A method for the synthesis of 1,3-diboron compounds

Abstract

The application belongs to the technical field of diboron compound synthesis, and particularly relates to a synthesis method of 1,3-diboron compound. The method comprises the following steps: taking an olefin compound, pinacol diboron and iodo-methylene boronic acid ester as raw materials, performing an olefin carbon boronation reaction in a reaction system composed of a Cu-based catalyst, sodium ethoxide and a solvent under a protective atmosphere to obtain the 1,3-diboron compound. The application provides a copper-catalyzed olefin boronation strategy, uses iodo-methylene boronic acid ester as an electrophilic reagent, constructs a series of racemic 1,3-diboron compounds through a Cu-catalyzed olefin carbon boronation reaction with an excellent yield, realizes an effective 1,3-diboron compound modular synthesis method, and the reaction has the characteristics of mild reaction condition, wide raw material source, simple reaction process and high yield.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of synthesis of diboron compounds, and particularly relates to a synthesis method of 1,3-diboron compounds. BACKGROUND

[0002] Boronic acids, boronic esters and the like are powerful tools for constructing carbon-carbon bonds, which can not only undergo Suzuki-Miyaura coupling reactions with halogenated hydrocarbons under palladium catalysis, but also undergo Chan-Lam coupling reactions with compounds containing nitrogen-hydrogen bonds or oxygen-hydrogen bonds under copper catalysis. Boronic ester functional groups (such as Bpin) can be stereospecifically converted in reactions, such as stereoselectively undergoing oxidation, amination, halogenation, Matteson homologation, Zweifel alkenylation, alkynylization, dehydrogenation and the like to obtain compounds containing hydroxyl, amino, halogen, alkenyl, alkynyl and the like functional groups, which makes them widely used in the construction of natural products and drug intermediates.

[0003] In the field of synthetic chemistry, diboron compounds have attracted widespread attention due to their unique synthetic value. They can be selectively subjected to multiple catalytic coupling and chemical conversion, providing an effective way for the synthesis of more delicate and complex drug molecules. At present, many drugs on the market contain chiral 1,3-bifunctional structures, such as rosuvastatin for treating high cholesterol, aliskiren for treating hypertension and sacubitril for treating heart failure. The stereospecific preparation of such drug molecules through chiral 1,3-diboron compounds can improve the convenience of their synthesis.

[0004] However, the synthesis method of 1,3-diboron compounds is still limited. For example, in 2016, Aggarwal's group obtained 1,2-diboron compounds through Morken / Nishiyama diboron reaction, reacted them with enantiomerically enriched lithiated carbamates, and underwent 1,2-boron migration process to stereoselectively prepare chiral 1,3-diboron compounds, and the synthesis route is as follows:

[0005] .

[0006] In 2017, Aggarwal's group reported a method for preparing chiral 1,2- and 1,3-diboron compounds based on 1,2-boron migration process through different lithium reagents, using gem-diboron reagent as raw material based on homologation reaction of diboron compounds, and the synthesis route is as follows:

[0007] .

[0008] In 2020, the Studer group synthesized a series of racemic 1,3-diboron compounds based on the easily prepared vinyl boronate and commercially available iodo-methylene boronate, which undergoes two 1,2-alkyl / aryl migration processes under the action of lithium reagent, and the synthesis route is as follows:

[0009] .

[0010] However, the above-mentioned construction of chiral 1,3-diboron compounds still relies on the homology of 1,1- or 1,2-diboronate, and these transformations require the pre-synthesis of chiral diboronate or the preparation of stoichiometric air and humidity sensitive chiral organic lithium reagent, which has complicated synthesis steps and high requirements for reaction conditions. Modular and practical synthesis is still a challenge. SUMMARY

[0011] In order to solve the above problems, the present application provides a synthesis method of 1,3-diboron compound, and provides a copper-catalyzed olefin boronation strategy, which uses iodo-methylene boronate as an electrophile, and constructs a series of racemic 1,3-diboron compounds through Cu-catalyzed olefin carbon boronation reaction with excellent yield, realizes an effective 1,3-diboron compound modular synthesis method, and the reaction is simple and has high yield under simple and mild reaction conditions. 1,3-diboron compound is synthesized efficiently and widely from a source.

[0012] The present application solves the above technical problems through the following technical solutions.

[0013] The object of the present application is to provide a synthesis method of 1,3-diboron compound, comprising the following steps:

[0014] The olefin compound, pinacol diboron and iodo-methylene boronate are used as raw materials, the olefin carbon boronation reaction is carried out in a reaction system composed of Cu-based catalyst, sodium ethoxide and solvent under a protective atmosphere, and 1,3-diboron compound is obtained.

[0015] Further, the molar ratio of the olefin compound, pinacol diboron and iodo-methylene boronate is 1:1-1.5:1-1.5.

[0016] Further, the molar ratio of the Cu-based catalyst, sodium ethoxide and olefin compound is 0.08-0.15:4:2.

[0017] Further, the Cu-based catalyst is a nitrogen heterocyclic carbene copper complex.

[0018] Further, the iodo-methylene boronate is pinacol iodo-methylene boronate or 2-iodomethyl-4,4,5,5-tetraethyl-1,3,2-dioxaborolane.

[0019] Further, the solvent is 1,4-dioxane, tetrahydrofuran, chlorobenzene or toluene.

[0020] Further, the temperature of the olefin carbon-boron reaction is room temperature, and the reaction time is 10-15 hours.

[0021] Further, the structure of the olefin compound is as follows:

[0022] .

[0023] wherein R is phenyl, substituted phenyl, substituted indole, substituted pyridine, thiophene, ethoxydimethylsilyl or dimethylphenylsilyl.

[0024] The substituent of the phenyl is C1-C4 alkyl, C1-C3 alkoxy, R1COOR2, halogen, benzene, furan, pyrazole, diketone, benzo-fused ring compound, naphthalene derivative, aromatic ketone compound, oxygen-containing heterocyclic compound; R1 is C1-C3 alkyl, and R2 is C1-C4 alkyl.

[0025] The substituent of the indole is R3COOR4, R3 is C1-C3 alkyl, and R4 is C1-C4 alkyl.

[0026] The substituent of the pyridine is C1-C3 alkoxy.

[0027] Further, the substituent of the phenyl is C3-C4 alkyl, C1-C2 alkoxy, R1COOR2, fluorine, chlorine, bromine, benzene, furan, pyrazole, isoindoline-1,3-dione, 2,2-difluorobenzodioxole, 2-(6-methoxynaphthalen-2-yl)propionic acid, 3-benzoylphenyl)propionic acid, 5-(3,4,5-trimethoxyphenyl)-9-oxo-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one, 13-methyl-3-oxo-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one or 13-methyl-1-3-oxo)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl valerate; R1 is C1-C2 alkyl, and R2 is C1-C2 alkyl.

[0028] The substituent of the indole is R3COOR4, R3 is C1-C2 alkyl, and R4 is C3-C4.

[0029] The substituent of the pyridine is C1-C2 alkoxy.

