Preparation method and application of β-chiral boron compound

Abstract

The invention relates to a preparation method and application of a β-chiral boron compound, and the preparation steps are as follows: an α,β-unsaturated compound, a pinacol diborate, a catalyst, and an amine chiral ligand are added to a mixed solvent of toluene / water, mixed and stirred at room temperature for reaction, and the β-chiral boron compound is obtained after purification treatment, wherein the catalyst PI-CB-Cu is a catalytic material obtained by heating and crosslinking a block polymer, Ketjen black, and CuCl and microencapsulating, and the process has a high conversion rate and selectivity. The chiral addition reaction process has mild conditions and simple components, and can be successfully applied to chiral conjugate addition reactions of different types of α,β-unsaturated compounds.

Description

Technical Field

[0001] The invention relates to the field of organic synthesis, and in particular to a preparation method and application of a β-chiral boron compound. Background Art

[0002] Organoboron compounds are important building blocks in the fields of organic synthesis and biomedicine. Organoboron compounds containing chiral centers not only have good biological activity and unique catalytic properties, but also, as important intermediates in organic synthesis, can achieve a series of stereoselective and stereospecific transformations. Among them, asymmetric catalysis is one of the practical and efficient strategies for the direct preparation of chiral organoboron compounds. Using transition metal catalysis with chiral ligands, carbon-boron, carbon-carbon and other carbon heteroatom bonds can be efficiently constructed through asymmetric borylation addition, asymmetric allylic borylation and stereoselective cross-coupling borylation. At the same time, the constructed carbon-boron bond can be converted into other types of chemical bonds through coupling reactions, migration reactions, redox reactions, etc., to achieve the synthesis of multiple types of compounds.

[0003] Since the introduction of catalytic technology into industrial chemistry, the field of heterogeneous catalysis has aroused great interest among scientists. Compared with homogeneous catalysis, heterogeneous catalysis has many advantages. It not only simplifies the product processing and separation, recovery and reuse of catalysts, but also heterogeneous catalysts usually have good stability, low toxicity, functionality and the ability to solve environmental incompatibility problems. As early as 2003, the literature (JACS., 2003, 125, 3412-3413) developed a new method for preparing heterogeneous palladium catalytic materials called "polymer embedding (PI) method". By microencapsulating the copolymer with Pd in ​​Pd(PPh3)4 and then heating and crosslinking, the method is simple to operate, and the prepared Pd catalytic material (PI-Pd) has good catalytic activity for hydrogenation reactions, CC bond and CO bond formation.

[0004] There have been many reports on the use of cheap and readily available transition metal copper as a catalyst to synthesize asymmetric chiral boride. The literature (Asian J.Org.Chem., 2013, 2, 961-966) reported the use of zero-valent copper and 2,2'-bipyridine ligands to achieve asymmetric boron addition reactions of α,β-unsaturated compounds, yielding borylation products with a yield of 13%-92% and an enantiomeric selectivity of up to 83%. This method has the disadvantages of a narrow substrate range, low yield and optical activity.

[0005] In addition, most of these borylation reactions are based on monovalent copper and divalent copper catalytic systems with high metal loading, and there are few reports on zero-valent copper catalyzed boron addition reactions. In addition, due to the limitations of reaction conditions, high costs, environmental pollution, and the inability to recycle catalysts, such methods are rarely used in actual production. Summary of the invention

[0006] The present invention provides a preparation method and application of a β-chiral boron compound, wherein a block polymer copper metal catalyst material is used to prepare a chiral β-boryl compound, and the biocompatibility of the block polymer copper metal catalyst material and the complexation of hydroxyl and epoxy groups to metal ions are utilized to make the compound have higher catalytic activity, and at the same time, no strong base needs to be added in the reaction system, and the reaction can be carried out only in a mixed solvent of toluene / water, and the catalyst can be recycled for multiple times, so the method is more environmentally friendly and meets the concept of sustainable industrial production. The above-mentioned technical problems are solved.

[0007] The present invention solves the above technical problems by the following scheme: A method for preparing a β-chiral boron compound, the synthesis route is as follows:

[0008]

[0009] Wherein, R1 is phenyl, and R2 is phenyl, p-chlorophenyl, p-methoxyphenyl, p-bromophenyl, m-bromophenyl or naphthyl;

[0010] The synthesis steps are: add α,β-unsaturated compound I, pinacol borate, catalyst PI-CB-Cu, and amine chiral ligand into a mixed solvent of toluene / water, mix and stir to react for 8 to 16 hours at room temperature, and purify after the reaction (centrifuge and filter the mixed system after the reaction. Extract the obtained liquid phase with ethyl acetate solution, dry with anhydrous Na2SO4 and rotary evaporate) to obtain liquid phase β-chiral boron compound II and precipitate, wash and dry the precipitate, and then recover the catalyst.

