A 3-boronic acid aniline compound and a method for preparing the same

Abstract

The application discloses a preparation method of a metal catalyst catalyzed synthesis of 3-boronate aniline, and relates to the field of organic synthesis. The specific reaction steps are as follows: under the condition of inert gas protection, imine (I) and pinacol diboron are used as raw materials, mixed with a certain amount of metal catalyst and ligand, reacted in an organic solvent, and then hydrolyzed with saturated ammonium chloride aqueous solution. After the reaction is completed, the 3-boronate aniline compound shown in structural formula (II) is obtained through the following steps: extracting three times with ethyl acetate, combining the organic phase and removing the solvent under reduced pressure, column chromatography separation and purification. The reaction of the chemical preparation method provided by the application can be carried out under normal pressure and at medium temperature, the operation is simple, the reaction condition is mild, the process condition is stable, the product is easy to purify, the production cost is low, the method is easy to realize in a standard organic synthesis laboratory, the reproducibility is good, and the method is suitable for industrial large-scale production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to 3-boronate aniline compounds and their preparation methods. Background Technology

[0002] In existing methods, the ortho-CH borylation of aniline includes strategies based on N-protected directing groups, but the deprotection process may lead to the decomposition of the borylated product. A traceless directing group strategy can achieve ortho-CH borylation of primary aniline. The para-CH borylation of aniline includes strategies based on ion-pair directing groups and steric hindrance control of ligands, which has achieved para-CH borylation of primary aniline. For meta-CH borylation of aniline, an electrostatically directed meta-CH borylation of tertiary aniline was reported in 2021, but highly selective meta-CH borylation of primary aniline has not yet been achieved. Therefore, it is essential to develop synthetic methods for meta-boration products of primary aniline.

[0003] In addition, further functionalization and structural optimization of aniline compounds is an important research direction in the field of medicinal chemistry. Boration reaction, as an efficient functionalization method, introduces boron groups that not only have ultra-high reactivity but also some biological activity. Therefore, it is of great significance to develop efficient and selective synthetic methods to construct boronized primary aniline compounds. Summary of the Invention

[0004] The technical problem to be solved by this invention is: how to control the site selectivity of the borylation reaction.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: On the one hand, the present invention provides a 3-boronate aniline compound, the compound being represented by structural formula (II): ; Wherein: R is selected from halogen, hydrocarbon group, alkoxy group, cyano group, ester group, amino group, diethylamino group, morpholine group or carbonyl group.

[0006] Furthermore, the halogen is any one of fluorine, chlorine, bromine, and iodine; the hydrocarbon group is any one of methyl and trifluoromethyl; and the alkoxy group is any one of methoxy and trifluoromethoxy.

[0007] Furthermore, the 3-boronate aniline structure ( )as follows: .

[0008] On the other hand, the present invention provides a method for preparing 3-boronate aniline compounds, wherein imine (I) and pinacol diboronate are mixed with a metal catalyst and a ligand and dissolved in an organic solvent, and reacted under metal catalysis, followed by hydrolysis with a saturated ammonium chloride aqueous solution, and then extracted three times with an extraction solvent. The organic phases are combined and the solvent is removed under reduced pressure to obtain the compound.

[0009] Furthermore, the reaction temperature is 80℃-100℃, and the reaction time is 1-3 hours.

[0010] Furthermore, the preparation method also includes separating and purifying the compound using column chromatography.

[0011] Furthermore, the organic solvent is an inert organic solvent selected from one or more of 1,2-dimethoxyethane, toluene, tetrahydrofuran, 1,4-dioxane, acetonitrile, N,N-dimethylformamide, dichloromethane, chloroform, and n-hexane.

[0012] Furthermore, the extraction solvent is selected from one or more of ethyl acetate, dichloromethane, diethyl ether, and methyl tert-butyl ether.

[0013] Furthermore, the reaction is carried out in an inert gas atmosphere.

[0014] Furthermore, the inert gas is nitrogen or argon.

[0015] Furthermore, the metal catalysis is iridium catalysis, a transition metal.

[0016] Furthermore, the metal catalyst is [Ir(OMe)(COD)]2.

[0017] Furthermore, the ligand is selected from one or more of dtbpy, 4,4'-Me2bpy, 4,4'-(OMe)2bpy, and bpy.

[0018] Furthermore, the molar ratio of imine, pinacol diboronic acid ester, metal catalyst, and ligand is (1-3):(2-6):(0.025-0.05):(0.05-0.1).

