A kind of allyl aromatic hydrocarbon derivative and its preparation method and application

Abstract

The present invention relates to the technical field of chemical synthesis, and specifically discloses an allyl aromatic hydrocarbon derivative, a preparation method and an application thereof. An allyl aromatic hydrocarbon derivative, whose structure is shown in formula (I): wherein R1 is nitro, cyano or trifluoromethyl, and R2 is hydrogen, halogen, methoxy, ethoxy, methyl, ethyl, isopropyl, nitro, dimethylamino, benzyloxy or trifluoromethyl. The allyl aromatic hydrocarbon derivative provided by the present invention has high functionality and structural diversity, and can provide diversified choices for the application of allyl aromatic hydrocarbon derivatives in drug synthesis, spices and food flavorings; the preparation method provided by the present invention realizes Michael addition of the distal site of allyl aromatic hydrocarbon, is easy to operate, has high atom economy, has a wide range of substrate applications, has low production costs, and is easy to realize industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and in particular to an allyl aromatic hydrocarbon derivative and a preparation method and application thereof. Background Art

[0002] Allyl aromatic derivatives are commonly found in some natural products, drug molecules and organic functional materials. They can be used as structural skeletons or reaction intermediates of natural products and bioactive molecules. For example, safrole is a derivative of allyl aromatics. In addition, allyl aromatic derivatives can be used in the flavor and fragrance industry because of their pleasant smell, such as eugenol and estragole. Eugenol is mainly obtained by drying and distilling the clove buds in nature. It has antibacterial, blood pressure lowering, and can be used to make flavors. Estragole can be obtained by fractionating turpentine or tarragon oil and can be used to prepare spices and other seasonings. At the same time, the allyl aromatic derivatives extracted from the stem bark of the Moraceae plant Chinese mulberry have a better therapeutic effect on five types of human cancer cell lines: lung cancer, liver cancer, gastric cancer, intestinal cancer and ovarian cancer.

[0003] With the rapid development of asymmetric synthesis technology, allyl aromatic derivatives with chiral centers have attracted the attention of technicians due to their potential biological activity, but the synthesis methods of different allyl aromatic derivatives need further study. Summary of the invention

[0004] In view of the above problems, the present invention provides an allyl aromatic hydrocarbon derivative and a preparation method and application thereof. The allyl aromatic hydrocarbon derivative provided by the present invention has high functionality and structural diversity, and can provide diversified choices for the application of allyl aromatic hydrocarbon derivatives in drug synthesis, fragrances and food flavorings; the addition of the distal site of the allyl aromatic hydrocarbon is realized, the operation is convenient, the atom economy is high, the substrate has a wide range of application, the production cost is low, and it is easy to realize industrial production.

[0005] In order to achieve the above-mentioned object of the invention, the present invention adopts the following technical solutions:

[0006] An allyl aromatic derivative, characterized in that its structure is as shown in formula (I):

[0007]

[0008] Wherein, R1 is nitro, cyano or trifluoromethyl, and R2 is hydrogen, halogen, methoxy, ethoxy, methyl, ethyl, isopropyl, nitro, dimethylamino, benzyloxy or trifluoromethyl.

[0009] Compared with the prior art, the allyl aromatic hydrocarbon derivatives provided by the present invention have high functionality and structural diversity, and can provide diversified choices for the application of allyl aromatic hydrocarbon derivatives in drug synthesis, perfumes and food flavoring agents.

[0010] Optionally, its structure is as shown in formula (Ⅰ1)-formula (Ⅰ25):

[0011]

[0012]

[0013]

[0014] Another aspect of the present invention provides a method for adding an allyl aromatic derivative, comprising the following steps:

[0015] The allyl aromatic compound represented by formula (II), the cinnamaldehyde derivative represented by formula (III) and diaryl prolinol silyl ether are subjected to Michael addition reaction in an organic solvent to obtain a reaction intermediate represented by formula (IV);

[0016] Reducing the reaction intermediate to obtain a compound with a structure as shown in formula (I);

[0017]

[0018] Wherein, R1 is nitro, cyano or trifluoromethyl, and R2 is hydrogen, halogen, methoxy, ethoxy, methyl, ethyl, isopropyl, nitro, dimethylamino, benzyloxy or trifluoromethyl.

[0019] In the allyl aromatic compound shown in formula (II), R1 and nitro are both electron-withdrawing groups, the carbon adjacent to the benzene ring in the allyl group is the α position, and the carbon far from the benzene ring is the distal position. Most of the reactions of existing allyl aromatic compounds are concentrated in the α position. How to activate the distal site of allyl aromatics and then cause an asymmetric addition reaction is still a challenge. The inventors have found through a large number of studies that the allyl aromatic compound shown in formula (II) and the cinnamaldehyde derivative shown in formula (III) are used as raw materials, and diaryl proline alcohol silyl ether is used as a catalyst to prepare a reaction intermediate through Michael addition reaction, and then reduce to obtain a compound shown in the general structural formula (I). During the reaction, the distal site of the allyl aromatic compound shown in formula (II) participates in the reaction. Diaryl proline alcohol silyl ether can accelerate the reaction, shorten the reaction time, reduce the occurrence of side reactions, and improve the purity of the product. The present invention adopts an organic small molecule asymmetric catalytic system to realize Michael addition at the distal site of allylic aromatic hydrocarbons, has convenient operation, high atom economy, wide substrate application range, low production cost, and is easy to realize industrial production.

[0020] It should be noted that R1 is nitro, cyano or trifluoromethyl, all of which are electron-withdrawing groups, and their positions on the benzene ring do not affect the Michael addition in the present invention.

[0021] Optionally, the method for adding an allyl aromatic derivative comprises the following steps:

[0022] S1, dissolving the allyl aromatic compound represented by formula (II) in a first organic solvent to obtain an allyl aromatic compound solution;

[0023] S2, dissolving a diaryl prolinol silyl ether in a first organic solvent, then adding a cinnamaldehyde derivative represented by formula (III), adding the allyl aromatic compound solution in an inert atmosphere, and then reacting at 25 to 40° C. for 20 to 24 hours, extracting, and subjecting the extract to silica gel column chromatography to obtain a reaction intermediate represented by formula (IV);

[0024] S3, adding the reaction intermediate into a second organic solvent, adding a reducing agent at 0-5°C, reacting for 20-30 minutes, and obtaining a compound having a structure as shown in formula (I).

[0025] Further optionally, in step S3, the reducing agent is sodium borohydride, potassium borohydride or lithium aluminum tetrahydride.

