Polysubstituted cyclobutanone compound and preparation method thereof
Through the photoreaction of diketone compounds, trialkyl phosphite and photocatalyst, combined with the purification step, the problems of poor instability and compatibility of the enone precursor are solved, and the efficient synthesis of multi-substituted cyclobutanone compounds is achieved.
Patent Information
- Application Number
- CN202510619430.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-14
- Publication Date
- 2025-08-08
AI Technical Summary
Existing enone precursors such as diazo compounds or 2-halogenated acid chlorides are unstable and have poor compatibility in the cycloaddition reaction of enone and olefins, limiting the synthesis of polysubstituted cyclobutanone compounds.
The reaction of diketone compounds, trialkyl phosphite, olefins and photocatalysts under light conditions was used, and the solution was irradiated by LED blue lamp, combined with column chromatography or thin-layer chromatography was prepared to prepare multi-substituted cyclobutanone compounds.
The range of reaction substrates has been expanded, the synthesis steps have been simplified, and the synthesis efficiency of multi-substituted cyclobutanone compounds has been improved.
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Figure CN120441427A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of organic synthesis, in particular to a method for preparing polysubstituted cyclobutanone compounds. Background Art
[0002] Cyclobutanone structures are widely present in drug molecules and natural product molecules, so their synthesis methods are also highly valued. Among the many synthetic methods, the [2+2] cycloaddition method is the most direct and effective method for synthesizing this type of compound. Related literature: (a) Fan, Y.-Y.; Gao, X.-H.; Yue, J.-M. Sci. China Chem. 2016, 59, 1126-1141; (b) Beniddir, MA; Evanno, L.; Joseph, D.; Skiredj, A.; Poupon, E. Nat. Prod. Rep. 2016, 33, 820-842; (c) J. Wang and W. Yu, Org. Lett., 2019, 21, 9236; (d) Wang, M.; Lu, P. Org. Chem. Front. 2018, 5, 254-259; (d) Li, J.; Gao, K.; Bian, M.; Ding, H. Org. Che m.Front.2020,7,136-154; (e)Depres,J.-P.;Delair,P.;Poisson,J.-F.;Kanazawa,A.;Greene,AEAcc.Chem.Res.2016,49,252-261.
[0003] The [2+2] cycloaddition reaction between enones and alkenes is widely used in the synthesis of cyclobutanone compounds. However, common enone precursors such as diazo compounds or 2-haloacyl chlorides require pre-preparation and suffer from instability and poor compatibility, which greatly limits their application in organic synthesis. Summary of the Invention
[0004] In response to the above technical problems, the present invention provides a polysubstituted cyclobutanone compound and a preparation method thereof.
[0005] To achieve the above object, the technical solution of the present invention is implemented as follows:
[0006] A method for preparing a polysubstituted cyclobutanone compound comprises the following steps:
[0007] (1) Add a diketone compound, a trialkyl phosphite, an olefin, a photocatalyst, and a reaction solvent into a reaction vessel and dissolve them; use argon or nitrogen for degassing protection; wherein the structural formula of the diketone compound is Among them, Ar 1 and Ar2 Each is independently phenyl, or substituted phenyl (selected from o-, m-, p-substituted or polysubstituted phenyl); the structural formula of the olefin is where R 1 and R 2 Each independently represents H, a C1-C18 straight-chain or branched substituted alkyl group, and X represents an O or S atom; the structural formula of the trialkyl phosphite is as follows: P(OR′)3, wherein R′ represents a C1-C10 straight-chain or branched alkyl group;
[0008] (2) irradiating the reaction solution with a suitable light source and stirring until the reaction is complete;
[0009] (3) After the reaction is completed, the solvent is recovered under reduced pressure and purified to obtain a polysubstituted cyclobutanone compound. Purification refers to purification by column chromatography or preparative thin layer chromatography.
[0010] The preparation reaction formula of polysubstituted cyclobutanone compounds is as follows:
[0011]
[0012] The photocatalyst in the above step (1) is an organic photosensitizer or a metal photocatalyst.
