Preparation method of chiral benzyl borate compound and chiral hydroxyl compound thereof

Abstract

The invention provides a preparation method of a chiral benzyl borate compound, and belongs to the technical field of preparation of organic compounds, and the preparation method comprises the following steps: mixing a p-methylene benzoquinone compound, bis (pinacolato) diboron, a Bolm chiral ligand, a PS-CS-SiO2 (at) Cu catalytic material and a reaction solvent, stirring, reacting for set time, carrying out reduced pressure suction filtration after the reaction is completed, and drying to obtain the chiral benzyl borate compound. Filtering to obtain filtrate and filter residues; sequentially extracting the filtrate by using ethyl acetate and a saturated saline solution, then drying an organic phase by using anhydrous Na2SO4, carrying out reduced-pressure suction filtration, and carrying out rotary drying to obtain a crude product; and carrying out thin layer chromatography purification on the crude product to obtain the 1, 6-chiral benzyl borate compound. The raw materials used in the invention are cheap and easily available, the synthesis operation steps are simple, the reaction conditions are mild, the obtained 1, 6-chiral benzyl borate compound has high yield and enantioselectivity, and the catalytic material can be biologically degraded and recycled.

Description

Technical Field

[0001] The invention relates to the technical field of preparation of organic compounds, and in particular to a method for preparing chiral benzyl borate compounds and chiral hydroxyl compounds thereof. Background Art

[0002] The growing demand for chiral candidates in medicinal chemistry has prompted efforts to employ innovative enantioselective approaches to construct universal building blocks. Chiral boronate esters (CBEs) are considered an important class of building blocks that are frequently used in organic synthesis laboratories due to their versatile subsequent transformations. 3 Driven by the increasing development of methods for stereospecific transformations of )-B bonds, the synthesis of chiral boric esters (CBEs) has attracted widespread attention.

[0003] In 2015, Professor Mariola Tortosa's research group at the Autonomous University of Madrid ACS The above report achieved the synthesis of diphenylborates by boroyl aromatization of benzoquinone compounds under mild reaction conditions using commercially available chiral phosphine ligands with high yield and enantioselectivity.

[0004] In 2016, Professor Gregory C. Fu's research group at California Institute of Technology Science The above report achieved the α -Halogenated borate esters are used as catalysts to react with organozinc reagents in the presence of nickel and chiral diamines as ligands to generate chiral alkyl borate ester compounds. The reaction has high yield, good enantioselectivity, mild conditions and good functional group compatibility.

[0005] At present, the synthesis methods of benzyl borate compounds mainly include: 1. Benzyl chloride or benzyl bromide reacts with iron filings to prepare a Grignard reagent, which is then reacted with diboric acid pinacol ester under alkaline conditions of triethylamine to obtain benzyl borate compounds; 2. Benzyl chloride or benzyl bromide is catalyzed by transition metal (Fe or Ni) in a strong alkaline environment to react with pinacol diboric acid to obtain benzyl borate compounds; 3. Substituted styrene reacts with biboric acid pinacol ester in a strong alkaline environment catalyzed by transition metal (Fe, Co, Cu, Zr or Rh) to obtain benzyl borate compounds; 4. Substituted phenylacetic acid in MgBr 2 Under the action of , catalyzed by transition metal Cu, it reacts with biboric acid pinacol ester to obtain benzyl borate ester compounds; 5. Using para-benzoquinone compounds as reaction substrates, transition metal Cu catalyzes an asymmetric 1,6-boron addition reaction to obtain benzyl borate ester compounds.

[0006] The existing technology has problems such as non-recyclable catalysts, harsh reaction conditions and cumbersome operations, which are not conducive to industrial application; at the same time, due to the unique skeleton structure and special electrophilic activity of para-benzoquinone compounds, they are favored by scientific researchers. Based on this, it is necessary to develop a method for preparing chiral benzyl borate compounds using a new catalytic material. Summary of the invention

[0007] In view of the technical problems existing in the background technology, the present application provides a method for preparing chiral benzyl borate compounds and chiral hydroxyl compounds thereof, aiming to solve the technical problems of the prior art that the catalyst is non-recyclable, the reaction conditions are harsh and the operation is cumbersome.

[0008] In a first aspect, the present invention provides a method for preparing a chiral benzyl borate compound, comprising the following steps: S1, p-methylene benzoquinone compounds, biboric acid pinacol ester, Bolm chiral ligand, PS-CS-SiO 2 @Cu catalytic material and reaction solvent are mixed, stirred and reacted for a set time. After the reaction is completed, the filtrate and filter residue are obtained by vacuum filtration. The structural formula of the p-methylbenzoquinone compound is as follows: ; R 1 , R 2 are selected from alkyl, cycloalkyl, aryl, heterocyclic, alkoxy, aryloxy, alkylamino, arylamino or halogen; R 3 is selected from alkyl, cycloalkyl, aromatic or heterocyclic groups; S2, the filtrate in step S1 was extracted with ethyl acetate and saturated brine, and then with anhydrous Na 2 SO 4 The organic phase was dried, filtered under reduced pressure using a sand core funnel and rotary dried to obtain a crude product; S3. Purify the crude product by thin layer chromatography to obtain a 1,6-chiral benzyl borate compound with the following structural formula: ; Where R 1 , R 2 and R 3 Same as in the corresponding benzoquinone compounds.

[0009] In the technical solution of the embodiment of the present application, p-methylene benzoquinone compounds and biboric acid pinacol ester are used as raw materials, and Bolm chiral ligands and PS-CS-SiO 2 @Cu catalytic material undergoes 1,6-boron addition reaction to obtain chiral benzyl borate compounds.

[0010] Using PS-CS-SiO 2 @Cu catalytic material is used as a catalyst to catalyze the chiral boron addition reaction of methylene benzoquinone compounds, PS-CS-SiO 2 @Cu catalytic material is a new type of catalytic material that is recyclable and environmentally friendly.

[0011] Preferably, R 1 , R 2 is selected from tert-butyl; R 3 is selected from phenyl, 4-methylphenyl, 2-methylphenyl or naphthyl, and the p-methylene benzoquinone compound is selected from the following compounds: ; The corresponding 1,6-chiral benzyl borate ester compounds are selected from the following compounds: .

[0012] Preferably, in step S1, 0.24 mmol of biboric acid pinacol ester, 0.5-1.0 mg of Bolm chiral ligand, 2 mL of reaction solvent and 2-6 mg of PS-CS-SiO are added to every 0.2 mmol of p-methylene benzoquinone compound. 2 @Cu catalytic material, stir the reaction at room temperature for 10~14h.

[0013] Preferably, the Bolm chiral ligand is Bolm Ligand, and the structural formula is: .

