Planar chiral boronic acid compounds based on a cycloaralkane skeleton, and synthesis method and application thereof

Abstract

The application provides a kind of plane chiral boronic acid compound based on cycloaralkane skeleton and its synthesis method and application, the plane chiral compound has the structure shown in formula I;R 1 It is selected from one of C1-C8 alkyl, C1-C8 alkoxy, C1-C20 aryloxy.R 2 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester group, nitro group, phenyl, benzyl, tert-butyl, isopropyl.The application can effectively synthesize plane chiral boronic acid catalyst based on cycloaralkane skeleton, and the plane chiral boronic acid catalyst based on cycloaralkane skeleton can realize diol desymmetrization reaction.

Description

Technical Field

[0001] This application relates to a class of planar chiral boric acid compounds based on cycloaryl skeletons, their synthesis methods, and applications, belonging to the field of organic synthesis technology. Background Technology

[0002] Catalysts are the core of chemical reactions. There are many types of catalysts, among which transition metal catalysts are the most extensively studied and widely used. Transition metal catalysts have the advantages of high catalytic activity, but their disadvantages include high cost, harsh reaction conditions, difficulty in catalyst recovery, and heavy metal toxicity. Organic small molecule catalysis, as the third class of catalysts after enzyme catalysis and metal catalysis, has advantages such as mild reaction conditions, environmental friendliness, and easy recycling, meeting the requirements of green chemistry and becoming a new hot topic in chiral catalysis research in recent years. Among organic small molecule catalysts, boric acid catalysts are a relatively special type. Currently, very few chiral boric acid catalysts have been published, and they can only be used for later functional group derivatization; a series of chiral boric acids cannot be synthesized using universal methods. Summary of the Invention

[0003] The purpose of this invention is to provide a method for synthesizing and applying a class of planar chiral boronic acid compounds based on cycloaryl skeletons. To expand the variety of chiral cycloaryl skeleton boronic acids and explore their potential in the desymmetry reactions of diols, this invention designs a series of planar chiral boronic acid compounds with cycloaryl skeletons and uses them as catalysts to achieve excellent results in catalyzing the desymmetry reactions of diols.

[0004] The technical solution of the present invention is as follows:

[0005] On the one hand, the present invention provides a class of planar chiral boric acid compounds based on a cycloaryl skeleton, having the structure shown in Formula I.

[0006]

[0007] In Formula I:

[0008] R 1 It is selected from one of C1-C8 alkyl groups (e.g., methyl, ethyl, tert-butyl), C1-C8 alkoxy groups (e.g., methoxy, ethoxy), and C1-C20 aryloxy groups (e.g., phenyl groups bonded to oxygen); the aryloxy group includes unsubstituted or substituted aryloxy groups, for example, the substituents of the aryloxy group are selected from hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, isopropyl;

[0009] R 2 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl.

[0010] As an optional technical solution, the planar chiral compound is selected from those having structures represented by formula Ia, Ib, Ic, Id, or Ie.

[0011]

[0012] R 3 It is selected from one of C1 to C8 alkyl groups (e.g., methyl, ethyl, tert-butyl, isopropyl), C1 to C8 alkoxy groups (e.g., methoxy, ethoxy), and C1 to C19 aryl groups (e.g., phenyl); the aryl group includes unsubstituted or substituted aryl groups, for example, the substituent of the aryl group is selected from fluorine, methyl, ethyl, methoxy, tert-butyl, isopropyl.

[0013] R 3 'Selected from one of C1-C7 alkyl (e.g., methyl, ethyl, tert-butyl, isopropyl), C1-C7 alkoxy (e.g., methoxy, ethoxy), and C1-C20 aryl (e.g., phenyl); the aryl group includes unsubstituted or substituted aryl groups, for example, the substituents of the aryl group are selected from fluorine, methyl, ethyl, methoxy, tert-butyl, and isopropyl.'

[0014] R 3 "Selected from one of C1-C7 alkyl (e.g., methyl, ethyl, tert-butyl, isopropyl), C1-C7 alkoxy (e.g., methoxy, ethoxy), and C1-C19 aryl (e.g., phenyl); the aryl group includes unsubstituted or substituted aryl groups, for example, the substituents of the aryl group are selected from fluorine, methyl, ethyl, methoxy, tert-butyl, and isopropyl."