[0026] Further optionally, in step S2, the first organic solvent is at least one of toluene, tetrahydrofuran, acetonitrile, dichloromethane, dichloroethane or 1,4-dioxane. By limiting the organic solvent, the reaction rate can be increased, the reaction raw materials can be fully reacted, and the occurrence of side reactions can be reduced.

[0027] Further optionally, in step S2, the extraction liquid is at least one of dichloromethane or ethyl acetate.

[0028] Further optionally, in step S3, the second solvent is a mixed solution of dichloromethane and ethanol, wherein the volume ratio of dichloromethane to ethanol is 2:1 to 3:2.

[0029] Further optionally, the molar ratio of cinnamaldehyde derivatives, diarylprolinol silyl ethers and allyl aromatic compounds is 0.3-1:0.1-0.2:1. By limiting the ratio of cinnamaldehyde derivatives and allyl aromatic compounds, the amount of raw materials can be reduced, the reaction can be promoted to proceed in the forward direction, and the yield can be improved. By limiting the amount of catalyst, it can be ensured that the reaction activity, reaction rate and product yield are maximized under the premise of minimum catalyst dosage; too little catalyst dosage has an insignificant catalytic effect, too much catalyst dosage has an insignificant yield improvement, and the catalyst is wasted and the product purity is reduced.

[0030] Further optionally, in step S2, the allyl aromatic compound solution is added dropwise for 10 to 20 minutes.

[0031] Further optionally, in step S2, the inert atmosphere is nitrogen or argon.

[0032] Further optionally, in step S2, the developing solvent in the silica gel column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5 to 300:1.

[0033] Further optionally, in step S1, the molar ratio of the volume of the organic solvent to the molar ratio of the allyl aromatic compound is 0.5-3.5 mL:1 mmol.

[0034] Further optionally, in step S2, the molar ratio of the volume of the organic solvent to the molar ratio of the allyl aromatic compound is 1.5-10.5 mL:1 mmol.

[0035] By limiting the amount of organic solvent used, the reaction raw materials can be fully dissolved, the reaction raw materials can be fully reacted, and the yield can be improved.

[0036] Optionally, a refining step is also included:

[0037] Adding a saturated ammonium chloride solution to the compound having the structure shown in formula (I) for quenching, and then adding dichloromethane for extraction to obtain an extract;

[0038] A saturated sodium chloride solution is added to the extract to wash, and then the extract is dehydrated, concentrated, separated by silica gel column chromatography, and dried to obtain a refined product.

[0039] The third aspect of the present invention provides the use of the allyl aromatic derivative or the allyl aromatic derivative prepared by the addition method of the allyl aromatic derivative in the synthesis of pharmaceutical intermediates, fragrance intermediates and food flavoring intermediates.

[0040] The allyl aromatic derivative or the allyl aromatic derivative prepared by the addition method of the allyl aromatic derivative provided by the present invention can provide raw materials or reaction intermediates for the synthesis of medicines, spices and food flavorings, and can be widely used in the synthesis fields of medicines, spices and food flavorings. DETAILED DESCRIPTION

[0041] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0042] In order to better illustrate the present invention, further examples are given below.

[0043] Example 1

[0044] The structure of the compound in this example is shown in formula (I1):

[0045]

[0046] The preparation steps are as follows:

[0047] (1) 1 mL of tert-butyl nitrite, 7.1 mL of 3-bromopropylene and 1 g of 2-cyano-4-nitroaniline were added to 5.5 mL of acetonitrile in sequence and mixed evenly. Then, 0.3 mL of tert-butyl nitrite was added in an argon atmosphere and reacted at 25°C for 24 h to obtain 2-allyl-5-nitrobenzonitrile shown in (II1).

[0048] (2) 1 mmol of the 2-allyl-5-nitrobenzonitrile prepared above was dissolved in 2.0 mL of dichloroethane to obtain a mixed solution A.

[0049] (3) 0.15 mmol of diaryl prolinol silyl ether and 0.5 mmol of cinnamaldehyde represented by formula (III1) are dissolved in 5.0 mL of dichloroethane in sequence. Then, in a nitrogen atmosphere, the mixed solution A is added dropwise and the addition time is controlled to be 15 min. After the addition is completed, the mixture is reacted at 30°C for 22 h. The reaction mixture is extracted with 10 mL of dichloromethane to obtain an organic layer; then, the organic layer is separated by silica gel column chromatography, and the developing solvent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 150:1, to obtain a reaction intermediate having a structure shown in formula (IV1).

[0050] (4) The above reaction intermediate was added to 8 mL of a mixed solution of dichloromethane and ethanol in a volume ratio of 1.8:1, and then 1.5 mmol of sodium borohydride was added at 2°C and reacted for 25 min. After the reaction was completed, 18 ml of a saturated ammonium chloride solution was added to quench, and then 22 ml of dichloromethane was added for extraction. A saturated sodium chloride solution was added to the extract for washing, and then anhydrous sodium sulfate was used for dehydration, filtration, concentration, and separation by 200-300 mesh silica gel column chromatography. The developing solvent was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 150:1, and drying was performed to obtain 146.7 mg of a refined product of the compound represented by the general structural formula (I1), with a yield of 91% and an ee value of 99%.

[0051]

[0052] The obtained product was subjected to NMR detection. 1 The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (s, 1H), 8.4 (dd, J = 8.7, 2.7 Hz, 1H), 7.9 (dd, J = 9.2, 4.5 Hz, 1H), 7.4-7.1 (m, 5H), 6.8-6.6 (m, 2H), 4.4 (s, 1H), 3.3 (dd, J = 15.6, 9.6 Hz, 2H), 3.0 (m, 1H), 2.7 (m, 2H), 1.8 (m, 2H).

[0053] 13 C NMR (126 MHz, DMSO-d6) detection results are: δ145.25, 143.88, 140.17, 128.04, 127.76, 127.26, 127.02, 126.14, 125.60, 124.79, 115.41, 109.55, 58.07, 40.72, 39.51, 38.17.

[0054] Example 2

[0055] The structural formula of the compound in this example is the same as that in Example 1.

[0056] The preparation steps are as follows:

[0057] (1) The preparation method of 2-allyl-5-nitrobenzonitrile represented by formula (II1) is the same as that in Example 1.

[0058] (2) 1 mmol of the 2-allyl-5-nitrobenzonitrile prepared above was dissolved in 0.5 mL of dichloroethane to obtain a mixed solution A.

