LU601268B1

LU601268B1 - APPLICATION OF A BIOMASS-BASED CS-PNIPAAM-MBAA@Cu²+ CATALYST IN THE SYNTHESIS OF CHIRAL BORON COMPOUNDS

Info

Publication number: LU601268B1
Application number: LU601268A
Authority: LU
Inventors: Weishuang Li; Yaoyao Zhang; Lei Zhu; Bojie Li
Original assignee: Univ Hubei Engineering
Priority date: 2023-09-07
Filing date: 2024-06-12
Publication date: 2025-06-24
Also published as: CN117209344A; WO2025050741A1

Abstract

This application involves the use of a biomass-based CS-PNIPAAm-MBAA@Cu²⁺ catalyst in the synthesis of chiral boron compounds. In this synthetic reaction, chalcone and bis(pinacolato)diboron are used as starting materials, with the addition of a chiral ligand. The prepared catalyst is applied in an aqueous medium for a boron addition reaction, synthesizing chiral boron-containing compounds. The catalyst used in this reaction is characterized by its ability to be recycled through filtration, easy operation, high catalytic efficiency, and environmentally friendly nature. The entire synthetic reaction achieves high yields and excellent enantiomeric selectivity. (FIG 1)

Description

DESCRIPTION LU601268

APPLICATION OF A BIOMASS-BASED CS-PNIPAAM-MBAA@Cu?* CATALYST IN

THE SYNTHESIS OF CHIRAL BORON COMPOUNDS

This application claims priority to the Chinese patent application filed with the China

Patent Office on September 7, 2023, with application number 202311162781.X and the invention title "Application of a Biomass-Based CS-PNIPAAm-MBAA@Cu?* Catalyst in the Synthesis of Chiral Boron Compounds." The entire content of that application is hereby incorporated by reference into this application.

TECHNICAL FIELD

The present invention relates to the chiral catalysis field, particularly the application of a biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst in synthesizing chiral organic boron compounds.

BACKGROUND ART

Chiral organic boron compounds are essential synthetic intermediates for effectively constructing optically active molecules, with significant applications in pharmaceutical synthesis. Therefore, the synthesis of chiral organic boron compounds is of critical importance. In recent years, synthetic chemists have developed a series of efficient synthetic reactions, including asymmetric hydroboration, asymmetric addition to unsaturated bonds, and C-H borylation, to construct chiral organic boron compounds.

Transition metal-catalyzed boron conjugate addition to a,B-unsaturated carbonyl compounds and related compounds provides the most efficient and direct approach to form functionalized organoboron reagents. The products generated from these reactions serve as essential intermediates in synthesis and can be converted into critical functional groups, such as hydroxyl, aryl, and alkenyl, through Suzuki coupling reactions.

These compounds hold significant value in fine chemicals, pharmaceuticalsU601268 materials science, and other fields.

Chitosan is one of the few essential polysaccharides in natural polymers. It is insoluble in water and organic solvents but dissolves in dilute acid with pH <6.5. In dilute acid, the glucosamine group in chitosan converts into R-NH3*, forming a polycationic gel solution while containing both hydroxyl and amino groups. These groups can undergo reactions such as acylation, carboxylation, hydroxylation, cyanation, etherification, alkylation, esterification, imination, azidation, salification, chelation, hydrolysis, oxidation, halogenation, grafting, and cross-linking to generate derivatives with various structures and properties.

In 1811, French scientist H. Braconnot extracted chitin from the shells of animals. In 1859, French scientist Rouget boiled chitin in concentrated KOH solution, washed it, and obtained a product soluble in organic acids - chitosan. In 1934, the first patents related to preparing chitosan and its related substances appeared in the United States. By 1941, chitosan was successfully used to develop artificial skin and surgical sutures. By the 1990s, the application and production of chitosan reached a peak, with an annual global output of tens of thousands of tons.

Chitosan with a degree of deacetylation greater than 95% has high purity and vigorous activity. The product used in this invention relies on highly deacetylated chitosan.