[0015] R 4 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl;

[0016] R 6 It is selected from one of C1 to C6 alkyl groups (e.g., methyl, ethyl, tert-butyl, isopropyl) and C1 to C18 aryl groups (e.g., phenyl); the aryl group includes unsubstituted or substituted aryl groups, for example, the substituents of the aryl group are selected from fluorine, methyl, ethyl, methoxy, tert-butyl, isopropyl.

[0017] As an optional technical solution, the planar chiral boric acid compound is selected from one of Formula 1-1, Formula 1-2, Formula 1-3, Formula 2-1, Formula 2-2, Formula 2-3, Formula 3-1, Formula 4-1, and Formula 5-1;

[0018]

[0019] Optionally, the planar chiral compound is in the R configuration or the S configuration.

[0020] In another aspect, the present invention provides a method for preparing the planar chiral boric acid compound with the cycloaryl skeleton described above, one embodiment of which is prepared by method one; the reaction formula is shown in formula II;

[0021]

[0022] The method is as follows: a mixture containing compounds a and b as shown in Formula II and a solvent undergoes a substitution reaction in an inactive atmosphere to obtain compound c; then compound c undergoes a boron lithiation reaction under conditions of solvent, butyllithium and d to obtain the compound shown in Formula Ia.

[0023] In formula II, R 3 The aryl group is selected from C1 to C8 alkyl groups (e.g., methyl, ethyl, tert-butyl, isopropyl), C1 to C8 alkoxy groups (e.g., methoxy, ethoxy), and C1 to C20 aryl groups (e.g., phenyl); the aryl group includes unsubstituted or substituted aryl groups, for example, the substituents of the aryl group are selected from fluorine, methyl, ethyl, methoxy, tert-butyl, and isopropyl.

[0024] In formula II, R 2 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl.

[0025] In Formula II, X is selected from at least one of iodine, bromine, and chlorine.

[0026] As an optional technical solution, in method one:

[0027] In the reaction formula II, the molar ratio of compound a to compound b is 1:1.1 to 1:3.

[0028] Optionally, the reaction conditions for the substitution reaction are a temperature of 0–70°C and a reaction time of 6–48 hours.

[0029] Optionally, the inactive atmosphere in the substitution reaction is selected from at least one of nitrogen and argon.

[0030] Optionally, the solvent in the substitution reaction is selected from at least one of acetone and tetrahydrofuran.

[0031] Optionally, the substitution reaction is carried out under alkaline conditions, wherein the alkaline is selected from at least one of potassium carbonate and sodium hydride.

[0032] Optionally, the molar ratio of compound a to the base in the reaction formula II is 1:1.1 to 1:5.

[0033] Optionally, the concentration of compound a in the solvent during the substitution reaction is 0.1–5 mol / L.

[0034] As an optional technical solution, in method one:

[0035] In the reaction shown in Formula II, the molar ratio of compound c to compound d is 1:1.1 to 1:1.5;

[0036] The molar ratio of compound c shown in Formula II to the lithium reagent is 1:1 to 1:2, preferably 1:1.5.

[0037] Optionally, the reaction conditions for the lithiation-boron reaction are 0°C to room temperature and 12 to 18 hours.

[0038] Optionally, the lithium reagent in the lithiation-boron reaction is at least one of n-butyllithium, sec-butyllithium, tert-butyllithium, or diisopropylaminolithium.

[0039] Optionally, the lithiation and boronization reaction is carried out in an inactive atmosphere, which is selected from at least one of nitrogen and argon.

[0040] Optionally, the solvent in the lithiation boronization reaction is one of diethyl ether and tetrahydrofuran.

[0041] Optionally, the concentration of compound c in the lithiation boron reaction is 0.1–3 mol / L in the solvent.

[0042] Another implementation method is to prepare it using method two; the reaction formula is shown in formula III.