[0013] Furthermore, the organic photosensitizer is 4CzIPN or MesAcrClO4, and the metal photocatalyst is [Ru(dtbbpy)3](PF6)2 or [Ir(dtbbpy)(ppy)2]PF6.
[0014] Furthermore, the solvent in the above step (1) is any one of dichloroethane, acetonitrile, dichloromethane, ethyl acetate and toluene.
[0015] Furthermore, in the above step (1), the molar ratio of the diketone compound, the olefin, the trialkyl phosphite, and the photocatalyst is 1:(1-10):(1-2):(0.01-0.1). For example, the molar ratio of the diketone compound, the olefin, the trialkyl phosphite, and the photocatalyst is 1:5:1.2:0.01; the molar ratio of the diketone compound, the olefin, the trialkyl phosphite, and the photocatalyst is 1:10:1.2:0.01; the molar ratio of the diketone compound, the olefin, the trialkyl phosphite, and the photocatalyst is 1:10:1.5:0.01; the molar ratio of the diketone compound, the olefin, the trialkyl phosphite, and the photocatalyst is 1:10:2:0.01; the molar ratio of the diketone compound, the olefin, the trialkyl phosphite, and the photocatalyst is 1:10:1.2:0.02, etc., and any ratio within the range of 1:(1-10):(1-2):(0.01-0.1) is sufficient.
[0016] In the above step (2), the light source is an LED blue light, the wavelength of the LED blue light corresponds to the maximum absorption of the photocatalyst, and the power is 1-45W.
[0017] The polysubstituted cyclobutanone compound prepared by the above preparation method has the structural formula Among them, Ar 1 and Ar 2 Each is independently phenyl or substituted phenyl; R 1 and R 2 Each is independently H, a C1-C18 straight-chain or branched substituted alkyl group, and X is an O or S atom.
[0018] Furthermore, the above-mentioned polysubstituted cyclobutanone compounds include but are not limited to any one of the following compounds:
[0019]
[0020]
[0021] The beneficial effects of the present invention are as follows: the synthesis method of the polysubstituted cyclobutanone compound provided by the present invention expands the scope of reaction substrates and greatly simplifies the synthesis steps. BRIEF DESCRIPTION OF THE DRAWINGS
[0022] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.
[0023] Figure 1 The present invention provides a reaction formula for preparing polysubstituted cyclobutanone compounds.
[0024] Figure 2 This is the reaction formula for preparing polysubstituted cyclobutanone compounds according to Example 1 of the present invention.
[0025] Figure 3 This is the reaction formula for preparing polysubstituted cyclobutanone compounds in Example 8 of the present invention. DETAILED DESCRIPTION
[0026] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without creative work are within the scope of protection of the present invention.
[0027] Example 1
[0028] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0029]
[0030] In a 10 mL Schlenk tube, diketone compound 1a (21 mg, 0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. Alkene 2a (96 μL, 1.0 mmol, 10.0 equiv.) was then added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (PE:EA = 20:1 by volume, the same below) to afford compound 3aa (21.5 mg, 81% yield).
[0031] 1 H NMR(300MHz,Chloroform-d)δ7.84-7.72(m,2H),7.33(d,J=8.1Hz,2H),3.75(t,J=6.3Hz,2H),3.37 (t,J=6.4Hz,2H),3.26(t,J=6.7Hz,2H),2.44(s,3H),1.42(h,J=7.1Hz,2H),0.78(t,J=7.4Hz,3H); 13 C NMR(75MHz,Chloroform-d)δ144.66,136.95,129.75,128.12,72.94,64.00,56.39,22.62,21.65,10.39; HRMS(ESI-TOF)m / z[M+H] + calcdfor C 18 H 19 O2 + :267.1380;found:267.1380.
[0032] Example 2
[0033] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0034]
[0035] In a 10 mL Schlenk tube, diketone compound 1a (21 mg, 0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. Alkene 2b (112 μL, 1.0 mmol, 10.0 equiv.) was then added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (PE:EA = 20:1 by volume, the same below) to afford compound 3ab (19.9 mg, 71% yield).
