Chiral spiral polyisocyanide catalyst modified by proline dipeptide and preparation method of chiral spiral polyisocyanide catalyst

Abstract

The invention discloses a chiral spiral polyisocyanide catalyst modified by proline dipeptide and a preparation method of the chiral spiral polyisocyanide catalyst, the structural formula of the catalyst is as follows: # imgabs0 #, and # imgabs1 # n = 50-250. The preparation method comprises the following steps: carrying out ester exchange on three sections of proline chains and pentafluorophenol isonitrile to prepare a monomer, initiating living polymerization of the monomer by using a Pd (II) catalyst to prepare a chiral spiral polymer, and removing a t-butyloxycarboryl protecting group to prepare the chiral spiral polyisocyanide catalyst with a catalytic function. The proline dipeptide modified chiral spiral polyisocyanide catalyst prepared by the invention can be prepared by active controllable polymerization of corresponding monomers, has controllable molecular weight and narrower molecular weight distribution, can be used for catalyzing asymmetric Aldol and Michael addition and other reactions, and has the advantages of simple and environment-friendly preparation method and high yield.

Description

Technical Field

[0001] The invention relates to the field of polymer materials, and in particular to a chiral helical polyisonitrile catalyst modified by proline dipeptide and a preparation method thereof. Background Art

[0002] The helical structure is a complex topological structure, but it is essentially an asymmetric chiral structure. In nature, whether in macroscopic animals and plants or microscopic molecular systems, the helical structure is widely present. From the back of a snail to the stems and leaves of spring grass, to proteins and DNA in organisms, all biological macromolecules have a helical structure. Inspired by the special functions of helical molecules in nature, chemists are trying to imitate the types and functions of natural and artificially synthesized helical polymers, and their application fields are becoming more and more extensive.

[0003] Chiral helical polymers are widely used in the fields of chiral recognition, chiral separation, chiral sensing, asymmetric catalysis and liquid crystal materials because of their optical activity. Asymmetric catalytic reaction is one of the important methods to construct chiral centers in molecules, and is widely used in the synthesis of drug intermediates and natural products. Traditional asymmetric catalysts mainly include three systems: metal and chiral ligands, enzymes, and organic small molecules. Compared with asymmetric metal catalysis and enzyme catalysis, organic small molecule catalysis has the advantages of mild reaction conditions, no transition metal residues and a wide range of substrate applications, but the disadvantage is that the amount of organic small molecule catalysts is generally large and difficult to recycle. In order to make up for the shortcomings of organic catalysis, many chemists have developed asymmetric catalytic systems loaded with organic catalysts in recent years. Compared with traditional carriers such as silica gel and polymers, helical polymers have many advantages as carriers of organic small molecule catalysts: helical polymers with appropriate structures can provide a microenvironment for asymmetric reactions that small molecules do not have, thereby regulating the stereoselectivity of the reaction; the synergistic effect of the helical main chain of the polymer and the side groups with catalytic function can further improve the catalytic efficiency of small molecule catalysts; due to their large molecular weight, helical polymers can be easily separated from the reaction system, thereby achieving the recycling of the catalyst.

[0004] Proline is one of the most widely used organic asymmetric catalysts and can be used to efficiently catalyze asymmetric aldehyde and ketone addition reactions. However, some amino acid peptide derivatives have shortcomings such as low catalytic activity and reaction stereoselectivity. Therefore, it is of great significance to prepare a highly active helical polyisocyanide catalyst modified with proline dipeptide, and to achieve a catalytic effect of one plus one greater than two through the synergistic effect of the polymer main chain helical structure and the side group catalytic sites, thereby improving its reaction activity and stereoselectivity. Summary of the invention

[0005] The purpose of the present invention is to provide a chiral helical polyisocyanide catalyst modified by proline dipeptide and a preparation method thereof, which is simple to operate and synthesize, and has great potential application value in catalyzing asymmetric Aldol (aldol condensation) and Michael (Michael) addition reactions.

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

[0007]

[0008] in, n=50~250.