[0030] Further, the olefin compound is styrene, 4-tert-butylstyrene, 3,4-dimethoxystyrene, 3-methoxystyrene, 4-vinylphenyl acetate, 2-bromo-4,5-dimethoxystyrene, 4-fluorostyrene, 4-chlorostyrene, 4-phenylstyrene, 5-vinyl-lH-indole-l-carboxylate tert-butyl ester, 5-vinylbenzofuran, l-(4-vinylphenyl)-lH-pyrazole, 2-(4-vinylbenzyl)isoindoline-l,3-dione, 2,2-difluoro-5-vinyl[ d ][1,3]benzodioxole, 2-methoxy-5-vinylpyridine, 2-vinylnaphthalene, 1,4-dihydro-l,4-oxonaphthalene, 3-vinylthiophene, 2-(ethoxydimethylsilyl)ethene, 2-(dimethylphenylsilyl)ethene, 1-phenyl-1,3-butadiene, 2-(6-methoxynaphthalen-2-yl)propionic acid-4-vinylbenzyl ester, (5 R ,9 R )-5-(3,4,5-trimethoxyphenyl)-9-((4-vinylbenzyl)oxy)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3- d ][1,3]dioxin-6(5aH)-one, (8 R ,9 S ,13 S ,14 S )-13-methyl-3-((4-vinylbenzyl)oxy)-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one, 2-(3-benzoylphenyl)propionic acid-4-vinylbenzyl ester, or (8 R ,9 S ,13 S ,14 S )-13-methyl-3-((4-vinylbenzyl)oxy)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl valerate.

[0031] The present application has the following beneficial effects compared with the prior art:

[0032] The application provides a synthesis method of 1,3-diboron compound, and provides a copper-catalyzed asymmetric boronation strategy of olefin, which uses simple and readily available olefin compound, pinacol diboron and iodo methylene borate as starting materials, uses iodo alkyl borate as an electrophilic reagent, and first generates boron copper through reaction of sodium ethoxide, a copper catalyst and pinacol diboron, then adds to the olefin through Cu-catalyzed olefin carboboration to obtain a beta-boronyl copper complex intermediate, reacts with a halogenated hydrocarbon, and after reductive elimination, forms a desired final product, and the active Cu catalyst is regenerated, so that an effective 1,3-diboron compound modular synthesis method is realized, and a series of racemic 1,3-diboron compounds are constructed with excellent yield. The reaction can efficiently synthesize 1,3-diboron compounds under simple and mild reaction conditions, the reaction process is simple and the yield is high, and the harsh reaction conditions such as high temperature and strong base, the complex substrate synthesis, the range limitation and the use of expensive photocatalysts and other limitations are overcome.

[0033] The 1,3-diboron compound prepared in the application can not only be scaled up in a gram scale, but also can be used to prepare 1,3-difunctional compounds through oxidation and amination reactions. In addition, the product can be used to prepare 1,5-difunctional compounds through carbonation reactions. BRIEF DESCRIPTION OF DRAWINGS

[0034] Figure 1 The H NMR chart of 2,2'-(2-phenylpropane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) prepared for the embodiment 1 of the application is as follows: 1 H NMR chart.

[0035] Figure 2 The H NMR chart of 2,2'-(2-phenylpropane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) prepared for the embodiment 1 of the application is as follows: 13 C NMR chart. DETAILED DESCRIPTION

[0036] The technical solutions in the embodiments of the application will be clearly and completely described below with reference to the drawings in the embodiments of the application. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the application.

[0037] The application provides a synthesis method of 1,3-diboron compound, and the method comprises the following steps:

[0038] The olefin carbon boronation reaction is carried out in a reaction system composed of an olefin compound, pinacol diboron and iodo methylene boronic acid ester, a Cu-based catalyst, sodium ethoxide and a solvent under a protective atmosphere to obtain a 1,3-diboron compound; the synthesis route is as follows:

[0039] .

[0040] The application provides a copper-catalyzed asymmetric boronation strategy of an olefin, which is based on a copper-catalyzed bifunctional strategy, uses simple and readily available olefin compounds and pinacol diboron and iodo methylene pinacol boronic acid ester as starting materials, uses an iodo alkyl borate as an electrophilic reagent, and is synthesized through a Cu-catalyzed olefin carbon boronation reaction, and the reaction mechanism is as follows:

[0041] .

[0042] First, sodium ethoxide, a copper catalyst and pinacol diboron are reacted to generate a boron-based copper, then the Cu-catalyzed olefin carbon boronation reaction is added to the olefin to obtain a β-borane copper complex intermediate, the intermediate is reacted with a halogenated hydrocarbon, and after reduction elimination, the desired final product is formed, and the active Cu catalyst is regenerated, realizing an effective 1,3-diboron compound modular synthesis method, and a series of racemic 1,3-diboron compounds are constructed with excellent yield. The reaction is simple and high-yield under simple and mild reaction conditions, and 1,3-diboron compounds are efficiently synthesized from a wide range of sources, the reaction process is simple and the yield is high, and the reaction conditions such as high temperature and strong base are overcome. The reaction conditions are harsh, the synthesis of the substrate is complex, the range is limited, and the use of a relatively expensive photocatalyst and other obstacles are overcome.

[0043] In specific embodiments, the Cu-based catalyst is a nitrogen heterocyclic carbene copper complex. The chemical formula of the nitrogen heterocyclic carbene copper complex is SIMesCuCl, and the structural formula is as shown below:

[0044] .

[0045] The following is further illustrated through specific embodiments.

[0046] Example 1

[0047] A synthesis method of a 1,3-diboron compound, the 1,3-diboron compound being 2,2'-(2-phenylpropane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (compound 4a), comprising the following steps:

[0048] In a 10 mL reaction tube, under a glove box nitrogen atmosphere, the azolide copper complex SIMesCuCl (0.01 mmol, 5 mol %) was added to the reaction vessel and stirred at room temperature for about 15 minutes. Then, sodium ethoxide (EtONa, 0.4 mmol, 2.0 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added to the reaction vessel and stirred at room temperature for about 15 minutes. Then, the styrene 1a (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction vessel. The reaction mixture was stirred at room temperature for 10 hours. The crude product was purified by flash chromatography to obtain the desired compound 4a as a colorless oil in 81 % yield. The synthetic route is as follows:

[0049] .

[0050] Compound 4a was characterized, 1 H NMR (400 MHz, CDCl3) as shown in Figure 1 , 13 C NMR (400 MHz, CDCl3) as shown in Figure 2 , Figure 1 and Figure 2 It can be seen that compound 4a was successfully synthesized.

[0051] H NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 7.22 (dt, J = 14.9, 7.3 Hz, 4H), 7.09 (t, J = 7.1 Hz, 1H), 3.15 (p, J = 7.8 Hz, 1H), 1.20 (dd, J = 7.9, 4.9 Hz, 4H), 1.07 (d, J = 2.4 Hz, 24H).

[0052] C NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 148.9, 128.0 (2C), 127.3 (2C), 125.7, 82.9 (4C), 37.5, 24.8 (4C), 24.7 (4C), 22.4 (2C).

[0053] Mass spectrometry characterization: HRMS m / z (ESI) calcd for C 21 H 34 B2O4[M+Na] + 395.25354; found: 395.25446.

[0054] Example 2

[0055] A method of synthesizing a 1,3-boron compound, 2,2'-(2-(4-(tert-butyl)phenyl)propane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (Compound 4b), comprising the following steps:

[0056] In a 10 mL reaction tube, under a glove box nitrogen atmosphere, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.), and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 4-tert-butylstyrene 1b (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4b, which was a foamy solid with a yield of 82 %. The synthetic route thereof is as follows:

[0057] .

[0058] NMR hydrogen spectrum characterization: 1 H NMR (400 MHz, CDCl3) δ 7.24 – 7.20 (m, 2H), 7.17 (d, J =8.4 Hz, 2H), 3.12 (ddd, J = 15.8, 8.7, 7.1 Hz, 1H), 1.25 (s, 9H), 1.22 – 1.16(m, 4H), 1.06 (d, J = 4.1 Hz, 24H).

[0059] NMR carbon spectrum characterization: 13C NMR (100 MHz, CDCl3) δ 147.7, 145.2, 126.2 (2C),124.1 (2C), 82.1 (4C), 36.3, 33.6, 30.8 (3C), 24.1 (4C), 24.0 (4C), 21.7(2C)。

[0060] Mass spectrometry characterization: HRMS m / z (ESI) calcd for C 25 H 42 B2O4[M+Na] + 451.31614; found: 451.31653.

[0061] Example 3

[0062] A method of synthesizing a 1,3-diboron compound, 2,2'-(2-(3,4- dimethoxycyclohexa-1,5-dien-1-yl)propane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2- dioxaborolane) (compound 4c), comprising the steps of:

[0063] In a 10 mL reaction tube, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 3,4-dimethoxystyrene 1c (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, then the crude product was purified by flash chromatography to obtain the desired compound 4c, which was a foamy solid with a yield of 80 %. The synthetic route thereof is as follows:

[0064] .

[0065] NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 6.83 – 6.76 (m, 2H), 6.73 (d, J = 8.2 Hz, 1H), 3.83 (d, J = 14.6 Hz, 6H), 1.17 (dd, J= 7.9, 4.0 Hz, 4H), 1.08 (d, J = 3.4 Hz, 24H)。

[0066] NMR characterization of carbon: 13 C NMR (100 MHz, CDCl3) δ 148.2, 146.8, 141.9, 118.9,110.9, 110.8, 82.9 (4C), 56.0, 55.7, 37.1, 24.8 (4C), 24.8 (4C), 22.7 (2C)。

[0067] Mass characterization: HRMS m / z (ESI) calcd for C 23 H 40 B2O6[M+H] + 435.30838; found: 435.30659.

[0068] Example 4

[0069] A method for synthesizing a 1,3-boron compound, 2-(1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)propan-2-yl)-3-methoxyphenol (compound 4d), comprising the following steps:

[0070] In a 10 mL reaction tube, under a nitrogen atmosphere in a glove box, SIMesCuCl (0.01 mmol, 5 mol %) was added and stirred at room temperature for about 15 minutes, then EtONa (0.4 mmol, 2.0 equiv.) was added to the reaction system, and B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 3-methoxyphenylstyrene 1d (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4d, which was a foamy solid, with a yield of 71 %. The synthetic route thereof is as follows:

[0071] .

[0072] NMR characterization of hydrogen: 1 H NMR (400 MHz, CDCl3) δ 7.18 (d, J = 8.9 Hz, 1H), 6.82(d,J = 3.0 Hz, 1H), 6.61 (dd, J = 8.8, 3.1 Hz, 1H), 5.62 (s, 1H), 3.74 (s, 3H),3.56 (p, J = 7.9 Hz, 1H), 1.25 – 1.20 (m, 4H), 1.08 (d, J = 14.2 Hz, 24H)。

[0073] NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 154.8, 149.2, 139.6, 117.8,113.0, 111.8, 82.8 (4C), 55.7, 30.5, 24.8 (4C), 24.7 (4C), 20.6 (2C).

[0074] Example 5

[0075] A method for synthesizing a 1,3-boron compound, 4-(1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)propan-2-yl)phenyl acetate (compound 4e), comprising the following steps:

[0076] In a 10 mL reaction tube, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 4-vinylphenyl acetate 1e (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4e, which was a colorless oil with a yield of 72 %. The synthetic route thereof is as follows:

[0077] .

[0078] NMR characterization: 1 H NMR (400 MHz, CDCl 3) δ 7.25 (dd, J= 8.3, 1.8 Hz, 2H),6.94 – 6.88 (m, 2H), 3.16 (tt, J = 8.9, 6.9 Hz, 1H), 2.25 (s, 3H), 1.19 (d, J =7.2 Hz, 3H), 1.16 (s, 1H), 1.08 (d, J = 3.9 Hz, 24H)。

[0079] NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 169.6, 148.7, 146.5, 128.2(2C), 120.9 (2C), 8 3.0(4C), 36.9, 24.8 (4C), 24.7 (4C), 22.5 (2C), 21.2。

[0080] Mass characterization: HRMS m / z (ESI) calcd for C 23 H 36 B2O6[M+H] + 431.27708; found: 431.27688.

[0081] Example 6

[0082] A method for synthesizing a 1,3-diboron compound, 2,2'-(2-(2-bromo-4,5- dimethoxyphenyl)propane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (compound 4f), comprising the following steps:

[0083] In a 10 ml reaction tube, under a nitrogen atmosphere in a glove box, SIMesCuCl (0.01 mmol, 5 mol %) was added and stirred at room temperature for about 15 minutes, then EtONa (0.4 mmol, 2.0 equiv.) was added into the reaction system, and stirred at room temperature for about 15 minutes, then B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added into the reaction system, and stirred at room temperature for about 15 minutes, then 2-bromo-4,5-dimethoxystyrene 1f (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added into the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4f, which was a colorless oil, with a yield of 70 %. The synthetic route thereof is as follows:

[0084] .

[0085] NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 6.92 (s, 1H), 6.85 (s, 1H),3.84 (s, 3H), 3.80 (s, 3H), 3.54 (p, J = 7.7 Hz, 1H), 1.19 (dd, J = 7.8, 2.1 Hz,4H), 1.10 (s, 12H), 1.07 (s, 12H)。

[0086] NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 148.2, 147.3, 139.9, 115.2,113.8, 110.8, 82.9 (4C), 56.2, 55.9, 35.6, 24.9 (4C), 24.7 (4C), 20.6 (2C).

[0087] Example 7

[0088] A method for synthesizing a 1,3-boron compound, 2,2'-(2-(4- fluorophenyl)propane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (compound 4g), comprising the following steps:

[0089] In a 10 mL reaction tube, under a nitrogen atmosphere in a glove box, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.), and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 4-fluorostyrene 1g (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4g, which was a foamy solid, with a yield of 70 %. The synthesis route is as follows:

[0090] .

[0091] NMR characterization: 1H NMR (400 MHz, CDCl3) δ 7.23 – 7.18 (m, 2H), 6.92 –6.85 (m, 2H), 3.14 (tt, J = 9.1, 6.7 Hz, 1H), 1.20 – 1.12 (m, 4H), 1.07 (d, J =3.7 Hz, 24H)。

[0092] NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 162.4, 160.0, 144.6, 144.6,128.7, 128.6, 114.6, 114.4, 82.9 (4C), 36.8, 24.8 (4C), 24.7 (4C), 22.7 (2C).

[0093] Mass characterization: HRMS m / z (ESI) calcd for C 21 H 33 B2FO4[M+K] + 429.21806; found: 429.21769.

[0094] Example 8

[0095] A method of synthesizing a 1,3-boron compound, 2,2'-(2-(4- chlorophenyl)propane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (compound 4h), comprising the following steps:

[0096] Under a glove box nitrogen atmosphere, a 10 mL reaction tube was charged with stirring at room temperature for about 15 minutes, then the reaction system was sequentially added with SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.), and solvent 1,4-dioxane (1.0 mL, 0.2 M) stirring at room temperature for about 15 minutes, then the reaction system was added with 4-chlorostyrene 1h (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.); the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4h, which was a foamy solid, with a yield of 66 %. The synthetic route thereof is as follows:

[0097] .

[0098] NMR hydrogen spectrum characterization: 1 H NMR (400 MHz, CDCl3) δ 7.18 (s, 4H), 3.13 (tt, J = 8.8,6.7 Hz, 1H), 1.20 – 1.14 (m, 4H), 1.08 (d, J = 4.8 Hz, 24H)。

[0099] NMR carbon spectrum characterization: 13 C NMR (100 MHz, CDCl3) δ 147.5, 131.1, 128.7 (2C),128.0 (2C), 83.0 (4C), 36.9, 24.8 (4C), 24.7 (4C), 21.8 (2C)。

[0100] Example 9

[0101] A method for synthesizing a 1,3-boron compound, 2,2'-(2-([1,1'-biphenyl]-4-yl)propane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (compound 4i), comprising the following steps:

[0102] In a 10 mL reaction tube, under a glove box nitrogen atmosphere, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.), and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 4-phenylstyrene 1i (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4i, which was a foamy solid with a yield of 82 %. The synthesis route is as follows:

[0103] .

[0104] NMR hydrogen spectrum characterization: 1 H NMR (400 MHz, CDCl3) δ 7.6 – 7.5 (m, 2H), 7.5 – 7.5(m, 2H), 7.4 (dd, J= 8.3, 6.8 Hz, 2H), 7.4 – 7.3 (m, 3H), 3.3 – 3.2 (m, 1H),1.3 – 1.2 (m, 4H), 1.1 (s, 24H).

[0105] NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 148.2, 141.6, 138.5, 128.7(2C), 127.7 (2C), 127.0 (2C), 126.9, 126.7 (2C), 82.9 (4C), 37.1, 24.8 (4C),24.8 (4C), 22.4 (2C)。

[0106] Mass characterization: HRMS m / z (ESI) calcd for C 27 H 38 B2O4[M+Na] + 471.28484; found: 471.28517.

[0107] Example 10

[0108] A method for synthesizing a 1,3-diboron compound, the 1,3-diboron compound being tert-butyl-5-(1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)propan-2-yl)-1 H -Indole-1-carboxylate (compound 4j), comprising the following steps:

[0109] In a 10 mL reaction tube, under a nitrogen atmosphere in a glove box, SIMesCuCl (0.01 mmol, 5 mol%) was added and stirred at room temperature for about 15 minutes, then EtONa (0.4 mmol, 2.0 equiv.) was added into the reaction system, and B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 5-vinyl-1H-indole-1- carboxylic acid tert-butyl ester 1j (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added into the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4j, which was a colorless oil, with a yield of 82 %. The synthetic route thereof is as follows:

[0110] .

[0111] NMR characterization:1 H NMR (400 MHz, CDCl3) δ 7.55 – 7.51 (m, 2H), 7.45 –7.42 (m, 2H), 7.38 (dd, J = 8.3, 6.8 Hz, 2H), 7.32 – 7.25 (m, 3H), 3.23 – 3.14(m, 1H), 1.21 (dd, J = 6.3, 2.4 Hz, 4H), 1.06 (s, 24H)。

[0112] NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 143.5, 131.5, 130.4, 129.8,129.5, 125.5, 123.9, 119.1, 114.5, 83.0, 82.8 (4C), 37.2, 28.2 (3C), 24.8(4C), 24.6 (4C),22.75 (2C)。

[0113] Mass characterization: HRMS m / z (ESI) calcd for C 28 H 43 B2NO6[M+Na] + 534.31687; Found: 534.31758.

[0114] Example 11

[0115] A method of synthesizing a 1,3-diboron compound, 2,2'-(2-(benzofuran-5-yl)propane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (compound 4k), comprising the following steps:

[0116] In a 10 mL reaction tube was added SIMesCuCl (0.01 mmol, 5 mol %) and EtONa (0.4 mmol, 2.0 equiv.) under nitrogen atmosphere at room temperature with stirring for about 15 minutes, then 5-vinylbenzofuran 1k (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, then the crude product was purified by flash chromatography to obtain the desired compound 4k, compound 4k was a colorless oil, yield 70 %. The synthetic route is as follows:

[0117] .

[0118] NMR characterization of hydrogen: 1 H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 2.2 Hz, 1H), 7.47(d, J = 1.8 Hz, 1H), 7.34 (d, J = 8.4 Hz, 1H), 7.21 (dd, J = 8.5, 1.9 Hz, 1H),6.68 (d, J = 2.0 Hz, 1H), 3.28 (ddd, J = 15.7, 8.8, 7.0 Hz, 1H), 1.27 – 1.23 (m,4H), 1.04 (d, J = 1.4 Hz, 24H)。

[0119] NMR characterization of carbon: 13 C NMR (100 MHz, CDCl3) δ 153.6, 144.8, 143.6, 127.0,124.0, 119.3, 110.5, 106.6, 82.9 (4C), 37.4, 24.8 (4C), 24.7 (4C), 22.9 (2C)。

[0120] Mass spectrometry characterization: HRMS m / z (ESI) calculated value: C 23 H 34 B2O5[M+H] + 534.31687; measured value: 534.31758.

[0121] Example 12

[0122] A method for the synthesis of a 1,3-boronic acid compound, 1-(4-(1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-2-yl)phenyl)-1 H -pyrazole (compound 4l) comprising the following steps:

[0123] In a 10 ml reaction tube, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added successively under nitrogen atmosphere in a glove box and stirred at room temperature for about 15 minutes. Then, 1-(4-vinylphenyl)-1 H -pyrazole 1l (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.); the reaction mixture was stirred at room temperature for 10 hours, after which the crude was purified by flash chromatography to obtain the desired compound 4l as a colorless oil in 66 % yield. The synthetic route is as follows:

[0124] .

[0125] NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 2.5 Hz, 1H), 7.69(d, J = 1.8 Hz, 1H), 7.57 – 7.51 (m, 2H), 7.36 – 7.32 (m, 2H), 6.43 (t, J = 2.2Hz, 1H), 3.26 – 3.16 (m, 1H), 1.21 (d, J = 5.0 Hz, 4H), 1.09 (d, J = 4.2 Hz,24H)。

[0126] NMR characterization: 13C NMR (100 MHz, CDCl3) δ 147.5, 140.7, 138.1, 128.3(2C), 126.8, 118.9 (2C), 107.3, 83.0 (4C), 36.9, 24.8 (4C), 24.7 (4C), 22.4(2C).

[0127] Mass spectrometry characterization: HRMS m / z (ESI) calcd for C 24 H 36 B2N2O4[M+H] + 439.29340; found: 439.29477.

[0128] Example 13

[0129] A method of synthesizing a 1,3-diboron compound, 2-(4-(1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-2-yl)benzyl)isoindoline-1,3-dione (compound 4m), comprising the steps of:

[0130] In a 10 mL reaction tube, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 2-(4-vinylbenzyl)isoindoline-1,3-dione 1m (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system. The reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4m, which was a white solid with a yield of 85 %. The synthetic route thereof is as follows:

[0131] .

[0132] Nuclear magnetic resonance hydrogen spectrum characterization: 1 H NMR (400 MHz, CDCl3) δ 7.79 (dd, J = 5.5, 3.0 Hz, 2H),7.66 (dd, J = 5.4, 3.1 Hz, 2H), 7.25 (d, J= 8.2 Hz, 2H), 7.17 (d, J = 8.2 Hz, 2H),4.76 (s, 2H), 3.09 (tt, J = 8.8, 6.9 Hz, 1H), 1.18 – 1.08 (m, 4H), 1.01 (s,24H)。

[0133] NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 168.0 (2C), 148.7, 134.0 (2C),133.7, 132.3 (2C), 128.3 (2C), 127.6 (2C), 123.3 (2C), 82.9 (4C), 41.5, 37.1,24.7 (4C), 24.7 (4C), 22.3 (2C)。

[0134] Mass characterization: HRMS m / z (ESI) calcd for C 30 H 39 B2NO6[M+Na] + 554.28557; found: 554.28621.

[0135] Example 14

[0136] A method of synthesizing a 1,3-diboron compound, 2-(4-(1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-2-yl)benzyl)isoindoline-1,3-dione (Compound 4n), comprising the steps of:

[0137] In a 10 mL reaction tube, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin2 (0.24 mmol, 1.2 equiv.), and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 2,2-difluoro-5-vinyl[ d ][1,3]benzodioxole 1n (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added; the reaction mixture was stirred at room temperature for 10 hours, then the crude product was purified by flash chromatography to obtain the desired compound 4n, which was a colorless oil, with a yield of 54 %. The synthetic route is as follows:

[0138] .

[0139] NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 7.0 (s, 1H), 7.0 (dd, J = 8.3,1.7 Hz, 1H), 6.9 (d, J = 8.2 Hz, 1H), 3.2 (tt, J = 9.0, 6.6 Hz, 1H), 1.2 (dd, J =14.9, 7.7 Hz, 4H), 1.1 (d, J = 4.2 Hz, 24H)。

[0140] NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 145.4, 143.5, 141.7, 131.7,122.1, 108.8, 108.6, 83.1 (4C), 37.4, 24.8 (4C), 24.7 (4C), 22.7 (2C)。

[0141] Mass characterization: HRMS m / z (ESI) calculated for C 22 H 32 B2F2O6[M+NH4] + 470.26913; found: 470.27325.

[0142] Example 15

[0143] A method of synthesizing a 1,3-diboron compound, 5-(1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)propan-2-yl)-2-methoxyphenyl (Compound 4o), comprising the steps of:

[0144] In a 10 mL reaction tube was added SIMesCuCl (0.01 mmol, 5 mol %) and EtONa (0.4 mmol, 2.0 equiv.) under nitrogen atmosphere at room temperature with stirring for about 15 minutes, then 2-methoxy-5-vinylpyridine 1o (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction mixture at room temperature; the reaction mixture was stirred at room temperature for 10 hours, then the crude product was purified by flash chromatography to obtain the desired compound 4o as a colorless oil in 81 % yield. The synthetic route is as follows:

[0145] .

[0146] NMR characterization of hydrogen: 1 H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 2.4 Hz, 1H), 7.48(dd, J = 8.5, 2.5 Hz, 1H), 6.62 (d, J = 8.5 Hz, 1H), 3.86 (s, 3H), 3.11 (tt, J =9.0, 6.5 Hz, 1H), 1.19 – 1.11 (m, 4H), 1.08 (d, J = 3.0 Hz, 24H).

[0147] NMR characterization of carbon: 13 C NMR (100 MHz, CDCl3) δ 162.5, 145.6, 137.6, 136.8,110.1, 83.0 (4C), 53.4, 34.0, 24.8 (4C), 24.7 (4C), 22.0 (2C).

[0148] Mass spectrometry characterization: HRMS m / z (ESI) calculated for C 21 H 35 B2NO5[M+H] + 404.27741; found: 404.27784.

[0149] Example 16

[0150] A method of synthesizing a 1,3-diboron compound, 2,2'-(2-(naphthalen-2-yl)propane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (Compound 4p), comprising the steps of:

[0151] In a 10 mL reaction tube, under a glove box nitrogen atmosphere, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.), and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 2-vinyl naphthalene 1p (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, then the crude product was purified by flash chromatography to obtain the desired compound 4p, which was a light yellow solid with a yield of 74 %. The synthetic route thereof is as follows:

[0152] .

[0153] NMR characterization of hydrogen: 1 H NMR (400 MHz, CDCl3) δ 7.77 – 7.66 (m, 4H), 7.46 –7.42 (m, 1H), 7.41 – 7.35 (m, 2H), 3.35 (p, J = 7.8 Hz, 1H), 1.30 (d, J = 7.1 Hz,4H), 1.04 (d, J = 2.4 Hz, 24H)。

[0154] NMR characterization of carbon: 13 C NMR (100 MHz, CDCl3) δ 146.5, 133.6, 132.2, 127.7,127.6, 127.6, 126.3, 125.5, 125.3, 124.8, 82.9 (4C), 37.5, 24.8 (4C), 24.7(4C), 22.0 (2C)。

[0155] Mass spectrometry characterization: HRMS m / z (ESI) calculated value: C 21 H 35 B2NO5[M+Na] +445.26919; found: 445.27077.

[0156] Example 17

[0157] A method of synthesizing a 1,3-boronic compound, 4,4,5,5-tetramethyl-2-((3-(4,4,5,5-tetramethyl-1,3,2-dioxaborinan-2-yl)-1,2,3,4-tetrahydro-1,4- naphthoquinone-2-yl)methyl)-1,3,2-dioxaborinane (Compound 4q), comprising the steps of:

[0158] In a 10 mL reaction tube, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 1,4-dihydro-1,4- naphthoquinone 1q (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4q, which was a colorless oil with a yield of 61 %. The synthetic route thereof is as follows:

[0159] .

[0160] NMR characterization of hydrogen: 1 H NMR (400 MHz, CDCl3) δ 7.22 (dd, J = 5.6, 2.7 Hz, 1H),7.19 – 7.15 (m, 1H), 7.11 – 7.08 (m, 2H), 5.40 (s, 1H), 5.03 (s, 1H), 2.13(ddd, J = 11.0, 9.0, 5.0 Hz, 1H), 1.30 – 1.27 (m, 18H), 1.27 (s, 6H), 1.24 –1.19 (m, 2H), 1.06 (dd, J = 16.1, 11.2 Hz, 1H)。

[0161] NMR characterization of carbon: 13C NMR (100 MHz, CDCl3) δ 147.2, 145.9, 126.3, 126.0,119.0, 118.2, 85.4, 83.6 (2C), 83.1 (2C), 81.3, 39.1, 25.2 (2C), 25.1 (2C),25.0 (2C), 24.9 (2C). The carbon atoms attached to boron are shielded.