[0014] In the technical solution of the embodiment of the present application, the chiral ligand is a BolmLigand tetradentate ligand, which is beneficial to coordination with Cu during the reaction process and improves the chiral catalytic effect.

[0015] Preferably, the filter residue in step S1 is washed with petroleum ether and vacuum dried to recover PS-CS-SiO 2 @Cu catalytic material is recycled.

[0016] In the technical solution of the embodiment of the present application, toluene-water is selected as the reaction solvent. Water is green and environmentally friendly, has no environmental pollution, and acts as a protic solvent in the reaction process; the toluene solvent can help dissolve the organic reaction substrate and the Bolm Ligand chiral ligand in the reaction process. The mixed use of the two can accelerate the reaction process, is green and environmentally friendly, and also helps to separate the catalyst after the reaction is completed.

[0017] Preferably, PS-CS-SiO 2 @Cu catalytic material carrier is PS-CS-SiO2 Nanocomposite microspheres, PS-CS-SiO 2 Nanocomposite microspheres are composed of PS monodisperse microsphere powder, SiO 2 and chitosan, PS-CS-SiO 2 Active component Cu loaded on nanocomposite microspheres 2+ , and obtain PS-CS-SiO 2 @Cu catalytic material.

[0018] In the technical solution of the embodiment of the present application, the polystyrene (PS) monodisperse microsphere powder has the characteristics of small particle size, large specific surface area, strong adsorption, good dispersibility, easy modification and modification, and also exhibits good stability, strong hydrophobicity and low adhesion and other physical and chemical properties, and has low production cost; silicon dioxide (SiO 2 ) Microspheres have the characteristics of controllable surface area, high mechanical strength, and stable thermal and physical and chemical properties. The control of the surface structure of silica can effectively increase the specific surface area of ​​the microspheres, and have many micro-region-specific structural properties; Chitosan (CS) has the advantages of wide availability, strong hydrophilicity, high metal ion binding activity, good biocompatibility, biodegradability and non-toxicity, and is an ideal adsorbent for organic synthesis catalysis. At the same time, chitosan has a strong affinity for Cu 2+ It has a high adsorption capacity and can achieve efficient catalysis under mild conditions, which is in line with the development concept of green chemistry.

[0019] Preferably, PS-CS-SiO 2 The preparation method of @Cu catalytic material comprises the following steps: P1. Prepare PS monodisperse microsphere powder in advance. Add 0.8-1.0 g of hexadecyltrimethylammonium bromide, 100-150 mL of anhydrous ethanol and 80-120 mL of distilled water to every 0.8-1.2 g of PS monodisperse microsphere powder. Stir for 0.2-0.5 h, then add 0.5-1.0 mL of concentrated ammonia water and 0.5-0.8 mL of tetraethyl silicate. Stir at room temperature for 4-8 h, heat in an oil bath at 80 ° C for 10-18 h, and vacuum dry at 40-60 ° C for 10-18 h to obtain PS-SiO 2 powder; P2, add 0.4~0.6g PS-SiO 2 The powder was mixed with 102 mL of 1-5% v / v acetic acid aqueous solution to obtain system A; P3. Add 40-60 mL of anhydrous ethanol and 40-60 mL of distilled water to every 10.0-15.0 g of sodium hydroxide, stir until colorless and clear, and cool to room temperature to obtain system B; P4, add system A dropwise into system B to form microspheres, filter, wash with anhydrous ethanol, and dry at room temperature to obtain PS-CS-SiO 2 Nanocomposite microspheres; P5, in PS-CS-SiO 2 Cu loaded on nanocomposite microspheres 2+ , and obtain PS-CS-SiO 2 @Cu nanocomposite microspheres loaded with copper catalyst.

[0020] Preferably, the method for preparing the PS monodisperse microsphere powder in step P1 comprises the following steps: P11, add 2.0-2.5 g of polyvinyl pyrrolidone, 0.4-0.6 g of azobisisobutyronitrile, 20-40 mL of styrene, and 2-5 mL of distilled water to every 80-100 mL of anhydrous ethanol, perform ultrasonic dispersion at room temperature for 0.5-1 h, and stir at 60-100 °C for 18-30 h under inert gas protection to obtain a mixed solution; P12. The mixed solution was centrifuged to obtain a precipitate, and the precipitate was washed with anhydrous ethanol to obtain PS monodisperse microsphere powder.

[0021] Preferably, in step P5, PS-CS-SiO 2 The preparation method of @Cu nanocomposite microspheres comprises the following steps: P51, the PS-CS-SiO obtained in step S4 2 The nanocomposite microspheres were placed in a water bath at 40-60°C for 1-2 h to obtain system C; P52, add 3.0~5.0g of copper acetate to every 40~60mL of distilled water, stir at room temperature for 4~8h to obtain system D; P53, stir and mix system C and system D, adsorb for 4-8 hours, filter, rinse with distilled water, and dry to obtain PS-CS-SiO 2 @Cu nanocomposite microspheres loaded with copper catalyst.

[0022] In a second aspect, the present invention provides a method for preparing a chiral hydroxy compound, comprising the following steps: (1) Add NaBO to the 1,6-chiral benzyl borate compound obtained in step S3 3 ·4H 2 O 240~250mg and THF-H 2 O mixed solvent 4~6mL, stirred at room temperature for 3~6h, extracted with ethyl acetate and saturated brine, and then washed with anhydrous Na 2 SO 4 Dry the organic phase, filter under reduced pressure and spin dry; (2) The residue is spin-dried and purified by thin layer chromatography to obtain a chiral hydroxy compound.

[0023] Different from the existing technical solutions, the beneficial effects of this application include: 1. This application uses p-methylene benzoquinone compounds and biboric acid pinacol ester as raw materials, and combines Bolm chiral ligands and PS-CS-SiO 2 @Cu catalytic material undergoes boron addition reaction to obtain 1,6-chiral benzyl borate compounds, and can be used to successfully prepare a variety of 1,6-chiral benzyl borate compounds. The raw materials used are cheap and easily available, the synthesis operation steps are simple, and the reaction conditions are mild. The obtained 1,6-chiral benzyl borate compounds have high yield and enantioselectivity, and the catalytic material is biodegradable and recyclable, which is suitable for the mass preparation and large-scale production of 1,6-chiral benzyl borate compounds.

[0024] 2. This application is in TL-H 2 O reaction solvent, Bolm Ligand as chiral ligand combined with nanocomposite microspheres supported copper catalyst catalyzes the chiral boron addition reaction of methylene benzoquinone compounds. TL-H 2 O as the reaction solvent, H 2 O acts as a protic solvent during the reaction, and TL helps dissolve the organic reaction substrate and the Bolm Ligand chiral ligand during the reaction, which can accelerate the chiral boron addition reaction. The use of this reaction solvent to prepare 1,6-chiral boron compounds has a higher yield and enantioselectivity.

