A method for synthesizing a pyrrolidine compound

Abstract

This invention belongs to the field of synthetic technology of aliphatic heterocyclic compounds, specifically relating to a method for synthesizing pyrrolidine compounds. The synthetic method includes: mixing an N-acyl-protected β-amino acid ester, an aryl olefin, and a protic acid in a solvent to obtain a mixed solution; and reacting the mixed solution at room temperature under continuous light irradiation to obtain the pyrrolidine compound. This synthetic method uses readily available raw materials, does not use a photocatalyst, is simple to operate, has mild reaction conditions, and yields a high product yield.

Description

Technical Field

[0001] This invention belongs to the field of synthetic technology of aliphatic heterocyclic compounds, and specifically relates to a method for synthesizing pyrrolidine compounds. Background Technology

[0002] Pyrrolidine is an important structural unit in drug development. It is not only a classic five-membered nitrogen-containing saturated heterocycle, but also a key module for modern medicinal chemists to construct molecules with complexity and bioactivity. The introduction of pyrrolidine can increase the molecule's hydrophilicity and impart appropriate basicity, which helps improve the overall water solubility of the molecule and is an important means of optimizing pharmacokinetic properties such as drug absorption and distribution in vivo. Unlike planar aromatic rings, the pyrrolidine ring is a saturated three-dimensional structure. It can fix key functional groups in the molecule in a specific spatial orientation; this "stereoscopic effect" plays a crucial role in the precise recognition and binding of drug molecules to target proteins. Although pyrrolidine has a wide range of applications, its efficient and precise synthesis, especially the direct construction of structurally complex pyrrolidine molecules, has always been a core challenge in the field of synthetic chemistry.

[0003] Currently, the main methods for synthesizing pyrrolidine compounds are as follows:

[0004] 1. Patent CN110590706A reports a method for synthesizing N-methylpyrrolidine using 1,4-dichlorobutane and methylamine via two nucleophilic substitution cyclization reactions. This method requires the addition of an excess of strong base and high-temperature conditions for the reaction to occur. Furthermore, substituted dihalobutane starting materials are not readily available, which limits the structural possibilities when preparing pyrrolidine derivatives using this method.

[0005]

[0006] 2. The preparation of pyrrolidine compounds via a three-component cycloaddition reaction of aldehydes, amines, and electron-deficient alkenes involves converting the imine intermediate formed by the condensation of aldehydes and amines into a 1,3-dipolar compound under catalytic or direct heating conditions, followed by a [3+2] cycloaddition reaction with the alkene (J. Org. Chem. 2005, 70, 10868-10871.). This method is suitable for reactive alkenes; however, when using sterically hindered or inert alkenes, a transition metal catalyst is required, and the conversion efficiency decreases.

[0007]

[0008] 3. Currently, the more widely applicable method is radical cyclization to construct pyrrolidine structures. As shown in the figure below, Cbz-protected potassium aminoethyltrifluoroborate is converted into a carbon radical under copper catalysis, which adds to the olefin, and then the pyrrolidine structure is prepared by radical oxidation intramolecular nucleophilic cyclization (Org. Lett. 2016, 18, 2515-2518.). In addition to transition metal catalysis, photocatalysis can also obtain pyrrolidine products through a similar reaction process (ACS Catal. 2022, 12, 13732-13740). These methods usually use neutral reaction conditions and have a wider range of applicable substrates, including internal alkenes and common alkyl alkenes. However, they require expensive transition metal catalysts, ligands, photocatalysts, and additional additives, increasing the synthesis cost of pyrrolidine compounds and making large-scale application difficult.

[0009]

[0010] In summary, the synthetic methods for pyrrolidine compounds are still imperfect, especially lacking research on synthesis using low-cost reagents or catalysts and without the involvement of transition metals. Pyrrolidines are also important structures in drug molecules, and the development of a synthetic method for pyrrolidine compounds that avoids the use of expensive catalysts and operates under mild conditions is crucial for the construction of the core framework of related drugs. Summary of the Invention

[0011] In view of this, the technical problem to be solved by the present invention is to provide a method for synthesizing pyrrolidine compounds. This method uses readily available raw materials, does not use photocatalysts, is simple to operate, has mild reaction conditions, and yields high product yields.

[0012] The technical solution adopted in this invention is as follows:

[0013] This invention provides a method for synthesizing pyrrolidine compounds, the method comprising the following steps:

[0014] Compound 1, an aryl olefin, and a protic acid were mixed in a solvent to obtain a mixed solution; wherein, compound 1 is an N-acyl protected β-amino acid ester;

[0015] The mixed solution was reacted at room temperature under continuous light irradiation to obtain a pyrrolidine compound;

[0016] When the aryl olefin is compound 2, the pyrrolidine compound is obtained as compound 3. The synthetic route of the synthetic method is shown in the following formula:

[0017] ;

[0018] When the aryl olefin is compound 4, the pyrrolidine compound is obtained as compound 5. The synthetic route of the synthetic method is shown in the following formula:

[0019] ;

[0020] Among them, R 1 Indicates phenyl, methyl, or hydrogen; R 2 Indicates phenyl, methyl, or hydrogen; R 3 It represents phenyl, methyl, or hydrogen; PG represents one of benzyloxycarbonyl, tert-butoxycarbonyl, acetyl, benzoyl, and p-toluenesulfonyl; Ar represents one of phenyl, 4-methoxyphenyl, 4-methylphenyl, 3-methylphenyl, 3,5-dimethylphenyl, 4-tert-butylphenyl, 3-methoxyphenyl, 3,4-dimethoxyphenyl, 2-methoxyphenyl, 4-dimethylaminophenyl, 4-fluorophenyl, 4-acetaminophenyl, naphth-2-yl, and benzofuran-5-yl.

[0021] In some embodiments of the present invention, compound 1 is one of N-benzyloxycarbonylalanine phthalimide ester, N-tert-butoxycarbonylalanine phthalimide ester, N-acetylalanine phthalimide ester, N-benzoylalanine phthalimide ester, N-toluenesulfonylalanine phthalimide ester, N-benzyloxycarbonyl-2-methylalanine phthalimide ester, and N-benzyloxycarbonyl-2-phenylalanine phthalimide ester.