[0162] Mass spectrometry characterization: HRMS m / z (ESI) calcd for C 23 H 34 B2O5[M+Na] + 435.24846; found: 435.24978.

[0163] Example 18

[0164] A method of synthesizing a 1,3-diboron compound, 2,2'-(2-(thiophen-3-yl)propane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (compound 4r), comprising the steps of:

[0165] In a 10 mL reaction tube, under a nitrogen atmosphere in a glove box, SIMesCuCl (0.01 mmol, 5 mol %) was added and stirred at room temperature for about 15 minutes, then EtONa (0.4 mmol, 2.0 equiv.) was added to the reaction system, and B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 3-vinylthiophene 1r (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4r, which was a colorless oil, with a yield of 63 %. The synthetic route thereof is as follows:

[0166] .

[0167] Nuclear magnetic hydrogen spectrum characterization: 1 H NMR (400 MHz, CDCl3) δ 7.13 (dd, J = 5.0, 3.0 Hz, 1H), 7.01 (dd, J = 5.0, 1.3 Hz, 1H), 6.95 (dd, J= 3.0, 1.3 Hz, 1H), 3.29 (p, J = 7.7Hz, 1H), 1.18 (d, J = 8.1 Hz, 4H), 1.11 (d, J = 3.3 Hz, 24H)。

[0168] NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 150.0, 127.3, 124.6, 119.1,82.9 (4C), 32.8, 24.8 (4C), 24.8 (4C), 22.0 (2C)。

[0169] Mass characterization: HRMS m / z (ESI) calcd for C 19 H 32 B2O4S [M+Na] + 401.20996; found: 401.21376.

[0170] Example 19

[0171] A method for synthesizing a 1,3-diboron compound, (1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)propan-2-yl)(ethoxy)dimethylsilane (compound 4s), comprising the following steps:

[0172] In a 10 mL reaction tube, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 2-(ethoxydimethylsilyl)ethene 1s (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4s, which was a colorless oil with a yield of 70 %. The synthetic route thereof is as follows:

[0173] .

[0174] NMR characterization: 1H NMR (400 MHz, CDCl3) δ 3.65 (q, J = 7.1 Hz, 2H), 1.22(d, J = 2.0 Hz, 24H), 1.15 (t, J = 7.0 Hz, 3H), 0.96 (dd, J = 16.1, 7.3 Hz, 2H),0.77 (dd, J = 16.0, 7.2 Hz, 2H), 0.06 (s, 6H)。

[0175] NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 83.4 (2C), 82.9 (2C), 58.4,25.1 (2C), 25.0 (2C), 24.9 (2C), 24.8 (2C), 18.7, 18.5, 17.3, 15.8, -1.8, -3.5.

[0176] Mass characterization: HRMS m / z (ESI) calcd for C 19 H 40 B2O5Si [M+NH4] + 374.36075; found: 374.36277.

[0177] Example 20

[0178] A method of synthesizing a 1,3-diboron compound, 1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)propan-2-yl)dimethyl(phenyl)silane (compound 4t), comprising the steps of:

[0179] In a 10 mL reaction tube, SIMesCuCl (0.01 mmol, 5 mol %) was added and stirred at room temperature for about 15 minutes, then EtONa (0.4 mmol, 2.0 equiv.) was added into the reaction system, and stirred at room temperature for about 15 minutes, then B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added into the reaction system, and stirred at room temperature for about 15 minutes, then 2-(dimethylphenylsilyl)ethene 1t (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added into the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4t, which was a colorless oil with a yield of 82 %. The synthetic route thereof is as follows:

[0180] .

[0181] NMR characterization of hydrogen: 1 H NMR (400 MHz, CDCl3) δ 7.54 – 7.50 (m, 2H), 7.32 –7.27 (m, 3H), 1.19 (d, J = 4.1 Hz, 24H), 0.96 (dd, J = 16.2, 6.9 Hz, 2H), 0.76(dd, J = 16.2, 7.5 Hz, 2H), 0.25 (s, 6H)。

[0182] NMR characterization of carbon: 13 C NMR (100 MHz, CDCl3) δ 138.9, 134.4 (2C), 128.7,127.6 (2C), 82.9 (4C), 25.1 (4C), 24.7 (4C), 15.0, -4.4 (2C). The carbon atoms connected with boron are shielded.

[0183] Mass spectrometry characterization: HRMS m / z (ESI) calculated value: C 23 H 40 B2O4Si [M+Na] + 453.27742; measured value: 453.27884.

[0184] Example 21

[0185] A method for synthesizing a 1,3-diboron compound, the 1,3-diboron compound being E)-2,2'-(2-phenylvinylpropane-1,3-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (Compound 4u) comprising the following steps:

[0186] In a 10 mL reaction tube, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then 1-phenyl-1,3-butadiene 1u (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4u, which was a colorless oil with a yield of 47 %. The synthetic route is as follows:

[0187] .

[0188] NMR characterization of hydrogen: 1 H NMR (400 MHz, CDCl3) δ 7.30 (td, J = 8.2, 7.8, 2.2 Hz,3H), 7.18 – 7.13 (m, 2H), 6.36 (d, J = 15.9 Hz, 1H), 6.21 (dd, J = 15.9, 8.0 Hz,1H), 2.82 – 2.72 (m, 1H), 1.20 (s, 24H), 1.17 (d, J = 5.3 Hz, 4H)。

[0189] NMR characterization of carbon: 13 C NMR (100 MHz, CDCl3) δ 137.6, 137.3, 127.8(2C),126.8, 126.0, 125.5(2C), 82.4(4C), 34.5, 24.4(4C), 24.2(4C). The carbon atoms connected to boron are shielded.

[0190] Mass spectrometry characterization: HRMS m / z (ESI) calculated for C 23 H 36 B2O4[M+Na] +421.26919; measured: 421.27088.

[0191] Example 22

[0192] A method of synthesizing a 1,3-boronic compound, 4,4,5,5-tetraethyl-2-(2-phenyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborinan-2-yl)propyl)-1,3,2-dioxaborinane (compound 4v), comprising the steps of:

[0193] In a 10 mL reaction tube, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added and stirred at room temperature for about 15 minutes, then styrene 1a (0.2 mmol, 1.0 equiv.) and 2-iodomethyl-4,4,5,5-tetraethyl-1,3,2-dioxaborolane 3a’ (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, then the crude product was purified by flash chromatography to obtain the desired compound 4v, which was a colorless oil with a yield of 72 %. The synthetic route thereof is as follows:

[0194] .

[0195] NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 7.3 – 7.2 (m, 2H), 7.2 – 7.2(m, 2H), 7.1 – 7.0 (m, 1H), 3.2 – 3.1 (m, 1H), 1.5 (qd, J = 7.4, 2.0 Hz, 8H),1.2 – 1.2 (m, 4H), 1.1 (s, 12H), 0.8 (td, J = 7.5, 1.3 Hz, 12H).