[0025] 3. PS-CS-SiO is used in this application 2 @Cu catalytic material catalyzes the chiral boron addition reaction of p-methylene benzoquinone compounds. The metal ion binding activity in the catalytic material is high, and it can achieve efficient catalysis under mild conditions without adding additional additives. It has high catalytic efficiency for the chiral boron addition reaction of p-methylene benzoquinone compounds.

[0026] 4. PS-CS-SiO of this application 2 @Cu catalytic material is a nanocomposite material, which has the characteristics of organic phase, inorganic phase and nanoparticles, and has the characteristics of small particle size, large specific surface area, strong adsorption, stable thermal and physical and chemical properties. Compared with the traditional Cu(II) homogeneous catalyst, the PS-CS-SiO 2 @Cu catalytic materials can be recycled in a simple way and have excellent reusability. The above description is only an overview of the technical solution of this application. In order to more clearly understand the technical means of this application, it can be implemented according to the contents of the specification. In order to make the above and other purposes, features and advantages of this application more obvious and easy to understand, the specific implementation methods of this application are listed below. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solution of the present application, the following is a brief introduction to the drawings used in the present application. Obviously, the drawings described below are only some embodiments of the present application, and for ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0028] Figure 1 PS raw material, PS-CS-SiO 2 Nanocomposite microspheres and PS-CS-SiO 2 @Infrared spectrum of Cu catalyst; Figure 2 PS-CS-SiO 2 @SEM image of Cu catalyst (magnification 8000 times). DETAILED DESCRIPTION

[0029] The following embodiments of the technical solution of the present application are described in detail in conjunction with the accompanying drawings. The following embodiments are only used to more clearly illustrate the technical solution of the present application, and are therefore only used as examples, and cannot be used to limit the scope of protection of the present application.

[0030] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by technicians in the technical field to which this application belongs; the terms used herein are only for the purpose of describing specific embodiments and are not intended to limit this application; the terms "including" and "having" in the specification and claims of this application and the above-mentioned figure descriptions and any variations thereof are intended to cover non-exclusive inclusions.

[0031] Reference to "embodiments" herein means that a particular feature, structure, or characteristic described in conjunction with the embodiments may be included in at least one embodiment of the present application. The appearance of the phrase in various locations in the specification does not necessarily refer to the same embodiment, nor is it an independent or alternative embodiment that is mutually exclusive with other embodiments. It is explicitly and implicitly understood by those skilled in the art that the embodiments described herein may be combined with other embodiments.

[0032] In the description of the embodiments of the present application, the term "multiple" refers to more than two (including two). Similarly, "multiple groups" refers to more than two groups (including two groups), and "multiple pieces" refers to more than two pieces (including two pieces).

[0033] The existing technology has problems such as non-recyclable catalysts, harsh reaction conditions and complicated operations, which are not conducive to industrial applications.

[0034] In order to solve the technical problems of non-recyclable catalysts, harsh reaction conditions and complicated operations, the present application provides a method for preparing chiral benzyl borate compounds and chiral hydroxyl compounds thereof. The raw materials used in the preparation method of the present application are cheap and easily available, the synthesis operation steps are simple, the reaction conditions are mild, the obtained chiral benzyl borate compounds have high yield and enantioselectivity, and the catalytic material is biodegradable and recyclable, which is suitable for mass preparation and large-scale production of chiral benzyl borate compounds.

[0035] In a first aspect, the present invention provides a method for preparing a chiral benzyl borate compound, comprising the following steps: S1, p-methylene benzoquinone compounds, biboric acid pinacol ester, Bolm chiral ligand, PS-CS-SiO 2 @Cu catalytic material and reaction solvent are mixed, stirred and reacted for a set time. After the reaction is completed, the filtrate and filter residue are obtained by vacuum filtration. The structural formula of the p-methylbenzoquinone compound is as follows: ; R 1 , R 2 are selected from alkyl, cycloalkyl, aryl, heterocyclic, alkoxy, aryloxy, alkylamino, arylamino or halogen; R 3 is selected from alkyl, cycloalkyl, aromatic or heterocyclic groups; S2, the filtrate in step S1 was extracted with ethyl acetate and saturated brine, and then with anhydrous Na 2 SO 4 The organic phase was dried, filtered under reduced pressure using a sand core funnel and rotary dried to obtain a crude product; S3. Purify the crude product by thin layer chromatography to obtain a 1,6-chiral benzyl borate compound with the following structural formula: ; Where R 1 , R 2 and R 3 Same as in the corresponding benzoquinone compounds.

[0036] In the technical solution of the embodiment of the present application, p-methylene benzoquinone compounds and biboric acid pinacol ester are used as raw materials, and Bolm chiral ligands and PS-CS-SiO are combined in a reaction solvent. 2 @Cu catalytic material undergoes 1,6-boron addition reaction to obtain chiral benzyl borate compounds. The reaction equation is as follows:

[0037] Using PS-CS-SiO 2@Cu catalytic material is used as a catalyst to catalyze the chiral boron addition reaction of methylene benzoquinone compounds, PS-CS-SiO 2 @Cu catalytic material is a new type of catalytic material that is recyclable and environmentally friendly.

[0038] The preparation method of the present application has simple operation steps and mild reaction conditions, does not require strict control of an anhydrous and oxygen-free environment, and can obtain a higher yield and enantioselectivity, conforms to the concept of green chemistry development, and is suitable for the mass preparation and large-scale production of chiral benzyl borate compounds.

[0039] Preferably, R 1 , R 2 is selected from tert-butyl; R 3 is selected from phenyl, 4-methylphenyl, 2-methylphenyl or naphthyl, and the p-methylene benzoquinone compound is selected from the following compounds: ; The corresponding 1,6-chiral benzyl borate ester compounds are selected from the following compounds: .

[0040] Preferably, in step S1, 0.24 mmol of biboric acid pinacol ester, 0.5-1.0 mg of Bolm chiral ligand, 2 mL of reaction solvent and 2-6 mg of PS-CS-SiO are added to every 0.2 mmol of p-methylene benzoquinone compound. 2 @Cu catalytic material, stir the reaction at room temperature for 10~14h.

[0041] Preferably, the Bolm chiral ligand is Bolm Ligand, and the structural formula is: .

[0042] In the technical solution of the embodiment of the present application, the chiral ligand is a BolmLigand tetradentate ligand, which is beneficial to coordination with Cu during the reaction process and improves the chiral catalytic effect.

[0043] Preferably, the filter residue in step S1 is washed with petroleum ether and vacuum dried to recover PS-CS-SiO 2 @Cu catalytic material is recycled.

