A block polymer copper metal catalytic material and a preparation method thereof, and application in the preparation of N-heteroaryl boride

Abstract

The present invention relates to a block polymer copper metal catalytic material and a preparation method thereof, and an application in the preparation of N-heteroaryl boride. The catalytic material is obtained by microencapsulation and cross-linking of a terpolymer, a mixed ether solution of Ketjen black, and a mixed ether solution of CuCl by blocking. A heterogeneous catalytic system is constructed based on the catalytic material, and N-heteroaryl olefin compound I and biboric acid pinacol ester are stirred and reacted at room temperature to obtain N-heteroaryl boride. The catalytic material provided by the present invention has the characteristics of high catalytic activity, and the reaction is carried out at room temperature in a simple mixed solvent, with mild conditions, a wide range of substrate applications, and excellent yield; in addition, this catalytic material can be recycled and reused for multiple times, with low cost and green environmental protection, and provides a new method for industrial production of N-heteroaryl boron compounds.

Description

Technical Field

[0001] The invention relates to the field of organic synthesis, and in particular to a block polymer copper metal catalytic material and a preparation method thereof, and application thereof in the preparation of N-heteroaryl boride. Background Art

[0002] Functionalized nitrogen-containing aromatic heterocyclic structures are ubiquitous motifs in bioactive drug molecules and are special units in drug molecules, advanced materials, chiral ligands and natural products. Therefore, scientists have made great efforts in developing functionalization methods for nitrogen-heteroaromatic hydrocarbons and their derivatives. Currently, a large number of heterocyclic-based bioactive compounds are undergoing preclinical studies. For example, chloroquinoxaline sulfonamide and brimonidine containing quinoxaline structures have been incorporated into commercially available drugs. At the same time, drugs with anti-tumor activity, anti-glaucoma activity and anti-inflammatory activity also have nitrogen-containing aromatic heterocyclic structures. The catalytic selective formation of multifunctional CB bonds is one of the most important strategies for constructing other functional small molecule compounds. Based on the fact that CB is easily converted into other chemical bonds such as CC, CO, and CN, the catalytic selective boron addition to olefins is a powerful method for generating new CB bonds. In this case, the catalytic addition of boron nucleophiles to conjugated heteroaryl olefins is an attractive strategy for generating valuable heterocyclic aromatic compounds. In the existing literature, there are few reports on transition metal copper-catalyzed boron addition of carbon nucleophiles to β-substituted N-heteroaromatic alkenyl compounds; the literature (Org. Lett., 2017, 19, 6610-6613.) reported the first case of monovalent copper-catalyzed boron addition reaction of N-heteroaromatic alkenes. This work used cuprous chloride as a catalyst, tetrahydrofuran as a solvent, methanol as an additive, and sodium tert-butoxide as a strong base. A series of versatile alkyl boron products were provided using chiral phosphine ligands. This monovalent copper system has problems such as harsh reaction conditions, high cost, environmental pollution, and the inability to recycle the catalyst, all of which greatly limit the application of such methods in actual production. Summary of the invention

[0003] The present invention provides a block polymer copper metal catalytic material and a preparation method thereof, and an application thereof in the preparation of N-heteroaryl boride. A mixed ether solution of a terpolymer and Ketjen black is microencapsulated and cross-linked to obtain a block polymer copper metal catalytic material, and a catalyst material is used to construct a heterogeneous catalytic system. The heterogeneous catalytic system can overcome many problems existing in a homogeneous catalytic system, such as difficulty in separating and recovering the catalyst, serious loss of transition metals, high cost of use, many by-products, metal residues, and easy environmental pollution. The organic reaction conditions used for catalytic acquisition of N-heteroaryl boride are simple, and no complex salts or strong bases are required, as well as anhydrous and oxygen-free operation. The reaction is efficiently carried out using simple implementation conditions, providing a feasible method for large-scale production of N-heteroaryl boride and a green and efficient idea for preparing organic boride.