Due to the excellent properties of chitosan, such as biodegradability, low toxicity, and good biocompatibility, it is widely applied in the fields of medicine, hygiene, personal care, cosmetics, food, agriculture, and chemical engineering, covering aspects of people's clothing, food, housing, and transportation. Furthermore, with their low cost and low toxicity, chitosan-supported metal catalytic materials show great potential for application.

SUMMARY LU601268

This application aims to provide a biomass-based catalyst material loaded with copper for the synthesis of chiral organic boron compounds. This catalytic material introduces hydrophilic materials and utilizes the abundant availability and low cost of chitosan to achieve temperature-controlled recovery. The catalyst exhibits catalytic activity by loading divalent copper salts, which can be applied to chiral organoboron addition reactions in an aqueous medium. This catalytic material improves catalytic activity, enhances chiral catalytic efficiency, and produces compounds with high yields and high enantiomeric excess (ee). The biomass material described in this invention enables the catalyst to be filtered and recovered after the reaction, allowing effective reuse.

To achieve the objective above, the present application provides the following technical solution:

A biomass-based CS-PNIPAAM-MBAA@Cu?** catalyst, comprising a

CS-PNIPAAm-MBAA material and Cu?* ions loaded within the pore structure of the

CS-PNIPAAm-MBAA material.

Preferably, the preparation method of the CS-PNIPAAm-MBAA material includes the following steps:

Step 1.1: Dissolve chitosan: Add chitosan powder to a solvent and stir thoroughly to obtain a mixed solution.

Step 1.2: Polymerization with hydrophilic materials: Mix the chitosan mixed solution with N-isopropylacrylamide (NIPAAm) and N,N’-methylenebisacrylamide (MBAA), then add an initiator to initiate the polymerization reaction under sealed conditions at room temperature. Dry the resulting product from the polymerization reaction in a vacuum to obtain the CS-PNIPAAm-MBAA material.

Preferably, in Step 1.1, the solvent is a 1%-3% aqueous acetic acid solution, and stirring is conducted at room temperature for 6-12 hours.

Preferably, chitosan is a natural polycationic linear polysaccharide derived from chitin, with a degree of deacetylation greater than 95%.

Preferably, after completing the reaction in Step 1.2, the process also includd4/601268 alternating vacuum evacuation and nitrogen purging 15 times, and the final step is conducted in a nitrogen atmosphere.

Preferably, in step 1.2, the mass ratio of N,N'-methylenebisacrylamide to chitosan is 1:5-15, and the mass ratio of N-isopropylacrylamide to chitosan is 1:0.1-1.

Preferably, in Step 1.2, the initiator is N,N,N’ N'-tetramethylethylenediamine (TMEDA) and ammonium persulfate (APS). The ratio of

N,N,N’ ,N'-tetramethylethylenediamine to ammonium persulfate is 20 uL:1.2741 g; the mass ratio of ammonium persulfate to chitosan is 1~3:1.

Preferably, the polymerization reaction time is 12 hours.

Preferably, in Step 1.2, the drying temperature is 50 °C, and the drying time is 12 hours.

Preparation of Biomass-Based CS-PNIPAAM-MBAA@Cu?* Catalyst

This invention also provides a preparation method for the aforementioned biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst, which includes the following steps:

Mix the CS-PNIPAAm-MBAA material with a divalent copper salt solution and stir at room temperature. Filter the mixture and place it in a vacuum-drying oven to dry, obtaining the biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst.

Preferably, the divalent copper salt in the solution is copper sulphate and/or copper chloride.

Preferably, the stirring reaction time is 12 hours.

Preferably, the drying temperature is 50°C, and the drying time is 6~9 hours.

Preferably, before filtration, the reaction system is placed in a water bath for heating, and filtration is performed while the mixture is still hot. The water bath temperature is set to 70°C, and the water bath heating time is 10~30 minutes.

Application in the Synthesis of Chiral Boron-Based Compounds

This invention also provides a method for using the biomass-based

CS-PNIPAAm-MBAA@Cu?* catalyst in the synthesis of chiral boron-based compounds, which includes the following steps:

Step (1): Use a,B-unsaturated aldehyde or ketone compounds and pinacol dibordr/601268 as raw materials, with the biomass-based CS-PNIPAAM-MBAA@Cu?* as the catalyst.