[0044] In the technical solution of the embodiment of the present application, toluene-water is selected as the reaction solvent. Water is green and environmentally friendly, has no environmental pollution, and acts as a protic solvent in the reaction process; the toluene solvent can help dissolve the organic reaction substrate and the Bolm Ligand chiral ligand in the reaction process. The mixed use of the two can accelerate the reaction process, is green and environmentally friendly, and also helps to separate the catalyst after the reaction is completed.

[0045] Preferably, PS-CS-SiO 2 @Cu catalytic material carrier is PS-CS-SiO 2 Nanocomposite microspheres, PS-CS-SiO 2 Nanocomposite microspheres are composed of PS monodisperse microsphere powder, SiO 2 and chitosan, PS-CS-SiO 2 Active component Cu loaded on nanocomposite microspheres 2+ , and obtain PS-CS-SiO 2 @Cu catalytic material.

[0046] Preferably, PS-CS-SiO 2 The preparation method of @Cu catalytic material comprises the following steps: P1. Prepare PS monodisperse microsphere powder in advance. Add 0.8-1.0 g of hexadecyltrimethylammonium bromide, 100-150 mL of anhydrous ethanol and 80-120 mL of distilled water to every 0.8-1.2 g of PS monodisperse microsphere powder. Stir for 0.2-0.5 h, then add 0.5-1.0 mL of concentrated ammonia water and 0.5-0.8 mL of tetraethyl silicate. Stir at room temperature for 4-8 h, heat in an oil bath at 80 ° C for 10-18 h, and vacuum dry at 40-60 ° C for 10-18 h to obtain PS-SiO 2 powder; P2, add 0.4~0.6g PS-SiO 2 The powder was mixed with 102 mL of 1-5% v / v acetic acid aqueous solution to obtain system A; P3. Add 40-60 mL of anhydrous ethanol and 40-60 mL of distilled water to every 10.0-15.0 g of sodium hydroxide, stir until colorless and clear, and cool to room temperature to obtain system B; P4, add system A dropwise into system B to form microspheres, filter, wash with anhydrous ethanol, and dry at room temperature to obtain PS-CS-SiO 2 Nanocomposite microspheres; P5, in PS-CS-SiO 2 Cu loaded on nanocomposite microspheres 2+ , and obtain PS-CS-SiO 2 @Cu nanocomposite microspheres loaded with copper catalyst.

[0047] Preferably, the method for preparing the PS monodisperse microsphere powder in step P1 comprises the following steps: P11, add 2.0-2.5 g of polyvinyl pyrrolidone, 0.4-0.6 g of azobisisobutyronitrile, 20-40 mL of styrene, and 2-5 mL of distilled water to every 80-100 mL of anhydrous ethanol, perform ultrasonic dispersion at room temperature for 0.5-1 h, and stir at 60-100 °C for 18-30 h under inert gas protection to obtain a mixed solution; P12. The mixed solution was centrifuged to obtain a precipitate, and the precipitate was washed with anhydrous ethanol to obtain PS monodisperse microsphere powder.

[0048] Preferably, in step P5, PS-CS-SiO 2 The preparation method of @Cu nanocomposite microspheres comprises the following steps: P51, the PS-CS-SiO obtained in step S4 2 The nanocomposite microspheres were placed in a water bath at 40-60°C for 1-2 h to obtain system C; P52, add 3.0~5.0g of copper acetate to every 40~60mL of distilled water, stir at room temperature for 4~8h to obtain system D; P53, stir and mix system C and system D, adsorb for 4-8 hours, filter, rinse with distilled water, and dry to obtain PS-CS-SiO 2 @Cu catalytic material.

[0049] In the technical solution of the embodiment of the present application, chitosan (CS) is used as the matrix, tetraethyl silicate (TEOS) is used as the silicon source, and hexadecyltrimethylammonium bromide (CTAB) is used as the surfactant to prepare PS-CS-SiO 2 Nanocomposite microspheres, PS-CS-SiO 2 The surface of the nanocomposite microspheres contains abundant functional groups, such as amino and hydroxyl groups, so they can be well complexed with metals. The material can be combined with copper salts through coordination bonds, has good catalytic effects, and can be stably recycled.

[0050] SiO 2 The Si-OH functional groups on the surface can react with the amino groups of chitosan to graft chitosan onto PS-SiO 2 PS-CS-SiO 2 Nanocomposite microspheres produce more complexing sites, which are convenient for subsequent coordination with copper ions; adding SiO 2 It can form abundant Si-OH on the surface of PS microspheres, enhance the hardness of the material, and make the microsphere structure more stable. 2PS-CS-SiO 2 Nanocomposite microspheres have stable structure, cheap raw materials, low preparation cost, and are made of PS-CS-SiO 2 Nanocomposite microspheres were used as carriers to load copper acetate (Cu(OAc) 2 ), to obtain PS-CS-SiO 2 @Cu catalytic material.

[0051] PS-SiO 2 Nanocomposite microspheres have unique compatibility and spatial structure, and have a larger surface area than chitosan materials because chitosan is loaded onto PS-SiO 2 Microsphere surface, PS-SiO 2 The microspheres have a large specific surface area and make chitosan in PS-SiO 2 The microspheres are evenly dispersed on the surface, exposing more complexing sites, thus significantly enhancing the complexing ability of copper and making it more fully in contact with the reaction substrate, thus achieving higher catalytic activity when preparing chiral organic boron compounds. 2 ), provides an alkaline environment for the reaction, and can realize catalytic reaction in a mixed solvent of organic reagent and water, which reduces the amount of organic reagent and alkali to a certain extent, and is in line with the concept of green chemistry development; in addition, the catalytic material can be recycled and reused many times and maintain excellent performance, which is very suitable for large-scale industrial application.

[0052] In a second aspect, the present invention provides a method for preparing a chiral hydroxy compound, comprising the following steps: (1) Add NaBO to the 1,6-chiral benzyl borate compound obtained in step S3 3 ·4H 2 O 240~250mg and THF-H 2 O mixed solvent 4~6mL, stirred at room temperature for 3~6h, extracted with ethyl acetate and saturated brine, and then washed with anhydrous Na 2 SO 4 The organic phase was dried, filtered under reduced pressure and rotary dried. The reaction equation is as follows: ; (2) The residue is spin-dried and purified by thin layer chromatography to obtain a chiral hydroxy compound.

[0053] In the technical scheme of the embodiment of the present application, in order to determine the enantioselectivity and stereochemical configuration of 1,6-chiral benzyl borate compounds, the prepared chiral benzyl borate compounds need to be oxidized and further converted into corresponding chiral hydroxyl compounds. The corresponding chiral hydroxyl compound has the following structural formula: .

[0054] Some specific embodiments are listed below. It should be noted that the embodiments described below are exemplary and are only used to explain the present application, and should not be construed as limiting the present application. If specific techniques or conditions are not specified in the embodiments, the techniques or conditions described in the literature in this area or the product specifications are used. The reagents or instruments used without specifying the manufacturer are all conventional products that can be obtained commercially.