[0011] The synthesis steps of the catalyst are as follows: 1) in a protective atmosphere, monomer 1, monomer 2, and monomer 3 are dissolved in anhydrous dichloromethane, an initiator is added, and the reaction is carried out for 40-80 hours, and then the copolymer P1 is obtained after purification (the polymer solution obtained after the reaction is slowly poured into an Et2O solution, and the solvent and excess monomers are removed by decantation. The polymer solution is slowly poured into ether again. The same procedure is repeated three times in total to precipitate the polymer, and after filtering, it is rinsed with ether for multiple times and then dried in a vacuum) The synthesis route of the copolymer P1 is as follows:

[0012]

[0013] 2) dissolving the copolymer P1 in a diethylene glycol dimethyl ether solvent, adding Ketjen black, stirring at room temperature for 30-40 minutes, adding CuCl / diethylene glycol dimethyl ether solution dropwise thereto in an ice-water bath and stirring for 30-40 minutes, then adding sodium borohydride (200-300 mg) / diethylene glycol dimethyl ether solution dropwise thereto, reacting sufficiently for 12-16 hours, washing and drying (adding an excess of Et2O solution to the reaction solution, filtering and washing with Et2O solution, vacuum drying, and repeating three times) to obtain a pre-crosslinked product; placing the pre-crosslinked product in a protective atmosphere, reacting at 150-170° C. for 5-8 hours, cooling to room temperature, and pulverizing and purifying (preliminarily grinding into powder, washing with H2O, THF and DCM in sequence, vacuum drying, and ball milling twice) to obtain a block polymer copper metal catalyst PI-CB-Cu.

[0014] Preferably, the molar ratio of the α,β-unsaturated compound I, the bipyraclostrobin, the catalyst PI-CB-Cu, and the amine chiral ligand is 2:(4-5):(0.04-0.08):(0.04-0.08).

[0015] Preferably, the volume ratio of toluene to water in the toluene / water mixed solvent is 7:1 to 9:1; 2 to 4 mL of the methanol / water mixed solvent is added for every 1 mmol of Cu loaded in the block polymer copper metal catalyst material PI-CB-Cu.

[0016] Further preferably, the volume ratio of toluene to water in the toluene / water mixed solvent is 9:1; and 2 mL of the methanol / water mixed solvent is added for every 1 mmol of Cu loaded in the block polymer copper metal catalyst material PI-CB-Cu.

[0017] Preferably, in the step 1), the ratio of the total molar amount of monomer 1, monomer 2, and monomer 3 to the molar amount of initiator is 1:0.3-0.7; the feeding ratio of the total molar amount of monomer 1, monomer 2, and monomer 3 to anhydrous dichloromethane is 1 mmol:0.4-0.8 ml; the molar ratio between monomer 1, monomer 2, and monomer 3 is (1-2):(1-2):(1-2).

[0018] Further preferably, in the step 1), the ratio of the total molar amount of monomer 1, monomer 2, and monomer 3 to the molar amount of initiator is 1:0.3; the feeding ratio of the total molar amount of monomer 1, monomer 2, and monomer 3 to anhydrous dichloromethane is 1 mmol:0.4-0.8 ml; and the molar ratio between monomer 1, monomer 2, and monomer 3 is 1:1:1.

[0019] Preferably, the synthesis route of the monomer 2 is as follows:

[0020]

[0021] The synthesis steps are as follows: NaH / mineral oil solution and tetrahydrofuran are mixed evenly, tetraethylene glycol is added under ice bath conditions, the reaction is stirred at room temperature for 1-2 hours, 4-chloromethylstyrene is added, and the mixture is further stirred for 12-14 hours, and then quenched and purified (quenched by saturated NH4Cl solution, extracted with EA solution, dried with anhydrous Na2SO4 and rotary evaporated to obtain a crude product, and the crude product is purified by column chromatography) to obtain monomer 2. The input ratio of 4-chloromethylstyrene, tetraethylene glycol, and NaH is: 1-2:1.5-2:1.5-2. The amount of THF solution added is 51-60 mL.

[0022] Preferably, the synthesis route of the monomer 3 is as follows:

[0023]

[0024] The synthesis steps are as follows: NaH / mineral oil solution and dimethylformamide are mixed evenly, glycidol and 4-chloromethylstyrene are added under ice bath conditions, reacted at room temperature for 4-5 hours, quenched and purified (after the reaction is completed, quenched with saturated NH4Cl solution, extracted with ethyl acetate, dried with anhydrous Na2SO4 and distilled under reduced pressure to remove the solvent to obtain a crude product, which is purified by column chromatography) to obtain monomer 3. The input ratio of 4-chloromethylstyrene, glycidol, NaH, is 1-2:2.5-3:2-3. The amount of DMF solution added is 45-50 mL.