[0043]

[0044] Method 2 involves a mixture containing compound e and compound d of Formula III, a lithium reagent, N,N,N',N'-tetramethylethylenediamine, and a solvent, which undergoes a boron lithiation reaction in an inactive atmosphere to obtain the compound of Formula Ib.

[0045] In Formula III, R2 is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl.

[0046] As an optional technical solution, in method two:

[0047] The molar ratio of compound e and compound d shown in Formula III is 1:1.1 to 1:1.5.

[0048] The molar ratio of compound e shown in Formula III to the lithium reagent is 1:1.1 to 1:2, preferably 1:1.5;

[0049] The molar ratio of lithium reagent to N,N,N',N'-tetramethylethylenediamine in the lithiation boronization reaction is 1:0.5 to 1:1.5, preferably 1:1.

[0050] Optionally, the lithium reagent in the lithiation-boron reaction is n-butyllithium, sec-butyllithium, tert-butyllithium, or diisopropylaminolithium.

[0051] Optionally, the temperature conditions for the lithiation and boronization reaction are 0°C to room temperature, and the reaction time is 10 to 48 hours.

[0052] Optionally, the lithiation and boronization reaction is carried out in an inactive atmosphere, which is selected from at least one of nitrogen and argon.

[0053] Optionally, the solvent in the lithiation boronization reaction is one of diethyl ether and tetrahydrofuran.

[0054] Optionally, the concentration of e in the solvent of the compound in the lithiation boron reaction is 0.1 to 3 mol / L.

[0055] Another implementation method is to prepare it using method three; the reaction formula is shown in formula IV.

[0056]

[0057] Method 3 involves a mixture containing compound e and compound f (shown in Formula IV) and a solvent undergoing a substitution reaction in an inactive atmosphere to obtain compound g; then, compound g undergoes a lithiation reaction with boron under the conditions of solvent, lithium reagent, and boron reagent d to obtain the compound shown in Formula Ic.

[0058] In formula IV, R 4 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl;

[0059] In formula IV, R 5 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl 2,4,6-tri-Ome;

[0060] In formula IV, R 2 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl.

[0061] As an optional technical solution, in method three:

[0062] In the reaction shown in Formula IV, the molar ratio of compound e to compound f is 1:1.1 to 1:2.

[0063] Optionally, the substitution reaction is carried out under the following conditions: a temperature of 0–30°C and a reaction time of 6–48 hours.

[0064] Optionally, the inactive atmosphere in the substitution reaction is selected from at least one of nitrogen and argon.

[0065] Optionally, the solvent in the substitution reaction is selected from at least one of acetone and tetrahydrofuran.

[0066] Optionally, the substitution reaction is carried out under alkaline conditions, wherein the base is selected from at least one of potassium carbonate, potassium tert-butoxide, and sodium hydride.

[0067] Optionally, the molar ratio of compound e to the base in the reaction shown in Formula IV is 1:1.1 to 1:5.

[0068] Optionally, the concentration of compound e in the solvent during the substitution reaction is 0.1–5 mol / L.

[0069] As an optional technical solution, in method three:

[0070] The molar ratio of compound e to compound d shown in Formula IV is 1:1.1 to 1:1.5;

[0071] The molar ratio of compound e shown in Formula IV to the lithium reagent is 1:1.1 to 1:2, preferably 1:1.5.

[0072] Optionally, the lithium reagent in the lithiation-boron reaction is at least one of n-butyllithium, sec-butyllithium, tert-butyllithium, or diisopropylaminolithium.

[0073] Optionally, the temperature conditions for the lithiation and boronization reaction are 0°C to room temperature, and the reaction time is 10 to 48 hours.

[0074] Optionally, the lithiation and boronization reaction is carried out in an inactive atmosphere, which is selected from at least one of nitrogen and argon.

[0075] Optionally, the solvent in the lithiation boronization reaction is one of diethyl ether and tetrahydrofuran.

[0076] Optionally, the concentration of compound g in the lithiation boron reaction is 0.1–3 mol / L in the solvent.

[0077] Another implementation method is to prepare it using method four; the reaction formula is shown in formula V.

