2-alkylboronic acid pinacol ester-2,1-borazaphenalenoid compounds and methods of preparation

Abstract

This invention discloses a method for preparing 2-alkylboronic acid pinacol ester-2,1-boronazonaphthalene compounds, belonging to the field of organic synthetic chemistry. The structural formula of the 2-alkylboronic acid pinacol ester-2,1-boronazonaphthalene compound is as follows: R 1 It can be placed at any of the 3 to 8 sites, R 1 Selected from any one of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted alkoxy, and halogen, R 2 Selected from hydrogen, unsubstituted or substituted alkyl groups, unsubstituted or substituted haloalkyl groups, and halogens, the core of which is a boronization bifunctionalization strategy based on inexpensive copper-based catalysis, to efficiently construct a series of novel 2,1-boronazonaphthalene compounds.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis chemistry, specifically relating to a method for preparing 2-alkylboronic acid pinacol ester-2,1-borazonaphthalene compounds. Background Technology

[0002] 2,1-Borazanaphthalenes are a unique class of benzene isosteres, widely found in drugs, bioactive molecules, optoelectronic materials, and novel ligands (Angew. Chem. Int. Ed. 2022, 61, e202201464). The synthesis of 2,1-borazanaphthalenes by simulating biomimetic C=C bonds using the electron isostere BN bond has become one of the research hotspots in the chemical community (Angew. Chem. Int. Ed. 2012, 51, 6074-6092). 2,1-Borazanaphthalene, as an important organic boron-nitrogen heterocyclic compound, is a key structural unit in drug design and material preparation, possessing both potential biological activity and significant application value. In the pharmaceutical field, it can bind to biological targets, showing great potential in the development of novel therapeutic drugs for anticancer, anti-inflammatory, and antibacterial purposes. In the field of functional materials, it not only exhibits good thermal stability but can also improve electrode conductivity, stability, and energy storage capacity, thereby optimizing battery charge-discharge performance, cycle life, and increasing specific capacitance to achieve fast charging, providing new ideas for the development of new energy batteries. Therefore, establishing a synthetic system for this type of compound and preparing its novel derivatives is of significant research value.

[0003] In the field of boron-nitrogen heterocyclic compound synthesis, although some progress has been made, previous studies on constructing 2,1-boronazonaphthalene compounds using 2-vinylaniline as a starting material have significant limitations: firstly, the reagents used are not only highly hazardous but also difficult to synthesize themselves (Org. Lett. 2016, 18, 1606-1609); secondly, the operational procedures of this synthetic method are relatively complex. Subsequently, Uchiyama, M.'s research group used the n-butyllithium system to synthesize boronazonaphthalene compounds, which can efficiently synthesize boron-nitrogen heterocyclic compounds (Org. Lett. 2024, 26, 247-251), but the method is relatively dangerous and not conducive to operation. Recently, Song's research group has further expanded the research in this field (Nat. Chem. 2024, 16, 1312-1319). The team developed a copper-catalyzed enantioselective hydroboration reaction to obtain enantiomeric-enriched α-carbon-centered chiral borazananes and allene-type axially chiral borazananes from various alkenes and 2,1-borazananes.

[0004] Given the crucial role of 2,1-boronazananes in pharmaceuticals and materials, developing inexpensive metal-catalyzed systems to achieve their efficient synthesis via a borylation bifunctionalization strategy can provide a universal route for the preparation of this key framework. Simultaneously, the borate ester groups in the product molecules possess high reactivity, readily undergoing functional group transformations, thus creating more possibilities for subsequent structural modification and derivatization. Therefore, this study efficiently synthesized a series of novel 2,1-boronazananes based on an inexpensive copper-based catalytic borylation bifunctionalization strategy. This method combines high efficiency with excellent substrate versatility, demonstrating significant synthetic value and broad industrial application prospects.

[0005] In this invention, a novel 2-alkylboronic acid pinacol ester-2,1-boronazonaphthalene compound was successfully prepared using a copper-based catalytic system, with 2-vinyl-2,1-boronazonaphthalene as the starting material, pinacol ester (B2pin2) as the boron source, and allyl halides as the electrophilic reagent. Both the copper-based catalyst and the reactants involved in this method can be synthesized from readily available and inexpensive upstream raw materials. This preparation strategy is highly efficient, simple to operate, and has a wide range of applicable substrates. Summary of the Invention

[0006] The purpose of this invention is to provide a method for preparing 2-alkylboronic acid pinacol ester-2,1-boronazonaphthalene compounds: Under an inexpensive copper-based catalytic system, using 2-vinyl-2,1-boronazonaphthalene as the reactant, pinacol ester (B2pin2) as the boron source, and allyl halide as the electrophilic reagent, a novel 2-alkylboronic acid pinacol ester-2,1-boronazonaphthalene compound was successfully prepared.

