Method for organic catalytic synthesis of 2-functional-2, 5-dihydrofuran

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a 2-functional-2, 5-dihydrofuran compound and a preparation method thereof. According to the preparation method, gamma-hydroxyl-alpha, beta-unsaturated olefine aldehyde is taken as a reaction raw material, organic amine and Bronsted acid are taken as co-catalysts, and the 2-functional-2, 5-dihydrofuran compound can be prepared at normal temperature and normal pressure. The preparation method provided by the invention is simple and easy to operate, the raw materials are cheap and easy to obtain, the reaction conditions are mild, and only a water byproduct is generated in the reaction and meets the requirements of green chemical development. The 2-functional-2, 5-dihydrofuran compound prepared according to the preparation method provided by the invention has relatively high yield and purity, and has good applicability and economic benefits.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a 2-functionalized-2,5-dihydrofuran compound and its preparation method. Background Technology

[0002] 2-Functionalized 2,5-dihydrofurans are not only fundamental building blocks in many natural compounds and bioactive molecules, but also play a crucial role in organic synthesis. Currently, methods for rapidly, conveniently, and diversely obtaining 2-functionalized 2,5-dihydrofurans are still limited, often involving multi-step synthetic modifications of starting materials. Therefore, developing modular methods for the synthesis of 2-functionalized 2,5-dihydrofurans that are economical, broadly applicable, and highly efficient is of great significance to organic chemistry and medicinal chemistry. Summary of the Invention

[0003] In view of this, the present invention provides a 2-functionalized-2,5-dihydrofuran compound and its preparation method. The preparation method of the 2-functionalized-2,5-dihydrofuran compound provided by the present invention utilizes organic amine catalysis, is simple and easy to operate, and yields a high amount of the 2-functionalized-2,5-dihydrofuran compound.

[0004] This invention provides a method for preparing a 2-functionalized 2,5-dihydrofuran compound, comprising the following steps:

[0005] The γ-hydroxy-α,β-unsaturated enaldehyde, compound 1, organic amine catalyst, Brønsted acid catalyst, and organic solvent were mixed and subjected to a cyclization reaction to obtain the 2-functionalized-2,5-dihydrofuran compound.

[0006] The γ-hydroxy-α,β-unsaturated enaldehyde has the structure shown in Formula 1 or is... Compound 1 has the structure shown in any one of Formulas 2 to 6:

[0007] HOR 3 Equation 2,

[0008] When the γ-hydroxy-α,β-unsaturated enal is When compound 1 is MeOH, the 2-functionalized-2,5-dihydrofuran compound is...

[0009] When the γ-hydroxy-α,β-unsaturated enal is When compound 1 is MeOH, the 2-functionalized-2,5-dihydrofuran compound is...

[0010] When the γ-hydroxy-α,β-unsaturated enal is When compound 1 has the structure shown in any of formulas 2 to 6; when compound 1 is HOR 3 When the 2-functionalized-2,5-dihydrofuran compound has the structure shown in Formula I, and when compound 1 is When the 2-functionalized-2,5-dihydrofuran compound has the structure shown in Formula II, when compound 1 is When the 2-functionalized-2,5-dihydrofuran compound has the structure shown in Formula III, when compound 1 is When the 2-functionalized-2,5-dihydrofuran compound has the structure shown in Formula IV, and when compound 1 is At that time, the 2-functionalized-2,5-dihydrofuran compound has the structure shown in Formula V:

[0011]

[0012] Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, and alkyl;

[0013] R 3 Independently, it can be hydrogen or alkyl;

[0014] R 4 Independently, it can be hydrogen, phenyl, methyl, p-toluenesulfonyl, benzoyl, 4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonyl or 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonyl;

[0015] R 5 Independently, it can be hydrogen, phenyl, methyl, p-toluenesulfonyl, benzoyl, 4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonyl or 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonyl;

[0016] R 6 Independently, they are alkyl and phenyl;

[0017] R 7 Independently, they are hydrogen and alkyl.

[0018] Preferably, the Including γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-bromophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-methylphenyl)-4-hydroxy-2-butenal, (E)-4-hydroxy-4,4-bis(naphthyl-2-yl)-2-butenal, (E)-3-(9-hydroxy-9H-fluoren-9-yl)propenal, (E)-3-(5-hydroxy-5H-dibenzo[a,d][7]annulen-5-yl)propenal, and (E)-4-hydroxy-4,4-dibenzyl-2-butenal.

[0019] Preferably, the organic amine catalyst comprises racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one or (S)-2-[bis(3,5-bis(trifluoromethyl)phenyl)(((2,3-dimethylbutan-2-yl)dimethylsilyl)oxy)methyl]-4,4-difluoropyrrolidine;

[0020] The molar ratio of the γ-hydroxy-α,β-unsaturated enaldehyde compound to the organic amine is 1:0.05 to 0.2.

[0021] Preferably, the Brønsted acid catalyst comprises a dioxane solution of hydrogen chloride (4 mol / L), p-toluenesulfonic acid monohydrate, or trifluoroacetic acid;

[0022] The molar ratio of the γ-hydroxy-α,β-unsaturated enaldehyde and Brønsted acid catalyst is 1:0.05 to 0.2.

[0023] Preferably, the HOR 3 Including methanol, isopropanol, benzyl alcohol, 3-phenyl-2-propyn-1-ol, 3-methyl-2-buten-1-ol, water, and geraniol;

[0024] The Including N-methylaniline, benzamide, p-toluenesulfonamide, celecoxib, and detacoxib;

[0025] The Including 2,3-dimethyl-1H-indole and 3-phenyl-1H-indole;

[0026] Preferably, the molar ratio of the γ-hydroxy-α,β-unsaturated enaldehyde to compound 1 is 1:1.5 to 2.5.

[0027] Preferably, the cyclization reaction is carried out at room temperature (20-30°C) for 10-15 hours.

[0028] This invention also provides a 2-functionalized 2,5-dihydrofuran compound prepared according to the preparation method described above, having the structure shown in any one of formulas I to V:

[0029]

[0030]

[0031] Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, and alkyl;

[0032] R 3 Independently, it can be hydrogen or alkyl;

[0033] R 4 Independently, it can be hydrogen, phenyl, methyl, p-toluenesulfonyl, benzoyl, 4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonyl or 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonyl;

[0034] R 5 Independently, it can be hydrogen, phenyl, methyl, p-toluenesulfonyl, benzoyl, 4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonyl or 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonyl;

[0035] R 6 Independently, they are alkyl and phenyl;

[0036] R 7 Independently, they are hydrogen and alkyl groups;

[0037] Preferably, it has the structure shown in any one of the following formulas: I-1 to I-15, II-1 to I-5, III-1 to III-2, IV, and V:

[0038]

[0039]

[0040] This invention utilizes γ-hydroxy-α,β-unsaturated enal and compound 1 as reactants, and employs an organic amine catalyst and Brønsted acid as catalysts to prepare 2-functionalized-2,5-dihydrofuran compounds at room temperature and pressure. The preparation method provided by this invention is simple and easy to operate, uses inexpensive and readily available raw materials, operates under mild reaction conditions, and produces only water as a byproduct, meeting the requirements of green chemistry development. The 2-functionalized-2,5-dihydrofuran compounds prepared according to the method provided by this invention exhibit high yield and purity, demonstrating good applicability and economic benefits. Detailed Implementation

[0041] This invention provides a method for preparing a 2-functionalized 2,5-dihydrofuran compound, comprising the following steps:

[0042] The γ-hydroxy-α,β-unsaturated enaldehyde, compound 1, organic amine catalyst, Brønsted acid catalyst and organic solvent were mixed and subjected to a cyclization reaction to obtain the 2-functionalized-2,5-dihydrofuran compound.

[0043] The γ-hydroxy-α,β-unsaturated enaldehyde has the structure shown in Formula 1 or is... Compound 1 has the structure shown in any one of Formulas 2 to 6:

[0044]

[0045] In one specific embodiment of the present invention, when the γ-hydroxy-α,β-unsaturated enal is When compound 1 is MeOH, the 2-functionalized-2,5-dihydrofuran compound is...