[0025] Preferably, in the step 2), the mass ratio of copolymer P1 to Ketjen black is (1-2):1, and the copper ion concentration in the CuCl / diethylene glycol dimethyl ether solution is 0.16-0.24 mol / L.

[0026] More preferably, in the step 2), the mass ratio of copolymer P1 to Ketjen black is 1:1, and the copper ion concentration in the CuCl / diethylene glycol dimethyl ether solution is 0.24 mol / L.

[0027] Preferably, the copper content in the catalyst PI-CB-Cu is 0.6 to 1.8 mmol / g.

[0028] Application of a β-chiral boron compound in the synthesis of β-substituted alcohol compounds, the synthesis route is as follows:

[0029]

[0030] The synthesis steps are: react β-chiral boron compound II, sodium borate tetrahydrate, tetrahydrofuran and water at room temperature for 3-6 hours, and then purify (extract, dry, rotary evaporation, column chromatography) to obtain β-substituted alcohol compound III.

[0031] The beneficial effects of the present invention are as follows:

[0032] 1. The present invention provides a method for preparing β-chiral boron compounds, which is based on the block polymer copper catalyst catalyzing α, β-unsaturated compounds, combined with amine ligands to prepare enantioselective, and obtain optically active chiral boride, and the whole reaction conditions are mild, the components are simple, the amount of catalyst is small, the conversion rate is high, and the substrate applicability is wide, and it can be successfully applied to the chiral conjugate addition reaction of different types of α, β-unsaturated compounds.

[0033] 2. The block polymer copper catalyst prepared by the present invention is a catalytic material obtained by cross-linking the block polymer by heating. The adsorption of metal copper by the block polymer is mainly based on the complexation of carbonyl groups and epoxy groups. The heating cross-linking makes the copper metal load more solid. The catalyst has a long cycle life. The block polymer copper metal catalytic material can be separated by simple filtration of the solid and liquid phases after the reaction, and can be recycled again after repeated washing, and the reusability is maintained well, which can reduce the cost of industrial reactions and reduce damage to the environment.

[0034] The above description is only an overview of the technical solution of the present invention. In order to more clearly understand the technical means of the present invention and implement it according to the contents of the specification, the following is a detailed description of the preferred embodiments of the present invention in conjunction with the accompanying drawings. The specific implementation of the present invention is given in detail by the following embodiments and their accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] The drawings described herein are used to provide a further understanding of the present invention and constitute a part of this application. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0036] Figure 1 is the H NMR spectrum of the β-substituted alcohol compound III-1 in Example 1;

[0037] Figure 2 is the NMR carbon spectrum of the β-substituted alcohol compound III-1 in Example 2;

[0038] Figure 3 This is the HPLC spectrum of β-substituted alcohol compound III-1 in Example 2. DETAILED DESCRIPTION

[0039] The principles and features of the present invention are described below in conjunction with the accompanying drawings. The examples given are only used to explain the present invention and are not used to limit the scope of the present invention.

[0040] The working principle of the present invention is as follows: in the present invention, the CB bond of the biboric acid pinacol ester is broken under the catalysis of the active copper in the PI-CB-Cu catalytic material to form a copper borane complex and a corresponding byproduct Bpin-OH, and the intermediate undergoes a chiral conjugate addition reaction of α,β-unsaturated compounds through the electron-guiding effect of the carbonyl group. In the reaction, the proton source comes from pure water, and the desired target product is obtained through protonation, and the catalytic material is regenerated and can be recycled for the next time. In the reaction, water has a dual role, serving as a proton source and a solvent. The hydroxyl group and the epoxy group in the material and the O atom in the α,β-unsaturated compound have a strong complexation with Cu, and the protonation process affects and gives the catalyst stable properties.

[0041] Example 1

[0042] A method for preparing a β-chiral boron compound and its application in synthesizing β-substituted alcohol compounds, the specific steps are as follows:

[0043] Step 1: Preparation of catalyst PI-CB-Cu, the steps are as follows:

[0044] 1) A column chromatography purification method is used to remove the phenolic polymerization inhibitor in the styrene monomer to obtain a purified monomer 1.

[0045] 2) Place a 100 mL two-necked flask under an argon atmosphere, add NaH (60% in mineral oil) and 51 mL THF solution in sequence, and then add tetraethylene glycol in an ice-water bath. After stirring the reaction at room temperature for 2 hours, add 4-chloromethylstyrene, and further stir the mixture for 14 hours. After the reaction is completed, quench with saturated NH4Cl solution, extract with EA solution, dry with anhydrous Na2SO4, and rotary evaporate to obtain a crude product. The residue is purified by column chromatography to obtain a (2-(2-(4-vinylbenzyloxy)ethoxy)ethanol ether product (monomer 2), wherein the molar ratio of 4-chloromethylstyrene, tetraethylene glycol, and NaH is 1:1:1.

