A method for preparing isoindoline compounds using α-amino acetal as substrate

Abstract

The present invention discloses a method for preparing isoindoline compounds using α-amino acetal as a substrate, the method comprising the following steps: adding an aryl α-amino acetal, an olefin coupling reagent, a catalyst, an oxidant, a base, and a ligand to a reaction solvent and stirring at 105° C. for 36 hours. The obtained reaction solution is desolvated and purified to obtain an isoindoline compound. The method for preparing isoindoline compounds using α-amino acetal as a substrate of the present invention prepares a series of isoindoline compounds, all of which are new and unreported substances, and the preparation method of such substances has not been reported. The method of the present invention has good substrate universality, uses a relatively cheap palladium catalyst to replace a rhodium catalyst, improves atom economy, uses pyridine ligands for collaborative catalysis, and directly and efficiently realizes a molecular C-H bond alkenylation / cyclization tandem reaction using a one-pot method.

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemical synthesis, and in particular relates to a method for constructing an isoindoline skeleton by using α-amino acetal as a substrate. Background Art

[0002] Nitrogen heterocycles are a common class of compounds found in natural products, bioactive molecules, and functional materials. Isoindoline heterocyclic compounds, with their diverse biological activities, form the core skeletons of many natural products, pharmaceuticals, and biologically important molecules. Currently, the isoindoline skeleton is primarily found in various natural products and pharmaceutical compounds with antipsychotic and antifungal activity, such as selective PPAR agonists, which play a key role in regulating cell differentiation, development, metabolism, and tumorigenesis in higher organisms. In addition, molecules such as endothelin receptor antagonists, molecular chaperone HSP90 inhibitors, and dipeptidyl peptidase inhibitors are also found. Chemists have also discovered that some isoindoline derivatives exhibit strong blue fluorescence and can be used to prepare a range of polymers, demonstrating their considerable potential in materials science.

[0003] Due to the potential applications of isoindole compounds, the development of efficient synthetic methods for their derivatives has attracted particular attention. However, many current research methods still have many shortcomings, such as harsh reaction conditions, environmental unfriendliness, and low atom economy. Therefore, exploring new strategies for the synthesis of biologically active isoindole derivatives is a major challenge facing the field of organic chemistry today. Summary of the Invention

[0004] To overcome the shortcomings and deficiencies of the prior art, the present invention provides a method for preparing isoindoline compounds using α-amino acetal as a substrate. The method of the present invention, using α-amino acetal as a substrate, prepares a series of isoindoline compounds, all of which are novel and previously unreported, and methods for preparing such compounds have also been previously unreported. These heterocyclic isoindoline compounds, due to their diverse biological activities, constitute the core frameworks of many natural products, pharmaceutical products, and biologically important molecules. The method of the present invention has good substrate universality, utilizes a relatively inexpensive palladium catalyst instead of a rhodium catalyst, improving atom economy, and utilizes a pyridine ligand for cooperative catalysis, directly and efficiently achieving a molecular C-H bond olefination / cyclization tandem reaction in a one-pot process.

[0005] In order to solve the technical problem of the present invention, the technical solution proposed is: a method for preparing isoindoline compounds using α-amino acetal as a substrate,

[0006] (1) An aromatic α-amino acetal (Compound I), an olefin coupling reagent (Compound II), a catalyst, an oxidant, a base, and a ligand are added to a reaction solvent and stirred at 105° C. for 36 hours to obtain a reaction solution. The catalyst is palladium acetate, the oxidant is 1,4-benzoquinone and silver carbonate, the base is sodium acetate, the ligand is 4-trifluoromethylpyridine, and the reaction solvent is 1,2-dichloroethane.