[0009] In another aspect of the present invention, the present invention provides a method for preparing a chiral helical polyisocyanide catalyst modified by proline dipeptide. According to an embodiment of the present invention, the method comprises the following steps:

[0010] (1) reacting a proline dipeptide-modified isonitrile monomer with a Pd(II) catalyst, and then centrifuging to obtain a solid product;

[0011] (2) washing and drying the obtained solid product, adding trifluoroacetic acid to react, and then washing and concentrating to obtain a crude product;

[0012] (3) washing and drying the obtained crude product to obtain the chiral helical polyisonitrile catalyst modified by proline dipeptide.

[0013] The synthetic route of the chiral helical polyisocyanide catalyst modified by proline dipeptide is as follows:

[0014]

[0015] in,

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

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

[0018]

[0019] In some embodiments of the present invention, the preparation method of the proline dipeptide modified isonitrile monomer comprises the following steps: under N2 atmosphere, pentafluorophenol isonitrile, three segments of proline chain, and 4-dimethylaminopyridine in a molar ratio of 1:2 to 4:4 to 6 are stirred in anhydrous tetrahydrofuran for reaction; after the reaction is complete, the reaction mixture is washed with water, saturated sodium bicarbonate solution, and saturated sodium chloride solution in sequence, the organic phases are combined, the organic phases are dried over anhydrous sodium sulfate and then filtered, the filtrate is spin-dried to obtain a crude product, the crude product is separated by column chromatography, the product is collected, and the proline dipeptide modified isonitrile monomer is obtained after drying.

[0020] The synthetic route of the proline dipeptide-modified isonitrile monomer is as follows:

[0021]

[0022] In some embodiments of the present invention, the reaction is carried out in an oil bath, the reaction temperature is 55-60° C., and the reaction time is 8-12 h.

[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 the step (1), the molar ratio of the Pd(II) catalyst to the isonitrile monomer modified with proline dipeptide is 1.0:50.0-250.0, the Pd(II) catalyst is dissolved in dry chlorobenzene and then reacted with the isonitrile monomer modified with proline dipeptide, and the mixed solution after the reaction is added to ether for centrifugal separation, the reaction temperature is 55-60°C, and the reaction time is 8-12h.

[0025] In some embodiments of the present invention, in step (2), the solid product obtained is washed with ether, and the mixed solution after the reaction is washed with ammonium hydroxide, the molar ratio of trifluoroacetic acid to the solid product is 1.0:5.0-10.0, and the reaction is carried out at room temperature for 6-12 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 present invention, the present invention provides an application of a chiral helical polyisonitrile catalyst modified by proline dipeptide. According to an embodiment of the present invention, the chiral helical polyisonitrile catalyst modified by proline dipeptide is used to catalyze asymmetric Aldol and Michael addition reactions.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The present invention first obtains a proline dipeptide-modified isonitrile monomer by a direct synthesis method, then uses a Pd(II) catalyst to initiate active polymerization thereof to obtain a chiral helical polyisocyanide modified by proline dipeptide, and then removes the tert-butyloxycarbonyl protecting group to obtain a chiral helical polyisocyanide catalyst modified by proline dipeptide. The present invention innovatively obtains a proline dipeptide-modified chiral helical polymer by active controllable polymerization. The present invention has the advantages of simple synthesis of chiral helical polymers, controllable molecular weight and molecular weight distribution, mild experimental conditions, and a wide range of raw material sources. The prepared polymer has great potential application value in catalyzing asymmetric Aldol and Michael addition reactions. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0031] Figure 2 is the H NMR spectrum of the chiral helical polyisocyanide modified with proline dipeptide in Example 1 of the present invention;

[0032] Figure 3 is the nuclear magnetic hydrogen spectrum of the chiral helical polyisonitrile catalyst modified with proline dipeptide in Example 1 of the present invention;

[0033] Figure 4 is a gel permeation chromatogram of the chiral helical polyisonitrile catalyst modified with proline dipeptide of different molecular weights in Examples 1-5 of the present invention;

[0034] Figure 5 Circular dichroism spectra and ultraviolet-visible spectra of chiral helical polyisonitrile catalysts modified with proline dipeptides of different molecular weights in Examples 1-5 of the present invention. DETAILED DESCRIPTION

[0035] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0036] Example 1

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

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

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

[0040]

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

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

[0043] like Figure 2 As shown, the successful preparation of chiral helical polyisocyanide modified with proline dipeptide was confirmed by H NMR spectroscopy.