Add a chiral ligand while stirring uniformly at room temperature in an aqueous organic mixed solvent to obtain a reaction mixture containing B-boryl-substituted carbonyl compounds.

Step (2): Perform pretreatment on the reaction mixture obtained in Step (1) to yield chiral boron-based compounds.

The structural formula of the described a,B-unsaturated aldehyde or ketone compound is:

The structural formula of the described B-boronic ester substituted carbonyl compound is:

The structural formula of the described chiral boron-containing compound is:

Wherein R1 is one of phenyl, p-tolyl (para-methylphenyl), p-methoxyphenyl (para-methoxyphenyl), or m-tolyl (meta-methylphenyl);

R2 is one of phenyl p-tolyl, p-methoxyphenyl, p-fluorophenyl, p-chlorophenylJ601268 p-bromophenyl, o-chlorophenyl (ortho-chlorophenyl), m-bromopheny! (meta-bromophenyl), or m-chlorophenyl (meta-chlorophenyl);

The chiral ligand is (R)-1-1[(S)-2-(diphenylphosphino)ferrocenyl]ethyl-dicyclohexylphosphine.

Preferably, after the completion of step (2), it further includes step (3):

The step (3) is mixing the obtained chiral boron-containing compound with sodium perborate tetrahydrate, tetrahydrofuran, and deionized water, reacting at room temperature, and after secondary treatment, receiving a chiral hydroxyl-containing compound.

The structural formula of the described chiral hydroxyl-containing compound is:

Preferably, in step (1), the aqueous organic mixed solvent is a mixture of toluene and distilled water in a volume ratio of 10:1 to 7:1.

Preferred conditions: In step (1), the ratio of catalyst to aqueous-organic mixed solvent is 1-10 mg: 2 mL.

Preferred conditions: The molar ratio of a,B-unsaturated aldehyde/ketone compound, bis(pinacolato)diboron, catalyst, and chiral ligand is 1 : (1.0-3.0) : (1%-10% mol) : (1%-10% mol).

Preferably, in step (1), the mixing and stirring time is 10-20 hours.

Preferably, in step (3), the reaction time at room temperature is 4-8 hours.

Preferably, in step (3), the dosage ratio of sodium perborate tetrahydraté/601268 tetrahydrofuran (THF), and deionized water is 244 mg: 3 mL: 2 mL.

Preferably, the secondary treatment includes extraction, rotary evaporation, and thin-layer chromatography (TLC).

Compared with the prior art, the catalyst prepared by the present invention has the following advantages in the synthesis of chiral boron compounds: 1. The catalyst material uses inexpensive and readily available chitosan as the raw material of the catalyst. Chitosan is widely sourced, cost-effective, and has excellent properties such as good biocompatibility, safety, and microbial degradability. Meanwhile, introducing the temperature-sensitive material N-isopropylacrylamide imparts hydrophilicity to the product. During the reaction, it enhances the interaction with hydrophobic substrates, accelerating the reaction. The application of this catalyst to boration reactions allows the synthesis of chiral organoboron compounds, broadening its application field. 2. This catalyst enables catalysis under room-temperature conditions without light exposure, expanding the usage conditions of the catalyst and increasing its application scope with broad prospects. Furthermore, the catalytic reaction is an organic catalysis in an aqueous medium, achieving green catalysis with high efficiency, good stability, and environmental friendliness. 3. After the reaction, the catalyst material can be recovered simply through filtration and reused. Because the catalyst contains chitosan, which is hydrophobic and insoluble in water, it can be filtered and recovered directly. In synthesizing chiral boron compounds, excessively high temperatures are not energy-efficient, so lowering the temperature to room temperature also allows direct filtration to recycle the catalyst. 4. The preparation of the catalyst involves mild reaction conditions. Most reactions occur at room temperature using an aqueous acetic acid solution as the solvent, making the process simple and easy to operate. Additionally, there are fewer by-products, and the yield is high.

5. The catalyst is compatible with commercially available chiral ligands such 44/601268 (R)-1-1[(S)-2-(diphenylphosphino)ferrocenyl]ethyl-dicyclohexylphosphine. A high yield of chiral organoboron compounds can be achieved using a small amount of ligand (2% of the substrate).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG 1: The SEM image of CS-PNIPAAM-MBAA.

