Preparation method of alpha-hydroxyl cyclopentenone compound containing tertiary carbon and quaternary carbon
By reacting a 1,2-diketone compound with an alkali solution and a phase transfer catalyst at room temperature, the problem of difficulty in synthesizing α-hydroxycyclopentenone compounds containing tertiary carbon and quaternary carbon in the existing technology is solved, and the reaction is realized Highly efficient and economical, it provides intermediate products for the synthesis of natural products.
Patent Information
- Application Number
- CN202411454464.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-17
- Publication Date
- 2025-01-21
AI Technical Summary
It is difficult to effectively synthesize α-hydroxycyclopentenone compounds containing tertiary carbon and quaternary carbon. These compounds exhibit good antibacterial and anti-cancer activities in natural products, but existing methods are not suitable for their synthesis.
Use 1,2-dioneized compounds to dissolve in the solvents, add alkaline solution and phase metastatic catalyst (such as tetrabuitrafluoride, tetrazblite ammonium chloride, or tetrazbamium bromide), and stir at room temperature 6 to 8 hours, then separated and purified, obtained an alpha-hydroxyl cylinone ketone-based compounds containing uncle carbon and seasonal carbon.
This method can effectively catalyze the reaction of 1,2-dione substrates, and generate a series of anti-alpha-hydroxyl cylinder pentahydrone compounds. It has the advantages of simple response operations, mild conditions, atomic economy and step economy. The intermediate product is used for the synthesis of related compounds.
Smart Images
Figure QLYQS_1 
Figure QLYQS_2 
Figure QLYQS_3
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for preparing alpha-hydroxycyclopentenone compounds containing tertiary carbon and quaternary carbon. Background Art
[0002] α-Hydroxycyclopentenone compounds containing tertiary and quaternary carbons are the core structures of many natural products and show good antibacterial and anticancer activities. For example, pentenomycin has moderate inhibitory activity against Gram-negative bacteria (J.Org.Chem.2005,70,6884), and phorbol produces antitumor activity by activating protein kinase C (Chin.J.Nat.Med.2024,22,146). The development of new methods for preparing α-hydroxycyclopentenone compounds containing tertiary and quaternary carbons is of great significance for the discovery of drug-forming molecular lead compounds. Although methods for preparing α-hydroxycyclopentenone, such as Nazarov cyclization of alkenyl ketones, metal-catalyzed hydroxylation of cyclopentenone, and multi-step reactions have been widely reported, existing methods are not suitable for the synthesis of α-hydroxycyclopentenone molecules containing tertiary and quaternary carbons. Summary of the invention
[0003] In view of the above-mentioned prior art, the present invention provides a method for preparing α-hydroxycyclopentenone compounds containing tertiary carbon and quaternary carbon, so as to solve the technical problem of the difficulty in synthesizing α-hydroxycyclopentenone compounds containing tertiary carbon and quaternary carbon.
[0004] In order to achieve the above object, the technical solution adopted by the present invention is: to provide a method for preparing α-hydroxycyclopentenone compounds containing tertiary carbon and quaternary carbon, comprising the following steps:
[0005] S1: dissolving a 1,2-diketone compound in a solvent to obtain a substrate solution; the structural formula of the 1,2-diketone compound is as shown in Formula I,
[0006]
[0007] Wherein, Ar is phenyl, phenyl with electron withdrawing or electron donating, or heteroaryl; R is methyl, ethyl, or benzyl;
[0008] S2: adding alkali solution and phase transfer catalyst to the substrate solution, stirring the reaction at room temperature for 6 to 8 hours, and then separating and purifying to obtain α-hydroxycyclopentenone compounds containing tertiary carbon and quaternary carbon; the phase transfer catalyst is tetrabutylammonium fluoride, tetrabutylammonium chloride or tetrabutylammonium bromide; the structural formula of the α-hydroxycyclopentenone compounds containing tertiary carbon and quaternary carbon is shown in Formula II,
[0009]
[0010] Based on the above technical solution, the present invention can also be improved as follows.
[0011] Furthermore, the solvent is at least one of toluene, tetrahydrofuran, dichloromethane and methyl tert-butyl ether.