[0004] The solution of the present invention to solve the above technical problems is as follows: a block polymer copper metal catalytic material, which includes a block copolymer / carbon black cross-linked network carrier and copper nano-microcapsules wrapped in the carrier, and the content of the copper nano-microcapsules is 0.9-1.8 mmol / g.

[0005] The method for preparing the block polymer copper metal catalytic material as described above comprises the following steps:

[0006] 1) In a protective atmosphere, monomer 1, monomer 2, and monomer 3 were dissolved in anhydrous dichloromethane, initiator was added, and the reaction was continued for 40-80 hours. After purification (the polymer solution obtained after the reaction was slowly poured into Et 2 O, and the solvent and excess monomers were removed by decantation. The polymer solution was slowly poured into ether again. The same procedure was repeated three times in total to precipitate the polymer, which was filtered, rinsed with ether for multiple times, and then dried in a vacuum to obtain copolymer P1. The synthesis route is as follows:

[0007]

[0008] 2) The copolymer P1 was dissolved in diethylene glycol dimethyl ether solvent, and Ketjen black was added, and the mixture was stirred at room temperature for 30-40 min. In an ice water bath, CuCl / diethylene glycol dimethyl ether solution was added dropwise and stirred for 30-40 min. Then, sodium borohydride (about 200-300 mg) / diethylene glycol dimethyl ether solution was added dropwise. After fully reacting for 12-16 h, the mixture was washed and dried (excess Et 2 O, filtered and washed with Et 2 O washing, vacuum drying, repeated three times) to obtain a pre-crosslinked product; the pre-crosslinked product was placed in a protective atmosphere, reacted at 150-170° C. for 5-8 hours, cooled to room temperature, and pulverized and purified (preliminarily ground into powder, using H2 O, THF and DCM in sequence, vacuum drying and ball milling twice to obtain a block polymer copper metal catalyst material PI-CB-Cu.

[0009] The mixed ether solution of the terpolymer and Ketjen black is microencapsulated and cross-linked to obtain a composite copper functional material, and then the composite copper functional material is ball-milled to make the distribution of metallic copper in the material more uniform.

[0010] 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).

[0011] 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 15mmol:8ml; and the molar ratio between monomer 1, monomer 2, and monomer 3 is 1:1:1.

[0012] 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.

[0013] 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.

[0014] The cuprous chloride solution provides sufficient copper ions to the catalytic material, so that the catalytic material can adsorb copper ions through its own adsorption capacity, which is a routine operation in the art.

[0015] Preferably, the synthesis route of the monomer 2 is as follows:

[0016]

[0017] 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 (after the reaction is completed, quenched with saturated NH 4 Cl solution quenching, ethyl acetate extraction, anhydrous Na 2 SO 4The solvent is removed by drying and distillation under reduced pressure to obtain a crude product, which is purified by column chromatography to obtain monomer 2. The input ratio of 4-chloromethylstyrene, glycidol, and NaH is 1-2: 2.5-3: 2-3. The amount of DMF solution added is 45-50 mL.

[0018] Preferably, the synthesis route of the monomer 3 is as follows:

[0019]

[0020] 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 (after saturated NH 4 Cl solution quenching, ethyl acetate extraction, anhydrous Na 2 SO 4 The organic solvent is removed by drying and distillation under reduced pressure to obtain a crude product, which is purified by column chromatography to obtain monomer 3. 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.

[0021] The use of the block polymer copper metal catalytic material as described above in the preparation of N-heteroaryl boride comprises the following steps:

[0022] N-heteroaryl olefin compound I, biboric acid pinacol ester, and block polymer copper metal catalyst material PI-CB-Cu are added to a methanol / water mixed solvent, mixed and stirred at room temperature for 8-16 hours, and purified after the reaction (after the reaction, the obtained mixed solution is centrifuged and filtered, and then extracted with ethyl acetate, anhydrous Na 2 SO 4 Drying and rotary evaporation) to obtain a liquid N-heteroaryl boride;

[0023] The obtained N-heteroaryl boride was further subjected to alcoholization reaction. The specific steps were as follows: the crude boride product was transferred to a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF (3 mL), H 2 O (3 mL) was reacted at room temperature for 3-6 h, followed by extraction, drying, rotary evaporation and column chromatography to obtain N-heteroaryl compound II.