[0022] In some embodiments of the present invention, the aryl olefin is one of styrene, 4-methoxystyrene, 4-methylstyrene, 3-methylstyrene, 3,5-dimethylstyrene, 4-tert-butylstyrene, 3-methoxystyrene, 3,4-dimethoxystyrene, 2-methoxystyrene, 4-dimethylaminostyrene, 4-acetoxystyrene, 4-fluorostyrene, 4-acetaminostyrene, 2-naphthylene, 5-vinylbenzofuran, α-methylstyrene, β-methylstyrene, 1,1-diphenylethylene, 1,2-diphenylethylene, and indene.

[0023] In some embodiments of the present invention, the pyrrolidine compound is N-benzyloxycarbonyl-2-(4-methoxyphenyl)pyrrolidine (3a), N-benzyloxycarbonyl-2-phenylpyrrolidine (3b), N-benzyloxycarbonyl-2-(3-methylphenyl)pyrrolidine (3c), N-benzyloxycarbonyl-2-(3,4-dimethoxyphenyl)pyrrolidine (3d), N-benzyloxycarbonyl-2-(4-dimethylaminophenyl)pyrrolidine (3e), N-benzyloxycarbonyl-2-(4-acetamidophenyl)pyrrolidine (3f), N-benzyloxycarbonyl-2-(naphth-2-yl)pyrrolidine (3g), N-benzyloxycarbonyl-2- One of the following: methyl-2-phenylpyrrolidine (3h), N-benzyloxycarbonyl-3-methyl-2-(4-methoxyphenyl)pyrrolidine (3i), N-tert-butoxycarbonyl-2-(4-methoxyphenyl)pyrrolidine (3j), N-acetyl-2-(4-methoxyphenyl)pyrrolidine (3k), N-benzoyl-2-(4-methoxyphenyl)pyrrolidine (3l), N-p-toluenesulfonyl-2-(4-methoxyphenyl)pyrrolidine (3m), N-benzyloxycarbonyl-5-methyl-2-(4-methoxyphenyl)pyrrolidine (3n), and N-benzyloxycarbonyltetrahydroindenopyrrolidine (5a).

[0024] When the pyrrolidine compound is N-benzyloxycarbonyl-2-(4-methoxyphenyl)pyrrolidine (3a), R 1 For hydrogen, R 2 For hydrogen, R 3 It is hydrogen.

[0025] When the pyrrolidine compound is N-benzyloxycarbonyl-2-phenylpyrrolidine (3b), R 1 For hydrogen, R 2 For hydrogen, R 3 It is hydrogen.

[0026] When the pyrrolidine compound is N-benzyloxycarbonyl-2-(3-methylphenyl)pyrrolidine (3c), R 1 For hydrogen, R 2 For hydrogen, R 3 It is hydrogen.

[0027] When the pyrrolidine compound is N-benzyloxycarbonyl-2-(3,4-dimethoxyphenyl)pyrrolidine (3d), R 1 For hydrogen, R 2 For hydrogen, R 3 It is hydrogen.

[0028] When the pyrrolidine compound is N-benzyloxycarbonyl-2-(4-dimethylaminophenyl)pyrrolidine (3e), R 1 For hydrogen, R 2 For hydrogen, R 3 It is hydrogen.

[0029] When the pyrrolidine compound is N-benzyloxycarbonyl-2-(4-acetamidophenyl)pyrrolidine (3f), R 1 For hydrogen, R 2 For hydrogen, R 3 It is hydrogen.

[0030] When the pyrrolidine compound is N-benzyloxycarbonyl-2-(naphth-2-yl)pyrrolidine (3g), R 1 For hydrogen, R 2 For hydrogen, R 3 It is hydrogen.

[0031] When the pyrrolidine compound is N-benzyloxycarbonyl-2-methyl-2-phenylpyrrolidine (3h), R 1 For methyl, R 2 For hydrogen, R 3 It is hydrogen.

[0032] When the pyrrolidine compound is N-benzyloxycarbonyl-3-methyl-2-(4-methoxyphenyl)pyrrolidine (3i), R 1 For hydrogen, R 2 For methyl, R 3 It is hydrogen.

[0033] When the pyrrolidine compound is N-tert-butoxycarbonyl-2-(4-methoxyphenyl)pyrrolidine (3j), R 1 For hydrogen, R 2 For hydrogen, R 3 It is hydrogen.

[0034] When the pyrrolidine compound is N-acetyl-2-(4-methoxyphenyl)pyrrolidine (3k), R 1 For hydrogen, R 2 For hydrogen, R 3 It is hydrogen.

[0035] When the pyrrolidine compound is N-benzoyl-2-(4-methoxyphenyl)pyrrolidine (3l), R 1 For hydrogen, R 2 For hydrogen, R 3 It is hydrogen.

[0036] When the pyrrolidine compound is N-p-toluenesulfonyl-2-(4-methoxyphenyl)pyrrolidine (3m), R 1 For hydrogen, R 2 For hydrogen, R 3 It is hydrogen.

[0037] When the pyrrolidine compound is N-benzyloxycarbonyl-5-methyl-2-(4-methoxyphenyl)pyrrolidine (3n), R 1 For hydrogen, R 2 For hydrogen, R 3 It is a methyl group.

[0038] When the pyrrolidine compound is N-benzyloxycarbonyltetrahydroindenepyrrolidine (5a), the aryl olefin is indene, R 3 It is hydrogen.

[0039] In some embodiments of the present invention, the protic acid is one of concentrated hydrochloric acid, trifluoroacetic acid, acetic acid, phosphoric acid, diphenyl phosphate, dibenzyl phosphate, ditert-butyl phosphate, naphthol phosphate, and monophenyl phosphate, more preferably diphenyl phosphate.

[0040] In some embodiments of the present invention, the solvent is any one or more of dichloromethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, methanol, hexafluoroisopropanol, acetone and ethyl acetate, more preferably dimethyl sulfoxide.