FIG 2: The SEM image of CS-PNIPAAm-MBAA@Cu?*.

FIG 3: The infrared spectra of CS (chitosan), NIPAAm, CS-PNIPAAm-MBAA, and

CS-PNIPAAM-MBAA@Cu?*.

DETAILED DESCRIPTION OF THE EMBODIMENTS

To better understand this invention, the following provides a detailed explanation based on the accompanying figures and specific examples. The described embodiments represent part of the implementation examples of this invention rather than all possible embodiments.

Here, the invention is elaborated using the accompanying figures and specific examples. The invention uses chitosan (with a degree of deacetylation greater than 95%), hydrophilic material N-isopropylacrylamide, and N,N'-methylene bisacrylamide as raw materials. N-isopropylacrylamide serves as the hydrophilic monomer, while TEMED (tetramethylethylenediamine) and APS (ammonium persulfate) are used as initiators.

The system is prepared in deionized water, followed by the adsorption of copper ions, forming the biomass-based catalytic material CS-PNIPAAM-MBAA@Cu?*.

The prepared material is characterized using SEM, infrared spectroscopy, and various other methods to study its structural morphology and composition.

Example 1

1. At room temperature, weigh 0.5 g of chitosan powder and place it into a 50 nHU601268 single-neck flask. Measure 30 mL of deionized water and 1 mL of glacial acetic acid with a graduated cylinder and sequentially add them to the aforementioned flask. Select a suitably sized magnetic stirrer bar, place it into the flask, seal the system, and start the magnetic stirrer. Stir until the chitosan is completely dissolved to obtain the CS-HAc solution set aside for later use. 2. At room temperature, weigh 46.4 mg of MBAA, 1 g of NIPAAm, and 1.2741 g of

APS, and place them into a 50 mL Schlenk tube. Transfer the CS-HAc solution prepared in step 1 with 20 pL of TEMED into the Schlenk tube. Place a suitably sized magnetic stirrer bar into the tube and perform 15 cycles of vacuuming and nitrogen purging at room temperature. Seal the system and stir for 12 hours at room temperature. 3. After the reaction in step 2 is complete, transfer the solution from the Schlenk tube into a suitably-sized Petri dish. Dry it in a vacuum oven at 50°C for 12 hours to obtain the dried CS-PNIPAAm-MBAA material. Remove the product, grind it to a fine powder, and then set it aside. Conduct SEM characterization on the

CS-PNIPAAm-MBAA material, with results shown in Figure 1. The product has an irregular shape and exhibits an overall porous structure, which is beneficial for loading metal ions. 4. Weigh 4.9936 g of copper sulfate pentahydrate into a beaker. Measure 50 mL of deionized water with a graduated cylinder and add it to the beaker. Add a suitably sized magnetic stirrer bar and stir evenly to obtain a 0.4 mol/L copper solution, which is set aside for later use. 5. Take the CS-PNIPAAm-MBAA material synthesized in step 3 and the copper solution prepared in step 4, and transfer them into a 100 mL single-neck flask for copper loading. The copper-loading process lasts for 12 hours. 6. Place the reaction system in step 5 into a 70°C water bath to heat for 10 to 30 minutes. Use a Buchner funnel to filter the hot mixture, wash it with hot water, and transfer the product into a Petri dish. Dry it in a vacuum oven at 50°C for 12 hours to obtain the dried biomass-based CS-PNIPAAm-MBAA@Cu”* catalyst. Remove the product, grind it to a fine powder, and set it aside.

Conduct SEM characterization of the biomass-based CS-PNIPAAm-MBAA@Cu*U601268 with results shown in Figure 2. The surface of the material becomes smoother after copper loading. Perform infrared characterization on the prepared catalytic material, with results shown in Figure 3. The 1638 cm™ peak is a characteristic peak for hydrophilic materials in the catalyst, and the 681 cm™ peak represents the coordination characteristic peak of copper ions.