[0059] (3) 0.1 mmol of diarylprolinol silyl ether and 0.3 mmol of cinnamaldehyde represented by formula (III1) are dissolved in 1.5 mL of dichloroethane. Then, in a nitrogen atmosphere, the mixed solution A is added dropwise and the addition time is controlled to be 10 min. After the addition is completed, the mixture is reacted at 25°C for 24 h. The reaction mixture is extracted with 5 mL of ethyl acetate to obtain an organic layer; the organic layer is then separated by silica gel column chromatography, and the developing solvent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1, to obtain a reaction intermediate with a structure shown in formula (IV1).

[0060] (4) The above reaction intermediate was added to 15 mL of a mixed solution of dichloromethane and ethanol in a volume ratio of 3:2, and then 1.0 mmol of sodium borohydride was added at 0°C and reacted for 20 min. After the reaction was completed, 15 ml of a saturated ammonium chloride solution was added to quench, and then 20 ml of dichloromethane was added for extraction. A saturated sodium chloride solution was added to the extract for washing, and then anhydrous sodium sulfate was used for dehydration, filtration, concentration, and separation by 200-300 mesh silica gel column chromatography. The developing solvent was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1, and drying was performed to obtain 77.5 mg of a refined product of the compound represented by the general structural formula (Ⅰ1), with a yield of 80.9% and an ee value of 99%.

[0061] The obtained product was subjected to NMR detection. 1The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (s, 1H), 8.4 (dd, J = 8.7, 2.7 Hz, 1H), 7.9 (dd, J = 9.2, 4.5 Hz, 1H), 7.4-7.1 (m, 5H), 6.8-6.6 (m, 2H), 4.4 (s, 1H), 3.3 (dd, J = 15.6, 9.6 Hz, 2H), 3.0 (m, 1H), 2.7 (m, 2H), 1.8 (m, 2H).

[0062] 13 C NMR (126 MHz, DMSO-d6) detection results are: δ145.25, 143.88, 140.17, 128.04, 127.76, 127.26, 127.02, 126.14, 125.60, 124.79, 115.41, 109.55, 58.07, 40.72, 39.51, 38.17.

[0063] Example 3

[0064] The structural formula of the compound in this example is the same as that in Example 1.

[0065] The preparation steps are as follows:

[0066] (1) The preparation method of 2-allyl-5-nitrobenzonitrile represented by formula (II1) is the same as that in Example 1.

[0067] (2) 1 mmol of the 2-allyl-5-nitrobenzonitrile prepared above was dissolved in 3.5 mL of dichloroethane to obtain a mixed solution A.

[0068] (3) 0.2 mmol of diaryl prolinol silyl ether and 1 mmol of cinnamaldehyde represented by formula (III1) are dissolved in 10.5 mL of dichloroethane in sequence. Then, in a nitrogen atmosphere, the mixed solution A is added dropwise and the addition time is controlled to be 20 min. After the addition is completed, the mixture is reacted at 40°C for 20 h. The reaction mixture is extracted with 20 mL of dichloromethane to obtain an organic layer; then, the organic layer is separated by silica gel column chromatography, and the developing solvent is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 300:1, to obtain a reaction intermediate having a structure shown in formula (IV1).

[0069] (4) The above reaction intermediate was added to 5 mL of a mixed solution of dichloromethane and ethanol in a volume ratio of 2:1, and then 2.0 mmol of sodium borohydride was added at 5°C and reacted for 30 min. After the reaction was completed, 20 ml of saturated ammonium chloride solution was added to quench, and then 25 ml of dichloromethane was added for extraction. A saturated sodium chloride solution was added to the extract for washing, and then anhydrous sodium sulfate was used for dehydration, filtration, concentration, and separation by 200-300 mesh silica gel column chromatography. The developing solvent was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 300:1, and drying was performed to obtain 260.8 mg of a refined product of the compound represented by the general structural formula (Ⅰ1), with a yield of 80.1% and an ee value of 99%.

[0070] The obtained product was subjected to NMR detection. 1 The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (s, 1H), 8.4 (dd, J = 8.7, 2.7 Hz, 1H), 7.9 (dd, J = 9.2, 4.5 Hz, 1H), 7.4-7.1 (m, 5H), 6.8-6.6 (m, 2H), 4.4 (s, 1H), 3.3 (dd, J = 15.6, 9.6 Hz, 2H), 3.0 (m, 1H), 2.7 (m, 2H), 1.8 (m, 2H).

[0071] 13 C NMR (126MHz, DMSO-d6) detection results are: δ145.25, 143.88, 140.17, 128.04, 127.76, 127.26, 127.02, 126.14, 125.60, 124.79, 115.41, 109.55, 58.07, 40.72, 39.51, 38.17.

[0072] Example 4

[0073] The structure of the compound in this example is shown in formula (I2):

[0074]

[0075] The preparation method thereof refers to Example 1, except that, in step (3), the cinnamaldehyde represented by formula (III1) is replaced by p-methoxycinnamaldehyde represented by formula (III2); and a reaction intermediate having a structure represented by formula (IV2) is obtained.

[0076]

[0077] Finally, 153.3 mg of a purified product of the compound represented by the general structural formula (Ⅰ2) was obtained with a yield of 87% and an ee value of 99%.

[0078] The obtained product was subjected to NMR detection. 1 The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.9, 2.4 Hz, 1H), 7.9 (d, J=8.9 Hz, 1H), 7.2 (d, J=8.4 Hz, 2H), 6.9 (d, J=8.4 Hz, 2H), 6.7 (dt, J=15.7, 6.8 Hz, 1H), 6.7 (d, J=15.8 Hz, 1H), 4.4 (s, 1H), 3.7 (s, 3H), 3.3-3.2 (m, 2H), 2.9 (td, J=8.9, 4.4 Hz, 1H), 2.6 (m, 2H), 1.9-1.7 (m, 2H).

[0079] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 158.02, 146.33, 146.25, 141.38, 136.71, 129.07, 128.93, 128.29, 127.17, 125.75, 116.47, 114.17, 110.57, 59.14, 55.40, 40.92, 40.76, 39.40.

[0080] Example 5

[0081] The structure of the compound in this example is shown in formula (I3):

[0082]

[0083] The preparation method is similar to that of Example 1, except that in step (3), the cinnamaldehyde of formula (III1) is replaced by p-methylcinnamaldehyde of formula (III3); and a reaction intermediate having a structure as shown in formula (IV3) is obtained.

[0084]

[0085] Finally, 149.7 mg of a purified product of the compound represented by the general structural formula (Ⅰ3) was obtained with a yield of 89% and an ee value of 99%.