[0046] The synthetic route of monomer 2 is as follows:

[0047]

[0048] 3) Place a 100mL two-necked flask under an argon atmosphere, add NaH (60% in mineral oil) and 50mL DMF solution in turn and stir evenly, then slowly add glycidol and 4-chloromethylstyrene in an ice-water bath. After reacting at room temperature for 5 hours, after the reaction is completed, quench with saturated NH4Cl solution, extract with EA solution, dry with anhydrous Na2SO4 and rotary evaporate to obtain a crude product. Purify by column chromatography to obtain 4-vinylbenzyl glycidyl ether product (monomer 3), wherein the molar ratio of 4-chloromethylstyrene, glycidol and NaH is 2:3:3.

[0049] The synthetic route of monomer 3 is as follows:

[0050]

[0051] 4) Take 25mL Schlenk tube, under argon protection, 10mmol monomer 1, 10mmol monomer 2, 10mmol monomer 3 are dissolved in 16mL anhydrous DCM, 21mmol initiator AIBN is added, after replacing nitrogen three times, react 60h under argon atmosphere at room temperature. After reaction finishes, the obtained polymer solution is slowly poured into Et2O solution, and solvent and unnecessary monomer are removed by decantation. The polymer solution is slowly poured into ether again. The same procedure is repeated three times in total to precipitate the polymer, and after filtering, it is repeatedly rinsed with ether, and then dried in a vacuum to obtain copolymer P1.

[0052] The synthesis route of copolymer P1 is as follows:

[0053]

[0054] The weight average molecular weight Mw of polymer P1 measured by GPC was 71445 and the PDI was 2.2.

[0055] 5) Dissolve 500 mg of copolymer P1 in 15 mL of diglyme solution, add 500 mg of Ketjen black thereto, stir at room temperature for 30 minutes to form a uniform suspension, add 5 mL of CuCl / diglyme solution (copper ion concentration is 0.2 mol / L) in an ice-water bath and stir for 30 minutes, then add 6 mL of sodium borohydride / diglyme solution thereto and react for 12 hours. Subsequently, add an excess of Et2O solution to the reaction solution, filter and wash with Et2O solution, repeat the filter and wash steps three times, and vacuum dry to obtain a pre-crosslinked solid. The solid is placed in a nitrogen atmosphere and crosslinked at 150°C for 6 hours. Cool to room temperature, grind into powder, wash with H2O, THF and DCM in sequence, vacuum dry, and ball mill twice to obtain the catalyst PI-CB-Cu.

[0056] The copper content in the catalyst PI-CB-Cu was determined by ICP to be 1.6 mmol / g.

[0057] Step 2: Preparation of β-chiral boron compound II-1 and synthesis of β-substituted alcohol compound III-1, the steps are as follows:

[0058] 1) 0.2 mmol ɑ, β-unsaturated compound I-1, 0.005 mmol Bolm chiral ligand, 0.4 mmol biboric acid pinacol ester reagent and 0.005 mmol PI-CB-Cu catalyst were added to a mixed solvent of toluene / water = 9:1 (v / v), and the mixture was stirred at room temperature for 16 hours. In this embodiment, R1 is phenyl and R2 is phenyl in the ɑ, β-unsaturated compound I-1;

[0059] 2) After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is extracted with ethyl acetate solution, dried with anhydrous Na2SO4 and rotary evaporated to obtain β-chiral boron compound II-1. The β-chiral boron compound II-1 product is transferred to a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF solution (3 mL), and H2O solution (3 mL) are added in sequence to react at room temperature for 3-6 hours, followed by extraction, drying, rotary evaporation, and column chromatography to obtain β-substituted alcohol compound III-1 (R1 is phenyl, R2 is phenyl).

[0060] The synthetic route is as follows:

[0061]

[0062] When the PI-CB-Cu catalytic material is used in the reaction, the yield and enantioselectivity of the target product alcohol compound III-1 are 98% and 96%, respectively. (After alcoholization, the material is more stable, and it is easier and more accurate to test the yield and chiral column, and the yield of the boride can be indirectly obtained.)

[0063] After the PI-CB-Cu catalytic material was used for catalytic recycling for 5 times, it was applied to the chiral boron addition reaction of (E)-chalcone for the 6th time, and the yield and enantioselectivity of the obtained product were 95% and 85% respectively.

[0064] The NMR hydrogen spectrum and carbon spectrum of the target product are shown below. Figure 1 and Figure 2 As shown:

[0065] 1 H NMR(400MHz,Chloroform-d)δ7.98-7.96(m,2H),7.63-7.62(m,1H),7.59-7.45(m,4H),7.42- 7.37(m,2H),7.34-7.27(m,1H),5.38-5.34(m,1H),3.63(d,J=3.7Hz,1H),3.40-3.38(m,2H).

