substantially free or completely free of undesired aldehyde products. Additionally, silyl protected allylic alcohols proceed to product at a significantly faster rate, allowing for the use of lower catalyst loadings (entry 2). An acetal-protecting group, was stable to Lewis acidic, aqueous reaction conditions (entry 3). A homoallylic alcohol also was converted to the methyl ketone in excellent yield (entry 5).The corresponding ketones were each confirmed using NMR, IR and HRMS analyses. The 2-oxooctan-3-yl acetate, 3-(tert-butyldimethylsiloxy)octan-2-one, 3-(ethoxymethoxy)octan-2-one, 1-cyclohexyl-2-oxopropyl acetate, 4-(tert-butyldimethylsolxy)-4-phenylbutan-2-one, 2-decanone, methyl 10-oxoundecanoate, 6-(2,2-dimethyl-1,3-dioxolan-4-yl)hexan-2-one, 11-chloroundecan-2-one, 1-p-tolyethanone were recovered as colorless oils. The 11-hydroxyundecan-2-one, tert-butyl 4-acetylphenylcarbamate, and 1-(3-nitro)ethanone were recovered as a white solid having a melting point of 39-40° C., 113-114° C., and 68-70° C., respectively. Similarly, 11-hydroxyundecan-2-one was isolated as a white solid.The catalytic system was further evaluated to determine whether it was a general catalyst for the Wacker oxidation. Excitingly, the current system rapidly consumes decene leading to 2-decanone in good yield with no appreciable amounts of internal isomers (entry 6). Lowering the amount of TBHP led to conversion of decene without significant loss of yield or increase in isomerization (entry 7). Other functional groups were evaluated including an alkene with a free distal alcohol, which was used to demonstrate the scalability of the reaction using a reduced catalyst loading (entries 8 and 9). Additionally, alkenes containing common functional groups including a methyl ester, acetonide, and primary chloride are well tolerated (entries 10-12). A number of styrene derivatives, another challenging substrate class for the Tsuji-Wacker oxidation, were also evaluated. Substituted styrenes with various functional groups were efficiently oxidized, although a highly electron-deficient system led to a lower yield and a trace amount of m-nitro benzaldehyde (entries 13-15). It should be noted that these reactions are exothermic; therefore the oxidations were initiated at 0° C.
93%
With p-benzoquinone; palladium dichloride In water; N,N-dimethyl-formamide at 90℃; for 4h;
93%
With water; oxygen; copper(l) chloride In tetrahydrofuran at 20℃; for 36h;
91%
With tert.-butylhydroperoxide; silver hexafluoroantimonate; [Pd(Quinox)Cl2] In dichloromethane; water at 0 - 20℃; Darkness;
91%
With chromium(VI) oxide; palladium dichloride In water; acetonitrile at 20 - 60℃; for 7h;
4.2 General procedure for oxidation of terminal olefins
General procedure: To a stirred solution of olefin (0.4mmol) in CH3CN (3.5mL) and H2O (0.5mL) were added PdCl2 (3.6mg, 0.02mmol, 5mol%) and CrO3 (20mg, 0.6mmol, 0.5equiv) at room temperature. The reaction mixture was warmed to 60°C and stirred for specified time (see Tables 5-7) in a closed flask. The reaction mixture was then filtered through a small pad of silica gel and washed with EtOAc and the filtrate concentrated. The residue in some cases contained virtually pure compound and no further purification was necessary. In other cases the residue was purified by silica gel column chromatography using petroleum ether/EtOAc as an eluent to afford the methyl ketones.
85%
With pyridine; palladium diacetate; oxygen In isopropyl alcohol; toluene at 60℃; for 25h;
85%
With iron(III) sulfate hydrate; palladium dichloride In water; acetonitrile at 45℃; for 3h; Inert atmosphere;
77%
With [PdCl2(tBu-BINC)]; oxygen In N,N-dimethyl acetamide; water at 70℃; for 48h;
72%
With Pd((-)-sparteine)2Cl2; oxygen In N,N-dimethyl acetamide; water at 70℃; for 18h;
71%
With pyridine; oxygen; isopropyl alcohol In toluene at 60℃; for 27h;
57%
With manganese(IV) oxide; palladium dichloride In water; acetonitrile at 60℃; for 21h;
51%
With oxygen; sodium chloride; palladium dichloride In N,N-dimethyl acetamide; water at 80℃; for 15h;
1; 2 Example 1
10-Undecenol (9 g), DMAc (30 ml), and water (3 ml) were added to the container. PdCl2 (0.5 mol %) and NaCl (0.17 eq.) were added thereto, and the inside of the container was placed in an oxygen atmosphere. Thereafter, by heating at 80° C. for 15 hours, 11-hydroxy-undecane-2-one, which was a target product, was obtained with a yield of 51%.
With oxygen at 100℃; for 16h;
Multi-step reaction with 3 steps
1: Br2 / CCl4 / 4 h / Ambient temperature
2: Na, anhydrous FeCl3 / liquid ammonia / 6 h
3: 90 percent / 70percent H2SO4, HgSO4 / methanol / 5 h / Heating
Multi-step reaction with 3 steps
1: HBr / 130 °C
2: potassium acetate; glacial acetic acid / nachfolgendes Verseifen des neben anderen Produkten entstandenen Diacetats des Undecandiols-(1.10)
3: chromium acetic acid
Multi-step reaction with 3 steps
1: HBr / 130 °C
2: potassium acetate; glacial acetic acid / nachfolgendes Verseifen des neben anderen Produkten entstandenen Diacetats des Undecandiols-(1.10)
3: chromium trioxide; glacial acetic acid / man reinigt ueber die Disulfitverbindung
Multi-step reaction with 3 steps
1: HBr / 130 °C
2: potassium acetate; glacial acetic acid / Destillieren des Reaktionsgemischs und nachfolgenden Verseifen mit alkoh.Kalilauge
3: chromium acetic acid
Multi-step reaction with 3 steps
1: HBr / 130 °C
2: potassium acetate; glacial acetic acid / Destillieren des Reaktionsgemischs und nachfolgenden Verseifen mit alkoh.Kalilauge
3: chromium trioxide; glacial acetic acid / man reinigt ueber die Disulfitverbindung
Multi-step reaction with 3 steps
1: hydrogen bromide / 130 °C
2: potassium acetate; glacial acetic acid / nachfolgendes Verseifen des neben anderen Produkten entstandenen Diacetats des Undecandiols-(1.10)
3: chromium acetic acid
Multi-step reaction with 3 steps
1: hydrogen bromide / 130 °C
2: potassium acetate; glacial acetic acid / nachfolgendes Verseifen des neben anderen Produkten entstandenen Diacetats des Undecandiols-(1.10)
3: chromium trioxide; glacial acetic acid / man reinigt ueber die Disulfitverbindung
Multi-step reaction with 3 steps
1: hydrogen bromide / 130 °C
2: potassium acetate; glacial acetic acid / Destillieren des Reaktionsgemischs und nachfolgenden Verseifen mit alkoh.Kalilauge
3: chromium acetic acid
Multi-step reaction with 3 steps
1: hydrogen bromide / 130 °C
2: potassium acetate; glacial acetic acid / Destillieren des Reaktionsgemischs und nachfolgenden Verseifen mit alkoh.Kalilauge