[0036] 1 H NMR (300MHz, CDCl3) δ7.47(d,J=8.4Hz,2H),7.37(t,J=7.5Hz,2H),7.32-7.12(m,6H),4.83(dd,J=7.4,5.5H z,1H),3.53-3.25(m,3H),3.20(dd,J=18.0,5.4Hz,1H),1.47(qd,J=7.1,2.5Hz,2H),0.79(t,J=7.4Hz,3H). 13 C NMR(75MHz,Chloroform-d)δ207.8,140.0,138.0,128.8,128.75,128.72,128.0,127.48 127.45,127.2,127.0,79.8,73.7,71.8,51.8,22.8,10.6; HRMS(ESI-TOF)m / z[M+H] + calcd for C 19 H 21 O2 + :281.1536; found:281.1535.
[0037] Example 3
[0038] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0039]
[0040] In a 10 mL Schlenk tube, diketone compound 1a (21 mg, 0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. Alkene 2c (129 μL, 1.0 mmol, 10.0 equiv.) was then added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (PE:EA = 20:1 by volume, the same below) to afford compound 3ac (21.5 mg, 73% yield).
[0041] 1 H NMR(300MHz,Chloroform-d)δ7.47(d,J=7.3Hz,2H),7.40-7.31(m,2H),7.31-7.14(m,6H),4.91-4.73(m,1H), 3.54-3.26(m,3H),3.19(dd,J=18.0,5.4Hz,1H),1.50-1.35(m,2H),1.26-1.15(m,2H),0.83(t,J=7.3Hz,3H). 13 C NMR(75MHz,Chloroform-d)δ207.7,140.0,138.0,128.8,128.7,127.9,127.4,1 27.2,127.0,79.8,73.8,70.0,51.8,31.6,19.2,13.8; HRMS(ESI-TOF)m / z[M+H] + calcd for C 20 H 23 O2 + :295.1693; found:295.1694.
[0042] Example 4
[0043] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0044]
[0045] In a 10 mL Schlenk tube, diketone compound 1a (21 mg, 0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. Alkene 2d (130 μL, 1.0 mmol, 10.0 equiv.) was then added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (PE:EA = 20:1 by volume, the same below) to afford compound 3ad (13.5 mg, 46% yield).
[0046] 1 H NMR(300MHz,Chloroform-d)δ7.49(d,J=7.6Hz,2H),7.38(t,J=7.6Hz,2H),7.34-7.16(m,6H),4.83(dd,J=7.3,5.4Hz,1H) ,3.41(dd,J=18.0,7.3Hz,1H),3.31-3.10(m,3H),1.75(hept,J=6.6Hz,1H),0.82(d,J=6.7Hz,3H),0.77(d,J=6.7Hz,3H). 13 C NMR(75MHz,Chloroform-d)δ207.9,140.1,138.0,128.8,128.7,127.9,127.4,127.2,127.0,79.7,76.8,73.7,51.7,28.5,19.3; HRMS(ESI-TOF)m / z[M+Na] + calcd for C 20 H 22 O2N a + :317.1512; found:317.1513.
[0047] Example 5
[0048] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0049]
[0050] In a 10 mL Schlenk tube, diketone compound 1a (21 mg, 0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. Alkene 2e (129 μL, 1.0 mmol, 10.0 equiv.) was then added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (PE:EA = 20:1 by volume, the same below) to afford compound 3ae (16 mg, 55% yield).
[0051] 1 H NMR(300MHz,Chloroform-d)δ7.44(d,J=7.1Hz,2H),7.37-7.16(m,8H),4.98(t,J=6 .7Hz,1H),3.31(dd,J=17.5,7.0Hz,1H),3.16(dd,J=17.5,6.4Hz,1H),1.25(s,9H). 13 C NMR(75MHz,Chloroform-d)δ208.0,141.7,138.2,128.9,128.7,127.8,126.9,126.7,126.5,78.9,75.1,66.3,54.7,28.4; HRMS(ESI-TOF)m / z[M+H] + calcd for C 20 H 23 O2 + :295.1693; found:295.2194.