[0012] Furthermore, the concentration of the 1,2-diketone compound in the substrate solution is 0.1 to 0.25M.
[0013] Furthermore, the 1,2-diketone compound is one of the following compounds:
[0014]
[0015]
[0016] Furthermore, alkali solution is an aqueous solution of alkali; the alkali is KOH, NaOH, NaHCO 3 、Na 2 CO 3 or K 3 PO 4 .
[0017] Furthermore, the mass concentration of the alkali solution is 5 to 10%.
[0018] Further, the volume of the added alkali solution is the same as that of the solvent.
[0019] Furthermore, the molar ratio of the phase transfer catalyst to the 1,2-diketone compound is 1:5.
[0020] Furthermore, the separation and purification in S2 includes the following steps: diluting the reaction solution after the stirring reaction with ethyl acetate and water and separating the liquids, washing the aqueous phase with ethyl acetate three times, and combining the organic phases; then washing the organic phase with saturated brine, drying over anhydrous sodium sulfate, and distilling off the solvent under reduced pressure to obtain a crude product; then purifying the crude product by chromatography on a silica gel column to obtain α-hydroxycyclopentenone compounds containing tertiary carbon and quaternary carbon.
[0021] Furthermore, the mobile phase used for chromatography on a silica gel column was a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1.
[0022] The beneficial effects of the present invention are as follows: the method of the present invention utilizes a green and environmentally friendly phase transfer catalyst to catalyze the reaction of a 1,2-diketone substrate, thereby obtaining a series of trans-α-hydroxycyclopentenone compounds. The method has the advantages of simple reaction operation, mild conditions, atom economy and step economy. At the same time, the α-hydroxycyclopentenone compound prepared by the method contains adjacent tertiary carbon and quaternary carbon, has a relatively special structure, and can provide a suitable intermediate product for the synthesis of related compounds. DETAILED DESCRIPTION
[0023] The specific implementation modes of the present invention are described in detail below with reference to the embodiments.
[0024] Example 1
[0025] An α-hydroxycyclopentenone compound containing tertiary carbon and quaternary carbon, the synthesis formula of which is as follows:
[0026]
[0027] The specific synthesis method comprises the following steps:
[0028] S1: Add 1 mmol of compound 1 (162.2 mg) into a round-bottom flask, and then add 5 mL of toluene into the round-bottom flask to dissolve compound 1;
[0029] S2: 5 mL of a 10% KOH aqueous solution and 0.2 mmol of tetrabutylammonium fluoride (added in the form of a solution obtained by dissolving 0.2 mmol of tetrabutylammonium fluoride in 0.2 mL of THF) were added to a round-bottom flask under stirring to obtain a reaction mixture;
[0030] S3: The reaction mixture was stirred at room temperature at a stirring rate of 100 rpm for 8 h;
[0031] S4: After the reaction is complete, the reaction solution is diluted with ethyl acetate and water and separated, the aqueous phase is washed with ethyl acetate three times, and the organic phases are combined; the organic phase is then washed with saturated brine, and then dried over anhydrous sodium sulfate, and then the solvent is removed by distillation under reduced pressure to obtain a crude product;
[0032] S5: The crude product was separated and purified by silica gel column chromatography (PE:EA=10:1) to obtain compound 2 (115 mg, 75%).
[0033] The characterization data of compound 2 are as follows:
[0034] 1 HNMR(600MHz,Chloroform-d)δ7.85(dd,J=8.3,1.3Hz,2H),7.69–7.63(m,1H),7.56–7.50(m,2H),7.44–7.41(m,2H) ,7.40–7.34(m,2H),7.34–7.28(m,1H),3.60–3.56(m,1H),3.00(s,1H),1.73(d,J=1.9Hz,3H),1.24(d,J=7.2Hz,3H);
[0035] 13CNMR(151MHz,Chloroform-d)δ209.14,196.24,169.16,142.66,136.25,135.9 5,134.75,129.35,129.31,128.88,128.10,124.92,80.17,50.04,14.34,9.99;
[0036] HRMS (ESI) calculation for C 20 H 18 NaO 3 [M+Na] + 329.1154, found 329.1160.