3: chromium trioxide; glacial acetic acid / man reinigt ueber die Disulfitverbindung
Multi-step reaction with 4 steps
1: hydrogen bromide / 130 °C
2: HBr
3: potassium acetate; glacial acetic acid / nachfolgendes Verseifen des neben anderen Produkten entstandenen Diacetats des Undecandiols-(1.10)
4: chromium acetic acid
Multi-step reaction with 4 steps
1: hydrogen bromide / 130 °C
2: HBr
3: potassium acetate; glacial acetic acid / nachfolgendes Verseifen des neben anderen Produkten entstandenen Diacetats des Undecandiols-(1.10)
4: chromium trioxide; glacial acetic acid / man reinigt ueber die Disulfitverbindung
Multi-step reaction with 4 steps
1: hydrogen bromide / 130 °C
2: HBr
3: potassium acetate; glacial acetic acid / Destillieren des Reaktionsgemischs und nachfolgenden Verseifen mit alkoh.Kalilauge
4: chromium acetic acid
Multi-step reaction with 4 steps
1: hydrogen bromide / 130 °C
2: HBr
3: potassium acetate; glacial acetic acid / Destillieren des Reaktionsgemischs und nachfolgenden Verseifen mit alkoh.Kalilauge
4: chromium trioxide; glacial acetic acid / man reinigt ueber die Disulfitverbindung
Multi-step reaction with 3 steps
1: hydrogen bromide
2: potassium acetate; glacial acetic acid / 150 °C / Verseifung des entstandenen Monoacetats des Undecandiols-(1.10) mit alkoh.Kalilauge
3: chromium acetic acid
Multi-step reaction with 3 steps
1: hydrogen bromide
2: potassium acetate; glacial acetic acid / 150 °C / Verseifung des entstandenen Monoacetats des Undecandiols-(1.10) mit alkoh.Kalilauge
3: chromium trioxide; glacial acetic acid / man reinigt ueber die Disulfitverbindung
Multi-step reaction with 3 steps
1: hydrogen bromide
2: potassium acetate; glacial acetic acid / Destillieren des Reaktionsgemischs und nachfolgenden Verseifen mit alkoh.Kalilauge
3: chromium acetic acid
Multi-step reaction with 3 steps
1: hydrogen bromide
2: potassium acetate; glacial acetic acid / Destillieren des Reaktionsgemischs und nachfolgenden Verseifen mit alkoh.Kalilauge
3: chromium trioxide; glacial acetic acid / man reinigt ueber die Disulfitverbindung
Multi-step reaction with 4 steps
1: hydrogen bromide
2: HBr
3: potassium acetate; glacial acetic acid / nachfolgendes Verseifen des neben anderen Produkten entstandenen Diacetats des Undecandiols-(1.10)
4: chromium acetic acid
Multi-step reaction with 4 steps
1: hydrogen bromide
2: HBr
3: potassium acetate; glacial acetic acid / nachfolgendes Verseifen des neben anderen Produkten entstandenen Diacetats des Undecandiols-(1.10)
4: chromium trioxide; glacial acetic acid / man reinigt ueber die Disulfitverbindung
Multi-step reaction with 4 steps
1: hydrogen bromide
2: HBr
3: potassium acetate; glacial acetic acid / Destillieren des Reaktionsgemischs und nachfolgenden Verseifen mit alkoh.Kalilauge
4: chromium acetic acid
Multi-step reaction with 4 steps
1: hydrogen bromide
2: HBr
3: potassium acetate; glacial acetic acid / Destillieren des Reaktionsgemischs und nachfolgenden Verseifen mit alkoh.Kalilauge
4: chromium trioxide; glacial acetic acid / man reinigt ueber die Disulfitverbindung
With water; p-benzoquinone; palladium dichloride In N,N-dimethyl-formamide at 90℃; for 12h;
1 Example 1
A mixture of 10-undecen-1-ol (16 g), 1,4-benzoquinone (10.2 g), DMF (160 mL), water (16 mL), and PdCl2 (0.34 g) was heated and stirred at 90° C. for 12 hours. The solvent was then evaporated under reduced pressure. The resulting residue was subjected to liquid separation and purified by column chromatography, whereby 11-hydroxyundecan-2-one (15.4 g) was obtained. The spectrum data of the resulting 11-hydroxyundecan-2-one are the following. 1H-NMR (CDCl3) δ ppm: 1.29-1.49 (m, 14H), 2.08 (s, 3H), 2.45 (J=7.6, t, 2H), 3.51 (J=6.5, t, 2H)
With tetrabutyl-ammonium chloride In methanol at 20℃; for 2h; Inert atmosphere; Photolysis;
With 2,2'-azobis(isobutyronitrile) at 80℃; for 4h;
With 2,2'-azobis(isobutyronitrile) at 80℃; for 4h;
With 2,2'-azobis(isobutyronitrile) for 5h; Heating;
With sodium dithionite; sodium hydrogencarbonate In water; acetonitrile at 20℃;
2
Example 2 Synthesis of 12,12,13,13,14,14,15,15,16,16,17,17,18,18,19,19,19-Heptadecafluoro-1-nonadecyl Benzotriazole-5-carboxylate [C8F17-(CH2)11-O2C-C6H4N3]. To a solution of 41.10 grams (75 mmol) of perfluorooctyl iodide and 11.92 grams (70 mmol) of 10-undecen-1-ol in a mixture of 100 milliliters of acetonitrile and 40 milliliters of water was added a mixture of 6.89 grams (82 mmol) of NaHCO3 and 13.58 grams (78 mmol) of Na2S2O4 in small portions with stirring. The reaction mixture was stirred at room temperature overnight and acidified with 1 N hydrochloric acid. The mixture was extracted with diethyl ether, and the combined organic phases were washed with saturated aqueous NaHCO3 and saturated aqueous NaCl and dried over MgSO4. Concentration afforded 43.2 grams of 12,12,13,13,14,14,15,15,16,16,17,17,18,18,19,19,19-heptadecafluoro-10-iodo-1-nonadecanol as a white solid, which was used in the next step without further purification.
With sodium dithionite; sodium hydrogencarbonate In water; acetonitrile at 20 - 24℃; for 14 - 16h;
CF3 (CF2) [7] (CH2) [LOCH2OH] was prepared according to the following method: To a mixture of [41.] 10 g of perfluoro-n-octyl iodide and 11.92 g of [10-UNDECEN-1-OL] in a mixture of 100 mL of acetonitrile and 40 mL of water was added a mixture of 6.89 g of sodium bicarbonate and 13.58 g of sodium dithionite in small portions with stirring. The reaction mixture was stirred at room temperature overnight and acidified with 1 N hydrochloric acid. The mixture was extracted with diethyl ether, and the combined organic phases were washed sequentially with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. Concentration afforded 43.2 g of crude [CF3 (CF2) 7CH2CHI (CH2) GCH2OH] as a white solid, which was used without further purification. To a slurry of 19.6 g of Zn powder in 150 mL of ethanol was added 4.0 g of acetic acid. A solution of the crude CF3 (CF2) [7CH2CHI] [(CH2)] [8CH20H] prepared above in 50 mL of ethanol was added dropwise with stirring over 1 hr, and the reaction mixture was heated at [50 °C] for 4 hr. The mixture was filtered, and the filtrate was concentrated to approximately 45 g of a soft, white solid. The crude [CF3 (CF2) 7 (CH2) L0CH2OH] so obtained was used without further purification.
With triethylamine pentahydrogen fluoride salt; triethylammonium iodide In dichloromethane at 20℃; Electrochemical reaction;
86 %Spectr.
