Mechanochemical Synthesis of α-Haloalkylboronic Acid Esters

Abstract

The present invention discloses a mechanochemical synthesis method of α-haloalkyl boronic acid ester, which belongs to the field of chemical synthesis technology. The method uses tetrafluoroborate diazonium salt as a free radical source, alkenyl boronic acid ester or olefin derivative as an acceptor, and metal halide as a halide source, and realizes the sufficient coupling reaction of the above-mentioned free radical source, acceptor and halide source by mechanical force to generate α-haloalkyl boronic acid ester. The present invention can well solve the problems existing in the traditional synthesis of α-haloalkyl boronic acid ester and significantly reduce industrial production costs. In addition to synthesizing α-haloalkyl boronic acid ester, the method is also applicable to react with other types of olefins, such as styrene or other types of substituted aryl olefins or alkyl olefins.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and particularly relates to a mechanochemical synthesis method of α-haloalkyl boron ester. Background Art

[0002] α-Haloalkyl boron esters are a class of stable bifunctional molecules that play an important role as useful multifunctional intermediates in fields such as pharmaceutical science and organic chemistry. Due to the functional differences between carbon-halogen bonds and carbon-boron bonds, they have both nucleophilic and electrophilic properties. Carbon-boron and carbon-halogen bonds can be easily converted into a wide range of carbon-x bonds (where x is carbon, nitrogen, oxygen, and halogen, etc.) through electrophilic or nucleophilic reactions, achieving the effect of inserting a variety of different substituents at the same site. They have been widely used to simplify the synthesis of various complex compound molecules. Traditional methods for synthesizing α-haloalkyl boron esters usually require the use of large amounts of toxic solvents, and the reagents or reaction systems are sensitive to air / moisture, rely on expensive metal catalysts, and require long reaction times. In recent years, some progress has been made in the synthesis of α-haloalkyl boron esters, mainly including: (1) Obtaining α-haloalkyl boron esters by difunctionalization of boryl olefins (SJ Roseblade, E. Casas-Arcé, U. Nettekoven, I. A. Zanotti-Gerosa,Z. Synthesis 2013, 45, 2824-2831; SJ Roseblade, IGSmilovic, Z. Casar, Tetrahedron 2014, 70, 2654-2660.); (2) Obtaining α-haloalkylboryl esters by atom transfer radical addition (M. Ueda, Y. Kato, N. Taniguchi, T. Morisaki, Org. Lett. 2020, 22, 6234-6238; T. Fang, J. Qiu, K. Yang, Q. Song, Org. Chem. Front. 2021, 8, 1991-1996; T. D. Ho, B. J. Lee, C. Tan, J. A. Utley, NQNgo, KLHull, J.Am.Chem.Soc.2023,145,27230-27235.); (3) conversion of carbonyl compounds into α-haloalkylboron esters via borylation / halogen substitution sequence (D.Wang, J.Zhou, Z.Hu, T.Xu, J.Am.Chem.Soc.2022,144,22870-22876.); (4) synthesis of α-chloroalkylboron esters via visible light redox catalysis (B.Li, A.Bunescu, MJGaunt, Chem 2023,9,216-226.). However, among the existing synthetic methods introduced above, there is no report on the synthesis of α-haloalkylboron esters via mechanochemical methods. Although the latest existing technology has synthesized α-chloroalkylboronic acid esters through a visible light-mediated dual catalytic cycle system (B. Li, A. Bunescu, MJ Gaunt, Chem 2023, 9, 216-226.), compared with the mechanochemical strategy, this method still has defects such as the requirement of a large amount of organic reagents, long reaction time, and the need for expensive metal ligands and catalysts.

[0003] Visible-light redox catalysis is a hot and important development in contemporary organic synthesis. In these transformations, photoexcited catalysts can act as efficient single-electron oxidants, transferring electrons to acceptors. Subsequently, with the concomitant regeneration of the ground-state catalyst, the single-electron oxidation of the donor affords the product. The success of photoredox catalysis hinges on the sensitivity of the coupling agent to redox activation and the efficiency and selectivity of the subsequent bond-forming reaction. Gaunt et al. successfully synthesized α-chloroalkylboronates by adding aryl and chlorine atoms to vinylboronates via a visible-light-mediated dual-catalytic system. This multicomponent reaction of a diaryliodonium salt, a substituted vinylboronate, and potassium chloride was carried out under the influence of visible light over a photocatalyst, triggering the formation of an aryl radical that subsequently added to the vinylboronate. A group transfer catalyst then facilitated the transfer of the chlorine group to the newly formed α-boronyl radical, forming the α-chloroalkylboronate. This technology uses a diaryl iodonium salt as a free radical donor. Under the action of the photocatalyst [Ru(II)(bpy)3](PF6)2, the diaryl iodonium salt is irradiated with blue light to produce an aryl radical. The resulting aryl radical adds to a vinyl borane ester to form an α-borane radical intermediate. Under the action of the group transfer catalyst (bpmen)Fe(II)Cl2, the chlorine group of potassium chloride is transferred to the α-borane radical intermediate to obtain the final product, an α-chloroalkyl borane ester. The process undergoes a dual catalytic cycle of photocatalysis and group transfer catalysis. The specific operation of this technical solution is as follows: a 4.0 mL glass vial with a magnetic stirring bar was added with all non-volatile reagents [(bpmen)FeIICl2 (4.0 mg, 0.010 mmol, 5.0 mol%), [RuII(bpy)3](PF6)2 (1.7 mg, 0.002 mmol, 1.0 mol%), diphenyliodonium salt (0.200 mmol, 1.0 equiv) and potassium chloride KCl (30.0 mg, 0.400 mmol, 2.0 equiv)] under air, the vial was sealed with a polytetrafluoroethylene-lined septum screw cap, and vacuum backfilled with nitrogen for 3 cycles. Anhydrous acetonitrile (1.0 mL) was added by syringe under nitrogen, followed by the addition of vinyl boron ester (0.400 mmol, 2.0 equiv). The vial was sealed with additional parfilm. TMThe vial was sealed and the perforation on the septum was sealed with vacuum grease. The sealed vial was then fixed to a stirrer 5 cm away from the Kessil lamp and a desktop fan was placed on the top of the reaction head for cooling. The vial was irradiated with vigorous stirring (1000 rpm) and reacted overnight. After the reaction was complete, the reaction mixture was concentrated in vacuo, 10% Et2O / PE (2.0 mL) was added to induce precipitation, the mixture was filtered through diatomaceous earth to remove all insoluble matter, and the filtrate was then concentrated in vacuo. The resulting filtrate was purified by flash column chromatography (0-95% MeCN / H2O, C18 column, 10 min) to isolate the desired product.

[0004] While the technical solution for synthesizing α-chloroalkyl boron esters reported by Gaunt et al. is highly innovative, it still retains many of the shortcomings of traditional methods for synthesizing α-haloalkyl boron esters. First, this method can only synthesize α-chloroalkyl boron esters and cannot produce other halogenated products. Second, this method still belongs to the traditional solution environment stirring reaction, which requires the use of large amounts of organic solvents, long reaction times, and is not suitable for poorly soluble substrates. Finally, this method requires the use of expensive photoredox catalysts and difficult-to-obtain group transfer catalysts. Summary of the Invention

[0005] In order to overcome the shortcomings of the above-mentioned prior art, the purpose of the present invention is to provide a mechanochemical synthesis method for α-haloalkyl boron esters to solve the technical problems that the existing synthesis method requires the use of a large amount of organic solvents, has a long reaction time, requires the use of a large amount of catalysts and has a relatively simple structure of the synthetic product.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] The invention discloses a mechanochemical synthesis method for α-haloalkyl boronic esters. The method uses diazonium tetrafluoroborate as a free radical source, alkenyl boronic esters or olefin derivatives as an acceptor, and metal halide as a halide source. Mechanical force is used to achieve a full coupling reaction of the free radical source, the acceptor, and the halide source to generate the α-haloalkyl boronic ester.

[0008] Preferably, the mechanochemical synthesis method of the above-mentioned α-haloalkyl boronic ester comprises: mixing diazonium tetrafluoroborate, alkenyl boronic ester or olefin derivative, metal halide and ultra-dry liquid auxiliary grinding agent under nitrogen atmosphere, and then subjecting the mixture to mechanical ball milling, and purifying the mixture after the ball milling to obtain the α-haloalkyl boronic ester.

[0009] Further preferably, the structural formula of the diazonium tetrafluoroborate is as follows:

[0010]

[0011] Wherein, R is selected from H, halogen, trifluoromethyl, ester, amide, alkoxy, trifluoromethoxy, phenyl or azole derivatives;

[0012] More preferably, R is a polyhalogen substituent;

[0013] More preferably, the azole derivative is 1-methyl-1H-pyrazole or 9-ethyl-9H-carbazole.

[0014] More preferably, R is selected from one of H, fluorine, chlorine, bromine, trifluoromethyl, phenyl, formate, methoxy, formamide, methyl, ethyl, isopropyl, trifluoromethoxy, 1-methyl-1H-pyrazole, 2,3-dihydrobenzo[b][1,4]dioxin, 9-ethyl-9H-carbazole and dibenzo[b,d]furan.

[0015] Further preferably, the alkenyl boronate or olefin derivative includes: isopropenylboronic acid pinacol ester, vinylboronic acid pinacol ester, 4,4,5,5-tetramethyl-2-(1-phenylvinyl)-1,3,2-dioxaborane, 4,4,5,5-tetramethyl-2-(1-methylene-3-phenylpropyl)-1,3,2-dioxaborane, 4,4,5,5-tetramethyl-2-[1-methylene-3-(phenylmethoxy)propyl]-1,3,2-dioxaborane, styrene, 4-methylstyrene, 1-(trifluoromethyl)-4-vinylbenzene, 1-vinyl-3,5-bis(trifluoromethyl)benzene, 2,6-dichlorostyrene, dimethylphenylvinylsilane, vinyltrimethylsilane, N-phenylmethylacrylamide, N,N-dimethylacrylamide, and 1,1-dimethylethyl-2-acrylate.