[0078] Method four involves a mixture containing compound h and compound b (shown in formula V) and a solvent undergoing a substitution reaction in an inactive atmosphere to obtain compound i; then, compound i undergoes a lithiation reaction with boron in the presence of a solvent, butyllithium, and boron reagent d to obtain the compound shown in formula Id.

[0079]

[0080] In formula V, R 3 The aryl group is selected from C1 to C7 alkyl groups (e.g., methyl, ethyl, tert-butyl, isopropyl), C1 to C7 alkoxy groups (e.g., methoxy, ethoxy), and C1 to C20 aryl groups (e.g., phenyl); the aryl group includes unsubstituted or substituted aryl groups, for example, the substituents of the aryl group are selected from hydrogen, fluorine, methyl, ethyl, methoxy, tert-butyl, and isopropyl.

[0081] In formula V, R 2 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl.

[0082] In formula V, X is selected from at least one of iodine, bromine, and chlorine.

[0083] As an optional technical solution, in method four:

[0084] In the substitution reaction, the molar ratio of compound h to compound b is 1:1.1 to 1:2.

[0085] Optionally, the reaction conditions for the substitution reaction are a temperature of 0–70°C and a reaction time of 6–48 hours.

[0086] Optionally, the inactive atmosphere in the substitution reaction is selected from at least one of nitrogen and argon.

[0087] Optionally, the solvent in the substitution reaction is selected from at least one of acetone and tetrahydrofuran.

[0088] The substitution reaction is carried out under alkaline conditions, and the base is selected from at least one of potassium carbonate and sodium hydride.

[0089] Optionally, the molar ratio of compound h to base in the reaction formula II is 1:1.1 to 1:5.

[0090] Optionally, the concentration of compound h in the solvent during the substitution reaction is 0.1–5 mol / L.

[0091] As an optional technical solution, in method four:

[0092] In the equation shown in Formula V, the molar ratio of compound i to compound d is 1:1.1 to 1:1.5;

[0093] The molar ratio of compound i (as shown in Formula V) to lithium reagent is 1:1.1 to 1:2, preferably 1:1.5.

[0094] Optionally, the reaction conditions for the lithiation-boron reaction are 0°C to room temperature and 12 to 18 hours.

[0095] Optionally, the lithium reagent in the lithiation-boron reaction is at least one of n-butyllithium, sec-butyllithium, tert-butyllithium, or diisopropylaminolithium.

[0096] Optionally, the lithiation and boronization reaction is carried out in an inactive atmosphere, which is selected from at least one of nitrogen and argon.

[0097] Optionally, the solvent in the lithiation boronization reaction is one of diethyl ether and tetrahydrofuran.

[0098] Optionally, the concentration of compound i in the lithiation boron reaction is 0.1–3 mol / L in the solvent.

[0099] Another implementation method is to prepare it using method five; the reaction formula is shown in formula VI.

[0100] Method 5 involves a mixture containing compound j (shown in formula VI), compound k (shown in formula VI), and a solvent, undergoing a substitution reaction a in an inactive atmosphere to obtain compound l; then, a mixture of compound l, compound b, and a solvent undergoes a substitution reaction b in an inactive atmosphere to obtain compound m; finally, compound m undergoes a lithiation-boronization reaction under conditions of solvent, lithium reagent, and boron reagent d to obtain the compound shown in formula Ie.

[0101]

[0102] In formula VI, R 6 The aryl group is selected from C1 to C6 alkyl groups (e.g., methyl, ethyl, tert-butyl, isopropyl) and C1 to C18 aryl groups (e.g., phenyl); the aryl group includes unsubstituted or substituted aryl groups, for example, the substituents of the aryl group are selected from fluorine, methyl, ethyl, methoxy, tert-butyl, isopropyl.

[0103] In formula VI, R 2 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl;

[0104] In formula VI, R 3 "Selected from C1 to C7 alkyl groups (e.g., methyl, ethyl, tert-butyl, isopropyl), C1 to C7 alkoxy groups (e.g., methoxy, ethoxy), and C1 to C20 aryl groups (e.g., phenyl); the aryl group includes unsubstituted or substituted aryl groups, for example, the substituents of the aryl group are selected from fluorine, methyl, ethyl, methoxy, tert-butyl, and isopropyl."