With tin; iodine pentafluoride-pyridine-hydrogen fluoride In dichloromethane at 0 - 20℃; for 17.5h; regioselective reaction;
Iodofluorination of Alkenes Using Sn Powder as a Reductant; General Procedure
General procedure: To a solution of an alkene (0.5 mmol) and IF5-pyridine-HF (481 mg,1.5 mmol) in CH2Cl2 (3 mL) at 0 °C was added Sn powder (119 mg, 1.0mmol), and the mixture was stirred at 0 °C for 30 min and at r.t. for 17h. Then, the solid was removed by filtration through Celite, and the filtrate was poured into water (20 mL). The product was extracted with Et2O (3 × 20 mL), and the combined organic layers were washed with aq. Na2S2O3 (20 mL) and aq. NaHCO3 (20 mL), and dried (MgSO4). After concentration, the product was isolated by column chromatography (silica gel).
With 1H-imidazole; iodine; triphenylphosphine In diethyl ether; acetonitrile for 0.333333h;
98%
With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 0 - 23℃; for 3h;
96%
With 1H-imidazole; iodine; triphenylphosphine In benzene at 20℃; for 3h;
90%
With 1H-imidazole; iodine; triphenylphosphine
As shown in Scheme 1 below, undecylenic acid (1) was esterified with isobutyl alcohol under acid catalysis to yield the isobutyl ester (2) (95% yield, purified by distillation) which was then reduced with metallic sodium by the Boulevenault-Blanc procedure to give 10-Undecen-l-ol (3) (82% yield, purified by distillation). The alcohol was then iodinated by reaction with triphenylphosphine, iodine and imidazole to yield l-iodo-10 undecene (4) (90% yield, purified by distillation). Reaction of the iodide with triethyl phosphite under reflux afforded the diethoxy phosphonite (5) (87% yield, purified by distillation), which was then converted to the ethoxyhydroxy phosphonite (6) by treatment with trimethylsilyl bromide (TMSBr) (56% yield). The double bond of (6) was oxidatively cleaved with ruthenium trichloride and sodium periodate to yield the terminal carboxylate (7). (81 % yield, purified by crystallization of the Na salt). Treatment of (7) with excess Bis- (2- methoxyethyl) aminosulfur trifluoride yielded the difluoro compound (8) (not isolated). The identity of compounds 6 and 7 was confirmed by FTIR, MALDI, and C13 NMR. Treatment of (8) with N-hydroxysuccinimide afforded the active ester (9), which is then immediately reacted with 5- (biotinamido) pentylamine (10). (obtained from Pierce Chemical) to generate the fluorophosphonate monoester immobilizing reagent/probe (11). This compound was analyzed by electrospray mass spectrometry and was shown to have the expected formula weight of 593 Da (see Fig 2).
73%
With toluene-4-sulfonic acid; 1-propyl-3-methyl-1H-imidazol-3-ium iodide at 200℃; for 0.00833333h; microwave irradiation;
With 1H-imidazole; iodine; triphenylphosphine In dichloromethane
With 1H-imidazole; iodine; triphenylphosphine In benzene
Multi-step reaction with 2 steps
1: triethylamine / CH2Cl2 / 2 h / 20 °C
2: sodium iodide / acetone / 20 °C
Multi-step reaction with 2 steps
1: 70 percent / thionyl chloride; pyridine / 2 h / 50 °C
2: 89 percent / sodium iodide / acetone / 72 h / Heating
Multi-step reaction with 2 steps
1: KOH / tetrahydrofuran / 1.) 0 deg C, 4 h, 2.) RT, 6 h
2: 95 percent / NaI, NaHCO3 / acetone / 50 h / Ambient temperature
Multi-step reaction with 2 steps
1: pyridine / 12 h / 0 °C
2: NaI / acetone / 1.) reflux, 1.5 h, 2.) 20 deg C, 48 h
Multi-step reaction with 2 steps
1: pyridine
2: NaI / acetone
Multi-step reaction with 2 steps
1: 142 g / triethylamine / CH2Cl2 / 0 °C
2: 90 percent / sodium iodide, dicyclohexano-18-crown-6 / H2O / 5 h / Heating
Multi-step reaction with 2 steps
1: thionyl chloride, pyridine / 24 h / Heating
2: 100 percent / sodium iodide / acetone / 12 h / Heating
Multi-step reaction with 2 steps
1: 73 percent / triethylamine / CH2Cl2 / 0.25 h / 0 °C
2: 93 percent / NaI / acetone / 2 h
Multi-step reaction with 2 steps
1: SOCl2
2: NaI / acetone
With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 20℃; for 5h;
With 2,2-Dimethyl-1-oxa-2-silacyclohexan In methanol; water at 25℃; for 19h;
68%
In dichloromethane Heating;
51%
With [1,3-bis(2,6-di-i-propylphenyl)imidazolidin-2-ylidene]{2-[[1-(methoxy(methyl)amino)-1-oxopropan-2-yl]oxy]benzylidene}ruthenium(ll) dichloride In dichloromethane at 40℃; for 18h; Schlenk technique; Inert atmosphere; chemoselective reaction;
100 % Chromat.
With butyldiethylsilyl polystyrene-supported Ru carbene In dichloromethane at 45℃; for 4h;
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride at 20 - 80℃; for 5.16667h;
With C70H113Cl2N3O4Ru In neat (no solvent) at 40℃; for 16h; Inert atmosphere;
With acetylacetonatodicarbonylrhodium(l); hydrogen; (2-oxo-1,2-dihydro-6-pyridyl)diphenylphosphine In toluene at 70℃; for 20h;
With 3-diphenylphosphinoisoquinolone; 6-(diphenylphosphino)-N-pivaloyl-2-aminopyridine; hydrogen In toluene at 70℃; for 20h;
With hydrogen In toluene at 70℃; for 20h;
20 EXAMPLE 20; Hydroformylation of Different Substrates Using 2-DPPAP/3-DPICon
EXAMPLE 20; Hydroformylation of Different Substrates Using 2-DPPAP/3-DPICon; 1.8 mg (6.98 μmol) of [Rh(CO)2acac] were dissolved in 10 ml of toluene and admixed with 0.14 mmol of the two ligands (1:1 mixture). The solution was stirred for 5 min, gently heated if necessary for complete dissolution and then admixed with 6.98 mmol of the particular substrate. The solution was transferred to the autoclave, 10 bar of CO/H2 (1:1) were injected and the autoclave was heated to 70° C. After 20 h, the reaction was stopped by cooling to room temperature and decompressing the autoclave. The solution was filtered through a little silica gel together with approx. 50 ml of ethyl acetate and concentrated under reduced pressure. The crude products were analyzed by means of 1H and 13C NMR spectroscopy.
With dicarbonylacetylacetonato rhodium (I); 3,3'-(methoxyphosphanediyl)bis(N,N-diethylaniline); hydrogen In toluene at 100℃; for 16h; Autoclave; Glovebox; Inert atmosphere; regioselective reaction;
2.7 General procedure for hydroformylation
General procedure: In a typical hydroformylation experiment a stainless steelautoclave (450 mL) equipped with pressure regulator and asafety valve was used. Individual vials were charged withmetal precursor [Rh(acac)(CO)2] (2 mg)}, ligand (as inTables 1 and 2), solvent (1 mL), substrate (100 equiv.) andstirring bars in a glove box. The vials were transferred to autoclaveand the autoclave was purged three times with syngas(CO: H2 = 1:1) before pressurizing it to the desired pressure.Suitable temperature and pressure were maintained duringthe reaction. After completion of the reaction, the autoclavewas cooled to 0C, and excess gas was vented off in a wellventilatedfume-hood. The conversion and regio-selectivitieswere determined by proton NMR spectroscopy and gas chromatography.