[0016] Further preferably, the metal halide is sodium halide;

[0017] More preferably, it is selected from sodium chloride, sodium bromide, and sodium iodide.

[0018] Further preferably, the molar ratio of diazonium tetrafluoroborate to the alkenyl borate ester or olefin derivative is 1.5:1; and the molar ratio of metal halide to alkenyl borate ester or olefin derivative is 1.5:1.

[0019] More preferably, the ultra-dry liquid auxiliary grinding agent is selected from acetonitrile, methanol, tetrahydrofuran or N,N-dimethylformamide, and the amount used is 0.2 μL / mg. (First weigh the mass of the solid material, and add the liquid amount according to the solid mass)

[0020] More preferably, the ball milling treatment is carried out at 20 to 35 Hz for 1 to 3 hours.

[0021] Further preferably, the purification treatment comprises adding an organic solvent to the system after the ball milling reaction for dilution treatment, then eluting on a diatomaceous earth column to remove inorganic salts, and then removing the solvent by concentrating under reduced pressure. The concentrated residue is separated by column chromatography using a mixed solvent of n-hexane / ethyl acetate as an eluent, collecting the eluate containing the α-haloalkyl boronic ester, and distilling off the solvent to obtain the α-haloalkyl boronic ester.

[0022] Wherein, the organic extractant is dichloromethane or ethyl acetate; in the n-hexane / ethyl acetate mixed solvent, the volume ratio of n-hexane to ethyl acetate is 5 to 10:1.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] This invention successfully and innovatively achieves the first direct synthesis of α-haloalkyl boronic esters using a mechanochemical method without external catalysts or solvents. This method utilizes mechanical energy as the initiating energy source, diazonium tetrafluoroborate as the free radical source, an alkenyl boronic ester or olefin derivative as the acceptor, and a metal halide as the halide source. With the addition of only a trace amount of liquid-assisted abrasive, mechanical force enables a three-component coupling reaction to produce the α-haloalkyl boronic ester. Compared to the prior art technique for synthesizing α-chloroalkyl boronic esters reported by Gaunt et al., the present invention offers significant advantages. First, the method reported by Gaunt et al. only synthesizes α-chloroalkyl boronic esters and cannot produce other halogenated products. However, the present invention can synthesize products of different halogenated types by varying the halide ion species of the sodium salt. Second, the Gaunt et al. method employs a traditional solution-based stirring reaction, requiring a large amount of organic solvent, a long reaction time, and being unsuitable for poorly soluble substrates. The present invention, however, uses only a trace amount of liquid-assisted abrasive, completes the reaction in just one hour, and exhibits excellent adaptability to the mechanochemical conditions for poorly soluble substrates. Finally, while Gaunt et al.'s method requires the use of expensive photoredox catalysts and difficult-to-obtain group transfer catalysts, the present invention does not require the addition of additional catalysts. Instead, the reaction is catalyzed by a single-electron transfer catalytic cycle of Fe(0) within a stainless steel ball mill and the stainless steel balls themselves. Therefore, it can be seen that the present invention can effectively address the problems associated with traditional synthesis of α-haloalkyl boron esters, significantly reducing industrial production costs. In addition to synthesizing α-haloalkyl boron esters, this method is also applicable to reactions with other types of olefins, such as styrene or other types of substituted aromatic or alkyl olefins. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is a mechanism diagram of the present invention;

[0026] Figure 2This is the hydrogen spectrum of methyl 4-(2-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)benzoate prepared in Example 24;

[0027] Figure 3 This is the carbon spectrum of methyl 4-(2-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)benzoate prepared in Example 24;

[0028] Figure 4 This is the hydrogen spectrum of 4-(2-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)-N-methylbenzamide prepared in Example 25;

[0029] Figure 5 This is the carbon spectrum of 4-(2-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)-N-methylbenzamide prepared in Example 25;

[0030] Figure 6 This is the hydrogen spectrum of 2-(2-chloro-1-(2,4,6-trichlorophenyl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 33;

[0031] Figure 7 This is the carbon spectrum of 2-(2-chloro-1-(2,4,6-trichlorophenyl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 33;

[0032] Figure 8 This is the hydrogen spectrum of 2-(1-([1,1'-biphenyl]-4-yl)-2-chloropropyl-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 34;

[0033] Figure 9 This is the carbon spectrum of 2-(1-([1,1'-biphenyl]-4-yl)-2-chloropropyl-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 34;

[0034] Figure 10 This is the hydrogen spectrum of 2-(2-chloro-1-(naphthalen-2-yl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 35;

[0035] Figure 11 This is the carbon spectrum of 2-(2-chloro-1-(naphthalen-2-yl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 35;

[0036] Figure 12 This is the hydrogen spectrum of 3-(2-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)-1-methyl-1H-pyrazole prepared in Example 36;

[0037] Figure 13 This is the carbon spectrum of 3-(2-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)-1-methyl-1H-pyrazole prepared in Example 36;

[0038] Figure 14 This is the hydrogen spectrum of 2-(2-chloro-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 37;

[0039] Figure 15 The carbon spectrum of 2-(2-chloro-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 37;

[0040] Figure 16 This is the hydrogen spectrum of 3-(2-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)-9-ethyl-9H-carbazole prepared in Example 38;

[0041] Figure 17 This is the carbon spectrum of 3-(2-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)-9-ethyl-9H-carbazole prepared in Example 38;

[0042] Figure 18 This is the hydrogen spectrum of 2-(2-chloro-1-(dibenzo[b,d]furan-3-yl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 39;

[0043] Figure 19 This is the carbon spectrum of 2-(2-chloro-1-(dibenzo[b,d]furan-3-yl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 39;

[0044] Figure 20 This is the hydrogen spectrum of 2-(2-(4-bromophenyl)-1-chloroethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 44;

[0045] Figure 21This is the carbon spectrum of 2-(2-(4-bromophenyl)-1-chloroethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 44;

[0046] Figure 22 This is the hydrogen spectrum of 2-(1-(4-bromophenyl)-2-chloro-4-phenyl-2-butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 47;

[0047] Figure 23 This is the carbon spectrum of 2-(1-(4-bromophenyl)-2-chloro-4-phenyl-2-butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 47;

[0048] Figure 24 This is the hydrogen spectrum of 2-(4-benzyloxy)-1-(4-bromophenyl)-2-chlorobutan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 48;

[0049] Figure 25 This is the carbon spectrum of 2-(4-benzyloxy)-1-(4-bromophenyl)-2-chlorobutan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane prepared in Example 48;

[0050] Figure 26 This is the hydrogen spectrum of 1-bromo-4-(2-chloro-2-phenylethyl)benzene prepared in Example 49;

[0051] Figure 27 This is the carbon spectrum of 1-bromo-4-(2-chloro-2-phenylethyl)benzene prepared in Example 49;

[0052] Figure 28 This is the hydrogen spectrum of 1-bromo-4-(2-chloro-2-(p-tolyl)ethyl)benzene prepared in Example 50;

[0053] Figure 29 This is the carbon fiber spectrum of 1-bromo-4-(2-chloro-2-(p-tolyl)ethyl)benzene prepared in Example 50;

[0054] Figure 30 This is the hydrogen spectrum of 1-bromo-4-(2-chloro-2-(4-(trifluoromethyl)phenyl)ethyl)benzene prepared in Example 51;

[0055] Figure 31 This is the carbon chromatogram of 1-bromo-4-(2-chloro-2-(4-(trifluoromethyl)phenyl)ethyl)benzene prepared in Example 51;

[0056] Figure 32This is the fluorine spectrum of 1-bromo-4-(2-chloro-2-(4-(trifluoromethyl)phenyl)ethyl)benzene prepared in Example 51;

[0057] Figure 33 This is the hydrogen spectrum of 1-(2-(4-bromophenyl)-1-chloroethyl)-3,5-bis(trifluoromethyl)benzene prepared in Example 52;

[0058] Figure 34 This is the carbon spectrum of 1-(2-(4-bromophenyl)-1-chloroethyl)-3,5-bis(trifluoromethyl)benzene prepared in Example 52;

[0059] Figure 35 This is the fluorine spectrum of 1-(2-(4-bromophenyl)-1-chloroethyl)-3,5-bis(trifluoromethyl)benzene prepared in Example 52;

[0060] Figure 36 This is the hydrogen spectrum of 2-(2-(4-bromophenyl)-1-chloroethyl)-1,3-dichlorobenzene prepared in Example 53;

[0061] Figure 37 This is the carbon spectrum of 2-(2-(4-bromophenyl)-1-chloroethyl)-1,3-dichlorobenzene prepared in Example 53;

[0062] Figure 38 This is the hydrogen spectrum of (2-(4-bromophenyl)-1-chloroethyl)dimethyl(phenyl)silane prepared in Example 54;

[0063] Figure 39 This is the carbon spectrum of (2-(4-bromophenyl)-1-chloroethyl)dimethyl(phenyl)silane prepared in Example 54;

[0064] Figure 40 This is the hydrogen spectrum of (2-(4-bromophenyl)-1-chloroethyl)trimethylsilane prepared in Example 55;

[0065] Figure 41 This is the carbon spectrum of (2-(4-bromophenyl)-1-chloroethyl)trimethylsilane prepared in Example 55;

[0066] Figure 42 This is the hydrogen spectrum of 3-(4-bromophenyl)-2-chloro-2-methyl-N-phenylpropionamide prepared in Example 56;

[0067] Figure 43 This is the carbon spectrum of 3-(4-bromophenyl)-2-chloro-2-methyl-N-phenylpropionamide prepared in Example 56. DETAILED DESCRIPTION

[0068] In order to enable those skilled in the art to better understand the solutions of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts should fall within the scope of protection of the present invention.