[0019] Furthermore, the compound imine is shown in structural formula (I): .

[0020] Wherein: R is selected from halogen, hydrocarbon group, alkoxy group, cyano group, ester group, amino group, diethylamino group, morpholine group or carbonyl group.

[0021] Furthermore, in R, the halogen is any one of fluorine, chlorine, bromine, or iodine; the hydrocarbon group is any one of methyl or trifluoromethyl; and the alkoxy group is any one of methoxy or trifluoromethoxy.

[0022] Furthermore, the structural formula of the compound imine (I) is as follows: .

[0023] Preferably, the compound imine is 1.0 equivalent, pinacol diboronic acid is 2.0 equivalent, the metal catalyst is 0.025 equivalent, the ligand is 0.05 equivalent, the organic solvent is 1 mL / equivalent, the inert gas is nitrogen, the reaction temperature is 80℃, and the reaction time is 1 h.

[0024] Compared with the prior art, the present invention has the following significant advantages: 1. Some of the products prepared in this invention are novel 3-boronate aniline compounds, which supplement the lack of meta-boronated primary aniline in natural 3-boronate aniline compounds. The obtained compounds were confirmed by nuclear magnetic resonance spectroscopy.

[0025] 2. This invention employs a transient protecting group strategy to introduce imine in situ, which can also act as a steric hindrance group to prevent the borylation reaction from occurring at the ortho position, thus achieving primary aniline C(sp) 2 The regioselective coupling between H-H and pinacol diboronic acid ester, and the imine group generated in situ during the reaction can be rapidly removed by hydrolysis.

[0026] 3. This invention utilizes a one-pot, multi-component reaction strategy to chemically synthesize the aforementioned primary aniline compounds containing meta-boron groups. By integrating multiple transformations into a single-step reaction, a reliable preparation method suitable for industrial production is obtained. This preparation method is highly efficient and simple, thus improving the synthesis efficiency.

[0027] 4. The chemical preparation method of the present invention uses imine and pinacol diboronic acid ester as raw materials. The reaction can be carried out at normal pressure and moderate temperature. The operation is simple, the reaction conditions are mild, the process conditions are stable, the product is easy to purify, the production cost is low, it is easy to realize in a standard organic synthesis laboratory, the reproducibility is good, and it is suitable for large-scale industrial production.

[0028] 5. The method has a wide substrate range and good tolerance to functional groups. It has good compatibility with a variety of functional groups (such as halogen, hydrocarbon, alkoxy, cyano, ester or carbonyl groups, etc.) and can be used to construct a diverse library of compounds. Attached Figure Description

[0029] The accompanying drawings of this invention are described below: Figure 1 This is a schematic diagram of the synthesis process of the present invention.

[0030] Figure 2 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 1.

[0031] Figure 3 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 2.

[0032] Figure 4 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 3.

[0033] Figure 5 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 4.

[0034] Figure 6 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 5.

[0035] Figure 7 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 6.

[0036] Figure 8 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 7.

[0037] Figure 9 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 8.

[0038] Figure 10 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 9.

[0039] Figure 11 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 10.

[0040] Figure 12 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 11.

[0041] Figure 13 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 12.

[0042] Figure 14 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 13.

[0043] Figure 15 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 14.

[0044] Figure 16 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 15.

[0045] Figure 17 The image shows the nuclear magnetic resonance (NMR) spectrum of the compound prepared in Example 16. Detailed Implementation

[0046] The present invention will be further described below with reference to the accompanying drawings and embodiments. However, it should not be construed as limiting the scope of the invention to the following embodiments. All technologies implemented based on the above content of the present invention fall within the scope of the present invention. Unless otherwise specified, the reagents and raw materials used in the following embodiments are commercially available chemically pure or analytically pure products. The product structure was confirmed by 1H NMR and 1C NMR spectroscopy. 200-300 mesh silica gel was used for column chromatography.

[0047] A schematic diagram illustrating the preparation of boron-containing primary aniline compounds of the present invention is shown below. Figure 1 As shown, the specific synthesis steps are as follows: Under inert conditions, 1.0-3.0 equivalents of imine (I), 2.0-6.0 equivalents of pinacol diboronate, 0.025-0.05 equivalents of [Ir(OMe)(COD)]2, and 0.05-0.1 equivalents of dtbpy (4,4'-di-tert-butyl-2,2'-bipyridine) were mixed sequentially and reacted at 80-100°C in 1-2 mL / equivalent of organic solvent for 1-3 h. Then, the mixture was hydrolyzed with saturated ammonium chloride aqueous solution at room temperature for 3-6 h. After the reaction was completed, the mixture was extracted three times with ethyl acetate (5-8 mL each time). The organic phases were combined and the solvent was removed under reduced pressure to obtain the crude product. The crude product was purified by column chromatography to obtain boron-containing primary aniline compounds.