[0041] In some embodiments, in the above synthesis method, the molar ratio of compound 1, aryl olefin and protic acid is 1:(1~3):(0.05~1), more preferably 1:1.5:0.25.

[0042] In some embodiments, in the above synthesis method, the concentration of compound 1 in the mixed solution is 0.05~0.3 mol / L, more preferably 0.1 mol / L.

[0043] In some embodiments, the illumination conditions specifically involve irradiating the reaction with a light source of wavelength 365-420 nm, more preferably 395 nm.

[0044] In some embodiments, the reaction time in the above synthesis method is 12-30 h.

[0045] The post-processing operation of this invention is simple and is a conventional processing method for organic synthesis reactions, including the purification operation of the pyrrolidine compound.

[0046] In some specific embodiments of the present invention, the purification steps are as follows: the reaction solution is transferred from the reaction tube to a separatory funnel, diluted with water, and extracted with ethyl acetate. The solvent in the extracted organic phase is removed by vacuum distillation. The crude product is then separated by silica gel column chromatography to obtain a high-purity pyrrolidine compound. The separated pyrrolidine compound generally contains both cis and trans isomers. Pyrrolidines with multiple substituents contain multiple isomers, and the separated pyrrolidine is the sum of all isomers. The column chromatography separation operation uses 300-400 mesh silica gel, and the eluent is a mixture of ethyl acetate and petroleum ether.

[0047] Compared with existing technologies, the method for synthesizing pyrrolidine compounds provided by this invention uses readily available and inexpensive chemical reagents such as aryl alkenes and β-amino acids. The reaction process does not use photocatalysts or transition metal catalysts, but only a small amount of protic acid additives, reducing reagent costs and having no impact on the structure of the raw materials. The reaction conditions are mild, requiring only direct irradiation from a light source, without the need for inert gas protection or an anhydrous reaction environment. It produces few byproducts, has a high yield, and can synthesize a wide range of pyrrolidine compounds, making it suitable for large-scale production. Attached Figure Description

[0048] Figure 1 The 1H NMR spectrum of N-benzyloxycarbonyl-2-(4-methoxyphenyl)-pyrrolidine (3a) prepared in Example 1;

[0049] Figure 2 The carbon NMR spectrum of N-benzyloxycarbonyl-2-(4-methoxyphenyl)-pyrrolidine (3a) prepared in Example 1;

[0050] Figure 3 The 1H NMR spectrum of N-benzyloxycarbonyl-2-phenyl-pyrrolidine (3b) prepared in Example 2;

[0051] Figure 4 The carbon NMR spectrum of N-benzyloxycarbonyl-2-phenyl-pyrrolidine (3b) prepared in Example 2;

[0052] Figure 5 The 1H NMR spectrum of N-benzyloxycarbonyl-2-(3-methylphenyl)-pyrrolidine (3c) prepared in Example 3;

[0053] Figure 6 The carbon NMR spectrum of N-benzyloxycarbonyl-2-(3-methylphenyl)-pyrrolidine (3c) prepared in Example 3;

[0054] Figure 7 The 1H NMR spectrum of N-benzyloxycarbonyl-2-(3,4-dimethoxyphenyl)-pyrrolidine (3d) prepared in Example 4;

[0055] Figure 8 The carbon NMR spectrum of N-benzyloxycarbonyl-2-(3,4-dimethoxyphenyl)-pyrrolidine (3d) prepared in Example 4;

[0056] Figure 9 The 1H NMR spectrum of N-benzyloxycarbonyl-2-(4-dimethylaminophenyl)-pyrrolidine (3e) prepared in Example 5;

[0057] Figure 10The carbon NMR spectrum of N-benzyloxycarbonyl-2-(4-dimethylaminophenyl)-pyrrolidine (3e) prepared in Example 5. Detailed Implementation

[0058] The technical solution of the present invention will be further described in detail below through embodiments and in conjunction with the accompanying drawings. In this specification, the same or similar reference numerals indicate the same or similar components. The following description of the embodiments of the present invention with reference to the accompanying drawings is intended to explain the overall inventive concept of the present invention and should not be construed as a limitation thereof.

[0059] To further illustrate the present invention, the method for synthesizing pyrrolidine compounds provided by the present invention will be described in detail below with reference to embodiments.

[0060] In the synthesis steps of the pyrrolidine compounds in the following embodiments of the present invention, compound 1 was synthesized from N-acyl-protected β-amino acid and N-hydroxyphthalimide by a known synthetic method (ACS Catal. 2022, 12, 13732-13740).

[0061] Example 1

[0062] Preparation of N-benzyloxycarbonyl-2-(4-methoxyphenyl)pyrrolidine (3a)

[0063] 73.6 mg (0.2 mmol) of N-benzyloxycarbonylalanine phthalimide ester, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide were added to a 10 mL dry Schlenk tube. Finally, 40.2 mg (0.3 mmol) of 4-methoxystyrene was added. The Schlenk stopcock was tightened, and the tube was stirred at room temperature for 12 h under 395 nm LED illumination. After the reaction was complete, the reaction mixture was transferred to a separatory funnel with ethyl acetate, 5 mL of water was added, and the mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated sodium chloride solution. The solvent was removed by vacuum distillation. The crude product was separated by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a 1:20 mixture of ethyl acetate and petroleum ether), yielding 45.6 mg of a colorless liquid product, with a yield of 73%.

[0064] The structure and NMR spectral data of compound 3a are as follows:

[0065]

[0066] See Figure 1 , 1¹H NMR (400 MHz, CDCl₃) δ 7.49 – 7.28 (m, 2H), 7.24 – 7.02 (m, 4H), 7.00 – 6.89 (m, 1H), 6.89 – 6.78 (m, 2H), 5.24 – 4.81 (m, 3H), 3.87 – 3.75 (m, 3H), 3.73 – 3.55 (m, 2H), 2.37 – 2.21 (m, 1H), 2.02 – 1.79 (m, 3H). See also Figure 2 , 13 C NMR (101 MHz, CDCl3) δ 158.4, 155.0, 154.8, 137.0, 136.8, 136.4,135.6, 128.5, 128.4, 128.1, 127.8, 127.4, 127.2, 126.6, 113.8, 113.7, 66.6,66.4, 60.7, 60.5, 55.2, 47.5, 47.0, 35.9, 34.7, 23.6, 22.8.