[0086] The obtained product was subjected to NMR detection. 1The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.9, 2.4 Hz, 1H), 7.9 (d, J=8.9 Hz, 1H), 7.2-7.1 (m, 4H), 6.7 (dt, J=15.7, 6.7 Hz, 1H), 6.7 (d, J=15.8 Hz, 1H), 3.4-3.2 (m, 2H), 2.9 (m, 1H), 2.6 (m, 2H), 2.3 (s, 3H), 1.9-1.7 (m, 2H).

[0087] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 146.3, 146.2, 141.8, 141.3, 135.5, 129.4, 129.1, 128.3, 127.9, 127.2, 125.8, 116.4, 110.6, 59.1, 41.3, 39.3, 21.1.

[0088] Example 6

[0089] The structure of the compound in this example is shown in formula (I4):

[0090]

[0091] The preparation method is similar to that of Example 1, except that in step (3), the cinnamaldehyde of formula (III1) is replaced by o-methoxycinnamaldehyde of formula (III4); and a reaction intermediate having a structure as shown in formula (IV4) is obtained.

[0092]

[0093] Finally, 153.3 mg of a purified product of the compound represented by the general structural formula (Ⅰ4) was obtained with a yield of 87% and an ee value of 99%.

[0094] The obtained product was subjected to NMR detection. 1 The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (d, J=2.5 Hz, 1H), 8.4 (dd, J=8.9, 2.5 Hz, 1H), 8.0 (d, J=8.9 Hz, 1H), 7.3-7.2 (m, 3H), 7.0-6.9 (m, 3H), 6.8 (dt, J=14.6, 7.0 Hz, 1H), 6.6 (d, J=15.7 Hz, 1H), 4.4 (d, J=4.9 Hz, 1H), 3.8 (s, 4H), 3.4 (t, J=7.3 Hz, 1H), 3.3 (s, 3H), 2.6 (m, 3H), 1.9-1.8 (m, 3H).

[0095] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 157.4, 146.4, 146.2, 141.5, 132.5, 129.1, 128.3, 128.0, 127.6, 127.1, 125.5, 120.9, 116.4, 111.4, 59.4, 59.4, 55.9, 39.3, 37.8.

[0096] Example 7

[0097] The structure of the compound in this example is shown in formula (I4):

[0098]

[0099] The preparation method thereof is similar to that of Example 1, except that, in step (3), the cinnamaldehyde represented by formula (III1) is replaced by p-dimethylaminocinnamaldehyde represented by formula (III5); and a reaction intermediate having a structure represented by formula (IV5) is obtained.

[0100]

[0101] Finally, 146.2 mg of a purified product of the compound represented by the general structural formula (Ⅰ5) was obtained with a yield of 80% and an ee value of 99%.

[0102] The obtained product was subjected to NMR detection. 1 The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.9, 2.4 Hz, 1H), 8.0 (d, J=8.9 Hz, 1H), 7.1 (d, J=8.3 Hz, 2H), 6.7 (dt, J=15.7, 6.7 Hz, 1H), 6.7-6.7 (m, 3H), 4.4 (s, 1H), 3.2 (dt, J=13.8, 5.2 Hz, 2H), 2.9 (s, 6H), 2.6 (m, 2H), 2.4 (q, J=7.1 Hz, 1H), 1.9-1.7 (m, 2H).

[0103] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 149.4, 146.4, 146.2, 141.7, 132.4, 129.1, 128.4, 128.3, 127.1, 125.6, 116.5, 113.0, 110.6, 59.3, 55.4, 46.2, 40.8, 39.5.

[0104] Example 8

[0105] The structure of the compound in this example is shown in formula (I6):

[0106]

[0107] The preparation method thereof is similar to that of Example 1, except that, in step (3), cinnamaldehyde represented by formula (III1) is replaced by p-nitrocinnamaldehyde represented by formula (III6); and a reaction intermediate having a structure represented by formula (IV6) is obtained.

[0108]

[0109] Finally, 156.1 mg of a purified product of the compound represented by the general structural formula (Ⅰ6) was obtained with a yield of 85% and an ee value of 99%.

[0110] The obtained product was subjected to NMR detection. 1 The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (d, J=2.5 Hz, 1H), 8.4 (dd, J=8.9, 2.5 Hz, 1H), 8.2-8.2 (m, 2H), 8.0 (d, J=8.9 Hz, 1H), 7.6 (d, J=8.7 Hz, 2H), 6.7 (dt, J=15.7, 7.1 Hz, 1H), 6.6 (d, J=15.8 Hz, 1H), 4.5 (s, 1H), 3.2 (m, 3H), 2.8 (dt, J=13.7, 6.6 Hz, 1H), 2.7 (dt, J=14.8, 7.9 Hz, 1H), 2.0-1.9 (m, 1H), 1.9-1.8 (m, 1H).

[0111] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 153.3, 146.4, 146.2, 140.3, 129.5, 129.1, 128.3, 127.3, 126.4, 123.9, 116.4, 110.7, 58.8, 55.4, 41.7.

[0112] Example 9

[0113] The structure of the compound in this example is shown in formula (I7):

[0114]

[0115] The preparation method thereof is similar to that of Example 1, except that, in step (3), the cinnamaldehyde represented by formula (III1) is replaced by o-nitrocinnamaldehyde represented by formula (III7); and a reaction intermediate having a structure represented by formula (IV7) is obtained.

[0116]

[0117] Finally, 152.5 mg of a purified product of the compound represented by the general structural formula (Ⅰ7) was obtained with a yield of 83% and an ee value of 99%.

[0118] The obtained product was subjected to NMR detection. 1 The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.9, 2.4 Hz, 1H), 8.0 (d, J=8.9 Hz, 1H), 7.8-7.7 (m, 3H), 7.4 (m, 1H), 6.7 (dt, J=14.7, 7.2 Hz, 1H), 6.6 (d, J=15.7 Hz, 1H), 4.4 (t, J=4.8 Hz, 1H), 3.4 (m, 1H), 3.3 (s, 1H), 3.3-3.2 (m, 1H), 2.8 (m, 2H), 2.0-1.8 (m, 2H).

[0119] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 151.1, 146.4, 146.1, 140.1, 138.0, 133.2, 129.3, 129.1, 128.3, 127.9, 127.2, 126.3, 123.8, 116.4, 110.7, 58.9, 38.4, 35.7.

[0120] Example 10

[0121] The structure of the compound in this example is shown in formula (I8):

[0122]

[0123] The preparation method thereof refers to Example 1, except that, in step (3), the cinnamaldehyde represented by formula (III1) is replaced by p-ethylcinnamaldehyde represented by formula (III8); and a reaction intermediate having a structure represented by formula (IV8) is obtained.

[0124]

[0125] Finally, 147.2 mg of a purified product of the compound represented by the general structural formula (Ⅰ8) was obtained with a yield of 84% and an ee value of 99%.

[0126] The obtained product was subjected to NMR detection. 1The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.7 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.9, 2.5 Hz, 1H), 8.0 (d, J=8.9 Hz, 1H), 7.2 (q, J=8.1 Hz, 4H), 6.8 (dt, J=15.8, 6.9 Hz, 1H), 6.7 (d, J=15.8 Hz, 1H), 4.4 (s, 1H), 3.3-3.2 (m, 2H), 3.0-2.9 (m, 1H), 2.7-2.6 (m, 2H), 2.6 (q, J=7.6 Hz, 2H), 1.9-1.8 (m, 1H), 1.8-1.7 (m, 1H), 1.2 (t, J=7.6 Hz, 3H).

[0127] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 146.3, 146.3, 142.1, 141.8, 141.3, 129.1, 128.3, 128.2, 127.9, 127.2, 125.8, 116.5, 110.6, 59.1, 41.3, 39.2, 28.2, 16.0.

[0128] Embodiment 11

[0129] The structure of the compound in this example is shown in formula (I9):

[0130]

[0131] The preparation method thereof is similar to that of Example 1, except that, in step (3), cinnamaldehyde represented by formula (III1) is replaced by p-trifluoromethylcinnamaldehyde represented by formula (III9); and a reaction intermediate having a structure represented by formula (IV9) is obtained.

[0132]

[0133] Finally, 167.9 mg of a purified product of the compound represented by the general structural formula (Ⅰ9) was obtained with a yield of 86% and an ee value of 88%.

[0134] The obtained product was subjected to NMR detection. 1The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (d, J=2.4 Hz, 1H), 8.3 (dd, J=8.9, 2.4 Hz, 1H), 7.9 (d, J=8.9 Hz, 1H), 7.6-7.5 (m, 3H), 7.5 (d, J=5.1 Hz, 3H), 6.7 (dt, J=14.8, 7.1 Hz, 1H), 6.6 (d, J=15.7 Hz, 1H), 4.4 (t, J=5.0 Hz, 1H), 3.3-3.1 (m, 2H), 3.1 (td, J=8.6, 4.3 Hz, 1H), 2.7 (m, 3H), 2.0-1.7 (m, 3H).

[0135] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 146.4, 146.3, 146.2, 140.7, 132.3, 129.8, 129.0, 128.2, 127.2, 126.2, 124.8, 124.7, 123.5, 123.4, 116.4, 110.6, 58.9, 41.5, 38.8.

[0136] Example 12

[0137] The structure of the compound in this example is shown in formula (I10):

[0138]

[0139] The preparation method is similar to that of Example 1, except that in step (3), cinnamaldehyde represented by formula (III1) is replaced by p-ethoxycinnamaldehyde represented by formula (III10); and a reaction intermediate having a structure represented by formula (IV10) is obtained.

[0140]

[0141] Finally, 152.1 mg of a purified product of the compound represented by the general structural formula (Ⅰ10) was obtained with a yield of 83% and an ee value of 99%.

[0142] The obtained product was subjected to NMR detection. 1The results of H NMR (500 MHz, DMSO-d6) were as follows: δ8.6 (d, J = 2.4 Hz, 1H), 8.4 (dd, J = 8.9, 2.4 Hz, 1H), 8.0 (d, J = 8.9 Hz, 1H), 7.2 (d, J = 8.4 Hz, 2H), 6.8 (d, J = 8.3 Hz, 2H), 6.7 (dt, J = 15.9, 6.8 Hz ,1H),6.7(d,J=15.8Hz,1H),4.4(s,1H),4.0(q,J=7.0Hz,2H),3.9(s,1H),3.4-3.3( m,2H),2.9(td,J=8.4,4.2Hz,1H),2.6(m,2H),1.9-1.7(m,2H),1.3(t,J=6.9Hz,3H).

[0143] 13 C NMR (126 MHz, DMSO-d 6) The detection results are: δ157.3, 146.3, 146.3, 141.4, 136.6, 129.1, 128.9, 128.3, 127.2, 125.7, 116.5, 114.6, 110.6, 63.3, 59.1, 45.6, 40.9, 40.8, 39.4, 15.2.

[0144] Example 13

[0145] The structure of the compound in this example is shown in formula (I11):

[0146]

[0147] The preparation method thereof refers to Example 1, except that, in step (3), the cinnamaldehyde represented by formula (III1) is replaced by m-methoxycinnamaldehyde represented by formula (III11); and a reaction intermediate having a structure represented by formula (IV11) is obtained.

[0148]

[0149] Finally, 144.5 mg of a purified product of the compound represented by the general structural formula (Ⅰ11) was obtained with a yield of 82% and an ee value of 99%.

[0150] The obtained product was subjected to NMR detection. 1The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.9, 2.5 Hz, 1H), 8.0 (d, J=8.9 Hz, 1H), 7.2 (t, J=7.9 Hz, 1H), 6.9-6.8 (m, 2H), 6.8 (m, 2H), 6.7 (d, J=15.8 Hz, 1H), 4.4 (t, J=5.0 Hz, 1H), 3.7 (s, 3H), 3.3-3.2 (m, 2H), 3.0 (m, 1H), 2.7 (m, 2H), 1.9-1.7 (m, 2H).

[0151] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 159.8, 146.6, 146.3, 146.3, 141.2, 129.8, 129.1, 128.3, 127.2, 125.8, 120.3, 116.5, 113.8, 111.9, 110.6, 59.1, 55.4, 41.8, 40.4, 39.2.

[0152] Embodiment 14

[0153] The structure of the compound in this example is shown in formula (I12):

[0154]

[0155] The preparation method is similar to that of Example 1, except that in step (3), cinnamaldehyde of formula (III1) is replaced with p-ethoxycinnamaldehyde of formula (III12); and a reaction intermediate having a structure as shown in formula (IV12) is obtained.

[0156]

[0157] Finally, 164.0 mg of a purified product of the compound represented by the general structural formula (Ⅰ12) was obtained with a yield of 90% and an ee value of 99%.

[0158] The obtained product was subjected to NMR detection. 1The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.9, 2.5 Hz, 1H), 8.0 (d, J=8.9 Hz, 1H), 7.2 (t, J=7.6 Hz, 1H), 7.1 (d, J=1.7 Hz, 1H), 7.1-7.0 (m, 2H), 6.8 (dt, J=14.6, 7.1 Hz, 1H), 6.7 (d, J=15.7 Hz, 1H), 4.4 (s, 1H), 3.3-3.2 (m, 2H), 3.0 (m, 1H), 2.9 (p, J=6.9 Hz, 1H), 2.7 (m, 2H), 1.9-1.7 (m, 2H), 1.2 (d, J=6.9 Hz, 6H).

[0159] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 148.8, 146.3, 146.3, 144.8, 141.3, 129.1, 128.7, 128.3, 127.2, 126.2, 125.8, 125.3, 124.4, 116.4, 110.6, 59.2, 41.7, 40.6, 39.1, 33.9, 24.4, 24.4.

[0160] Embodiment 15

[0161] The structure of the compound in this example is shown in formula (I13):

[0162]

[0163] The preparation method thereof refers to Example 1, except that, in step (3), the cinnamaldehyde represented by formula (III1) is replaced by m-methylcinnamaldehyde represented by formula (III13); and a reaction intermediate having a structure represented by formula (IV13) is obtained.

[0164]

[0165] Finally, 149.7 mg of a purified product of the compound represented by the general structural formula (Ⅰ13) was obtained with a yield of 89% and an ee value of 99%.

[0166] The obtained product was subjected to NMR detection. 1The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.9, 2.4 Hz, 1H), 8.0 (d, J=8.9 Hz, 1H), 7.2 (t, J=7.6 Hz, 1H), 7.1-7.0 (m, 4H), 6.7 (dt, J=15.6, 6.7 Hz, 1H), 6.7 (d, J=15.8 Hz, 1H), 4.4 (s, 1H), 3.2 (dt, J=9.5, 4.4 Hz, 2H), 2.9 (m, 1H), 2.7 (m, 2H), 2.3 (s, 3H), 1.9-1.7 (m, 2H).

[0167] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 146.3, 146.3, 144.9, 141.3, 137.8, 129.1, 128.7, 128.7, 128.3, 127.3, 127.2, 125.8, 125.1, 116.5, 110.6, 59.1, 41.7, 39.2, 21.6.

[0168] Example 16

[0169] The structure of the compound in this example is shown in formula (I14):

[0170]

[0171] The preparation method thereof refers to Example 1, except that, in step (3), the cinnamaldehyde represented by formula (III1) is replaced by o-isopropylcinnamaldehyde represented by formula (III14); and a reaction intermediate having a structure represented by formula (IV14) is obtained.

[0172]

[0173] Finally, 158.5 mg of a purified product of the compound represented by the general structural formula (Ⅰ14) was obtained with a yield of 87% and an ee value of 99%.

[0174] The obtained product was subjected to NMR detection. 1The results of H NMR (500 MHz, DMSO-d6) were as follows: δ8.6 (d, J = 2.5 Hz, 1H), 8.4 (dd, J = 8.9, 2.5 Hz, 1H), 7.9 (d, J = 8.9 Hz, 1H), 7.3-7.3 (m, 1H), 7.2 (dd, J = 7.1, 2.2 Hz, 1H), 7.2 (m, 2H), 6.8 (dt, J = 14.5, 7.1H z,1H),6.7(d,J=15.8Hz,1H),4.4(d,J=4.8Hz,1H),3.4-3.4(m,1H),3.3(s,2H),3.3(td,J =10.9,5.9Hz,1H),2.6(m,2H),2.0-1.7(m,2H),1.2(d,J=6.8Hz,4H),1.1(d,J=6.9Hz,4H).

[0175] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 146.7, 146.2, 141.6, 141.2, 129.1, 128.3, 127.1, 126.5, 126.3, 125.8, 125.4, 116.4, 110.6, 59.1, 40.9, 39.5, 28.1, 24.5, 24.4.

[0176] Embodiment 17

[0177] The structure of the compound in this example is shown in formula (I15):

[0178]

[0179] The preparation method thereof refers to Example 1, except that, in step (3), the cinnamaldehyde represented by formula (III1) is replaced by o-methylcinnamaldehyde represented by formula (III15); and a reaction intermediate having a structure represented by formula (IV15) is obtained.

[0180]

[0181] Finally, 156.4 mg of a purified product of the compound represented by the general structural formula (Ⅰ15) was obtained with a yield of 93% and an ee value of 99%.

[0182] The obtained product was subjected to NMR detection. 1The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.9, 2.4 Hz, 1H), 7.9 (d, J=8.9 Hz, 1H), 7.3-7.3 (m, 1H), 7.2-7.2 (m, 1H), 7.1 (d, J=7.5 Hz, 1H), 7.1-7.0 (m, 1H), 6.8–6.7 (m, 1H), 6.7 (d, J=15.7 Hz, 1H), 4.4 (s, 1H), 3.4-3.3 (m, 2H), 3.2 (dt, J=10.6, 7.1 Hz, 1H), 2.6 (m, 2H), 2.3 (s, 3H), 2.0-1.7 (m, 2H).

[0183] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 146.3, 143.1, 141.2, 136.1, 130.5, 129.1, 128.3, 127.2, 126.6, 126.3, 126.1, 125.8, 116.4, 110.6, 59.0, 40.3, 39.2, 36.2, 20.0.

[0184] Embodiment 18

[0185] The structure of the compound in this example is shown in formula (I16):

[0186]

[0187] The preparation method thereof refers to Example 1, except that, in step (3), the cinnamaldehyde represented by formula (III1) is replaced by p-benzyloxycinnamaldehyde represented by formula (III16); and a reaction intermediate having a structure represented by formula (IV16) is obtained.

[0188]

[0189] Finally, 182.1 mg of a purified product of the compound represented by the general structural formula (Ⅰ16) was obtained with a yield of 85% and an ee value of 99%.

[0190] The obtained product was subjected to NMR detection. 1The results of H NMR (500 MHz, DMSO-d6) were as follows: δ8.7 (d, J = 2.4 Hz, 1H), 8.4 (dd, J = 8.9, 2.5 Hz, 1H), 8.0 (d, J = 8.9 Hz, 1H), 7.5 (d, J = 7.0 Hz, 2H), 7.4 (t, J = 7.5 Hz, 2H), 7.4-7.3 (m, 1H), 7.2 (t, J = 7.9 Hz, 1H), 6 .9(t,J=2.0Hz,1H),6.9-6.8(m,2H),6.8(dt,J=15.5,6.7Hz,1H),6.7(d,J=15.7Hz,1H),5.1 (s,2H),4.4(s,1H),3.3-3.2(m,3H),3.0(td,J=9.1,4.5Hz,1H),2.7(m,2H),1.9-1.7(m,2H).