[0048] Example 1: Preparation of 3-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (1) Preparation method Under nitrogen atmosphere, (E)-N-(3-chlorophenyl)-2,2-dimethylpropane-1-imine (39 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were sequentially added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 15:1, V / V) to obtain the compound.

[0049] (2) Experimental results Figure 2 This is the NMR spectrum of the compound obtained in this embodiment. Figure 2 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance.13 The C-chromatogram showed that the product was a yellow solid with a yield of 89%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ = 7.15 (dd, J= 0.6, 1.8 Hz, 1H), 6.97 (dd, J= 0.6, 2.2 Hz, 1H), 6.75 (t, J= 2.2 Hz, 1H) 3.70 (brs, 2H),1.33(s, 12H); 13 C NMR (101 MHz, CDCl3, 25 ℃): δ=147.2, 134.8, 124.5, 119.3,117.6, 84.2, 25.0.

[0050] Example 2: Preparation of 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (1) Preparation method Under nitrogen atmosphere, (E)-N-(3-methoxyphenyl)-2,2-dimethylpropane-1-imine (38 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were sequentially added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 10:1, V / V) to obtain the compound.

[0051] (2) Experimental results Figure 3 This is the NMR spectrum of the compound obtained in this embodiment. Figure 3 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a yellow solid with a yield of 82%. Product characterization: 1H NMR (400 MHz, CDCl3, 25 ℃): δ = 6.75 (t, J = 2.9 Hz, 2H), 6.35 (t, J= 2.3 Hz, 1H), 3.79 (s, 3H), 3.64 (brs, 2H), 1.33 (s, 12H); 13 C NMR (101 MHz, CDCl3, 25 ℃): δ =160.4, 147.4, 114.5, 108.9, 104.9, 83.9, 55.4, 25.0.

[0052] Example 3: Preparation of 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (1) Preparation method Under nitrogen atmosphere, (E)-N-(3-methylphenyl)-2,2-dimethylpropane-1-imine (35 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were sequentially added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 10:1, V / V) to obtain the compound.

[0053] (2) Experimental results Figure 4 This is the NMR spectrum of the compound obtained in this embodiment. Figure 4 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a yellow solid with a yield of 87%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ = 7.05 (s, 1H), 6.95 (s,1H), 6.63 (s, 1H), 3.58 (brs, 2H), 2.27 (s, 3H), 1.33 (s, 12H); 13C NMR (101MHz, CDCl3, 25℃): δ =145.9, 138.7, 125.9, 119.1, 118.5, 83.8, 25.0, 21.3.

[0054] Example 4: Preparation of 3-bromo-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (1) Preparation method Under nitrogen atmosphere, (E)-N-(3-bromophenyl)-2,2-dimethylpropane-1-imine (48 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were added sequentially to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 10:1, V / V) to obtain the compound.

[0055] (2) Experimental results Figure 5 This is the NMR spectrum of the compound obtained in this embodiment. Figure 5 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a yellow solid with a yield of 86%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ = 7.30 (d, J = 1.6 Hz 1H), 7.01 (d, J= 2.2 Hz, 1H), 6.92 (t, J= 1.9 Hz, 1H) 3.68 (brs, 2H), 1.33 (s,12H); 13 C NMR (101 MHz, CDCl3, 25 ℃): δ =147.4, 127.4, 123.1, 120.5, 119.8,84.2, 25.0.

[0056] Example 5: Preparation of 3-iodo-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (1) Preparation method Under nitrogen atmosphere, (E)-N-(3-iodophenyl)-2,2-dimethylpropane-1-imine (57 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were sequentially added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 10:1, V / V) to obtain the compound.

[0057] (2) Experimental results Figure 6 This is the NMR spectrum of the compound obtained in this embodiment. Figure 6 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a pale yellow oily liquid with a yield of 87%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ =7.51 (dd, J = 0.8, 1.6 Hz,1H), 7.14 (dd, J= 1.6, 2.3 Hz, 1H), 7.05 (dd, J= 0.8, 2.3 Hz, 1H), 3.74 (brs,2H), 1.32 (s, 12H); 13 C NMR (101 MHz, CDCl3, 25 ℃): δ =147.1, 133.5, 126.4, 120.4, 95.2, 84.2, 25.0.