[0105] In Formula VI, X is selected from at least one of iodine, bromine, and chlorine.

[0106] As an optional technical solution, in method five:

[0107] In the reaction shown in Formula VI, the molar ratio of compound j to compound k is 1:1.1 to 1:2;

[0108] Optionally, the reaction conditions for the substitution reaction a are a temperature of 0–70°C and a reaction time of 6–48 hours.

[0109] Optionally, the inactive atmosphere in the substitution reaction a is selected from at least one of nitrogen and argon.

[0110] Optionally, the solvent in the substitution reaction a is selected from at least one of acetone and tetrahydrofuran.

[0111] The substitution reaction is carried out under alkaline conditions, and the base is selected from at least one of potassium carbonate and sodium hydride.

[0112] Optionally, the molar ratio of compound i to base in the reaction formula shown in Formula VI is 1:1.1 to 1:5;

[0113] Optionally, the concentration of compound j in the substitution reaction in the solvent is 0.1–5 mol / L.

[0114] As an optional technical solution, in method five:

[0115] In the reaction shown in Formula VI, the molar ratio of compound 1 to compound b is 1:1.1 to 1:2.

[0116] Optionally, the reaction conditions for the substitution reaction b are a temperature of 0–70°C and a reaction time of 6–48 hours.

[0117] Optionally, the inactive atmosphere in the substitution reaction b is selected from at least one of nitrogen and argon.

[0118] Optionally, the solvent in the substitution reaction b is selected from at least one of tetrahydrofuran, N,N-dimethylformamide, and diethyl ether.

[0119] Optionally, the concentration of compound 1 in the solvent during the substitution reaction is 0.1–5 mol / L.

[0120] As an optional technical solution, in method five:

[0121] In the reaction shown in Formula VI, the molar ratio of compound m to compound d is 1:1.1 to 1:1.5;

[0122] The molar ratio of compound m shown in Formula VI to the lithium reagent is 1:1.1 to 1:2, preferably 1:1.5.

[0123] Optionally, the reaction conditions for the lithiation-boron reaction are 0°C to room temperature and 12 to 18 hours.

[0124] Optionally, the lithium reagent in the lithiation-boron reaction is at least one of n-butyllithium, sec-butyllithium, tert-butyllithium, or diisopropylaminolithium.

[0125] Optionally, the lithiation and boronization reaction is carried out in an inactive atmosphere, which is selected from at least one of nitrogen and argon.

[0126] Optionally, the solvent in the lithiation boronization reaction is one of diethyl ether and tetrahydrofuran.

[0127] Optionally, the concentration of compound m in the lithiation boron reaction is 0.1–3 mol / L in the solvent.

[0128] In another aspect, the present invention also provides the application of at least one of the chiral cycloaryl skeletal boronic acid compounds described above and the chiral cycloaryl skeletal boronic acid compounds prepared by the above preparation method as a catalyst in the desymmetrization reaction of diols. A mixture containing 2-substituted-1,3-propanediol, benzyl chloride, a base, potassium iodide, a boric acid catalyst, and a solvent undergoes a substitution reaction in an inactive atmosphere to obtain the desymmetrized compound.

[0129] The structure of the 2-aryl-1,3-propanediol is as follows: R 7 It is selected from one of phenyl, substituted phenyl (the substituent of the substituted phenyl is selected from methyl, ethyl, methoxy, fluorine, chlorine, bromine, iodine, phenyl, nitro, ester, trifluoromethyl, tert-butyl, isopropyl), thiophene, indole, methyl, methoxy, and trifluoromethyl;

[0130] The structure of the benzyl chloride is as follows: R 8 Selected from one of H, phenyl, methyl, ethyl, methoxy, fluorine, chlorine, bromine, ester, nitro, and trifluoromethyl;

[0131] The product of the desymmetry reaction is

[0132] Optionally, the solvent for the asymmetric addition reaction is at least one of acetonitrile, acetone, butanone, and N,N-dimethylformamide.

[0133] Optionally, the molar concentration of the 2-substituted-1,3-propanediol in the solvent is 0.05 to 0.5 mol / L.