With toluene-4-sulfonic acid; lithium bromide at 20℃; for 60h;
86%
With toluene-4-sulfonic acid; lithium bromide at 20℃; for 12h;
1.a.1 a) Stage 1: Synthesis of 11-(methoxymethoxy)undec-1-ene
Lithium bromide (3.06 g, 35 mmol, 0.4 eq) and para-toluenesulphonic acid (1.67 g, 8.8 mmol, 0.1 eq) are added to a solution of undecenol (15 g, 17.65 ml, 88 mmol) dissolved in 225 ml of dimethoxymethane (12.9 g, 170 mmol, 28.3 eq). The reaction takes place at ambient temperature for 12 hours. After addition of 500 ml of ether, the reaction mixture is washed successively with deionized water (twice) and with a saturated sodium chloride solution, dried over anhydrous magnesium sulphate and then concentrated. The residue is purified by chromatography on a column of silica gel (pentane/ether: 97.5/12.5) to give a yellowish liquid. The characteristics of the product obtained are as follows: Weight: 16.26 g Yield: 86% 1H NMR (200 MHz, CDCl3): 1.31 (12H, m, H5-10), 1.57 (2H, m, H4), 2.03 (2H, m, H11), 3.37 (3H, s, H1), 3.52 (2H, t, H3, 3JH-H=6.6 Hz), 4.62 (2H, s, H2), 4.96 (2H, m, H13) 5.82 (1H, m, H12) ;13C NMR (200 MHz, CDCl3): 26.59, 29.30, 29.49, 29.80 (2C), 29.91, 30.12, 34.18 (C11), 55.37 (C1), 68.20 (C3), 96.74 (C2), 114.47 (C13), 139.50 (C12) ;Mass spectrometry m/z (NBA): 154 [M+H]+-O-CH2OCH3
1',2',3',6',2,3,4,6-octa-O-acetyl-β-D-lactose[ No CAS ]
[ 134078-52-7 ]
Yield
Reaction Conditions
Operation in experiment
83.9%
With boron trifluoride diethyl etherate In dichloromethane for 24h; Cooling with ice;
7.1 (1) Synthesis of Compound 11
(0151) In a 500 mL round bottom flask, compound 9 (20 g, 29.5 mmol), and 10-undecenol (6 g, 35.4 mmol) were dissolved in 200 mL of anhydrous DCM; BF3-OEt2 (14.8 mL) was added dropwise in an ice bath; the reaction was maintained in an ice bath for 24 hours and the completion of the reaction was monitored by TLC. The reaction was filtered by diatomite; and the filtrate was dissolved in 500 mL of ethyl acetate and washed with 200 mL saturated sodium bicarbonate solution and 200 mL saturated brine successively. The organic phase was dried over anhydrous magnesium sulfate, concentrated under reduced pressure and passed through a silica gel column (petroleum ether:ethyl acetate V:V=3.2) to isolate 19.5 g of a white solid with a yield of 83.9%, MS (ESI), m/z: 811.25 ([M+Na]+).
56%
With tin(IV) chloride In dichloromethane at 20℃;
Stage #1: 1',2',3',6',2,3,4,6-octa-O-acetyl-β-D-lactose With hydrogen bromide In acetic acid at 0 - 20℃; for 5h;
Stage #2: 10-Undecen-1-ol With silver trifluoromethanesulfonate In toluene at -78 - 20℃;
With Oxone; 2-Iodobenzoic acid; tetra(n-butyl)ammonium hydrogensulfate In ethyl acetate at 70℃; for 7h;
80%
With 1-hydroxycyclohexyl phenyl ketone; sodium hydroxide In 1,2-dimethoxyethane at 80℃; Sealed tube; chemoselective reaction;
Multi-step reaction with 2 steps
1: pyridinium chlorochromate / dichloromethane / 16 h / 23 °C / Inert atmosphere; Molecular sieve
2: sodium dihydrogenphosphate; sodium chlorite; 2-methyl-but-2-ene / <i>tert</i>-butyl alcohol / 2 h / 0 °C / Inert atmosphere
With chromium (VI) oxide; periodic acid In water; acetonitrile at 20℃; for 1h; chemoselective reaction;
General Procedure for Oxidation of Alcohols
General procedure: Chemicals and reagents were purchased fromAldrich or Fisher and used without further purification unless noted. The required amount of H5IO6(see Table 2) and CrO2 (0.042 g, 0.5 mmol) were ground together in amortar to produce a uniform gray-black mixture, which was then transferred to a50 mL round-bottomed flask along with a magnetic stir bar. Water (5.0 mL) was added, and the mixture wasstirred for 5-10 minutes to dissolve the H5IO6. Then 20.0 mL acetonitrile (ACN) was added andthe mixture was stirred vigorously to disperse the black CrO2solid. At this point the solution phasewas dark yellow. The alcohol reactant(5.0 mmol, weighed if solid, via pipette if liquid) was added in one portionwith vigorous stirring, and within one minute the solution phase became muchlighter (although it gradually darkened during the reaction period).