[0066] 13C NMR (100MHz, Chloroform-d) δ200.18,142.83,136.44,133.64,128.67,128.54,128.11,127.65,125.70,69.97,47.34.

[0067] HPLC(Dialcel Chiralcel OD-H,nC6H 14 / iso-propanol=90 / 10,flow

[0068] rate 1.0mL / min); t R =12.7min(S,major),t R =11.8min(R, minor). According to the integrated difference of the two peak areas in the HPLC test results, the chirality value of the compound was 96%ee.

[0069] The results of this example show that under the boron addition reaction with the PI-CB-Cu catalyst, the conversion rate and enantioselectivity of (E)-3-phenyl-1-phenylprop-2-ene-1-one (ɑ,β-unsaturated compound I-1) are high, and the yield and enantioselectivity of the chiral boron addition product reach 98% and 96%, respectively.

[0070] Example 2

[0071] A method for preparing a β-chiral boron compound and its application in synthesizing β-substituted alcohol compounds, the specific steps are as follows:

[0072] Step 1: Same as step 1 in Example 1.

[0073] Step 2: Preparation of β-chiral boron compound II-2 and synthesis of β-substituted alcohol compound III-2, the steps are as follows:

[0074] 1) 0.2 mmol ɑ, β-unsaturated compound I-2, 0.005 mmol Bolm chiral ligand, 0.4 mmol biboric acid pinacol ester reagent and 0.005 mmol PI-CB-Cu catalyst were added to a mixed solvent of toluene / water = 9:1 (v / v), and the mixture was stirred at room temperature for 16 hours. In this embodiment, R1 is phenyl and R2 is p-chlorophenyl in the ɑ, β-unsaturated compound I-2;

[0075] 2) After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is extracted with ethyl acetate solution, dried with anhydrous Na2SO4 and rotary evaporated to obtain β-chiral boron compound II-2. The β-chiral boron compound II-2 product is transferred to a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF solution (3 mL), and H2O solution (3 mL) are added in sequence to react at room temperature for 3-6 hours, followed by extraction, drying, rotary evaporation, and column chromatography to obtain β-substituted alcohol compound III-2 (R1 is phenyl, and R2 is p-chlorophenyl).

[0076] The synthetic route is as follows:

[0077]

[0078] When the PI-CB-Cu catalytic material is used in the reaction, the yield and enantioselectivity of the target product alcohol compound III-2 are 96% and 96% respectively.

[0079] The NMR hydrogen spectrum and carbon spectrum of the target product are shown below:

[0080] 1 H NMR(400MHz,Chloroform-d)δ7.95(dd,J=8.2,1.4Hz,2H),7.65-7.55(m,1H),7.49(t,J=7 .7Hz,2H),7.44-7.31(m,4H),5.33(dd,J=7.8,4.4Hz,1H),3.68(s,1H),3.40-3.26(m,2H).

[0081] 13 C NMR (100MHz, Chloroform-d) δ200.21,141.56,136.54,134.02,133.52,129.44,128.96,128.89,128.33,127.35,69.59,47.42.

[0082] HPLC(Dialcel Chiralcel OD-H,nC6H 14 / iso-propanol=90 / 10,flow

[0083] rate 1.0mL / min); t R =9.9min(S,major),t R =8.9min(R,minor).

[0084] The results of this example show that under the boron addition reaction with the PI-CB-Cu catalyst, the conversion rate and enantioselectivity of (E)-3-(4-chlorophenyl)-1-phenylprop-2-ene-1-one (ɑ,β-unsaturated compound I-2) are high, and the yield and enantioselectivity of the chiral boron addition product reach 96% and 96%, respectively.

[0085] Example 3

[0086] A method for preparing a β-chiral boron compound and its application in synthesizing β-substituted alcohol compounds, the specific steps are as follows:

[0087] Step 1: Same as step 1 in Example 1.

[0088] Step 2: Preparation of β-chiral boron compound II-3 and synthesis of β-substituted alcohol compound III-3, the steps are as follows:

[0089] 1) 0.2 mmol ɑ, β-unsaturated compound I-3, 0.005 mmol Bolm chiral ligand, 0.4 mmol biboric acid pinacol ester reagent and 0.005 mmol PI-CB-Cu catalyst were added to a mixed solvent of toluene / water = 9:1 (v / v), and the mixture was stirred at room temperature for 16 hours. In this embodiment, R1 is phenyl and R2 is p-methoxyphenyl in the ɑ, β-unsaturated compound I-3;

[0090] 2) After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is extracted with ethyl acetate solution, dried with anhydrous Na2SO4 and rotary evaporated to obtain β-chiral boron compound II-3. The β-chiral boron compound II-3 product is transferred to a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF solution (3 mL), and H2O solution (3 mL) are added in sequence to react at room temperature for 3-6 hours, followed by extraction, drying, rotary evaporation, and column chromatography to obtain β-substituted alcohol compound III-3 (R1 is phenyl, and R2 is p-methoxyphenyl).