[0134] Optionally, the molar ratio of the 2-substituted-1,3-propanediol to benzyl chloride is 1:1 to 1:2.

[0135] Optionally, the molar ratio of the boric acid catalyst to 2-substituted-1,3-propanediol is 0.05:1 to 0.20:1, preferably 0.10:1.

[0136] Optionally, the alkali is selected from at least one of potassium carbonate, anhydrous potassium phosphate, potassium phosphate trihydrate, and cesium carbonate.

[0137] Optionally, the molar ratio of the 2-substituted-1,3-propanediol to the base is 1:1 to 1:2, preferably 1:1 to 1:1.7.

[0138] Optionally, the molar ratio of potassium iodide to 2-substituted-1,3-propanediol is 0.1:1 to 2:1, preferably 1:1.

[0139] Optionally, the reaction temperature of the asymmetric addition reaction is 10 to 30°C; the temperature is selected from any value of 10°C, 30°C, or any value between any two of the above.

[0140] Optionally, the reaction time is 36 to 72 hours; the time is selected from any value among 36 hours, 48 ​​hours, and 72 hours or any value between any two of the above.

[0141] The beneficial effects that this application can produce include:

[0142] 1) This invention can effectively synthesize a new type of chiral cycloaryl skeletal boric acid compound with a short synthetic route and can obtain the target compound with a high yield (up to 70%).

[0143] 2) The chiral cycloaryl skeleton boronic acid compound synthesized in this invention can be applied to the desymmetry reaction of diols and has excellent catalytic activity and enantioselective control ability. Detailed Implementation

[0144] The present application is described in detail below with reference to the embodiments, but the present application is not limited to these embodiments.

[0145] This invention provides a class of chiral chiral cycloaryl skeletal boronic acid compounds, which may be racemic or optically active. The structural formula of the chiral cycloaryl skeletal boronic acid compound is as follows: [Structure of compound I]

[0146]

[0147] in:

[0148] R 1 It is selected from one of C1-C8 alkyl groups (e.g., methyl, ethyl, tert-butyl), C1-C8 alkoxy groups (e.g., methoxy, ethoxy), and C1-C20 aryloxy groups (e.g., phenyl groups bonded to oxygen); the aryloxy group includes unsubstituted or substituted aryloxy groups, for example, the substituents of the aryloxy group are selected from hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, isopropyl;

[0149] R 2 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl.

[0150] The present invention provides a design and synthesis method for a class of chiral cycloaryl skeletal boronic acid compounds, the synthetic route of which is as follows:

[0151]

[0152] R 2 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl;

[0153] R 3 It is selected from one of C1 to C8 alkyl groups (e.g., methyl, ethyl, tert-butyl, isopropyl), C1 to C8 alkoxy groups (e.g., methoxy, ethoxy), and C1 to C20 aryl groups (e.g., phenyl); the aryl group includes unsubstituted or substituted aryl groups, for example, the substituents of the aryl group are selected from hydrogen, fluorine, methyl, ethyl, methoxy, tert-butyl, and isopropyl.

[0154] R 3 'Selected from one of C1-C7 alkyl (e.g., methyl, ethyl, tert-butyl, isopropyl), C1-C7 alkoxy (e.g., methoxy, ethoxy), and C1-C20 aryl (e.g., phenyl); the aryl group includes unsubstituted or substituted aryl groups, for example, the substituents of the aryl group are selected from fluorine, methyl, ethyl, methoxy, tert-butyl, and isopropyl.'

[0155] R 3 "Selected from one of C1-C7 alkyl (e.g., methyl, ethyl, tert-butyl, isopropyl), C1-C7 alkoxy (e.g., methoxy, ethoxy), and C1-C20 aryl (e.g., phenyl); the aryl group includes unsubstituted or substituted aryl groups, for example, the substituents of the aryl group are selected from fluorine, methyl, ethyl, methoxy, tert-butyl, and isopropyl."