[0067] Example 2

[0068] Preparation of N-benzyloxycarbonyl-2-phenylpyrrolidine (3b)

[0069] 73.6 mg (0.2 mmol) of N-benzyloxycarbonylalanine phthalimide ester, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide were added to a 10 mL dry Schlenk tube. Finally, 31.2 mg (0.3 mmol) of styrene was added. The Schlenk stopcock was tightened, and the tube was stirred at room temperature for 24 h under 395 nm LED illumination. After the reaction was complete, the reaction mixture was transferred to a separatory funnel with ethyl acetate, 5 mL of water was added, and the mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated sodium chloride solution. The solvent was removed by vacuum distillation. The crude product was separated by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a 1:20 mixture of ethyl acetate and petroleum ether), yielding 37.7 mg of a colorless liquid product, with a yield of 67%.

[0070] The structure and NMR spectral data of compound 3b are as follows:

[0071]

[0072] See Figure 3 , 1¹H NMR (400 MHz, CDCl₃) δ 7.48 – 7.09 (m, 9H), 6.87 (d, J = 6.0 Hz, 1H), 5.23 – 4.85 (m, 3H), 3.78 – 3.52 (m, 2H), 2.40 – 2.21 (m, 1H), 1.99 – 1.80 (m, 3H). See also Figure 4 , 13 C NMR (101 MHz, CDCl3) δ 154.9, 154.8, 144.2,143.4, 136.9, 136.6, 128.4, 128.34, 128.28, 128.0, 127.8, 127.3, 127.1,126.7, 126.6, 125.4, 66.6, 66.4, 61.2, 61.0, 47.5, 47.0, 35.8, 34.6, 23.4,22.8.

[0073] Example 3

[0074] Preparation of N-benzyloxycarbonyl-2-(3-methylphenyl)pyrrolidine (3c)

[0075] 73.6 mg (0.2 mmol) of N-benzyloxycarbonylalanine phthalimide ester, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide were added to a 10 mL dry Schlenk tube. Finally, 35.4 mg (0.3 mmol) of 3-methylstyrene was added, and the tube was stirred at room temperature for 24 h under 395 nm LED illumination. After the reaction was complete, the reaction mixture was transferred to a separatory funnel with ethyl acetate, 5 mL of water was added, and the mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated sodium chloride solution. The solvent was removed by vacuum distillation. The crude product was separated by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a 1:20 mixture of ethyl acetate and petroleum ether), yielding 37.8 mg of a colorless liquid product, with a yield of 64%.

[0076] The 3c structure and NMR spectral data of the compound are as follows:

[0077]

[0078] See Figure 5 , 1¹H NMR (400 MHz, CDCl₃) δ 7.48 – 7.28 (m, 2.3H), 7.25 – 7.13 (m, 2.7H), 7.10 – 6.94 (m, 3H), 6.90 (d, J = 6.1 Hz, 1H), 5.22 – 5.02 (m, 1.5H), 5.01 – 4.84 (m, 1.5H), 3.77 – 3.56 (m, 2H), 2.39 – 2.24 (m, 4H), 2.03– 1.79 (m, 3H). See also Figure 6 , 13 C NMR (101 MHz, CDCl3) δ 155.0, 154.8, 144.3, 143.4,137.9, 136.8, 128.5, 128.4, 128.2, 128.1, 127.9, 127.5, 127.4, 127.2, 126.2,122.54, 122.48, 66.6, 66.4, 61.3, 61.0, 47.6, 47.1, 35.9, 34.8, 23.6, 22.9,21.5.

[0079] Example 4

[0080] Preparation of N-benzyloxycarbonyl-2-(3,4-dimethoxyphenyl)pyrrolidine (3d)

[0081] 73.6 mg (0.2 mmol) of N-benzyloxycarbonylalanine phthalimide, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide were added to a 10 mL dry Schlenk tube. Finally, 49.2 mg (0.3 mmol) of 3,4-dimethoxystyrene was added. The Schlenk stopcock was tightened, and the tube was stirred at room temperature for 12 h under 395 nm LED illumination. After the reaction was complete, the reaction mixture was transferred to a separatory funnel with ethyl acetate, 5 mL of water was added, and the mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated sodium chloride solution. The solvent was removed by vacuum distillation. The crude product was separated by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a 1:10 mixture of ethyl acetate and petroleum ether), yielding 50.5 mg of a colorless liquid product, with a yield of 74%.

[0082] The 3d structure and NMR spectral data of the compound are as follows:

[0083]

[0084] See Figure 7 ,1 H NMR (400 MHz, CDCl3) δ 7.49 – 7.28 (m, 2.3H), 7.25 – 7.10(m, 1.7H), 7.04 – 6.89 (m, 1H), 6.80 (d, J = 7.9 Hz, 1H), 6.72 (t, J = 10.3Hz, 1.4H), 6.62 (s, 0.6H), 5.20 – 5.02 (m, 1.5H), 5.02 – 4.81 (m, 1.5H), 3.97– 3.73 (m, 6H), 3.73 – 3.55 (m, 2H), 2.39 – 2.19 (m, 1H), 2.05 – 1.78 (m,3H). See Figure 8 , 13 C NMR (101 MHz, CDCl3) δ 155.1, 154.8, 148.8, 147.7, 136.9,136.6, 136.1, 128.5, 128.4, 128.1, 127.9, 127.5, 127.3, 117.3, 117.2, 111.0,110.9, 108.9, 108.8, 66.6, 66.5, 61.0, 60.8, 55.9, 55.7, 47.5, 47.1, 35.9,34.7, 29.0, 26.9, 23.6, 22.9.