[0007] A 2-alkylboronic acid pinacol ester-2,1-boronazonaphthalene compound, the structural formula of which is as follows:

[0008]

[0009] R1 can be placed at any one of positions 3 to 8, and R1 is selected from any one of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted alkoxy, and halogen.

[0010] R2 is selected from any one of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, and halogen.

[0011] The substitution of R1 above refers to its substitution by at least one of the following groups: hydrogen, halogen, alkyl, alkoxy, aryl;

[0012] The substitution of R2 above refers to its substitution by at least one of the following groups: hydrogen, halogen, alkyl, haloalkyl;

[0013] This invention proposes a method for preparing 2-alkylboronic acid pinacol ester-2,1-borazonaphthalene compounds, the synthetic route of which is shown below:

[0014]

[0015] A method for preparing a 2-alkylboronic acid pinacol ester-2,1-borazonaphthalene compound, comprising the following steps:

[0016] A base, pinacol ester of borate (B2pin2) as shown in general formula 2, a copper-based catalyst, an activated 4Å molecular sieve, and a 2,1-boronazonaphthalene compound as shown in general formula 1 were sequentially added to a dry Schlenk reaction tube equipped with a stir bar. A vacuum was created using a Schlenk double-row tube, and argon gas was introduced, repeated three times. While under argon gas, a solvent was added, and the reaction was carried out at 25±3 °C to produce a yellow-green pre-stirred liquid. Subsequently, an allyl halide as shown in general formula 3 was added, the reaction tube was sealed, and the reaction was carried out at 80~100 °C for 24 h~36 h. After cooling to room temperature, the reaction solution was concentrated, and the concentrate was separated by silica gel column chromatography to obtain the 2-alkylboronazol ester-2,1-boronazonaphthalene compound as shown in general formula 4.

[0017] In general formulas 1, 3, and 4, R 1 Selected from hydrogen, alkyl, alkoxy, aryl or halogen, R 2 Selected from hydrogen, alkyl, haloalkyl or halogen, R 3 Selected from halogens;

[0018] The copper-based catalyst is selected from either IMesCuCl or CuCl / SPhos;

[0019] The base is selected from either sodium tert-butoxide or potassium tert-butoxide;

[0020] The solvent is selected from benzene, toluene, or 1,4-dioxane.

[0021] 2,1-Borazanene: Pinaryl diboronate (B2pin2): Copper-based catalyst (calculated as copper): Base: Allyl halide in a molar ratio of 1.0 : 1.5 ~ 2.0 : 0.1 ~ 0.15 : 3.0 ~ 4.0 : 2.0 ~ 3.0.

[0022] The present invention has the following beneficial effects:

[0023] This method employs a copper-based catalytic system, using 2-vinyl-2,1-boronazanaphthalene as the starting material, pinacol diboronate as the boron source, and allyl halides as electrophiles, to synthesize novel target compounds through reagent synergy. Its advantages include: both the copper-based catalyst and the reactants are derived from inexpensive and readily available upstream raw materials; high reaction efficiency and simple operation effectively lower the application threshold; and a wide range of applicable substrates, adaptable to various related substrates. This method provides a key synthetic route for the pharmaceutical, materials, and fine chemical industries, and is of great significance for promoting technological innovation and industrial development in these fields. Attached Figure Description

[0024] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0025] Figure 1 The general formula of the compounds of this invention is given;

[0026] Figure 2 This is the general formula 1 of the present invention;

[0027] Figure 3 This is Formula 2 of the present invention;

[0028] Figure 4 This is Formula 3 of the present invention;

[0029] Figure 5 This is Formula 4 of the present invention. Detailed Implementation

[0030] The following examples will help to understand the present invention, but are not intended to limit the scope of the invention.

[0031] A 2-alkylboronic acid pinacol ester-2,1-boronazonaphthalene compound, the structural formula of which is as follows:

[0032]

[0033] R1 can be placed at any one of positions 3 to 8, and R1 is selected from any one of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted alkoxy, and halogen.

[0034] R2 is selected from any one of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, and halogen.