[0052] Example 6
[0053] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0054]
[0055] In a 10 mL Schlenk tube, diketone compound 1a (21 mg, 0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. Alkene 2f (142 μL, 1.0 mmol, 10.0 equiv.) was then added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (PE:EA = 20:1 by volume, the same below) to afford compound 3af (15.7 mg, 55% yield).
[0056] 1 H NMR(300MHz,Chloroform-d)δ7.47(d,J=7.1Hz,2H),7.39(t,J=7.5Hz,2H),7.27(dp,J=10.4,5.0Hz,6H),5.02(dd,J=7.3 ,5.7Hz,1H),3.49-3.30(m,2H),3.21(dd,J=17.9,5.7Hz,1H),1.93(m,1H),1.71(m,2H),1.52(m,1H),1.39-1.12(m,6H). 13 C NMR(75MHz,Chloroform-d)δ208.1,140.5,138.3,128.8,127.9,127.2,127.1,1 26.9,79.8,70.6,52.4,32.1,32.0,25.8,23.9,23.9; HRMS(ESI-TOF)m / z[M+Na] + calcd for C 22 H 24 O2N a + :343.1669; found:343.1670.
[0057] Example 7
[0058] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0059]
[0060] In a 10 mL Schlenk tube, diketone compound 1b (23.8 mg, 0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. Alkene 2a (96 μL, 1.0 mmol, 10.0 equiv.) was then added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (PE:EA = 20:1 by volume, the same below) to afford compound 3ba (20.6 mg, 70% yield).
[0061] 1 H NMR(300MHz,Chloroform-d)δ7.37(d,J=7.8Hz,2H),7.21(d,J=7.9Hz,2H),7.11(s,4H),4.84(dd,J=7.9,4.9Hz ,1H),3.58(m,1H),3.43(m,2H),3.21(dd,J=18.0,5.3Hz,1H),2.38(s,3H),2.34(s,3H),1.12(t,J=7.0Hz,3H). 13 C NMR(75MHz,Chloroform-d)δ207.2,136.0,135.8,135.5,134.1,128.4,127.6,127.5,126.3,78.3,2.6,64.6,50.7,20.0,13.9; HRMS(ESI-TOF)m / z[M+H] + calcd for C 20 H 23 O2 + :295.1693; found:295.1689.
[0062] Example 8
[0063] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0064]
[0065] In a 10 mL Schlenk tube, diketone compound 1c (24.6 mg, 0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. Alkene 2a (96 μL, 1.0 mmol, 10.0 equiv.) was then added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (PE:EA = 20:1 by volume, the same below) to afford compound 3ca (12.4 mg, 41% yield).
[0066] 1 H NMR(300MHz,Chloroform-d)δ7.46-7.35(m,2H),7.17-7.03(m,4H),6.96(td,J=9.4,2.7Hz,2H),4.76(dd,J =7.4,5.4Hz,1H),3.61-3.49(m,1H),3.49-3.31(m,2H),3.18(dd,J=18.1,5.4Hz,1H),1.08(t,J=7.0Hz,3H). 13 C NMR(75MHz,Chloroform-d)δ207.3,163.6,163.6,160.3,160.3,135.5,133.5,130.4,130.3,12 9.1,129.0,116.0,115.7,115.1,114.8,78.3,73.6,65.7,51.9,15.0; HRMS(ESI-TOF)m / z[M+H] + calcd for C 18 H 17 F2O2 + :303.1191; found:303.1197.
[0067] Example 9
[0068] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0069]
[0070] In a 10 mL Schlenk tube, diketone compound 1d (24.6 mg, 0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. Alkene 2a (96 μL, 1.0 mmol, 10.0 equiv.) was then added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (PE:EA = 20:1 by volume, the same below) to afford compound 3da (16.6 mg, 55% yield).
