Alkali-promoted system for synthesizing alkenyl boronate from propargyl alcohol compounds and application thereof

Abstract

The application provides a base-promoted system for synthesizing alkenyl borate from propargyl alcohol compounds, which comprises propargyl alcohol compounds, a diboron reagent, a base and a solvent. The application also provides an application of the base-promoted system, which is used for synthesizing alkenyl borate from propargyl alcohol compounds through a borohydride reaction. The method is as follows: under the action of a base and a solvent, a borohydride reaction of propargyl alcohol compounds is promoted by using a diboron reagent as a boron source, so as to synthesize alkenyl borate in a trans stereospecific and beta-regioselective manner. In the reaction system, the trans stereospecific and beta-regioselectivity of the borohydride addition of propargyl alcohol compounds are realized, and a transition metal catalyst is not needed, and the system has the advantages of wide substrate application range, high conversion rate and mild reaction conditions.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis, and particularly relates to a base-promoted system for synthesizing alkenyl boronate from propargyl alcohol compounds and application thereof. BACKGROUND

[0002] As a highly versatile organic synthesis building block, alkenyl boronate has extremely high synthetic application value and can be used for Suzuki-Miyaura cross-coupling reaction and Chan-Lam coupling reaction to convert C-B bond into C-O bond, C-N bond, C-S bond and C-C bond, so as to construct complex drug molecules; and can be widely applied to the fields of medicine, liquid crystal material, organic functional material and the like.

[0003] The stereoselectivity and regioselectivity of the borohydration reaction of alkynes are important factors for determining the structure of products, and how to realize the control of stereoselectivity and regioselectivity has always been a core problem in the research of the borohydration reaction of alkynes. In most precedents, the borohydration reaction of alkynes usually follows cis stereoselectivity and anti Markovnikov regioselectivity, while trans stereoselectivity, Markovnikov regioselectivity and the regioselectivity of internal alkynes are still challenging. Although in recent years, these uncommon selectivities can be realized through the strategy of transition metal catalysis. However, the use of transition metal catalysts greatly limits the economy of the reaction in large-scale production, and in addition, the removal of residual toxic transition metals in the product also requires additional operations and costs in drug synthesis. In addition, although there are several studies on trans borohydration reactions without transition metal catalysts, these reactions need to use non-commercial boron reagents or are limited to a narrow range of substrates.

[0004] The core of the present application is to establish a base-promoted system for synthesizing alkenyl boronate through the trans stereoselectivity and beta-regioselectivity of the borohydration reaction of propargyl alcohol compounds, so as to provide a green, economical and efficient reaction system for the borohydration reaction of propargyl alcohol compounds. SUMMARY

[0005] The technical problem to be solved by the present application is to provide a base-promoted system for synthesizing alkenyl boronate from propargyl alcohol compounds and application thereof, which realizes the control of the trans stereoselectivity and beta-regioselectivity of the borohydration reaction, and the reaction conditions are simple and mild, without the use of transition metals, the reagents used are cheap and easy to obtain, and the substrate range is wide, so as to provide a green, economical and efficient reaction system for the borohydration reaction of propargyl alcohol compounds.

[0006] To solve the above technical problems, the technical scheme adopted by the present application is that a base-promoted system for synthesizing alkenyl boronate from propargyl alcohol compounds comprises propargyl alcohol compounds, diboron reagent, base and solvent.

[0007] the molar ratio of the base to the propargyl alcohol compound is 1:1 to 3:1;

[0008] the molar ratio of the double-boron reagent to the propargyl alcohol compound is 1:1 to 3:1.

[0009] Preferably, the propargyl alcohol compound includes secondary, tertiary internal propargyl alcohol and terminal propargyl alcohol, which general formula is as follows:

[0010]

[0011] R 1 , R 2 , R 3 = hydrogen, alkyl, alkenyl or aryl.

[0012] Preferably, the base is an alkoxy base, an organic metal lithium compound or an inorganic strong base;

[0013] the alkoxy base includes lithium alkoxide, sodium alkoxide or potassium alkoxide; the alkoxy in the alkoxy base includes methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy or tert-amyl;

[0014] the organic lithium compound includes butyl lithium, diisopropylamine lithium or benzyl lithium;

[0015] the inorganic strong base includes an amino compound, an alkali metal hydride or a fluoride; the amino compound includes lithium amide, potassium amide or sodium amide; the alkali metal hydride includes sodium hydride or potassium hydride; the fluoride includes hydrofluoric acid or potassium fluoride.

[0016] Preferably, the solvent is an aprotic polar solvent or a mixed solvent of an aprotic polar solvent and other solvents; the aprotic polar solvent includes a sulfoxide solvent or an amide solvent, and the other solvents include an ether solvent, a benzene solvent or an alkane solvent;

[0017] the sulfoxide solvent includes dimethyl sulfoxide, diethyl sulfoxide, dibutyl sulfoxide or benzyl phenyl sulfoxide;

[0018] the amide solvent includes N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl pyrrolidone, 1,3-dimethyl-2-imidazolidinone or hexamethylphosphoric triamide;

[0019] the ether solvent includes diethyl ether, methyl tert-butyl ether, isopropyl ether, n-butyl ether, anisole, tetrahydrofuran, tetrahydropyran, 1,4-dioxane;

[0020] the benzene solvent includes benzene, toluene, o-xylene, p-xylene, m-xylene, ethylbenzene, mesitylene;

[0021] The alkane solvent includes n-hexane, n-heptane and petroleum ether.