[0091] The synthetic route is as follows:

[0092]

[0093] When the PI-CB-Cu catalytic material is used in the reaction, the yield and enantioselectivity of the target product alcohol compound III-3 are 95% and 96%, respectively.

[0094] The NMR hydrogen spectrum and carbon spectrum of the target product are shown below:

[0095] 1H NMR(400MHz,Chloroform-d)δ7.94(d,J=7.8Hz,2H),7.81-7.59(m,1H),7.48-7.47(m,2H),7.38-7.28 (m,2H),6.92-6.90(m,2H),5.31(dd,J=7.8,5.3Hz,1H),3.61(s,3H),3.58(s,1H),3.37-3.35(m,2H).

[0096] 13 C NMR (100MHz, Chloroform-d) δ200.21,159.04,136.52,135.10,133.58,128.65,128.10,126.99,113.87,69.63,55.27,47.29.

[0097] HPLC(Dialcel Chiralcel OD-H,nC6H 14 / iso-propanol=90 / 10,flow

[0098] rate 1.0mL / min); t R =18.9min(S,major),t R =16.0min(R,minor).

[0099] The results of this example show that under the boron addition reaction with the PI-CB-Cu catalyst, the conversion rate and enantioselectivity of (E)-3-(4-methoxy)-1-phenylprop-2-en-1-one (ɑ,β-unsaturated compound I-3) are high, and the yield and enantioselectivity of the chiral boron addition product reach 95% and 96%, respectively.

[0100] Example 4

[0101] A method for preparing a β-chiral boron compound and its application in synthesizing β-substituted alcohol compounds, the specific steps are as follows:

[0102] Step 1: Same as step 1 in Example 1.

[0103] Step 2: Preparation of β-chiral boron compound II-4 and synthesis of β-substituted alcohol compound III-4, the steps are as follows:

[0104] 1) 0.2 mmol ɑ, β-unsaturated compound I-4, 0.005 mmol Bolm chiral ligand, 0.4 mmol biboric acid pinacol ester reagent and 0.005 mmol PI-CB-Cu catalyst were added to a mixed solvent of toluene / water = 9:1 (v / v), and the mixture was stirred at room temperature for 16 hours. In this embodiment, R1 is phenyl and R2 is p-bromophenyl in the ɑ, β-unsaturated compound I-4;

[0105] 2) After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is extracted with ethyl acetate solution, dried with anhydrous Na2SO4 and rotary evaporated to obtain β-chiral boron compound II-4. The β-chiral boron compound II-4 product is transferred to a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF solution (3 mL), and H2O solution (3 mL) are added in sequence to react at room temperature for 3-6 hours, followed by extraction, drying, rotary evaporation, and column chromatography to obtain β-substituted alcohol compound III-4 (R1 is phenyl, and R2 is p-bromophenyl).

[0106] The synthetic route is as follows:

[0107]

[0108] When the PI-CB-Cu catalytic material is used in the reaction, the yield and enantioselectivity of the target product alcohol compound III-4 are 96% and 95%, respectively.

[0109] The NMR hydrogen spectrum and carbon spectrum of the target product are shown below:

[0110] 1 H NMR(400MHz,Chloroform-d)δ7.95(d,J=7.7Hz,2H),7.60(t,J=7.5Hz,1H),7.48(q,J=7.8H z,4H),7.32(d,J=8.1Hz,2H),5.31(dd,J=7.8,4.3Hz,1H),3.67(s,1H),3.43-3.25(m,2H).

[0111] 13 C NMR(100MHz,Chloroform-d)δ200.04,142.05,136.44,133.93,131.74,128.8 7,128.25,127.62,121.52,77.48,77.36,77.16,76.84,69.52,47.31,24.95.

[0112] HPLC(Dialcel Chiralcel OD-H,nC6H 14 / iso-propanol=90 / 10,flow

[0113] rate 1.0mL / min); t R =14.1min(S,major),t R =12.5min(R,minor).

[0114] The results of this example show that under the boron addition reaction with the PI-CB-Cu catalyst, the conversion rate and enantioselectivity of (E)-3-(4-bromo)-1-phenylprop-2-en-1-one (ɑ,β-unsaturated compound I-4) are high, and the yield and enantioselectivity of the chiral boron addition product reach 96% and 95%, respectively.

[0115] Example 5

[0116] A method for preparing a β-chiral boron compound and its application in synthesizing β-substituted alcohol compounds, the specific steps are as follows:

[0117] Step 1: Same as step 1 in Example 1.