With alcohol dehydrogenase from Escherichia coli; nicotinamide adenine dinucleotide In dimethyl sulfoxide at 25℃; Enzymatic reaction;
Multi-step reaction with 2 steps
1: alcohol dehydrogenase from Escherichia coli; nicotinamide adenine dinucleotide / dimethyl sulfoxide / 25 °C / pH 7 / Enzymatic reaction
2: alcohol dehydrogenase from Escherichia coli; nicotinamide adenine dinucleotide / dimethyl sulfoxide / 25 °C / pH 7 / Enzymatic reaction
With pyridine In dichloromethane at 0 - 25℃; for 24h; Inert atmosphere;
94%
With pyridine In dichloromethane at 0 - 25℃; for 24h; Cooling with ice;
Heating;
With diethyl ether; <i>N</i>,<i>N</i>-dimethyl-aniline for 3.16667h; Heating / reflux;
A mixed solution comprising 20.64 g of benzoyl chloride and 10 ML of anhydrous diethyl ether, was dropwise added to a mixed solution comprising 25.0 g of 10-UNDECEN-1-OL, 17.79 g of N, N-dimethylaniline and 60 ml of anhydrous diethyl ether and reacted for 3 hours and 10 minutes under reflux. After completion of the reaction, the mixture was cooled to room temperature, and the reaction mixture was filtered. The crystals were washed with a mixed solution of diethyl ether and hexane. The filtrate was distilled off under reduced pressure, and then residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=95/5) to obtain 30.42 g of oily 10-undecenyl benzoate. The NMR spectrum data thereof are as follows. 1H-NMR BPPM (SOLVENT : CDC13/400MHZ) 8.03 (2H, d, J=8.4Hz), 7.53 (lH, t, J=7.6Hz), 7.42 (2H, t, J=7.6Hz), 5.74-5. 84 (LH, m), 4.90-5. 00 (2H, m), 4.29 (2H, t, J=6.6Hz), 1. 99- 2.05 (2H, m), 1.71-1. 78 (2H, m), 1.24-1. 45 (14H, m)
General Procedure for the Synthesis of Carbonates
General procedure: Pyridine (1.1 eq) was added to a solution of the alcohol(undec-10-en-1-ol (0.25 mol), oleyl alcohol (15 mmol), stearyl alcohol (8.3 mmol), and octadec-9-ene-1,18-diol(7.3 mmol)) (1.0 eq) in dry THF (25-250 mL). After coolingto 0 °C with an ice bath, the chloroformate (1.1 eq) was added dropwise. The suspension with the white precipitate was then stirred at room temperature for 20-24 hours. The white pyridinium salt was removed by suction, the filtrate-after drying over Na2SO4, was freed from the solvent using a rotary evaporator and the crude product was distilled in a high vacuum apparatus or a Kugelrohr distillation apparatus. In case of 6-8 the reaction mixture was quenched by addition of water and extracted with ethyl acetate(3x). The organic layers were combined and washed with HCl (2N, 2x), sat. NaHCO3-solution and brine. After drying over Na2SO4 the solvent was removed by a rotary evaporator and the crude product was purified by flash chromatography on silica gel (increasing the gradient of polarity applying n-hexane/ethyl acetate mixtures). Allyl undec-10-en-1-yl carbonate (5): Scale: Undec-10-en-1-ol 45.50 g, 0.25 mol. Yield 58.61 g, 0.23 mol,92%. Colorless oil. Bp. (0.2 mbar) = 165 C. 1H NMR(400 MHz, CDCl3): δ 5.93 (m, 1H), 5.80 (m, 1H), 5.30 (m,2H), 5.02-4.88 (m, 2H), 4.61 (dt, J = 5.8 Hz, 1.4 Hz, 2H),4.13 (t, J = 6.7 Hz, 2H), 2.03 (m, 2H), 1.71-1.60 (m, 2H),and 1.43-1.22 (m, 13H); 13C NMR (101 MHz, CDCl3): δ155.24, 139.29, 131.84, 118.89, 114.25, 77.48, 77.16,76.84, 68.40, 68.36, 33.91, 29.53, 29.49, 29.30, 29.20,29.03, 28.78, and 25.80. IR (ATR): ν = 3078 (w), 2925(m), 2854 (m), 1744 (s), 1641 (w), 1456 (w), 1394 (w),1362 (w), 1245 (s), 992 (m), 959 (m), 909 (m), 791 (m),723 (w), 638 (w), and 553 cm-1 (w); EIMS m/z (%):192 (0.06), 163 (1), 151 (16), 143 (0), 135 (4), 123 (10),109 (44), 103 (22), 97 (40), 95 (76), 81 (71), 67 (69),55 (88), 41 (100), 39 (33), and 29 (20).
Stage #1: 10-Undecen-1-ol With sodium hydride In N,N-dimethyl-formamide at 20℃; for 3h;
Stage #2: 10-Undecen-1-ol In N,N-dimethyl-formamide at 20 - 80℃; for 4h;
9
Into a clean flame dried 1 L RBF under current of N2, was added 100 mL of dry DMF and 20 mL (96 mmols) of commercially available 53. 2.3 g (57.6 mmol) of NaH was added to the reaction and the mixture was stirred for 3 h at room temperature. 18g (48 mmols) of 52 was dissolved in 50 mL of DMF and was slowly added to the above reaction mixture. After complete addition the stirring was continued for 2 h at room temperature and at 800C for 2 h. The reaction was then cooled in an ice bath and quenched with a solution of saturated aq. NH4Cl. 300 mL of water was then added and reaction mixture was extracted with DCM (4x). The combined DCM layers were then washed with H2O (3x), brine (Ix), dried over MgSO4, filtered and the solvent was evaporated under vacuum. The residue was then purified using combiflash (120 g silica column) with hexane/ethyl acetate as eluent to furnish 12.86 g (72%) of the target product 54 as colorless oil.
7.7a 7a. undec-10-en-1-ol
A mixture of undec-10-yn-1-ol (0.84 g, 5.0 mmol), quinoline (0.13 ml), lindlar's catalyst (100 mg, 17% w/w) and EtOH (20 ML) was hydrogenated in a Parr apparatus at 50 psi of H2 for 1 h.The mixture was filtered through Celite, and the filtrate was concentrated in vacuo to dryness to give undec-10-en-1-ol (0.86 g, 100%) as a colorless oil, which was used in the next step without further purification: 1H NMR (300 MHz, CDCl3) δ 5.78 (1H, m), 4.92 (2H, m), 3.61 (2H, t, J=6.6 Hz), 2.01 (2H, m), 1.53 (3H, m), 1.21-1.40 (12H, m); 13C NMR (75 MHz, CDCl3) δ 139.43, 114.31, 63.24, 34.00, 32.98, 29.74, 29.61, 29.31, 29.11, 25.92.
With pyridine; nitrogen In (2S)-N-methyl-1-phenylpropan-2-amine hydrate
Synthesis of 10-Undecen-1-yl tosylate (I-0)
Synthesis of 10-Undecen-1-yl tosylate (I-0) Nitrogen was introduced into a three necks flask containing 50 ml anhydrous pyridine which was stirred at 10° C. 17 g (0.1 mole) 10-undecen-1-ol was added to the stirred pyridine, and then p-tolysufonyl chloride was added slowly such that the temperature of the stirred mixture was not high than 20° C. The stirring was maintained for 10 hours at room temperature, 250 ml ice water was added to the stirred mixture and then extracted with ethyl ether. The ethyl ether layer was collected, washed with 50% HCl aqueous solution, dried over anhydrous MgSO4, filtered and then concentrated to yield 26.81 g colorless liquid. Yield: 79.6%. 1 H-NMR (CDCl3, δ): I-0 1.11-1.65(m,14H, --(CH2)7 --, 2.04-2.10 (q,2H,--CH2 --CH=),2.49(s,3H, -ph--CH3), 4.05-4.10 (t,2H, --O--CH2 --CH2 --), 4.93-5.05(m,2H,--CH=CH2), 5.78-5.88(m,1H, --CH=CH2), 7.49-7.36(q,4H,ArH)
79.6%
With pyridine; nitrogen In (2S)-N-methyl-1-phenylpropan-2-amine hydrate
P.17 Synthesis of 10-Undecen-1-yl tosylate (I-17)
PREPARATION EXAMPLE 17 Synthesis of 10-Undecen-1-yl tosylate (I-17) Nitrogen was introduced into a three-neck flask containing 50 ml anhydrous pyridine which was stirred at 10° C. 17 g (0.1 mole) 10-undecen-1-ol was added to the stirred pyridine, and then p-tolysufonyl chloride was added slowly such that the temperature of the stirred mixture was not high than 20° C. The stirring was maintained for 10 hours at room temperature, 250 ml ice water was added to the stirred mixture and then extracted with ethyl ether. The ethyl ether layer was collected, washed with 50% HCl aqueous solution, dried over anhydrous MgSO4, filtered and then concentrated to yield 26.81 g colorless liquid. Yield: 79.6%. 1 H-NMR (CDCl3,TMS,δppm): 1.20-1.60(m,14N,--(CH2)7 --CH2 O--),1.95(m,2H,=CH --CH3 --),2.40(s,3H,--CH3),3.50(t,2H,--OCH2 --), 4.8 (m,2H,--CH=CH2), 5.00 (m,1H,--CH=CH,), 7.20-7.70 (m,4H,aromatic protons).
With hydrogen; sodium methylate In tetrahydrofuran at 100℃; for 2.5h; Title compound not separated from byproducts.;
1: 90 %Chromat.
2: 6 %Chromat.