[0022] Preferably, the double boron reagent includes pinacol boronate, bis(+)-pinane diol boronate, bis-dimethylaminonaphthalene boronate or (dimethylaminonaphthalene) pinacol borate.

[0023] The application also provides an alkali-promoted system for synthesizing alkenyl borate from propargyl alcohol compounds.

[0024] The application also provides a method for synthesizing alkenyl borate from propargyl alcohol compounds, wherein the reaction system is the alkali-promoted system, and the method comprises the following steps:

[0025] S1, adding alkali and double boron reagent into a reactor;

[0026] S2, tightly plugging the reactor with vacuum silicone grease, vacuumizing and filling argon for 3 times, and sealing the reactor;

[0027] S3, under the protection of argon, injecting propargyl alcohol compounds and solvent into the reactor in sequence by using a syringe; the molar ratio of the alkali to the propargyl alcohol compounds is 1:1-3:1; and the molar ratio of the double boron reagent to the propargyl alcohol compounds is 1:1-3:1;

[0028] S4, stirring the reaction for 30 min at a temperature of 25℃;

[0029] S5, after the reaction is completed, quenching the reaction by adding water first, and then extracting the reaction solution with petroleum ether and ethyl acetate for 3 times, and then taking the organic phase; drying the organic phase with anhydrous sodium sulfate, and then drying by using a rotary evaporator to obtain a crude product; and then performing column chromatography on the crude product, and then drying by using a rotary evaporator to obtain alkenyl borate.

[0030] Preferably, the temperature of 25℃ in S4 is achieved by placing the reactor in an oil bath pot at 25℃ and stirring the reaction.

[0031] Preferably, the volume ratio of petroleum ether to ethyl acetate in the extractant in S5 is 1:1-10:1.

[0032] Preferably, the eluent of the column chromatography in S5 is petroleum ether: ethyl acetate = 1:1-10:1.

[0033] In the method for synthesizing alkenyl borate from propargyl alcohol compounds by borohydride reaction, the borohydride reaction exhibits trans-stereospecificity and β-regioselectivity, as shown below:

[0034]

[0035] R 1 , R 2 , R 3 = hydrogen, alkyl, alkenyl or aryl.

[0036] The present application has the following advantages compared with the prior art:

[0037] 1. The base-promoted system for synthesizing alkenyl borate of the propargyl alcohol compound of the present application realizes the specific control of trans-stereoselectivity and β-regioselectivity of the borohydration reaction, and the reaction condition is simple and mild, without using transition metal catalyst, and the reagent is cheap and easy to obtain, and the substrate range is wide, thus providing a green, economic and efficient reaction system for the borohydration reaction of the propargyl alcohol compound.

[0038] 2. The reaction system of the present application is suitable for various internal and terminal propargyl alcohol compounds with different types of structures and different functional groups, especially related complex bioactive molecules.

[0039] The present application will be further described in detail below in combination with the drawings and examples. BRIEF DESCRIPTION OF DRAWINGS

[0040] Figure 1 is the reaction mechanism diagram of the present application.

[0041] Figure 2 and Figure 3 are the nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of Example 1 of the present application, respectively.

[0042] Figure 4 and Figure 5 are the nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of Example 2 of the present application, respectively.

[0043] Figure 6 and Figure 7 are the nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of Example 3 of the present application, respectively.

[0044] Figure 8 and Figure 9 are the nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of Example 4 of the present application, respectively.

[0045] Figure 10 and Figure 11 are the nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of Example 5 of the present application, respectively.

[0046] Figure 12 and Figure 13 are the nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of Example 6 of the present application, respectively.

[0047] Figure 14 and Figure 15 are the nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of Example 7 of the present application, respectively.

[0048] Figure 16 and Figure 17 are the nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of the present application embodiment 8 respectively.

[0049] Figure 18 and Figure 19 are the nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of the present application embodiment 9 respectively.

[0050] Figure 20 and Figure 21 are the nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of the present application embodiment 10 respectively.

[0051] Figure 22 and Figure 23 are the nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of the present application embodiment 11 respectively. DETAILED DESCRIPTION

[0052] All the reactions of the present application are carried out in argon and degassed solvents.