[0055] 1. Preparation method Example 1 PS-CS-SiO 2 The preparation method of @Cu catalytic material comprises the steps of: (1) Preparation of PS monodisperse microsphere powder S1, add 2.25g polyvinyl pyrrolidone, 0.5g azobisisobutyronitrile, 30mL styrene, 95mL anhydrous ethanol and 3mL distilled water into the reaction bottle, and ultrasonically disperse at room temperature for 0.5h; S2, in N 2 Under inert gas protection, stir at 70 °C for 24 h; S3. Centrifuge and wash with anhydrous ethanol several times to obtain PS monodisperse microsphere powder.

[0056] (2) PS-SiO 2 Powder preparation S1. Add 1.0 g of PS monodisperse microsphere powder, 0.92 g of hexadecyltrimethylammonium bromide, 120 mL of anhydrous ethanol and 100 mL of distilled water to a reaction bottle, stir and dissolve for 20 min, then quickly add 0.8 mL of concentrated ammonia and 0.6 mL of tetraethyl silicate, stir at room temperature for 6 h, then transfer to an oil bath at 80 ° C and heat for 12 h to obtain a white suspension; S2, vacuum filter, wash with anhydrous ethanol several times, and vacuum dry at 50 ° C for 12 h to obtain PS-SiO 2 White fluffy powder.

[0057] (3) PS-CS-SiO 2 Preparation of nanocomposite microspheres S1. Add 1.0 g chitosan (CS) powder and 0.5 g PS-SiO 2 powder and 100 mL of 1% v / v acetic acid aqueous solution to obtain System A; S2. Add 12.0 g of sodium hydroxide, 50 mL of anhydrous ethanol and 50 mL of distilled water to the reaction bottle, stir until colorless and clear, and cool to room temperature to obtain system B; S3, using a syringe to drip system A into system B, filter through a mesh, wash with anhydrous ethanol several times, and dry at room temperature to obtain PS-CS-SiO 2 Nanocomposite microspheres.

[0058] (4) PS-CS-SiO 2 Preparation of @Cu nanocomposite microspheres S1, 1.0g PS-CS-SiO 2 The nanocomposite microspheres were placed in a reaction bottle in a water bath at 50°C for 1 h to obtain system C; S2. Add 3.7 g of copper acetate and 50 mL of distilled water to the reaction bottle and stir at room temperature for 6 h to obtain system D; S3, the system C and the system D were stirred and mixed, adsorbed for 5 hours, filtered through a mesh, rinsed with distilled water, and dried at 50°C for 12 hours to obtain PS-CS-SiO 2 @Cu catalytic material.

[0059] Example 2 The PS-CS-SiO obtained in Example 1 2 @Cu catalytic material is used to prepare chiral benzyl borate ester compounds, that is, in TL-H 2 O mixed solvent, p-benzoquinone compound (compound I) and diboric acid pinacol ester (compound II) in PS-CS-SiO 2 @ Under the action of Cu catalytic material and Bolm chiral ligand, chiral benzyl borate compounds (compound III) are obtained through 1,6-boron addition reaction.

[0060] The reaction equation is:

[0061] In this embodiment, the p-methylene benzoquinone compound is 2,6-di-tert-butyl-4-benzylidenecyclohexa-2,5-diene-1-one, and the specific catalytic process is: S1. Add 58.9 mg 2,6-di-tert-butyl-4-benzylidenecyclohexa-2,5-diene-1-one (Compound I-1), 60.9 mg biboric acid pinacol ester (Compound II), 0.8 mg Bolm chiral ligand, 5 mg PS-CS-SiO 2 @Cu catalytic material and 2mL TL-H 2 O mixed solvent, TL and H in the mixed solvent 2 The volume ratio of O was 1:9, and the mixture was stirred at room temperature for 12 h to obtain a chiral benzyl borate ester compound (Compound III-1). The reaction equation is as follows:

[0062] S2. After the above reaction was completed, the filtrate was filtered under reduced pressure, and the filtrate was extracted 3 times with ethyl acetate and 1 time with saturated brine. 2 SO 4 The organic phase was dried, filtered under reduced pressure using a sand core funnel and rotary dried to remove excess ethyl acetate, and the crude product was purified by thin layer chromatography to obtain a purified chiral benzyl borate compound (Compound III-1); S3, add 244 mg of sodium borate tetrahydrate (NaBO 3 ·4H 2 O) and 5 mL THF-H 2 O (V:V = 3:2) mixed solvent, stirred at room temperature for 4 h; S4. After the above reaction, the mixture was extracted with ethyl acetate 3 times, saturated brine 1 time, and anhydrous Na 2 SO 4 The organic phase was dried, filtered under reduced pressure using a sand core funnel and dried by rotation to remove excess ethyl acetate, and the spin-dried residue was then purified by thin layer chromatography to obtain a chiral hydroxy compound (Compound IV-1). The reaction equation is as follows: .

[0063] Example 3 The difference between Example 3 and Example 2 is that the reaction substrate is different, and the other steps are the same. The reaction substrate p-methylene benzoquinone compound in Example 3 is 2,6-di-tert-butyl-4-(4-methylbenzylidene)cyclohexa-2,5-diene-1-one, 2,6-di-tert-butyl-4-(2-methylbenzylidene)cyclohexa-2,5-diene-1-one and 2,6-di-tert-butyl-4-(naphthalene-2-methylene)cyclohexa-2,5-diene-1-one, and the structural formula is as follows: , The corresponding chiral benzyl borate compounds and chiral hydroxy compounds have the following structural formulas: ; .

[0064] Example 4 The difference between Example 4 and Example 2 is that the reaction substrate is different, and the other steps are the same. The reaction substrate in Example 4 is a p-methylene benzoquinone compound with the structural formula: ; The corresponding chiral benzyl borate compounds and chiral hydroxy compounds have the following structural formulas: ; .

[0065] Example 5 The difference between Example 5 and Example 2 is that the reaction substrate is different, and the other steps are the same. The reaction substrate p-methylene benzoquinone compound in Example 5 has the structural formula: ; The corresponding chiral benzyl borate compounds and chiral hydroxy compounds have the following structural formulas: ; .

[0066] Example 6 The difference between Example 6 and Example 2 is that in Example 6, the filter residue obtained by vacuum filtration in step S2 of Example 2 is washed with petroleum ether (PE) three times, and vacuum dried at 50° C. for 12 h to remove the petroleum ether (PE), and the PS-CS-SiO 2 @Cu catalytic material is recycled, PS-CS-SiO used in Example 6 2 @The number of cycles of the Cu catalytic material is 1, and the other steps are the same as those in Example 2.