[0037] Example 2
[0038] An α-hydroxycyclopentenone compound containing tertiary carbon and quaternary carbon, the synthesis formula of which is as follows:
[0039]
[0040] The specific synthesis method comprises the following steps:
[0041] S1: Add 1 mmol of compound 3 (238.3 mg) into a round-bottom flask, and then add 5 mL of toluene into the round-bottom flask to dissolve compound 3;
[0042] S2: 5 mL of a 10% aqueous NaOH solution and 0.2 mmol of tetrabutylammonium fluoride (added in the form of a solution obtained by dissolving 0.2 mmol of tetrabutylammonium fluoride in 0.2 mL of THF) were added to a round-bottom flask under stirring to obtain a reaction mixture;
[0043] S3: The reaction mixture was stirred at room temperature at a stirring rate of 100 rpm for 6 h;
[0044] S4: After the reaction is complete, the reaction solution is diluted with ethyl acetate and water and separated, the aqueous phase is washed with ethyl acetate three times, and the organic phases are combined; the organic phase is then washed with saturated brine, and then dried over anhydrous sodium sulfate, and then the solvent is removed by distillation under reduced pressure to obtain a crude product;
[0045] S5: The crude product was separated and purified by silica gel column chromatography (PE:EA=10:1) to obtain compound 4 (185.7 mg, 81%).
[0046] The characterization data of compound 4 are as follows:
[0047] 1 HNMR (600MHz, CDCl 3)δ7.57–7.52(m,3H),7.36(t,2H),7.23–7.19(m,3H),7.13–7.08(m,5H),7.05–7.02(m,5H),6.96–6.93(m,2H),3.97(t,J=7.3H z,1H),3.66(d,J=14.5Hz,1H),3.49(d,J=14.5Hz,1H),3.33(dd,J=14.4,7.6Hz,1H),3.09(s,1H),2.77(dd,J=14.4,7.1Hz,1H);
[0048] 13 CNMR (151MHz, CDCl 3 )δ208.50,195.52,167.75,142.93,140.74,138.26,136.83,135.61,134.29,129.50,129.13,128. 97,128.85,128.69,128.56,128.18,127.95,126.67,126.43,125.04,80.85,56.85,36.07,30.48;
[0049] HRMS (ESI) calculation for C 32 H 27 O 3 [M+H] + 459.1960, found 459.1957.
[0050] Example 3
[0051] An α-hydroxycyclopentenone compound containing tertiary carbon and quaternary carbon, the synthesis formula of which is as follows:
[0052]
[0053] The specific synthesis method comprises the following steps:
[0054] S1: Add 1 mmol of compound 5 (192.2 mg) into a round-bottom flask, and then add 10 mL of toluene into the round-bottom flask to dissolve compound 5;
[0055] S2: 10 mL of a 5% KOH aqueous solution and 0.2 mmol of tetrabutylammonium chloride (added in the form of a solution obtained by dissolving 0.2 mmol of tetrabutylammonium chloride in 0.2 mL of THF) were added to a round-bottom flask under stirring to obtain a reaction mixture;
[0056] S3: The reaction mixture was stirred at room temperature at a stirring rate of 100 rpm for 8 h;
[0057] S4: After the reaction is complete, the reaction solution is diluted with ethyl acetate and water and separated, the aqueous phase is washed with ethyl acetate three times, and the organic phases are combined; the organic phase is then washed with saturated brine, and then dried over anhydrous sodium sulfate, and then the solvent is removed by distillation under reduced pressure to obtain a crude product;
[0058] S5: The crude product was separated and purified by chromatography on a silica gel column (PE:EA=10:1) to obtain compound 6 (157.5 mg, 86%).
[0059] The characterization data of compound 6 are as follows:
[0060] 1 H NMR (600 MHz, CDCl 3 )δ7.83(d,J=8.9Hz,2H),7.36(d,J=8.8Hz,2H),6.98(d,J=8.9Hz,2H),6.89(d,J=8.8Hz,2H),3.90 (s,3H),3.80(s,3H),3.57–3.51(m,1H),2.99(s,1H),1.71(d,J=1.9Hz,3H),1.21(d,J=7.2Hz,3H);
[0061] 13 C NMR (151 MHz, CDCl 3 )δ209.18,194.58,169.59,164.94,159.39,135.29,134.63,131.85,12 8.99,126.35,114.60,114.20,79.92,55.80,55.46,49.91,14.47,9.92;
[0062] HRMS(ESI)calcd for C 22 H 23 O 5 [M+H] + 367.1545, found 367.1539.