[0007] The exemplary chemical equation for the reaction is:

[0008]

[0009] In the reaction formula, compound I is an aromatic α-amino acetal, R 1 Any one selected from a hydrogen atom, a fluorine atom, a methyl group, a trifluoromethyl group, a tert-butyl group, a methoxy group, and a phenyl group;

[0010] Compound II is an olefin coupling reagent, R 2 Any one selected from ester group, phenyl group, substituted aryl group, and benzoyl group;

[0011] Compound III is an isoindoline compound;

[0012] (2) After the reaction is complete as monitored by TLC, the reaction solution obtained in step (1) is freed from the solvent and purified to obtain an isoindoline compound (Compound III).

[0013] Preferably, the aromatic α-amino acetal is selected from N-(2,2-dimethoxy-1-phenylethyl)-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(p-tolyl)ethyl)-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(4-methoxyphenyl)ethyl)-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-4-nitrobenzenesulfonamide, N-(1-(4-(tert-butyl)phenyl)-2,2-dimethoxyethyl)-4-nitrobenzenesulfonamide, N-(1-([1,1'-biphenyl]-4-yl)-2,2-dimethoxyethyl)-4-nitrobenzenesulfonamide, )-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(m-tolyl)ethyl)-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(3-methoxyphenyl)ethyl)-4-nitrobenzenesulfonamide, N-(1-(3-fluorophenyl)-2,2-dimethoxyethyl)-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(o-tolyl)ethyl)-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(2-methoxyphenyl)ethyl)-4-nitrobenzenesulfonamide, and N-(2,2-dimethoxy-1-(naphthalen-2-yl)ethyl)-4-nitrobenzenesulfonamide.

[0014] Preferably, the olefin coupling reagent is selected from any one of butyl acrylate, methyl acrylate, ethyl acrylate, tert-butyl acrylate, benzyl acrylate, phenyl acrylate, styrene, 1-methyl-4-vinylbenzene, 1-fluoro-4-vinylbenzene, 1-chloro-4-vinylbenzene, 1-(trifluoromethyl)-3-vinylbenzene, 1-phenylprop-2-en-1-one, and (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl acrylate.

[0015] Preferably, in step (1), the molar volume ratio of the aromatic α-amino acetal, olefin coupling reagent, catalyst, oxidant (1,4-benzoquinone / silver carbonate), base, ligand, and reaction solvent is 0.2 mmol: 0.8 mmol: 0.02 mmol: 0.2 mmol / 0.5 mmol: 0.8 mmol: 0.06 mmol: 2.0 mL.

[0016] Preferably, in step (2), the solvent removal is to remove the reaction solvent using a vacuum rotary evaporator, and the purification is to purify by column chromatography, with a developing solvent system of petroleum ether / ethyl acetate = 10 / 1 (volume ratio).

[0017] Preferably, the reaction formula of the method for preparing isoindoline compounds using α-amino acetal as a substrate is any one of the following:

[0018]

[0019]

[0020] Compared with the shortcomings and deficiencies of the prior art, the present invention has the following beneficial effects:

[0021] (1) The method of preparing isoindoline compounds using α-amino acetal as a substrate of the present invention prepares a series of isoindoline compounds, all of which are completely new and unreported substances, and the preparation method of such substances has also not been reported.

[0022] Due to their diverse biological activities, isoindoline heterocyclic compounds form the core skeletons of numerous natural products, pharmaceuticals, and biologically important molecules. Currently, the isoindoline skeleton is primarily found in various natural products and pharmaceutical compounds with antipsychotic and antifungal activity, such as selective PPAR agonists, which play a key role in regulating cell differentiation, development, metabolism, and tumorigenesis in higher organisms. In addition, there are molecules such as endothelin receptor antagonists, molecular chaperone HSP90 inhibitors, and dipeptidyl peptidase inhibitors. Chemists have also discovered that some isoindoline derivatives exhibit strong blue fluorescence and can be used to prepare a range of polymers, demonstrating their considerable potential in materials science.

[0023] (2) Using pyridine ligands as co-catalysts, a one-pot method was used to directly and efficiently achieve a molecular C-H bond olefination / cyclization tandem reaction.