Application Example 1

The biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst synthesized in Example 1 is used in this application example. The specific steps are as follows:

The chemical reaction equation for Step 1 is as follows: a 8 Bipisi

N À ,[ ; Bafpindy yg 1 ai LG, =F y LR S)iosiphos u “~~ A uv hg CS INIPAABMBAA GCE O =

SE

: A N :

DB

L Ri) esipbes

The chemical reaction equation for Step 3 is as follows:

D Bi) uo OH

AU > NaS Oy <H;0 a ANA,

At room temperature, weigh 0.2 mmol (41.7 mg) benzylideneacetophenone (chalcone), 0.24 mmol (60.9 mg) pinacol diborane, 0.002 mmol of the chiral ligand (R)-1-1[(S)-2-(diphenylphosphino)ferrocenyl]ethyl-dicyclohexylphosphine (1.0% molar equivalent of benzylideneacetophenone), and 0.002 mmol of the biomass-based

CS-PNIPAAm-MBAA@Cu?* catalyst (the amount of Cu?" corresponds to 1.0% molar equivalent of benzylideneacetophenone). Place them into a sample vial. Then, add 1.8 mL of toluene and 0.2 mL of deionized water to the vial.

Put a magnetic stir bar of appropriate size into the vial, seal it, and stir with a magnetic stirrer at room temperature for 12 hours. This generates a mixture containing

B-borylated substituted carbonyl compounds.

After the reaction in Step 1, extract the mixture containing B-borylated substituted carbonyl compounds using ethyl acetate as the extraction solvent. Separate the organic phase, dry it with anhydrous NazSO,, filter, and remove ethyl acetate using a rotary evaporator to obtain a chiral boron-based compound.

Add 244 mg of sodium perborate tetrahydrate, 3 mL of tetrahydrofuran (THF), and 2 mL of deionized water to the reaction flask from Step 2. Insert a magnetic stir bar of appropriate size into the flask. Stir at room temperature using a magnetic stirrer for 4 hours.

After the reaction in Step 3 is complete, extract the reaction mixture with ethyl acetate to separate the organic phase. Dry the organic phase using anhydrous Na,SO,, filter, and remove ethyl acetate with a rotary evaporator. Finally, column chromatography purifies the resulting product (chiral hydroxy compound). The elution solvent used for column chromatography is a mixture of ethyl acetate and petroleum ether at a volume ratio of 1:4.

Dissolve the product obtained in Step 4 in a suitable amount of isopropanol. Use a nylon membrane for sample preparation. Employ high-performance liquid chromatography (HPLC) to determine the enantiomeric selectivity of the chiral hydroxy compound, which is 60%, and the product yield is 58%.

Application Example 2

The chemical reaction equation for Step 1 is as follows: i Halpinky

FF Ri : L{R,S-esiahos A Na

GO CS-PNIPAA-MBAA@Us u ae : PP i, :

The chemical reaction equation for Step 3 is as follows: LU601268 a Bipin) 8 OR

TN ~ TN Maloy SRO ra A ; ess

VA va 3h Va Sa

In this application example, the biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst from Example 1 is used, and the same method as in Example 1 is applied to prepare chiral boron compounds. The difference is that the chiral ligand used in this application example is (R)-1-1[(S)-2-(diphenylphosphino)ferrocenyl]ethyl-dicyclohexylphosphine, and the amount of this ligand is 1.5% of the substrate. The detailed steps are as follows: 1. At room temperature, 0.2 mmol (41.7 mg) benzylideneacetophenone, 0.24 mmol (60.9 mg) pinacolborane, 0.003 mmol chiral ligand (R)-1-1[(S)-2-(diphenylphosphino)ferrocenyl]ethyl-dicyclohexylphosphine, and 0.002 mmol biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst (the molar amount of Cu** is 1.0% of the molar amount of benzylideneacetophenone substrate) are added into a sample vial. Then, 1.8 mL toluene and 0.2 mL deionized water are added to the vial. A suitably sized magnetic stir bar is placed into the vial, and the mixture is magnetically stirred under sealed conditions at room temperature for 12 hours, forming a mixture system containing B-boronic ester-substituted carbonyl compounds. 2. After the reaction, the mixture system containing B-boronic ester-substituted carbonyl compounds from Step 1 is extracted and separated using ethyl acetate as the extraction solvent. The organic phase is isolated, dried over anhydrous Na,SO,, and filtered, and the ethyl acetate is removed using a rotary evaporator to obtain chiral boron-containing compounds. 3. Into the reaction vial from Step 2, 244 mg sodium perborate tetrahydrate, 3 mL tetrahydrofuran, and 2 mL deionized water are added. A suitably sized magnetic stir bar is placed into the reaction vial. The mixture is stirred at room temperature using a magnetic stirrer for 4 hours.