[0058] Example 6: Preparation of N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)phenyl-1,3-diamine (1) Preparation method Under nitrogen atmosphere, (E)-2,2-dimethyl-N-(3-((E)-methyldiazeninyl)phenyl)prop-1-imine (41 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 4:1, V / V).

[0059] (2) Experimental results Figure 7 This is the NMR spectrum of the compound obtained in this embodiment. Figure 7 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a pale yellow oily liquid with a yield of 90%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ =6.65 (d, J = 2.2 Hz, 1H), 6.56 (d, J = 1.7 Hz, 1H), 6.20 (t, J = 2.2 Hz, 1H), 3.61 (brs, 2H), 2.93 (s.6H), 1.33 (s, 12H); 13 C NMR (101 MHz, CDCl3, 25 ℃): δ =151.6, 146.9, 110.6, 110.0, 102.8, 83.7, 40.9, 24.9.

[0060] Example 7: Preparation of 3-morpholino-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (1) Preparation method Under nitrogen atmosphere, (E)-2,2-dimethyl-N-(3-morpholinylphenyl)prop-1-imine (50 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 3:1, V / V).

[0061] (2) Experimental results Figure 8 This is the NMR spectrum of the compound obtained in this embodiment. Figure 8 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a pale yellow solid with a yield of 89%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ = 6.80 (d, J= 2.2 Hz 1H), 6.69 (d, J= 1.9 Hz, 1H), 6.36 (s, 1H), 3.83 (t, J= 4.8 Hz, 4H), 3.69 (brs,2H), 3.15 (t, J= 4.9 Hz, 4H), 1.31 (s, 12H). 13 C NMR (101 MHz, CDCl3, 25 ℃): δ=152.2, 147.0, 113.6, 112.7, 105.7, 83.8, 67.1, 49.6, 25.0 Example 8: Preparation of 5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)phenyl-1,3-diamine (1) Preparation method Under nitrogen atmosphere, (1E,1'E)-N,N'-(1,3-phenylene)bis(2,2-dimethylpropyl-1-imine) (49 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 3:1, V / V).

[0062] (2) Experimental results Figure 9 This is the NMR spectrum of the compound obtained in this embodiment. Figure 9 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a pale yellow solid with a yield of 84%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ =6.56 (d, J= 2.3 Hz, 2H), 6.14 (t, J = 2.2 Hz, 1H), 3.56 (brs, 4H), 1.32 (s, 12H); 13 C NMR (101 MHz, CDCl3, 25 ℃): δ =147.2, 112.2, 104.9, 83.8, 25.0.

[0063] Example 9: Preparation of 3-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)benzonitrile (1) Preparation method Under nitrogen atmosphere, (E)-3-((2,2-dimethylpropylene)amino)benzonitrile (37 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 6:1, V / V).

[0064] (2) Experimental results Figure 10 This is the NMR spectrum of the compound obtained in this embodiment. Figure 10 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a pale yellow solid with a yield of 74%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ =7.45 (dd, J = 0.9, 1.4 Hz,1H), 7.27 (dd, J= 0.8, 2.5 Hz, 1H), 6.96 (dd, J= 1.5, 2.5 Hz, 1H), 3.85 (brs,2H), 1.37 (s, 12H); 13 C NMR (101 MHz, CDCl3, 25 ℃): δ =146.4. 128.4, 125.3, 119.7, 119.2. 112.8, 84.5, 25.0.

[0065] Example 10: Preparation of 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (1) Preparation method Under nitrogen atmosphere, (E)-2,2-dimethyl-N-(p-tolyl)prop-1-imine (35 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 10:1, V / V) to obtain the compound.

[0066] (2) Experimental results Figure 11 This is the NMR spectrum of the compound obtained in this embodiment. Figure 11 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a yellow solid with a yield of 40%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ =7.11 (d, J= 2.7 Hz, 1H), 6.97 (d, J= 8.1 Hz, 1H), 6.68 (dd, J= 2.4, 8.1 Hz, 1H), 3.51 (brs, 2H), 2.42(s. 3H), 1.33 (s, 12H); 13 C NMR (101 MHz, CDCl3, 25 ℃): δ =143.2, 135.0, 130.8, 122.6, 118.1, 83.5, 25.0, 21.3.