[0191] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 159.0, 146.7, 146.3, 141.3, 137.7, 129.8, 129.1, 128.9, 128.3, 128.3, 128.2, 127.2, 125.8, 120.6, 116.5, 114.6, 112.8, 110.6, 69.6, 59.1, 41.8, 39.2.

[0192] Embodiment 19

[0193] The structure of the compound in this example is shown in formula (I17):

[0194]

[0195] The preparation method thereof refers to Example 1, except that, in step (3), the cinnamaldehyde represented by formula (III1) is replaced by m-trifluoromethylcinnamaldehyde represented by formula (III17); and a reaction intermediate having a structure represented by formula (IV17) is obtained.

[0196]

[0197] Finally, 160.0 mg of a purified product of the compound represented by the general structural formula (Ⅰ17) was obtained with a yield of 82% and an ee value of 99%.

[0198] The obtained product was subjected to NMR detection. 1The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.7 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.9, 2.4 Hz, 1H), 8.0 (d, J=8.9 Hz, 1H), 7.6-7.5 (m, 4H), 6.8 (dt, J=14.7, 7.1 Hz, 1H), 6.6 (d, J=15.7 Hz, 1H), 4.5 (t, J=5.0 Hz, 1H), 3.3-3.1 (m, 2H), 2.7 (m, 2H), 2.0 (dd, J=13.3, 6.8 Hz, 1H), 1.8 (m, 1H).

[0199] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 146.4, 146.3, 146.2, 140.7, 132.3, 129.8, 129.1, 128.3, 127.3, 126.2, 124.8, 123.5, 116.4, 110.6, 58.9, 41.5, 38.8.

[0200] Embodiment 20

[0201] The structure of the compound in this example is shown in formula (I18):

[0202]

[0203] The preparation method is similar to that of Example 1, except that in step (3), cinnamaldehyde represented by formula (III1) is replaced by p-chlorocinnamaldehyde represented by formula (III18); and a reaction intermediate having a structure represented by formula (IV18) is obtained.

[0204]

[0205] Finally, 153.4 mg of a purified product of the compound represented by the general structural formula (Ⅰ18) was obtained with a yield of 86% and an ee value of 99%.

[0206] The obtained product was subjected to NMR detection. 1 H NMR (500 MHz, DMSO-d 6) The detection results are: δ8.6 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.9, 2.4 Hz, 1H), 8.0 (d, J=8.9 Hz, 1H), 7.4-7.2 (m, 4H), 6.8-6.6 (m, 2H), 4.4 (s, 1H), 3.5-3.3 (m, 2H), 3.0 (td, J=9.0, 4.4 Hz, 1H), 2.7 (m, 2H), 2.0-1.7 (m, 2H).

[0207] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 146.29, 146.23, 143.88, 140.87, 131.10, 129.99, 129.06, 128.70, 128.29, 127.24, 126.02, 116.43, 110.62, 58.94, 41.15, 40.53, 39.06.

[0208] Embodiment 21

[0209] The structure of the compound in this example is shown in formula (I19):

[0210]

[0211] The preparation method thereof refers to Example 1, except that, in step (3), the cinnamaldehyde represented by formula (III1) is replaced by p-bromocinnamaldehyde represented by formula (III19); and a reaction intermediate having a structure represented by formula (IV19) is obtained.

[0212]

[0213] Finally, 166.5 mg of a purified product of the compound represented by the general structural formula (Ⅰ19) was obtained with a yield of 83% and an ee value of 99%.

[0214] The obtained product was subjected to NMR detection. 1 The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.7 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.9, 2.4 Hz, 1H), 8.0 (d, J=8.9 Hz, 1H), 7.5 (d, J=8.2 Hz, 2H), 7.2 (d, J=8.2 Hz, 2H), 6.8-6.6 (m, 2H), 4.4 (d, J=5.2 Hz, 1H), 3.3-3.1 (m, 2H), 3.0 (td, J=8.9, 4.4 Hz, 1H), 2.7 (m, 2H), 2.0-1.7 (m, 2H).

[0215] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 146.3, 146.2, 144.3, 140.9, 131.6, 130.4, 129.1, 128.3, 127.3, 126.0, 119.6, 116.5, 110.6, 58.9, 41.2, 39.0.

[0216] Embodiment 22

[0217] The structure of the compound in this example is shown in formula (I20):

[0218]

[0219] The preparation method is similar to that of Example 1, except that in step (3), cinnamaldehyde represented by formula (III1) is replaced by o-chlorocinnamaldehyde represented by formula (III20); and a reaction intermediate having a structure represented by formula (IV20) is obtained.

[0220]

[0221] Finally, 160.6 mg of a purified product of the compound represented by the general structural formula (Ⅰ20) was obtained with a yield of 90% and an ee value of 99%.

[0222] The obtained product was subjected to NMR detection. 1 The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.6 (d, J=2.5 Hz, 1H), 8.4 (dd, J=8.9, 2.5 Hz, 1H), 8.0 (d, J=8.9 Hz, 1H), 7.5 (dd, J=7.8, 1.7 Hz, 1H), 7.4-7.3 (m, 2H), 7.2 (td, J=7.6, 1.6 Hz, 1H), 6.7 (dt, J=14.7, 7.1 Hz, 1H), 6.6 (d, J=15.7 Hz, 1H), 4.5 (t, J=4.9 Hz, 1H), 3.6-3.5 (m, 1H), 3.3 (d, J=2.0 Hz, 2H), 2.7 (m, 2H), 2.0-1.8 (m, 2H).

[0223] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 146.3, 146.2, 141.9, 140.3, 133.7, 129.7, 129.1, 128.9, 128.3, 128.2, 127.9, 127.2, 126.1, 116.4, 110.6, 59.0, 39.5, 38.1, 37.5.

[0224] Embodiment 23

[0225] The structure of the compound in this example is shown in formula (I21):

[0226]

[0227] The preparation method is similar to that of Example 1, except that in step (1), 2-allyl-5-nitrobenzonitrile of formula (II1) is replaced by 1-allyl-4-nitro-2-(trifluoromethyl)benzene of formula (II2); and in step (3), a reaction intermediate having a structure as shown in formula (IV21) is obtained.

[0228] The preparation method of 1-allyl-4-nitro-2-(trifluoromethyl)benzene shown in formula (II2) in step (1) is as follows: 1 mL of tert-butyl nitrite, 7.1 mL of 3-bromopropylene and 1 g of 2-trifluoromethyl-4-nitroaniline are added to 5.5 mL of acetonitrile in sequence, mixed evenly, and then 0.3 mL of tert-butyl nitrite is added in an argon atmosphere, and the mixture is reacted at 25° C. for 24 hours to obtain 2-allyl-5-nitrobenzonitrile shown in (II1).