[0046] In one specific embodiment of the present invention, when the γ-hydroxy-α,β-unsaturated enal is When compound 1 is MeOH, the 2-functionalized-2,5-dihydrofuran compound is...

[0047] When the γ-hydroxy-α,β-unsaturated enal is When compound 1 has the structure shown in any of formulas 2 to 6; when compound 1 is HOR 3 When the 2-functionalized-2,5-dihydrofuran compound has the structure shown in Formula I, and when compound 1 is When the 2-functionalized-2,5-dihydrofuran compound has the structure shown in Formula II, when compound 1 is When the 2-functionalized-2,5-dihydrofuran compound has the structure shown in Formula III, when compound 1 is When the 2-functionalized-2,5-dihydrofuran compound has the structure shown in Formula IV, and when compound 1 is At that time, the 2-functionalized-2,5-dihydrofuran compound has the structure shown in Formula V:

[0048]

[0049] In this invention, R 1 The R is an aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, or alkyl compound. 1The aryl group can be naphthyl, and the R 1 The halogenated phenyl group can be 4-fluorophenyl, 4-chlorophenyl, or 4-bromophenyl, wherein R 1 The alkyl-substituted phenyl group can be 4-methylphenyl, wherein R 1 The alkyl group can be benzyl; R 2 The R is an aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, or alkyl compound. 2 The aryl group can be naphthyl, and the R 2 The halogenated phenyl group can be 4-fluorophenyl, 4-chlorophenyl, or 4-bromophenyl, wherein R 2 The alkyl-substituted phenyl group can be 4-methylphenyl, wherein R 2 The alkyl group can be benzyl.

[0050] As a specific embodiment of the present invention, R 1 and R 2 It can be naphthyl, phenyl, 4-fluorophenyl, 4-bromophenyl, 4-chlorophenyl, 4-methylphenyl, or benzyl.

[0051] As a specific embodiment of the present invention, the Including γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-bromophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-methylphenyl)-4-hydroxy-2-butenal, (E)-4-hydroxy-4,4-bis(naphthyl-2-yl)-2-butenal, (E)-3-(9-hydroxy-9H-fluoren-9-yl)propenal, (E)-3-(5-hydroxy-5H-dibenzo[a,d][7]annulen-5-yl)propenal, and (E)-4-hydroxy-4,4-dibenzyl-2-butenal.

[0052] In this invention, R 3 The R is hydrogen or alkyl. 3 The alkyl group can be methyl, isopropyl, benzyl, 3-phenyl-2-propynyl, 3-methyl-2-buten-1-yl, or (E)-3,7-dimethyl-2,6-octadien-1-yl.

[0053] As a specific embodiment of the present invention, the HOR 3 Including methanol, isopropanol, benzyl alcohol, 3-phenyl-2-propyn-1-ol, 3-methyl-2-buten-1-ol, water, and geraniol.

[0054] In this invention, R 4The R is hydrogen, phenyl, methyl, p-toluenesulfonyl, benzoyl, 4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonyl or 4-(5-methyl-3-phenylisoxazo-4-yl)benzenesulfonyl, 5 It can be hydrogen, phenyl, methyl, p-toluenesulfonyl, benzoyl, 4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl)benzenesulfonyl or 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonyl.

[0055] As a specific embodiment of the present invention, R 4 When R is phenyl, 5 Methyl; R 4 When it is benzoyl, R 5 It is hydrogen; R 4 When it is p-benzoyl, R 5 It is hydrogen; R 4 When R is 4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonyl, 5 It is hydrogen; R 4 When R is 4-(5-methyl-3-phenylisoxazo-4-yl)benzenesulfonyl, 5 It is hydrogen.

[0056] As a specific embodiment of the present invention, the Including N-methylaniline, benzamide, p-toluenesulfonamide, celecoxib, and detacoxib.

[0057] In this invention, R 6 R is an alkyl or phenyl group. 6 The alkyl group can be methyl; R 7 The R is hydrogen or alkyl. 7 The alkyl group can be methyl.

[0058] As a specific embodiment of the present invention, R 6 and R 7 It can be methyl at the same time; when R 6 When R is phenyl, 7 It can also be hydrogen.

[0059] As a specific embodiment of the present invention, the Including 2,3-dimethyl-1H-indole and 3-phenyl-1H-indole;

[0060] In one specific embodiment of the present invention, the organic amine catalyst comprises racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one or (S)-2-[bis(3,5-bis(trifluoromethyl)phenyl)(((2,3-dimethylbutan-2-yl)dimethylsilyl)oxy)methyl]-4,4-difluoropyrrolidine.

[0061] In one specific embodiment of the present invention, the Brønsted acid catalyst comprises a dioxane solution of hydrogen chloride (4 mol / L), p-toluenesulfonic acid monohydrate, or trifluoroacetic acid.

[0062] In this invention, the organic amine catalyst and Brønsted acid catalyst can promote the transformation of γ-hydroxyenal from E configuration to Z configuration by forming an enimine ion intermediate, thereby promoting the efficient and highly selective synthesis of the product. The synthesis of 2-functionalized 2,5-dihydrofuran compounds can be achieved under ambient temperature and pressure. During the reaction, it is not necessary to activate the reactants in advance.

[0063] In one specific embodiment of the present invention, the molar ratio of the γ-hydroxy-α,β-unsaturated enal and the organic amine catalyst can be 1:0.05 to 0.2. Reducing the amount of organic amine catalyst will decrease the yield.

[0064] In one specific embodiment of the present invention, the molar ratio of the γ-hydroxy-α,β-unsaturated enal and the Brønsted acid catalyst can be 1:0.05 to 0.2. Reducing the amount of Brønsted acid will decrease the yield.

[0065] In one specific embodiment of the present invention, the organic solvent may be acetonitrile, dichloromethane, toluene or ethyl acetate; the molar concentration of γ-hydroxy-α,β-unsaturated enal in the reaction solution system of the cyclization reaction may be 0.08 to 0.12 mol / L, specifically 0.1 mol / L.

[0066] In one specific embodiment of the present invention, the molar ratio of the γ-hydroxy-α,β-unsaturated enaldehyde and compound 1 can be 1:1.5 to 2.5, and more specifically 1:2.

[0067] In one specific embodiment of the present invention, the temperature of the cyclization reaction can be room temperature (20-30°C); the time of the cyclization reaction can be 10-15 hours.

[0068] As a specific embodiment of the present invention, preparation The reaction equation is: preparation The reaction equation is: preparation The reaction equation is:

[0069] In this invention, the cyclization reaction further includes: concentrating the cyclization reaction system and then separating and purifying it using silica gel column chromatography to obtain the 2-functionalized-2,5-dihydrofuran compound. This invention does not have special requirements for the concentration and silica gel column chromatography; conventional methods in the art can be used.

[0070] This invention also provides a 2-functionalized-2,5-dihydrofuran compound prepared according to the preparation method described above, having the structure shown in any of formulas I to V:

[0071]

[0072] Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, and alkyl;

[0073] R 3 Independently, it can be hydrogen or alkyl;

[0074] R 4 Independently, it can be hydrogen, phenyl, methyl, p-toluenesulfonyl, benzoyl, 4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonyl or 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonyl;

[0075] R 5 Independently, it can be hydrogen, phenyl, methyl, p-toluenesulfonyl, benzoyl, 4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonyl or 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonyl;

[0076] R 6 Independently, they are alkyl and phenyl;

[0077] R 7 Independently, they are hydrogen and alkyl groups;

[0078] As a specific embodiment of the present invention, the 2-functionalized 2,5-dihydrofuran compound may have any of the structures shown in Formula I-1 to I-15, Formula II-1 to ⅠI-5, Formula III-1 to Ⅲ-2, Formula IV, and Formula V:

[0079]

[0080]

[0081] To further illustrate the present invention, the technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0082] After the preparation of each embodiment was completed, in order to further verify that the purified compound was indeed the target product to be prepared in this embodiment, the obtained solid product was analyzed. The analytical methods used were nuclear magnetic resonance and high-resolution mass spectrometry, and the detection results are listed in each embodiment.