[0118] Step 2: Preparation of β-chiral boron compound II-5 and synthesis of β-substituted alcohol compound III-5, the steps are as follows:

[0119] 1) 0.2 mmol ɑ, β-unsaturated compound I-5, 0.005 mmol Bolm chiral ligand, 0.4 mmol biboric acid pinacol ester reagent and 0.005 mmol PI-CB-Cu catalyst were added to a mixed solvent of toluene / water = 9:1 (v / v), and the mixture was stirred at room temperature for 16 hours. In this embodiment, R1 is phenyl and R2 is m-bromophenyl in the ɑ, β-unsaturated compound I-5;

[0120] 2) After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is extracted with ethyl acetate solution, dried with anhydrous Na2SO4 and rotary evaporated to obtain β-chiral boron compound II-5. The β-chiral boron compound II-5 product is transferred to a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF solution (3 mL), and H2O solution (3 mL) are added in sequence to react at room temperature for 3-6 hours, followed by extraction, drying, rotary evaporation, and column chromatography to obtain β-substituted alcohol compound III-5 (R1 is phenyl, and R2 is m-bromophenyl).

[0121] The synthetic route is as follows:

[0122]

[0123] When the PI-CB-Cu catalytic material is used in the reaction, the yield and enantioselectivity of the target product alcohol compound III-5 are 97% and 96%, respectively.

[0124] The NMR hydrogen spectrum and carbon spectrum of the target product are shown below:

[0125] 1 H NMR(400MHz,Chloroform-d)δ7.98(d,J=7.7Hz,2H),7.65-7.61(m,2H),7.53-7.30(m ,4H),7.27-7.26(m,1H),5.34(dd,J=7.7,5.4Hz,1H),3.72(s,1H),3.40-3.37(m,2H).

[0126] 13 C NMR (100MHz, Chloroform-d) δ199.88,145.18,138.30,133.81,130.69,130.12,128.89,128.74,128.14,124.36,122.69,69.33,47.20.

[0127] HPLC(Dialcel Chiralcel OD-H,nC6H 14 / iso-propanol=90 / 10,flow

[0128] rate 1.0mL / min); t R =12.5min(S,major),t R =11.6min(R,minor).

[0129] The results of this example show that under the boron addition reaction with the PI-CB-Cu catalyst, the conversion rate and enantioselectivity of (E)-3-(3-bromo)-1-phenylprop-2-en-1-one (ɑ,β-unsaturated compound I-5) are high, and the yield and enantioselectivity of the chiral boron addition product reach 97% and 96%, respectively.

[0130] Example 6

[0131] A method for preparing a β-chiral boron compound and its application in synthesizing β-substituted alcohol compounds, the specific steps are as follows:

[0132] Step 1: Same as step 1 in Example 1.

[0133] Step 2: Preparation of β-chiral boron compound II-6 and synthesis of β-substituted alcohol compound III-6, the steps are as follows:

[0134] 1) 0.2 mmol ɑ, β-unsaturated compound I-5, 0.005 mmol Bolm chiral ligand, 0.4 mmol biboric acid pinacol ester reagent and 0.005 mmol PI-CB-Cu catalyst were added to a mixed solvent of toluene / water = 9:1 (v / v), and the mixture was stirred at room temperature for 16 hours. In this embodiment, R1 is phenyl and R2 is naphthyl in the ɑ, β-unsaturated compound I-6;

[0135] 2) After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is extracted with ethyl acetate solution, dried with anhydrous Na2SO4 and rotary evaporated to obtain β-chiral boron compound II-6. The β-chiral boron compound II-6 product is transferred to a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF solution (3 mL), and H2O solution (3 mL) are added in sequence to react at room temperature for 3-6 hours, followed by extraction, drying, rotary evaporation, and column chromatography to obtain β-substituted alcohol compound III-6 (R1 is phenyl, R2 is naphthyl).

[0136] The synthetic route is as follows:

[0137]

[0138] When the PI-CB-Cu catalytic material is used in the reaction, the yield and enantioselectivity of the target product alcohol compound III-6 are 95% and 96%, respectively.

[0139] The NMR hydrogen spectrum and carbon spectrum of the target product are shown below:

[0140] 1 H NMR(400MHz,Chloroform-d)δ8.09-8.01(m,1H),8.00-7.94(m,2H),7.94-7.87(m,1H),7.82 (t,J=6.7Hz,2H),7.61-7.44(m,6H),6.16(d,J=9.4Hz,1H),3.73(s,1H),3.62-3.42(m,2H).

[0141] 13 C NMR(100MHz,Chloroform-d))δ200.38,138.58,136.55,133.84,133.77,129.96,129 .13,128.78,128.28,128.13,126.32,125.73,125.64,123.23,122.88,66.85,46.88.

[0142] HPLC(Dialcel Chiralcel OD-H,nC6H14 / iso-propanol=95 / 5,flow

[0143] rate 1.0mL / min); t R =33.0min(S,major),t R =24.0min(R,minor).