4. After the reaction in Step 3, the mixture is extracted and separated using ethyV601268 acetate as the extraction solvent. The organic phase is isolated, dried over anhydrous

Na,SO,, and filtered, and the ethyl acetate is removed using a rotary evaporator. Chiral hydroxyl compounds are obtained after separation by column chromatography, where the volume ratio of ethyl acetate to petroleum ether used in the chromatography is 1:4. 5. Finally, an appropriate amount of isopropanol is added to the reaction vial from

Step 4 to dissolve the product. A nylon filter membrane is used for pretreatment.

High-performance liquid chromatography (HPLC) measures the enantioselectivity of the chiral hydroxyl compounds, which was determined to be 85%, and the product yield is 78%.

The chemical reaction equation for Step 1 in Application Example 3 is as follows: 2 % Bipin ; ; Bein

ANF CSSS LiRshesehes LA,

TV uv C5-PNIPAAm-MBAA GOUT y =

The chemical reaction equation for Step 3 in Application Example 3 is as follows: a Bin} a OH

A ANA NO 40 NNN

Se Sa An Sy Se

The biomass-based CS-PNIPAAm-MBAA@Cu?* catalyst from Example 1 is used in this application example. The same method as in Example 2 is applied to prepare chiral boron compound catalytic materials. The difference is that in this application example, the amount of the chiral ligand (R)-1-1[(S)-2-(diphenylphosphino)ferrocenyl]ethyl-dicyclohexylphosphine used is 2.0% (0.004 mmol) of the substrate benzylideneacetophenone.

The amount of Cu?" in the biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst is 1.5% (0.003 mmol) of the substrate benzylideneacetophenone. High-performance liquid chromatography (HPLC) measured the enantioselectivity of the chiral hydroxyl compound to be 93%, with a product yield of 97%.

Application Example 4

This example provides an application method for the biomass-based

CS-PNIPAAm-MBAA@Cu?* catalytic material in synthesizing chiral boron-containing compounds using (E)-3-(4-chlorophenyl)-1-2-en-1-one as the substrate. The specific experimental steps refer to those in Application Example 3. The chemical reaction equation for Step (1) is as follows:

NEN > ct

The chemical reaction equation for Step (3) is as follows: 3 Sein) 9 OH

The biomass-based CS-PNIPAAMm-MBAA@Cu?* catalytic material is applied to the chiral boron addition reaction of (E)-3-(4-chlorophenyl)-1-2-en-1-one. In Step (3), the yield of the target product (a chiral hydroxyl compound) and its enantioselectivity values are 92% and 90%, respectively.

Application Example 5

This example provides an application method for the biomass-based

CS-PNIPAAm-MBAA@Cu?* catalytic material in synthesizing chiral boron-containing compounds using (E)-3-(4-bromophenyl)-1-2-en-1-one as the substrate. The specific experimental steps refer to those in Application Example 3. The chemical reaction equation for Step (1) is as follows:

9 . Lu Q Bfpmi LU601268 ® Hm G ; 020 SC AA, <a, as Lo” LiRSHosiphos 0 Lo Br

The chemical reaction equation for Step (3) is as follows: spin) o ou

THES O=32 ® N æ SE an R- : Br

The biomass-based CS-PNIPAAM-MBAA@Cu?* catalytic material is applied to the chiral boron addition reaction of (E)-3-(4-bromophenyl)-1-2-en-1-one. In Step (3), the yield of the target product (a chiral hydroxyl compound) and its enantioselectivity values are 86% and 89%, respectively.