[0067] Example 11: Preparation of 4-fluoro-3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (1) Preparation method Under nitrogen atmosphere, (E)-N-(4-fluoro-3-methoxyphenyl)-2,2-dimethylpropane-1-imine (42 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 8:1, V / V) to obtain the compound.

[0068] (2) Experimental results Figure 12 This is the NMR spectrum of the compound obtained in this embodiment. Figure 12 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a green liquid with a yield of 90%. Product characterization 1 H NMR (400 MHz, CDCl3, 25 ℃): δ =6.55 (t, J= 3.0 Hz, 1H), 6.42 (dd, J= 2.8, 7.1 Hz), 3.82 (s, 3H), 3.53 (brs, 2H), 1.34 (s, 12H); 13 C NMR (101 MHz, CDCl3, 25 ℃): δ =150.7 (d, J= 243.0 Hz), 148.0 (d, J= 13.6 Hz), 142.4 (d, J = 1.5 Hz), 112.4 (d, J = 6.8 Hz), 105.1, 84.0, 56.6, 24.9.

[0069] Example 12: Preparation of 4-bromo-4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (1) Preparation method Under nitrogen atmosphere, (E)-N-(3-bromo-4-fluorophenyl)-2,2-dimethylpropane-1-imine (52 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 10:1, V / V).

[0070] (2) Experimental results Figure 13 This is the NMR spectrum of the compound obtained in this embodiment. Figure 13 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a pale yellow solid with a yield of 88%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ =6.96-6.92 (m, 2H), 3.56(brs, 2H), 1.35 (s, 12H); 13 C NMR (101 MHz, CDCl3, 25 ℃): δ =157.5 (d, J =243.5 Hz), 143.0 (d, J= 2.7 Hz), 122.5, 121.4 (d, J= 6.7 Hz), 109.5 (d, J=24.9 Hz), 84.2, 24.9.

[0071] Example 13: Preparation of 5-bromo-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (1) Preparation method Under nitrogen atmosphere, (E)-N-(5-bromo-2-fluorophenyl)-2,2-dimethylpropane-1-imine (52 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 10:1, V / V) to obtain the compound.

[0072] (2) Experimental results Figure 14 This is the NMR spectrum of the compound obtained in this embodiment. Figure 14 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a pale yellow solid with a yield of 82%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ =7.15 (dd, J= 2.5, 4.2 Hz, 1H), 6.97 (d, J = 2.5, 7.9 Hz), 3.77 (brs, 2H), 1.34 (s, 12H). 13 C NMR (101MHz, CDCl3, 25 ℃): δ =154.8 (d, J= 245.1 Hz), 136.0 (d, J= 16.2 Hz), 127.1(d, J = 7.4 Hz), 122.0 (d, J = 4.3 Hz), 116.7 (d, J = 2.7 Hz) 84.3, 24.9.

[0073] Example 14: Preparation of 4-chloro-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (1) Preparation method Under nitrogen atmosphere, (E)-N-(3-chloro-2-methylphenyl)-2,2-dimethylpropane-1-imine (42 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 10:1, V / V) to obtain the compound.

[0074] (2) Experimental results Figure 15 This is the NMR spectrum of the compound obtained in this embodiment. Figure 15 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a pale yellow solid with a yield of 92%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ = 7.25 (s, 1H), 6.99 (s,1H), 3.67 (brs, 2H), 2.24 (s, 3H), 1.33 (s, 12H); 13 C NMR (101 MHz, CDCl3, 25℃): δ =145.6, 134.9, 125.5, 123.5, 119.4, 84.0. 24.9, 14.0.

[0075] Example 15: Preparation of 3,7-bis(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)naphthalene-1,5-diamine (1) Preparation method Under nitrogen atmosphere, (1E,1'E)-N,N'-(naphthalene-1,5-diyl)bis(2,2-dimethylpropyl-1-imine) (59 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 10:1, V / V) to obtain the compound.

[0076] (2) Experimental results Figure 16 This is the NMR spectrum of the compound obtained in this embodiment. Figure 16 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a pale yellow solid with a yield of 98%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ =7.79 (s, 2H), 7.12 (s,2H), 4.25 (brs, 4H), 1.37 (s, 24H); 13 C NMR (101 MHz, CDCl3, 25 ℃): δ =142.7, 125.5, 119.5, 114.2, 84.0, 25.0.

[0077] Example 16: Preparation of bis(3-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)phenyl) ketone (1) Preparation method Under nitrogen atmosphere, (E)-N-tert-butyl-1-(2-(cyclopent-1-en-1-yl)-6-methylphenyl)methylimine (70 mg, 0.2 mmol), pinacol diboronate (101 mg, 0.4 mmol), [Ir(OMe)(COD)]2 (3.1 mg, 0.005 mmol), dtbpy (2.7 mg, 0.01 mmol), and 1,2-dimethoxyethane (2 mL) were added to a dry Schlenk tube (10 mL). The reaction tube was placed at 80 °C for 1 hour, followed by hydrolysis with saturated ammonium chloride aqueous solution for 3 hours. After the reaction was completed, the mixture was extracted three times with ethyl acetate. The organic phases were combined and the solvent was removed under reduced pressure. The compound was then purified by column chromatography (200–300 mesh, petroleum ether:ethyl acetate = 10:1, V / V) to obtain the compound.

[0078] (2) Experimental results Figure 17 This is the NMR spectrum of the compound obtained in this embodiment. Figure 17 The image in the middle left is an MRI scan. 1 H spectrum, right image is nuclear magnetic resonance. 13 The C-chromatogram showed that the product was a colorless oily liquid with a yield of 95%. Product characterization: 1 H NMR (400 MHz, CDCl3, 25 ℃): δ =7.57 (dd, J= 0.9, 1.4 Hz2H), 7.31 (dd, J= 0.8, 2.5 Hz 2H), 7.16 (dd, J= 1.6, 2.5 Hz 2H), 3.77 (brs,4H), 1.32 (s, 24H); 13 C NMR (101 MHz, CDCl3, 25 ℃): δ =197.6, 145.9, 138.7,126.8, 125.0, 118.7, 84.1, 25.0.

[0079] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A 3-boronate aniline compound, characterized in that, The compound is represented by structural formula (II): ； Wherein: R is selected from halogen, hydrocarbon group, alkoxy group, cyano group, ester group, amino group, diethylamino group, morpholine group or carbonyl group.

2. The 3-boronate aniline compound according to claim 1, characterized in that, The halogen is one of fluorine, chlorine, bromine, and iodine; the hydrocarbon group is one of methyl, ethyl, and trifluoromethyl; and the alkoxy group is one of methoxy and trifluoromethoxy.

3. The 3-boronate aniline compound according to claim 1, characterized in that, The structure (II) of 3-boronate aniline is as follows: 。 4. The method for preparing the 3-boronate aniline compound according to any one of claims 1-3, characterized in that, The imine (I), pinacol diboronic acid ester, metal catalyst, and ligand were mixed and dissolved in an organic solvent. The reaction was carried out under metal catalysis, followed by hydrolysis with a saturated ammonium chloride aqueous solution. The mixture was then extracted three times with an extraction solvent. The organic phases were combined and the solvent was removed under reduced pressure to obtain the compound.

5. The method for preparing 3-boronate aniline compounds according to claim 4, characterized in that, The preparation method also includes separating and purifying the compound using column chromatography.

6. The method for preparing 3-boronate aniline compounds according to claim 5, characterized in that, Column chromatography was performed using a 200-300 mesh silica gel column, with petroleum ether and ethyl acetate in a volume ratio of 3-15:1 as the solvent.

7. The method for preparing the 3-boronate aniline compound according to any one of claims 4-6, characterized in that, The reaction is carried out under an inert gas atmosphere; and / or the metal catalysis is iridium catalysis; and / or the ligand is one or more of dtbpy, 4,4'-Me2bpy, 4,4'-(OMe)2bpy, and bpy; the molar ratio of the imine, pinacol diboronic acid ester, metal catalyst and ligand is (1-3):(2-6):(0.025-0.05):(0.05-0.1).

8. The method for preparing 3-boronate aniline compounds according to claim 7, characterized in that, The metal catalyst is [Ir(OMe)(COD)]2.

9. The method for preparing 3-boronate aniline compounds according to claim 7, characterized in that, The structural formula of imine (I) is as follows: R is selected from halogen, hydrocarbon group, alkoxy group, cyano group, ester group, amino group, diethylamino group, morpholine group or carbonyl group.

10. The method for preparing the 3-boronate aniline compound according to claim 7, characterized in that, The structure of imine is as follows: 。

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