[0024] The synthesis route is as follows:

[0025]

[0026] Wherein, R is phenyl, p-methylphenyl, m-methylphenyl, o-methylphenyl, m-fluorophenyl or p-chlorophenyl.

[0027] Preferably, the application method further comprises the following steps:

[0028] The precipitate obtained after the purification treatment is washed and dried to obtain the recovered block polymer copper metal catalyst material PI-CB-Cu.

[0029] Preferably, the molar ratio of the N-heteroaryl olefin compound I, the biphenyl pinacol borate, and the block polymer copper metal catalyst material PI-CB-Cu is 1:(1-2):(0.01-0.05).

[0030] Preferably, the volume ratio of methanol to water in the methanol / water mixed solvent is 1:1 to 5:1; 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.

[0031] Further preferably, the volume ratio of methanol to water in the methanol / water mixed solvent is 4:1; 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.

[0032] The beneficial effects of the present invention are as follows:

[0033] 1. The copper in the block polymer copper metal catalytic material prepared by the present invention is zero-valent copper, has high catalytic activity and good reaction selectivity, has affinity for water, has a simple separation and recovery method, and can be reused many times, and the catalyst can still maintain good stability, which is an efficient, green, and recyclable heterogeneous catalytic material. Transition metal copper has the advantages of abundant reserves, low price, stability to air, high catalytic activity, wide application range, and environmental friendliness. Using copper instead of precious metals in industrial production can greatly reduce production costs and improve economic benefits.

[0034] 2. The present invention constructs a heterogeneous catalytic system through block polymer copper metal catalytic materials, thereby overcoming many problems existing in the homogeneous catalytic system, such as difficulty in separating and recovering the catalyst, serious loss of transition metals, high cost of use, many by-products, metal residues, and easy environmental pollution.

[0035] 3. The block polymer copper metal catalytic material prepared by the present invention is applied to the boron addition reaction of N-heteroaryl compounds, avoiding the disadvantages of existing conditions, not requiring the addition of complex salts and strong bases, and anhydrous and oxygen-free operation, and using simple implementation conditions to efficiently carry out the reaction, thereby expanding the synthesis method for constructing CB bonds. This provides a green and efficient idea for the large-scale production of N-heteroaryl boron compounds.

[0036] 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

[0037] 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:

[0038] Figure 1 is the H NMR spectrum of compound II-1 in Example 2;

[0039] Figure 2 This is the NMR carbon spectrum of compound II-1 in Example 2. DETAILED DESCRIPTION

[0040] 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.

[0041] The working principle of the present invention is as follows: the present invention prepares the catalytic material through two steps of microencapsulation and crosslinking. Microencapsulation can maintain the high efficiency and stability of the metal-based catalytic material. The interaction between the metal catalytic material and the benzene ring in the polymer can effectively prevent the metal from leaching, but the weak interaction force also makes the catalytic material easy to deactivate after repeated use. Through further crosslinking, it can be ensured that the composite copper functional material is not easily dissolved in organic solvents, and the metal species are further "locked" in the polymer network, thereby achieving high catalytic activity in liquid phase reactions.

[0042] Example 1

[0043] This embodiment provides a block polymer copper metal catalyst material PI-CB-Cu, and the preparation method thereof is 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 50 mL DMF solution in sequence 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 complete, add saturated NH 4 Cl solution quenching, ethyl acetate extraction, anhydrous Na 2 SO 4The organic solvent was removed by drying and vacuum distillation to obtain a crude product. The product 4-vinylbenzyl glycidyl ether (monomer 2) was purified by column chromatography, wherein the molar ratio of 4-chloromethylstyrene, glycidol and NaH was 2:3:3.