[0063] Example 4
[0064] An α-hydroxycyclopentenone compound containing tertiary carbon and quaternary carbon, the synthesis formula of which is as follows:
[0065]
[0066] The specific synthesis method comprises the following steps:
[0067] S1: Add 1 mmol of compound 7 (176.2 mg) into a round-bottom flask, and then add 4 mL of toluene into the round-bottom flask to dissolve compound 7;
[0068] S2: Add 4 mL of 10% NaHCO to the round-bottom flask under stirring. 3 The aqueous solution and 0.2 mmol tetrabutylammonium bromide (added in the form of a solution obtained by dissolving 0.2 mmol tetrabutylammonium bromide in 0.2 mL THF) to obtain a reaction mixture;
[0069] S3: The reaction mixture was stirred at room temperature at a stirring rate of 100 rpm for 6 h;
[0070] S4: After the reaction is complete, the reaction solution is diluted with ethyl acetate and water and separated, the aqueous phase is washed with ethyl acetate three times, and the organic phases are combined; the organic phase is then washed with saturated brine, and then dried over anhydrous sodium sulfate, and then the solvent is removed by distillation under reduced pressure to obtain a crude product;
[0071] S5: The crude product was separated and purified by silica gel column chromatography (PE:EA=10:1) to obtain compound 8 (117 mg, 70%).
[0072] The characterization data of compound 8 are as follows:
[0073] 1 HNMR (600MHz, CDCl 3 )δ7.85–7.81(m,2H),7.64(t,J=7.4Hz,1H),7.52–7.46(m,2H),7.43(d,J=8.1Hz,2H),7.37(t,J=7.7Hz,2H),7.30(t,J=7.3Hz,1H),3. 44(dd,J=7.2,5.8Hz,1H),3.09(s,1H),2.31–2.22(m,1H),2.18–2.10(m,1H),1.91–1.83(m,1H),1.61–1.56(m,1H),0.97–0.91(m,6H);
[0074] 13 CNMR (151MHz, CDCl 3 )δ209.25,196.55,168.06,143.52,142.28,135.83,134.67,129.30,129 .24,128.84,127.94,124.88,80.83,57.03,23.54,18.11,12.92,12.41;
[0075] HRMS (ESI) calculation for C22 H 21 O 2 [MH 2 O+H] + 317.1542, found 317.1542.
[0076] Example 5
[0077] An α-hydroxycyclopentenone compound containing tertiary carbon and quaternary carbon, the synthesis formula of which is as follows:
[0078]
[0079] The specific synthesis method comprises the following steps:
[0080] S1: Add 1 mmol of compound 9 (192.2 mg) into a round-bottom flask, and then add 5 mL of toluene into the round-bottom flask to dissolve compound 9;
[0081] S2: Add 5 mL of 10% NaCO to the round-bottom flask under stirring. 3 The aqueous solution and 0.2 mmol tetrabutylammonium fluoride (added in the form of a solution obtained by dissolving 0.2 mmol tetrabutylammonium fluoride in 0.2 mL THF) to obtain a reaction mixture;
[0082] S3: The reaction mixture was stirred at room temperature at a stirring rate of 100 rpm for 8 h;
[0083] S4: After the reaction is complete, the reaction solution is diluted with ethyl acetate and water and separated, the aqueous phase is washed with ethyl acetate three times, and the organic phases are combined; the organic phase is then washed with saturated brine, and then dried over anhydrous sodium sulfate, and then the solvent is removed by distillation under reduced pressure to obtain a crude product;
[0084] S5: The crude product was separated and purified by silica gel column chromatography (PE:EA=10:1) to obtain compound 10 (117.2 mg, 64%).