[0083] Example 1

[0084] Using R 1 =R 2 The reaction was carried out using (E)-4-hydroxy-4,4-diphenyl-2-butenal (a phenyl group) and methanol as reactants, with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0085] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.7 mg, 0.4 mmol), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.9 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), were added with stirring at 25 °C to methanol (32.4 μL, 0.8 mmol, 2.0 equiv, 0.791 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane). The reaction was carried out at 25 °C for 11 h. The reaction equation is as follows:

[0086]

[0087] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 81.3 mg of an oily product, with a calculated yield of 81%.

[0088] The analysis of the test is as follows:

[0089] 1. Proton and carbon NMR spectra:

[0090] 1 H NMR (300MHz, CDCl3) δ7.43-7.19(m,10H),6.64(dd,J1=5.8Hz,J2=1.2Hz,1H),5.98(t,J=1.2Hz,1H),5.91(dd,J1=5.8Hz,J2=1.1Hz,1H),3.42(s,3H)ppm.

[0091] 13C NMR (75MHz, CDCl3) δ144.4,144.3,138.5,128.2,128.1,127.4,127.2,126.5,125.5,109.4,94.6,54.6ppm.

[0092] 2. High-resolution mass spectrometry: HRMS(ESI)C 17 H 17 O2[M+H] + :253.1223,Found:253.1220.

[0093] The results show that the theoretical mass is 253.1223, while the observed value of the peak in the actual mass spectrum is 253.1220. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0094] This is a product of this embodiment.

[0095] Example 2

[0096] Using R 1 =R 2 Using (E)-4-hydroxy-4,4-diphenyl-2-butenal (a phenyl group) and isopropanol as reactants, and employing racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one as a catalyst and hydrogen chloride, the reaction is carried out as follows:

[0097] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.8 mg, 0.4 mmol), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.7 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), was added with stirring at 25 °C to isopropanol (61.0 μL, 0.8 mmol, 2.0 equiv, 0.785 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane), and the reaction was carried out at 25 °C for 12 h. The reaction equation is as follows:

[0098]

[0099] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 77.3 mg of an oily product, with a calculated yield of 69%.

[0100] The analysis of the test is as follows:

[0101] 1. Proton and carbon NMR spectra:

[0102] 1H NMR (300MHz, CDCl3) δ7.44-7.35(m,2H),7.34-7.17(m,8H),6.59(dd,J1=5.8Hz,J2=1.3Hz,1H),6.11(t,J=1.2Hz,1 H), 5.89 (dd, J1 = 5.8Hz, J2 = 1.2Hz, 1H), 4.08 (hept, J = 6.2Hz, 1H), 1.22 (d, J = 6.2Hz, 3H), 1.18 (d, J = 6.1Hz, 3H) ppm.

[0103] 13 C NMR (75MHz, CDCl3) δ144.7,144.5,138.0,128.2,127.9,127.3,127.0,126.70,126.65,126.2,106.9,94.5,70.2,23.6,22.1ppm.

[0104] 2. High-resolution mass spectrometry: HRMS(ESI)C 19 H 21 O2[M+H] + :281.1536,Found:281.1529.

[0105] The results show that the theoretical mass is 281.1536, while the observed value of the peak in the actual mass spectrum is 281.1529. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0106] This is a product of this embodiment.

[0107] Example 3

[0108] Using R 1 =R 2 Using (E)-4-hydroxy-4,4-diphenyl-2-butenal and benzyl alcohol as reactants, the reaction was carried out with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolium-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0109] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.4 mg, 0.4 mmol), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (10.3 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), were added with benzyl alcohol (83.0 μL, 0.8 mmol, 2.0 equiv, 1.045 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane) under stirring at 25 °C. The reaction was carried out at 25 °C for 12 h. The reaction equation is as follows:

[0110]

[0111] The reaction solution was concentrated and purified by silica gel column chromatography to obtain an oily product of 109.3 mg, with a calculated yield of 83%.

[0112] The analysis of the test is as follows:

[0113] 1. Proton and carbon NMR spectra:

[0114] 1 H NMR (300MHz, CDCl3) δ7.43-7.37(m,2H),7.35-7.20(m,13H),6.64(dd,J1=5.9Hz,J2=1.2Hz,1H),6.15( t,J=1.2Hz,1H),5.95(dd,J1=5.8Hz,J2=1.1Hz,1H),4.84(d,J=11.6Hz,1H),4.56(d,J=11.6Hz,1H)ppm.

[0115] 13 C NMR (75MHz, CDCl3) δ144.4,144.3,138.4,138.0,128.3,128.2,128.1,128.0,127.5,127.4,127.2,126.7,126.5,125.8,107.9,94.8,69.2ppm.

[0116] 2. High-resolution mass spectrometry: HRMS(ESI)C 23 H 21 O2[M+H] + :329.1536,Found:329.1527.

[0117] The results show that the theoretical mass is 329.1536, while the observed value of the peak found in the actual mass spectrum is 329.1527. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0118] This is a product of this embodiment.

[0119] Example 4

[0120] Using R 1 =R 2 The reaction proceeds using (E)-4-hydroxy-4,4-diphenyl-2-butenal and 3-phenyl-2-propyn-1-ol as phenyl groups, with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0121] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.3 mg, 0.4 mmol), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.6 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), were added with stirring at 25 °C to 3-phenyl-2-propyn-1-ol (100.0 μL, 0.8 mmol, 2.0 equiv, 1.06 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane). The reaction was carried out at 25 °C for 12 h. The reaction equation is as follows:

[0122]

[0123] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 114.5 mg of an oily product, with a calculated yield of 81%.

[0124] The analysis of the test is as follows:

[0125] 1. Proton and carbon NMR spectra:

[0126] 1 H NMR (300MHz, CDCl3) δ7.47-7.41(m,2H),7.41-7.35(m,2H),7.34-7.21(m,11H),6.67(dd,J1=5. 9Hz, J2=1.2Hz, 1H), 6.29 (t, J=1.2Hz, 1H), 6.00 (dd, J1=5.9Hz, J2=1.2Hz, 1H), 4.54(s, 2H)ppm.

[0127] 13C NMR (75MHz, CDCl3) δ144.2,144.1,138.7,131.8,128.4,128.24,128.23,128.1 7,127.5,127.3,126.6,126.5,125.6,122.7,107.1,95.0,86.1,85.1,55.1ppm.

[0128] 2. High-resolution mass spectrometry: HRMS(ESI)C 25 H 21 O2[M+H] + :353.1536,Found:353.1528.

[0129] The results show that the theoretical mass is 353.1536, while the observed value of the peak found in the actual mass spectrum is 353.1528. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0130] This is a product of this embodiment.

[0131] Example 5

[0132] Using R 1 =R 2 The reaction proceeds using (E)-4-hydroxy-4,4-diphenyl-2-butenal and 3-methyl-2-buten-1-ol (both phenyl groups) as reactants, and with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0133] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.8 mg, 0.4 mmol), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.5 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), were added with stirring at 25 °C to 3-methyl-2-buten-1-ol (81.0 μL, 0.8 mmol, 2.0 equiv, 0.848 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane). The reaction was carried out at 25 °C for 12 h. The reaction equation is as follows:

[0134]

[0135] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 84.5 mg of an oily product, with a calculated yield of 69%.

[0136] The analysis of the test is as follows:

[0137] 1. Proton and carbon NMR spectra:

[0138] 1 H NMR (300MHz, CDCl3) δ7.41-7.35(m,2H),7.34-7.19(m,8H),6.62(dd,J1=5.8Hz,J2=1.2Hz,1H),6.08(t,J=1.2Hz,1H),5.93(dd,J1=5.8Hz, J2=1.2Hz,1H),5.40-5.31(m,1H),4.29(dd,J1=11.3Hz,J2=6.9Hz,1H),4.04(dd,J1=11.3Hz,J2=7.4Hz,1H),1.72(s,3H),1.62(s,3H)ppm.

[0139] 13 C NMR (75MHz, CDCl3) δ144.5,138.2,137.6,128.2,128.0,127.3,127.1,126.64,126.55,125.9,120.6,107.8,94.6,63.8,25.8,17.9ppm.

[0140] 2. High-resolution mass spectrometry: HRMS(ESI)C 21 H 23 O2[M+H] + :307.1693,Found:307.1688.