[0067] Example 7 The difference between Example 7 and Example 2 is that in Example 7, the filter residue obtained by vacuum filtration in step S2 of Example 2 is washed with petroleum ether (PE) three times, and vacuum dried at 50° C. for 12 h to remove the petroleum ether (PE), and the PS-CS-SiO 2 @Cu catalytic material is recycled, PS-CS-SiO used in Example 7 2 The number of cycles of @Cu catalytic material is 2, and the other steps are the same as Example 2.

[0068] Example 8 The difference between Example 8 and Example 2 is that in Example 8, the filter residue obtained by vacuum filtration in step S2 of Example 2 is washed with petroleum ether (PE) three times, and vacuum dried at 50° C. for 12 h to remove the petroleum ether (PE), and the PS-CS-SiO 2 @Cu catalytic material is recycled, PS-CS-SiO used in Example 8 2 The number of cycles of the @Cu catalytic material was 3 times, and the other steps were the same as in Example 2.

[0069] Example 9 The difference between Example 9 and Example 2 is that in Example 9, the filter residue obtained by vacuum filtration in step S2 of Example 2 is washed with petroleum ether (PE) three times, and vacuum dried at 50° C. for 12 h to remove the petroleum ether (PE), and the PS-CS-SiO 2@Cu catalytic material is recycled, PS-CS-SiO used in Example 9 2 The number of cycles of @Cu catalytic material was 4 times, and the other steps were the same as in Example 2.

[0070] Example 10 The difference between Example 10 and Example 2 is that in Example 10, the filter residue obtained by vacuum filtration in step S2 of Example 2 is washed with petroleum ether (PE) three times, and vacuum dried at 50° C. for 12 h to remove the petroleum ether (PE), and the PS-CS-SiO 2 @Cu catalytic material is recycled, PS-CS-SiO used in Example 10 2 The number of cycles of @Cu catalytic material was 5 times, and the other steps were the same as in Example 2.

[0071] Embodiment 11 The difference between Example 11 and Example 2 is that in step S1, the PS-CS-SiO 2 @The amount of Cu catalytic material added is 2 mg, and the other steps are the same as in Example 2.

[0072] Example 12 The difference between Example 12 and Example 2 is that in step S1, the PS-CS-SiO 2 @The amount of Cu catalytic material added is 3 mg, and the other steps are the same as in Example 2.

[0073] Embodiment 13 The difference between Example 13 and Example 2 is that in step S1, the PS-CS-SiO 2 @The amount of Cu catalytic material added was 4 mg, and the other steps were the same as in Example 2.

[0074] Embodiment 14 The difference between Example 14 and Example 2 is that in step S1, the PS-CS-SiO 2 @The amount of Cu catalytic material added was 6 mg, and the other steps were the same as in Example 2.

[0075] Comparative Example 1 The difference between Comparative Example 1 and Example 2 is that in Comparative Example 1, Cu(CH 3 CN) 4 PF 6 As a catalyst, based on Example 2, an equal amount of Cu(CH 3 CN) 4 PF 6 The catalytic material is used to prepare chiral benzyl borate compounds, that is, in TL-H2 O mixed solvent, p-benzoquinone compound (compound I) and diboric acid pinacol ester (compound II) in Cu(CH 3 CN) 4 PF 6 Under the action of catalytic materials and Bolm chiral ligands, a chiral benzyl borate compound (Compound III) is obtained through 1,6-boron addition reaction.

[0076] The reaction equation is:

[0077] In this embodiment, the p-methylene benzoquinone compound is 2,6-di-tert-butyl-4-benzylidenecyclohexa-2,5-diene-1-one, and the specific catalytic process is: S1. Add 58.9 mg of 2,6-di-tert-butyl-4-benzylidenecyclohexa-2,5-diene-1-one (Compound I-1), 60.9 mg of biboric acid pinacol ester (Compound II), 0.8 mg of Bolm chiral ligand, and 1.5 mg of Cu(CH 3 CN) 4 PF 6 Catalytic material, 1.2 mg NaO t -Bu as additive and 2mL TL-H 2 O mixed solvent, TL and H in the mixed solvent 2 The volume ratio of O was 1:9, and the mixture was stirred at room temperature for 12 h to obtain a chiral benzyl borate ester compound (Compound III-1). The reaction equation is as follows:

[0078] S2. After the above reaction was completed, the filtrate was filtered under reduced pressure, and the filtrate was extracted 3 times with ethyl acetate and 1 time with saturated brine. 2 SO 4 The organic phase was dried, filtered under reduced pressure using a sand core funnel and rotary dried to remove excess ethyl acetate, and the crude product was purified by thin layer chromatography to obtain a purified chiral benzyl borate compound (Compound III-1); S3, add 244 mg of sodium borate tetrahydrate (NaBO 3 ·4H 2 O) and 5 mL THF-H 2 O (V:V = 3:2) mixed solvent, stirred at room temperature for 4 h; S4. After the above reaction, the mixture was extracted with ethyl acetate 3 times, saturated brine 1 time, and anhydrous Na 2 SO 4The organic phase was dried, filtered under reduced pressure using a sand core funnel and dried by rotation to remove excess ethyl acetate, and the spin-dried residue was then purified by thin layer chromatography to obtain a chiral hydroxy compound (Compound IV-1). The reaction equation is as follows: .

[0079] Comparative Example 2 The difference between Comparative Example 1 and Example 2 is that in Comparative Example 1, CuCl is used as a catalyst, and on the basis of Example 2, an equal amount of CuCl catalytic material is used to prepare chiral benzyl borate compounds, that is, in TL-H 2 In an O mixed solvent, p-methylenebenzoquinone compounds (compound I) and biboric acid pinacol ester (compound II) undergo 1,6-boron addition reaction under the action of CuCl catalytic material and Bolm chiral ligand to obtain chiral benzyl borate ester compounds (compound III).

[0080] The reaction equation is:

[0081] In this embodiment, the p-methylene benzoquinone compound is 2,6-di-tert-butyl-4-benzylidenecyclohexa-2,5-diene-1-one, and the specific catalytic process is: S1. Add 58.9 mg 2,6-di-tert-butyl-4-benzylidenecyclohexa-2,5-diene-1-one (Compound I-1), 60.9 mg biboric acid pinacol ester (Compound II), 0.8 mg Bolm chiral ligand, 0.4 mg CuCl catalytic material, and 1.2 mg NaO into the reaction bottle. t -Bu as additive and 2mL TL-H 2 O mixed solvent, the volume ratio of TL and H2O in the mixed solvent is 1:9, stirred at room temperature for 12h, and a chiral benzyl borate compound (Compound III-1) was obtained. The reaction equation is as follows:

[0082] S2. After the above reaction was completed, the filtrate was filtered under reduced pressure, and the filtrate was extracted 3 times with ethyl acetate and 1 time with saturated brine. 2 SO 4 The organic phase was dried, filtered under reduced pressure using a sand core funnel and rotary dried to remove excess ethyl acetate, and the crude product was purified by thin layer chromatography to obtain a purified chiral benzyl borate compound (Compound III-1); S3, add 244 mg of sodium borate tetrahydrate (NaBO 3 ·4H 2 O) and 5 mL THF-H2 O (V:V = 3:2) mixed solvent, stirred at room temperature for 4 h; S4. After the above reaction, the mixture was extracted with ethyl acetate 3 times, saturated brine 1 time, and anhydrous Na 2 SO 4 The organic phase was dried, filtered under reduced pressure using a sand core funnel and dried by rotation to remove excess ethyl acetate, and the spin-dried residue was then purified by thin layer chromatography to obtain a chiral hydroxy compound (Compound IV-1). The reaction equation is as follows: .