[0085] The characterization data of compound 10 are as follows:
[0086] 1 HNMR (600MHz, CDCl 3)δ7.43–7.37(m,3H),7.28(d,J=8.0Hz,1H),7.20(d,J=9.3Hz,1H),7.03–7.01(m,1H),6.95(d,J=8.6Hz,1H),6.84(dd,J= 8.2,2.6Hz,1H),3.84(s,3H),3.82(s,3H),3.57–3.52(m,1H),3.08(s,1H),1.74(d,J=1.9Hz,3H),1.22(d,J=7.2Hz,3H);
[0087] 13 CNMR (151MHz, CDCl 3 )δ208.89,195.99,169.42,160.39,160.03,144.43,137.16,136.30,130.37,129.93,12 2.32,121.52,117.07,113.46,112.66,110.86,80.08,55.64,55.43,50.18,14.34,9.93;
[0088] HRMS (ESI) calculation for C 22 H 21 O 4 [MH 2 O+H] + 349.1440, found 349.1426.
[0089] Example 6
[0090] An α-hydroxycyclopentenone compound containing tertiary carbon and quaternary carbon, the synthesis formula of which is as follows:
[0091]
[0092] The specific synthesis method comprises the following steps:
[0093] S1: Add 1 mmol of compound 11 (168.2 mg) into a round-bottom flask, and then add 5 mL of toluene into the round-bottom flask to dissolve compound 11;
[0094] S2: 5 mL of a 10% KOH aqueous solution and 0.2 mmol of tetrabutylammonium fluoride (added in the form of a solution obtained by dissolving 0.2 mmol of tetrabutylammonium fluoride in 0.2 mL of THF) were added to a round-bottom flask under stirring to obtain a reaction mixture;
[0095] S3: The reaction mixture was stirred at room temperature at a stirring rate of 100 rpm for 6 h;
[0096] S4: After the reaction is complete, the reaction solution is diluted with ethyl acetate and water and separated, the aqueous phase is washed with ethyl acetate three times, and the organic phases are combined; the organic phase is then washed with saturated brine, and then dried over anhydrous sodium sulfate, and then the solvent is removed by distillation under reduced pressure to obtain a crude product;
[0097] S5: The crude product was separated and purified by silica gel column chromatography (PE:EA=10:1) to obtain compound 12 (150 mg, 94%).
[0098] The characterization data of compound 12 are as follows:
[0099] 1 H NMR (600 MHz, CDCl 3 )δ7.83(dd,J=4.9,1.1Hz,1H),7.58(dd,J=3.8,1.1Hz,1H),7.27(dd,J=5.1,1.2Hz,1H),7.19(dd,J=4.9,3.8Hz,1H),7.03(dd ,J=3.6,1.2Hz,1H),6.97(dd,J=5.1,3.6Hz,1H),3.70–3.65(m,1H),3.25(s,1H),1.82(d,J=1.8Hz,3H),1.29(d,J=4.0Hz,3H);
[0100] 13 C NMR (151 MHz, CDCl 3 )δ206.41,187.41,167.84,146.31,142.98,136.68,135.31,135.12,128.98,127.24,125.58,124.12,78.67,50.28,15.15,10.19;
[0101] HRMS(ESI)calcd for C 16 H 13 O 2 S 2 [MH 2 O+H] + 301.0357, found 301.0373.
[0102] Example 7
[0103] An α-hydroxycyclopentenone compound containing tertiary carbon and quaternary carbon, the synthesis formula of which is as follows:
[0104]
[0105] The specific synthesis method comprises the following steps:
[0106] S1: Add 1 mmol of compound 13 (196.6 mg) into a round-bottom flask, and then add 5 mL of toluene into the round-bottom flask to dissolve compound 13;
[0107] S2: 5 mL of a 10% KOH aqueous solution and 0.2 mmol of tetrabutylammonium fluoride (added in the form of a solution obtained by dissolving 0.2 mmol of tetrabutylammonium fluoride in 0.2 mL of THF) were added to a round-bottom flask under stirring to obtain a reaction mixture;
[0108] S3: The reaction mixture was stirred at room temperature at a stirring rate of 100 rpm for 8 h;
[0109] S4: After the reaction is complete, the reaction solution is diluted with ethyl acetate and water and separated, the aqueous phase is washed with ethyl acetate three times, and the organic phases are combined; the organic phase is then washed with saturated brine, and then dried over anhydrous sodium sulfate, and then the solvent is removed by distillation under reduced pressure to obtain a crude product;
[0110] S5: The crude product was separated and purified by silica gel column chromatography (PE:EA=10:1) to obtain compound 14 (109.5 mg, 58.4%).