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

[0047]

[0048] 3) 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 h, add 4-chloromethylstyrene and stir the mixture for further 14 h. After the reaction is completed, add saturated NH 4 Cl solution quenching, ethyl acetate extraction, anhydrous Na 2 SO 4 The organic solvent was removed by drying and distillation under reduced pressure to obtain a crude product. The residue was purified by column chromatography to obtain (2-(2-(4-vinylbenzyloxy)ethoxy)ethanol ether product (monomer 3), wherein the molar ratio of 4-chloromethylstyrene, tetraethylene glycol and NaH was 1:1:1.

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

[0050]

[0051] 4) Take a 25mL Schlenk tube, under argon protection, dissolve 10mmol monomer 1, 10mmol monomer 2, and 10mmol monomer 3 in 16mL anhydrous DCM, add 21mmol initiator AIBN, replace nitrogen three times, and react at room temperature under argon atmosphere for 60h. After the reaction is completed, slowly pour the obtained polymer solution into Et 2 O, and the solvent and excess monomers were removed by decantation. The polymer solution was slowly poured into diethyl ether again. The same procedure was repeated three times in total to precipitate the polymer, which was filtered, washed with diethyl ether for several times, 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) 500 mg of copolymer P1 was dissolved in 15 mL of diglyme solution, 500 ketjen black was added thereto, and the mixture was stirred at room temperature for 30 min to form a uniform suspension. 5 mL of CuCl / diglyme solution (copper ion concentration was 0.2 mol / L) was added thereto under an ice-water bath and stirred for 30 min. Then 6 mL of sodium borohydride (200-300 mg) / diglyme solution was added thereto and the mixture was fully reacted for 12 h. Then, an excess of Et 2 O, filtered and washed with Et 2 O washing, repeated the suction filtration washing steps three times, and vacuum dried to obtain a pre-crosslinked solid. The solid was placed in a nitrogen atmosphere and crosslinked at 150 ° C for 6 h. Cooled to room temperature, preliminarily ground into powder, and used H 2 O, THF and DCM were washed in sequence, vacuum dried and ball milled twice to obtain the catalytic material PI-CB-Cu.

[0056] The copper content in the PI-CB-Cu catalytic material was determined by ICP to be 0.9 mmol / g.

[0057] Example 2

[0058] This embodiment provides a method for preparing N-heteroaryl boride by catalysis of PI-CB-Cu and alcoholizing the N-heteroaryl boride, comprising the following steps:

[0059] 1) 0.2 mmol of N-heteroaryl olefin compound I-1, 0.4 mmol of biboric acid pinacol ester reagent and the catalyst material PI-CB-Cu (0.005 mmol) prepared in Example 1 were added to a mixed solvent of methanol / water = 4:1 (v / v), and the mixture was stirred at room temperature for 16 hours. In the N-heteroaryl olefin compound I-1 of this example, R is phenyl;

[0060] 2) After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is extracted with ethyl acetate and anhydrous Na 2 SO 4 The crude product of N-heteroaryl boride was transferred to a reaction flask, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF (3 mL), H 2 O (3 mL) was reacted at room temperature for 3-6 h, followed by extraction, drying, rotary evaporation and column chromatography to obtain N-heteroaryl alcohol compound II-1 (R is phenyl).

[0061] The synthetic route is as follows:

[0062]

[0063] The PI-CB-Cu catalytic material was used in the reaction, and the yield of the target product alcoholate II-1 was 94%. (After alcoholation, the material is more stable, and the yield is easier and more accurately tested, and the yield of the boride can be indirectly obtained.)

[0064] The PI-CB-Cu catalytic material was applied to the boron addition reaction of the N-heteroaryl olefin compound in a cycle of 6 times, and the yield of the product each time was 94%, 92%, 92%, 91%, 91%, and 91%, respectively.