Application Example 6

This example provides an application method for the biomass-based

CS-PNIPAAm-MBAA@Cu?* catalytic material in synthesizing chiral boron-containing compounds using (E)-3-(4-methoxyphenyl)-1-2-en-1-one as the substrate. The specific experimental steps refer to those in Application Example 3. The chemical reaction equation for Step (1) is as follows: i © Bipin) lo C . x os °C 5-20 LX G

Pr es oH, a) vtt L{R 5 josiphos À L oc,

The chemical reaction equation for Step (3) is as follows:

Binin} ox i - “HE tt

N & = LS A = VF SCH 5

The biomass-based CS-PNIPAAM-MBAA@Cu?* catalytic material is applied to the chiral boron addition reaction of (E)-3-(4-methoxyphenyl)-1-2-en-1-one. In Step (3), the yield of the target product (a chiral hydroxyl compound) and its enantioselectivity values are 94% and 92%, respectively.

Application Example 7 LU601268

After the reaction, the mixture is cooled to room temperature. The catalyst is recovered through filtration, washed with hexane, dried, and reused. The biomass-based

CS-PNIPAAm-MBAA@Cu?* catalytic material is applied for the fifth time to chalcone's chiral boron addition reaction. The specific experimental steps refer to those in

Application Example 3. The yield of the target product (a chiral hydroxyl compound) and its enantioselectivity values are 91% and 89%, respectively.

The results of this example demonstrate that the biomass-based

CS-PNIPAAM-MBAA@Cu?* catalytic material provided in Application Example 3 achieves the highest conversion rate and enantioselectivity for the boron addition reaction of chalcone. The yield of the target product (a chiral hydroxyl compound) and its enantioselectivity reach 97% and 93%, respectively. Furthermore, the catalyst is recyclable. After being reused in four catalytic cycles, the fifth application of this catalyst in chalcone's chiral boron addition reaction still yields 91% and 89% for the product yield and enantioselectivity, respectively.

The above description represents only the preferred embodiments of this application.

It should be noted that for an ordinary person skilled in the art, several improvements and modifications can be made without departing from the principles of this application.

These improvements and changes are also considered within the scope of protection of this application.

Claims

CLAIMS LU601268

1, A biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst, characterized by comprising a CS-PNIPAAm-MBAA material and Cu?* ions loaded within the pore structure of the CS-PNIPAAm-MBAA material.

2; The biomass-based CS-PNIPAAm-MBAA@Cu?* catalyst, according to claim 1, is characterized in that the preparation method of the CS-PNIPAAm-MBAA material comprises the following steps:

Step 1.1. dissolving chitosan: adding chitosan powder into a solvent, stirring thoroughly to obtain a chitosan mixed solution;

Step 1.2. polymerizing with a hydrophilic material: mixing the chitosan mixed solution, N-isopropylacrylamide, and N,N'-methylenebisacrylamide, then adding an initiator to initiate polymerization under a sealed environment at room temperature; the product obtained from the initiation polymerization reaction is dried in a vacuum to yield the CS-PNIPAAM-MBAA material.

3; The biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst, according to claim 2, is characterized in that, in step 1.1, the solvent is a 1%-3% acetic acid aqueous solution, and the stirring is continued for 6-12 hours at room temperature.

4; The biomass-based CS-PNIPAAm-MBAA@Cu?* catalyst, according to claim 2, is characterized in that the chitosan is a natural polycationic linear polysaccharide derived from chitin, with a degree of deacetylation greater than 95%.

5; The biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst, according to claim 2, is characterized in that, in step 1.2, the mass ratio of N,N'-methylenebisacrylamide to chitosan is 1:5 to 1:15, and the mass ratio of N-isopropylacrylamide to chitosan is 1:0.1 to 1:1.

6 The biomass-based CS-PNIPAAm-MBAA@Cu?* catalyst, according to claim 2, 601268 characterized in that, after the completion of step 1.2, the vacuum pumping and nitrogen purging steps are repeated 15 times, and the final procedure is carried out under a nitrogen environment.

7; The biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst according to claim 2 is characterized in that, in step 1.2, the initiator is N,N,N',N'-Tetramethylethylenediamine (TMEDA) and ammonium persulfate (APS); the usage ratio of TMEDA to APS is 20 uL:1.2741 g; and the mass ratio of ammonium persulfate to chitosan is 1-3:1.