[0069] The present invention is described in further detail below with reference to the accompanying drawings:

[0070] The present invention discloses a mechanochemical method for synthesizing α-haloalkyl boron esters, which is as follows:

[0071] In a nitrogen-filled glove box, a diazonium tetrafluoroborate substrate (free radical source), a metal halide (halide source), an alkenyl borate or olefin derivative (acceptor), and an ultra-dry liquid-assisted grinding agent are placed in a stainless steel ball mill jar filled with stainless steel balls. The ball mill jar is then tightened and placed in a ball mill. After grinding for one hour, the α-haloalkyl borate is purified.

[0072] The synthetic route is as follows:

[0073]

[0074] Wherein R is selected from H, halogen, trifluoromethyl, ester, amide, alkoxy, trifluoromethoxy, phenyl, and azole derivatives. R can be a polyhalogen substituent. The azole derivatives include 1-methyl-1H-pyrazole and 9-ethyl-9H-carbazole. M represents a metal.

[0075] Boron esters and olefin derivatives include isopropenylboronic acid pinacol ester, vinylboronic acid pinacol ester, 4,4,5,5-tetramethyl-2-(1-phenylvinyl)-1,3,2-dioxaborane, 4,4,5,5-tetramethyl-2-(1-methylene-3-phenylpropyl)-1,3,2-dioxaborane, 4,4,5,5-tetramethyl-2-[1-methylene-3-(phenylmethoxy)propyl]-1,3,2-dioxaborane, styrene, 4-methylstyrene, 1-(trifluoromethyl)-4-vinylbenzene, 1-vinyl-3,5-bis(trifluoromethyl)benzene, 2,6-dichlorostyrene, dimethylphenylvinylsilane, vinyltrimethylsilane, N-phenylmethylacrylamide, N,N-dimethylacrylamide, and 1,1-dimethylethyl-2-acrylate.

[0076] Preferably, R is selected from one of H, fluorine, chlorine, bromine, trifluoromethyl, phenyl, formate, methoxy, formamide, methyl, trifluoromethoxy, 1-methyl-1H-pyrazole, 2,3-dihydrobenzo[b][1,4]dioxin, 9-ethyl-9H-carbazole, and dibenzo[b,d]furan.

[0077] Preferably, the molar ratio of the tetrafluoroborate diazonium salt substrate to the alkenyl boron ester and olefin derivative is 1.5:1.

[0078] Preferably, the metal halide is a sodium halide selected from sodium chloride, sodium bromide, and sodium iodide. The molar ratio of the metal halide to the alkenyl boron ester and olefin derivative is 1.5:1.

[0079] Preferably, the liquid auxiliary grinding agent is selected from acetonitrile, methanol, tetrahydrofuran or N,N-dimethylformamide, and the amount used is 0.2 μL / mg.

[0080] Preferably, the grinding treatment condition is grinding at 30 Hz for 1 hour.

[0081] Preferably, the molar ratio of the tetrafluoroborate diazonium salt substrate to the alkenyl borate ester or olefin derivative is 1.5:1; the molar ratio of the metal halide is sodium chloride to the alkenyl borate ester and olefin derivative is 1.5:1; the liquid auxiliary grinding agent is acetonitrile, and the amount used is 0.2 μL / mg; and the mechanochemical conditions are grinding at 30 Hz for 1 hour.

[0082] Preferably, the purification process comprises the following steps: adding an organic solvent to a ball mill to dilute the reaction system, eluting the inorganic salts with the organic solvent on a diatomaceous earth column, removing the solvent by concentration under reduced pressure, and subjecting the residue to column chromatography using a mixed solvent of n-hexane / ethyl acetate as the eluent. The eluate containing the α-haloalkyl boronic acid ester is collected and the solvent is evaporated to obtain the α-haloalkyl boronic acid ester.

[0083] Preferably, the organic extractant is dichloromethane or ethyl acetate, more preferably dichloromethane; in the mixed solvent of n-hexane and ethyl acetate, the volume ratio of n-hexane to ethyl acetate is 5 to 10:1.

[0084] See also Figure 1 The present invention uses a stainless steel ball mill and stainless steel balls in the mechanical grinding process to participate in the catalytic process, which involves the single electron transfer of elemental iron and the valence increase and decrease cycle. The reaction mechanism of the present invention is analyzed and summarized as follows:

[0085] The reaction mechanism of the method of the present invention is demonstrated. First, in diazonium tetrafluoroborate, the NaCl anion exchanges with the non-coordinating tetrafluoroborate counterion. This exchange leads to the formation of an ion pair (I). Subsequently, the ion pair (I) generates an aryl radical (II) and a chloride radical through intramolecular charge transfer, and cleaves the CN bond under mechanochemical conditions. Fe(0), present in the stainless steel ball mill and stainless steel balls, may also react with the ion pair (I) through a single electron transfer process to produce Fe(I)-Cl(a). This process also releases nitrogen into the surrounding environment. After the aryl radical (II) is generated, it undergoes an addition reaction with the olefin acceptor (2) to generate a newly generated α-boryl radical (III). Subsequently, the radical (III) is captured by Fe(I)-Cl(a) to form a high-valent Fe(II) complex (B). Finally, the intermediate B undergoes reduction elimination to generate an α-haloalkyl boron ester, and Fe(0) is regenerated, ending the catalytic cycle.

[0086] Example 1

[0087] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0088] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.2 mmol, 54.2 mg), isopropenylboronic acid pinacol ester (0.4 mmol, 67.2 mg), and KCl (0.4 mmol, 29.8 mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, filtered through a diatomaceous earth short column to remove insoluble impurities, and the solvent was removed to obtain a crude yellow oily product of 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane; dibromomethane as an internal standard was added to the crude product, and the nuclear magnetic resonance yield was calculated to be 44% by observing characteristic peaks by hydrogen nuclear magnetic resonance spectrum (400 MHz); the product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent, and the eluate containing the target compound was collected. The solvent was evaporated and dried to obtain a colorless oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane; its chemical structure is:

[0089]

[0090] Characterization data: colorless oily liquid, 1H NMR (400MHz, CDCl3) δ7.39(d,J=8.4Hz,2H),7.17(d,J=8.5Hz,2H),3.16(d,J =13.5Hz,1H),3.02(d,J=13.5Hz,1H),1.48(s,3H),1.25(s,6H),1.25(s,6H); 13 C NMR (101MHz, CDCl3) δ136.33, 132.43, 131.14, 120.94, 84.74, 46.76, 26.31, 24.66 (d, J = 4.2Hz); 11 B NMR (128 MHz, CDCl3) δ 30.75.

[0091] Example 2

[0092] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0093] The preparation steps were the same as those in Example 1, except that dichloromethane (0.2 μL / mg) was added as a liquid auxiliary grinding agent to obtain a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 24%.

[0094] Example 3

[0095] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0096] The preparation steps were the same as those in Example 1, except that methanol (0.2 μL / mg) was added as a liquid auxiliary grinding agent to obtain a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 50%.

[0097] Example 4

[0098] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0099] The preparation steps were the same as those in Example 1, except that tetrahydrofuran (0.2 μL / mg) was added as a liquid auxiliary grinding agent to obtain a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 53%.

[0100] Example 5

[0101] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0102] The preparation steps were the same as those in Example 1, except that N,N-dimethylformamide (0.2 μL / mg) was added as a liquid auxiliary grinding agent to obtain a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 68%.

[0103] Example 6

[0104] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0105] The preparation steps were the same as those in Example 1, except that ultra-dry acetonitrile (0.2 μL / mg) was added as a liquid auxiliary grinding agent to obtain a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a nuclear magnetic resonance yield of 83%.

[0106] Example 7

[0107] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0108] The preparation steps were the same as those in Example 1, except that ultra-dry acetonitrile (0.3 μL / mg) was added as a liquid auxiliary grinding agent to obtain a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 83%.

[0109] Example 8

[0110] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0111] The preparation steps were the same as those in Example 1, except that ultra-dry acetonitrile (0.5 μL / mg) was added as a liquid auxiliary grinding agent to obtain a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 75%.

[0112] Example 9

[0113] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0114] The preparation steps were the same as those in Example 7, except that the amount of KCl was increased to KCl (1 mmol, 74.5 mg) to obtain a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 80%.

[0115] Example 10

[0116] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0117] The preparation steps were the same as those in Example 6, except that the amounts of isopropenylboronic acid pinacol ester and KCl were reduced to isopropenylboronic acid pinacol ester (0.3 mmol, 50.4 mg) and KCl (0.3 mmol, 22.4 mg) to give a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 82%.

[0118] Example 11

[0119] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0120] The preparation steps were the same as those in Example 6, except that the amounts of isopropenylboronic acid pinacol ester and KCl were reduced to isopropenylboronic acid pinacol ester (0.24 mmol, 40.3 mg) and KCl (0.24 mmol, 17.9 mg) to give a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 68%.

[0121] Example 12

[0122] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0123] The preparation steps were the same as those in Example 10, except that the reaction time was shortened to 0.5 h to obtain a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 72%.

[0124] Example 13

[0125] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0126] The preparation steps were the same as those in Example 10, except that KCl (0.3 mmol, 22.4 mg) was replaced with an equal amount of LiCl (0.3 mmol, 12.7 mg) to obtain a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 77%.

[0127] Example 14

[0128] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0129] The preparation steps were the same as those in Example 10, except that KCl (0.3 mmol, 22.4 mg) was replaced with an equal amount of NaCl (0.3 mmol, 17.5 mg) to give a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 93%.

[0130] Example 15

[0131] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0132] The preparation steps were the same as those in Example 10, except that KCl (0.3 mmol, 22.4 mg) was replaced with an equal amount of CsCl (0.3 mmol, 50.5 mg) to obtain a crude yellow oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a NMR yield of 99%.