With RuCl2(PNHNHP); potassium methanolate; hydrogen In tetrahydrofuran at 100℃; for 2h; Inert atmosphere; Autoclave; chemoselective reaction;
7 Example 7
The reaction is carried out as described in Example 6 but with RuCl2(PNHNHP) catalyst 4b. After 2 hours GC-analysis revealed 4% substrate la, 90% 10-undecenol 2a, 6% undecanol 2b and 1% methyl undec-10-enoate 1a. CO/DB selectivity: 94:6.
With OsHCl(CO)[(iPr)2PNH(CH2)2NHCH2Py]; potassium <i>tert</i>-butylate; hydrogen In tetrahydrofuran at 100℃; for 2.5h; Autoclave; regioselective reaction;
15
EXAMPLE 15. TYPICAL PROCEDURE FOR HYDROGENATION OF ESTERS USINGCOMPLEXES (la), AND (3).A solution of catalyst 1 (5.2 mg/mL) and a base (0.2 mmol) in THF was mixed with 0.02 mol of the ester substrate in 6 mL of THF. The mixture was then transferred into a 75 mL stainless-steel reactor (Parr 4740) equipped with a magnetic stir bar. The reactor was purged by two cycles of pressurization/venting with H2 (150 psi, 10 Bar), pressurized with H2 (725 psi, 50 Bar), and was disconnected from the H2 source. The hydrogenation was conducted at 40-100 °C. At the end of the required reaction time, the reactor was placed into a cold-water bath and depressurized afier cooling to the ambient temperature.
With zinc(II) chloride In toluene at 70℃; for 5h; optical yield given as %de; stereoselective reaction;
76%
With tin(IV) chloride In n-heptane; dichloromethane at 0 - 20℃; for 6h; stereoselective reaction;
Typical procedure for glycosylation with 1-O-pivaloyl donor
General procedure: 8-Chlorooctyl hepta-O-pivaloyl β-lactoside 4a. To a cooled solution of lactose octapivalate 2 (1 g, 0.99 mmol) and 8-chlorooctan-1-ol 3a (243 μL, 1.48 mmol) with or without an additive (1.2 equiv.) in CH2Cl2 (10 mL) was added dropwise 1.0 M solution of SnCl4 in heptanes (1.48 mL,1.48 mmol). The mixture was stirred at 0 °C to room temperature until most of the lactose octapivalate 2 was consumed. For the synthesis of α-lactoside the mixture was stirred at 50 °C for 20 h. The resulting mixture was diluted with EtOAc (20 mL) and aqueous NaHCO3 (20 mL) and stirred for 10 min, filtered through Hyflo and washed thoroughly with EtOAc (10 mL). The combined filtrate and washings were treated with H2O and brine. The aqueous phase was extracted with EtOAc (2 × 20 mL) and the combined organic layers were dried over Na2SO4. Removal ofthe solvent gave a residue that was purified by column chromatography (eluent EtOAc-petroleum ether, 1 : 7) to give 8-chlorooctyl lactoside 4a (0.88 g, 0.83 mmol, 83%) as a white foam.
With sodium metabisulfite In water at 80℃; for 4h;
8
A 250 ml four-necked Pyrex glass flask, fitted with a mechanical agitator and bubble condenser, heated in an oil bath was filled with 16 grams of undecylenyl alcohol CH2=CH(CH2)9OH (PM 170,29; (0.0939 moles) and 15 grams of an aqueous solution at 35% in weight of sodium metabisulphite. After heating to 80°C while stirring, 75.42 grams of C6F13I were added drop by drop over the space of an hour. Contemporaneously the reactor was filled with 0.08 grams of AIBN in two portions of 0.04 grams each at two-hour intervals. At the end of the four hours of reaction the procedure continued with rinsing in water, separation and distillation of the solvent and of the remaining reagents. 53.6 grams of product were obtained to which 23.58 grams of ethanol and 11.5 grams of 37% HCl solution were added. The system was heated to 65-70°C and then over two hours 10.52 grams of powdered Zn were added. At the end of the reaction, by means of distillation 38.53 grams of alcohol C6F13 (CH2) 11OH were obtained. 15 grams of this product (0.0306 moles) were placed in a 100 ml flask containing anhydrous tetrahydrofurane. The process was performed in a nitrogen atmosphere at a temperature of 10 to 15°C. Under agitation, 0.735 grams of NaH (0.0306 moles) were added over the space of two hours. At the end of this addition, the reaction was continued for another two hours. The reaction was monitored by means of IR analysis until complete disappearance of the oxydrilic group peak at 3400cm-1. The solvent was distilled at reduced pressure to obtain 14.8 grams (0.028 moles) of a light yellow solid. Lastly 3.6 grams (0.026 moles) of 1,4-butane sultone and 18.4 grams of anhydrous dioxane were added to this product. The reaction was conducted in a nitrogen atmosphere at 90°C for 7 hours until the complete disappearance of the peak corresponding to the 1,4-butansultone. The product was solubilised to 25% in a 50/50 mixture of water and isopropanol.
Stage #1: 2-bromoisobutyric acid bromide; 10-Undecen-1-ol With pyridine In tetrahydrofuran for 0.166667h;
Stage #2: In tetrahydrofuran at 20℃; Inert atmosphere;
75%
With triethylamine In dichloromethane at 0 - 20℃; for 26h; Schlenk technique; Inert atmosphere;
64%
With pyridine In tetrahydrofuran at 20℃; Schlenk technique; Inert atmosphere; Cooling with ice;
With pyridine In tetrahydrofuran
With pyridine In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique;
With pyridine In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique;
With sodium tetrahydroborate; ruthenium(III) trichloride hydrate In N-Methylformamide; N,N-dimethyl acetamide; water at 0℃; for 1h; chemoselective reaction;
General procedure for alkene reduction
General procedure: To a 15-mL 1-neck reaction flask fitted with a glass stopper [Note: A larger-scale reaction may require the use of a pressure vessel and/or addition of NaBH4 in small portions.] were added a small spin bar, 0.18-0.20 mmol of substrate, 0.60 mL of 5:1 (v/v) [10:1 (v/v) in Table 1, entry 3] liquid amide(s)/H2O, and 7.0 mg (0.034 mmol) of ruthenium(III) chloride hydrate (Sigma-Aldrich Catalog No. 206229). After cooling the latter mixture to 0 C (external ice-H2O bath), 9.0 mg (0.24 mmol) of NaBH4 powder was added in one portion; and the mixture was subsequently stirred at 0 C for 60 min. The reaction was then quenched by addition of 2.0 mL of 2 M aqueous HCl to the reaction flask, followed by 1.0 mL of pentane and subsequent stirring of the mixture at 0 C for 15 min. The product was then isolated by dilution of the reaction mixture with 10 mL of 4:1 (v/v) pentane/dichloromethane; and solid material was removed by filtration through a small pad of Hyflo Super-Cel filtering aid. After dilution of the filtrate with 10 mL of pentane, removal of the liquid amide(s) was accomplished by washing the filtrate with 10% (w/v) aqueous NaCl (4 15 mL portions). The organic layer was subsequently dried over anhydrous MgSO4, filtered, and the volatile organic solvents were removed by evaporation at reduced pressure.