[0196] NMR characterization: 13C NMR (100 MHz, CDCl3) δ 149.0, 127.8 (2C), 127.2 (2C),125.5, 87.9 (2C), 82.8 (2C), 37.3, 26.2 (2C), 26.1 (2C), 24.7 (2C), 24.7(2C), 8.7 (2C), 8.7 (2C). The carbon atoms attached to boron are shielded.

[0197] Mass spectrometry characterization: HRMS m / z (ESI) calcd for C 25 H 42 B2O4[M+Na] + 451.31614; found: 451.31653.

[0198] Example 23

[0199] A method for synthesizing a 1,3-diboron compound, 4-(1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-2-yl)benzyl S 2-(6-methoxynaphthalen-2-yl)propanoic acid (compound 4w), comprising the following steps:

[0200] In a 10 mL reaction tube, SIMesCuCl (0.01 mmol, 5 mol %) and EtONa (0.4 mmol, 2.0 equiv.) were added under nitrogen atmosphere in a glove box, and stirred at room temperature for about 15 minutes. Then 2-(6-methoxynaphthalen-2-yl)propanoic acid-4-vinyl benzyl ester 1w (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added into the reaction system. The reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4w, which was a white solid with a yield of 72 %. The synthetic route thereof is as follows:

[0201] .

[0202] Nuclear magnetic resonance hydrogen spectrum characterization: 1 H NMR (400 MHz, CDCl3) δ 7.70 – 7.63 (m, 3H), 7.39 (dd, J = 8.5, 1.9 Hz, 1H), 7.19 (d,J = 8.0 Hz, 2H), 7.15 – 7.09 (m, 4H), 5.10 – 4.96(m, 2H), 3.91 (s, 3H), 3.18 – 3.09 (m, 1H), 1.56 (d, J = 7.1 Hz, 3H), 1.22 –1.13 (m, 4H), 1.05 (d, J = 3.7 Hz, 24H).

[0203] Carbon NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 174.6, 157.7, 149.1, 135.7,133.8, 133.2, 129.4, 129.0, 127.9 (2C), 127.4 (2C), 127.2, 126.4, 126.1,119.0, 105.6, 82.9 (4C), 66.7, 55.4, 45.6, 37.2, 24.8 (4C), 24.7 (4C), 22.3(2C), 18.7.

[0204] Mass spectrometry characterization: HRMS m / z (ESI) calculated value: C 25 H 42 B2O4[M+Na] + 637.34784; Measured value: 637.35013.

[0205] Example 24

[0206] A method for synthesizing a 1,3-diboron compound, wherein the 1,3-diboron compound is (5 R 5 aR 8 aR 9 R )-9-((4-(1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)propane-2-yl)benzyl)oxy)-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9-tetrahydrofurano[3',4':6,7]naphtho[2,3-d][1,3]dioxacyclopentene-6(5 aH )-ketone (compound 4x), comprising the following steps:

[0207] In a 10 mL reaction tube, SIMesCuCl (0.01 mmol, 5 mol %), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.) and solvent 1,4-dioxane (1.0 mL, 0.2 M) were added successively under nitrogen atmosphere in a glove box and stirred at room temperature for about 15 minutes. Then (5 R ,9 R )-5-(3,4,5-trimethoxyphenyl)-9-((4-vinylbenzyl)oxy)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3- d ][1,3]dioxepin-6(5 aH )-one 1x (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added successively to the reaction mixture; the reaction mixture was stirred at room temperature for 10 hours, after which the crude product was purified by flash chromatography to obtain the desired compound 4x as a white solid in 76 % yield. The synthetic route is as follows:

[0208] .

[0209] NMR characterization: 1 H NMR (400 MHz, CDCl3) δ 7.3 (d, J = 8.1 Hz, 2H), 7.2 –7.2 (m, 2H), 6.9 (s, 1H), 6.5 (s, 2H), 6.4 (s, 1H), 5.9 (dd, J = 8.8, 1.5 Hz,2H), 4.7 (d, J = 11.5 Hz, 1H), 4.5 (d, J = 11.6 Hz, 1H), 4.4 (dd, J = 9.5, 7.0Hz, 1H), 4.3 (d, J = 7.0 Hz, 1H), 4.2 – 4.1 (m, 1H), 4.1 – 4.1 (m, 1H), 3.8 (s,3H), 3.8 (s, 6H), 3.2 – 3.2 (m, 2H), 2.9 (dtd, J = 10.2, 6.9, 3.4 Hz, 1H), 1.2(d, J = 8.5 Hz, 4H), 1.1 (d, J= 3.5 Hz, 24H).

[0210] Carbon NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 178.3, 153.4 (2C), 149.4,147.6, 146.8, 138.9, 136.8, 134.5, 131.4, 129.5, 127.7 (2C), 127.6 (2C),109.6, 107.0, 105.6 (2C), 101.3, 83.0 (4C), 72.3, 70.1, 60.9, 60.5, 56.2(2C), 45.3, 44.9, 41.1, 37.1, 24.9, 24.8 (4C), 24.8 (4C), 22.3 (2C).

[0211] Mass spectrometry characterization: HRMS m / z (ESI) calculated value: C 44 H 56 B2O 12 [M+H] + 821.38501; Measured value: 821.38783.

[0212] Example 25

[0213] A method for synthesizing a 1,3-diboron compound, wherein the 1,3-diboron compound is 8 R 9 S ,13 S ,14 S )-3-((4-(1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)propane-2-yl)benzyl)oxy)-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17 H -Cyclopentadieno[a]phenanthrene-17-one (compound 4y) includes the following steps:

[0214] Under a nitrogen atmosphere in a glove box, add SIMesCuCl (0.01 mmol, 5 mol%), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.), and solvent 1,4-dioxane (1.0 mL, 0.2 M) sequentially to the reaction system and stir at room temperature for about 15 minutes. Then add (8... R 9 S ,13 S ,14S )-13-methyl-3-((4-vinylbenzyl)oxy)-6,7,8,9,11,12,13,14,15,16-decahydro-17 H Cyclopenta[a]phenanthren-17-one 1y (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.); the reaction mixture was stirred at room temperature for 10 h, after which the crude was purified by flash chromatography to obtain the desired compound 4y as a foamy solid in 68% yield. The synthetic route is as follows:

[0215] .

[0216] NMR characterization: 1 H NMR (400 MHz, CDC13) δ 7.25 (s, 4H), 7.14 (dd, J = 11.2, 8.4 Hz, 1H), 6.75 - 6.67 (m, 2H), 4.96 (s, 2H), 3.21 - 3.11 (m, 1H), 2.89 - 2.84 (m, 2H), 2.49 (dd, J = 18.8, 8.6 Hz, 1H), 2.41 - 2.33 (m, 1H), 2.21 (d, J = 8.5 Hz, 1H), 2.18 - 2.10 (m, 1H), 2.09 - 2.02 (m, 1H), 1.95 (td, J = 9.9, 4.2 Hz, 2H), 1.61 - 1.54 (m, 2H), 1.54 - 1.50 (m, 1H), 1.46 (t, J = 10.0 Hz, 3H), 1.19 (t, J = 7.5 Hz, 4H), 1.07 (d, J = 3.0 Hz, 24H), 0.89 (s, 3H).