[0083] 2. Test Method Yield and enantioselectivity (ee value) detection method of chiral organic boron compound: The crude product of chiral organic boron compound is oxidized by sodium perborate tetrahydrate oxidation system to obtain hydroxyl compound for separation, and finally the final product is obtained by column chromatography, and its structure and yield are determined by nuclear magnetic resonance, and then its enantioselectivity is tested by liquid chromatography analyzer.

[0084] III. Analysis of test results of various embodiments and comparative examples (1) The PS monodisperse microsphere powder and PS-CS-SiO prepared in Example 1 were 2 Nanocomposite microspheres and PS-CS-SiO 2 @Cu nanocomposite microspheres were scanned by infrared spectra, and PS-CS-SiO 2 @Cu nanocomposite microspheres were scanned by SEM.

[0085] Figure 1 PS raw material, PS-CS-SiO 2 Nanocomposite microspheres and PS-CS-SiO 2 @Cu catalyst infrared spectrum; compared with the infrared spectrum of PS, in PS-CS-SiO 2 Some new absorption peaks appeared in the infrared spectrum of 740cm -1 The symmetrical stretching vibration absorption peak of Si-C is 438 cm -1 The bending vibration absorption peak of Si-O-Si can confirm that PS-CS-SiO 2 The microspheres were successfully prepared. 2 @Cu in the infrared spectrum at 1551cm -1 It is the vibration absorption peak of the amide II group in chitosan, 1046cm -1 The stretching vibration absorption peak and bending vibration absorption peak of the CH bond of copper acetate are shown in Figure 2. 2 The microspheres were successfully loaded with copper ions.

[0086] Prepared PS-CS-SiO 2 @Cu nanocomposite microspheres Figure 2 As shown in the figure, it can be seen that the morphology of the chitosan-based silica microspheres can be well maintained, and loaded particles, namely copper ion loads, can be seen on the surface.

[0087] (2) The PS-CS-SiO obtained in Example 2 2 @Cu catalytic material and the traditional catalyst Cu(CH 3 CN) 4 PF 6 Compared with CuCl for preparing chiral benzyl borate compounds, the results are shown in Table 1 below: Table 1 Comparison of different catalysts for the preparation of chiral benzyl borate esters

[0088] As can be seen from Table 1, compared with the traditional preparation method, the preparation method of chiral benzyl borate compounds designed in the present application has mild reaction conditions, does not require the use of a large amount of base, does not require strict control of anhydrous and oxygen-free environment, and can obtain higher yields and enantioselectivities; at the same time, the catalytic material has the advantages of cheap and readily available raw materials, low cost, and recyclability, which conforms to the concept of green chemistry development and is suitable for mass preparation and large-scale production of chiral benzyl borate compounds.

[0089] (3) In Examples 2 to 5, different reaction substrates were used to prepare chiral benzyl borate compounds. The yields and enantioselectivities of the chiral benzyl borate compounds prepared by using different reaction substrates in Examples 2 to 5 were tested. The test results are shown in Table 2 below: Table 2 Yields and enantioselectivities of chiral benzyl borate esters prepared from different reaction substrates

[0090] From the data in Table 2, it can be seen that the PS-CS-SiO prepared in Example 1 was 2@Cu catalytic material has excellent universality. When the reaction substrate is 2,6-di-tert-butyl-4-(4-methylbenzylidene)cyclohexa-2,5-diene-1-one, the yield (yield) is as high as 94%, and the enantioselectivity (ee value) is as high as 95%; when the reaction substrate is 2,6-di-tert-butyl-4-(2-methylbenzylidene)cyclohexa-2,5-diene-1-one, the yield (yield) is as high as 93%, and the enantioselectivity (ee value) is as high as 96%; when the reaction substrate is 2,6-di-tert-butyl-4-(naphthalene-2-methylene)cyclohexa-2,5-diene-1-one, the yield (yield) is as high as 89%, and the enantioselectivity (ee value) is as high as 92%. In summary, the PS-CS-SiO prepared in Example 1 2 @Cu catalytic materials are generally applicable to the preparation of chiral benzyl borate compounds.

[0091] (4) PS-CS-SiO in Example 2 2 @Cu catalytic material was recycled for 0 times. In Examples 6 to 10, PS-CS-SiO 2 @Cu catalyst, and the number of cycles was 1, 2, 3, 4 and 5 respectively, to investigate the performance of the recycled catalyst. The yield (yield) and enantioselectivity (ee value) of the chiral organoboron compound finally prepared are shown in Table 3: Table 3 Effect of catalyst recycling times on the yield and enantioselectivity of organic boron compounds

[0092] From the data in Table 3, we can see that PS-CS-SiO 2 The number of times the @Cu catalyst is recycled has almost no effect on the yield (yield) and enantioselectivity (ee value) of chiral benzyl borate compounds. The yield (yield) and enantioselectivity (ee value) of the catalyst that was not recycled and the catalyst that was recycled 5 times were both over 90%, and almost completely converted. This shows that the catalytic effect of the recycled catalyst is still significant, and the performance of the recycled catalyst is good, achieving the purpose of recycling, saving costs and responding to the concept of green chemistry development.

[0093] (5) PS-CS-SiO in Example 2 2 @The amount of Cu catalyst material added is 5 mg, and the PS-CS-SiO 2The addition amount of @Cu catalytic material was 2 mg, 3 mg, 4 mg, and 6 mg, respectively, to investigate the effect of the catalyst addition amount on the yield (yield) and enantioselectivity (ee value) of the prepared chiral organic boron compound. The yield (yield) and enantioselectivity (ee value) of the chiral organic boron compound prepared are shown in Table 4: Table 4 Effect of catalyst addition on the yield and enantioselectivity of the preparation of organoboron compounds

[0094] It can be seen from Table 4 that when the addition amount is 5 mg or more, the yield (yield) and enantioselectivity (ee value) are both as high as over 95%, almost achieving complete conversion.