[0035] The substitution of R1 above refers to its substitution by at least one of the following groups: hydrogen, halogen, alkyl, alkoxy, aryl;

[0036] The substitution of R2 above refers to its substitution by at least one of the following groups: hydrogen, halogen, alkyl, haloalkyl;

[0037] This invention proposes a method for preparing 2-alkylboronic acid pinacol ester-2,1-borazonaphthalene compounds, the synthetic route of which is shown below:

[0038]

[0039] A method for preparing a 2-alkylboronic acid pinacol ester-2,1-borazonaphthalene compound, comprising the following steps:

[0040] A base, pinacol ester of borate (B2pin2) as shown in general formula 2, a copper-based catalyst, an activated 4Å molecular sieve, and a 2,1-boronazonaphthalene compound as shown in general formula 1 were sequentially added to a dry Schlenk reaction tube equipped with a stir bar. A vacuum was created using a Schlenk double-row tube, and argon gas was introduced, repeated three times. While under argon gas, a solvent was added, and the reaction was carried out at 25±3 °C to produce a yellow-green pre-stirred liquid. Subsequently, an allyl halide as shown in general formula 3 was added, the reaction tube was sealed, and the reaction was carried out at 80~100 °C for 24 h~36 h. After cooling to room temperature, the reaction solution was concentrated, and the concentrate was separated by silica gel column chromatography to obtain the 2-alkylboronazol ester-2,1-boronazonaphthalene compound as shown in general formula 4.

[0041] In general formulas 1, 3, and 4, R 1 Selected from hydrogen, alkyl, alkoxy, aryl or halogen, R 2 Selected from hydrogen, alkyl, haloalkyl or halogen, R 3 Selected from halogens;

[0042] The copper-based catalyst is selected from either IMesCuCl or CuCl / SPhos;

[0043] The base is selected from either sodium tert-butoxide or potassium tert-butoxide;

[0044] The solvent is selected from benzene, toluene, or 1,4-dioxane.

[0045] 2,1-Borazanene: Pinaryl diboronate (B2pin2): Copper-based catalyst (calculated as copper): Base: Allyl halide in a molar ratio of 1.0 : 1.5 ~ 2.0 : 0.1 ~ 0.15 : 3.0 ~ 4.0 : 2.0 ~ 3.0.

[0046] Example 1:

[0047] Synthesis of 2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0048]

[0049] Add 4.05 mg (0.01 mmol) carbene copper IMesCuCl, 17.18 mg (0.15 mmol) KOtBu, 64.78 mg (0.25 mmol) pinacol diboronate (B2pin2), 50 mg activated 4Å molecular sieve, and 15.51 mg (0.1 mmol) 2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of benzene and 17.5 µL (0.2 mmol) 3-bromopropene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 80 ± 3 °C. Stir the reaction for 24 minutes. h, cooled to room temperature, and separated by silica gel column chromatography to obtain 2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborpan-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, yield 80%; 1 H NMR (500 MHz, Chloroform-d) δ 8.20 (s, 1H), 7.95 (d, J = 11.5 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.37 (t, J = 8.1 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.12 (t, J = 7.4 Hz, 1H), 6.85 (dd, J = 11.6, 1.9 Hz, 1H), 5.85 – 5.76 (m, 1H), 5.02 – 4.97 (m, 1H), 4.94 – 4.91 (m, 1H), 2.47 – 2.41 (m, 1H), 2.28 (dt, J = 14.2, 7.3 Hz, 1H), 1.70 – 1.65 (m, 1H), 1.19 (s, 12H), 1.06 (dd, J = 10.3, 5.6 Hz, 1H), 1.0 – 0.96 (m, 1H). 13C NMR (126 MHz, Chloroform-d) δ 147.66, 144.51, 140.22, 139.52, 129.42, 127.99, 125.44,120.61, 117.96, 115.15, 83.22, 39.92, 29.85, 25.03, 24.98. HRMS(ESI) m / z:calculated for [C 19 H 27 B2NO2+Na] + 346.2120, found 346.2126.

[0050] Example 2:

[0051] Synthesis of 2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0052]

[0053] Add 4.05 mg (0.01 mmol) carbene copper IMesCuCl, 34.35 mg (0.3 mmol) KOtBu, 38.87 mg (0.15 mmol) pinacol diboronate (B2pin2), 50 mg activated 4Å molecular sieve, and 15.51 mg (0.1 mmol) 2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of benzene and 17.5 µL (0.2 mmol) 3-bromopropene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 80 ± 3 °C. Stir the reaction for 24 minutes. After cooling to room temperature, the solution was separated by silica gel column chromatography to obtain 2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborpan-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, with a yield of 72%. 1H NMR (500 MHz, Chloroform-d) δ 8.20 (s, 1H), 7.95 (d, J = 11.5 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.37 (t, J = 8.1 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.12 (t, J = 7.4 Hz, 1H), 6.85 (dd, J = 11.6, 1.9 Hz, 1H), 5.85 – 5.76 (m, 1H), 5.02 – 4.97 (m, 1H), 4.94 – 4.91 (m, 1H), 2.47 – 2.41 (m, 1H), 2.28 (dt, J = 14.2, 7.3 Hz, 1H), 1.70 – 1.65 (m, 1H), 1.19 (s, 12H), 1.06 (dd, J = 10.3, 5.6 Hz, 1H), 1.0 – 0.96 (m, 1H). 13 C NMR (126 MHz, Chloroform-d) δ 147.66, 144.51, 140.22, 139.52, 129.42, 127.99, 125.44,120.61, 117.96, 115.15, 83.22, 39.92, 29.85, 25.03, 24.98. HRMS(ESI) m / z:calculated for [C 19 H 27 B2NO2+Na] + 346.2120, found 346.2126.