[0053] Example 1

[0054] The method of the present application embodiment 1 for synthesizing the alkenyl borate by the hydroboration reaction of the propargyl alcohol compound is carried out by using the following chemical reaction formula:

[0055]

[0056] First, a 10 mL Schlenk tube equipped with a magnetic stirrer was sequentially added with LiO t Bu (lithium tert-butoxide, 0.2 mmol) and (Bpin)2 (pinacol borate, 0.15 mmol), the Schlenk tube was vacuumed by a vacuum pump and filled with high-purity argon for three times; DMSO (dimethyl sulfoxide, 0.5 mL) and 2-methyl-3-octyn-2-ol (0.1 mmol) were sequentially added by using a syringe under the protection of argon, and the reaction solution was stirred at room temperature (25 °C) for 30 min; after the reaction was completed, the reaction was quenched by adding water first, and then the product was extracted by petroleum ether and ethyl acetate with a volume ratio of 10:1 for three times, and the combined organic phase was dried with anhydrous Na2SO4, followed by concentration and rotary evaporation to obtain the crude product; the crude product was separated and purified by a silica gel chromatographic column (eluent: petroleum ether: ethyl acetate = 10:1, v:v), and then concentrated and rotary evaporated, and the residual eluent on the product was removed by a vacuum pump to obtain the product (E)-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborinanyl) 3-octen-2-ol, which was weighed by using an analytical balance, and the yield was calculated to be 91%.

[0057] Figure 2 andFigure 3 The nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of this example are as follows, respectively:

[0058] Nuclear magnetic hydrogen spectrum data: 1 H NMR (500 MHz, DMSO-d6) δ 6.07 (t, J = 7.6 Hz, 1H), 4.31 (s, 1H), 2.15 (q, J = 7.2 Hz, 2H), 1.32 (ddt, J = 12.8, 9.4, 4.3 Hz, 4H), 1.25 (s, 12H), 1.22 (s, 6H), 0.90 (t, J = 7.0 Hz, 3H);

[0059] Nuclear magnetic carbon spectrum data: 13 C NMR (126 MHz, DMSO-d6) δ 137.25, 83.42, 72.29, 32.65, 31.59, 31.17, 25.43, 22.56, 14.67.

[0060] The base used in this example can be lithium methoxide, lithium ethoxide, lithium propoxide, lithium isopropoxide or lithium tert-pentoxide in addition to lithium tert-butoxide.

[0061] The solvent used in this example can be diethyl sulfoxide, dibutyl sulfoxide or benzyl phenyl sulfoxide in addition to dimethyl sulfoxide.

[0062] Example 2

[0063] The method for synthesizing alkenyl borate by borohydride reaction of the propargyl alcohol compound of this example is carried out using the following chemical reaction formula:

[0064]

[0065] First, 0.1 mL of LiOtBu (1.0 M in cyclohexane) was added to a 10 mL Schlenk tube equipped with a magnetic stirrer, followed by the addition of 0.1 mL of 2,4,6-trimethylphenol and 0.1 mL of 2,6-lutidine. tBu (tert-butyllithium, 0.2 mmol) and pinB-Bdan (dimethylaminonaphthalene-pinacol boronate, 0.15 mmol), the Schlenk tube was pumped with vacuum and filled with high-purity argon for three times; DMSO (dimethyl sulfoxide, 0.5 mL) and 2-methyl-3-octyn-2-ol (0.1 mmol) were added in sequence under argon protection using a syringe, and the reaction solution was stirred at room temperature (25 °C) for 30 min; after the reaction was completed, the reaction was quenched by adding water first, and then the product was extracted with petroleum ether and ethyl acetate in a volume ratio of 1:1, three times, and the combined organic phase was dried with anhydrous Na2SO4, followed by concentration and rotary evaporation to obtain a crude product; the crude product was separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 1:1, v:v), and then concentrated and rotary evaporated, and the residual eluent on the product was removed using a vacuum pump to obtain the product (E)-2-methyl-3-(1,8-diaminonaphthyl-1,3,2-diazaborolyl) 3-octen-2-ol, which was weighed using an analytical balance, and the yield was calculated to be 77%.

[0066] Figure 4 and Figure 5 The nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of the present example are shown in FIGS. 1 and 2, respectively, and the data are as follows:

[0067] Nuclear magnetic hydrogen spectrum data: 1 H NMR (500 MHz, DMSO-d6) δ 7.52 (s, 2H), 7.01 (dd, J = 8.2, 7.4 Hz, 2H), 6.84 (dd, J = 8.3, 1.0 Hz, 2H), 6.44 (dd, J = 7.4, 1.0 Hz, 2H), 5.81 (t, J = 7.3 Hz, 1H), 4.28 (s, 1H), 2.03 (q, J = 7.3 Hz, 2H), 1.34 (m, 4H), 1.27 (s, 6H), 0.84 (t, J = 7.2 Hz, 3H);

[0068] Nuclear magnetic carbon spectrum data: 13 C NMR (126 MHz, DMSO-d6) δ 143.39, 136.85, 131.73, 128.45, 120.33, 116.61, 106.08, 72.42, 32.85, 32.28, 32.20, 22.69, 14.86.