[0156] R 4 Selected from hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl;

[0157] R 5 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, isopropyl, and 2,4,6-tri-Ome;

[0158] R 6It is selected from one of C1 to C6 alkyl groups (e.g., methyl, ethyl, tert-butyl, isopropyl) and C1 to C18 aryl groups (e.g., phenyl); the aryl group includes unsubstituted or substituted aryl groups, for example, the substituents of the aryl group are selected from fluorine, methyl, ethyl, methoxy, tert-butyl, isopropyl.

[0159] The reaction steps are as follows:

[0160] Method 1: Includes one-step substitution reaction and one-step lithiation with boron.

[0161] Step 1 Substitution reaction

[0162] Under nitrogen protection, at 0°C, compounds a and b, potassium carbonate, and solvent were added to a Schlenk flask. The mixture was stirred at 70°C and reacted for 6–48 hours to obtain compound c.

[0163] Step 2: Lithification with Boron

[0164] Under nitrogen protection, at 0°C, compound c, solvent, and n-butyllithium were added to the reaction flask. The reaction was carried out at 0°C for 60 minutes. Then, compound d was added, and the reaction was carried out at room temperature for 12-18 hours to obtain a chiral cycloaryl skeletal boric acid compound (the compound shown in formula Ia).

[0165] Method 2: Includes a one-step lithiation and boron-addition reaction

[0166] Under nitrogen protection, at 0°C, compound e, solvent, n-butyllithium, and N,N,N',N'-tetramethylethylenediamine were added to the reaction flask. The reaction was carried out at 0°C for 3 hours. Then, compound d was added, and the reaction was carried out for 10-48 hours to obtain a chiral cycloarane skeleton boric acid compound (the compound shown in formula Ib).

[0167] Method 3: Includes one-step substitution reaction and one-step lithiation with boron.

[0168] Step 1 Substitution reaction

[0169] Under nitrogen protection, at 0°C, compounds e and f, potassium tert-butoxide, and solvent were added to a Schlenk flask. The mixture was stirred at room temperature for 6–48 hours to obtain compound g.

[0170] Step 2: Lithification with Boron

[0171] Under nitrogen protection, at 0°C, compound g, solvent, and n-butyllithium were added to the reaction flask. The reaction was carried out at 0°C for 60 minutes. Then, compound d was added, and the reaction was carried out for 10-48 hours to obtain a chiral cycloaryl skeleton boric acid compound (the compound shown in formula Ic).

[0172] Method 4: Includes one-step substitution reaction and one-step lithiation with boron.

[0173] Step 1 Substitution reaction

[0174] Under nitrogen protection, at 0°C, compound h, sodium hydride, and solvent were added to a Schlenk flask. After stirring at room temperature for 60 minutes, compound b was added, and the reaction was carried out for 6–48 hours to obtain compound i.

[0175] Step 2: Lithification with Boron

[0176] Under nitrogen protection, at 0°C, compound i, solvent, and n-butyllithium were added to the reaction flask. The reaction was carried out at 0°C for 60 minutes. Then, compound d was added, and the reaction was carried out for 10-48 hours to obtain a chiral cycloaryl skeleton boric acid compound (the compound shown in formula Id).

[0177] Method 5: Includes a two-step substitution reaction and a one-step lithiation and boron addition reaction.

[0178] Step 1 Substitution reaction

[0179] Under nitrogen protection and at 0°C, compound j and solvent were added to a Schlenk flask, and compound k was added dropwise. The mixture was stirred at room temperature for 6–48 hours to obtain compound l.

[0180] Step 2 Substitution Reaction

[0181] Under nitrogen protection and at 0°C, compound l, sodium hydride, and solvent were added to a Schlenk flask. After stirring at room temperature for 30 minutes, compound b was added, and the reaction was carried out for 6–48 hours to obtain compound m.

[0182] Step 2: Lithification with Boron

[0183] Under nitrogen protection, at 0°C, compound m, solvent, and n-butyllithium were added to the reaction flask. The reaction was carried out at 0°C for 60 minutes. Then, compound d was added, and the reaction was carried out for 10-48 hours to obtain a chiral cycloaryl skeleton boric acid compound (the compound shown in formula Ie).