With di-tert-amyl peroxide at 140℃; for 5h; Inert atmosphere;
S21 (11-Hydroxy-undecyl)-(2,4,4-trimethylpentyl)-phosphinic acid (121)
5 g (0.028 moles) of 2,4,4-trimethylpentyl phosphinic acid, 4.78 g (0.28 moles) of 10-undecen-1-ol and 0.3 mL (0.0014 moles) of di-tert-amylperoxide is mixed in a 50 mL single neck flask. The mixture is purged with argon to remove oxygen and is heated under argon for 5 hours at 140° C. Tert-amyl alcohol is removed by distillation and 9.8 g (quantitative yield) of (11-hydroxy-undecyl)-(2,4,4-trimethylpentyl)-phosphinic acid is obtained as a viscous oil.
With styrene; [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; potassium methanolate; hydrogen at 80℃; for 8h; Inert atmosphere; Autoclave; chemoselective reaction;
10 Example 10
Undec-10-en-l-yl undec-10-enoate 3a was prepared as described by B. Kowalczyk et al., Angew. Chem. Int. Ed. 49, 5737,2010. The reaction is carried out as described in Example 9 using catalyst 4a (4.2 mg, 0.02%) in styrene (1.25 g, 12 mmol) and KOMe (180 mg, 2,5 mmol) in undec-10-en-l-yl undec-10-enoate 3a (8.4 g, 25 mmol). After 8 hours an 98% conversion to 90% undec-10-enol 2a and 8% undecanol 2b was detected by GC. CO/DB selectivity 92:8.
With styrene; [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; potassium methanolate; hydrogen at 80℃; for 8h; Inert atmosphere; Autoclave; chemoselective reaction;
10
EXAMPLE 10 Undec-10-en-1-yl undec-10-enoate 3a was prepared as described by B. Kowalczyk et al., Angew. Chem. Int. Ed. 49, 5737, 2010. [0079] The reaction is carried out as described in Example 9 using catalyst 4a (4.2 mg, 0.02%) in styrene (1.25 g, 12 mmol) and KOMe (180 mg, 2.5 mmol) in undec-10-en-1-yl undec-10-enoate 3a (8.4 g, 25 mmol). After 8 hours an 98% conversion to 90% undec-10-enol 2a and 8% undecanol 2b was detected by GC. CO/DB selectivity 92:8.
With [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; hydrogen; sodium methylate In toluene at 100℃; for 4h; Inert atmosphere; Autoclave; Sonication; chemoselective reaction;
1 Example 1
Under argon, toluene (3 ml) is added to a glass vial (50 ml) containing RuCI2(PNNP) catalyst 4a (2.5 mg, 0.01 mol%) and NaOMe (0.163 g, 3 mmol). The suspension is treated in an ultrasonic bath until a reddish solution is obtained (3-5 min) to which a solution of ethyl 10-undecenoate (6.4 g, 29 mmol) in toluene (18 ml) is added. The vial is capped (crimp cap & silicone septum), punctured with a needle and put in a Parr autoclave. While stirring with a magnetic stirrer the autoclave is flushed three times with hydrogen, then put under hydrogen pressure (40 bar) and heated to 100 °C. After 4 hours the heating is stopped and the pressure released. To the colourless reaction mixture is added 2% H3P04 (4 ml) and diethyl ether (10 ml). The organic phase is washed with brine, dried over MgS04 and concentrated in vacuo. GC-MS analysis revealed 3% substrate 1b, 87% 10-undecenol 2a, 9% undecanol 2b, and 1% transesterification product 3. CO/DB selectivity: 91:9. The analytical data of ethyl undec-10-enoate 1b, 10-undecenol 2a and undecanol 2b were identical with the ones from commercial samples of these compounds.
With OsHCl(CO)[(iPr)2PNH(CH2)2NHCH2Py]; hydrogen; sodium ethanolate In tetrahydrofuran at 80℃; for 2.5h; Autoclave; regioselective reaction;
15
EXAMPLE 15. TYPICAL PROCEDURE FOR HYDROGENATION OF ESTERS USINGCOMPLEXES (la), AND (3).A solution of catalyst 1 (5.2 mg/mL) and a base (0.2 mmol) in THF was mixed with 0.02 mol of the ester substrate in 6 mL of THF. The mixture was then transferred into a 75 mL stainless-steel reactor (Parr 4740) equipped with a magnetic stir bar. The reactor was purged by two cycles of pressurization/venting with H2 (150 psi, 10 Bar), pressurized with H2 (725 psi, 50 Bar), and was disconnected from the H2 source. The hydrogenation was conducted at 40-100 °C. At the end of the required reaction time, the reactor was placed into a cold-water bath and depressurized afier cooling to the ambient temperature.
1: 94 %Chromat.
2: 6 %Chromat.
With [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; potassium methanolate; hydrogen In tetrahydrofuran at 100℃; for 5h; Inert atmosphere; Autoclave;
5
EXAMPLE 5 Under argon, RuCl2(PNNP) catalyst 4a (3.7 mg, 50 ppm) in distilled and degassed THF (5 ml) is treated for 5 min with ultrasound to give a fine suspension which is added to a suspension of KOMe_(0.63 g, 9 mmol) in ethyl 10-undecenoate 1b (19.2 g, 90 mmol) and distilled and degassed THF (58 ml) in a 120 ml Premex autoclave under argon. The autoclave is flushed three times with hydrogen and then heated at 100° C. under 50 bar hydrogen and 1200 rpm with overhead stirring. After 5 hours the heating is stopped, the pressure released and the content of the autoclave poured onto 2% H3PO4 (10 ml). After phase separation the organic phase is washed with water (2×30 ml), dried over MgSO4, filtered and evaporated. GC-analysis of the quantitatively obtained material revealed 94% 10-undecenol 2a and 6% undecanol 2b.
With C30H34Cl2N2P2Ru; potassium methanolate; hydrogen In tetrahydrofuran at 100℃; for 5h; Glovebox; Autoclave;
28 Example 28: Chemoselective hydrogenation of ester compounds catalyzed by ruthenium complex Ia
General procedure: In a glove box, add a ruthenium complex Ia (0.7 mg, 0.001 mmol),Potassium methoxide (35-175 mg, 0.5-2.5 mmol), tetrahydrofuran (5-20 mL), and ester compounds (10-50 mmol).After sealing the autoclave, take it out of the glove box and fill it with 50atm of hydrogen.The reaction kettle was heated and stirred in an oil bath at 100 ° C for 10 to 24 hours.After the reaction kettle was cooled in an ice-water bath for 1.5 hours, the excess hydrogen was slowly released.The solvent was removed from the reaction solution under reduced pressure, and the residue was purified with a short silica gel column to obtain an alcohol compound. The results are shown in Table 6.
With [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; hydrogen; sodium methylate In toluene at 100℃; for 3h; Inert atmosphere; Autoclave; chemoselective reaction;
3 Example 3
The reaction was carried out as described in Example 1 but with methyl undecenoate la and 0.05% RuCI2(PNNP) catalyst 4a. After 3 h a 87% conversion to 10-undecenol 2a (54%), 9-undecenol 2d (8%), undecanol 2b (15%), methyl undecanoate 2c (3%) and transesterification products 3 (7%) was detected by GC. The CO/terminal double bond (DB) selectivity was 68:32. The analytical data of 10-undecenol 2a, undecanol 2b and methyl undecanoate 2c are identical with the ones obtained from commercial samples of these compounds. The analytical data of 9-undecenol 2d (partially in J.Organomet.Chem.691, 5278, 2006 and references) and undecenoic acid undecenyl ester 3 (Tetrahedron 63, 11325, 2007) were identical with the ones described in the literature. MS of 2d: 152 (5%, [M-18]+), 124 (7%), 123 (8%), 110 (11%), 109 (14%), 96 (29%), 95 (30%), 82 (44%), 81 (49%), 68 (49%), 67 (54%), 55 (100%), 54 (36%), 41 (43%).
With [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; hydrogen; sodium methylate In toluene at 100℃; for 3h; Inert atmosphere; Autoclave; chemoselective reaction;
3
EXAMPLE 3 The reaction was carried out as described in Example 1 but with methyl undecenoate 1a and 0.05% RuCl2(PNNP) catalyst 4a. After 3 h a 87% conversion to 10-undecenol 2a (54%), 9-undecenol 2d (8%), undecanol 2b (15%), methyl undecanoate 2c (3%) and transesterification products 3 (7%) was detected by GC. The CO/terminal double bond (DB) selectivity was 68:32 The analytical data of 10-undecenol 2a, undecanol 2b and methyl undecanoate 2c are identical with the ones obtained from commercial samples of these compounds. The analytical data of 9-undecenol 2d (partially in J. Organomet. Chem. 691, 5278, 2006 and references) and undecenoic acid undecenyl ester 3 (Tetrahedron 63, 11325, 2007) were identical with the ones described in the literature. MS of 2d: 152 (5%, [M-18]+), 124 (7%), 123 (8%), 110 (11%), 109 (14%), 96 (29%), 95 (30%), 82 (44%), 81 (49%), 68 (49%), 67 (54%), 55 (100%), 54 (36%), 41 (43%).
With [RuCl2(N,N'-(ethane-1,2-diyl)bis(1-(2-(diphenylphosphaneyl)phenyl)methanimine))]; hydrogen; sodium methylate In toluene at 100℃; for 20h; Inert atmosphere; Autoclave; Overall yield = 15.6 g;
4
EXAMPLE 4 Under argon, RuCl2(PNNP) catalyst 4a (7.5 mg, 0.01 mol %) in toluene (5 ml) are treated 5 min with ultrasound to give a fine suspension which is added to a suspension of ethyl 10-undecenoate 1b (19.2 g, 90 mmol) and NaOMe (0.5 g, 9 mmol) in toluene (16 ml) in a 120 ml Premex autoclave under argon. The autoclave is flushed three times with hydrogen and then heated at 100° C. under 50 bar hydrogen and 1200 rpm with overhead stirring. After 6 hours the GC-analysis revealed 6% substrate 1b, 90% 10-undecenol 2a, 4% undecanol 2b. CO/DB selectivity: 96:4. After 20 h the autoclave is cooled, the pressure released and the content of the autoclave poured onto 2% H3PO4 (10 ml). After phase separation the organic phase is washed with water (2×30 ml), dried over MgSO4, filtered and evaporated. The residue of 15.6 g consisted of 80% 10-undecenol 2a, 15% undecanol 2b and 5% isomer 2d according to GCMS and NMR.
Stage #1: 10-Undecen-1-ol With sodium In tetrahydrofuran for 24h; Reflux; Inert atmosphere;
Stage #2: 2,6-bis-(bromomethyl)pyridine In tetrahydrofuran for 16h; Inert atmosphere; Reflux;
Preparationof1
10-undecen-1-ol(3.0g,17.6mmol)andsodiumcuts(0.37g,15.8mmol)wereplacedindry THF(50mL),andthemixtureheatedatrefluxfor24h.Thevolatileswereremovedundervacuum,andtheresultingwhitesolidwaswashedwithdiethylether(2x15mL)underanargonatmosphere,toaffordsodium10--undecenyloxideinquantitative yield(storedinaninertatmosphereglovebox).Sodium10--undecenyloxide(2.26g,11.7mmol)and2,6--bis(bromomethyl)pyridine(1.24g,4.7mmol)wereplacedindry THF(50mL),andthemixturewasheateda trefluxfor16h.Thesolutionwas filteredthroughCeliteand thevolatilesremovedundervacuum.The residue was dissolved in cold ethanol,then precipitated and washed with coldwater.Theresultingwhitesolidwasplacedontoasilicaplug(8x8cm),washedwithdichloromethane (ca.100mL),andthenelutedwithacetonetoaffordpure1asalowmeltingpointwhitesoliduponsolventremoval(1.53g,73%).
General procedure: Ozone-oxygen mixture was bubbled at 0C through a solution of0.99 g (5.0 mmol) of methyl 10-undecenoate (1) or 0.85 g(5.0 mmol) of 10-undecen-1-ol (2) in 20 mL of absolutealcohol (MeOH or PriOH), 20 mL of absolute THF, ora mixture of 20 mL of CH2Cl2 and 3 mL of upto the uptake of 6 mmol of ozone. The reaction mixturewas purged with argon, after which 1.21 g (17.5 mmol)of NH2OH·HCl (method ) or 1.95 g (17.5 mmol) ofNH2C(O)NHNH2·HCl (method b) was added at 0,the mixture was stirred at room temperature until theperoxides fully decomposed (checking by iodide-starchtest), the solvent was distilled off, the residue wasdissolved in CHCl3 (50 mL), and the solution was washedwith a saturated NaCl sol
Stage #1: 10-Undecen-1-ol; isopropyl alcohol With ozone at 0℃;
Stage #2: With semicarbazide hydrochloride at 0 - 20℃; Inert atmosphere;
General procedure for ozonolysis of methyl10-undecenoate (1) and 10-undecen-1-ol (2).
General procedure: Ozone-oxygen mixture was bubbled at 0°C through a solution of0.99 g (5.0 mmol) of methyl 10-undecenoate (1) or 0.85 g(5.0 mmol) of 10-undecen-1-ol (2) in 20 mL of absolutealcohol (MeOH or PriOH), 20 mL of absolute THF, ora mixture of 20 mL of CH2Cl2 and 3 mL of upto the uptake of 6 mmol of ozone. The reaction mixturewas purged with argon, after which 1.21 g (17.5 mmol)of NH2OH·HCl (method ) or 1.95 g (17.5 mmol) ofNH2C(O)NHNH2·HCl (method b) was added at 0°,the mixture was stirred at room temperature until theperoxides fully decomposed (checking by iodide-starchtest), the solvent was distilled off, the residue wasdissolved in CHCl3 (50 mL), and the solution was washedwith a saturated NaCl sol
Stage #1: methanol; 10-Undecen-1-ol With ozone at 0℃;
Stage #2: With semicarbazide hydrochloride at 0 - 20℃; Inert atmosphere;
General procedure for ozonolysis of methyl10-undecenoate (1) and 10-undecen-1-ol (2).
General procedure: Ozone-oxygen mixture was bubbled at 0°C through a solution of0.99 g (5.0 mmol) of methyl 10-undecenoate (1) or 0.85 g(5.0 mmol) of 10-undecen-1-ol (2) in 20 mL of absolutealcohol (MeOH or PriOH), 20 mL of absolute THF, ora mixture of 20 mL of CH2Cl2 and 3 mL of upto the uptake of 6 mmol of ozone. The reaction mixturewas purged with argon, after which 1.21 g (17.5 mmol)of NH2OH·HCl (method ) or 1.95 g (17.5 mmol) ofNH2C(O)NHNH2·HCl (method b) was added at 0°,the mixture was stirred at room temperature until theperoxides fully decomposed (checking by iodide-starchtest), the solvent was distilled off, the residue wasdissolved in CHCl3 (50 mL), and the solution was washedwith a saturated NaCl sol
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