[0111] The characterization data of compound 14 are as follows:
[0112] 1 HNMR (600MHz, CDCl 3 )δ7.79(d,J=8.6Hz,2H),7.51(d,J=8.5Hz,2H),7.35–7.32(m,4H),3.52–3.48(m,1H),3.23(s,1H),1.71(d,J=1.8Hz,3H),1.20(d,J=7.2Hz,3H);
[0113] 13 CNMR (151MHz, CDCl 3 )δ208.60,194.88,168.55,141.63,140.94,136.26,134.17,134.09,130.64,129.85,129.01,126.43,79.74,49.92,14.17,10.05;
[0114] HRMS (ESI) calculation for C 20 H 15 Cl 2 O 2 [MH 2 O+H]+ 357.0449, found 357.0448.
[0115] Example 8
[0116] An α-hydroxycyclopentenone compound containing tertiary carbon and quaternary carbon, the synthesis formula of which is as follows:
[0117]
[0118] The specific synthesis method comprises the following steps:
[0119] S1: Add 1 mmol of compound 15 (180.2 mg) into a round-bottom flask, and then add 5 mL of toluene into the round-bottom flask to dissolve compound 15;
[0120] S2: 5 mL of a 10% KOH aqueous solution and 0.2 mmol of tetrabutylammonium fluoride (added in the form of a solution obtained by dissolving 0.2 mmol of tetrabutylammonium fluoride in 0.2 mL of THF) were added to a round-bottom flask under stirring to obtain a reaction mixture;
[0121] S3: The reaction mixture was stirred at room temperature at a stirring rate of 100 rpm for 8 h;
[0122] S4: After the reaction is complete, the reaction solution is diluted with ethyl acetate and water and separated, the aqueous phase is washed with ethyl acetate three times, and the organic phases are combined; the organic phase is then washed with saturated brine, and then dried over anhydrous sodium sulfate, and then the solvent is removed by distillation under reduced pressure to obtain a crude product;
[0123] S5: The crude product was separated and purified by silica gel column chromatography (PE:EA=10:1) to obtain compound 16 (78 mg, 45.6%).
[0124] The characterization data of compound 16 are as follows:
[0125] 1 HNMR (600MHz, CDCl 3 )δ7.91–7.87(m,2H),7.40–7.37(m,2H),7.21(t,J=8.5Hz,2H),7.05(t,J=8.7Hz, 2H),3.54–3.50(m,1H),3.08(s,1H),1.72(d,J=2.0Hz,3H),1.21(d,J=7.2Hz,3H);
[0126] 13 CNMR (151MHz, CDCl 3)δ208.75,194.51,168.71,167.68,165.97,163.37,161.74,138.26,138.24,136.02,132.37,132. 35,132.14,132.08,126.87,126.81,116.84,116.69,115.83,115.69,79.74,49.99,14.26,10.01;
[0127] HRMS (ESI) calculation for C 20 H 15 F 2 O 2 [MH 2 O+H] + 325.1040, found 325.1051.
[0128] Example 9
[0129] An α-hydroxycyclopentenone compound containing tertiary carbon and quaternary carbon, the synthesis formula of which is as follows
[0130]
[0131] The specific synthesis method comprises the following steps:
[0132] S1: Add 1 mmol of compound 17 (241 mg) into a round-bottom flask, and then add 5 mL of toluene into the round-bottom flask to dissolve compound 15;
[0133] S2: 5 mL of a 10% KOH aqueous solution and 0.2 mmol of tetrabutylammonium fluoride (added in the form of a solution obtained by dissolving 0.2 mmol of tetrabutylammonium fluoride in 0.2 mL of THF) were added to a round-bottom flask under stirring to obtain a reaction mixture;
[0134] S3: The reaction mixture was stirred at room temperature at a stirring rate of 100 rpm for 6 h;
[0135] S4: After the reaction is complete, the reaction solution is diluted with ethyl acetate and water and separated, the aqueous phase is washed with ethyl acetate three times, and the organic phases are combined; the organic phase is then washed with saturated brine, and then dried over anhydrous sodium sulfate, and then the solvent is removed by distillation under reduced pressure to obtain a crude product;
[0136] S5: The crude product was separated and purified by silica gel column chromatography (PE:EA=10:1) to obtain compound 18 (70 mg, 30%).