[0085] Example 5

[0086] Preparation of N-benzyloxycarbonyl-2-(4-dimethylaminophenyl)pyrrolidine (3e)

[0087] 73.6 mg (0.2 mmol) of N-benzyloxycarbonylalanine phthalimide, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide were added to a 10 mL dry Schlenk tube. Finally, 44.1 mg (0.3 mmol) of 4-dimethylaminostyrene was added. The Schlenk stopcock was tightened, and the tube was stirred at room temperature for 12 h under 395 nm LED illumination. After the reaction was complete, the reaction mixture was transferred to a separatory funnel with ethyl acetate, 5 mL of water was added, and the mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated sodium chloride solution. The solvent was removed by vacuum distillation. The crude product was separated by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a 1:10 mixture of ethyl acetate and petroleum ether), yielding 50.0 mg of a colorless liquid product, with a yield of 77%.

[0088] The structure and NMR spectral data of compound 3e are as follows:

[0089]

[0090] See Figure 9 , 1 ¹H NMR (400 MHz, CDCl₃) δ 7.46 – 7.28 (m, 2H), 7.25 – 6.89 (m, 5H), 6.71 (d, J = 7.9 Hz, 2H), 5.27 – 4.82 (m, 3H), 3.79 – 3.53 (m, 2H), 3.10– 2.85 (m, 6H), 2.40 – 2.17 (m, 1H), 2.10 – 1.78 (m, 3H). See also Figure 10 , 13 C NMR(101 MHz, CDCl3) δ 155.1, 154.7, 149.6, 137.1, 136.9, 132.2, 131.5, 128.3,128.0, 127.8, 127.3, 127.2, 126.3, 112.7, 112.6, 66.5, 66.3, 60.7, 60.5,47.4, 46.9, 40.7, 35.8, 34.6, 23.6, 22.8.

[0091] Example 6

[0092] Preparation of N-benzyloxycarbonyl-2-(4-acetamidophenyl)pyrrolidine (3f)

[0093] 73.6 mg (0.2 mmol) of N-benzyloxycarbonylalanine phthalimide, 48.3 mg (0.3 mmol) of 4-acetamidostyrene, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide were added to a 10 mL dry Schlenk tube. The Schlenk stopcock was tightened, and the tube was stirred at room temperature for 24 h under 395 nm LED illumination. After the reaction was complete, the reaction solution was transferred to a separatory funnel with ethyl acetate, 5 mL of water was added, and the mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated sodium chloride solution. The solvent was removed by vacuum distillation. The crude product was separated by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a 1:5 mixture of ethyl acetate and petroleum ether), yielding 51.4 mg of a white solid product, with a yield of 76%.

[0094] The structure and NMR spectral data of compound 3f are as follows:

[0095]

[0096] 1 H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 45.3 Hz, 1H), 7.49 – 7.27 (m, 4.4H), 7.18 (s, 1.6H), 7.05 (d, J = 7.0 Hz, 2H), 6.98 – 6.86 (m, 1H), 5.13(q, J = 12.6 Hz, 1H), 5.05 – 4.86 (m, 2H), 3.76 – 3.53 (m, 2H), 2.28 (tt, J =19.4, 8.1 Hz, 1H), 2.20 – 2.07 (m, 3H), 1.98 – 1.76 (m, 3H). 13 C NMR (101 MHz, CDCl3) δ 168.50, 168.47, 155.1, 154.9, 139.9, 138.9, 136.8, 136.7, 136.6,128.4, 128.1, 127.9, 127.7, 127.5, 127.2, 125.9, 125.8, 120.1, 119.8, 66.8,66.5, 61.0, 60.6, 47.5, 47.1, 35.7, 34.7, 24.4, 24.3, 23.4, 22.8.

[0097] Example 7

[0098] Preparation of N-benzyloxycarbonyl-2-(naphth-2-yl)pyrrolidine (3g)

[0099] 73.6 mg (0.2 mmol) of N-benzyloxycarbonylalanine phthalimide ester, 46.2 mg (0.3 mmol) of 2-naphthylethylene, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide were added to a 10 mL dry Schlenk tube. The Schlenk stopcock was tightened, and the tube was stirred at room temperature for 24 h under 395 nm LED illumination. After the reaction was complete, the reaction solution was transferred to a separatory funnel with ethyl acetate, 5 mL of water was added, and the mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated sodium chloride solution. The solvent was removed by vacuum distillation. The crude product was separated by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a mixture of ethyl acetate and petroleum ether at a volume ratio of 1:20) to obtain 45.7 mg of a colorless liquid product, with a yield of 69%.

[0100] The structure and NMR spectral data of compound 3g are as follows:

[0101]

[0102] 1 H NMR (400 MHz, CDCl3) δ 7.91 – 7.71 (m, 3H), 7.60 (d, J = 15.7 Hz,1H), 7.53 – 7.28 (m, 5H), 7.10 (t, J = 6.9 Hz, 0.6H), 6.97 (t, J = 7.1 Hz,1.2H), 6.80 (d, J = 7.1 Hz, 1.2H), 5.25 – 4.88 (m, 3H), 3.88 – 3.62 (m, 2H), 2.50 – 2.29 (m, 1H), 2.07 – 1.85 (m, 3H). 13 C NMR (101 MHz, CDCl3) δ 155.1,154.9, 141.6, 140.8, 137.0, 136.6, 136.5, 133.3, 132.5, 128.5, 128.4, 128.2,128.0, 127.9, 127.8, 127.5, 127.4, 127.2, 126.1, 125.9, 125.5, 125.4, 124.0,123.9, 123.8, 66.7, 66.6, 61.4, 61.2, 47.7, 47.2, 35.7, 34.6, 23.6, 23.0.

[0103] Example 8

[0104] Preparation of N-benzyloxycarbonyl-2-methyl-2-phenylpyrrolidine (3h)

[0105] 73.6 mg (0.2 mmol) of N-benzyloxycarbonylalanine phthalimide ester, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide were added to a 10 mL dry Schlenk tube. Finally, 35.4 mg (0.3 mmol) of α-methylstyrene was added, and the tube was stirred at room temperature under 395 nm LED illumination for 30 h. After the reaction was complete, the reaction mixture was transferred to a separatory funnel with ethyl acetate, 5 mL of water was added, and the mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated sodium chloride solution. The solvent was removed by vacuum distillation. The crude product was separated by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a 1:20 mixture of ethyl acetate and petroleum ether), yielding 31.3 mg of a colorless liquid product, with a yield of 53%.