[0069] Example 3

[0070] The method for synthesizing alkenyl borate by propargyl alcohol borohydride reaction of the present example is carried out using the following chemical reaction formula:

[0071] The method for synthesizing alkenyl borate by propargyl alcohol borohydride reaction of the present example is carried out using the following chemical reaction formula:

[0072] First, a 10 mL Schlenk tube equipped with a magnetic stirrer was sequentially added with LiO t Bu (lithium tert-butoxide, 0.2 mmol) and (Bpin)2(frequency alcohol bisborate, 0.15 mmol), the Schlenk tube was pumped and filled with high-purity argon for three times; DMSO (dimethyl sulfoxide, 0.5 mL) and 4-cyclopropyl-2-methyl-3-butyn-2-ol (0.1 mmol) were sequentially added under argon protection using a syringe; the reaction solution was stirred at room temperature (25°C) for 30 min; after the reaction was completed, the reaction was quenched by adding water first, and then the product was extracted with petroleum ether and ethyl acetate in a volume ratio of 10:1, repeated three times, and the combined organic phase was dried with anhydrous Na2SO4, followed by concentration and rotary evaporation to obtain a crude product; the crude product was then separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1, v:v), and then concentrated and rotary evaporated, and the residual eluent on the product was removed using a vacuum pump to obtain the product (E)-4-cyclopropyl-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborinanyl)-3-butene-2-ol, which was weighed using an analytical balance, and the yield was calculated to be 87%.

[0073] Figure 6 and Figure 7 The nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of this example are shown in Figures 1 and 2, respectively, and the data are as follows:

[0074] Nuclear magnetic hydrogen spectrum data: 1 H NMR (500 MHz, Chloroform-d) δ 5.42 (d, J = 10.3 Hz, 1H), 2.87 (s, 1H), 2.23-2.04 (m, 1H), 1.31 (s, 6H), 1.29 (s, 12H), 0.82-0.73 (m, 2H), 0.44-0.31 (m, 2H);

[0075] Nuclear magnetic carbon spectrum data: 13 C NMR (126 MHz, Chloroform-d) δ 147.61, 83.42, 73.28, 30.06, 24.93, 12.90, 7.94.

[0076] Example 4

[0077] The method for synthesizing alkenyl borate by hydroboration of propargyl alcohol compounds in this example is carried out using the following chemical reaction formula:

[0078]

[0079] First, a 10 mL-Schlenk tube equipped with a magnetic stirrer was sequentially added with LiO t Bu (lithium tert-butoxide, 0.2 mmol) and (Bpin)2 (pinacol borate, 0.15 mmol), the Schlenk tube was vacuumed by a vacuum pump and filled with high-purity argon for three times; DMSO (dimethyl sulfoxide, 0.5 mL) and 4-(4-methoxyphenyl)-2-methyl-3-butyn-2-ol (0.1 mmol) were sequentially added by using a syringe under the protection of argon, and the reaction solution was stirred at room temperature (25 °C) for 30 min; after the reaction was completed, the reaction was quenched by adding water first, and then the product was extracted by petroleum ether and ethyl acetate with a volume ratio of 10:1 for three times, and the combined organic phase was dried with anhydrous Na2SO4, followed by concentration and rotary evaporation to obtain a crude product; the crude product was separated and purified by a silica gel chromatographic column (eluent: petroleum ether: ethyl acetate = 10:1, v:v), and then concentrated and rotary evaporated by using a rotary evaporator, and the residual eluent on the product was removed by a vacuum pump, to obtain (E)-4-(4-methoxyphenyl)-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-3-yl)-3-buten-2-ol, which was weighed by using an analytical balance, and the yield was calculated to be 80%.

[0080] Figure 8 and Figure 9 The nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of this example are shown in FIGS. 1 and 2, respectively, and the data are as follows:

[0081] Nuclear magnetic hydrogen spectrum data: 1 H NMR (500 MHz, DMSO-d6) δ 7.24 (d, J = 8.5 Hz, 2H), 6.93-6.77 (m, 3H), 4.64 (s, 1H), 3.73 (s, 3H), 1.29 (s, 6H), 1.22 (s, 13H);

[0082] Nuclear magnetic carbon spectrum data: 13 C NMR (126 MHz, DMSO-d6) δ 158.16, 132.08, 131.09, 128.63, 113.26, 82.88, 72.09, 54.88, 30.54, 24.57.

[0083] Example 5

[0084] The method for synthesizing alkenyl borate by borohydride reaction of the propargyl alcohol compound of this example is carried out by using the following chemical reaction formula:

[0085]

[0086] First, a 10 mL-Schlenk tube equipped with a magnetic stirrer was sequentially added with LiOt Bu (tert-butyllithium, 0.2 mmol) and (Bpin)2 (pinacolboronate, 0.15 mmol), the Schlenk tube was pumped with vacuum and filled with high-purity argon for three times; DMSO (dimethyl sulfoxide, 0.5 mL) and 1-cyclopropyl-1-octyn-3-ol (0.1 mmol) were added successively under argon protection using a syringe, and the reaction solution was stirred at room temperature (25 °C) for 30 min; after the reaction was completed, the reaction was quenched by adding water first, and then the product was extracted with petroleum ether and ethyl acetate in a volume ratio of 5:1, repeated three times, and the combined organic phase was dried with anhydrous Na2SO4, followed by concentration and rotary evaporation to obtain the crude product; the crude product was then separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 5:1, v:v), and then concentrated and rotary evaporated, and the residual eluent on the product was removed using a vacuum pump to obtain the product (E)-1-cyclopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-yl)-1-octen-3-ol, which was weighed using an analytical balance, and the yield was calculated to be 75%.