[0229]

[0230] Finally, 148.0 mg of a purified product of the compound represented by the general structural formula (Ⅰ21) was obtained with a yield of 81% and an ee value of 99%.

[0231] The obtained product was subjected to NMR detection. 1 The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.4-8.3 (m, 2H), 7.9 (d, J = 8.7 Hz, 1H), 7.3-7.2 (m, 4H), 7.2-7.2 (m, 1H), 6.6 (dd, J = 15.9, 2.5 Hz, 1H), 6.5 (dt, J = 15.1, 6.9 Hz, 1H), 4.4 (s, 1H), 3.3-3.2 (m, 2H), 3.0 (td, J = 8.9, 4.4 Hz, 1H), 2.7-2.6 (m, 2H), 1.9-1.8 (m, 1H), 1.8-1.7 (m, 1H).

[0232] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 146.1, 144.9, 140.1, 129.2, 128.7, 128.0, 127.8, 126.6, 121.7, 121.7, 59.1, 55.4, 41.8, 39.2.

[0233] Embodiment 24

[0234] The structure of the compound in this example is shown in formula (I22):

[0235]

[0236] The preparation method thereof refers to Example 1, except that, in step (1), 2-allyl-5-nitrobenzonitrile shown in formula (II1) is replaced by 1-allyl-2,4-dinitrobenzene shown in formula (II3); in step (3), a reaction intermediate having a structure shown in formula (IV22) is obtained.

[0237] Among them, the preparation method of 1-allyl-2,4-dinitrobenzene shown in (II3) in step (1) is: 1 mL of tert-butyl nitrite, 7.1 mL of 3-bromopropylene and 1 g of 2,4-dinitroaniline are added to 5.5 mL of acetonitrile in sequence, mixed evenly, and then 0.3 mL of tert-butyl nitrite is added in an argon atmosphere, and the mixture is reacted at 25° C. for 24 hours to obtain 2-allyl-5-nitrobenzonitrile shown in (II1).

[0238]

[0239] Finally, 138.7 mg of a purified product of the compound represented by the general structural formula (Ⅰ22) was obtained with a yield of 81% and an ee value of 99%.

[0240] The obtained product was subjected to NMR detection. 1 The detection results of H NMR (500 MHz, DMSO-d6) were: δ8.7 (d, J=2.4 Hz, 1H), 8.4 (dd, J=8.7, 2.4 Hz, 1H), 7.9 (d, J=8.8 Hz, 1H), 7.3 (t, J=7.5 Hz, 2H), 7.3-7.2 (m, 2H), 7.2 (t, J=7.2 Hz, 1H), 6.7 (d, J=15.7 Hz, 1H), 6.5 (dt, J=15.1, 7.1 Hz, 1H), 4.4 (t, J=5.0 Hz, 1H), 3.3-3.2 (m, 2H), 3.0 (m, 1H), 2.6 (m, 2H), 1.8 (m, 2H).

[0241] 13 C NMR (126 MHz, DMSO-d6) detection results: δ 147.4, 146.3, 145.0, 137.8, 129.7, 128.8, 128.0, 127.6, 126.6, 124.5, 120.4, 59.1, 41.8, 40.5, 39.1.

[0242] Comparative Example 1

[0243] The compound structure and preparation method provided in this comparative example refer to Example 1, except that an equimolar amount of proline is used as a catalyst in step (2). No target product is obtained and the reaction does not proceed.

[0244] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modification, equivalent substitution or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for adding an allyl aromatic derivative, characterized in that: The following steps are involved: The allyl aromatic compound represented by formula (II), the cinnamaldehyde derivative represented by formula (III) and diarylprolinol silyl ether are subjected to Michael addition reaction in an organic solvent to obtain a reaction intermediate represented by formula (IV); Reducing the reaction intermediate to obtain a compound with a structure as shown in formula (I); ； Wherein, R1 is nitro, cyano or trifluoromethyl, and R2 is hydrogen, halogen, methoxy, ethoxy, methyl, ethyl, isopropyl, nitro, dimethylamino, benzyloxy or trifluoromethyl.

2. The method for adding an allyl aromatic derivative according to claim 1, characterized in that: Its structure is shown in formula (Ⅰ1) to formula (Ⅰ25):

3. The method for adding an allyl aromatic derivative according to claim 1, characterized in that: The following steps are involved: S1, dissolving the allyl aromatic compound represented by formula (II) in a first organic solvent to obtain an allyl aromatic compound solution; S2, dissolving the diaryl prolinol silyl ether in a first organic solvent, then adding the cinnamaldehyde derivative represented by formula (III), adding the allyl aromatic compound solution in an inert atmosphere, and then reacting at 25-40° C. for 20-24 hours, extracting, and separating the extract by silica gel column chromatography to obtain a reaction intermediate represented by formula (IV); S3, adding the reaction intermediate into a second organic solvent, adding a reducing agent at 0-5°C, reacting for 20-30 minutes, and obtaining a compound having a structure as shown in formula (I).

4. The method for adding an allyl aromatic derivative according to claim 3, characterized in that: In step S3, the reducing agent is sodium borohydride, potassium borohydride or lithium aluminum tetrahydride.

5. The method for adding an allyl aromatic derivative according to claim 3, characterized in that: In step S2, the first organic solvent is at least one of toluene, tetrahydrofuran, acetonitrile, dichloromethane, dichloroethane or 1,4-dioxane; and / or In step S2, the extraction liquid is at least one of dichloromethane or ethyl acetate; and / or In step S3, the second solvent is a mixed solution of dichloromethane and ethanol, wherein the volume ratio of dichloromethane to ethanol is 2:1-3:

2.

6. The method for adding an allyl aromatic derivative according to claim 1, characterized in that: The molar ratio of the cinnamaldehyde derivative, the diarylprolinol silyl ether and the allyl aromatic compound is 0.3-1:0.1-0.2:

1.

7. The method for adding an allyl aromatic derivative according to claim 3, characterized in that: In step S2, the allyl aromatic compound solution is added dropwise for 10 to 20 minutes.

8. The method for adding an allyl aromatic derivative according to any one of claims 1 to 7, characterized in that: Also includes the refinement step: Adding a saturated ammonium chloride solution to the compound having the structure shown in formula (I) for quenching, and then adding dichloromethane for extraction to obtain an extract; A saturated sodium chloride solution is added to the extract to wash, and then the extract is dehydrated, concentrated, separated by silica gel column chromatography, and dried to obtain a refined product.

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