[0024] (3) The reaction has good substrate universality, and aromatic α-amino acetals with different substituents and a series of alkenes can provide the desired target products in good yields.

[0025] (4) The results of base screening showed (Examples 1, 12 and 13): the yield of sodium acetate as a base was 87%, while the reaction yields decreased significantly when sodium carbonate and sodium bicarbonate were used as oxidants, namely 51% and 47%, respectively. The results of reaction solvent screening showed (Examples 1, 8, 9, 10 and 11): when 1,2-dichloroethane was replaced by other solvents, such as dichloromethane, 1,4-dioxane and tetrahydrofuran, the reaction yields were 54%, 13% and 17%, respectively. When acetonitrile was used as the replacement, no reaction occurred. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The present invention will be further described below with reference to the accompanying drawings.

[0027] Figure 1 is the hydrogen nuclear magnetic resonance spectrum of compound 3 in Example 1 of the present invention;

[0028] Figure 2 is the carbon NMR spectrum of compound 3 in Example 1 of the present invention; DETAILED DESCRIPTION

[0029] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0030] Example 1

[0031] (1) In a 10 mL Shrek tube equipped with a magnet, add 0.2 mmol N-(2,2-dimethoxy-1-phenylethyl)-4-nitrobenzenesulfonamide, 0.8 mmol butyl acrylate, 0.02 mmol palladium acetate, 0.5 mmol silver carbonate, 0.8 mmol sodium acetate, and 0.2 mmol 1,4-benzoquinone. Then, add 2.0 mL of 1,2-dichloroethane and 0.06 mmol 4-trifluoromethylpyridine in air using a syringe. Cover the tube. Stir the reaction at 105°C for 36 hours. The reaction equation is:

[0032]

[0033] (2) After the reaction was completed as monitored by TLC, the product was separated by column chromatography using a petroleum ether / ethyl acetate system (petroleum ether / ethyl acetate (volume ratio) = 10 / 1) as the eluent. The product was a white solid (Compound 3) with a yield of 87%.

[0034] Compound 3 was characterized and the results were as follows Figures 1-2 As shown, the characterization results showed that compound 3 was (E)-butyl 2-(3-(dimethoxymethyl)-2-((4-nitrophenyl)sulfonyl)isoindol-1-ylidene)acetate.

[0035] Example 2

[0036] (1) In a 10 mL Shrek tube equipped with a magnet, add 0.2 mmol N-(2,2-dimethoxy-1-(p-tolyl)ethyl)-4-nitrobenzenesulfonamide, 0.8 mmol butyl acrylate, 0.02 mmol palladium acetate, 0.5 mmol silver carbonate, 0.8 mmol sodium acetate, and 0.2 mmol 1,4-benzoquinone. Then, add 2.0 mL of 1,2-dichloroethane and 0.06 mmol 4-trifluoromethylpyridine in air using a syringe, and cover the tube. Stir the reaction at 105°C for 36 hours. The reaction equation is:

[0037]

[0038] (2) After the reaction was completed as monitored by TLC, the product was separated by column chromatography using a petroleum ether / ethyl acetate system (petroleum ether / ethyl acetate (volume ratio) = 10 / 1) as the eluent. The product was a white solid (Compound 5) with a yield of 85%.

[0039] Compound 5 was characterized, and the results are shown in the following data. The characterization results indicate that compound 5 is butyl (E)-2-(3-(dimethoxymethyl)-6-methyl-2-((4-nitrophenyl)sulfonyl)isoindol-1-ylidene)acetate.