[0054] Example 3:

[0055] Synthesis of 2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0056]

[0057] Add 0.99 mg (0.01 mmol) of copper salt CuCl, 6.16 mg (0.15 mmol) of ligand SPhos, 34.35 mg (0.3 mmol) of KOtBu, 38.87 mg (0.15 mmol) of pinacol diboronate (B2pin2), 50 mg of activated 4Å molecular sieve, and 15.51 mg (0.1 mmol) of 2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of toluene and 17.5 µL (0.2 mmol) of 3-bromopropene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 80 ± 3 °C. Stir the reaction for 24 minutes. After cooling to room temperature, the sample was separated by silica gel column chromatography to obtain 2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, with a yield of 83%. 1 H NMR (500 MHz, Chloroform-d) δ8.20 (s, 1H), 7.95 (d, J = 11.5 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.37 (t, J =8.1 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.12 (t, J = 7.4 Hz, 1H), 6.85 (dd, J =11.6, 1.9 Hz, 1H), 5.85 – 5.76 (m, 1H), 5.02 – 4.97 (m, 1H), 4.94 – 4.91 (m, 1H), 2.47 – 2.41 (m, 1H), 2.28 (dt, J = 14.2, 7.3 Hz, 1H), 1.70 – 1.65 (m, 1H), 1.19 (s, 12H), 1.06 (dd, J = 10.3, 5.6 Hz, 1H), 1.0 – 0.96 (m, 1H). 13 C NMR (126MHz, Chloroform-d) δ 147.66, 144.51, 140.22, 139.52, 129.42, 127.99, 125.44,120.61, 117.96, 115.15, 83.22, 39.92, 29.85, 25.03, 24.98. HRMS(ESI) m / z:calculated for [C 19 H 27 B2NO2+Na]+ 346.2120, found 346.2126.

[0058] Example 4:

[0059] Synthesis of 2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0060]

[0061] Add 4.05 mg (0.01 mmol) carbene copper IMesCuCl, 34.35 mg (0.3 mmol) KOtBu, 38.87 mg (0.15 mmol) pinacol diboronate (B2pin2), 50 mg activated 4Å molecular sieve, and 15.51 mg (0.1 mmol) 2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of 1,4-dioxane and 17.5 µL (0.2 mmol) 3-bromopropene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 100 ± 3 °C. Stir the reaction for 24 hours. After cooling to room temperature, the sample was separated by silica gel column chromatography to obtain 2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborpan-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, with a yield of 88%. 1 H NMR (500 MHz, Chloroform-d) δ8.20 (s, 1H), 7.95 (d, J = 11.5 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.37 (t, J =8.1 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.12 (t, J = 7.4 Hz, 1H), 6.85 (dd, J =11.6, 1.9 Hz, 1H), 5.85 – 5.76 (m, 1H), 5.02 – 4.97 (m, 1H), 4.94 – 4.91 (m, 1H), 2.47 – 2.41 (m, 1H), 2.28 (dt, J = 14.2, 7.3 Hz, 1H), 1.70 – 1.65 (m, 1H), 1.19 (s, 12H), 1.06 (dd, J = 10.3, 5.6 Hz, 1H), 1.0 – 0.96 (m, 1H). 13C NMR (126MHz, Chloroform-d) δ 147.66, 144.51, 140.22, 139.52, 129.42, 127.99, 125.44,120.61, 117.96, 115.15, 83.22, 39.92, 29.85, 25.03, 24.98. HRMS(ESI) m / z:calculated for [C 19 H 27 B2NO2+Na] + 346.2120, found 346.2126.

[0062] Example 5:

[0063] 2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0064]

[0065] Add 0.99 mg (0.01 mmol) of copper salt CuCl, 6.16 mg (0.15 mmol) of ligand SPhos, 28.84 mg (0.3 mmol) of NaOtBu, 38.87 mg (0.15 mmol) of pinacol diboronate (B2pin2), 50 mg of activated 4Å molecular sieve, and 15.51 mg (0.1 mmol) of 2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of toluene and 17.5 µL (0.2 mmol) of 3-bromopropene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 80 ± 3 °C. Stir the reaction for 24 minutes. After cooling to room temperature, the sample was separated by silica gel column chromatography to obtain 2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborpan-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, with a yield of 69%. 1H NMR (500 MHz, Chloroform-d) δ8.20 (s, 1H), 7.95 (d, J = 11.5 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.37 (t, J =8.1 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.12 (t, J = 7.4 Hz, 1H), 6.85 (dd, J =11.6, 1.9 Hz, 1H), 5.85 – 5.76 (m, 1H), 5.02 – 4.97 (m, 1H), 4.94 – 4.91 (m, 1H), 2.47 – 2.41 (m, 1H), 2.28 (dt, J = 14.2, 7.3 Hz, 1H), 1.70 – 1.65 (m, 1H), 1.19 (s, 12H), 1.06 (dd, J = 10.3, 5.6 Hz, 1H), 1.0 – 0.96 (m, 1H). 13 C NMR (126MHz, Chloroform-d) δ 147.66, 144.51, 140.22, 139.52, 129.42, 127.99, 125.44,120.61, 117.96, 115.15, 83.22, 39.92, 29.85, 25.03, 24.98. HRMS(ESI) m / z:calculated for [C 19 H 27 B2NO2+Na] + 346.2120, found 346.2126.