[0065] The H-NMR and C-NMR spectra of the target product are as follows: Figure 1-2 As shown, the details are as follows:

[0066] 1 H NMR (400MHz, Chloroform-d) δ7.98 (dd, J=8.4, 6.6Hz, 2H), 7.78-7.56 (m, 2H), 7.42 (dd, J=20. 3,7.6Hz,3H),7.33-7.05(m,4H),6.19(s,1H),5.24(dd,J=8.4,3.8Hz,1H),3.32-3.12(m,2H).

[0067] 13 C NMR(100MHz,Chloroform-d)δ160.56,146.99,143.97,136.92,129.90,128. 70,128.41,127.65,127.37,126.89,126.30,125.94,122.15,73.03,46.14.

[0068] The results of this example show that when the PI-CB-Cu catalytic material provided in Example 1 of the present invention participates in the boron addition reaction, the conversion rate of (E)-2-phenylvinylquinoline (N-heteroaryl olefin compound I-1) is high, and the yield of its boron addition product reaches 94%.

[0069] Example 3

[0070] This embodiment provides a method for preparing N-heteroaryl boride by catalysis of PI-CB-Cu and alcoholizing the N-heteroaryl boride, comprising the following steps:

[0071] 1) 0.2 mmol of N-heteroaryl olefin compound I-2, 0.4 mmol of biboric acid pinacol ester reagent and the catalyst material PI-CB-Cu (0.005 mmol) prepared in Example 1 were added to a mixed solvent of methanol / water = 4:1 (v / v), and the mixture was stirred at room temperature for 16 hours. In the N-heteroaryl olefin compound I-2 of this example, R is p-methylphenyl;

[0072] 2) After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is extracted with ethyl acetate and anhydrous Na 2 SO 4 The crude product of the organic boron compound was transferred to a reaction flask, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF (3 mL), H 2 O (3 mL) was reacted at room temperature for 3-6 h, followed by extraction, drying, rotary evaporation and column chromatography to obtain N-heteroaryl alcohol compound II-2 (R is p-methylphenyl).

[0073] The synthetic route is as follows:

[0074]

[0075] The PI-CB-Cu catalytic material was used in the reaction, and the yield of the target product alcoholate II-2 was 86%.

[0076] The NMR hydrogen spectrum and carbon spectrum of the target product are shown below:

[0077] 1 H NMR(400MHz,Chloroform-d)δ7.98(dd,J=12.5,8.4Hz,2H),7.70(d,J=8.2Hz,1H),7.61(t,J=7.7Hz,1H),7.42(t,J=7.5Hz ,1H),7.27(d,J=7.6Hz,2H),7.20-7.03(m,3H),6.08(s,1H),5.19(dd,J=8.8,3.4Hz,1H),3.30-3.09(m,2H),2.25(s,3H).

[0078] 13 C NMR(100MHz,Chloroform-d)δ160.79,147.15,141.14,137.05,136.95,129.96, 129.18,128.86,127.73,126.98,126.35,125.95,122.25,72.95,46.29,21.30.

[0079] The results of this example show that when the PI-CB-Cu catalytic material provided in Example 1 of the present invention participates in the boron addition reaction, the conversion rate of (E)-2-(4-methylphenylvinyl)quinoline (N-heteroaryl olefin compound I-2) and the yield of its boron addition product reach 86%.

[0080] Example 4

[0081] This embodiment provides a method for preparing N-heteroaryl boride by catalysis of PI-CB-Cu and alcoholizing the N-heteroaryl boride, comprising the following steps:

[0082] 1) 0.2 mmol of N-heteroaryl olefin compound I-3, 0.4 mmol of biboric acid pinacol ester reagent and the catalyst material PI-CB-Cu (0.005 mmol) prepared in Example 1 were added to a mixed solvent of methanol / water = 4:1 (v / v), and the mixture was stirred at room temperature for 16 hours. In the N-heteroaryl olefin compound I-3 of this example, R is m-methylphenyl;

[0083] 2) After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is extracted with ethyl acetate and anhydrous Na 2 SO 4 The crude product of the organic boron compound was transferred to a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF (3 mL), H 2 O (3 mL) was reacted at room temperature for 3-6 h, followed by extraction, drying, rotary evaporation and column chromatography to obtain N-heteroaryl alcohol compound II-3 (R is m-methylphenyl).