[0087] Figure 10 and Figure 11 The nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of the present example are shown in Figures 1 and 2, respectively, and the data are as follows:

[0088] Nuclear magnetic hydrogen spectrum data: 1 H NMR (500 MHz, Chloroform-d) δ 5.42 (d, J = 10.4 Hz, 1H), 3.92 (t, J = 6.8 Hz, 1H), 2.41 (s, 1H), 2.25-2.14 (m, 1H), 1.61-1.43 (m, 2H), 1.28 (d, J = 2.5 Hz, 18H), 0.86 (t, J = 6.9 Hz, 3H), 0.80 (ddd, J = 8.0, 4.0, 2.1 Hz, 2H), 0.39 (td, J = 5.6, 5.0, 2.6 Hz, 2H);

[0089] Nuclear magnetic carbon spectrum data: 13 C NMR (126 MHz, Chloroform-d) δ 152.84, 83.29, 78.36, 38.47, 31.93, 25.94, 24.94 (d, J = 51.9 Hz), 22.74, 14.20, 12.96, 8.06, 8.01.

[0090] Example 6

[0091] The method for synthesizing alkenyl borate by hydroboration of propargyl alcohol compounds in the present example is carried out using the following chemical reaction formula:

[0092]

[0093] First, a 10 mL Schlenk tube equipped with a magnetic stir bar was charged with LiO t Bu (lithium tert-butoxide, 0.2 mmol) and (Bpin)2(pinacolboronate, 0.15 mmol), the Schlenk tube was evacuated with a vacuum pump and filled with high purity argon for three times; DMSO (dimethyl sulfoxide, 0.5 mL) and 1-cyclopropyl-5-phenyl-1-pentyn-3-ol (0.1 mmol) were added successively under argon protection using a syringe, the reaction solution was stirred at room temperature (25 °C) for 30 min; after the reaction was completed, the reaction was quenched by adding water first, then the product was extracted with petroleum ether and ethyl acetate in a volume ratio of 7.5:1 for three times, and the combined organic phase was dried with anhydrous Na2SO4, then concentrated and rotary evaporated to obtain the crude product; the crude product was separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 7.5:1, v:v), then concentrated and rotary evaporated, and the residual eluent on the product was removed using a vacuum pump, to obtain the product (E)-1-cyclopropyl-5-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-yl)-1-penten-3-ol, which was weighed using an analytical balance, and the yield was calculated to be 81%.

[0094] Figure 12 and Figure 13 The nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of the present example are shown in Figures 1 and 2 respectively, and the data are as follows:

[0095] Nuclear magnetic hydrogen spectrum data: 1 H NMR (500 MHz, DMSO-d6) δ 7.25 (t, J = 7.6 Hz, 2H), 7.20-7.07 (m, 3H), 5.51 (dd, J = 10.6, 1.3 Hz, 1H), 4.46 (d, J = 4.5 Hz, 1H), 4.15-3.97 (m, 1H), 2.69-2.44 (m, 2H), 2.21-2.07 (m, 1H), 1.83-1.50 (m, 2H), 1.21 (d, J = 3.7 Hz, 12H), 0.75 (dd, J = 7.9, 2.2 Hz, 2H), 0.33 (tq, J = 5.4, 3.5, 2.7 Hz, 2H);

[0096] Nuclear magnetic carbon spectrum data: 13 C NMR (126 MHz, DMSO-d6) δ 148.58, 142.50, 128.15, 128.12, 125.37, 82.46, 71.92, 39.46, 31.66, 24.54 (d, J = 51.5 Hz), 12.74, 7.39 (d, J = 7.8 Hz).

[0097] Example 7

[0098] The method for synthesizing alkenyl boronate ester by propargyl alcohol boron hydride reaction of this embodiment is carried out using the following chemical reaction formula:

[0099]

[0100] First, a 10 mL Schlenk tube equipped with a magnetic stirrer was sequentially added with LiO t Bu (lithium tert-butoxide, 0.2 mmol) and (Bpin)2 (pinacol borate, 0.15 mmol), the Schlenk tube was vacuumed by a vacuum pump and filled with high-purity argon for three times; DMSO (dimethyl sulfoxide, 0.5 mL) and 1-cyclohexyl-2-propargyl-1-ol (0.1 mmol) were sequentially added under argon protection using a syringe. The reaction solution was stirred at room temperature (25 °C) for 30 min; after the reaction was completed, water was first added to quench the reaction, then petroleum ether and ethyl acetate with a volume ratio of 2.5:1 were added to extract the product for three times, and the combined organic phase was dried with anhydrous Na2SO4, followed by concentration and rotary evaporation to obtain a crude product; the crude product was separated and purified by a silica gel chromatographic column (eluent: petroleum ether: ethyl acetate = 2.5:1, v:v), then concentrated and rotary evaporated, and the residual eluent on the product was removed using a vacuum pump to obtain 1-cyclohexyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-propen-1-ol, which was weighed using an analytical balance to calculate the yield of 81%.