[0106] The structure and NMR spectral data of compound 3h are as follows:

[0107]

[0108] 1 H NMR (400 MHz, CDCl3) δ 7.46 – 7.08 (m, 9H), 6.78 (d, J = 6.9 Hz,1H), 5.20 – 5.05 (m, 1H), 5.03 – 4.84 (m, 1H), 3.86 – 3.63 (m, 2H), 2.16 –2.00 (m, 2H), 1.96 – 1.67 (m, 5H). 13 C NMR (101 MHz, CDCl3) δ 154.9, 153.8,147.6, 146.4, 137.2, 136.5, 128.4, 128.2, 128.0, 127.8, 127.33, 127.28,126.3, 126.2, 124.9, 124.8, 66.5, 66.2, 66.1, 65.4, 49.3, 48.4, 45.9, 44.5,25.8, 25.5, 22.0, 21.9.

[0109] Example 9

[0110] Preparation of N-benzyloxycarbonyl-3-methyl-2-(4-methoxyphenyl)pyrrolidine (3i)

[0111] 73.6 mg (0.2 mmol) of N-benzyloxycarbonylalanine phthalimide ester, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide were added to a 10 mL dry Schlenk tube. Finally, 44.4 mg (0.3 mmol) of anisene was added. The Schlenk stopcock was tightened, and the tube was stirred at room temperature for 24 h under 395 nm LED illumination. After the reaction was complete, the reaction mixture was transferred to a separatory funnel with ethyl acetate, 5 mL of water was added, and the mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated sodium chloride solution. The solvent was removed by vacuum distillation. The crude product was separated by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a 1:20 mixture of ethyl acetate and petroleum ether), yielding 46.2 mg of a colorless liquid product, with a yield of 71%.

[0112] The structure and NMR spectral data of compound 3i are as follows:

[0113]

[0114] 1 H NMR (400 MHz, CDCl3) δ 7.55 – 7.29 (m, 2.5H), 7.24 – 7.03 (m, 3.5H), 6.97 – 6.70 (m, 3H), 5.26 – 4.80 (m, 2.1H), 4.40 – 4.16 (m, 0.9H), 3.98 – 3.71 (m, 4H), 3.68 – 3.56 (m, 1H), 2.19 – 1.99 (m, 2H), 1.70 – 1.48(m, 1.5H), 1.13 – 1.03 (m, 2.5H). 13 C NMR (101 MHz, CDCl3) δ 158.4, 155.2,154.8, 136.6, 135.9, 128.5, 128.4, 128.1, 128.0, 127.9, 127.8, 127.4, 127.2,126.8, 113.8, 113.7, 68.5, 68.3, 66.6, 66.5, 55.2, 47.1, 46.6, 44.4, 43.3,31.9, 31.5, 17.7, 17.5.

[0115] Example 10

[0116] Preparation of N-tert-butoxycarbonyl-2-(4-methoxyphenyl)pyrrolidine (3j)

[0117] To a 10 mL dry Schlenk tube, add 66.8 mg (0.2 mmol) of N-tert-butoxycarbonylalanine phthalimide ester, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide. Finally, add 40.2 mg (0.3 mmol) of 4-methoxystyrene, tighten the Schlenk stopcock, and stir at room temperature for 24 h under 395 nm LED illumination. After the reaction is complete, transfer the reaction solution to a separatory funnel with ethyl acetate, add 5 mL of water, extract with ethyl acetate, combine the organic phases, wash with saturated sodium chloride solution, remove the solvent under reduced pressure, and separate the crude product by column chromatography (using a 300-400 mesh silica gel column, with an eluent of 1:20 ethyl acetate and petroleum ether), yielding 39.9 mg of a colorless liquid product, with a yield of 72%.

[0118] The structure and NMR spectral data of compound 3j are as follows:

[0119]

[0120] 1 H NMR (400 MHz, CDCl3) δ 7.07 (d, J = 7.5 Hz, 2H), 6.83 (d, J = 8.4Hz, 2H), 4.96 – 4.56 (m, 1H), 3.79 (s, 3H), 3.66 – 3.42 (m, 2H), 2.35 – 2.18(m, 1H), 1.96 – 1.74 (m, 3H), 1.35 – 1.12 (m, 9H). 13 C NMR (101 MHz, CDCl3) δ158.1, 154.6, 137.2, 127.1, 126.6, 126.4, 113.9, 113.7, 113.4, 79.1, 60.7,60.1, 55.2, 47.3, 47.0, 36.0, 34.8, 28.5, 28.4, 28.2, 23.4, 23.1.

[0121] Example 11

[0122] Preparation of N-acetyl-2-(4-methoxyphenyl)pyrrolidine (3k)

[0123] Add 55.2 mg (0.2 mmol) of N-acetylalanine phthalimide, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide to a 10 mL dry Schlenk tube. Finally, add 40.2 mg (0.3 mmol) of 4-methoxystyrene. Tighten the Schlenk stopcock and stir at room temperature for 24 h under 395 nm LED illumination. After the reaction is complete, transfer the reaction solution to a separatory funnel with ethyl acetate, add 5 mL of water, extract with ethyl acetate, combine the organic phases, wash with saturated sodium chloride solution, remove the solvent under reduced pressure, and separate the crude product by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a 1:10 mixture of ethyl acetate and petroleum ether), to obtain 22.4 mg of colorless liquid product, with a yield of 51%.

[0124] The 3k structure and NMR spectral data of compound are as follows:

[0125]

[0126] 1 H NMR (400 MHz, CDCl3) δ 7.22 – 7.01 (m, 2H), 6.92 – 6.77 (m, 2H), 5.16 (d, J = 7.3 Hz, 0.2H), 4.85 (d, J = 7.9 Hz, 0.6H), 3.88 – 3.51 (m, 5H), 3.39 – 3.10 (m, 0.2H), 2.42 – 2.15 (m, 1H), 2.14 – 2.05 (m, 1H), 2.03 – 1.75 (m, 5H). 13 C NMR (101 MHz, CDCl3) δ 170.2, 169.1, 158.6, 158.2, 135.1, 134.9,126.5, 126.4, 114.0, 113.6, 61.7, 59.5, 55.20, 55.17, 48.2, 46.7, 36.3, 34.0,23.6, 22.8, 22.5, 21.8.

[0127] Example 12

[0128] Preparation of N-benzoyl-2-(4-methoxyphenyl)pyrrolidine (3l)

[0129] To a 10 mL dry Schlenk tube, add 67.6 mg (0.2 mmol) of N-benzoylalanine phthalimide, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide. Finally, add 40.2 mg (0.3 mmol) of 4-methoxystyrene, tighten the Schlenk stopcock, and stir at room temperature for 24 h under 395 nm LED illumination. After the reaction is complete, transfer the reaction solution to a separatory funnel with ethyl acetate, add 5 mL of water, extract with ethyl acetate, combine the organic phases, wash with saturated sodium chloride solution, remove the solvent under reduced pressure, and separate the crude product by column chromatography (using a 300-400 mesh silica gel column, with an eluent of 1:10 ethyl acetate and petroleum ether), yielding 29.8 mg of a colorless liquid product, with a yield of 53%.

[0130] The structure and NMR spectral data of compound 3l are as follows:

[0131]

[0132] 1 H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 5.3 Hz, 1H), 7.40 (d, J = 5.6Hz, 1.5H), 7.25 (d, J = 6.4 Hz, 1.5H), 7.17 (s, 2H), 6.93 (d, J = 8.3 Hz,1H), 6.87 (d, J = 8.2 Hz, 1H), 6.79 (d, J = 8.3 Hz, 1H), 5.29 (t, J = 6.4 Hz,0.5H), 4.83 (d, J = 6.6 Hz, 0.5H), 4.02 – 3.54 (m, 5H), 2.46 – 2.34 (m,0.5H), 2.31 – 2.16 (m, 0.5H), 2.03 – 1.74 (m, 3H). 13 C NMR (101 MHz, CDCl3) δ170.8, 169.8, 158.4, 137.1, 137.0, 135.9, 135.3, 130.0, 129.3, 128.1, 127.8,127.4, 126.8, 126.62, 126.55, 113.84, 113.80, 62.9, 60.4, 55.2, 50.9, 46.9,35.8, 34.7, 25.2, 21.6.

[0133] Example 13

[0134] Preparation of N-p-toluenesulfonyl-2-(4-methoxyphenyl)pyrrolidine (3m)

[0135] 77.6 mg (0.2 mmol) of N-toluenesulfonyl alanine phthalimide ester, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide were added to a 10 mL dry Schlenk tube. Finally, 40.2 mg (0.3 mmol) of 4-methoxystyrene was added. The Schlenk stopcock was tightened, and the tube was stirred at room temperature for 24 h under 395 nm LED illumination. After the reaction was complete, the reaction mixture was transferred to a separatory funnel with ethyl acetate, 5 mL of water was added, and the mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated sodium chloride solution. The solvent was removed by vacuum distillation. The crude product was separated by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a 1:10 mixture of ethyl acetate and petroleum ether), yielding 39.7 mg of a colorless liquid product, with a yield of 60%.

[0136] The 3m structure and NMR spectral data of the compound are as follows:

[0137]

[0138] 1 H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.1 Hz, 2H), 7.27 (d, J = 8.2Hz, 2H), 7.22 (d, J = 8.6 Hz, 2H), 6.83 (d, J = 8.5 Hz, 2H), 4.72 (dd, J =7.7, 3.7 Hz, 1H), 3.79 (s, 3H), 3.65 – 3.55 (m, 1H), 3.40 (dt, J = 9.9, 7.3Hz, 1H), 2.42 (s, 3H), 2.00 – 1.73 (m, 3H), 1.65 (dp, J = 12.1, 4.8 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 158.5, 143.1, 135.1, 129.5, 127.4, 127.2, 113.6,62.7, 55.2, 49.2, 35.7, 23.9, 21.5.

[0139] Example 14

[0140] Preparation of N-benzyloxycarbonyl-5-methyl-2-(4-methoxyphenyl)pyrrolidine (3n)

[0141] 76.4 mg (0.2 mmol) of N-benzyloxycarbonyl-3-methylalanine phthalimide ester, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide were added to a 10 mL dry Schlenk tube. Finally, 40.2 mg (0.3 mmol) of 4-methoxystyrene was added. The Schlenk stopcock was tightened, and the tube was stirred at room temperature for 24 h under 395 nm LED illumination. After the reaction was complete, the reaction mixture was transferred to a separatory funnel with ethyl acetate, 5 mL of water was added, and the mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated sodium chloride solution. The solvent was removed by vacuum distillation. The crude product was separated by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a 1:20 mixture of ethyl acetate and petroleum ether), yielding 44.9 mg of a colorless liquid product, with a yield of 69%.

[0142] The structure and NMR spectral data of compound 3n are as follows:

[0143]

[0144] 1 H NMR (400 MHz, CDCl3) δ 7.43 – 7.28 (m, 2H), 7.25 – 7.11 (m, 2.5H), 7.10 – 6.97 (m, 1.5H), 6.90 – 6.78 (m, 3H), 5.22 – 4.81 (m, 3H), 4.37 – 4.09 (m, 1H), 3.85 – 3.75 (m, 3H), 2.49 – 2.34 (m, 0.6H), 2.30 – 1.98 (m, 1.3H), 1.97 – 1.86 (m, 0.3H), 1.79 – 1.49 (m, 2H), 1.48 – 1.36 (m, 1H), 1.32 (d, J =6.3 Hz, 1.3H), 1.25 (d, J = 6.3 Hz, 0.7H). 13C NMR (101 MHz, CDCl3) δ 158.29,158.26, 155.3, 154.4, 137.0, 136.8, 136.7, 135.8, 128.4, 128.00, 127.96,127.8, 127.3, 127.2, 126.8, 126.24, 126.22, 113.74, 113.66, 113.6, 66.6,66.1, 61.0, 60.8, 55.24, 55.22, 55.19, 54.3, 53.7, 32.7, 31.8, 29.9, 28.9, 20.7, 19.6.