[0141] The results show that the theoretical mass is 307.1693, while the observed value of the peak found in the actual mass spectrum is 307.1688. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0142] This is a product of this embodiment.

[0143] Example 6

[0144] Using R 1 =R 2 The reaction was carried out using (E)-4-hydroxy-4,4-diphenyl-2-butenal (a phenyl group) and water as reactants, with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0145] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.0 mg, 0.4 mmol), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.5 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), were added with water (14.4 μL, 0.8 mmol, 2.0 equiv, 0.998 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 min 1,4-dixoane) under stirring at 25 °C. The reaction was carried out at 25 °C for 14 h. The reaction equation is as follows:

[0146]

[0147] The reaction solution was concentrated and purified by silica gel column chromatography to obtain a solid product of 37.8 mg, with a calculated yield of 40%.

[0148] The analysis of the test is as follows:

[0149] 1. Proton and carbon NMR spectra:

[0150] 1 H NMR (300MHz, Acetone-d6) δ7.60-7.11(m,10H),6.84(d,J=5.8Hz,1H),6.29(d,J=7.7Hz,1H),6.00(d,J=5.8Hz,1H),5.61(d,J=7.9Hz,1H)ppm.

[0151] 13 C NMR (75MHz, Acetone-d6) δ146.6,146.4,137.9,128.8,128.6,128.5,127.7,127.6,127.4,127.2,103.9,94.6ppm.

[0152] The structure of the product can be determined by combining nuclear magnetic resonance as follows:

[0153] 2. High-resolution mass spectrometry: HRMS(ESI)C 16 H 14 NaO2[M+Na] + :261.0886,Found:261.0881.

[0154] The results show that the theoretical mass is 261.0886, while the observed value of the peak in the actual mass spectrum is 261.0881. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0155] This is a product of this embodiment.

[0156] Example 7

[0157] Using R 1 =R 2 Using (E)-4-hydroxy-4,4-diphenyl-2-butenal and geraniol as reactants, the reaction was carried out with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0158] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.6 mg, 0.4 mmol, 1.0 equiv) and racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.8 mg, 0.04 mmol, 10 mol%) were dissolved in acetonitrile (4.0 mL). Geraniol (140.4 μL, 0.8 mmol, 2.0 equiv, 0.879 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane) were added with stirring at room temperature, and the reaction was carried out for 12 h at room temperature. The reaction equation is as follows:

[0159]

[0160] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 123.5 mg of oily product, with a calculated yield of 82%.

[0161] The analysis of the test is as follows:

[0162] 1. Proton and carbon NMR spectra:

[0163] 1 H NMR (300MHz, CDCl3) δ7.41-7.16(m,10H),6.61(d,J=5.8Hz,1H),6.08(s,1H),5.92(d,J=5.8Hz,1H),5.36(t,J=7.1Hz,1H), 5.09(t,J=6.8Hz,1H),4.36-4.25(m,1H),4.14-4.02(m,1H),2.15-1.96(m,4H),1.67(s,3H),1.61(s,3H),1.58(s,3H)ppm.

[0164] 13C NMR (75MHz, CDCl3) δ144.5,140.6,138.1,131.5,128.1,128.0,127.3,127.1,126. 6,126.5,125.9,124.0,120.3,107.7,94.5,63.8,39.5,26.3,25.6,17.6,16.3ppm.

[0165] 2. High-resolution mass spectrometry: HRMS(ESI)C 26 H 30 NaO2[M+Na] + :397.2138,Found:397.2128.

[0166] The results show that the theoretical mass is 397.2138, while the observed peak value in the actual mass spectrum is 397.2128. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0167] This is a product of this embodiment.

[0168] Example 8

[0169] Using R 1 =R 2 The reaction was carried out using (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-2-butenal and methanol as reactants, with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0170] (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-2-butenal (109.9 mg, 0.4 mmol, 1.0 equiv), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.8 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), were added with stirring at 25 °C to methanol (32.4 μL, 0.8 mmol, 2.0 equiv, 0.791 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane). The reaction was carried out at 25 °C for 11 h. The reaction equation is as follows:

[0171]

[0172] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 79.0 mg of an oily product, with a calculated yield of 68%.

[0173] The analysis of the test is as follows:

[0174] 1. Proton and carbon NMR spectra:

[0175] 1 H NMR (300MHz, CDCl3) δ7.38-7.18(m,4H),7.07-6.93(m,4H),6.59-6.53(m,1H),5.96-5.90(m,2H),3.43(s,3H)ppm.

[0176] 13 C NMR (75MHz, CDCl3) δ162.1 (d, J = 245.3Hz), 162.0 (d, J = 244.5Hz), 140.1 (d, J = 3.0Hz), 140.0 (d, J = 3.0Hz), 138.1, 1 28.29 (d, J = 8.3Hz), 128.27 (d, J = 7.5Hz), 125.9, 115.1 (d, J = 21.0Hz), 115.0 (d, J = 21.0Hz), 109.6, 93.7, 55.0ppm.

[0177] 19 F NMR (376MHz, CDCl3) δ-115.0,-115.4ppm.

[0178] 2. High-resolution mass spectrometry: HRMS(ESI)C 17 H 15 F2O2[M+H] + :289.1035,Found:289.1044.

[0179] The results show that the theoretical mass is 289.1035, while the observed value of the peak found in the actual mass spectrum is 289.1044. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0180] This is a product of this embodiment.

[0181] Example 9

[0182] Using R 1 =R 2 The reaction was carried out using (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-2-butenal and methanol as reactants, with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0183] (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-2-butenal (122.5 mg, 0.4 mmol, 1.0 equiv), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (10.2 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), were added with stirring at 25 °C to methanol (32.0 μL, 0.8 mmol, 2.0 equiv, 0.791 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane). The reaction was carried out at 25 °C for 11 h. The reaction equation is as follows:

[0184]

[0185] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 99.6 mg of an oily product, with a calculated yield of 78%.

[0186] The analysis of the test is as follows:

[0187] 1. Proton and carbon NMR spectra:

[0188] 1 H NMR (300MHz, CDCl3) δ7.34-7.17(m,8H),6.55(dd,J1=6.1Hz,J2=1.4Hz,1H),5.97-5.89(m,2H),3.42(s,3H)ppm.

[0189] 13 C NMR (75MHz, CDCl3) δ142.6,142.5,137.6,133.5,133.4,128.5,128.4,127.92,127.88,126.3,109.6,93.6,55.0ppm.

[0190] 2. High-resolution mass spectrometry: HRMS(ESI)C 17 H 15 Cl2O2[M+H] + :321.0444,Found:321.0445.

[0191] The results show that the theoretical mass is 321.0444, while the observed value of the peak found in the actual mass spectrum is 321.0445. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0192] This is a product of this embodiment.

[0193] Example 10

[0194] Using R 1 =R 2 The reaction was carried out using (E)-4,4-bis(4-bromophenyl)-4-hydroxy-2-butenal and methanol as reactants, with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0195] (E)-4,4-bis(4-bromophenyl)-4-hydroxy-2-butenal (159.0 mg, 0.4 mmol, 1.0 equiv), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.7 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), were added with stirring at 25 °C to methanol (32.0 μL, 0.8 mmol, 2.0 equiv, 0.791 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane), and the reaction was carried out at 25 °C for 12 h. The reaction equation is as follows:

[0196]

[0197] The reaction solution was concentrated and purified by silica gel column chromatography to obtain an oily product of 105.9 mg, with a calculated yield of 64%.

[0198] The analysis of the test is as follows:

[0199] 1. Proton and carbon NMR spectra:

[0200] 1 H NMR (300MHz, CDCl3) δ7.44(m,4H),7.18(m,4H),6.55(dd,J1=6.2Hz,J2=1.6Hz,1H),5.94(dd,J1=6.0Hz,J2=1.2Hz,2H),3.42(s,3H)ppm.

[0201] 13 C NMR (75MHz, CDCl3) δ143.0,142.9,137.4,131.42,131.35,128.3,128.2,126.4,121.7,121.6,109.6,93.7,55.0ppm.