[0084] The synthetic route is as follows:

[0085]

[0086] The PI-CB-Cu catalytic material was used in the reaction, and the yield of the target product alcoholate II-3 was 80%.

[0087] The NMR hydrogen spectrum and carbon spectrum of the target product are shown below:

[0088] 1 H NMR(400MHz,Chloroform-d)δ8.10(t,J=8.7Hz,2H),7.82(dd,J=8.1,1.4Hz,1H),7.76-7.72(m,J=8.3,6.8,1.5Hz,1H),7.55(t,J=7.3Hz,1 H),7.36(s,1H),7.33-7.22(m,3H),7.13(dt,J=4.2,2.0Hz,1H),6.26(s,1H),5.32(dd,J=9.0,3.3Hz,1H),3.42-3.25(m,2H),2.40(s,3H).

[0089] 13C NMR(100MHz,Chloroform-d)δ160.75,147.11,144.00,138.09,136.92,129.92,128.82, 128.37,128.18,127.70,126.95,126.71,126.32,123.07,122.20,73.07,46.26,21.63.

[0090] The results of this example show that when the PI-CB-Cu catalytic material provided in Example 1 of the present invention participates in the boron addition reaction, the conversion rate and enantioselectivity of (E)-2-(3-methylphenylvinyl)quinoline (N-heteroaryl olefin compound I-3) are high, and the yield of its boron addition product reaches 80%.

[0091] Example 5

[0092] This embodiment provides a method for preparing N-heteroaryl boride by catalysis of PI-CB-Cu and alcoholizing the N-heteroaryl boride, comprising the following steps:

[0093] 1) 0.2 mmol of N-heteroaryl olefin compound I-4, 0.4 mmol of biboric acid pinacol ester reagent and the catalytic material PI-CB-Cu (0.005 mmol) prepared in Example 1 were added to a mixed solvent of methanol / water = 4:1 (v / v), and the mixture was stirred and reacted at room temperature for 16 hours. In the N-heteroaryl olefin compound I-4 of this example, R is o-methylphenyl;

[0094] 2) After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is extracted with ethyl acetate and anhydrous Na 2 SO 4 The crude product of the organic boron compound was transferred to a reaction flask, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF (3 mL), H 2 O (3 mL) was reacted at room temperature for 3-6 h, followed by extraction, drying, rotary evaporation and column chromatography to obtain N-heteroaryl alcohol compound II-4 (R is o-methylphenyl).

[0095] The synthetic route is as follows:

[0096]

[0097] The PI-CB-Cu catalytic material was used in the reaction, and the yield of the target product alcoholate II-4 was 83%.

[0098] The NMR hydrogen spectrum and carbon spectrum of the target product are shown below:

[0099] 1 H NMR(400MHz,Chloroform-d)δ8.12(dd,J=8.4,4.1Hz,2H),7.84(d,J=8.1Hz,1H),7.76(t,J=8.0Hz,1H),7.70(d,J=7.5Hz ,1H),7.56(t,J=7.6Hz,1H),7.31-7.19(m,4H),6.20(s,1H),5.58(dd,J=8.7,3.3Hz,1H),3.36-3.21(m,2H),2.42(s,3H).

[0100] 13 C NMR(100MHz,Chloroform-d)δ160.78,147.15,141.93,136.96,134.18,130.33,129.94, 128.84,127.71,127.19,126.98,126.41,126.34,125.81,122.09,69.61,44.89,19.26.

[0101] The results of this example show that when the PI-CB-Cu catalytic material provided in Example 1 of the present invention participates in the boron addition reaction, the conversion rate and enantioselectivity of (E)-2-(2-methylphenylvinyl)quinoline (N-heteroaryl olefin compound I-4) are high, and the yield of its boron addition product reaches 83%.