[0133] Example 16

[0134] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0135] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and the insoluble impurities were filtered out using a diatomaceous earth short column. The solvent was removed by distillation under reduced pressure and concentrated to obtain a crude yellow oil. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated and dried to obtain 71.2 mg of a colorless oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 99%.

[0136] Example 17

[0137] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0138] The preparation steps were the same as those in Example 16, except that the amount of 4-bromobenzene diazonium tetrafluoroborate was reduced to (0.24 mmol, 65.0 mg) to obtain 70.3 mg of colorless oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 98%.

[0139] Example 18

[0140] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0141] The preparation steps were the same as those in Example 16, except that NaCl (0.3 mmol, 17.5 mg) was replaced with an equal amount of NaBr (0.3 mmol, 30.8 mg) to obtain 79.9 mg of a yellow oily liquid 2-(2-bromo-1-(4-bromophenyl)prop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 99%.

[0142] Example 19

[0143] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0144] The preparation steps were the same as those in Example 16, except that NaCl (0.3 mmol, 17.5 mg) was replaced with an equal amount of NaI (0.3 mmol, 45.0 mg) to obtain 38.7 mg of lavender oily liquid 2-(1-(4-bromophenyl)-2-iodoprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 43%.

[0145] Example 20

[0146] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0147] The preparation steps were the same as those in Example 16, except that the feed was added under air atmosphere to obtain 60.4 mg of colorless oily liquid 2-(1-(4-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 84%.

[0148] Example 21

[0149] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0150] In a nitrogen-filled glove box, 4-chlorobenzene diazonium tetrafluoroborate (0.3 mmol, 67.9 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball, which was placed in a Retsch MM400 ball mill and reacted at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 62.7 mg of a colorless oily liquid 2-(2-chloro-1-(4-chlorophenyl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 99%. The chemical structure is as follows:

[0151]

[0152] Characterization data: colorless oily liquid, 1 H NMR (400MHz, CDCl3) δ7.23 (s, 4H), 3.18 (d, J = 13.6Hz, 1H), 3.03 (d, J = 13.5Hz, 1H), 1.49 (s, 3H), 1.26 (s, 6H), 1.24 (s, 6H); 13 C NMR (101MHz, CDCl3) δ135.83, 132.80, 132.04, 128.18, 84.73, 46.73, 26.32, 24.65 (d, J = 3.9Hz); 11 B NMR (128 MHz, CDCl3) δ 30.36.

[0153] Example 22

[0154] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0155] In a nitrogen-filled glove box, 4-fluorobenzene tetrafluoroborate diazonium salt (0.3 mmol, 63.0 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate and filtered through a short diatomaceous earth column to remove insoluble impurities. The solvent was removed by distillation under reduced pressure and concentrated to obtain a crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated and dried to obtain 47.8 mg of a colorless oily liquid 2-(2-chloro-1-(4-fluorophenyl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with a yield of 80%. Its chemical structure is as follows:

[0156]

[0157] Characterization data: colorless oily liquid, 1 H NMR (400MHz, CDCl3) δ7.31–7.23(m,2H),6.95(t,J=8.6Hz,2H),3.19(d,J=13.7H z,1H),3.03(d,J=13.7Hz,1H),1.49(s,3H),1.26(d,J=5.8Hz,6H),1.24(s,6H); 13 C NMR (101MHz, CDCl3) δ163.23, 160.80, 133.08 (d, J = 2.5Hz), 132.15 (d, J = 8.1Hz), 114.82 (d, J = 21.1Hz), 84.68, 46.62, 26.32, 24.64; 19 F NMR (376MHz, CDCl3) δ-116.19; 11 B NMR (128 MHz, CDCl3) δ 30.51.

[0158] Example 23

[0159] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0160] In a nitrogen-filled glove box, 4-trifluoromethylbenzene diazonium tetrafluoroborate (0.3 mmol, 78.0 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, filtered through a diatomaceous earth short column to remove insoluble impurities, and concentrated by distillation under reduced pressure to remove the solvent to obtain a crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 50.1 mg of a colorless oily liquid 2-(2-chloro-1-(4-(trifluoromethyl)phenyl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 72%. Its chemical structure is as follows:

[0161]

[0162] Characterization data: colorless oily liquid, 1 H NMR (400MHz, CDCl3) δ7.53(d,J=8.1Hz,2H),7.42(d,J=8.1Hz,2H),3.25(d,J =13.5Hz,1H),3.14(d,J=13.5Hz,1H),1.50(s,3H),1.26(s,6H),1.25(s,6H); 13 C NMR (101MHz, CDCl3) δ141.40, 131.02, 124.93 (q, J = 3.5Hz), 84.82, 47.04, 26.41, 24.63 (d, J = 5.2Hz); 19 F NMR (376MHz, CDCl3) δ-62.32; 11 B NMR (128 MHz, CDCl3) δ 30.32.

[0163] Example 24

[0164] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0165] In a nitrogen-filled glove box, 4-methoxycarbonylbenzene diazonium tetrafluoroborate (0.3 mmol, 75.0 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, filtered through a diatomaceous earth short column to remove insoluble impurities, and concentrated by distillation under reduced pressure to remove the solvent to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated and dried to obtain 52.2 mg of colorless oily liquid 4-(2-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)benzoic acid methyl ester in a yield of 77%. Its chemical structure is:

[0166]

[0167] Characterization data: colorless oily liquid, 1 H NMR(400MHz, CDCl3) δ7.93(d,J=8.0Hz,2H),7.37(d,J=8.1Hz,2H),3.88(s,3H),3.2 7(d,J=13.3Hz,1H),3.11(d,J=13.3Hz,1H),1.49(s,3H),1.25(s,6H),1.24(s,6H); 13 C NMR (101MHz, CDCl3) δ167.16,142.79,131.07,130.71,129.35,128.78(d,J=6.5Hz),84.77,52.15,47.39,26.44,24.64(d,J=2.8Hz); 11 B NMR (128MHz, CDCl3) δ31.12; HRMS (ESI) m / z calcd for C 17 H 24 BO4[M-Cl] + :303.17676,found303.17609.

[0168] Example 25

[0169] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0170] In a nitrogen-filled glove box, 4-(N-methylcarbamoyl)benzene diazonium tetrafluoroborate (0.3 mmol, 74.7 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 36.0 mg of a colorless oily liquid 4-(2-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)-N-methylbenzamide in a yield of 53%. The chemical formula is:

[0171]

[0172] Characterization data: colorless oily liquid, 1 H NMR (400MHz, CDCl3) δ7.63–7.58(m,2H),7.30(d,J=8.1Hz,2H),6.10(s,1H),3.19(d,J=13.4H z,1H),3.05(d,J=13.4Hz,1H),2.94(d,J=4.7Hz,3H),1.43(s,3H),1.19(s,6H),1.18(s,6H); 13 C NMR (101MHz, CDCl3) δ168.15,141.00,137.60,133.02,130.80,128.82,128.58,1 28.31,126.83,126.52,84.68,50.87,47.12,26.92,26.86,26.34,24.59,24.56; 11 B NMR (128MHz, CDCl3) δ30.82; HRMS (ESI) m / zcalcd for C 17 H 26 BClNO3[M+H] + :338.16888,found 338.17173.

[0173] Example 26

[0174] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0175] In a nitrogen-filled glove box, phenyl diazonium tetrafluoroborate (0.3 mmol, 57.6 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 52.7 mg of a colorless oily liquid 2-(2-chloro-1-phenyl-2-propyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 94%. The chemical formula is as follows:

[0176]

[0177] Characterization data: colorless oily liquid, 1 H NMR (400MHz, CDCl3) δ7.32–7.22(m,5H),3.28(d,J=13.5Hz,1H),3.07(d,J=13.5Hz,1H),1.51(s,3H),1.27(s,6H),1.25(s,6H); 13 C NMR (101MHz, CDCl3) δ137.41,130.67,128.07,126.86,84.63,47.58,26.35,24.65; 11 B NMR (128 MHz, CDCl3) δ 30.83.

[0178] Example 27

[0179] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0180] In a nitrogen-filled glove box, 4-methoxybenzene diazonium tetrafluoroborate (0.3 mmol, 66.6 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 53.7 mg of a brown oily liquid 2-(2-chloro-1-(4-methoxyphenyl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 87%. Its chemical structure is as follows:

[0181]

[0182] Characterization data: brown oily liquid, 1 H NMR(400MHz, CDCl3) δ7.21(d,J=8.2Hz,2H),6.80(d,J=8.3Hz,2H),3.77(s,3H),3.2 0(d,J=13.5Hz,1H),2.99(d,J=13.5Hz,1H),1.49(s,3H),1.26(s,6H),1.24(s,6H); 13 C NMR (101MHz, CDCl3) δ158.57,131.67,129.53,113.45,84.58,55.29,46.70,26.25,24.66; 11 B NMR (128 MHz, CDCl3) δ 30.43.

[0183] Example 28

[0184] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0185] In a nitrogen-filled glove box, 4-trifluoromethoxybenzene diazonium tetrafluoroborate (0.3 mmol, 82.8 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 35.4 mg of a yellow oily liquid 2-(2-chloro-1-(4-(trifluoromethoxy)phenyl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 49%. The chemical formula is as follows:

[0186]

[0187] Characterization data: yellow oily liquid, 1 H NMR (400MHz, CDCl3) δ7.33(d,J=8.5Hz,2H),7.11(d,J=8.2Hz,2H),3.21(d,J =13.6Hz,1H),3.08(d,J=13.7Hz,1H),1.51(s,3H),1.25(s,6H),1.24(s,6H); 13 C NMR (101MHz, CDCl3) δ148.21, 136.03, 131.93, 120.42, 84.67, 46.61, 26.37, 24.53 (d, J = 4.4Hz); 19 F NMR (376MHz, CDCl3) δ-57.90; 11 B NMR (128 MHz, CDCl3) δ 29.96.