[0066] Example 6:

[0067] Synthesis of 2-(3-methyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)but-3-en-2-yl)-2,1-borazanaphthalene

[0068]

[0069] Add 4.05 mg (0.01 mmol) carbene copper IMesCuCl, 34.35 mg (0.3 mmol) KOtBu, 38.87 mg (0.15 mmol) pinacol diboronate (B2pin2), 50 mg of activated 4Å molecular sieve, and 15.51 mg (0.1 mmol) 2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stirrer. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of 1,4-dioxane and 20.16 µL (0.2 mmol) of 3-bromo-2-methyl-1-propene sequentially. Stir for 2 minutes, then seal the reaction system. Maintain the reaction temperature at 100 ± 3 °C and stir for 24 minutes. After cooling to room temperature, the sample was separated by silica gel column chromatography to obtain 2-(3-methyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborpan-2-yl)but-3-en-2-yl)-2,1-borazanaphthalene, with a yield of 95%. 1 H NMR (500 MHz, Chloroform-d) δ 8.25 (s, 1H), 7.98 (d, J = 11.5 Hz, 1H), 7.61 (d, J = 7.5 Hz, 1H), 7.40 (t, J = 7.2 Hz, 1H), 7.23 (d, J = 7.8 Hz, 1H), 7.15 (t, J = 7.3 Hz, 1H), 6.88 (d, J = 11.5 Hz, 1H), 4.73 (d, J = 21.4 Hz, 2H), 2.45 (dd, J = 13.8,7.1 Hz, 1H), 2.27 – 2.24 (m, 1H), 1.85 – 1.81 (m, 1H). 1.75 (s, 3H), 1.22 (s, 12H), 1.11 – 1.06 (m, 1H), 0.97 (ddd, J = 16.0, 9.8, 2.6 Hz, 1H). 13 C NMR (126MHz, Chloroform-d) δ 146.14, 144.45, 140.24, 129.41, 128.07, 127.95, 125.46,120.55, 117.92, 111.27, 83.16, 43.84, 29.47, 25.05, 24.99, 22.66.HRMS(ESI) m / z: calculated for [C 20 H 29 B2NO2+H] +338.2457, found 338.2460.

[0070] Example 7:

[0071] Synthesis of 6-chloro-2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborpan-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0072]

[0073] Add 4.05 mg (0.01 mmol) carbene copper IMesCuCl, 34.35 mg (0.3 mmol) KOtBu, 38.87 mg (0.15 mmol) pinacol diboronate (B2pin2), 50 mg of activated 4Å molecular sieve, and 19 mg (0.1 mmol) 6-chloro-2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stirrer. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of 1,4-dioxane and 17.5 µL (0.2 mmol) of 3-bromopropene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 100 ± 3 °C. Stir the reaction for 24 minutes. After cooling to room temperature, the solution was separated by silica gel column chromatography to obtain 6-chloro-2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborpan-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, with a yield of 85%. 1 H NMR (500 MHz, Chloroform-d) δ8.23 (s, 1H), 7.85 (d, J = 11.5 Hz, 1H), 7.55 (d, J = 2.3 Hz, 1H), 7.31 (dd, J =8.6, 2.4 Hz, 1H), 7.13 (d, J = 8.6 Hz, 1H), 6.89 (dd, J = 11.6, 1.9 Hz, 1H), 5.82 – 5.76 (m, 1H), 4.99 (d, J = 17.1 Hz, 1H), 4.93 (d, J = 10.2 Hz, 1H), 2.46– 2.40 (m, 1H), 2.30 – 2.25 (m, 1H), 1.69 (d, J = 7.2 Hz, 1H), 1.18 (s, 12H), 1.07 (dd, J = 15.9, 5.4 Hz, 1H), 0.98 (dd, J = 15.9, 9.8 Hz, 1H). 13C NMR (126MHz, Chloroform-d) δ 143.42, 139.31, 138.64, 130.78, 128.43, 128.07, 126.33,125.58, 119.16, 115.29, 83.25, 39.81, 29.84, 25.02, 24.08. HRMS(ESI) m / z:calculated for [C 19 H 26 B2NO2Cl+Na] + 380.1730, found 380.1740.