[0101] Figure 14 and Figure 15 The nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of this embodiment are shown in Figures 1 and 2, respectively, and the data are as follows:

[0102] Nuclear magnetic hydrogen spectrum data: 1 H NMR (500 MHz, Chloroform-d) δ 5.87 (d, J = 3.3 Hz, 1H), 5.68 (d, J = 3.2 Hz, 1H), 3.82 (d, J = 7.0 Hz, 1H), 2.22 (br, 1H), 1.92 (d, J = 12.9 Hz, 1H), 1.78-1.67 (m, 2H), 1.64-1.53 (m, 2H), 1.46-1.41 (m, 1H), 1.26 (d, J = 3.3 Hz, 12H), 1.19-1.09 (m, 3H), 0.97-0.84 (m, 2H);

[0103] Nuclear magnetic carbon spectrum data: 13C NMR (126 MHz, Chloroform-d) δ 130.02, 83.75, 81.13, 44.14, 29.76, 28.88, 26.64, 26.40, 26.26, 24.79 (d, J = 35.4 Hz).

[0104] The solvent used in this example can be a mixed solvent of dimethyl sulfoxide: tetrahydrofuran (1 :4) in addition to dimethyl sulfoxide.

[0105] Example 8

[0106] The method for synthesizing alkenyl borate by borohydration of propargyl alcohol compound of this example is carried out using the following chemical reaction formula:

[0107]

[0108] First, LiNH2(amino lithium, 0.1 mmol) and (Bpai)2(bis(+)-pinanediol dibo rate, 0.1 mmol) were sequentially added to a 10 mL Schlenk tube equipped with a magnetic stirrer, the Schlenk tube was vacuumed with a vacuum pump and filled with high-purity argon for three times; NMP (N-methyl pyrrolidone, 0.5 mL) and 2-methyl-3-octyn-2-ol (0.1 mmol) were sequentially added under argon protection using a syringe. The reaction solution was stirred at room temperature (25°C) for 30 min; after the reaction was completed, water was first added to quench the reaction, then petroleum ether and ethyl acetate in a volume ratio of 10:1 were added to extract the product, which was repeated three times, and the combined organic phase was dried with anhydrous Na2SO4, then concentrated and rotary evaporated to obtain a crude product; the crude product was separated and purified by silica gel chromatography column (eluent: petroleum ether: ethyl acetate = 10:1, v:v), then concentrated and rotary evaporated, and the residual eluent on the product was removed using a vacuum pump, to obtain 2-methyl-3-(3aR,4R,6R,7aS)-3a,5,5-trimethylhexahydro-4,6-toluene[d][1,3,2]dioxaborinanyl)-3octen-2-ol, which was weighed using an analytical balance, and the yield was calculated to be 83%.

[0109] Figure 16 and Figure 17 The nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of this example are as follows:

[0110] Nuclear magnetic hydrogen spectrum data: 1H NMR (500MHz, DMSO-d6) δ6.09(t,J=7.6Hz,1H),4.51-4.34(m,2H),2.44-2.33(m,1H),2.26-2.12(m,3H),2.03(t,J=5.5Hz,1H),1.91( tt,J=5.8,3.0Hz,1H),1.76(ddd,J=14.4,3.3,2.2Hz,1H),1.37(s,3H),1.35-1.26(m,8H),1.24(d,J=1.9Hz,6H),0.92–0.86(m,6H);

[0111] Carbon NMR data: 13 C NMR (126MHz, DMSO-d6) δ137.46,85.68,77.34,72.35,51.73,39.91,38.70,36.2 2,32.66,31.64(d,J=3.5Hz),31.39,29.48,27.77,27.02,24.63,22.61,14.73.

[0112] In this embodiment, the alkali used, in addition to lithium amino, can also be potassium amino or sodium amino.

[0113] In this embodiment, the solvent used, in addition to N-methylpyrrolidone, can also be 1,3-dimethyl-2-imidazolinone.

[0114] Example 9

[0115] The method for synthesizing alkenyl borate esters by the hydroboration reaction of propargyl alcohol compounds in this embodiment is carried out using the following chemical reaction formula:

[0116]

[0117] First, add the following ingredients sequentially to a 10 mL Schlenk tube equipped with a magnetic stir bar: nBuLi (n-butyllithium, 0.25 mmol) and (Bdan)2 (bisdimesitylaminoborane, 0.25 mmol), the Schlenk tube was vacuumed by vacuum pump and filled with high-purity argon for three times; DMAc (N,N-dimethylacetamide, 0.5 mL) and 2-methyl-3-octyn-2-ol (0.1 mmol) were added successively under argon protection by using a syringe, and the reaction solution was stirred at room temperature (25 °C) for 30 min; after the reaction was completed, the reaction was quenched by adding water first, and then the product was extracted by petroleum ether and ethyl acetate with a volume ratio of 10:1, repeated three times, and the combined organic phase was dried with anhydrous Na2SO4, followed by concentration and rotary evaporation to obtain a crude product; the crude product was separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1, v:v), and then concentrated and rotary evaporated, and the residual eluent on the product was removed by vacuum pump, to obtain (E)-2-methyl-3-(1,8-diaminonaphthyl-1,3,2-diazaborolyl) 3-octen-2-ol, which was weighed by using an analytical balance, and the yield was calculated to be 75%.