[0040] 1 H NMR(400MHz, CDCl3): δ8.69(s,1H),8.27–8.25(m,2H),7.98–7.96(m,2H), 7.38(d,J=7.8,1H),7.21(d,J=7.6,1H),6.50(s,1H),5.20(d,J=2.7,1H),4 .84(d,J=2.7,1H),4.17(td,J=6.8,2.1Hz,2H),3.55(s,3H),3.48(s,3H), 2.34(s,3H),1.73–1.66(m,2H),1.48–1.39(m,2H),0.98(t,J=7.4,3H)ppm; 13C NMR (100MHz, CDCl3): δ166.1,151.3,150.5,142.8,138.8,135.1,133.0,132.4,128.7, 127.9,124.3,123.7,107.2,101.4,67.7,64.4,59.2,56.5,30.7,21.6,19.2,13.8ppm.

[0041] Example 3

[0042] (1) In a 10 mL Shrek tube equipped with a magnet, add 0.2 mmol N-(1-([1,1'-biphenyl]-4-yl)-2,2-dimethoxyethyl)-4-nitrobenzenesulfonamide, 0.8 mmol butyl acrylate, 0.02 mmol palladium acetate, 0.5 mmol silver carbonate, 0.8 mmol sodium acetate, and 0.2 mmol 1,4-benzoquinone. Then, add 2.0 mL of 1,2-dichloroethane and 0.06 mmol 4-trifluoromethylpyridine in air using a syringe, and cover the tube. Stir the reaction at 105°C for 36 hours. The reaction equation is:

[0043]

[0044] (2) After the reaction was complete as monitored by TLC, the product was separated by column chromatography using a petroleum ether / ethyl acetate system (petroleum ether / ethyl acetate (volume ratio) = 10 / 1) as the eluent. The product was a white solid (Compound 7) with a yield of 65%.

[0045] Compound 7 was characterized, and the results are shown in the following data. The characterization results indicate that compound 7 is butyl (E)-2-(3-(dimethoxymethyl)-2-((4-nitrophenyl)sulfonyl)-6-phenylisoindol-1-ylidene)acetate.

[0046] 1 H NMR (400MHz, CDCl3): δ9.18 (d, J = 1.7Hz, 1H), 8.31–8.27 (m, 2H), 8.03–7.99 (m, 2H), 7. 63(dd,J=8.0,1.7Hz,1H),7.57–7.54(m,3H),7.44–7.40(m,2H),7.35–7.31(m,1H),6.5 6(s,1H),5.28(d,J=2.6Hz,1H),4.92(d,J=2.6Hz,1H),4.17(td,J=6.7,3.4Hz,2H),3.6 0(s,3H),3.54(s,3H),1.72–1.65(m,2H),1.48–1.38(m,2H),0.97(d,J=7.4Hz,3H)ppm;13 C NMR (100MHz, CDCl3): δ166.0,151.0,150.6,142.8,142.0,140.3,136.7,133.6,130.2,128.8,128 .7,127.6,127.2,126.3,124.4,124.3,107.2,101.9,67.8,64.4,59.3,56.7,30.7,19.2,13.8ppm.

[0047] Example 4

[0048] (1) In a 10 mL Shrek tube equipped with a magnet, add 0.2 mmol of N-(2,2-dimethoxy-1-(naphthalen-2-yl)ethyl)-4-nitrobenzenesulfonamide, 0.8 mmol of butyl acrylate, 0.02 mmol of palladium acetate, 0.5 mmol of silver carbonate, 0.8 mmol of sodium acetate, and 0.2 mmol of 1,4-benzoquinone. Then, add 2.0 mL of 1,2-dichloroethane and 0.06 mmol of 4-trifluoromethylpyridine in air using a syringe, and cover the tube. Stir the reaction at 105°C for 36 hours. The reaction equation is:

[0049]

[0050] (2) After the reaction was complete as monitored by TLC, the product was separated by column chromatography using a petroleum ether / ethyl acetate system (petroleum ether / ethyl acetate (volume ratio) = 10 / 1) as the eluent. The product was a white solid (Compound 9) with a yield of 81%.

[0051] Compound 9 was characterized, and the results are shown in the following data. The characterization results indicate that compound 9 is (E)-butyl 2-(3-(dimethoxymethyl)-2-((4-nitrophenyl)sulfonyl)-2,3-dihydro-1H-benzo[f]isoindol-1-yl)acetate.

[0052] 1 H NMR (400MHz, CDCl3): δ9.56(s,1H),8.24–8.21(m,2H),8.00–7.96(m,2H),7.92 (d,J=8.2Hz,2H),7.80(d,J=8.4Hz,1H),7.53–7.43(m,2H),6.63(s,1H),5.40( d,J=2.8Hz,1H),4.90(d,J=2.7Hz,1H),4.22(d,J=6.7,2.4Hz,2H),3.61(s,3H) ,3.51(s,3H),1.77–1.70(m,2H),1.53–1.42(m,2H),1.00(t,J=7.4Hz,3H)ppm;13 CNMR (100MHz, CDCl3): δ166.2, 150.9, 150.5, 142.8, 134.2, 133.5, 133.2, 130.4, 129.9, 129.0 (d, J = 4.3Hz), 128 .6,128.0,127.8,126.4,124.4,122.8,107.4(d,J=11.4Hz),102.6,67.3,64.5,59.2,56.7,30.7,19.2,13.8ppm.

[0053] Example 5

[0054] (1) In a 10 mL Shrek tube equipped with a magnet, add 0.2 mmol N-(2,2-dimethoxy-1-phenylethyl)-4-nitrobenzenesulfonamide, 0.8 mmol ethyl acrylate, 0.02 mmol palladium acetate, 0.5 mmol silver carbonate, 0.8 mmol sodium acetate, and 0.2 mmol 1,4-benzoquinone. Then, add 2.0 mL of 1,2-dichloroethane and 0.06 mmol 4-trifluoromethylpyridine in air using a syringe. Cover the tube. Stir the reaction at 105°C for 36 hours. The reaction equation is:

[0055]

[0056] (2) After the reaction was complete as monitored by TLC, the product was separated by column chromatography using a petroleum ether / ethyl acetate system (petroleum ether / ethyl acetate (volume ratio) = 10 / 1) as the eluent. The product was a yellow solid (Compound 11) with a yield of 71%.

[0057] Compound 11 was characterized, and the results are shown in the following data. The characterization results indicate that compound 11 is ethyl (E)-2-(3-(dimethoxymethyl)-2-((4-nitrophenyl)sulfonyl)isoindol-1-ylidene)acetate.

[0058] 1 H NMR (400MHz, CDCl3): δ8.88(d,J=7.2Hz,1H),8.28–8.25(m,2H),8.00–7.96(m,2H),7.49(dd,J=7.5,1.2Hz,1H),7.36(dtd,J=20.3,7.4,1. 3Hz,2H),6.51(s,1H),5.24(d,J=2.7Hz,1H),4.86(d,J=2.7Hz,1H),4.27–4.18(m,2H),3.56(s,3H),3.48(s,3H),1.34(t,J=7.1Hz,3H)ppm; 13C NMR (100MHz, CDCl3): δ165.9,151.2,150.6,142.8,137.9,132.9,131.1,128. 8,128.6,127.7,124.4,124.0,107.1,101.7,67.9,60.4,59.1,56.6,14.3ppm.

[0059] Example 6

[0060] (1) In a 10 mL Shrek tube equipped with a magnet, add 0.2 mmol N-(2,2-dimethoxy-1-phenylethyl)-4-nitrobenzenesulfonamide, 0.8 mmol tert-butyl acrylate, 0.02 mmol palladium acetate, 0.5 mmol silver carbonate, 0.8 mmol sodium acetate, and 0.2 mmol 1,4-benzoquinone. Then, add 2.0 mL of 1,2-dichloroethane and 0.06 mmol 4-trifluoromethylpyridine in air using a syringe. Cover the tube. Stir the reaction at 105°C for 36 hours. The reaction equation is:

[0061]

[0062] (2) After the reaction was complete as monitored by TLC, the product was separated by column chromatography using a petroleum ether / ethyl acetate system (petroleum ether / ethyl acetate (volume ratio) = 10 / 1) as the eluent. The product was a white solid (Compound 13) with a yield of 89%.

[0063] Compound 13 was characterized, and the results are shown in the following data. The characterization results indicate that compound 13 is tert-butyl (E)-2-(3-(dimethoxymethyl)-2-((4-nitrophenyl)sulfonyl)isoindol-1-ylidene)acetate.

[0064] 1 H NMR (400MHz, CDCl3): δ8.79–8.77(m,1H),8.27–8.24(m,2H),7.99–7.96(m,2H),7.47(dd,J=7.3,1.3Hz,1H),7.38– 7.30(m,2H),6.46(s,1H),5.20(dd,J=2.7Hz,1H),4.83(d,J=2.8Hz,1H),3.56(s,3H),3.48(s,3H),1.53(s,9H)ppm; 13C NMR (100MHz, CDCl3): δ165.3,150.5,149.9,142.8,137.6,133.0,130.9,128. 7,127.5,124.3,124.0,107.1,104.3,80.6,67.7,59.1,56.6,28.2,26.9ppm.

[0065] Example 7

[0066] (1) In a 10 mL Shrek tube equipped with a magnet, add 0.2 mmol N-(2,2-dimethoxy-1-phenylethyl)-4-nitrobenzenesulfonamide, 0.8 mmol benzyl acrylate, 0.02 mmol palladium acetate, 0.5 mmol silver carbonate, 0.8 mmol sodium acetate, and 0.2 mmol 1,4-benzoquinone. Then, add 2.0 mL of 1,2-dichloroethane and 0.06 mmol 4-trifluoromethylpyridine in air using a syringe. Cover the tube. Stir the reaction at 105°C for 36 hours. The reaction equation is:

[0067]

[0068] (2) After the reaction was completed as monitored by TLC, the product was separated by column chromatography using a petroleum ether / ethyl acetate system (petroleum ether / ethyl acetate (volume ratio) = 10 / 1) as the eluent. The product was a white solid (Compound 15) with a yield of 87%.

[0069] Compound 15 was characterized, and the results are shown in the following data. The characterization results indicate that compound 15 is benzyl (E)-2-(3-(dimethoxymethyl)-2-((4-nitrophenyl)sulfonyl)isoindol-1-ylidene)acetate.

[0070] 1 H NMR (400MHz, CDCl3): δ8.90(d,J=7.4Hz,1H),8.25–8.22(m,2H),7.98–7.95(m,2H),7.51(d,J=6.5Hz,1H),7.41–7 .32(m,7H),6.55(s,1H),5.27(d,J=2.6Hz,1H),5.22(s,2H),4.87(d,J=2.7Hz,1H),3.57(s,3H),3.48(s,3H)ppm; 13C NMR (100MHz, CDCl3): δ165.7,151.7,150.6,142.7,138.0,136.0,132.8,128.8,128.7 ,128.6,128.3,128.2,127.9,124.4,124.1,107.1,100.9,68.0,66.2,59.1,56.7ppm.

[0071] Examples 8-13

[0072] The Examples 8-13 are substantially the same as the above Example 1, and the obtained products are the same, except that they are shown in Table 1 below:

[0073] Table 1 Comparison of implementation differences

[0074]

[0075] The results of base screening showed (Examples 1, 12 and 13): the yield of sodium acetate as the base was 87%, while the reaction yields decreased significantly when sodium carbonate and sodium bicarbonate were used as oxidants, namely 51% and 47%, respectively. The results of reaction solvent screening showed (Examples 1, 8, 9, 10 and 11): when 1,2-dichloroethane was replaced by other solvents, such as dichloromethane, 1,4-dioxane and tetrahydrofuran, the reaction yields were 54%, 13% and 17%, respectively. When acetonitrile was used as the replacement, the reaction did not occur.

[0076] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for preparing isoindoline compounds using α-amino acetal as a substrate, characterized in that: The following steps are involved: (1) adding an aromatic α-amino acetal (Compound I), an olefin coupling reagent (Compound II), a catalyst, an oxidant, a base, and a ligand to a reaction solvent and stirring at 105° C. for 36 hours to obtain a reaction solution; the catalyst is palladium acetate, the oxidant is 1,4-benzoquinone and silver carbonate, the base is sodium acetate, the ligand is 4-trifluoromethylpyridine, and the reaction solvent is 1,2-dichloroethane; the reaction route of the method is: In this reaction route, compound I is an aromatic α-amino acetal, R 1 Any one selected from a hydrogen atom, a fluorine atom, a methyl group, a trifluoromethyl group, a tert-butyl group, a methoxy group, and a phenyl group; Compound II is an olefin coupling reagent, R 2 Any one selected from ester group, phenyl group, substituted aryl group, and benzoyl group; Compound III is an isoindoline compound; (2) After the reaction is complete as monitored by TLC, the reaction solution obtained in step (1) is freed from the solvent and purified to obtain an isoindoline compound (Compound III); The aromatic α-amino acetal is selected from N-(2,2-dimethoxy-1-phenylethyl)-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(p-tolyl)ethyl)-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(4-methoxyphenyl)ethyl)-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(4-(trifluoromethyl)phenyl)ethyl)-4-nitrobenzenesulfonamide, N-(1-(4-(tert-butyl)phenyl)-2,2-dimethoxyethyl)-4-nitrobenzenesulfonamide, N-(1-([1,1'-biphenyl]-4-yl)-2,2-dimethoxyethyl)- Any one of 4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(m-tolyl)ethyl)-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(3-methoxyphenyl)ethyl)-4-nitrobenzenesulfonamide, N-(1-(3-fluorophenyl)-2,2-dimethoxyethyl)-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(o-tolyl)ethyl)-4-nitrobenzenesulfonamide, N-(2,2-dimethoxy-1-(2-methoxyphenyl)ethyl)-4-nitrobenzenesulfonamide, and N-(2,2-dimethoxy-1-(naphthalen-2-yl)ethyl)-4-nitrobenzenesulfonamide; The olefin coupling reagent is selected from any one of butyl acrylate, methyl acrylate, ethyl acrylate, tert-butyl acrylate, benzyl acrylate, phenyl acrylate, styrene, 1-methyl-4-vinylbenzene, 1-fluoro-4-vinylbenzene, 1-chloro-4-vinylbenzene, 1-(trifluoromethyl)-3-vinylbenzene, 1-phenylprop-2-ene-1-one, and (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl acrylate.

2. The method for preparing isoindoline compounds using α-amino acetal as a substrate according to claim 1, wherein In step (1), the molar volume ratio of the aromatic α-amino acetal, olefin coupling reagent, catalyst, oxidant 1,4-benzoquinone / silver carbonate, base, ligand, and reaction solvent is 0.2 mmol: 0.8 mmol: 0.02 mmol: 0.2 mmol / 0.5 mmol: 0.8 mmol: 0.06 mmol: 2.0 mL.

3. The method for preparing isoindoline compounds using α-amino acetal as a substrate according to claim 1, wherein In step (2), the solvent removal is performed by using a vacuum rotary evaporator to remove the reaction solvent, and the purification is performed by column chromatography, with the developing solvent system being petroleum ether / ethyl acetate in a volume ratio of 10 / 1.

4. The method for preparing isoindoline compounds using α-amino acetal as a substrate according to claim 1, wherein The reaction formula of the method for preparing isoindoline compounds using α-amino acetal as a substrate is any one of the following:

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