[0044] (3) Weigh 18.0 mg of the prepared chiral helical polyisocyanide modified with proline dipeptide and add it to a reaction bottle, replace the reaction bottle with N2 atmosphere, add 0.5 mL of trifluoroacetic acid and 5.0 mL of dichloromethane, and stir at 25°C for 24 hours. As the reaction continues, 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, the reaction mixture is added to ammonium hydroxide for washing, and the filtrate is concentrated to obtain a crude product. The product is added to ether, centrifuged to obtain a solid product, and vacuum dried until the mass remains unchanged to obtain the chiral helical polyisocyanide catalyst modified with proline dipeptide, which is recorded as poly-1 50 .

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

[0046]

[0047] in, n=50.

[0048] like Figure 3 As shown, the nuclear magnetic hydrogen spectrum revealed that the tert-butyloxycarbonyl group was successfully removed, and the chiral helical polyisonitrile catalyst modified with proline dipeptide was successfully prepared.

[0049] Example 2

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

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

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

[0053] (3) Weigh 18.0 mg of the prepared chiral helical polyisocyanide modified with proline dipeptide and add it to a reaction bottle, replace the reaction bottle with N2 atmosphere, add 0.5 ml of trifluoroacetic acid and 5.0 ml of dichloromethane, and stir at 25°C for 24 hours. As the reaction continues, 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, the reaction mixture is added to ammonium hydroxide for washing, and the filtrate is concentrated to obtain a crude product. The product is added to ether, centrifuged to obtain a solid product, and vacuum dried until the mass remains unchanged to obtain the chiral helical polyisocyanide catalyst modified with proline dipeptide, which is recorded as poly-1 100 .

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

[0055]

[0056] in, n=100.

[0057] Example 3

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

[0059] (1) Preparation of isonitrile monomer modified with proline dipeptide: 1.00 g of pentafluorophenol isonitrile and 1.88 g of three-segment proline chain were weighed and placed in a two-necked flask, and the reaction system was replaced with N2 atmosphere. 50 ml of anhydrous tetrahydrofuran and 1.55 g of 4-dimethylaminopyridine were added to the reaction flask in sequence under N2 atmosphere. The reaction flask was placed on a magnetic stirring table for stirring and the oil bath temperature was set to 55°C. The reaction progress was tracked by thin layer chromatography (TLC). After 12 hours, the raw materials reacted completely and the reaction was stopped. The reaction mixture was washed with water, saturated sodium bicarbonate solution, and saturated sodium chloride solution in sequence, and the organic phases were combined, dried over anhydrous sodium sulfate, and then filtered. The filtrate was concentrated to obtain a crude product. The crude product was separated by column chromatography (eluent: ethyl acetate / methanol (v / v=30 / 1)), and the product was collected, concentrated, and vacuum dried 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 a reaction flask. Replace the reaction flask with a N2 atmosphere, add dry chlorobenzene and 0.13 mg of Pd(II) catalyst, and stir at 95°C for 12 h. As the reaction proceeds, a small amount of bubbles are generated in the reaction solution, and the color of the reaction solution gradually deepens. Use thin layer chromatography (TLC) to track the progress of the reaction (the developing solvent is ethyl acetate / methanol (v / v=30 / 1)). After the reaction is completed, the reaction mixture is added to ether and centrifuged to obtain a solid product. The obtained product is washed with ether and vacuum dried until the mass remains unchanged to obtain a proline dipeptide-modified chiral helical polyisocyanide.