8; The biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst, according to claim 2, is characterized by the reaction time of the initiation polymerization, which is 12 hours.

9; The biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst, according to claim 2, is characterized in that, in step 1.2, the drying temperature is 50°C, and the drying time is 12 hours.

10; A preparation method for the biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst according to any one of claims 1 to 9 is characterized in that it comprises the following steps: mixing the CS-PNIPAAm-MBAA material with a divalent copper salt solution, stirring the reaction at room temperature, and then filtering and drying in a vacuum drying oven to obtain the biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst.

11; According to claim 10, the preparation method is characterized by the divalent copper salt in the divalent copper salt solution being copper sulphate and/or copper chloride.

12; According to claim 10, the preparation method is characterized by the stirring reaction time being 12 hours.

13; According to claim 10, the preparation method is characterized in that the drying temperature is 50°C, and the drying time is 6 to 9 hours.

14; According to claim 10, the preparation method is characterized in that, before filtering, the method further comprises the following step: placing the reaction system in a water bath for heating and filtering while hot; The temperature of the water bath is 70°C, and the heating time in the water bath is 10 to 30 minutes.

15; An application of a biomass-based CS-PNIPAAM-MBAA@Cu?* catalyst in the synthesis of chiral boron compounds is characterized in that it comprises the following steps:

Step (1): using a,B-unsaturated aldehyde-ketone compounds and diboron pinacol ester as raw materials, employing biomass-based CS-PNIPAAm-MBAA@Cu?** as the catalyst, adding a chiral ligand, and mixing uniformly at room temperature in an aqueous-organic mixed solvent to obtain a mixed system containing B-boronate-substituted carbonyl compounds;

Step (2): to yield chiral boron compounds perform preliminary treatment on the mixed system containing B-boronate-substituted carbonyl compounds obtained in Step (1);

the structural formula of the a,B-unsaturated aldehyde-ketone compound is:

AA Ra the structural formula of the B-boronate-substituted carbonyl compound is: LU601268

O° A the structural formula of the described chiral boron-based compound is:

I among them, R1 is one of phenyl, para-methylphenyl, para-methoxyphenyl, or meta-methylphenyl;

R2 is one of phenyl, para-methylphenyl, para-methoxyphenyl, para-fluorophenylJ601268 para-chlorophenyl, para-bromophenyl, ortho-chlorophenyl, meta-bromophenyl, or meta-chloropheny!;

the described chiral ligand is (R)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyl dicyclohexylphosphine.

16; The application, as claimed in claim 1, is characterized in that, after completing step (2), it further includes step (3);

Step (3): the obtained chiral boron-based compound is mixed with sodium perborate tetrahydrate, tetrahydrofuran, and deionized water, reacted at room temperature, and after secondary processing, a chiral hydroxyl compound is obtained;

the structural formula of the described chiral hydroxyl compound is:

17; The application as claimed in claim 15, is characterized in that, in step (1), the aqueous organic mixed solvent is a mixture of toluene and distilled water in a volume ratio of 10:1~7:1.

18; The application as claimed in claim 15, is characterized in that, in step (1), the ratio of the catalyst to the aqueous organic mixed solvent used is 1~10 mg: 2 mL.

19; The application as claimed in any of claims 15 to 18, is characterized in that the molar ratio of the a,B-unsaturated aldehyde ketones, pinacol boronic ester, catalyst, and chiral ligand is 1:(1.0~3.0):(1%~10%):(1%~10%). LU601268 20; The application as claimed in claim 15 is characterized in that, in step (1), the mixing and stirring time is 10 to 20 hours.

21; The application as claimed in claim 16 is characterized in that, in step (3), the reaction time at room temperature is 4 to 8 hours.

22; The application as claimed in claim 16 is characterized in that, in step (3), the usage ratio of sodium perborate tetrahydrate, tetrahydrofuran, and deionized water is 244 mg: 3 mL: 2 ML.

23; The application as claimed in claim 16 is characterized in that the secondary treatment includes extraction, rotary drying, and thin-layer chromatography.