[0137] The characterization data of compound 18 are as follows:
[0138] 1 H NMR (600 MHz, CDCl 3 )δ7.72–7.70(m,2H),7.70–7.68(m,2H),7.51–7.48(m,2H),7.30–7.27(m,2H) ,3.53–3.48(m,1H),3.01(s,1H),1.72(d,J=1.9Hz,3H),1.20(d,J=7.2Hz,3H);
[0139] 13 C NMR (151 MHz, CDCl 3 )δ208.42,195.04,168.49,141.45,136.30,134.58,132.85,132.00,130.67,130.49,126.73,122.27,79.84,49.86,14.26,10.09;
[0140] HRMS(ESI)calcd for C 20 H 15 Br 2 O 2 [MH 2 O+H] + 444.9439, found 444.9448.
[0141] Although the specific implementation of the present invention is described in detail in conjunction with the embodiments, it should not be understood as limiting the scope of protection of this patent. Within the scope described in the claims, various modifications and variations that can be made by those skilled in the art without creative work still fall within the scope of protection of this patent.
Claims
1. A method for preparing an α-hydroxycyclopentenone compound containing tertiary carbon and quaternary carbon, characterized in that: The following steps are involved: S1: dissolving a 1,2-diketone compound in a solvent to obtain a substrate solution; the structural formula of the 1,2-diketone compound is as shown in Formula I, ， Wherein, Ar is phenyl, phenyl with electron withdrawing or electron donating, or heteroaryl; R is methyl, ethyl, or benzyl; S2: adding alkali solution and phase transfer catalyst to the substrate solution, stirring the reaction at room temperature for 6-8 hours, and then separating and purifying to obtain α-hydroxycyclopentenone compounds containing tertiary carbon and quaternary carbon; the phase transfer catalyst is tetrabutylammonium fluoride, tetrabutylammonium chloride or tetrabutylammonium bromide; the structural formula of the α-hydroxycyclopentenone compounds containing tertiary carbon and quaternary carbon is shown in Formula II, 。 2. The preparation method according to claim 1, characterized in that: The solvent is at least one of toluene, tetrahydrofuran, dichloromethane and methyl tert-butyl ether.
3. The preparation method according to claim 2, characterized in that: The concentration of the 1,2-diketone compound in the substrate solution is 0.1-0.25M.
4. The preparation method according to claim 1 or 3, characterized in that: The 1,2-diketone compound is one of the following compounds: 、 、 、 、 、 、 、 、 。 5. The preparation method according to claim 1, characterized in that: The alkali solution is an aqueous solution of alkali; the alkali is KOH, NaOH, NaHCO3, Na2CO3 or K3PO4.
6. The preparation method according to claim 5, characterized in that: The mass concentration of the alkali solution is 5-10%.
7. The preparation method according to claim 6, characterized in that: The volume of alkali solution added is the same as that of solvent.
8. The preparation method according to claim 1, characterized in that: The molar ratio of the phase transfer catalyst to the 1,2-diketone compound is 1:
5.
9. The preparation method according to claim 1, characterized in that: The separation and purification in S2 includes the following steps: diluting the reaction solution after the stirring reaction with ethyl acetate and water and separating the liquids, washing the aqueous phase with ethyl acetate three times, and combining the organic phases; then washing the organic phase with saturated brine, drying over anhydrous sodium sulfate, and removing the solvent by reduced pressure distillation to obtain a crude product; and then purifying the crude product by chromatography on a silica gel column to obtain α-hydroxycyclopentenone compounds containing tertiary carbon and quaternary carbon.
10. The preparation method according to claim 9, characterized in that: The mobile phase used for chromatography on a silica gel column was a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1.