[0145] Example 15

[0146] Preparation of N-benzyloxycarbonyl tetrahydroindenepyrrolidine (5a)

[0147] 73.6 mg (0.2 mmol) of N-benzyloxycarbonylalanine phthalimide ester, 12.5 mg (0.05 mmol) of diphenyl phosphate, and 2 mL of dimethyl sulfoxide were added to a 10 mL dry Schlenk tube. Finally, 34.8 mg (0.3 mmol) of indene was added, the Schlenk stopcock was tightened, and the tube was stirred at room temperature for 24 h under 395 nm LED illumination. After the reaction was complete, the reaction mixture was transferred to a separatory funnel with ethyl acetate, 5 mL of water was added, and the mixture was extracted with ethyl acetate. The organic phases were combined and washed with saturated sodium chloride solution. The solvent was removed by vacuum distillation. The crude product was separated by column chromatography (the column was packed with 300-400 mesh silica gel, and the eluent was a 1:20 mixture of ethyl acetate and petroleum ether), yielding 32.2 mg of a colorless liquid product, with a yield of 55%.

[0148] The structure and NMR spectral data of compound 5a are as follows:

[0149]

[0150] 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 6.6 Hz, 0.5H), 7.47 (d, J = 7.2Hz, 1H), 7.44 – 7.28 (m, 4.5H), 7.28 – 7.05 (m, 3H), 5.44 – 5.25 (m, 2H), 5.19 (q, J = 12.5 Hz, 1H), 3.69 – 3.50 (m, 1H), 3.49 – 3.36 (m, 1H), 3.22 –3.02 (m, 2H), 2.77 (d, J = 14.0 Hz, 1H), 2.17 – 2.05 (m, 1H), 1.72 – 1.54 (m, 1H). 13 C NMR (101 MHz, CDCl3) δ 155.5, 155.0, 143.4, 142.8, 141.8, 141.6,137.0, 136.7, 128.5, 128.4, 128.2, 128.0, 127.83, 127.76, 127.0, 126.9,126.8, 126.2, 125.1, 124.9, 67.0, 66.8, 66.7, 66.2, 46.7, 46.4, 42.3, 41.3,36.3, 36.1, 31.1, 30.2.

[0151] In summary, the preparation method described in this invention is characterized by mild conditions and simple operation. The synthesis reaction of the pyrrolidine compound described in this invention involves few side reactions, high yield, simple post-processing, and low production cost, which is beneficial for large-scale industrial production.

[0152] The above description of the embodiments is only for the purpose of helping to understand the method and core ideas of the present invention. It should be noted that those skilled in the art can make several improvements and modifications to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims

1. A method for synthesizing a pyrrolidine compound, characterized in that, The synthesis method is as follows: Compound 1, aryl olefin, and protic acid were mixed in a solvent to obtain a mixed solution; The mixed solution was reacted at room temperature under continuous light irradiation to obtain a pyrrolidine compound; When the aryl olefin is compound 2, the pyrrolidine compound is obtained as compound 3. The synthetic route of the synthetic method is shown in the following formula: ； When the aryl olefin is compound 4, the pyrrolidine compound is obtained as compound 5. The synthetic route of the synthetic method is shown in the following formula: ； Among them, R 1 Indicates phenyl, methyl, or hydrogen; R 2 Indicates phenyl, methyl, or hydrogen; R 3 It represents phenyl, methyl, or hydrogen; PG represents one of benzyloxycarbonyl, tert-butoxycarbonyl, acetyl, benzoyl, and p-toluenesulfonyl; Ar represents one of phenyl, 4-methoxyphenyl, 4-methylphenyl, 3-methylphenyl, 3,5-dimethylphenyl, 4-tert-butylphenyl, 3-methoxyphenyl, 3,4-dimethoxyphenyl, 2-methoxyphenyl, 4-dimethylaminophenyl, 4-fluorophenyl, 4-acetaminophenyl, naphth-2-yl, and benzofuran-5-yl.

2. The synthesis method according to claim 1, characterized in that, Compound 1 is one of N-benzyloxycarbonylalanine phthalimide ester, N-tert-butoxycarbonylalanine phthalimide ester, N-acetylalanine phthalimide ester, N-benzoylalanine phthalimide ester, N-toluenesulfonylalanine phthalimide ester, N-benzyloxycarbonyl-2-methylalanine phthalimide ester, and N-benzyloxycarbonyl-2-phenylalanine phthalimide ester.

3. The synthesis method according to claim 1, characterized in that, The aryl olefin is one of styrene, 4-methoxystyrene, 4-methylstyrene, 3-methylstyrene, 3,5-dimethylstyrene, 4-tert-butylstyrene, 3-methoxystyrene, 3,4-dimethoxystyrene, 2-methoxystyrene, 4-dimethylaminostyrene, 4-acetoxystyrene, 4-fluorostyrene, 4-acetaminostyrene, 2-naphthylene, 5-vinylbenzofuran, α-methylstyrene, β-methylstyrene, 1,1-diphenylethylene, 1,2-diphenylethylene, and indene.

4. The synthesis method according to claim 1, characterized in that, The protic acid is one of concentrated hydrochloric acid, trifluoroacetic acid, acetic acid, phosphoric acid, diphenyl phosphate, dibenzyl phosphate, ditert-butyl phosphate, naphthol phosphate, and monophenyl phosphate.

5. The synthesis method according to claim 1, characterized in that, The solvent is any one or more of dichloromethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, methanol, hexafluoroisopropanol, acetone, and ethyl acetate.

6. The synthesis method according to claim 1, characterized in that, The molar ratio of compound 1, aryl olefin and protic acid is 1 : (1~3) : (0.05~1).

7. The synthesis method according to claim 1, characterized in that, In the mixed solution, the concentration of compound 1 is 0.05~0.3 mol / L.

8. The synthesis method according to any one of claims 1-7, characterized in that, The illumination conditions are: wavelength 365~420 nm, power 3~30 W.

9. The synthesis method according to claim 5, characterized in that, The reaction time is 12-30 h.

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