[0188] Example 29

[0189] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0190] In a nitrogen-filled glove box, 2-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 68.3 mg of a light yellow solid 2-(1-(2-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 95%. The chemical formula is as follows:

[0191]

[0192] Characterization data: light yellow solid, 1 H NMR (400MHz, CDCl3) δ7.54(d,J=7.9Hz,2H),7.21(d,J=7.6Hz,1H),7.08(t,J= 7.7Hz,1H),3.41(s,1H),3.40(s,1H),1.56(s,3H),1.30(s,6H),1.28(s,6H); 13 C NMR (101MHz, CDCl3) δ137.14,132.96,131.97,128.33,126.98,126.08,84.63,45.14,25.81,24.57; 11 B NMR (128 MHz, CDCl3) δ 31.15.

[0193] Example 30

[0194] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0195] In a nitrogen-filled glove box, 3-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 71.5 mg of a light yellow solid 2-(1-(3-bromophenyl)-2-chloroprop-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 99%. The chemical formula is as follows:

[0196]

[0197] Characterization data: light yellow solid, 1 H NMR (400MHz, CDCl3) δ7.50(s,1H),7.35(d,J=7.9Hz,1H),7.21(d,J=7.7Hz,1H),7.13(t,J=7.8 Hz,1H),3.22(d,J=13.4Hz,1H),3.01(d,J=13.4Hz,1H),1.51(s,3H),1.27(s,6H),1.25(s,6H); 13 C NMR (101MHz, CDCl3) δ139.82, 133.44, 129.96, 129.66, 129.39, 122.18, 84.81, 47.23, 26.49, 24.69 (d, J = 3.9Hz); 11 B NMR (128 MHz, CDCl3) δ 30.38.

[0198] Example 31

[0199] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0200] In a nitrogen-filled glove box, 3,4-dichlorobenzene tetrafluoroborate diazonium salt (0.3 mmol, 78.2 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 67.8 mg of a light yellow oily liquid 2-(2-chloro-1-(3,4-dichlorophenyl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 97%. Its chemical structure is as follows:

[0201]

[0202] Characterization data: light yellow oily liquid, 1 H NMR (400MHz, CDCl3) δ7.44(d,J=2.1Hz,1H),7.33(d,J=8.2Hz,1H),7.12(dd,J=8.2,2.0Hz, 1H),3.16(d,J=13.5Hz,1H),3.01(d,J=13.5Hz,1H),1.50(s,3H),1.26(s,6H),1.25(s,6H); 13 C NMR (101MHz, CDCl3) δ137.71, 132.42, 131.99, 130.98, 130.19, 129.98, 84.89, 46.57, 26.48, 24.68 (d, J = 5.9Hz); 11 B NMR (128 MHz, CDCl3) δ 30.71.

[0203] Example 33

[0204] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0205] In a nitrogen-filled glove box, 2,4,6-trichlorobenzene tetrafluoroborate diazonium salt (0.3 mmol, 88.6 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 52.2 mg of a colorless oily liquid 2-(2-chloro-1-(2,4,6-trichlorophenyl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 68%. The chemical formula is as follows:

[0206]

[0207] Characterization data: colorless oily liquid, 1 H NMR (400MHz, CDCl3) δ7.59 (s, 2H), 3.92 (d, J = 14.6Hz, 1H), 3.76 (d, J = 14.6Hz, 1H), 1.84 (s, 3H), 1.55 (s, 12H); 13 C NMR (101MHz, CDCl3) δ138.06, 135.50, 133.76 (d, J = 13.2Hz), 129.46, 128.95, 85.31, 40.66, 28.07, 25.46 (d, J = 4.8Hz), 20.29; 11 B NMR (128MHz, CDCl3) δ29.30; HRMS (ESI) m / z calcd for C 15 H 19 BCl4O2[M] + :382.02322,found 382.02417.

[0208] Example 34

[0209] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0210] In a nitrogen-filled glove box, 4-biphenyl tetrafluoroborate diazonium salt (0.3 mmol, 80.4 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 70.6 mg of a brown solid 2-(1-([1,1'-biphenyl]-4-yl)-2-chloropropyl-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaboroborolane in a yield of 99%. The chemical formula is as follows:

[0211]

[0212] Characterization data: brown solid, 1 H NMR (400MHz, CDCl3) δ7.59(d,J=7.0Hz,2H),7.52(d,J=8.3Hz,2H),7.44(d,J=4.1Hz,2H),7.42(d,J=2.3Hz,1H) ,7.40(d,J=8.1Hz,2H),3.33(d,J=13.4Hz,1H),3.13(d,J=13.4Hz,1H),1.58(s,3H),1.30(s,6H),1.28(s,6H); 13 C NMR (101MHz, CDCl3) δ141.05,140.10,139.75,136.55,131.11,129.02,129.00,128.86,128.5 1,127.71,127.37,127.28,127.13,127.09,126.81,84.70,47.23,26.46,24.69(d,J=3.6Hz); 11 B NMR (128MHz, CDCl3) δ30.25; HRMS (ESI) m / z calcd for C 21 H 26 BO2[M-Cl] + :321.20259,found 321.20377.

[0213] Example 35

[0214] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0215] In a nitrogen-filled glove box, 2-naphthalene tetrafluoroborate (0.3 mmol, 70.2 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 60.0 mg of a brown solid 2-(2-chloro-1-(naphthalen-2-yl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaboroborolane in a yield of 91%. The chemical formula is:

[0216]

[0217] Characterization data: brown solid, 1 H NMR (400MHz, CDCl3) δ7.72–7.65(m,4H),7.38–7.33(m,3H),3.38(d,J=13.3Hz,1H),3.14(d,J=13.3Hz,1H),1.47(s,3H),1.19(s,6H),1.16(s,6H); 13 CNMR(101MHz, CDCl3)δ135.09,133.30,132.42,129.14,129.01,127.65,127.51,125.96,125.59,84.61,47.72,26.42,24.68,24.60; 11 B NMR (128MHz, CDCl3) δ30.63; HRMS (ESI) m / z calcd for C 19 H 28 BClNO2[M+NH4] + :348.18961,found 348.18834.

[0218] Example 36

[0219] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0220] In a nitrogen-filled glove box, 1-methyl-1H-pyrazole-3-tetrafluoroborate diazonium salt (0.3 mmol, 58.8 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 43.4 mg of a yellow oily liquid 3-(2-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)-1-methyl-1H-pyrazole. The yield was 76%, and the chemical formula thereof is:

[0221]

[0222] Characterization data: yellow oily liquid, 1 H NMR (400MHz, CDCl3) δ7.21(d,J=2.2Hz,1H),6.14(d,J=2.1Hz,1H),3.81(s,3H),3.2 4(d,J=14.3Hz,1H),3.09(d,J=14.3Hz,1H),1.54(s,3H),1.26(s,6H),1.25(s,6H); 13 C NMR (101MHz, CDCl3) δ148.81,130.45,106.09,84.48,40.41,38.74,26.50,24.67,24.63,24.56; 11 B NMR (128MHz, CDCl3) δ30.34; HRMS (ESI) m / z calcdfor C 13 H 23 BClN2O2[M+H] + :285.15356,found 285.15494.

[0223] Example 37

[0224] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0225] In a nitrogen-filled glove box, 2,3-dihydro-1,4-benzodioxane-6-tetrafluoroborate diazonium salt (0.3 mmol, 75.0 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 67.1 mg of a brown solid 2-(2-chloro-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 99%. Its chemical structure is as follows:

[0226]

[0227] Characterization data: brown solid, 1 H NMR (400MHz, CDCl3) δ6.82 (s, 1H), 6.74 (d, J = 1.2Hz, 2H), 4.21 (s, 4H), 3.16 (d, J=13.5Hz,1H),2.92(d,J=13.4Hz,1H),1.49(s,3H),1.27(s,6H),1.25(s,6H); 13 C NMR (101MHz, CDCl3) δ143.07,142.51,130.70,123.63,119.33,116.73,84.63,64.44,46.93,26.29,24.67; 11 B NMR (128MHz, CDCl3) δ29.62; HRMS (ESI) m / z calcdfor C 17 H 24 BNaClO4[M+Na] + :361.13484,found 361.13658.

[0228] Example 38

[0229] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0230] In a nitrogen-filled glove box, 9-ethyl-9H-carbazole-3-tetrafluoroborate diazonium salt (0.3 mmol, 92.7 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 63.1 mg of a brown solid 3-(2-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)-9-ethyl-9H-carbazole in a yield of 79%. The chemical structure thereof is as follows:

[0231]

[0232] Characterization data: brown solid, 1 H NMR (400MHz, CDCl3) δ8.15–8.11(m,1H),8.08(s,1H),7.38(d,J=31.0Hz,5H),4.40–4.34(m,2H),3.56( d,J=13.4Hz,1H),3.26(d,J=13.4Hz,1H),1.61(s,3H),1.44(d,J=5.8Hz,3H),1.32(s,6H),1.28(s,6H); 13 C NMR (101MHz, CDCl3) δ140.30,140.04,139.14,128.54,127.93,125.69(d,J=8.4Hz),123.04,122.97,122.87,122.29,120.4 6(d,J=15.4Hz),118.83(d,J=5.5Hz),108.57(d,J=3.7Hz),107.99,84.62,47.90,37.66,26.43,24.77(d,J=7.8Hz),13.93; 11 B NMR (128MHz, CDCl3) δ31.67; HRMS (ESI) m / z calcd for C 23 H 30 BClNO2[M+H] + :398.20526,found 398.20644.