[0102] Example 6

[0103] This embodiment provides a method for preparing N-heteroaryl boride by catalysis of PI-CB-Cu and alcoholizing the N-heteroaryl boride, comprising the following steps:

[0104] 1) 0.2 mmol of N-heteroaryl olefin compound I-5, 0.4 mmol of biboric acid pinacol ester reagent and the catalyst material PI-CB-Cu (0.005 mmol) prepared in Example 1 were added to a mixed solvent of methanol / water = 4:1 (v / v), and the mixture was stirred and reacted at room temperature for 16 hours. In the N-heteroaryl olefin compound I-5 of this example, R is m-chlorophenyl;

[0105] 2) After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is extracted with ethyl acetate and anhydrous Na 2 SO 4 The crude product of the organic boron compound was transferred to a reaction flask, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF (3 mL), H2 O (3 mL) was reacted at room temperature for 3-6 h, followed by extraction, drying, rotary evaporation and column chromatography to obtain N-heteroaryl alcohol compound II-5 (R is m-chlorophenyl).

[0106] The synthesis route is as follows:

[0107]

[0108] The PI-CB-Cu catalytic material was used in the reaction, and the yield of the target product alcoholate II-5 was 86%.

[0109] After the PI-CB-Cu catalytic material was used for catalytic recycling for 5 times, it was applied to the boron addition reaction of the N-heteroaryl olefin compound for the 6th time, and the yield of the obtained product was 82%.

[0110] The NMR hydrogen spectrum and carbon spectrum of the target product are shown below:

[0111] 1 H NMR(400MHz,Chloroform-d)δ8.00(dd,J=19.8,8.4Hz,2H),7.72(d,J=8.1Hz,1H),7.65-7.74(m,1H ),7.52-7.37(m,2H),7.32-7.07(m,4H),6.43(s,1H),5.22(t,J=6.1Hz,1H),3.19(d,J=6.1Hz,2H).

[0112] 13 C NMR(100MHz,Chloroform-d)δ160.19,146.93,146.10,137.04,134.27,129.98,129. 68,128.68,127.67,127.43,126.91,126.39,126.18,124.07,122.03,72.36,45.76.

[0113] The results of this example show that when the PI-CB-Cu catalytic material provided in Example 1 of the present invention participates in the boron addition reaction, the conversion rate and enantioselectivity of (E)-2-(3-chlorophenylvinyl)quinoline (N-heteroaryl olefin compound I-5) are high, and the yield of its boron addition product reaches 82%.

[0114] Example 7

[0115] This embodiment provides a method for preparing N-heteroaryl boride by catalysis of PI-CB-Cu and alcoholizing the N-heteroaryl boride, comprising the following steps:

[0116] 1) 0.2 mmol of N-heteroaryl olefin compound I-6, 0.4 mmol of biboric acid pinacol ester reagent and the catalytic material PI-CB-Cu (0.005 mmol) prepared in Example 1 were added to a mixed solvent of methanol / water = 4:1 (v / v), and the mixture was stirred and reacted at room temperature for 16 hours. In the N-heteroaryl olefin compound I-6 of this example, R is p-chlorophenyl;

[0117] 2) After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is extracted with ethyl acetate and anhydrous Na 2 SO 4 The crude product of the organic boron compound was transferred to a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), THF (3 mL), H 2 O (3 mL) was reacted at room temperature for 3-6 h, followed by extraction, drying, rotary evaporation and column chromatography to obtain N-heteroaryl alcohol compound II-6 (R is p-chlorophenyl).

[0118] The synthesis route is as follows:

[0119]

[0120] The PI-CB-Cu catalytic material was used in the reaction, and the yield of the target product alcoholate II-6 was 87%.

[0121] After the PI-CB-Cu catalytic material was used for catalytic recycling for 5 times, it was applied to the boron addition reaction of the N-heteroaryl olefin compound for the 6th time, and the yield of the obtained product was 73%.