[0202] 2. High-resolution mass spectrometry: HRMS(ESI)C 17 H 15 Br2O2[M+H] + :408.9433,Found:408.9429.

[0203] The results show that the theoretical mass is 408.9433, while the observed value of the peak found in the actual mass spectrum is 408.9429. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0204] This is a product of this embodiment.

[0205] Example 11

[0206] Using R 1 =R 2 Using (E)-4-hydroxy-4,4-di-p-tolyl-2-butenal (a 4-methylphenyl group) and methanol as reactants, and employing racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one as a catalyst and hydrogen chloride, the reaction was carried out as follows:

[0207] (E)-4-hydroxy-4,4-di-p-tolyl-2-butenal (106.5 mg, 0.4 mmol, 1.0 equiv), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.4 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), were added with stirring at 25 °C to methanol (32.0 μL, 0.8 mmol, 2.0 equiv, 0.791 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane). The reaction was carried out at 25 °C for 14 h. The reaction equation is as follows:

[0208]

[0209] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 74.9 mg of an oily product, with a calculated yield of 67%.

[0210] The analysis of the test is as follows:

[0211] 1. Proton and carbon NMR spectra:

[0212] 1 H NMR (300MHz, CDCl3) δ7.27-7.22(m,2H),7.21-7.16(m,2H),7.11(d,J=7.9Hz,4H),6.60(dd,J1=5.9Hz, J2=1.2Hz,1H),5.96(t,J=1.2Hz,1H),5.88(dd,J1=5.9Hz,J2=1.1Hz,1H),3.41(s,3H),2.32(s,6H)ppm.

[0213] 13C NMR (75MHz, CDCl3) δ141.7,141.6,138.7,137.0,136.8,128.9,128.8,126.5,126.4,125.2,109.3,94.5,54.5,21.04,21.02ppm.

[0214] 2. High-resolution mass spectrometry: HRMS(ESI)C 19 H 21 O2[M+H] + :281.1536,Found:281.1538.

[0215] The results show that the theoretical mass is 281.1536, while the observed value of the peak in the actual mass spectrum is 281.1538. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0216] This is a product of this embodiment.

[0217] Example 12

[0218] Using R 1 =R 2 The reaction was carried out using (E)-4-hydroxy-4,4-di(naphthyl-2-yl)-2-butenal and methanol as reactants, and racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one and hydrogen chloride. The specific implementation process is as follows:

[0219] (E)-4-hydroxy-4,4-bis(naphth-2-yl)-2-butenal (135.2 mg, 0.4 mmol, 1.0 equiv), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (10.7 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), were added with stirring at 25 °C to methanol (32.0 μL, 0.8 mmol, 2.0 equiv, 0.791 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane). The reaction was carried out at 25 °C for 12 h. The reaction equation is as follows:

[0220]

[0221] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 84.7 mg of an oily product, with a calculated yield of 60%.

[0222] The analysis of the test is as follows:

[0223] 1. Proton and carbon NMR spectra:

[0224] 1 H NMR (300MHz, CDCl3) δ7.87-7.73(m,8H),7.55-7.37(m,6H),6.80(dd,J1=5.9Hz,J2=1 .2Hz,1H),6.08(t,J=1.2Hz,1H),5.98(dd,J1=5.8Hz,J2=1.2Hz,1H),3.44(s,3H)ppm.

[0225] 13 C NMR (75MHz, CDCl3) δ141.63,141.61,138.2,133.01,132.98,132.7,132.6,128.3,128.2,128.1,128. 0,127.5,126.2,126.1,126.04,126.01,125.97,125.20,125.15,125.1,124.9,109.6,94.9,54.6ppm.

[0226] 2. High-resolution mass spectrometry: HRMS(ESI)C 25 H 21 O2[M+H] + :353.1536,Found:353.1539.

[0227] The results show that the theoretical mass is 353.1536, while the observed value of the peak found in the actual mass spectrum is 353.1539. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0228] This is a product of this embodiment.

[0229] Example 13

[0230] (E)-3-(9-hydroxy-9H-fluoren-9-yl)propenal and methanol were used as reactants, and the reaction was carried out using racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0231] (E)-3-(9-hydroxy-9H-fluorene-9-yl)propenal (94.3 mg, 0.4 mmol, 1.0 equiv), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (10.3 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), were added with stirring at 25 °C to methanol (32.0 μL, 0.8 mmol, 2.0 equiv, 0.791 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane), and the reaction was carried out at 25 °C for 12 h. The reaction equation is as follows:

[0232]

[0233] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 52.5 mg of an oily product, with a calculated yield of 52%.

[0234] The analysis of the test is as follows:

[0235] 1. Proton and carbon NMR spectra:

[0236] 1 H NMR (300MHz, CDCl3) δ7.66-7.59(m,2H),7.54-7.48(m,1H),7.40-7.34(m,2H),7.33-7.24(m,3H),6.19( dd, J1=5.8Hz, J2=1.1Hz, 1H), 6.06 (t, J=1.1Hz, 1H), 5.97 (dd, J1=5.8Hz, J2=1.0Hz, 1H), 3.52 (s, 3H)ppm.

[0237] 13 C NMR (75MHz, CDCl3) δ145.4,145.0,140.3,139.7,136.6,129.4,129.3,128.1,127.9,127.8,125.7,124.4,120.0,119.8,110.0,96.2,55.7ppm.

[0238] 2. High-resolution mass spectrometry: HRMS(ESI)C 17 H 15 O2[M+H] + :251.1067,Found:251.1069.

[0239] The results show that the theoretical mass is 251.1067, while the observed value of the peak in the actual mass spectrum is 251.1069. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0240] This is a product of this embodiment.

[0241] Example 14

[0242] The reaction was carried out using (E)-3-(5-hydroxy-5H-dibenzo[a,d][7]annulen-5-yl)propenal and methanol as reactants, with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0243] (E)-3-(5-hydroxy-5H-dibenzo[a,d][7]annulen-5-yl)propenal (105.5 mg, 0.4 mmol, 1.0 equiv), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.9 mg, 0.04 mmol, 10 mol%), dissolved in acetonitrile (4.0 mL), were added with methanol (32.0 μL, 0.8 mmol, 2.0 equiv, 0.791 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane) under stirring at 25 °C. The reaction was carried out at 25 °C for 11 h. The reaction equation is as follows:

[0244]

[0245] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 66.8 mg, with a calculated yield of 60%.

[0246] The analysis of the test is as follows:

[0247] 1. Proton and carbon NMR spectra:

[0248] 1 H NMR (300MHz, CDCl3) δ7.96 (dt, J1=7.9Hz, J2=1.6Hz, 2H), 7.43-7.36 (m, 2H), 7.34-7.20 (m, 4H), 7.07-6.97 (m, 2H ), 6.84 (dd, J1 = 5.9Hz, J2 = 1.3Hz, 1H), 6.07 (t, J = 1.2Hz, 1H), 5.55 (dd, J1 = 5.9Hz, J2 = 1.1Hz, 1H), 3.61 (s, 3H) ppm.

[0249] 13C NMR (75MHz, CDCl3) δ141.3,141.2,134.0,132.3,131.9,131.7,131.6,129. 1,129.0,128.9,128.8,126.8,124.3,123.5,123.3,109.0,91.9,54.8ppm.

[0250] 2. High-resolution mass spectrometry: HRMS(ESI)C 19 H 17 O2[M+H] + :277.1223,Found:277.1230.

[0251] The results show that the theoretical mass is 277.1223, while the observed value of the peak found in the actual mass spectrum is 277.1230. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0252] This is a product of this embodiment.

[0253] Example 15

[0254] Using R 1 =R 2 The reaction was carried out using benzyl (E)-4-hydroxy-4,4-dibenzyl-2-butenal and methanol as reactants, with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0255] (E)-4-hydroxy-4,4-dibenzyl-2-butenal (107.1 mg, 0.4 mmol, 1.0 equiv) and racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.7 mg, 0.04 mmol, 10 mol%) were dissolved in acetonitrile (4.0 mL). Methanol (32.0 μL, 0.8 mmol, 2.0 equiv, 0.791 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane) were added with stirring at 25 °C, and the reaction was carried out at 25 °C for 14 h. The reaction equation is as follows:

[0256]

[0257] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 84.2 mg of an oily product, with a calculated yield of 75%.