[0233] Example 39

[0234] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0235] In a nitrogen-filled glove box, 3-dibenzofuran tetrafluoroborate diazonium salt (0.3 mmol, 84.6 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, and insoluble impurities were filtered out using a short diatomaceous earth column. The solvent was removed to obtain a crude product, which was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 70.8 mg of a yellow solid 2-(2-chloro-1-(dibenzo[b,d]furan-3-yl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 96%. Its chemical structure is as follows:

[0236]

[0237] Characterization data: brown solid, 1 H NMR(400MHz, CDCl3)δ7.92(dd,J=7.7,1.3Hz,1H),7.84(s,1H),7.60–7.53(m,3H),7.46–7.43(m,1H) ,7.33(s,1H),3.46(d,J=13.4Hz,1H),3.24(d,J=13.4Hz,1H),1.58(s,3H),1.31(s,6H),1.28(s,6H); 13 C NMR (101MHz, CDCl3) δ156.39 (d, J = 16.6Hz), 137.09, 127.25, 127.03, 125.53, 124.26, 122.98 ,122.78,120.70(d,J=12.9Hz),120.04,113.66,111.76,84.76,47.93,26.45,24.72,24.71; 11 B NMR (128MHz, CDCl3) δ31.82; HRMS (ESI) m / z calcd for C 21 H 24 BNaClO3[M+Na] +:393.13992,found393.14087.

[0238] Example 40

[0239] A method for synthesizing an α-haloalkyl boron ester and its oxidation product comprises the following steps:

[0240] In a nitrogen-filled glove box, 4-iodobenzene diazonium tetrafluoroborate (0.3 mmol, 95.3 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg), and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The mill was tightened and placed in a Retsch MM400 ball mill. The mill was reacted at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, filtered through a short column of celite to remove insoluble impurities, and the solvent was removed to obtain crude 2-(2-chloro-1-(4-iodophenyl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane. Dibromomethane (an internal standard) was added to the crude product, and the NMR yield was calculated to be 96% by observing the characteristic peaks using a 400 MHz H NMR spectrum. Due to the poor stability of the structure on a silica gel column, it was necessary to oxidize the structure to obtain accurate structural information. The crude product was dissolved in a mixed solution of 1.5 mL of tetrahydrofuran and 0.5 mL of water, and NaBO3·4H2O (1.4 mmol, 135.0 mg) was added. The mixture was stirred at room temperature for 4 hours, then diluted with ether (5 mL) and water (5 mL), and the organic layer was extracted. The aqueous layer was extracted with ether (5 mL), and the combined organic extracts were dried over anhydrous Na2SO4 and concentrated by vacuum distillation to remove the solvent to obtain the crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 5:1 as the eluent. The eluent containing the target compound was collected, the solvent was evaporated, and the mixture was dried to obtain 25.3 mg of a colorless oily liquid 1-(4-iodophenyl)propan-2-one with a yield of 51%. Its chemical formula is:

[0241]

[0242] Characterization data: colorless oily liquid, 1 H NMR (400MHz, CDCl3) δ7.59 (d, J = 8.3Hz, 2H), 6.87 (d, J = 8.3Hz, 2H), 3.57 (s, 2H), 2.09 (s, 3H); 13 C NMR (101MHz, CDCl3) δ205.52,137.82,133.76,131.44,92.61,50.28,29.46.

[0243] Example 41

[0244] A method for synthesizing an α-haloalkyl boron ester and its oxidation product comprises the following steps:

[0245] In a nitrogen-filled glove box, 4-methylbenzene diazonium tetrafluoroborate (0.3 mmol, 61.8 mg), isopropenylboronic acid pinacol ester (0.2 mmol, 33.6 mg), NaCl (0.3 mmol, 17.5 mg), and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The mill was tightened and placed in a Retsch MM400 ball mill for 1 hour at 30 Hz. After the reaction, the product was extracted with ethyl acetate, filtered through a short column of celite to remove insoluble impurities, and concentrated by vacuum distillation to remove the solvent, yielding crude 2-(2-chloro-1-(p-tolyl)propan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane. Dibromomethane (an internal standard) was added to the crude product, and the NMR yield was calculated to be 45% based on characteristic peaks observed by H NMR (400 MHz). Due to the poor stability of the structure on the silica gel column, it was necessary to oxidize the structure to obtain accurate structural information. The crude product was dissolved in a mixed solution of 1.5 mL of tetrahydrofuran and 0.5 mL of water, and NaBO3·4H2O (1.4 mmol, 135.0 mg) was added. The mixture was stirred at room temperature for 4 hours, then diluted with ether (5 mL) and water (5 mL), and the organic layer was extracted. The aqueous layer was extracted with ether (5 mL), and the combined organic extracts were dried over anhydrous Na2SO4 and concentrated by vacuum distillation to remove the solvent to obtain the crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 5:1 as the eluent. The eluent containing the target compound was collected, the solvent was evaporated and dried to obtain 6.7 mg of colorless oily liquid 1-(4-methylphenyl)propan-2-one, with a yield of 50%. Its chemical formula is:

[0246]

[0247] Characterization data: colorless oily liquid, 1 H NMR (400MHz, CDCl3) δ7.08 (d, J = 7.9 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 3.58 (s, 2H), 2.27 (s, 3H), 2.07 (s, 3H); 13 C NMR (101MHz, CDCl3) δ206.89,136.82,131.27,129.57,129.35,50.76,29.28,21.17.

[0248] Example 44

[0249] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0250] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), vinylboronic acid pinacol ester (0.2 mmol, 30.8 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate and filtered through a short diatomaceous earth column to remove insoluble impurities. The solvent was then removed by vacuum distillation and concentrated to obtain a crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 48.7 mg of 2-(2-(4-bromophenyl)-1-chloroethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane as a yellow oily liquid, with a yield of 71%. Its chemical structure is:

[0251]

[0252] Characterization data: yellow oily liquid, 1 H NMR (400MHz, CDCl3) δ7.40(d,J=8.4Hz,2H),7.13(d,J=8.3Hz,2H),3.54(t,J=8.0Hz,1H ),3.12(dd,J=14.0,7.6Hz,1H),3.02(dd,J=14.0,8.5Hz,1H),1.23(s,6H),1.23(s,6H); 13 C NMR (101MHz, CDCl3) δ137.40,131.43,131.00,120.70,84.62,39.54,24.62,24.52. 11 B NMR (128MHz, CDCl3) δ30.51; HRMS (ESI) m / z calcdfor C 14 H 19 BBrO2[M-Cl] + :309.06615,found 309.06621.

[0253] Example 45

[0254] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0255] In a nitrogen-filled glove box, phenyl diazonium tetrafluoroborate (0.3 mmol, 57.6 mg), vinylboronic acid pinacol ester (0.2 mmol, 30.8 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate and filtered through a short diatomaceous earth column to remove insoluble impurities. The solvent was then removed by distillation under reduced pressure to concentrate and remove the solvent to obtain a crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 23.0 mg of a light yellow oily liquid 2-(2-(4-bromophenyl)-1-chloroethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 43%. Its chemical structure is:

[0256]

[0257] Characterization data: yellow oily liquid, 1 H NMR (400MHz, CDCl3) δ7.23–7.16(m,5H),3.52(t,J=8.2Hz,1H),3.10(dd,J=13.7,8.1Hz,1H),3.02(dd,J=13.8,8.3Hz,1H),1.16(s,6H),1.15(s,6H); 13 C NMR (101MHz, CDCl3) δ138.38,129.24,128.35,126.76,84.47,40.26,24.57,24.51. 11 B NMR (128 MHz, CDCl3) δ 30.35.

[0258] Example 46

[0259] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0260] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), 4,4,5,5-tetramethyl-2-(1-phenylvinyl)-1,3,2-dioxaborolane (0.2 mmol, 46.0 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate and filtered through a short column of celite to remove insoluble impurities. The solvent was then removed by distillation under reduced pressure to yield crude 2-(2-(4-bromophenyl)-1-chloro-1-phenylethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane. Dibromomethane, an internal standard, was added to the crude product. The H NMR yield was calculated to be 60% based on characteristic peaks observed by H NMR (400 MHz). Due to the poor stability of the structure on a silica gel column, oxidation was required to obtain accurate structural information. The crude product was dissolved in a mixture of 1.5 mL of tetrahydrofuran and 0.5 mL of water. NaBO₃·4H₂O (1.4 mmol, 135.0 mg) was added and stirred at room temperature for 4 hours. The reaction was then diluted with ether (5 mL) and water (5 mL), and the organic layer was extracted. The aqueous layer was then extracted with ether (5 mL). The combined organic extracts were dried over anhydrous Na₂SO₄ and concentrated by distillation under reduced pressure to yield the crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 5:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the mixture was dried to obtain 16.1 mg of a white solid 2-(4-bromophenyl)-1-phenylethan-1-one in a yield of 49%. Its chemical structure is as follows:

[0261]

[0262] Characterization data: white solid, 1 H NMR (400MHz, CDCl3) δ7.92 (d, J = 7.3Hz, 2H), 7.50 (t, J = 7.4Hz, 1H), 7.39 (dd, J = 10.8, 8.1Hz, 4H), 7.06 (d, J = 8.3Hz, 2H), 4.17 (s, 2H); 13 C NMR (101MHz, CDCl3) δ197.00,136.40,133.46,133.39,131.76,131.28,128.75,128.53,120.99,44.77.