[0144] The results of this example show that under the boron addition reaction with the PI-CB-Cu catalyst, the conversion rate and enantioselectivity of (E)-3-(naphthalene-2-yl)-1-phenylprop-2-en-1-one (ɑ,β-unsaturated compound I-6) are high, and the yield and enantioselectivity of the chiral boron addition product reach 95% and 96%, respectively.

[0145] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Any ordinary technician in the industry can smoothly implement the present invention as shown in the drawings and described above. However, any equivalent changes, modifications and evolutions made by technicians familiar with the profession without departing from the scope of the technical solution of the present invention using the technical content disclosed above are all equivalent embodiments of the present invention. At the same time, any equivalent changes, modifications and evolutions made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the technical solution of the present invention.

Claims

1. A method for preparing a β-chiral boron compound, characterized in that: The synthesis route is as follows: Wherein, R1 is phenyl, and R2 is phenyl, p-chlorophenyl, p-methoxyphenyl, p-bromophenyl, m-bromophenyl or naphthyl; The synthesis steps are as follows: adding α,β-unsaturated compound I, biboric acid pinacol ester, catalyst PI-CB-Cu, and amine chiral ligand into a mixed solvent of toluene / water, mixing and stirring at room temperature for reaction, performing purification after the reaction to obtain liquid phase β-chiral boron compound II and precipitate, washing and drying the precipitate, and recovering the catalyst; Wherein, the synthesis steps of the catalyst PI-CB-Cu are: 1) In a protective atmosphere, monomer 1, monomer 2, and monomer 3 are dissolved in anhydrous dichloromethane, an initiator is added, and the mixture is reacted for 40-80 hours, and then purified to obtain copolymer P1. The synthetic route of copolymer P1 is as follows: 2) dissolving the copolymer P1 in a diethylene glycol dimethyl ether solvent, adding Ketjen black, stirring at room temperature for 30-40 minutes, adding a CuCl / diethylene glycol dimethyl ether solution dropwise thereto in an ice water bath and stirring for 30-40 minutes, then adding a sodium borohydride / diethylene glycol dimethyl ether solution dropwise thereto, reacting fully for 12-16 hours, washing, and drying to obtain a pre-crosslinked product; placing the pre-crosslinked product in a protective atmosphere, reacting at 150-170° C. for 5-8 hours, cooling to room temperature, and crushing and purifying to obtain a catalyst PI-CB-Cu.

2. The method for preparing a β-chiral boron compound according to claim 1, characterized in that: The molar ratio of ɑ,β-unsaturated compound I, bipyraclostrobin, catalyst PI-CB-Cu, and amine chiral ligand is 2:(4~5):(0.04~0.08):(0.04~0.08).

3. The method for preparing a β-chiral boron compound according to claim 2, characterized in that: The volume ratio of toluene to water in the toluene / water mixed solvent is 7:1 to 9:1; 2 to 4 mL of the toluene / water mixed solvent is added for every 1 mmol of Cu loaded in the catalyst PI-CB-Cu.

4. The method for preparing a β-chiral boron compound according to claim 2, characterized in that: In the step 1), the ratio of the total molar amount of monomer 1, monomer 2, and monomer 3 to the molar amount of initiator is 1:0.3-0.7; the feeding ratio of the total molar amount of monomer 1, monomer 2, and monomer 3 to anhydrous dichloromethane is 1 mmol:0.4-0.8 ml; the molar ratio between monomer 1, monomer 2, and monomer 3 is (1-2):(1-2):(1-2).

5. The method for preparing a β-chiral boron compound according to claim 2, characterized in that: In the step 1), the synthesis route of the monomer 2 is as follows: The synthesis steps are as follows: NaH / mineral oil solution and tetrahydrofuran are mixed evenly, tetraethylene glycol is added under ice bath conditions, the reaction is stirred at room temperature for 1-2 hours, 4-chloromethylstyrene is added, and the mixture is further stirred for 12-14 hours, and then monomer 2 is obtained after quenching and purification.

6. The method for preparing a β-chiral boron compound according to claim 2, characterized in that: In the step 1), the synthesis route of the monomer 3 is as follows: The synthesis steps are as follows: NaH / mineral oil solution and dimethylformamide are mixed evenly, glycidol and 4-chloromethylstyrene are added under ice bath conditions, reacted at room temperature for 4-5 hours, and then quenched and purified to obtain monomer 3.

7. The method for preparing a β-chiral boron compound according to claim 2, characterized in that: In the step 2), the mass ratio of copolymer P1 to Ketjen black is (1-2):1, and the copper ion concentration in the CuCl / diethylene glycol dimethyl ether solution is 0.16-0.24 mol / L.

8. The method for preparing a β-chiral boron compound according to claim 2, characterized in that: The copper content in the catalyst PI-CB-Cu is 0.6-1.8 mmol / g.

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