[0258] The analysis of the test is as follows:

[0259] 1. Proton and carbon NMR spectra:

[0260] 1 H NMR (300MHz, CDCl3) δ7.35-7.03(m,10H),5.99(dd,J1=5.9Hz,J2=1.3Hz,1H),5.49(dd,J1=5.8Hz,J2=1.2Hz,1H),5.27(t,J= 1.4Hz,1H),3.34(s,3H),3.09(d,J=13.4Hz,1H),3.00(d,J=13.6Hz,1H),2.93(d,J=13.6Hz,1H),2.80(d,J=13.6Hz,1H)ppm.

[0261] 13 C NMR (75MHz, CDCl3) δ137.6,137.3,137.1,130.6,130.5,127.9,127.5,126.43,126.37,126.0,109.2,92.9,54.6,47.7,44.2ppm.

[0262] 2. High-resolution mass spectrometry: HRMS(ESI)C 19 H 20 NaO2[M+Na] + :303.1356,Found:303.1343.

[0263] The results show that the theoretical mass is 303.1356, while the observed value of the peak found in the actual mass spectrum is 303.1343. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0264] This is a product of this embodiment.

[0265] Example 16

[0266] Using R 1 =R 2 Using (E)-4-hydroxy-4,4-diphenyl-2-butenal and N-methylaniline as reactants, the reaction was carried out with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0267] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.5 mg, 0.4 mmol) and racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.9 mg, 0.04 mmol, 10 mol%) were dissolved in acetonitrile (4.0 mL). N-methylaniline (86.6 μL, 0.8 mmol, 2.0 equiv, 0.989 g / mL) and hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane) were added with stirring at 25 °C. The reaction was carried out at 25 °C for 12 h. The reaction equation is as follows:

[0268]

[0269] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 102.2 mg of an oily product, with a calculated yield of 78%.

[0270] The analysis of the test is as follows:

[0271] 1. Proton and carbon NMR spectra:

[0272] 1 H NMR (300MHz, CDCl3) δ7.40-7.18(m,12H),7.06(d,J=8.1Hz,2H),6.85(t,J=7.3Hz,1H),6.63(d d, J1=5.8Hz, J2=2.1Hz, 1H), 6.59 (s, 1H), 5.90 (dd, J1=5.8Hz, J2=1.5Hz, 1H), 2.66 (s, 3H)ppm.

[0273] 13 C NMR (75MHz, CDCl3) δ149.7,145.4,144.6,136.7,129.0,128.2,128.1,127.09,127.05,126.8,126.4,126.2,119.4,116.2,96.8,92.6,32.9ppm.

[0274] 2. High-resolution mass spectrometry: HRMS(ESI)C 23 H 22 NO[M+H] + :328.1696,Found:328.1691.

[0275] The results show that the theoretical mass is 328.1696, while the observed value of the peak found in the actual mass spectrum is 328.1691. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0276] This is a product of this embodiment.

[0277] Example 17

[0278] Using R 1 =R 2 Using (E)-4-hydroxy-4,4-diphenyl-2-butenal and benzamide as reactants, the reaction was carried out with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0279] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.2 mg, 0.4 mmol), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.6 mg, 0.04 mmol, 10 mol%), and benzamide (96.2 mg, 0.8 mmol, 2.0 equiv) were dissolved in acetonitrile (4.0 mL). Hydrogen chloride (20.0 μL, 0.08 mmol, 20 mol%, 4.0 M in 1,4-dixoane) was added with stirring at 25 °C, and the reaction was carried out at 25 °C for 11 h. The reaction equation is as follows:

[0280]

[0281] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 116.2 mg, with a calculated yield of 85%.

[0282] The analysis of the test is as follows:

[0283] 1. Proton and carbon NMR spectra:

[0284] 1 H NMR(300MHz, CDCl3)δ7.67(d,J=7.5Hz,2H),7.52-7.19(m,13H),6.98(d,J=9.5 Hz,1H),6.68(d,J=5.8Hz,1H),6.41(d,J=9.6Hz,1H),5.99(d,J=5.8Hz,1H)ppm.

[0285] 13 C NMR (75MHz, CDCl3) δ166.9,145.2,144.0,137.7,133.9,131.8,128.5,128.4,128.2,127.4,127.1,126.3,126.2,126.0,94.1,86.3ppm.

[0286] 2. High-resolution mass spectrometry: HRMS(ESI)C 23H 20 NO2[M+H] + :342.1489,Found:342.1493.

[0287] The results show that the theoretical mass is 342.1489, while the observed value of the peak in the actual mass spectrum is 342.1493. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0288] This is a product of this embodiment.

[0289] Example 18

[0290] Using R 1 =R 2 Using (E)-4-hydroxy-4,4-diphenyl-2-butenal (a phenyl group) and p-toluenesulfonamide as reactants, the reaction was carried out with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0291] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.4 mg, 0.4 mmol), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.4 mg, 0.04 mmol, 10 mol%), and p-toluenesulfonamide (137.2 mg, 0.8 mmol, 2.0 equiv) were dissolved in acetonitrile (4.0 mL). Hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane) was added with stirring at 25 °C, and the reaction was carried out at 25 °C for 12 h. The reaction equation is as follows:

[0292]

[0293] The reaction solution was concentrated and purified by silica gel column chromatography to obtain a solid product of 123.0 mg, with a calculated yield of 90%.

[0294] The analysis of the test is as follows:

[0295] 1. Proton and carbon NMR spectra:

[0296] 1H NMR (300MHz, CDCl3) δ7.79 (d, J=8.1Hz, 2H), 7.42-7.06 (m, 10H), 6.85 (d, J=6.9Hz, 2H), 6.62 (dd, J1=5.7Hz, J2= 1.7Hz, 1H), 6.38 (d, J = 10.9Hz, 1H), 5.88 (dd, J1 = 5.8Hz, J2 = 1.6Hz, 1H), 4.83 (d, J = 10.7Hz, 1H), 2.45 (s, 3H) ppm.

[0297] 13 C NMR (75MHz, CDCl3) δ144.6,143.8,143.4,138.6,138.0,129.4,128.2,127.4,127.2,126.1,125.6,125.2,94.2,90.4,21.6ppm.

[0298] 2. High-resolution mass spectrometry: HRMS(ESI)C 23 H 22 NO3S[M+H] + :392.1315,Found:392.1317.

[0299] The results show that the theoretical mass is 392.1315, while the observed value of the peak in the actual mass spectrum is 392.1317. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0300] This is a product of this embodiment.

[0301] Example 19

[0302] Using R 1 =R 2 Using (E)-4-hydroxy-4,4-diphenyl-2-butenal (a phenyl group) and celecoxib as reactants, the reaction was carried out with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0303] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.5 mg, 0.4 mmol, 1.0 equiv), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.6 mg, 0.04 mmol, 10 mol%), and celecoxib (305.0 mg, 0.8 mmol, 2.0 equiv) were dissolved in acetonitrile (4.0 mL). Hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane) was added with stirring at 25 °C, and the reaction was carried out at 25 °C for 10 h. The reaction equation is as follows:

[0304]

[0305] The reaction solution was concentrated and purified by silica gel column chromatography to obtain an oily product of 205.4 mg, with a calculated yield of 85%.

[0306] The analysis of the test is as follows:

[0307] 1. Proton and carbon NMR spectra:

[0308] 1 H NMR (300MHz, CDCl3) δ7.86 (dd, J1=8.8Hz, J2=2.1Hz, 2H), 7.45 (dd, J1=8.8Hz, J 2=2.1Hz,2H),7.30-7.04(m,10H),6.98(d,J=7.8Hz,2H),6.91-6.84(m,2H),6.7 3(s,1H),6.63(dd,J1=5.8Hz,J2=1.8Hz,1H),6.38(dt,J1=10.8Hz,J2=1.7Hz,1 H), 5.92 (dd, J1 = 5.8Hz, J2 = 1.7Hz, 1H), 4.93 (d, J = 10.7Hz, 1H), 2.24 (s, 3H) ppm.