[0217] NMR characterization: 13C NMR (100 MHz, CDCl3) δ 221.2, 157.0, 148.8, 137.7,134.5, 132.1, 127.4 (2C), 127.2 (2C), 126.3, 115.1, 112.5, 82.9 (4C), 70.0,50.5, 48.1, 44.1, 38.4, 37.2, 36.0, 31.7, 29.7, 26.6, 26.0, 24.8 (4C), 24.8(4C), 22.4 (2C), 21.7, 13.9.

[0218] Mass spectrometry characterization: HRMS m / z (ESI) calcd for C 40 H 56 B2O6[M+Na] + 661.34784; found: 661.35036.

[0219] Example 26

[0220] A method for synthesizing a 1,3-diboron compound, 4-(1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)propan-2-yl)benzyl 2-(3-benzoylphenyl) (Compound 4z), comprising the following steps:

[0221] In a 10 mL reaction tube, under a nitrogen atmosphere in a glove box, SIMesCuCl (0.01 mmol, 5 mol %) and EtONa (0.4 mmol, 2.0 equiv.) were added and stirred at room temperature for about 15 minutes, then 2-(3-benzoylphenyl)propanoic acid-4-vinyl benzyl ester 1z (0.2 mmol, 1.0 equiv.) and iodomethylboronic acid pinacol ester 3a (0.3 mmol, 1.5 equiv.) were added to the reaction system; the reaction mixture was stirred at room temperature for 10 hours, and then the crude product was purified by flash chromatography to obtain the desired compound 4z, which was a foamy solid, with a yield of 82 %. The synthetic route thereof is as follows:

[0222] .

[0223] Nuclear magnetic hydrogen spectrum characterization: 1H NMR (400 MHz, CDCl3) δ 7.80 – 7.73 (m, 3H), 7.67 (dt, J = 7.6, 1.5 Hz, 1H), 7.62 – 7.56 (m, 1H), 7.52 (dt, J = 7.8, 1.6 Hz, 1H), 7.47(t, J = 7.7 Hz, 2H), 7.42 (t, J = 7.7 Hz, 1H), 7.21 (d, J = 8.1 Hz, 2H), 7.12 (d, J =8.1 Hz, 2H), 5.11 – 4.97 (m, 2H), 3.80 (q, J = 7.2 Hz, 1H), 3.19 – 3.09 (m,1H), 1.52 (d, J = 7.2 Hz, 3H), 1.21 – 1.13 (m, 4H), 1.06 (d, J = 2.6 Hz, 24H)。

[0224] NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 196.6, 174.0, 149.3, 140.9,138.0, 137.6, 133.0, 132.6, 131.6, 130.2 (2C), 129.4, 129.1, 128.6, 128.4(2C), 127.9 (2C), 127.4 (2C), 82.9 (4C), 66.9, 45.5, 37.1, 24.8 (4C), 24.7(4C), 22.3 (2C), 18.6。

[0225] Mass characterization: HRMS m / z (ESI) calcd for C 38 H 48 B2O7[M+Na] + 661.34784; found: 661.34976.

[0226] Example 26

[0227] A method for synthesizing a 1,3-diboron compound, the 1,3-diboron compound being (8 R ,9 S ,13 S ,14 S)-3-((4-(1,3-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)propane-2-yl)benzyl)oxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6 H -Cyclopentadieno[a]phenanthrene-17-ylvalerate (compound 4aa), comprising the following steps:

[0228] Under a nitrogen atmosphere in a glove box, add SIMesCuCl (0.01 mmol, 5 mol%), EtONa (0.4 mmol, 2.0 equiv.), B2pin22a (0.24 mmol, 1.2 equiv.), and solvent 1,4-dioxane (1.0 mL, 0.2 M) sequentially to the reaction system and stir at room temperature for about 15 minutes. Then add (8... R 9 S ,13 S ,14 S )-13-methyl-1-3-((4-vinylbenzyl)oxy)-7,8,9,11,12,13,14,15,16,17-decahydro-6 H -Cyclopentadieno[a]phenanthrene-17-ylvalerate 1aa (0.2 mmol, 1.0 equiv.) and pinacol iodomethylborate 3a (0.3 mmol, 1.5 equiv.); the reaction mixture was stirred at room temperature for 10 hours, followed by rapid chromatographic purification of the crude product to obtain the desired compound 4aa, which was a white solid in 63% yield. The synthetic route is as follows:

[0229] .

[0230] Carbon NMR characterization: 13 C NMR (100 MHz, CDCl3) δ 174.1, 156.9, 148.8, 137.9,134.5, 132.6, 127.4 (2C), 127.2 (2C), 126.3, 115.0, 112.4, 82.9 (4C), 82.5,69.9, 49.9, 43.9, 43.0, 38.7, 37.2, 37.0, 34.4, 29.9, 27.7, 27.3, 27.3, 26.3,24.8(4C), 24.7 (4C), 23.4 (2C), 22.4 (2C), 13.9, 12.2.

[0231] Mass spectrometry characterization: HRMS m / z (ESI) calculated for C 45 H 66 B2O7[M+Na] + 763.48869; found: 763.48665.

[0232] It should be noted that when numerical ranges are used herein, the numerical range is intended to include every number between the two endpoints, and any fractions thereof. The preferred embodiments of the present application have been described herein. Obviously, modifications and alterations will occur to others upon reading and understanding the preceding detailed description. It is intended that the application be construed as including all such modifications and alterations insofar as they come within the scope of the appended claims and their equivalents.

[0233] Obviously, numerous modifications and variations of the present application are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims and their equivalents, the application can be practiced otherwise than as specifically described herein.

Claims

1. A method for the synthesis of 1,3-diboron compounds, characterized in that, The method comprises the following steps: The olefin carbon boronation reaction is carried out in a reaction system composed of an olefin compound, pinacol diboron and iodo-methylene boronic acid ester, a Cu-based catalyst, sodium ethoxide and a solvent under a protective atmosphere to obtain a 1,3-diboron compound; The solvent is 1,4-dioxane; The Cu-based catalyst is aza-cyclo-carben copper complex, and the chemical formula of the aza-cyclo-carben copper complex is SIMesCuCl, and the structural formula is as shown in the following formula: ； The olefin compound has one of the following structural formulas: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 ； The 1,3-diboron compound has one of the following structural formulas: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 2. The method for synthesizing the 1,3-diboron compound according to claim 1, characterized in that, The molar ratio of the olefin compound, pinacol diboron and iodo-methylene boronic acid ester is 1:1-1.5:1-1.

5.

3. The method for synthesizing the 1,3-diboron compound according to claim 1, characterized in that, The molar ratio of the Cu-based catalyst, sodium ethoxide and the olefin compound is 0.08-0.15:4:

2.

4. The method of claim 1, wherein the 1,3-diboron compound is represented by the following formula: ###0002### 4 The temperature of the olefin carbon boronation reaction is room temperature, and the reaction time is 10-15 hours.

Images