[0118] Figure 18 and Figure 19 The nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of the present example are shown in Figures 1 and 2, respectively, and the data are as follows:

[0119] Nuclear magnetic hydrogen spectrum data: 1 H NMR (500 MHz, DMSO-d6) δ 7.52 (s, 2H), 7.01 (dd, J = 8.2, 7.4 Hz, 2H), 6.84 (dd, J = 8.3, 1.0 Hz, 2H), 6.44 (dd, J = 7.4, 1.0 Hz, 2H), 5.81 (t, J = 7.3 Hz, 1H), 4.28 (s, 1H), 2.03 (q, J = 7.3 Hz, 2H), 1.34 (m, 4H), 1.27 (s, 6H), 0.84 (t, J = 7.2 Hz, 3H);

[0120] Nuclear magnetic carbon spectrum data: 13 C NMR (126 MHz, DMSO-d6) δ 143.39, 136.85, 131.73, 128.45, 120.33, 116.61, 106.08, 72.42, 32.85, 32.28, 32.20, 22.69, 14.86.

[0121] The base used in the present example can also be lithium diisopropylamide or benzyl lithium in addition to n-butyllithium.

[0122] The solvent used in the present example can also be a mixed solvent of N,N-dimethylacetamide: toluene (1:1) in addition to N,N-dimethylacetamide.

[0123] Example 10

[0124] The method for synthesizing alkenyl boronate ester by propargyl alcohol boron hydride reaction of this embodiment is carried out using the following chemical reaction formula:

[0125]

[0126] First, 10 mL-Schlenk tube equipped with magnetic stirrer was sequentially added with NaO t Bu (sodium tert-butoxide, 0.3 mmol) and (Bpin)2(frequency alcohol diboate, 0.15 mmol), the Schlenk tube was vacuumed by vacuum pump and filled with high-purity argon for three times; under the protection of argon, DMF (N, N-dimethylformamide, 0.5 mL) and 1-ethynylcyclohexane-1-ol (0.1 mmol) were sequentially added by using a syringe, and the reaction solution was stirred at room temperature (25°C) for 30 min; after the reaction was completed, the reaction was quenched by adding water first, and then the product was extracted by petroleum ether and ethyl acetate with a volume ratio of 10:1, repeated three times, and the combined organic phase was dried with anhydrous Na2SO4, followed by concentration and rotary evaporation to obtain the crude product; the crude product was separated and purified by silica gel chromatography column (eluent: petroleum ether: ethyl acetate = 10:1, v:v), then concentrated and rotary evaporated, and the residual eluent on the product was removed by vacuum pump to obtain the product (E)-1-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborinanyl)-1-propenyl)cyclohexane-1-ol, which was weighed by using an analytical balance, and the yield was calculated to be 83%.

[0127] Figure 20 and Figure 21 The nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of this embodiment are as follows:

[0128] Nuclear magnetic hydrogen spectrum data: 1 H NMR (500 MHz, Chloroform-d) δ 5.79 (d, J = 2.6 Hz, 1H), 5.73 (d, J = 2.7 Hz, 1H), 2.40 (s, 1H), 1.72-1.49 (m, 9H), 1.27 (s, 12H), 1.20-1.13 (m, 1H);

[0129] Nuclear magnetic carbon spectrum data: 13 C NMR (126 MHz, Chloroform-d) δ 126.12, 83.82, 73.51, 36.83, 25.85, 24.83, 22.02.

[0130] The base used in this example can be sodium methoxide, sodium ethoxide, sodium propoxide, sodium isopropoxide, sodium tert-pentoxide, potassium methoxide, potassium ethoxide, potassium propoxide, potassium isopropoxide, potassium tert-butoxide, or potassium tert-pentoxide, in addition to sodium tert-butoxide.

[0131] Example 11

[0132] The method for synthesizing alkenyl boronate ester by borohydration reaction of propargyl alcohol compound of this example is carried out using the following chemical reaction formula:

[0133]

[0134] First, KF (potassium fluoride, 0.3 mmol) and (Bpin)2 (pinacol borate, 0.3 mmol) were sequentially added to a 10 mL Schlenk tube equipped with a magnetic stirrer, the Schlenk tube was vacuumed with a vacuum pump and filled with high-purity argon for three times; under argon protection, HMPA (hexamethylphosphoramide, 0.5 mL) and 1-(cyclohexyl-3-ene)-2-propargyl-1-ol (0.1 mmol) were sequentially added using a syringe, and the reaction solution was stirred at room temperature (25°C) for 30 min; after the reaction was completed, water was first added to quench the reaction, then petroleum ether and ethyl acetate in a volume ratio of 10:1 were added to extract the product, which was repeated three times, and the combined organic phase was dried with anhydrous Na2SO4, then concentrated and rotary evaporated to obtain a crude product; the crude product was separated and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1, v:v), then concentrated and rotary evaporated, and the residual eluent on the product was removed using a vacuum pump, to obtain 1-(cyclohexyl-3-ene)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl)-2-propen-1-ol, which was weighed using an analytical balance, and the yield was calculated to be 72%.

[0135] Figure 22 and Figure 23 The nuclear magnetic hydrogen spectrum and the nuclear magnetic carbon spectrum of this example are shown in Figures 1 and 2, respectively, and the data are as follows:

[0136] Nuclear magnetic hydrogen spectrum data: 1 H NMR (500 MHz, Chloroform-d) δ 5.90 (dd, J = 10.6, 3.2 Hz, 1H), 5.72 (dd, J = 5.9, 3.3 Hz, 1H), 5.69-5.62 (m, 2H), 3.88 (dd, J = 30.3, 7.2 Hz, 1H), 2.26-1.64 (m, 8H), 1.27 (d, J = 2.6 Hz, 12H);

[0137] Nuclear magnetic carbon spectrum data: 13C NMR (126 MHz, Chloroform-d) δ 130.41 (d, J = 21.4 Hz), 127.07 (d, J = 51.8 Hz), 126.54 (d, J = 37.2 Hz), 83.84, 80.62 (d, J = 25.5 Hz), 39.87, 28.17 (d, J = 130.8 Hz), 25.40 (d, J = 34.5 Hz), 25.19, 24.82 (dd, J = 29.6, 5.0 Hz).

[0138] The base used in the present example can be sodium fluoride, sodium hydride or potassium hydride in addition to potassium fluoride.

[0139] The above description is only the preferred embodiment of the present application, and does not limit the present application. Any simple modification, change and equivalent change of the above embodiment according to the technical essence of the present application are still within the protection scope of the technical solution of the present application.

Claims

1. A method for synthesizing alkenylboronic esters by hydroboration of propargyl alcohol compounds, characterized in that, The reaction system for synthesizing alkenyl borate esters by the hydroboration of propargyl alcohols includes propargyl alcohols, diboron reagents, bases, and solvents, without the need for transition metals; The propargyl alcohols are secondary or tertiary internal propargyl alcohols or terminal propargyl alcohols, with the following general structural formula: ； The diboron reagent is pinacol diboron ester, bis(+)-pinenediol diboron ester, or bis(dimethylaminonaphthalene diboron ester; In the method for synthesizing alkenyl borate esters by hydroboration of propargyl alcohol compounds, the hydroboration reaction exhibits both trans stereospecificity and β-regiospecificity, and the general reaction formula is as follows: ， R2 comes from a bisboron reagent; The method for synthesizing alkenyl borate esters by the hydroboration reaction of propargyl alcohols includes the following steps: S1. Add the alkali and diboron reagent to the reactor; S2. Tightly plug the reactor with vacuum silicone grease, evacuate and purge with argon three times to seal the reactor; S3. Under argon protection, propargyl alcohol compounds and solvents are injected sequentially into the reactor using a syringe; the molar ratio of the base to the propargyl alcohol compound is 1:1 to 3:1; the molar ratio of the bisborone reagent to the propargyl alcohol compound is 1:1 to 3:

1. S4. Stir the reaction at 25℃ for 30 minutes. S5. After the reaction is complete, water is added to quench the reaction, and then petroleum ether and ethyl acetate are added to extract the reaction solution three times, leaving the organic phase; after drying with anhydrous sodium sulfate, the solution is evaporated to dryness, and then column chromatography is performed to obtain alkenyl borate ester.

2. The method according to claim 1, characterized in that, The base is an alkoxy base, an organometallic lithium compound, or an inorganic strong base.

3. The method according to claim 2, characterized in that, The alkoxy base is lithium alkoxy, sodium alkoxy, or potassium alkoxy; the alkoxy group in the alkoxy base is methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, or tert-pentoxy. The organometallic lithium compound is butyllithium, diisopropylaminolithium, or benzyllithium; The inorganic strong base is an amino compound, an alkali metal hydride, or a fluoride; the amino compound is lithium amine, potassium amine, or sodium amine; the alkali metal hydride is sodium hydride or potassium hydride; and the fluoride is sodium fluoride or potassium fluoride.

4. The method according to claim 1, characterized in that, The solvent is an aprotic polar solvent or a mixture of an aprotic polar solvent and other solvents; the aprotic polar solvent is a sulfoxide solvent or an amide solvent, and the other solvents are ether solvents, benzene solvents or alkane solvents.

5. The method according to claim 4, characterized in that, The sulfoxide solvent is dimethyl sulfoxide, diethyl sulfoxide, dibutyl sulfoxide, or benzylphenyl sulfoxide; The amide solvent is N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone or 1,3-dimethyl-2-imidazolinone; The ether solvent is diethyl ether, methyl tert-butyl ether, isopropyl ether, n-butyl ether, anisole, tetrahydrofuran, tetrahydropyran, or 1,4-dioxane; The benzene solvent is benzene, toluene, o-xylene, p-xylene, m-xylene, ethylbenzene, or trimethylbenzene; The alkane solvent is n-hexane, n-heptane, or petroleum ether.

6. The method according to claim 1, characterized in that, The volume ratio of petroleum ether to ethyl acetate in S5 is 1:1 to 10:1; the eluent for column chromatography is petroleum ether: ethyl acetate = 1:1 to 10:1.

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