[0122] The NMR hydrogen spectrum and carbon spectrum of the target product are shown below:

[0123] 1 H NMR(400MHz,Chloroform-d)δ8.01(dd,J=19.8,8.4Hz,2H),7.74(dd,J=8.2,1.4Hz,1H),7.66-7.49(m,1H),7.47-7.35(m ,1H),7.33-7.31(m,2H),7.27-7.23(m,2H),7.19-7.12(m,1H),6.37(s,1H),5.24(t,J=6.0Hz,1H),3.20(d,J=6.0Hz,2H).

[0124] 13C NMR (100MHz, Chloroform-d) δ160.35,147.06,142.62,137.13,130.09,128.80,128.61,127.77,127.41,127.01,126.49,122.16,72.44,45.93.

[0125] The results of this example show that when the PI-CB-Cu catalytic material provided in Example 1 of the present invention participates in the boron addition reaction, the conversion rate and enantioselectivity of (E)-2-(4-chlorophenylvinyl)quinoline (N-heteroaryl olefin compound I-6) are high, and the yield of its boron addition product reaches 73%.

[0126] 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 block polymer copper metal catalytic material, characterized in that: It comprises a block copolymer / carbon black cross-linked network carrier and copper nano-microcapsules wrapped in the carrier, wherein the content of the copper nano-microcapsules is 0.9-1.8 mmol / g; Wherein: the block copolymer is prepared by copolymerization of monomer 1, monomer 2, and monomer 3, and its synthesis route is as follows: The block copolymer and carbon black are stirred and cross-linked at room temperature to form a block copolymer / carbon black cross-linked network, and Cu is added to the block copolymer / carbon black cross-linked network under ice bath conditions. + The solution is stirred for reaction, and then sodium borohydride solution is added for sufficient reaction, and then purified to obtain a pre-crosslinked product. The pre-crosslinked product is reacted under high temperature conditions, and then crushed and purified to obtain the block polymer copper metal catalyst material.

2. A method for preparing the block polymer copper metal catalytic material according to claim 1, characterized in that: The following steps are involved: 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 continued for 40-80 hours. After purification, copolymer P1 is obtained. The synthesis route 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 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 block polymer copper metal catalyst material PI-CB-Cu.

3. The method for preparing a block polymer copper metal catalytic material 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 of monomer 1, monomer 2, and monomer 3 is 1-2:1-2:1-2.

4. The method for preparing a block polymer copper metal catalytic material 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.

5. The method for preparing a block polymer copper metal catalytic material according to claim 2, characterized in that: The synthesis route of the monomer 2 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 2.

6. The method for preparing a block polymer copper metal catalytic material according to claim 2, characterized in that: The synthesis route of the monomer 3 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 3 is obtained after quenching and purification.

7. Use of the block polymer copper metal catalytic material according to claim 1 in the preparation of N-heteroaryl boride, characterized in that: The following steps are involved: Adding N-heteroaryl olefin compound I, biboric acid pinacol ester, and block polymer copper metal catalyst material PI-CB-Cu into a methanol / water mixed solvent, mixing and stirring at room temperature for 8-16 hours, and performing purification after the reaction to obtain a liquid phase N-heteroaryl boride and a precipitate; The synthesis route is as follows: Wherein, R is phenyl, p-methylphenyl, m-methylphenyl, o-methylphenyl, m-fluorophenyl or p-chlorophenyl.

8. The use of a block polymer copper metal catalyst material in the preparation of N-heteroaryl boride according to claim 7, characterized in that: The following steps are also included: The precipitate obtained after the purification treatment is washed and dried to obtain the recovered block polymer copper metal catalyst material PI-CB-Cu.

9. The use of a block polymer copper metal catalyst material in the preparation of N-heteroaryl boride according to claim 7, characterized in that: The molar ratio of the N-heteroaryl olefin compound I, the biphenyl pinacol borate, and the block polymer copper metal catalyst material PI-CB-Cu is 1:1-2:0.01-0.

05.

10. The use of a block polymer copper metal catalyst material in the preparation of N-heteroaryl boride according to claim 7, characterized in that: The volume ratio of methanol to water in the methanol / water mixed solvent is 1:1 to 5:1; 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.

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