[0074] Example 8:

[0075] Synthesis of 2-(4-bromo-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0076]

[0077] Add 4.05 mg (0.01 mmol) carbene copper IMesCuCl, 34.35 mg (0.3 mmol) KOtBu, 38.87 mg (0.15 mmol) pinacol diboronate (B2pin2), 50 mg of activated 4Å molecular sieve, and 15.51 mg (0.1 mmol) 2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of 1,4-dioxane and 21 µL (0.2 mmol) of 2,3-dibromoprop-1-ene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 100 ± 3 °C. Stir the reaction for 24 minutes. After cooling to room temperature, the sample was separated by silica gel column chromatography to obtain 2-(4-bromo-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborpan-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, with a yield of 85%. 1H NMR (500 MHz, Chloroform-d) δ 8.28 (s, 1H), 7.97 (d, J = 11.5 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 7.22 (d, J = 8.1 Hz, 1H), 7.13 (t, J = 7.4 Hz, 1H), 6.83 (d, J =11.5 Hz, 1H), 5.52 (s, 1H), 5.38 (s, 1H), 2.80 (dd, J = 14.7, 6.9 Hz, 1H), 2.60 (dd, J = 14.7, 8.4 Hz, 1H), 2.02 – 1.95 (m, 1H), 1.18 (s, 12H), 1.12 – 1.08 (m, 1H), 0.95 (dd, J = 16.1, 10.0 Hz, 1H). HRMS(ESI) m / z: calculated for[C 19 H 26 B2NO2Br+H] + 402.1406 was found to be 402.1408.

[0078] Example 9:

[0079] Synthesis of 6-methoxy-2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0080]

[0081] Add 4.05 mg (0.01 mmol) carbene copper IMesCuCl, 34.35 mg (0.3 mmol) KOtBu, 38.87 mg (0.15 mmol) pinacol diboronate (B2pin2), 50 mg activated 4Å molecular sieve, and 18.71 mg (0.1 mmol) 6-methoxy-2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of 1,4-dioxane and 17.5 µL (0.2 mmol) 3-bromopropene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 100 ± 3 °C. Stir the reaction for 24 minutes. After cooling to room temperature, the solution was separated by silica gel column chromatography to obtain 6-methoxy-2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborpan-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, with a yield of 94%. 1 H NMR (400 MHz, Chloroform-d) δ 8.13 (s, 1H), 7.91 (d, J = 11.5 Hz, 1H), 7.15 – 7.12 (m, 1H), 7.04 – 7.02 (m, 2H), 6.86 (dd, J = 11.5, 2.0 Hz, 1H), 5.86 – 5.76 (m, 1H), 5.03 – 4.91 (m, 2H), 3.85 (s, 3H), 2.48 – 2.40 (m, 1H), 2.32 – 2.24 (m, 1H), 1.70 – 1.63 (m, 1H), 1.20 (s, 12H), 1.08 – 1.04 (m, 1H), 1.01 – 0.95 (m, 1H).HRMS(ESI) m / z: calculated for [C 20 H 29 B2NO3+Na] + 376.2226, found 376.2227.

[0082] Example 10:

[0083] Synthesis of 6-bromo-2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0084]

[0085] Add 4.05 mg (0.01 mmol) carbene copper IMesCuCl, 34.35 mg (0.3 mmol) KOtBu, 38.87 mg (0.15 mmol) pinacol diboronate (B2pin2), 50 mg activated 4Å molecular sieve, and 23.4 mg (0.1 mmol) 6-bromo-2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of 1,4-dioxane and 17.5 µL (0.2 mmol) 3-bromopropene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 100 ± 3 °C. Stir the reaction for 24 minutes. After cooling to room temperature, the solution was separated by silica gel column chromatography to obtain 6-bromo-2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborpan-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, with a yield of 89%. 1 H NMR (400 MHz, Chloroform-d)δ 8.15 (s, 1H), 7.78 (d, J = 11.5 Hz, 1H), 7.63 (d, J = 2.2 Hz, 1H), 7.37(dd, J = 8.6, 2.2 Hz, 1H), 7.01 (d, J = 8.6 Hz, 1H), 6.82 (dd, J = 11.6, 1.9Hz, 1H), 5.77 – 5.66 (m, 1H), 4.94 – 4.84 (m, 2H), 2.39 – 2.32 (m, 1H), 2.24– 2.16 (m, 1H), 1.61 – 1.57 (m, 1H), 1.12 (s, 12H), 0.99 (dd, J = 15.8, 5.4Hz, 1H), 0.90 (dd, J = 15.8, 9.7 Hz, 1H). 13 C NMR (101 MHz, Chloroform-d) δ146.45, 143.35, 139.30, 138.99, 131.52, 130.76, 126.91, 119.53, 115.32,112.94, 83.27, 39.81, 29.85, 25.03, 24.97.HRMS(ESI) m / z: calculated for[C 19 H 26 B2NO2Br+Na] +424.1225, found 424.1219.