[0061] (3) 18 mg of the prepared chiral helical polyisocyanide modified with proline dipeptide was weighed and added to a reaction bottle, and the reaction bottle was replaced with a N2 atmosphere, and 0.5 ml of trifluoroacetic acid and 5.0 ml of dichloromethane were added. The reaction was stirred at 25° C. for 24 h. As the reaction continued, a small amount of bubbles were generated in the reaction solution, and the color of the reaction solution gradually became lighter. After the reaction was completed, the reaction mixture was added to ammonium hydroxide for washing, and the filtrate was concentrated to obtain a crude product. The product was added to ether, centrifuged to obtain a solid product, and vacuum dried until the mass remained unchanged to obtain the chiral helical polyisocyanide catalyst modified with proline dipeptide, which was recorded as poly-1 150 .

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

[0063]

[0064] in, n=150.

[0065] Example 4

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

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

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

[0069] (3) Weigh 18.0 mg of the prepared chiral helical polyisocyanide modified with proline dipeptide and add it to a reaction bottle, replace the reaction bottle with N2 atmosphere, add 0.5 ml of trifluoroacetic acid and 5.0 ml of dichloromethane, and stir at 25°C for 24 hours. As the reaction continues, 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, the reaction mixture is added to ammonium hydroxide for washing, and the filtrate is concentrated to obtain a crude product. The product is added to ether, centrifuged to obtain a solid product, and vacuum dried until the mass remains unchanged to obtain the chiral helical polyisocyanide catalyst modified with proline dipeptide, which is recorded as poly-1 200 .

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

[0071]

[0072] in, n=200.

[0073] Example 5

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

[0075] (1) Preparation of isonitrile monomer modified with proline dipeptide: 1.00 g of pentafluorophenol isonitrile and 1.88 g of three-segment proline chain were weighed and placed in a two-necked flask, and the reaction system was replaced with N2 atmosphere. 50 ml of anhydrous tetrahydrofuran and 1.55 g of 4-dimethylaminopyridine were added to the reaction flask in sequence under N2 atmosphere. The reaction flask was placed on a magnetic stirring table for stirring and the oil bath temperature was set to 55°C. The reaction progress was tracked by thin layer chromatography (TLC). After 12 hours, the raw materials reacted completely and the reaction was stopped. The reaction mixture was washed with water, saturated sodium bicarbonate solution, and saturated sodium chloride solution in sequence, and the organic phases were combined, dried over anhydrous sodium sulfate, and then filtered. The filtrate was concentrated to obtain a crude product. The crude product was separated by column chromatography (eluent: ethyl acetate / methanol (v / v=30 / 1)), and the product was collected, concentrated, and vacuum dried 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 a reaction flask. Replace the reaction flask with a N2 atmosphere, add dry chlorobenzene and 0.078 mg of Pd(II) catalyst, and stir at 95°C for 12 h. As the reaction proceeds, a small amount of bubbles are generated in the reaction solution, and the color of the reaction solution gradually deepens. Use thin layer chromatography (TLC) to track the progress of the reaction (the developing solvent is ethyl acetate / methanol (v / v=30 / 1)). After the reaction is completed, the reaction mixture is added to ether and centrifuged to obtain a solid product. The obtained product is washed with ether and vacuum dried until the mass remains unchanged to obtain a chiral helical polyisocyanide modified with proline dipeptide.

[0077] (3) Weigh 18.0 mg of the prepared chiral helical polyisocyanide modified with proline dipeptide and add it to a reaction bottle, replace the reaction bottle with N2 atmosphere, add 0.5 ml of trifluoroacetic acid and 5.0 ml of dichloromethane, and stir at 25°C for 24 hours. As the reaction continues, 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, the reaction mixture is added to ammonium hydroxide for washing, and the filtrate is concentrated to obtain a crude product. The product is added to ether, centrifuged to obtain a solid product, and vacuum dried until the mass remains unchanged to obtain the chiral helical polyisocyanide catalyst modified with proline dipeptide, which is recorded as poly-1 250 .

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

[0079]

[0080] in, n=250.

[0081] Take 0.2-0.5g of chiral helical polyisocyanide catalysts modified with proline dipeptides of different polymerization degrees and dissolve them in 0.5-1.0ml of tetrahydrofuran, inject them into gel permeation chromatography and circular dichroism spectrometer, and obtain:

[0082] like Figure 4 As shown in Figure 2, with the increase of polymerization degree, the molecular weight of the prepared catalyst is increasing. Figure 5 As shown in the figure, with the increase of polymerization degree, the circular dichroism value of the prepared catalyst is increasing.

