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With sodium hydroxide In tetrahydrofuran; water for 3 h; Inert atmosphere
Triglycol dichloride (10.8g, 57.8mmol) was added to a stirred mixture of KOH (7.8g, 139.3mmol) in ethylene glycol (60mL) at room temperature under N2. The reaction mixture was stirred at refluxing temperature for 36h. After cooling to room temperature, the reaction mixture was filtered and concentrated under reduced pressure to yield a viscous oil. To a stirred solution of the above viscous oil and NaOH (4.8g, 120mmol) in THF/H2O (v/v=1/1 40mL) cooled to 0°C under N2 was slowly added portions of p-toluenesulfonyl chloride (22g, 115mmol). After stirring for 3h, water (100mL) was added to the reaction mixture. The product was extracted with CH2Cl2 (20mL×3) and washed with brine (20mL×3). The combined organic layer was dried over MgSO4 and the CH2Cl2 was evaporated off. The crude product was purified by column chromatography (petroleum ether: ethyl acetate=3:1) to give pure product (8.1g) as yellow oil. Yield 27.5percent, 1H NMR (CDCl3, 500MHz) δ 2.44 (3H, s), 3.57 (4H, s), 3.59 (2H, s), 3.67 (2H, t, J=4.8Hz), 4.14 (2H, t, J=4.8Hz), 7.33 (2H, d, J=8.1Hz), 7.78 (2H, d, J=8.2Hz).
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With sodium hydride; potassium tetrafluoroborate In tetrahydrofuran Heating;
With sodium hydride; potassium tetrafluoroborate In tetrahydrofuran for 46h; Reflux;
3
Preparation 3 (-)-(2fl,3fi)-2,3-Dimethyl-1 ,4,7,10,13,16-hexaoxacyclooctadecane (catalyst 14, see Table 1 )The crown ether PTC catalyst was prepared according to the procedure described in: K. Naemura, M. Ueno, Bull. Chem. Soc. Jpn. 1990, 63, 3695. A solution of (2R,3/:?)-butane-2,3-cliol (0.27 ml_, 3.0 mmol, 1.0 eq.) and pentaethylene glycol bis(p-toluenesulfonate) (1.8 g, 3.3 mmol, 1.1 eq) in THF (160 mL) was added dropwise over 10 hours to a suspension of sodium hydride (180 mg, 7.5 mmol, 2.5 eq.) and potassium tetrafluoroborate (425 mg, 3.3 mmol, 1.1 eq.) in refluxing THF (160 mL). Once the addition was complete the mixture was refluxed for a further 36 hours then allowed to cool to room temperature. The mixture was filtered and the filtrate concentrated in vacuo. The residue was taken up in chloroform. The resulting solution was washed with water and brine, dried over MgSO4, filtered and the solvent evaporated. The residue was purified by flash chromatography on neutral alumina (EtOAc eluent) to give 533 mg yellow oil. [α]D20 -7.69° (c 1.04, CHCI3) (lit. -7.36°), MS: m/z 315 [M+Na]+ .1H NMR (CDCI3, 300 MHz): δ 3.67 (m, 2OH, 10 x CH2), 3.49 (m, 2H, 2 x CH), 1.08 (d, 2 x CH3).
Stage #1: 3,4-dihydroxybenzaldehyde With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 0.5h; Inert atmosphere;
Stage #2: penta(ethylene glycol) bis(p-toluenesulfonate) In N,N-dimethyl-formamide at 160℃; for 20h; Inert atmosphere;
75%
Stage #1: 3,4-dihydroxybenzaldehyde With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 0.5h;
Stage #2: penta(ethylene glycol) bis(p-toluenesulfonate) In N,N-dimethyl-formamide at 80℃; for 20h;
75%
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 20h;
With potassium tert-butylate; In tetrahydrofuran-d8; at 40℃; for 2.5h;Inert atmosphere;
Synthesis was performed according to the published procedure[17] with some alterations as mentioned below. 2,2'-(Benzylazanediyl)bis(ethan-1-ol) (759 mg, 3.89 mmol) in anhydrous THF (40 mL) was transferred into the two-necked flask under argon atmosphere. A solution of 1 M potassium tert-butoxide in THF(8.03 g, 71.56 mmol) was slowly injected into the reaction mixture. Pentaethylene glycol di(p-toluenesulfonate) (2.12 g, 3.89 mmol) was dissolved in anhydrous THF (20 mL) and added to the reaction mixture dropwise. The mixture was stirred for 2.5 h at 40 C. TLCanalysis (ethyl acetate/MeOH 5:1, Rf of 4 = 0.29) indicated that thereaction was completed immediately. THF was evaporated under reduced pressure. The product was dissolved in ethyl acetate (50 mL) and extracted with 5% hydrochloric acid (v/v) (3 x 50 mL).T he water layer was collected, and neutralized by 1 M NaOH and the product was extracted three times with ethyl acetate(3 x 80 mL). The organic layer was collected and evaporated todryness. The crude product was purified by column chromatographyon silica with ethyl acetate/MeOH/TEA 15:1:0.1 as an eluent. After some impurities were washed out, the mobile phase was changed to ethyl acetate/MeOH/TEA 15:3:1 as the eluent. Yield: 792 mg (51%) of colorless oil. 1H NMR (500 MHz, CDCl3, 25 C):d 2.74-2.93 (m, 4H, CH2), 3.59-3.72 (m, 26 H, CH2) and 7.22e7.41 ppm (m, 5 H, Bn-H); MS (APCI): m/z 398.7 [MH]. The other analytical data corresponded well with data published in the literature
Stage #1: (RS)-(6,6'-dihydroxybiphenyl-2,2'-diyl)bis(diphenylphosphine oxide) With caesium carbonate In N,N-dimethyl-formamide at 60℃; for 1.5h; Inert atmosphere;
Stage #2: penta(ethylene glycol) bis(p-toluenesulfonate) In N,N-dimethyl-formamide at 60℃; Inert atmosphere;
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