[0263] Example 47

[0264] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0265] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), 4,4,5,5-tetramethyl-2-(4-phenylbut-1-en-2-yl)-1,3,2-dioxaborolane (0.2 mmol, 51.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate and filtered through a short diatomaceous earth column to remove insoluble impurities. The solvent was removed to obtain a crude product, which was then separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 69.6 mg of a colorless oily liquid, 2-(1-(4-bromophenyl)-2-chloro-4-phenyl-2-butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, with a yield of 77%. Its chemical structure is:

[0266]

[0267] Characterization data: colorless oily liquid, 1 H NMR(400MHz, CDCl3)δ7.32(d,J=8.4Hz,2H),7.22–7.11(m,5H),7.09(d,J=7.8Hz,2H), 3.07(d,J=1.9Hz,2H),2.85–2.65(m,2H),2.13–1.85(m,2H),1.19(s,6H),1.17(s,6H); 13 C NMR (101MHz, CDCl3) δ141.85,136.16,132.50,131.17,128.57,126.10,121.02,85.00,45.07,41.83,32.25,25.01,24.91,24.80; 11 B NMR (128MHz, CDCl3) δ29.87; HRMS (ESI) m / z calcd for C 22 H 27 BLiBrClO2[M+Li] + :455.11306,found 455.11805.

[0268] Example 48

[0269] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0270] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), 4,4,5,5-tetramethyl-2-(4-phenoxybut-1-en-2-yl)-1,3,2-dioxaborolane (0.2 mmol, 57.6 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, filtered through a diatomaceous earth short column to remove insoluble impurities, and concentrated by reduced pressure distillation to remove the solvent to obtain a crude product. Dibromomethane was added to the crude product as an internal standard. The nuclear magnetic resonance yield was calculated to be 85% by observing characteristic peaks by hydrogen nuclear magnetic resonance spectroscopy (400 MHz). The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain a colorless oily liquid (2-(4-benzyloxy)-1-(4-bromophenyl)-2-chlorobutan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane). Its chemical structure is:

[0271]

[0272] Characterization data: colorless oily liquid, 1 H NMR 7.37(d,J=8.4Hz,2H),7.33(d,J=4.1Hz,5H),7.21(d,J=8.3Hz,2H),4.51(s,2H),3.61(t,J=6.7Hz,2H),3.1 3(d,J=14.1Hz,1H),3.05(d,J=14.2Hz,1H),2.09(ddd,J=92.3,14.2,7.5Hz,2H),1.20(s,6H),1.15(s,6H); 13 C NMR (101MHz, CDCl3) δ138.24,135.85,132.71,130.89,128.38,128.29,127.81,1 27.66,127.62,120.86,84.72,73.08,66.87,45.32,39.38,24.90,24.75,24.63; 11 B NMR (128MHz, CDCl3) δ30.36; HRMS (ESI) m / z calcd for C 23 H 29BNaBrClO3[M+Na] + :501.09739,found501.09891.

[0273] Example 49

[0274] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0275] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), styrene (0.2 mmol, 20.8 mg), NaCl (0.3 mmol, 17.5 mg), and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The mill was tightened and placed in a Retsch MM400 ball mill at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, filtered through a short diatomaceous earth column to remove insoluble impurities, and concentrated by vacuum distillation to remove the solvent to obtain a crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 54.4 mg of a yellow solid, 1-bromo-4-(2-chloro-2-phenylethyl)benzene, in a yield of 92%. Its chemical formula is:

[0276]

[0277] Characterization data: yellow solid, 1 H NMR (400MHz, CDCl3) δ7.37(d,J=8.4Hz,2H),7.35–7.28(m,5H),6.97(d,J=8.2Hz,2H ),5.00(t,J=7.3Hz,1H),3.35(dd,J=14.0,7.8Hz,1H),3.28(dd,J=14.0,6.9Hz,1H); 13 C NMR (101MHz, CDCl3) δ140.82, 136.43, 131.53, 131.26, 128.65 (d, J = 14.7Hz), 127.20, 63.74, 45.96; HRMS (ESI) m / z calcd for C 14 H 12 LiBrCl[M+Li]+:300.99655, found 300.99684.

[0278] Example 50

[0279] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0280] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), 4-methylstyrene (0.2 mmol, 23.6 mg), NaCl (0.3 mmol, 17.5 mg), and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for 1 hour at 30 Hz. After the reaction, the product was extracted with ethyl acetate, filtered through a short diatomaceous earth column to remove insoluble impurities, and concentrated by vacuum distillation to remove the solvent to obtain a crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 18.1 mg of 1-bromo-4-(2-chloro-2-(p-tolyl)ethyl)benzene as a colorless oily liquid in a yield of 29%. Its chemical structural formula is:

[0281]

[0282] Characterization data: colorless oily liquid, 1 H NMR (400MHz, CDCl3) δ7.30(d,J=8.3Hz,2H),7.14(d,J=8.2Hz,2H),7.06(d,J=7.9Hz ,2H),6.90(d,J=8.3Hz,2H),4.90(t,J=7.3Hz,1H),3.30–3.17(m,2H),2.27(s,3H); 13 C NMR(101MHz, CDCl3)δ138.37,137.82,136.52,131.43,131.17,129.32,127.02,120.81,63.67,45.79,21.18; HRMS(ESI)m / z calcd forC 15 H 14 KBrCl[M+K] + :346.95990,found 346.96075.

[0283] Example 51

[0284] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0285] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), 1-(trifluoromethyl)-4-vinylbenzene (0.2 mmol, 34.4 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate and filtered through a short diatomaceous earth column to remove insoluble impurities. The solvent was then removed by vacuum distillation and concentrated to obtain a crude product. The crude product was then separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 61.1 mg of 1-bromo-4-(2-chloro-2-(4-(trifluoromethyl)phenyl)ethyl)benzene as a yellow oily liquid in an 84% yield. Its chemical structure is:

[0286]

[0287] Characterization data: yellow oily liquid, 1 H NMR (400MHz, CDCl3) δ7.51(d,J=8.2Hz,2H),7.35(d,J=8.1Hz,2H),7.31(d,J=8.2Hz,2H),6.87(d ,J=8.2Hz,2H),4.95(t,J=7.3Hz,1H),3.26(dd,J=14.0,7.6Hz,1H),3.18(dd,J=14.1,6.9Hz,1H); 13 C NMR (101MHz, CDCl3) δ144.55, 144.54, 135.64, 131.61, 131.13, 127.57, 125.65 (q, J = 3.7Hz), 121.17, 62.45, 45.78; 19 FNMR(376MHz, CDCl3)δ-62.63; HRMS(ESI)m / z calcd for C 15 H 11 NaBrClF3[M+Na] + :384.95770,found384.95844.

[0288] Example 52

[0289] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0290] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), 1-vinyl-3,5-bistrifluoromethylbenzene (0.2 mmol, 48.0 mg), NaCl (0.3 mmol, 17.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate and filtered through a short diatomaceous earth column to remove insoluble impurities. The solvent was then removed by vacuum distillation and concentrated to obtain a crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 52.5 mg of 1-(2-(4-bromophenyl)-1-chloroethyl)-3,5-bis(trifluoromethyl)benzene as a light yellow oily liquid, with a yield of 61%. Its chemical structure is:

[0291]

[0292] Characterization data: light yellow oily liquid, 1 H NMR (400MHz, CDCl3) δ7.71 (d, J = 32.0Hz, 3H), 7.34 (d, J = 8.2Hz, 2H), 6.89 (d, J = 8.2Hz, 2H), 5.01 (t, J = 7.2Hz, 1H), 3.28 (dd, J = 14.1, 8.0Hz, 1H), 3.19 (dd, J = 14.1, 6.5Hz, 1H); 13 C NMR (101MHz, CDCl3) δ146.02,143.26,137.38,134.95,132.23,132.04,131.90,131.78,131.59,131.07,130 .61,129.63,127.42,127.40,122.47,122.44,122.40,122.36,122.33,121.50,61.58,52.11,45.69,41.08; 19 FNMR(376MHz, CDCl3)δ-62.92; HRMS(ESI)m / z calcd for C 16 H 10 NaBrClF6[M+Na] + :452.94508,found 452.94681.

[0293] Example 53

[0294] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0295] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), 2,6-dichlorostyrene (0.2 mmol, 34.6 mg), NaCl (0.3 mmol, 17.5 mg), and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The mill was tightened and placed in a Retsch MM400 ball mill. The reaction was carried out at 30 Hz for 1 hour. After the reaction, the product was extracted with ethyl acetate, filtered through a short column of diatomaceous earth to remove insoluble impurities, and concentrated by vacuum distillation to remove the solvent to obtain a crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 37.2 mg of 2-(2-(4-bromophenyl)-1-chloroethyl)-1,3-dichlorobenzene as a yellow oily liquid in a yield of 51%. Its chemical structural formula is:

[0296]

[0297] Characterization data: yellow oily liquid, 1 H NMR (400MHz, CDCl3) δ7.29(d,J=8.4Hz,2H),7.20–7.11(m,2H),7.06(t,J=8.0Hz,1H),6.98(d,J =8.4Hz,2H),5.86(t,J=8.0Hz,1H),3.61(dd,J=13.9,8.2Hz,1H),3.52(dd,J=14.0,8.0Hz,1H); 13 C NMR(101MHz, CDCl3)δ136.14,135.78,135.17,134.28,131.55,130.92,130.73,129.82,128.46,121.04,57.47,41.02; HRMS(ESI)m / zcalcd for C 14 H 10 BrCl2[M-Cl] + :326.93429,found 326.93454.