[0086] Example 11:

[0087] 4-Methyl-2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0088]

[0089] Add 4.05 mg (0.01 mmol) carbene copper IMesCuCl, 34.35 mg (0.3 mmol) KOtBu, 38.87 mg (0.15 mmol) pinacol diboronate (B2pin2), 50 mg activated 4Å molecular sieve, and 16.91 mg (0.1 mmol) 4-methyl-2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stirrer. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of 1,4-dioxane and 17.5 µL (0.2 mmol) 3-bromopropene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 100 ± 3 °C. Stir the reaction for 24 minutes. h, cooled to room temperature, and separated by silica gel column chromatography to obtain 4-methyl-2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborpan-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, with a yield of 95%; 1 H NMR (400 MHz, Chloroform-d) δ 8.07 (s, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.40 – 7.36 (m, 1H), 7.21 – 7.14 (m, 2H), 6.67 (s, 1H), 5.87 – 5.77 (m, 1H), 5.03 – 4.91 (m, 2H), 2.57 (s, 3H), 2.49 – 2.41 (m, 1H), 2.32 – 2.24 (m, 1H), 1.66 – 1.62 (m, 1H), 1.20 (s, 12H), 1.06 (dd, J = 15.8, 5.6 Hz, 1H), 0.98 (dd, J = 15.8, 9.7 Hz, 1H). 13C NMR (101 MHz, Chloroform-d) δ 150.44, 140.46, 139.63, 129.35, 127.75,125.68, 125.44, 120.46, 118.45, 115.05, 83.15, 39.91, 29.85, 25.02, 24.98,23.04. HRMS(ESI) m / z: calculated for [C 20 H 29 B2NO2+H] + 338.2457, found 338.2466.

[0090] Example 12:

[0091] 7-Methoxy-2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0092]

[0093] Add 4.05 mg (0.01 mmol) carbene copper IMesCuCl, 34.35 mg (0.3 mmol) KOtBu, 38.87 mg (0.15 mmol) pinacol diboronate (B2pin2), 50 mg activated 4Å molecular sieve, and 18.71 mg (0.1 mmol) 7-methoxy-2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of 1,4-dioxane and 17.5 µL (0.2 mmol) 3-bromopropene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 100 ± 3 °C. Stir the reaction for 24 minutes. After cooling to room temperature, the sample was separated by silica gel column chromatography to obtain 7-methoxy-2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, with a yield of 98%. 1H NMR (400 MHz, Chloroform-d) δ 8.14 (s, 1H), 7.89 (d, J = 11.5 Hz, 1H), 7.47 (d, J = 8.6 Hz, 1H), 6.75 (dd, J = 8.6, 2.4 Hz, 1H), 6.69 – 6.66 (m, 2H), 5.86 – 5.78 (m,1H), 5.02 – 4.91 (m, 2H), 3.86 (s, 3H), 2.47 – 2.40 (m, 1H), 2.31 – 2.24 (m,1H), 1.67 – 1.64 (m, 1H), 1.20 (s, 12H), 1.07 (dd, J = 15.8, 5.6 Hz, 1H),0.98 (dd, J = 15.8, 9.7 Hz, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 159.77,147.25, 144.21, 141.56, 139.55, 130.50, 119.87, 115.11, 109.39, 100.93,83.19, 55.47, 39.98, 29.84, 25.03, 24.97. HRMS(ESI) m / z: calculated for[C 20 H 29 B2NO3+H] + 354.2406, found 354.2410.

[0094] Example 13:

[0095] 7-Phenylacetyl-2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0096]

[0097] Add 4.05 mg (0.01 mmol) carbene copper IMesCuCl, 34.35 mg (0.3 mmol) KOtBu, 38.87 mg (0.15 mmol) pinacol diboronate (B2pin2), 50 mg activated 4Å molecular sieve, and 23.11 mg (0.1 mmol) 7-phenyl-2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the system using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of 1,4-dioxane and 17.5 µL (0.2 mmol) 3-bromopropene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 100 ± 3 °C. Stir the reaction for 24 minutes. After cooling to room temperature, the sample was separated by silica gel column chromatography to obtain 7-phenyl-2-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, with a yield of 82%. 1 H NMR (400 MHz, Chloroform-d) δ 8.27 (s, 1H), 7.99 (d, J = 11.5 Hz, 1H), 7.68 – 7.64 (m, 3H), 7.50 – 7.38 (m, 5H), 6.88 (dd, J = 11.5, 1.9 Hz, 1H), 5.89 – 5.78 (m, 1H), 5.05 – 4.94 (m, 2H), 2.51 – 2.43 (m, 1H), 2.35 – 2.28 (m, 1H), 1.75 – 1.68(m, 1H), 1.22 (s, 12H), 1.13 – 1.08 (m, 1H), 1.06 – 0.99 (m, 1H). HRMS(ESI)m / z: calculated for [C 25 H 31 B2NO2+H] + 400.2614, found 400.2604.

[0098] Example 14:

[0099] 2-(4-(bromomethyl)-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene

[0100]

[0101] Add 4.05 mg (0.01 mmol) carbene copper IMesCuCl, 34.35 mg (0.3 mmol) KOtBu, 38.87 mg (0.15 mmol) pinacol diboronate (B2pin2), 50 mg of activated 4Å molecular sieve, and 15.51 mg (0.1 mmol) 2-vinyl-2,1-borazonaphthalene to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of 1,4-dioxane and 23.47 µL (0.2 mmol) of 3-bromo-2-(bromomethyl)propene sequentially. After stirring for 2 minutes, seal the reaction system and maintain the temperature at 100 ± 3 °C. Stir the reaction for 24 minutes. After cooling to room temperature, the sample was separated by silica gel column chromatography to obtain 2-(4-(bromomethyl)-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pent-4-en-2-yl)-2,1-borazanaphthalene, with a yield of 35%. 1 H NMR (400MHz, Chloroform-d) δ 8.21 (s, 1H), 7.97 (d, J = 11.5 Hz, 1H), 7.58 (d, J =7.7 Hz, 1H), 7.40 – 7.36 (m, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.15 – 7.11 (m,1H), 6.86 (dd, J = 11.5, 1.9 Hz, 1H), 5.17 (s, 1H), 4.94 (d, J = 1.2 Hz, 1H), 4.02 – 3.96 (m, 2H), 2.72 – 2.66 (m, 1H), 2.40 – 2.34 (m, 1H), 1.82 – 1.78(m, 1H), 1.20 (s, 12H), 1.05 (dd, J = 15.9, 5.6 Hz, 1H), 0.96 (dd, J = 15.9,9.4 Hz, 1H).

[0102] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the invention to the specific implementations described. Clearly, many modifications and variations can be made based on the content of this specification. This specification selects and specifically describes these embodiments to better explain the principles and practical applications of the invention, thereby enabling those skilled in the art to better understand and utilize the invention.

Claims

1. A method for preparing a 2-alkylboronic acid pinacol ester-2,1-borazonaphthalene compound, characterized in that: Includes the following steps: Step 1: Add the base and general formula 2 sequentially to the dry Schlenk reaction tube equipped with a stir bar. The pinacol diboron ester shown Copper-based catalysts, activated 4Å molecular sieves, and general formula 1 The 2,1-borazonaphthalene compounds shown; Step 2: Use a Schlenk double-row tube to evacuate and introduce argon gas, repeating three times. While argon gas is introduced, add solvent and react at 25±3 ℃ to generate a yellow-green pre-stirred liquid. Step 3: Add general formula 3 The allyl halide shown was reacted in a sealed reaction tube at 80-100 °C for 24-36 h, and then cooled to room temperature. Step 4: Concentrate the reaction solution. The concentrate is then separated by silica gel column chromatography to obtain the product of general formula 4. The 2-alkylboronic acid pinacol ester-2,1-borazonaphthalene compound shown; General formula 1 General Formula 3 and general formula 4 R in 1 Selected from hydrogen, alkyl, alkoxy, aryl or halogen, R 2 Selected from hydrogen, alkyl, haloalkyl or halogen, R 3 The catalyst is selected from halogens; the copper-based catalyst is selected from either IMesCuCl or CuCl / SPhos.

2. The method for preparing the 2-alkylboronic acid pinacol ester-2,1-borazonaphthalene compound according to claim 1, characterized in that: The base is selected from either sodium tert-butoxide or potassium tert-butoxide.

3. The method for preparing the 2-alkylboronic acid pinacol ester-2,1-borazonaphthalene compound according to claim 1, characterized in that: The solvent is selected from benzene, toluene, or 1,4-dioxane.

4. The method for preparing the 2-alkylboronic acid pinacol ester-2,1-borazonaphthalene compound according to claim 1, characterized in that: 2,1-Borazonaphthalene: Pinaryl diboronate B2pin2: Copper-based catalyst (calculated as copper): Base: Allyl halide in a molar ratio of 1.0 : 1.5 ~ 2.0 : 0.1 ~ 0.15 : 3.0 ~ 4.0 : 2.0 ~ 3.0.

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