[0309] 13 C NMR (75MHz, CDCl3) δ145.1, 144.4, 144.0 (q, J = 38.5Hz), 143.6, 142.5, 140.9, 139.6, 138.4, 129.7, 128.6, 128.4 ,128.2,127.5,126.1,125.8,125.7,125.1,124.8,121.1(q,J=267.5Hz),106.32,106.29,94.5,90.4,21.2ppm.

[0310] 19F NMR (376MHz, CDCl3) δ-62.4ppm.

[0311] 2. High-resolution mass spectrometry: HRMS(ESI)C 33 H 26 F3N3NaO3S[M+Na] + :624.1539,Found:624.1524.

[0312] The results show that the theoretical mass is 624.1539, while the observed value of the peak found in the actual mass spectrum is 624.1524. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0313] This is a product of this embodiment.

[0314] Example 20

[0315] Using R 1 =R 2 Using (E)-4-hydroxy-4,4-diphenyl-2-butenal and detacoxib as reactants, the reaction was carried out with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolium-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0316] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.4 mg, 0.4 mmol, 1.0 equiv), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.5 mg, 0.04 mmol, 10 mol%), and detacoxib (251.0 mg, 0.8 mmol, 2.0 equiv) were dissolved in acetonitrile (4.0 mL). Hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane) was added with stirring at 25 °C, and the reaction was carried out at 25 °C for 12 h. The reaction equation is as follows:

[0317]

[0318] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 162.7 mg, with a calculated yield of 74%.

[0319] The analysis of the test is as follows:

[0320] 1. Proton and carbon NMR spectra:

[0321] 1H NMR (300MHz, CDCl3) δ7.92 (d, J = 8.1Hz, 2H), 7.40-7.22 (m, 8H), 7.20-7.06 (m, 7H), 6.89 (d, J = 7.4Hz, 2H), 6. 64(d,J=5.4Hz,1H), 6.40(d,J=10.7Hz,1H), 5.92(d,J=5.7Hz,1H), 4.97(d,J=10.7Hz,1H), 2.45(s,3H)ppm.

[0322] 13 C NMR (75MHz, CDCl3) δ167.2,161.0,144.6,143.6,140.6,138.1,135.1,129.9,129.5,128 .6,128.3,128.2,127.9,127.5,127.3,126.0,125.6,125.0,114.5,94.4,90.4,11.6ppm.

[0323] 2. High-resolution mass spectrometry: HRMS(ESI)C 32 H 27 N₂O₄S[M+H] + :535.1686,Found:535.1681.

[0324] The results show that the theoretical mass is 535.1686, while the observed value of the peak found in the actual mass spectrum is 535.1681. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0325] This is a product of this embodiment.

[0326] Example 21

[0327] Using R 1 =R 2 Using (E)-4-hydroxy-4,4-diphenyl-2-butenal and 2,3-dimethyl-1H-indole as reactants, and racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one as catalyst and hydrogen chloride as reaction raw materials, the reaction is carried out as follows:

[0328] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.2 mg, 0.4 mmol), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.9 mg, 0.04 mmol, 10 mol%), and 2,3-dimethyl-1H-indole (116.2 mg, 0.8 mmol, 2.0 equiv) were dissolved in acetonitrile (4.0 mL). Hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane) was added with stirring at 25 °C, and the reaction was carried out at 25 °C for 11 h. The reaction equation is as follows:

[0329]

[0330] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain 91.0 mg of solid product, with a calculated yield of 62%.

[0331] The analysis of the test is as follows:

[0332] 1. Proton and carbon NMR spectra:

[0333] 1 H NMR(300MHz, CDCl3)δ7.46-7.39(m,3H),7.38-7.27(m,6H),7.26-7.17(m,3H),7.07-7.02(m,1H),7.01-6.98(m,1H),6 .95-6.90(m,1H),6.84(dd,J1=5.8Hz,J2=2.4Hz,1H),6.22(dd,J1=5.8Hz,J2=1.4Hz,1H),2.33(s,3H),2.21(s,3H)ppm.

[0334] 13 C NMR (75MHz, CDCl3) δ144.8,143.5,136.7,136.0,132.6,129.8,128.4,128.2,127.4,127 .2,126.9,126.27,126.25,120.8,119.5,117.8,111.3,108.8,93.5,89.8,10.9,8.7ppm.

[0335] 2. High-resolution mass spectrometry: HRMS(ESI)C 26 H 24 NO[M+H] + :366.1852,Found:366.1847.

[0336] The results show that the theoretical mass is 366.1852, while the observed value of the peak found in the actual mass spectrum is 366.1847. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0337] This is a product of this embodiment.

[0338] Example 22

[0339] Using R 1 =R 2 Using (E)-4-hydroxy-4,4-diphenyl-2-butenal and 3-phenyl-1H-indole as reactants, and racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one as catalyst and hydrogen chloride as reaction ingredients, the reaction is carried out as follows:

[0340] (E)-4-hydroxy-4,4-diphenyl-2-butenal (96.1 mg, 0.4 mmol), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.7 mg, 0.04 mmol, 10 mol%), and 3-phenyl-1H-indole (154.0 mg, 0.8 mmol, 2.0 equiv) were dissolved in acetonitrile (4.0 mL). Hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane) was added with stirring at 25 °C, and the reaction was carried out at 25 °C for 11 h. The reaction equation is as follows:

[0341]

[0342] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 102.5 mg of an oily product, with a calculated yield of 62%.

[0343] The analysis of the test is as follows:

[0344] 1. Proton and carbon NMR spectra:

[0345] 1 H NMR (300MHz, CDCl3) δ7.91(d,J=7.8Hz,1H),7.59(d,J=8.1Hz,1H),7.48(d,J=7.6Hz,2H),7. 42-7.15(m,16H),7.06(s,1H),6.90(dd,J1=5.8Hz,J2=2.0Hz,1H),6.15(d,J=5.8Hz,1H)ppm.

[0346] 13C NMR (75MHz, CDCl3) δ144.2,143.7,138.8,137.0,135.3,128.6,128.4,128.3,127.7,127.5,127. 4,127.1,126.6,126.2,126.0,125.0,123.0,122.4,120.7,119.9,118.4,110.1,95.0,89.9ppm.

[0347] 2. High-resolution mass spectrometry: HRMS(ESI)C 30 H 24 NO[M+H] + :414.1852,Found:414.1849.

[0348] The results show that the theoretical mass is 414.1852, while the observed peak value in the actual mass spectrum is 414.1849. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0349] This is a product of this embodiment.

[0350] Example 23

[0351] Using R 1 =R 2 The reaction was carried out using (E)-4-hydroxy-4,4-diphenyl-2-butenal (a phenyl group) and methyl 1H-indole-2-carboxylate as reactants, with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0352] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.5 mg, 0.4 mmol), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (10.1 mg, 0.04 mmol, 10 mol%), and methyl 1H-indole-2-carboxylate (140.5 mg, 0.8 mmol, 2.0 equiv) were dissolved in acetonitrile (4.0 mL). Hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane) was added with stirring at 25 °C, and the reaction was carried out at 25 °C for 11 h. The reaction equation is as follows:

[0353]

[0354] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 108.3 mg, with a calculated yield of 68%.

[0355] The analysis of the test is as follows:

[0356] 1. Proton and carbon NMR spectra:

[0357] 1 H NMR (300MHz, CDCl3) δ8.92 (s, 1H), 7.52-7.40 (m, 5H), 7.40-7.17 (m, 8H), 6.99 (dd, J1=2.8Hz, J2=1.5Hz, 1H) ,6.85-6.76(m,1H),6.62(dd,J1=5.9Hz,J2=2.7Hz,1H),6.17(dd,J1=5.8Hz,J2=1.6Hz,1H),3.91(s,3H)ppm.

[0358] 13 C NMR (75MHz, CDCl3) δ162.3,145.5,144.4,136.1,132.8,130.3,128.2,128.1,127.2,127 .0,126.9,126.4,126.1,125.4,123.7,123.2,121.0,120.1,111.5,94.5,80.1,52.0ppm.

[0359] 2. High-resolution mass spectrometry: HRMS(ESI)C 26 H 22 NO3[M+H] + :396.1594,Found:396.1604.