[0298] Example 54

[0299] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0300] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), dimethylphenylvinylsilane (0.2 mmol, 32.5 mg), NaCl (0.3 mmol, 17.5 mg), and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The mill was tightened and placed in a Retsch MM400 ball mill for 1 hour at 30 Hz. After the reaction, the product was extracted with ethyl acetate, filtered through a short diatomaceous earth column to remove insoluble impurities, and concentrated by vacuum distillation to remove the solvent to obtain a crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 42.1 mg of a yellow oily liquid (2-(4-bromophenyl)-1-chloroethyl)dimethyl(phenyl)silane (60% yield). Its chemical structural formula is:

[0301]

[0302] Characterization data: yellow oily liquid, 1 H NMR (400MHz, CDCl3) δ7.57(d,J=5.7Hz,2H),7.44–7.35(m,5H),7.01(d,J=8.3Hz,2H),3.58(dd,J=1 1.8,3.3Hz,1H),3.00(dd,J=14.9,3.3Hz,1H),2.73(dd,J=14.8,11.8Hz,1H),0.45(d,J=8.5Hz,6H); 13 C NMR(101MHz, CDCl3)δ138.52,135.43,134.23,131.40,130.75,129.90,128.15,120.48,50.97,38.98,-4.40,-5.70; HRMS(ESI)m / z calcd for C 16 H 19 BrClSi[M+H] + :353.01224,found 353.01499.

[0303] Example 55

[0304] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0305] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), vinyltrimethylsilane (0.2 mmol, 20.0 mg), NaCl (0.3 mmol, 17.5 mg), and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The mill was tightened and placed in a Retsch MM400 ball mill for 1 hour at 30 Hz. After the reaction, the product was extracted with ethyl acetate, filtered through a short diatomaceous earth column to remove insoluble impurities, and concentrated by vacuum distillation to remove the solvent to obtain a crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as the eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 24.3 mg of a colorless oily liquid (2-(4-bromophenyl)-1-chloroethyl)trimethylsilane, with a yield of 42%. Its chemical structural formula is:

[0306]

[0307] Characterization data: colorless oily liquid, 1 H NMR (400MHz, CDCl3) δ7.29 (d, J = 8.4Hz, 2H), 6.97 (d, J = 8.4Hz, 2H), 3.26 (dd, J = 11.7, 3.6Hz, 1H), 2.93 (dd, J=14.7, 3.6Hz, 1H), 2.65 (dd, J=14.7, 11.7Hz, 1H), 0.00 (s, 9H); 13 C NMR(101MHz, CDCl3)δ138.60,131.39,130.68,120.40,51.50,38.96,-3.47; HRMS(ESI)m / z calcd for C 11 H 16 NaBrClSi[M+Na] + :312.97854,found312.97809.

[0308] Example 56

[0309] A method for synthesizing the reaction product of α-haloalkyl boron ester and other olefins comprises the following steps:

[0310] In a nitrogen-filled glove box, 4-bromobenzene diazonium tetrafluoroborate (0.3 mmol, 81.3 mg), N-phenylmethylacrylamide (0.2 mmol, 32.2 mg), NaCl (0.3 mmol, 17.5 mg), and ultra-dry acetonitrile (0.2 μL / mg) were added to a 1.5 ml ball mill containing a 5 mm stainless steel ball. The mill was tightened and placed in a Retsch MM400 ball mill for 1 hour at 30 Hz. After completion of the reaction, the product was extracted with ethyl acetate, filtered through a short diatomaceous earth column to remove insoluble impurities, and concentrated by vacuum distillation to remove the solvent to obtain a crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as eluent. The eluate containing the target compound was collected, the solvent was evaporated, and the product was dried to obtain 40.4 mg of 3-(4-bromophenyl)-2-chloro-2-methyl-N-phenylpropionamide as a light yellow oily liquid in a yield of 57%. Its chemical structural formula is:

[0311]

[0312] Characterization data: light yellow oily liquid, 1 H NMR(400MHz, CDCl3)δ8.53(s,1H),7.67–7.60(m,4H),7.56(t,J=7.9Hz,2H),7 .41–7.34(m,3H),3.77(d,J=14.0Hz,1H),3.32(d,J=14.0Hz,1H),2.16(s,3H); 13 C NMR(101MHz, CDCl3)δ168.83,136.82,134.46,132.49,131.30,129.15,125.30,121.62,120.44,74.07,47.61,30.22; HRMS(ESI)m / z calcd forC 16 H 16 BrClNO[M+H] + :352.00983,found 352.01072.

[0313] Example 57

[0314] The synthesis method of α-haloalkyl boron ester comprises the following steps:

[0315] In a nitrogen-filled glove box, phenyl diazonium tetrafluoroborate (6.8 mmol, 1.3 g), isopropenylboronic acid pinacol ester (4.5 mmol, 756.2 mg), NaCl (6.8 mmol, 394.5 mg) and ultra-dry acetonitrile (0.2 μL / mg) were added to a 10 ml ball mill containing nine 7 mm stainless steel balls. The ball mill was tightened and placed in a Retsch MM400 ball mill for reaction at 30 Hz for 2 h. After the reaction, the product was extracted with ethyl acetate, and the insoluble impurities were filtered out using a diatomaceous earth column. The solvent was removed and concentrated by distillation under reduced pressure to obtain a crude product. The crude product was separated by column chromatography using a mixture of n-hexane and ethyl acetate in a volume ratio of 10:1 as an eluent. The eluate containing the target compound was collected, the solvent was evaporated and dried to obtain 1.2 g of a colorless oily liquid 2-(2-chloro-1-phenyl-2-propyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane in a yield of 94%.

[0316] In summary, the mechanochemical synthesis method of α-haloalkyl boron ester disclosed in the present invention has significant advantages, mainly reflected in:

[0317] 1. The present invention does not require the addition of a large amount of organic solvents, but only requires a small amount of liquid auxiliary grinding agent, which is more in line with the requirements of the green and environmentally friendly era.

[0318] 2. The present invention does not require the addition of additional catalysts, and compared with the existing technology, the cost is lower, which is conducive to saving industrial preparation costs.

[0319] 3. The reaction efficiency of the present invention is high and the reaction speed is fast, and the reaction can be completed in only 1 hour.

[0320] 4. Compared with the complicated operation of the prior art, the operation of the present invention is simpler.

[0321] 5. The traditional solution reaction system is difficult to apply to poorly soluble substrates, while the mechanochemical method of the present invention also has good adaptability to poorly soluble substrates.

[0322] 6. Different from traditional solution reaction and photocatalytic reaction, the present invention is a mechanochemical reaction.

[0323] The above content is only for explaining the technical idea of ​​the present invention and cannot be used to limit the protection scope of the present invention. Any changes made on the basis of the technical solution in accordance with the technical idea proposed by the present invention shall fall within the protection scope of the claims of the present invention.

Claims

1. A mechanochemical synthesis method of α-haloalkyl boron ester, characterized in that: Under a nitrogen atmosphere, using diazonium tetrafluoroborate as a free radical source, an alkenyl boron ester as an acceptor, a metal halide as a halide source, and an ultra-dry liquid as an auxiliary grinding agent, a stainless steel ball milling process is performed to achieve a full coupling reaction of the free radical source, acceptor, and halide source to generate an α-haloalkyl boron ester; wherein: The structural formula of the diazonium tetrafluoroborate is as follows: ； wherein R is selected from H, halogen, trifluoromethyl, ester, amide, alkoxy, trifluoromethoxy, phenyl, 1-methyl-1H-pyrazole, 2,3-dihydrobenzo[b][1,4]dioxin, 9-ethyl-9H-carbazole, or dibenzo[b,d]furan; The alkenyl boronate is selected from isopropenylboronic acid pinacol ester, vinylboronic acid pinacol ester, 4,4,5,5-tetramethyl-2-(1-phenylvinyl)-1,3,2-dioxaborolane, 4,4,5,5-tetramethyl-2-(1-methylene-3-phenylpropyl)-1,3,2-dioxaborolane or 4,4,5,5-tetramethyl-2-[1-methylene-3-(phenylmethoxy)propyl]-1,3,2-dioxaborolane.

2. The mechanochemical synthesis method of α-haloalkyl boron ester according to claim 1, characterized in that: R is selected from fluorine, chlorine, bromine, formate, methoxy, formamido, methyl, ethyl, isopropyl, 1-methyl-1H-pyrazole, 2,3-dihydrobenzo[b][1,4]dioxin, 9-ethyl-9H-carbazole or dibenzo[b,d]furan.

3. The mechanochemical synthesis method of α-haloalkyl boron ester according to claim 1, characterized in that: The metal halide is sodium halide.

4. The mechanochemical synthesis method of α-haloalkyl boron ester according to claim 3, characterized in that: The sodium halide is selected from sodium chloride, sodium bromide or sodium iodide.

5. The mechanochemical synthesis method of α-haloalkyl boron ester according to claim 1, characterized in that: The molar ratio of diazonium tetrafluoroborate to the alkenyl boron ester is 1.5:1; the molar ratio of metal halide to alkenyl boron ester is 1.5:

1.

6. The mechanochemical synthesis method of α-haloalkyl boron ester according to claim 1, characterized in that: The ultra-dry liquid auxiliary grinding agent is selected from acetonitrile, methanol, tetrahydrofuran or N,N-dimethylformamide, and the amount used is 0.2 μL / mg.

7. The mechanochemical synthesis method of α-haloalkyl boron ester according to any one of claims 1 to 6, characterized in that: The ball milling treatment was carried out at 20-35 Hz for 1-3 h.

8. The mechanochemical synthesis method of α-haloalkyl boron ester according to claim 1, characterized in that: After being ball-milled with stainless steel, α-halogenated alkyl boron ester is obtained through purification.

9. The mechanochemical synthesis method of α-haloalkyl boron ester according to claim 8, characterized in that: The purification process comprises adding an organic solvent to the system after the ball milling reaction for dilution, then eluting on a diatomaceous earth column to remove inorganic salts, and then removing the solvent by vacuum concentration. The concentrated residue is separated by column chromatography using a mixed solvent of n-hexane / ethyl acetate as an eluent, collecting the eluate containing the α-haloalkyl boronic ester, and distilling off the solvent to obtain the α-haloalkyl boronic ester. Wherein, the organic extractant is dichloromethane or ethyl acetate; in the n-hexane / ethyl acetate mixed solvent, the volume ratio of n-hexane to ethyl acetate is 5~10:1.

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