[0095] It should be noted that the present application is not limited to the above-mentioned embodiments. The above-mentioned embodiments are only examples, and the embodiments having the same structure as the technical idea and exerting the same effect within the scope of the technical solution of the present application are all included in the technical scope of the present application. In addition, without departing from the scope of the main purpose of the present application, various modifications that can be thought of by those skilled in the art to the embodiments and other methods of combining some of the constituent elements in the embodiments are also included in the scope of the present application.

Claims

1. A method for preparing a chiral benzyl borate compound, characterized in that: The steps include: S1. Mix p-methylene benzoquinone compound, bipyraclostrobin, Bolm chiral ligand, PS-CS-SiO2@Cu catalytic material and reaction solvent, stir and react for a set time, and after the reaction is completed, reduce pressure and filter to obtain filtrate and filter residue. The structural formula of the p-methylene benzoquinone compound is as follows: ； wherein R1 and R2 are independently selected from alkyl, cycloalkyl, aromatic, heterocyclic, alkoxy, aryloxy, alkylamino, aromatic amino or halogen; R3 is selected from alkyl, cycloalkyl, aromatic or heterocyclic groups; S2, extracting the filtrate in step S1 with ethyl acetate and saturated brine in sequence, then drying the organic phase with anhydrous Na2SO4, filtering under reduced pressure and rotary drying to obtain a crude product; S3. Purify the crude product by thin layer chromatography to obtain a 1,6-chiral benzyl borate compound with the following structural formula: ； wherein R1, R2 and R3 are the same as those in the corresponding methylene benzoquinone compounds.

2. The method for preparing a chiral benzyl borate compound according to claim 1, characterized in that: In the p-methylene benzoquinone compound and the correspondingly prepared 1,6-chiral benzyl borate compound, R1 and R2 are selected from tert-butyl; R3 is selected from phenyl, 4-methylphenyl, 2-methylphenyl or naphthyl, and the p-methylene benzoquinone compound is selected from the following compounds: ； The corresponding 1,6-chiral benzyl borate ester compounds are selected from the following compounds: 。 3. The method for preparing a chiral benzyl borate compound according to claim 1, characterized in that: In step S1, 0.24 mmol of bipyraclostrobin, 0.5-1.0 mg of Bolm chiral ligand, 2 mL of reaction solvent and 2-6 mg of PS-CS-SiO2@Cu catalyst material were added to every 0.2 mmol of p-methylene benzoquinone compound, and the reaction was stirred at room temperature for 10-14 h.

4. The method for preparing a chiral benzyl borate compound according to claim 1, characterized in that: The Bolm chiral ligand is Bolm Ligand, and its structural formula is: 。 5. The method for preparing a chiral benzyl borate compound according to claim 1, characterized in that: The filter residue in step S1 is washed with petroleum ether and vacuum dried, and the PS-CS-SiO2@Cu catalytic material is recovered and recycled.

6. The method for preparing a chiral benzyl borate compound according to claim 1, characterized in that: The carrier of the PS-CS-SiO2@Cu catalytic material is PS-CS-SiO2 nanocomposite microspheres, which are composed of PS monodisperse microsphere powder, SiO2 and chitosan. The active component Cu is loaded on the PS-CS-SiO2 nanocomposite microspheres. 2 + , and obtained PS-CS-SiO2@Cu catalytic material.

7. The method for preparing a chiral benzyl borate compound according to any one of claims 1 to 6, characterized in that: The preparation method of the PS-CS-SiO2@Cu catalytic material comprises the following steps: P1. Prepare PS monodisperse microsphere powder in advance, add 0.8-1.0 g of hexadecyltrimethylammonium bromide, 100-150 mL of anhydrous ethanol and 80-120 mL of distilled water to every 0.8-1.2 g of PS monodisperse microsphere powder, stir for 0.2-0.5 h, then add 0.5-1.0 mL of concentrated ammonia water and 0.5-0.8 mL of tetraethyl silicate, stir at room temperature for 4-8 h, heat in an oil bath at 80 ° C for 10-18 h, and vacuum dry at 40-60 ° C for 10-18 h to obtain PS-SiO2 powder; P2, add 0.4~0.6g PS-SiO2 powder and 102mL 1~5% v / v acetic acid aqueous solution to every 0.8~1.2g chitosan to obtain system A; P3. Add 40-60 mL of anhydrous ethanol and 40-60 mL of distilled water to every 10.0-15.0 g of sodium hydroxide, stir until colorless and clear, and cool to room temperature to obtain system B; P4, adding system A dropwise into system B to form microspheres, filtering, washing with anhydrous ethanol, and drying at room temperature to obtain PS-CS-SiO2 nanocomposite microspheres; P5. Loading Cu on PS-CS-SiO2 nanocomposite microspheres 2+ , and obtained PS-CS-SiO2@Cu catalytic material.

8. The method for preparing a chiral benzyl borate compound according to claim 7, characterized in that: The method for preparing the PS monodisperse microsphere powder in step P1 comprises the following steps: P11, add 2.0-2.5 g of polyvinyl pyrrolidone, 0.4-0.6 g of azobisisobutyronitrile, 20-40 mL of styrene, and 2-5 mL of distilled water to every 80-100 mL of anhydrous ethanol, perform ultrasonic dispersion at room temperature for 0.5-1 h, and stir at 60-100 °C for 18-30 h under inert gas protection to obtain a mixed solution; P12. The mixed solution was centrifuged to obtain a precipitate, and the precipitate was washed with anhydrous ethanol to obtain PS monodisperse microsphere powder.

9. The method for preparing a chiral benzyl borate compound according to claim 7, characterized in that: The preparation method of the PS-CS-SiO2@Cu catalytic material in step P5 comprises the following steps: P51, placing the PS-CS-SiO2 nanocomposite microspheres obtained in step S4 in a water bath at 40-60°C for 1-2h to obtain system C; P52, add 3.0~5.0g of copper acetate to every 40~60mL of distilled water, stir at room temperature for 4~8h to obtain system D; P53. Stir and mix system C and system D, adsorb for 4 to 8 hours, filter, rinse with distilled water, and dry to obtain PS-CS-SiO2@Cu catalytic material.

10. The method for preparing a chiral hydroxy compound from a 1,6-chiral benzyl borate compound according to any one of claims 1 to 6, characterized in that: The steps include: (1) Add 240-250 mg of NaBO3·4H2O and 4-6 mL of a THF-H2O mixed solvent to the 1,6-chiral benzyl borate compound obtained in step S3, stir at room temperature for 3-6 h, extract with ethyl acetate and saturated brine in sequence, then dry the organic phase with anhydrous Na2SO4, filter under reduced pressure and spin dry; (2) The residue is spin-dried and purified by thin layer chromatography to obtain a chiral hydroxy compound.

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