[0071] 1 HNMR(300MHz,Chloroform-d)δ7.40-7.30(m,1H),7.24(t,J=7.5Hz,2H),7.16(dt,J=10.0,2.2Hz,1H),7.09-6.87(m,4H) ,4.80(dd,J=7.4,5.6Hz,1H),3.70-3.52(m,1H),3.51-3.32(m,2H),3.21(dd,J=18.1,5.6Hz,1H),1.12(t,J=7.0Hz,3H). 13 C NMR(75MHz,Chloroform-d)δ205.8,164.6,164.1,161.4,160.9,142.0,141.9,139.8,139.7,130.5,130.4,129.5,129.4,12 4.2,124.1,122.9,122.8,116.0,115.7,114.6,114.4,114.3,114.1,78.8,73.6,65.8,51.8,14.9; HRMS(ESI-TOF)m / z[M+H] + calcd for C 18 H 17 F2O2 + :303.1191; found:303.1196.
[0072] Example 10
[0073] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0074]
[0075] In a 10 mL Schlenk tube, the diketone compound 1e (24.6 mg, 0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. Then, the olefin 2a (96 μL, 1.0 mmol, 10.0 equiv.) was added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (PE:EA = 20:1 by volume, the same below) to afford compound 3ea (22 mg, 74% yield).
[0076] 1 H NMR(300MHz,Chloroform-d)δ7.47-7.38(m,1H),7.37-7.22(m,2H),7.21-6.98(m,4H),6.90( t,J=7.6Hz,1H),4.87(t,J=6.7Hz,1H),3.58-3.44(m,2H),3.36(m,2H),0.99(t,J=7.0Hz,3H). 13 C NMR(75MHz,Chloroform-d)δ205.5,162.9,162.6,159.6,159.3,130.0,130.0,129.8,129.7,129.7,129.7,129.6,129.5,124 .7,124.6,123.9,123.9,116.7,116.4,115.8,115.5,74.7,73.3,73.2,66.1,66.1,51.8,51.7,15.0; HRMS(ESI-TOF)m / z[M+H] + calcd for C 18 H 17 F2O2 + :303.1191; found:303.1183.
[0077] Example 11
[0078] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0079]
[0080] In a 10 mL Schlenk tube, the diketone compound 1f (0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. Then, the olefin 2a (96 μL, 1.0 mmol, 10.0 equiv.) was added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (volume ratio, PE:EA = 20:1, the same below) to afford compound 3fa (19 mg, 64% yield, dr = 1.5:1).
[0081] 1 H NMR (300MHz, CDCl3): δ7.44–7.36(m,0.75H),7.33(d,J=8.6Hz,1.25H),7.19–7.00(m,3H),6.99–6.86(m,2.25H),6.84–6.75(m,0.75H),4.82– 4.68(m,1H),3.80(s,1.8H),3.77(s,1.2H),3.51(dt,J=14.5,8.0Hz,1 H),3.44–3.20(m,2H),3.14(dd,J=17.9,4.9Hz,1H),1.12–0.98(m,3H). 13 C NMR (75MHz, CDCl3): δ160.21,158.85,158.62,129.79,128.67,114.34,113.4 8,78.50,73.62,65.71,65.62,55.23,51.83,51.81; HRMS(ESI-TOF)m / z[M+Na] + calcd for C 19 H 19 FO3Na + :337.121; found:337.1211.
[0082] Example 12
[0083] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0084]
[0085] In a 10 mL Schlenk tube, diketone compound 1a (0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. Then, olefin (2 g, 1.0 mmol, 10.0 equiv.) was added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (PE:EA = 20:1 by volume, the same below) to afford compound 3ag (13 mg, 46% yield).
[0086] 1 H NMR (300MHz, CDCl3) δ7.48(s,2H),7.36(s,3H),7.25(s,4H),7.19(s,2H),4.38(s,1H),3.65–3.49(m,1H),3.22(s,1H),2.52(s,2H),1.22(s,4H). 13 C NMR (75MHz, CDCl3) δ206.89,140.53,139.09,128.75,128.12,128.10,127.51, 127.31,126.92,79.60,53.35,40.15,26.18,14.60; HRMS(ESI-TOF)m / z[M+Na] + calcd for C 18 H 18 SO2Na + :305.0971;found:305.0971.