[0083] Example 6

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

[0085] Weigh 50 mg of p-nitrobenzaldehyde and 4.5 mg of a chiral helical polyisocyanide catalyst modified with a polymerization degree of 150 and placed in a two-necked flask, replace the reaction system with a N2 atmosphere, add 500 ul of tetrahydrofuran solution to the reaction bottle in the N2 atmosphere, stir the reaction bottle at room temperature for 30 min, add 34 ul of nitrocyclohexanone to the reaction bottle, react for 7 days, and concentrate the filtrate to obtain a crude product. The crude product is separated by column chromatography (eluent: petroleum ether / ethyl acetate (v / v=12 / 1)), the product is collected and concentrated, and then vacuum dried to obtain a yellow solid. The enantiomeric excess (ee) is determined to be 71% by HPLC analysis (AD chromatographic column, 2-propanol / n-hexane=85 / 15 (v / v), 0.5 mL / min, =254 nm).

[0086] The above contents are merely examples and explanations of the present invention. Those skilled in the art may make various modifications or additions to the specific embodiments described or replace them in a similar manner. As long as they do not deviate from the structure of the present invention or exceed the scope defined by the claims, they shall all fall within the protection scope of the present invention.

Claims

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

2. A method for preparing a chiral helical polyisonitrile catalyst modified by proline dipeptide according to claim 1, characterized in that: The following steps are involved: (1) reacting a proline dipeptide-modified isonitrile monomer with a Pd(II) catalyst, and then centrifuging to obtain a solid product; (2) washing and drying the obtained solid product, adding trifluoroacetic acid to react, and then washing and concentrating to obtain a crude product; (3) washing and drying the obtained crude product to obtain the chiral helical polyisonitrile catalyst modified by proline dipeptide.

3. The method for preparing a chiral helical polyisonitrile catalyst modified by proline dipeptide according to claim 2, characterized in that: In the step (1), the structural formula of the isonitrile monomer modified with proline dipeptide is as follows:

4. The method for preparing a chiral helical polyisonitrile catalyst modified by proline dipeptide according to claim 3, characterized in that: The preparation method of the proline dipeptide modified isonitrile monomer comprises the following steps: in a N2 atmosphere, pentafluorophenol isonitrile, three segments of proline chains and 4-dimethylaminopyridine in a molar ratio of 1:2 to 4:4 to 6 are stirred for reaction in anhydrous tetrahydrofuran; after the reaction is complete, the reaction mixture is washed with water, a saturated sodium bicarbonate solution and a saturated sodium chloride solution in sequence, the organic phases are combined, the organic phases are dried over anhydrous sodium sulfate and then filtered, the filtrate is spin-dried to obtain a crude product, the crude product is separated by column chromatography, the product is collected, and the proline dipeptide modified isonitrile monomer is obtained after drying.

5. The method for preparing a chiral helical polyisonitrile catalyst modified by proline dipeptide according to claim 4, characterized in that: The reaction is carried out in an oil bath at a temperature of 55 to 60° C. and a reaction time of 8 to 12 hours.

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

1.

7. The method for preparing a chiral helical polyisocyanide catalyst modified by proline dipeptide according to claim 2, characterized in that: In the step (1), the molar ratio of the Pd(II) catalyst to the isonitrile monomer modified with proline dipeptide is 1.0:50.0-250.0, the Pd(II) catalyst is dissolved in dry chlorobenzene, and then reacts with the isonitrile monomer modified with proline dipeptide, and the mixed solution after the reaction is added to ether for centrifugal separation, the reaction temperature is 55-60°C, and the reaction time is 8-12h.

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

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

10. An application of the chiral helical polyisonitrile catalyst modified by proline dipeptide according to claim 1, characterized in that: The chiral helical polyisonitrile catalyst modified by proline dipeptide is used for catalyzing asymmetric Aldol and Michael addition reactions.

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