[0360] The results show that the theoretical mass is 396.1594, while the observed value of the peak found in the actual mass spectrum is 396.1604. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0361] This is a product of this embodiment.

[0362] Example 24

[0363] Using R 1 =R 2 Using (E)-4-hydroxy-4,4-diphenyl-2-butenal and 1,3-cyclohexanedione as reactants, the reaction was carried out with racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one catalyst and hydrogen chloride. The specific implementation process is as follows:

[0364] (E)-4-hydroxy-4,4-diphenyl-2-butenal (95.4 mg, 0.4 mmol), racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-one (9.7 mg, 0.04 mmol, 10 mol%), and 1,3-cyclohexanedione (89.7 mg, 0.8 mmol, 2.0 equiv) were dissolved in acetonitrile (4.0 mL). Hydrogen chloride (10.0 μL, 0.04 mmol, 10 mol%, 4.0 M in 1,4-dixoane) was added with stirring at 25 °C, and the reaction was carried out at 25 °C for 11 h. The reaction equation is as follows:

[0365]

[0366] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain 84.3 mg of solid product, with a calculated yield of 63%.

[0367] The analysis of the test is as follows:

[0368] 1. Proton and carbon NMR spectra:

[0369] 1 H NMR (300MHz, CDCl3) δ10.06 (s, 1H), 7.41-7.19 (m, 10H), 6.36 (dd, J1=6.0Hz, J2=2.5H z,1H),6.18(d,J=6.0Hz,1H),6.09(s,1H),2.47-2.23(m,4H),2.06-1.83(m,2H)ppm.

[0370] 13 C NMR (75MHz, CDCl3) δ197.6,174.7,143.3,143.0,130.4,130.0,128.7,128.6,128.3,127.3,127.2,125.3,110.7,95.5,85.3,36.8,29.5,20.6ppm.

[0371] 2. High-resolution mass spectrometry: HRMS(ESI)C 22 H 21 O3[M+H] + :333.1485,Found:333.1492.

[0372] The results show that the theoretical mass is 333.1485, while the observed value of the peak found in the actual mass spectrum is 333.1492. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0373] This is a product of this embodiment.

[0374] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for producing a 2-functionalized 2,5-dihydrofuran compound, characterized by, The method comprises the following steps: mixing a γ-hydroxy-α,β-unsaturated aldehyde, compound 1, an organic amine catalyst, a Bronsted acid catalyst and an organic solvent to perform a cyclization reaction to obtain the 2-functionalized-2,5-dihydrofuran compound; The γ-hydroxy-α,β-unsaturated aldehyde has a structure shown in Formula 1 or is The compound 1 has a structure shown in any one of Formulas 2 to 6: HOR 3 Formula 2, when the γ-hydroxy-α,β-unsaturated aldehyde is MeOH, the 2-functionalized-2,5-dihydrofuran compound is when the γ-hydroxy-α,β-unsaturated aldehyde is MeOH, the 2-functionalized-2,5-dihydrofuran compound is when the γ-hydroxy-α,β-unsaturated aldehyde is then the compound 1 is of the structure of any one of formulas 2-6; when the compound 1 is HOR 3 then the 2-functionalized-2,5-dihydrofuran compound is of the structure of formula I, when the compound 1 is then the 2-functionalized-2,5-dihydrofuran compound is of the structure of formula II, when the compound 1 is then the 2-functionalized-2,5-dihydrofuran compound is of the structure of formula III, when the compound 1 is then the 2-functionalized-2,5-dihydrofuran compound is of the structure of formula IV, when the compound 1 is then the 2-functionalized-2,5-dihydrofuran compound is of the structure of formula V: wherein R 1 and R 2 are independently aryl, phenyl, halo-substituted phenyl, alkyl-substituted phenyl, alkyl; R 3 independently hydrogen or alkyl; R 4 independently hydrogen, phenyl, methyl, p-tolylsulfonyl, benzoyl, 4-(5-(p-tolyl)-3- (trifluoromethyl)-1 H-pyrazol-1 -yl)benzene sulfonyl, or 4-(5-methyl-3-phenylisoxazol-4- yl)benzene sulfonyl; R 5 independently hydrogen, phenyl, methyl, p-tolylsulfonyl, benzoyl, 4-(5-(p-tolyl)-3- (trifluoromethyl)-1 H-pyrazol-1 -yl)benzene sulfonyl, or 4-(5-methyl-3-phenylisoxazol-4- yl)benzene sulfonyl; R 6 independently alkyl, phenyl; R 7 independently hydrogen, alkyl.

2. The method of claim 1, wherein, The including gamma-hydroxy-gamma-diphenyl-alpha, beta-unsaturated aldehydes, (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-bromophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-methylphenyl)-4-hydroxy-2-butenal, (E)-4-hydroxy-4,4-di(naphthalen-2-yl)-2-butenal, (E)-3-(9-hydroxy-9H-fluoren-9-yl)acrolein, (E)-3-(5-hydroxy-5H-dibenzo[a,d][7]annulen-5-yl)acrolein, (E)-4-hydroxy-4,4-dibenzyl-2-butenal.

3. The method of claim 1 or 2, wherein the method further comprises, the organic amine catalyst comprises racemic (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidine-4-ketone or (S)-2-[bis(3,5-bis(trifluoromethyl)phenyl)(((2,3-dimethylbutane-2-yl)dimethylsilyl)oxy)methyl]-4,4-difluoropyrrolidine; the γ-hydroxy-α,β-unsaturated organic amine catalyst has a mass ratio of 1:0.05-0.

2.

4. The method of claim 1 or 2, wherein the method is carried out at a temperature of from 20 to 100°C. the Bronsted acid catalyst comprises a hydrogen chloride dioxane solution (4 mol / L), p-toluenesulfonic acid monohydrate or trifluoroacetic acid; the γ-hydroxy-α,β-unsaturated aldehyde and the Bronsted acid catalyst have a mass ratio of 1:0.05-0.

2.

5. The method of claim 1, wherein the step of forming the first and second layers is performed by a process selected from the group consisting of: sputtering, evaporation, and chemical vapor deposition. the HOR 3 including methanol, isopropyl alcohol, benzyl alcohol, 3-phenyl-2-propyn-1-ol, 3-methyl-2-buten-1-ol, water, geraniol; The including N-methylaniline, benzamide, p-toluenesulfonamide, celecoxib, deracoxib; The including 2,3-dimethyl-1 H-indole, 3-phenyl-1 H-indole.

6. The method of claim 1 or 5, wherein the step of preparing the mixture is performed at a temperature of 20 to 30°C. the γ-hydroxy-α,β-unsaturated aldehyde and compound 1 have a mass ratio of 1:1.5-2.

5. the cyclization reaction has a temperature of room temperature (20-30℃) and a time of 10-15 h.

7. The preparation method according to claim 1, characterized in that, has any one of structures of formula I-V:

8. A 2-functionalized-2,5-dihydrofuran compound, when prepared according to the process of any one of claims 1 to 7, characterized in that, has any one of structures of formula I-1-I-15, formula II-1-II-5, formula III-1-III-2, formula IV, formula V: wherein R 1 and R 2 are independently aryl, phenyl, halo-substituted phenyl, alkyl-substituted phenyl, alkyl; R 3 independently hydrogen or alkyl; R 4 independently hydrogen, phenyl, methyl, p-tolylsulfonyl, benzoyl, 4-(5-(p-tolyl)-3- (trifluoromethyl)-1 H-pyrazol-1 -yl)benzene sulfonyl, or 4-(5-methyl-3-phenylisoxazol-4- yl)benzene sulfonyl; R 5 independently hydrogen, phenyl, methyl, p-tolylsulfonyl, benzoyl, 4-(5-(p-tolyl)-3- (trifluoromethyl)-1 H-pyrazol-1 -yl)benzene sulfonyl, or 4-(5-methyl-3-phenylisoxazol-4- yl)benzene sulfonyl; R 6 independently alkyl, phenyl; R 7 independently hydrogen, alkyl.

9. The 2-functionalized-2,5-dihydrofuran compound according to claim 8, wherein ​

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