[0087] Example 13
[0088] The preparation method of the polysubstituted cyclobutanone compounds of this embodiment, the reaction formula and steps are as follows:
[0089]
[0090] In a 10 mL Schlenk tube, diketone compound 1a (0.1 mmol, 1.0 equiv.) and P(OEt)₃ (21 μL, 0.12 mmol, 1.2 equiv.) were dissolved in dichloroethane (1.5 mL). The photocatalyst [Ru(dtbbpy)₃](PF₆)₂ (0.002 mmol) was added and stirred for 15 min. The olefin 2h (1.0 mmol, 10.0 equiv.) was then added. The reaction was performed by a freeze-decompression-thaw method with argon protection. The reaction was stirred at room temperature for 48 hours under illumination (LED blue light, 3 W power, 450 nm wavelength). The reaction solution was concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (PE:EA = 20:1 by volume, the same below) to afford compound 3ah (15 mg, 49% yield).
[0091] 1 H NMR (300MHz, CDCl3) δ7.44(d,J=7.6Hz,2H),7.34(t,J=7.6Hz,2H),7.25(dd,J=6.7,4.0Hz,7H),4.44(d, J=6.8Hz,1H),3.65(p,J=6.9Hz,2H),3.46(p,J=7.2Hz,1H),1.28(d,J=7.3Hz,4H),1.17(t,J=7.0Hz,3H); 13 C NMR(75MHz, CDCl3)δ128.66,128.60,128.15,127.19,126.98,126.90,58.81; HRMS(ESI-TOF)m / z[M+H] + calcd for C 19 H 21 O2 + :281.1536;found:281.1536.
[0092] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.
Claims
1. A method for preparing a polysubstituted cyclobutanone compound, characterized in that: The steps are as follows: adding a diketone compound, a trialkyl phosphite, an olefin and a photocatalyst into a solvent for degassing protection; irradiating with a light source, stirring and reacting; after the reaction is complete, reducing pressure to recover the solvent and purifying the solvent to obtain the product.
2. The method for preparing a polysubstituted cyclobutanone compound according to claim 1, wherein: The structural formula of the diketone compound is Among them, Ar 1 and Ar 2 Each is independently phenyl or substituted phenyl; the structural formula of olefin is where R 1 and R 2 Each is independently H, a C1-C18 straight-chain or branched substituted alkyl group, and X is an O or S atom.
3. The method for preparing a polysubstituted cyclobutanone compound according to claim 2, wherein: The structural formula of the trialkyl phosphite is P(OR')3, wherein R' is a C1-C10 straight-chain or branched-chain alkyl group.
4. The method for preparing a polysubstituted cyclobutanone compound according to claim 3, wherein: The photocatalyst is an organic photosensitizer or a metal photocatalyst.
5. The method for preparing a polysubstituted cyclobutanone compound according to claim 4, wherein: The organic photosensitizer is 4CzIPN or MesAcrClO4, and the metal photocatalyst is [Ru(dtbbpy)3](PF6)2 or [Ir(dtbbpy)(ppy)2]PF6.
6. The method for preparing a polysubstituted cyclobutanone compound according to claim 4, wherein: The solvent is any one of dichloroethane, acetonitrile, dichloromethane, ethyl acetate and toluene.
7. The method for preparing a polysubstituted cyclobutanone compound according to claim 6, wherein: The molar ratio of the diketone compound, trialkyl phosphite, olefin and photocatalyst is 1:(1-10):(1-2):(0.01-0.1).
8. The method for preparing a polysubstituted cyclobutanone compound according to claim 7, wherein: The light source is an LED blue light, the wavelength of the LED blue light corresponds to the maximum absorption of the photocatalyst, and the power is 1-45W.
9. A polysubstituted cyclobutanone compound prepared by the preparation method according to any one of claims 1 to 8, characterized in that: The structural formula of the polysubstituted cyclobutanone compound is as follows: Among them, Ar 1 and Ar 2 Each is independently phenyl or substituted phenyl; R 1 and R 2 Each is independently H, a C1-C18 straight-chain or branched substituted alkyl group, and X is an O or S atom.
10. The polysubstituted cyclobutanone compound according to claim 9, characterized in that The polysubstituted cyclobutanone compound is any one of the following compounds: