Chiral helical polyisocyanide catalysts modified by proline dipeptides and methods of preparation

Abstract

The application discloses a kind of chiral helical polyisocyanide catalysts modified by proline dipeptide and preparation method, the structural formula of the catalyst is as follows:Wherein, n=50~250.The preparation method is as follows, ester exchange is carried out by three proline chains and pentafluorophenol isocyanide to prepare monomer, and the monomer is initiated by Pd (II) catalyst to prepare chiral helical polymer, and then the tert-butyloxycarbonyl protecting group is removed to prepare chiral helical polyisocyanide catalyst with catalytic function.The proline dipeptide modified chiral helical polyisocyanide catalyst prepared by the application can be prepared by active controlled polymerization of corresponding monomer, the molecular weight is controllable, the molecular weight distribution is relatively narrow, and can be used for catalyzing asymmetric aldol and Michael addition reaction, and the preparation method is simple, environment-friendly, and the yield is high.

Description

Technical Field

[0001] This invention relates to the field of polymer materials, specifically to a chiral helical polyisocyanate catalyst modified with proline dipeptide and its preparation method. Background Technology

[0002] Helical structures are complex topological structures, but are essentially asymmetrical chiral structures. They are widely found in nature, from macroscopic plants and animals to microscopic molecular systems. From the backs of snails and the stems and leaves of spring grass to proteins and DNA in organisms, biological macromolecules all possess helical structures. Inspired by the unique functions of helical molecules in nature, chemists have attempted to mimic nature, and the types and functions of artificially synthesized helical polymers are becoming increasingly diverse, with applications expanding into ever wider fields.

[0003] Chiral helical polymers, due to their optical activity, have wide applications in chiral recognition, chiral separation, chiral sensing, asymmetric catalysis, and liquid crystal materials. Asymmetric catalysis is one of the important methods for constructing chiral centers in molecules, and it has wide applications in the synthesis of pharmaceutical intermediates and natural products. Traditional asymmetric catalysts mainly include three systems: metal and chiral ligands, enzymes, and small organic molecules. Compared with asymmetric metal catalysis and enzyme catalysis, small organic molecule catalysis has the advantages of mild reaction conditions, no transition metal residues, and a wide range of applicable substrates. However, its disadvantages include the generally large amount of small organic molecule catalysts used and the difficulty in recycling them. To overcome the shortcomings of organic catalysis, many chemists have developed asymmetric catalytic systems supported on organic catalysts in recent years. Compared with traditional supports such as silica gel and polymers, helical polymers have many advantages as supports for small organic molecule catalysts: appropriately structured helical polymers can provide microenvironments that small molecules do not have for asymmetric reactions, thereby enabling the regulation of the stereoselectivity of the reaction; the synergistic effect of the helical backbone of the polymer and the catalytically functional side groups can further improve the catalytic efficiency of small molecule catalysts; due to their large molecular weight, helical polymers are easily separated from the reaction system, enabling the recycling of catalysts.

[0004] Proline, as one of the most widely used organic asymmetric catalysts, can be used for highly efficient catalysis of asymmetric aldehyde and ketone addition reactions. However, some amino acid peptide derivatives have shortcomings such as low catalytic activity and stereoselectivity. Therefore, it is of great significance to prepare highly active helical polyisocyanate catalysts modified with proline dipeptides. By leveraging the synergistic effect of the polymer backbone helical structure and the side group catalytic sites, the catalytic effect can be greater than the sum of its parts, thus improving its reactivity and stereoselectivity. Summary of the Invention

[0005] The purpose of this invention is to provide a chiral helical polyisocyanate catalyst modified with proline dipeptide and its preparation method. The method is simple to operate and easy to synthesize, and has great potential application value in catalyzing asymmetric Aldol (aldol condensation) and Michael (Michael) addition reactions.

[0006] In one aspect of the invention, a chiral helical polyisocyanate catalyst modified with a proline dipeptide is provided. According to an embodiment of the invention, the structural formula is as follows:

[0007]

[0008] in, n = 50 to 250.

[0009] In another aspect of the invention, a method for preparing a chiral helical polyisocyanate catalyst modified with proline dipeptide is provided. According to an embodiment of the invention, the method includes the following steps:

[0010] (1) The proline dipeptide-modified isonitrile monomer and Pd(II) catalyst were reacted and then centrifuged to obtain the solid product;

[0011] (2) The obtained solid product was washed and dried, and then trifluoroacetic acid was added to carry out the reaction. Then the product was washed and concentrated to obtain the crude product.

[0012] (3) The crude product is washed and dried to obtain the chiral helical polyisocyanate catalyst modified with proline dipeptide.

[0013] The synthetic route for the chiral helical polyisocyanate catalyst modified with proline dipeptide is as follows:

[0014]

[0015] in,

[0016] In addition, the method for preparing a chiral helical polyisocyanate catalyst modified with proline dipeptide according to the above embodiments of the present invention may also have the following additional technical features:

[0017] In some embodiments of the present invention, the structural formula of the proline dipeptide-modified isonitrile monomer in step (1) is as follows:

[0018]

[0019] In some embodiments of the present invention, the preparation method of the proline dipeptide-modified isonitrile monomer includes the following steps: under a N2 atmosphere, pentafluorophenol isonitrile, three proline chains, and 4-dimethylaminopyridine in anhydrous tetrahydrofuran are stirred and reacted. After the reaction is complete, the reaction mixture is washed sequentially with water, saturated sodium bicarbonate solution, and saturated sodium chloride solution. The organic phases are combined, dried with anhydrous sodium sulfate, and filtered. The filtrate is evaporated to dryness to obtain a crude product. The crude product is separated by column chromatography, the product is collected, and dried to obtain the proline dipeptide-modified isonitrile monomer.

[0020] The synthetic route for proline dipeptide-modified isonitrile monomers is as follows:

[0021]

[0022] In some embodiments of the present invention, the reaction is carried out in an oil bath at a temperature of 55–60°C for 8–12 hours.

[0023] In some embodiments of the present invention, the eluent used in the column chromatography separation is ethyl acetate and methanol in a volume ratio of 50 to 30:1.

[0024] In some embodiments of the present invention, in step (1), the molar ratio of Pd(II) catalyst and proline dipeptide-modified isonitrile monomer is 1.0:50.0-250.0. The Pd(II) catalyst is dissolved in dry chlorobenzene and then reacted with the proline dipeptide-modified isonitrile monomer. After the reaction is completed, the mixture is added to diethyl ether for centrifugation. The reaction temperature is 55-60°C and the reaction time is 8-12 h.

[0025] In some embodiments of the present invention, in step (2), the obtained solid product is washed with diethyl ether, the mixture after the reaction is completed is washed with ammonium hydroxide, the molar ratio of trifluoroacetic acid to solid product is 1.0:5.0 to 10.0, and the reaction is carried out at room temperature for 6 to 12 hours.

[0026] In some embodiments of the present invention, in step (3), the crude product obtained is washed with diethyl ether.

[0027] In another aspect of the invention, the present invention proposes the application of a chiral helical polyisocyanate catalyst modified with a proline dipeptide. According to embodiments of the invention, the chiral helical polyisocyanate catalyst modified with a proline dipeptide is used to catalyze asymmetric Aldol and Michael addition reactions.

[0028] Compared with the prior art, the beneficial effects of the present invention are:

[0029] This invention first obtains a proline dipeptide-modified isonitrile monomer via direct synthesis, then uses a Pd(II) catalyst to initiate its living polymerization, yielding a chiral helical polyisocyanate modified with the proline dipeptide. Further, the proline dipeptide-modified chiral helical polyisocyanate catalyst is obtained by removing the tert-butyloxycarbonyl protecting group. This invention innovatively obtains proline dipeptide-modified chiral helical polymers via living-controlled polymerization. Furthermore, this invention offers advantages such as simple synthesis of chiral helical polymers, controllable molecular weight and molecular weight distribution, mild experimental conditions, and widely available raw materials. The prepared polymers have significant potential applications in catalyzing asymmetric Aldol and Michael addition reactions. Attached Figure Description

[0030] Figure 1 This is the 1H NMR spectrum of the isonitrile monomer modified with proline dipeptide in Example 1 of this invention;

[0031] Figure 2 This is the 1H NMR spectrum of the proline dipeptide-modified chiral helical polyisocyanate in Example 1 of this invention;

[0032] Figure 3 This is the 1H NMR spectrum of the proline dipeptide-modified chiral helical polyisocyanate catalyst in Example 1 of this invention;

[0033] Figure 4 These are gel permeation chromatograms of chiral helical polyisocyanate catalysts modified with proline dipeptides of different molecular weights in Examples 1-5 of this invention.

[0034] Figure 5 These are circular dichroism and UV-Vis spectra of chiral helical polyisocyanate catalysts modified with proline dipeptides of different molecular weights in Examples 1-5 of this invention. Detailed Implementation

[0035] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0036] Example 1

[0037] A method for preparing a chiral helical polyisocyanate catalyst with a degree of polymerization of 50 modified by proline dipeptide includes the following steps:

[0038] (1) Preparation of proline dipeptide-modified isonitrile monomer: 1.00 g of pentafluorophenol isonitrile and 1.88 g of three proline chains were weighed and placed in a two-necked flask. The reaction system was replaced with N2 atmosphere. Under N2 atmosphere, 50 mL of anhydrous tetrahydrofuran and 1.55 g of 4-dimethylaminopyridine were added to the reaction flask sequentially. The reaction flask was placed on a magnetic stirrer and the oil bath temperature was set to 55 °C. The reaction progress was monitored using thin-layer chromatography (TLC). After 12 h, the reactants were completely reacted and the reaction was stopped. The reaction mixture was washed sequentially with water, saturated sodium bicarbonate solution, and saturated sodium chloride solution. The organic phases were combined, dried with anhydrous sodium sulfate, and filtered. The filtrate was concentrated to obtain the crude product. The crude product was separated by column chromatography (eluent: ethyl acetate / methanol (v / v = 30 / 1)). The product was collected, concentrated, and vacuum dried to obtain the proline dipeptide-modified isonitrile monomer.

[0039] The structural formula of the proline dipeptide-modified isonitrile monomer is as follows:

[0040]

[0041] like Figure 1 As shown, the successful preparation of the proline dipeptide-modified isonitrile monomer was confirmed by 1H NMR spectroscopy.

[0042] (2) Weigh 20.0 mg of the proline dipeptide-modified isonitrile monomer obtained in the preparation and add it to the reaction flask. Replace the reaction flask with N2 atmosphere, add dry chlorobenzene and 0.38 mg of Pd(II) catalyst, and stir for 12 h at 95 °C. As the reaction proceeds, a small amount of bubbles are generated in the reaction solution and the color of the reaction solution gradually deepens. The reaction process is tracked by thin layer chromatography (TLC) (the developing solvent is ethyl acetate / methanol (v / v = 30 / 1)). After the reaction is completed, add the reaction mixture to diethyl ether, centrifuge to separate the solid product, wash the obtained product with diethyl ether, and vacuum dry until the mass remains unchanged to obtain the proline dipeptide-modified chiral helical polyisocyanate.

[0043] like Figure 2 As shown, proline dipeptide-modified chiral helical polyisocyanates were successfully prepared, as confirmed by 1H NMR spectroscopy.

[0044] (3) Weigh 18.0 mg of the proline dipeptide-modified chiral helical polyisocyanate obtained in the preparation and add it to the reaction flask. Replace the reaction flask with N2 atmosphere, add 0.5 mL of trifluoroacetic acid and 5.0 mL of dichloromethane, and stir for 24 h at 25 °C. As the reaction proceeds, a small amount of bubbles are generated in the reaction solution, and the color of the reaction solution gradually becomes lighter. After the reaction is completed, wash the reaction mixture with ammonium hydroxide, concentrate the filtrate to obtain the crude product, add the product to diethyl ether, centrifuge to obtain the solid product, and vacuum dry until the mass remains unchanged to obtain the chiral helical polyisocyanate catalyst modified with proline dipeptide, denoted as poly-1. 50 .

[0045] The structural formula of the chiral helical polyisocyanate catalyst modified with proline dipeptide is as follows:

[0046]

[0047] in, n = 50.

[0048] like Figure 3 As shown, the tert-butyloxycarbonyl group was successfully removed, and the proline dipeptide-modified chiral helical polyisocyanate catalyst was successfully prepared, as revealed by the 1H NMR spectrum.

[0049] Example 2

[0050] A method for preparing a chiral helical polyisocyanate catalyst with a degree of polymerization of 100 modified by proline dipeptide includes the following steps:

[0051] (1) Preparation of proline dipeptide-modified isonitrile monomer: 1.00 g of pentafluorophenol isonitrile and 1.88 g of three proline chains were weighed and placed in a two-necked flask. The reaction system was replaced with N2 atmosphere. Under N2 atmosphere, 50 mL of anhydrous tetrahydrofuran and 1.55 g of 4-dimethylaminopyridine were added to the reaction flask sequentially. The reaction flask was placed on a magnetic stirrer and the oil bath temperature was set to 55 °C. The reaction progress was monitored using thin-layer chromatography (TLC). After 12 h, the reactants were completely reacted and the reaction was stopped. The reaction mixture was washed sequentially with water, saturated sodium bicarbonate solution, and saturated sodium chloride solution. The organic phases were combined, dried with anhydrous sodium sulfate, and filtered. The filtrate was concentrated to obtain the crude product. The crude product was separated by column chromatography (eluent: ethyl acetate / methanol (v / v = 30 / 1)). The product was collected, concentrated, and vacuum dried to obtain the proline dipeptide-modified isonitrile monomer.

[0052] (2) Weigh 20.0 mg of the proline dipeptide-modified isonitrile monomer obtained in the preparation and add it to the reaction flask. Replace the reaction flask with N2 atmosphere, add dry chlorobenzene and 0.19 mg of Pd(II) catalyst, and stir for 12 h at 95 °C. As the reaction proceeds, a small amount of bubbles are generated in the reaction solution and the color of the reaction solution gradually deepens. The reaction process is tracked by thin layer chromatography (TLC) (the developing solvent is ethyl acetate / methanol (v / v = 30 / 1)). After the reaction is completed, add the reaction mixture to diethyl ether, centrifuge to separate the solid product, wash the obtained product with diethyl ether, and vacuum dry until the mass remains unchanged to obtain the proline dipeptide-modified chiral helical polyisocyanate.

[0053] (3) Weigh 18.0 mg of the proline dipeptide-modified chiral helical polyisocyanate obtained in the preparation and add it to the reaction flask. Replace the reaction flask with N2 atmosphere, add 0.5 ml of trifluoroacetic acid and 5.0 ml of dichloromethane, and stir for 24 h at 25 °C. As the reaction proceeds, a small amount of bubbles are generated in the reaction solution, and the color of the reaction solution gradually becomes lighter. After the reaction is completed, wash the reaction mixture with ammonium hydroxide, concentrate the filtrate to obtain the crude product, add the product to diethyl ether, centrifuge to obtain the solid product, and vacuum dry until the mass remains unchanged to obtain the proline dipeptide-modified chiral helical polyisocyanate catalyst, denoted as poly-1. 100 .

[0054] The structural formula of the chiral helical polyisocyanate catalyst modified with proline dipeptide is as follows:

[0055]

[0056] in, n = 100.

[0057] Example 3

[0058] A method for preparing a chiral helical polyisocyanate catalyst with a degree of polymerization of 150 modified by proline dipeptide includes the following steps:

[0059] (1) Preparation of proline dipeptide-modified isonitrile monomer: 1.00 g of pentafluorophenol isonitrile and 1.88 g of three proline chains were weighed and placed in a two-necked flask. The reaction system was replaced with N2 atmosphere. Under N2 atmosphere, 50 ml of anhydrous tetrahydrofuran and 1.55 g of 4-dimethylaminopyridine were added to the reaction flask sequentially. The reaction flask was placed on a magnetic stirrer and the oil bath temperature was set to 55 °C. The reaction progress was monitored using thin-layer chromatography (TLC). After 12 h, the reactants were completely reacted and the reaction was stopped. The reaction mixture was washed sequentially with water, saturated sodium bicarbonate solution, and saturated sodium chloride solution. The organic phases were combined, dried with anhydrous sodium sulfate, and filtered. The filtrate was concentrated to obtain the crude product. The crude product was separated by column chromatography (eluent: ethyl acetate / methanol (v / v = 30 / 1)). The product was collected, concentrated, and dried under vacuum to obtain the proline dipeptide-modified isonitrile monomer.

[0060] (2) Weigh 20 mg of the prepared proline dipeptide-modified isonitrile monomer and add it to the reaction flask. Replace the reaction flask with N2 atmosphere, add dry chlorobenzene and 0.13 mg of Pd(II) catalyst, and stir for 12 h at 95 °C. As the reaction proceeds, a small amount of bubbles are generated in the reaction solution and the color of the reaction solution gradually deepens. The reaction process is tracked by thin-layer chromatography (TLC) (the developing solvent is ethyl acetate / methanol (v / v = 30 / 1)). After the reaction is completed, add the reaction mixture to diethyl ether, centrifuge to separate the solid product, wash the obtained product with diethyl ether, and vacuum dry until the mass remains unchanged to obtain the proline dipeptide-modified chiral helical polyisocyanate.

[0061] (3) Weigh 18 mg of the proline dipeptide-modified chiral helical polyisocyanate obtained in the preparation and add it to the reaction flask. Replace the reaction flask with N2 atmosphere, add 0.5 ml of trifluoroacetic acid and 5.0 ml of dichloromethane, and stir for 24 h at 25 °C. As the reaction proceeds, a small amount of bubbles are generated in the reaction solution, and the color of the reaction solution gradually becomes lighter. After the reaction is completed, wash the reaction mixture with ammonium hydroxide, concentrate the filtrate to obtain the crude product, add the product to diethyl ether, centrifuge to obtain the solid product, and vacuum dry until the mass remains unchanged to obtain the chiral helical polyisocyanate catalyst modified with proline dipeptide, denoted as poly-1. 150 .

[0062] The structural formula of the chiral helical polyisocyanate catalyst modified with proline dipeptide is as follows:

[0063]

[0064] in, n = 150.

[0065] Example 4

[0066] A method for preparing a chiral helical polyisocyanate catalyst with a degree of polymerization of 200 modified by proline dipeptide includes the following steps:

[0067] (1) Preparation of proline dipeptide-modified isonitrile monomer: 1.00 g of pentafluorophenol isonitrile and 1.88 g of three proline chains were weighed and placed in a two-necked flask. The reaction system was replaced with N2 atmosphere. Under N2 atmosphere, 50 ml of anhydrous tetrahydrofuran and 1.55 g of 4-dimethylaminopyridine were added to the reaction flask sequentially. The reaction flask was placed on a magnetic stirrer and the oil bath temperature was set to 55 °C. The reaction progress was monitored using thin-layer chromatography (TLC). After 12 h, the reactants were completely reacted and the reaction was stopped. The reaction mixture was washed sequentially with water, saturated sodium bicarbonate solution, and saturated sodium chloride solution. The organic phases were combined, dried with anhydrous sodium sulfate, and filtered. The filtrate was concentrated to obtain the crude product. The crude product was separated by column chromatography (eluent: ethyl acetate / methanol (v / v = 30 / 1)). The product was collected, concentrated, and dried under vacuum to obtain the proline dipeptide-modified isonitrile monomer.

[0068] (2) Weigh 20.0 mg of the proline dipeptide-modified isonitrile monomer obtained in the preparation and add it to the reaction flask. Replace the reaction flask with N2 atmosphere, add dry chlorobenzene and 0.10 mg of Pd(II) catalyst, and stir for 12 h at 95 °C. As the reaction proceeds, a small amount of bubbles are generated in the reaction solution and the color of the reaction solution gradually deepens. The reaction process is tracked by thin layer chromatography (TLC) (the developing solvent is ethyl acetate / methanol (v / v = 30 / 1)). After the reaction is completed, add the reaction mixture to diethyl ether, centrifuge to separate the solid product, wash the obtained product with diethyl ether, and vacuum dry until the mass remains unchanged to obtain the proline dipeptide-modified chiral helical polyisocyanate.

[0069] (3) Weigh 18.0 mg of the proline dipeptide-modified chiral helical polyisocyanate obtained in the preparation and add it to the reaction flask. Replace the reaction flask with N2 atmosphere, add 0.5 ml of trifluoroacetic acid and 5.0 ml of dichloromethane, and stir for 24 h at 25 °C. As the reaction proceeds, a small amount of bubbles are generated in the reaction solution, and the color of the reaction solution gradually becomes lighter. After the reaction is completed, wash the reaction mixture with ammonium hydroxide, concentrate the filtrate to obtain the crude product, add the product to diethyl ether, centrifuge to obtain the solid product, and vacuum dry until the mass remains unchanged to obtain the proline dipeptide-modified chiral helical polyisocyanate catalyst, denoted as poly-1. 200 .

[0070] The structural formula of the chiral helical polyisocyanate catalyst modified with proline dipeptide is as follows:

[0071]

[0072] in, n = 200.

[0073] Example 5

[0074] A method for preparing a chiral helical polyisocyanate catalyst with a degree of polymerization of 250 modified by proline dipeptide includes the following steps:

[0075] (1) Preparation of proline dipeptide-modified isonitrile monomer: 1.00 g of pentafluorophenol isonitrile and 1.88 g of three proline chains were weighed and placed in a two-necked flask. The reaction system was replaced with N2 atmosphere. Under N2 atmosphere, 50 ml of anhydrous tetrahydrofuran and 1.55 g of 4-dimethylaminopyridine were added to the reaction flask sequentially. The reaction flask was placed on a magnetic stirrer and the oil bath temperature was set to 55 °C. The reaction progress was monitored using thin-layer chromatography (TLC). After 12 h, the reactants were completely reacted and the reaction was stopped. The reaction mixture was washed sequentially with water, saturated sodium bicarbonate solution, and saturated sodium chloride solution. The organic phases were combined, dried with anhydrous sodium sulfate, and filtered. The filtrate was concentrated to obtain the crude product. The crude product was separated by column chromatography (eluent: ethyl acetate / methanol (v / v = 30 / 1)). The product was collected, concentrated, and dried under vacuum to obtain the proline dipeptide-modified isonitrile monomer.

[0076] (2) Weigh 20.0 mg of the prepared proline dipeptide-modified isonitrile monomer and add it to the reaction flask. Replace the reaction flask with N2 atmosphere, add dry chlorobenzene and 0.078 mg of Pd(II) catalyst, and stir for 12 h at 95 °C. As the reaction proceeds, a small amount of bubbles are generated in the reaction solution and the color of the reaction solution gradually deepens. The reaction process is tracked by thin layer chromatography (TLC) (the developing solvent is ethyl acetate / methanol (v / v = 30 / 1)). After the reaction is completed, add the reaction mixture to diethyl ether, centrifuge to separate the solid product, wash the obtained product with diethyl ether, and vacuum dry until the mass remains unchanged to obtain the proline dipeptide-modified chiral helical polyisocyanate.

[0077] (3) Weigh 18.0 mg of the proline dipeptide-modified chiral helical polyisocyanate obtained in the preparation and add it to the reaction flask. Replace the reaction flask with N2 atmosphere, add 0.5 ml of trifluoroacetic acid and 5.0 ml of dichloromethane, and stir for 24 h at 25 °C. As the reaction proceeds, a small amount of bubbles are generated in the reaction solution, and the color of the reaction solution gradually becomes lighter. After the reaction is completed, wash the reaction mixture with ammonium hydroxide, concentrate the filtrate to obtain the crude product, add the product to diethyl ether, centrifuge to obtain the solid product, and vacuum dry until the mass remains unchanged to obtain the proline dipeptide-modified chiral helical polyisocyanate catalyst, denoted as poly-1. 250 .

[0078] The structural formula of the chiral helical polyisocyanate catalyst modified with proline dipeptide is as follows:

[0079]

[0080] in, n = 250.

[0081] Dissolve 0.2–0.5 g of proline dipeptide-modified chiral helical polyisocyanate catalysts with different degrees of polymerization in 0.5–1.0 ml of tetrahydrofuran, respectively, and inject the solutions into a gel permeation chromatograph and a circular dichroism chromatograph to obtain:

[0082] like Figure 4 As shown, the molecular weight of the prepared catalyst continuously increases with the increase of the degree of polymerization. Figure 5 As shown, the circular dichroism value of the prepared catalyst continuously increases with the increase of the degree of polymerization.

[0083] Example 6

[0084] The chiral helical polyisocyanate catalyst with a degree of polymerization of 200, modified with the proline dipeptide prepared in Example 4, catalyzes the aldehyde-ketone reaction of p-nitrobenzaldehyde and cyclohexanone, including the following steps:

[0085] 50 mg of p-nitrobenzaldehyde and 4.5 mg of a chiral spiral polyisocyanate catalyst with a degree of polymerization of 150 modified with proline dipeptide were weighed and placed in a two-necked flask. The reaction system was replaced with N2 atmosphere. Under N2 atmosphere, 500 μL of tetrahydrofuran solution was added to the reaction flask sequentially. The reaction flask was stirred at room temperature for 30 min, and then 34 μL of nitrocyclohexanone was added. After reacting for 7 days, the mixture was filtered, and the filtrate was concentrated to obtain the crude product. The crude product was separated by column chromatography (eluent: petroleum ether / ethyl acetate (v / v = 12 / 1)). The product was collected, concentrated, and dried under vacuum to obtain a yellow solid. HPLC analysis determined that the enantiomeric excess (ee) was 71% (AD column, 2-propanol / n-hexane = 85 / 15 (v / v), 0.5 mL / min, = 254 nm).

[0086] The above description is merely an example and illustration of the present invention. Those skilled in the art can make various modifications or additions to the specific embodiments described or use similar methods to replace them, as long as they do not deviate from the structure of the present invention or exceed the scope defined in the claims, they should all fall within the protection scope of the present invention.

Claims

1. A chiral helical polyisocyanate catalyst modified with proline dipeptide, characterized in that, The structural formula is as follows: ， in, n = 50~250.

2. A method for preparing the chiral helical polyisocyanate catalyst modified with proline dipeptide as described in claim 1, characterized in that, Includes the following steps: (1) The proline dipeptide-modified isonitrile monomer was reacted with a Pd(II) catalyst, and then the solid product was obtained by centrifugation. The structural formula of the proline dipeptide-modified isonitrile monomer is as follows: ； The preparation method of the proline dipeptide-modified isonitrile monomer includes the following steps: under N2 atmosphere, pentafluorophenol isonitrile, three proline chains and 4-dimethylaminopyridine in anhydrous tetrahydrofuran are stirred and reacted. After the reaction is complete, the reaction mixture is washed successively with water, saturated sodium bicarbonate solution and saturated sodium chloride solution. The organic phases are combined, dried with anhydrous sodium sulfate and filtered. The filtrate is evaporated to dryness to obtain crude product. The crude product is separated by column chromatography, the product is collected and dried to obtain the proline dipeptide-modified isonitrile monomer. (2) The obtained solid product is washed and dried, then trifluoroacetic acid is added to carry out the reaction, and then washed and concentrated to obtain the crude product; (3) The crude product is washed and dried to obtain the chiral helical polyisocyanate catalyst modified with proline dipeptide.

3. The method for preparing a chiral helical polyisocyanate catalyst modified with proline dipeptide according to claim 2, characterized in that: The reaction is carried out in an oil bath at a temperature of 55-60°C for 8-12 hours.

4. The method for preparing a chiral helical polyisocyanate catalyst modified with proline dipeptide according to claim 2, characterized in that: The eluent used in the column chromatography separation is ethyl acetate and methanol in a volume ratio of 50~30:

1.

5. The method for preparing a chiral helical polyisocyanate catalyst modified with proline dipeptide according to claim 2, characterized in that: In step (1), the molar ratio of Pd(II) catalyst and proline dipeptide-modified isonitrile monomer is 1.0:50.0~250.

0. Pd(II) catalyst is dissolved in dry chlorobenzene and then reacted with proline dipeptide-modified isonitrile monomer. After the reaction, the mixture is added to diethyl ether for centrifugation. The reaction temperature is 55~60℃ and the reaction time is 8~12 h.

6. The method for preparing a chiral helical polyisocyanate catalyst modified with proline dipeptide according to claim 2, characterized in that: In step (2), the obtained solid product is washed with diethyl ether, and the mixture after the reaction is completed is washed with ammonium hydroxide. The molar ratio of trifluoroacetic acid to solid product is 1.0:5.0~10.0, and the reaction is carried out at room temperature for 6~12 h.

7. The method for preparing a chiral helical polyisocyanate catalyst modified with proline dipeptide according to claim 2, characterized in that: In step (3), the crude product is washed with diethyl ether.

8. The application of the chiral helical polyisocyanate catalyst modified with proline dipeptide as described in claim 1, characterized in that: The chiral helical polyisocyanate catalyst modified with proline dipeptide is used to catalyze asymmetric Aldol and Michael addition reactions.

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