[0184] Unless otherwise specified, all raw materials used in the embodiments of this invention were purchased commercially. Compound a1 in the following embodiments was prepared according to the synthetic methods described in the following literature: Wack, H.; France, S.; Hafez, AM; Drury III, WJ; Weatherwax, A.; Lecka, T. J. J. G. Chem. 2004, 69, 4531-4533; Compound e1 was prepared according to the synthetic methods described in the following literature: Polat, E.; Turbedaroglu, O.; Cakici, M. Tetrahedron Lett. 2021, 67, 152871. Compounds h1 and j1 were prepared according to the synthetic methods described in the following literature: Zhu, Z.-H.; Ding, Y.-X.; Wu, B.; Zhou, Y.-G. Chem. Sci. 2020, 11, 10220-10224.

[0185] The analysis method in the embodiments of the present invention is as follows:

[0186] 1H NMR spectrum 1 H-NMR was measured on a Bruker 400MHz nuclear magnetic resonance spectrometer.

[0187] The ee value in this embodiment of the invention was determined using an Agilent LC 1100 liquid chromatograph.

[0188] Example 1: Synthesis of compound formula I-1

[0189]

[0190] Under nitrogen protection, compound a1 (1.389 g, 3.9 mmol), potassium carbonate (2.695 g, 19.5 mmol), and 30 mL of acetone were added to a 100 mL reaction flask. The reaction was carried out at 70 °C for 30 minutes. Iodomethane b1 (1.391 g, 9.8 mmol) was then added, and the reaction was continued for 48 hours. The reaction was quenched with 10 mL of water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 1.332 g of a white solid, which was compound c1, in 94% yield. Subsequently, compound c1 (1.389 g, 3.9 mmol) was added to a 50 mL reaction flask under nitrogen protection, followed by 10 mL of anhydrous diethyl ether. Then, n-butyllithium (1.9 mL, 3.1 mmol) was added at 0 °C and stirred for 1 hour. 4-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl)fluorobenzene d1 (0.66 mL, 3.1 mmol) was added. After reacting at room temperature for 18 hours, 10 mL of saturated ammonium chloride solution was added and stirred for 30 minutes. The mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 0.426 g of a white solid, compound I-1, in 46% yield.1 H NMR (400MHz, CDCl3) δ7.96-7.67(m,3H),7.15-6.98(m,2H),6.94-6.86(m,1H),6.68-6. 38(m,5H),3.68-3.55(m,3H),3.38-3.30(m,1H),3.20-3.04(m,2H),2.99-2.63(m,5H). 13 C NMR (100MHz, CDCl3) δ165.2(d,J=250.6Hz),163.4,149.0,140.0,139.2,138.1,137.4(d,J=8.1H z),133.4,132.8,132.0,130.7,130.6,128.5,114.8(d,J=20.0Hz),61.8,37.3,35.7,34.6,31.5. 19 F NMR (376MHz, CDCl3) δ -108.92. 11 B NMR(128MHz,CDCl3)δ44.8(brs).HRMS(ESI)m / z:[M+H] + Calcdfor C 23 H 24 BFO2361.1774; Found:361.1793.

[0191] Example 2: Synthesis of compound formula I-2

[0192]

[0193] Under nitrogen protection, compound a1 (1.401 g, 4 mmol), potassium carbonate (2.764 g, 20 mmol), and 30 mL of acetone were added to a 100 mL reaction flask. The reaction was carried out at 70 °C for 30 minutes. Then, 2-methoxyethoxymethyl chloride b2 (1.142 mL, 10 mmol) was added, and the reaction was allowed to proceed for 18 hours. After adding 10 mL of water, the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 1.581 g of a white solid, which was compound c2, in 90% yield. Subsequently, compound C2 (1.139 g, 2.6 mmol) was added to a 50 mL reaction flask under nitrogen protection, followed by 10 mL of anhydrous diethyl ether. Then, n-butyllithium (2.4 mL, 3.9 mmol) was added at 0 °C. After stirring for 1 hour, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl)fluorobenzene D1 (0.83 mL, 3.9 mmol) was added. After reacting at 0 °C for 18 hours, 10 mL of saturated ammonium chloride solution was added and stirred for 30 minutes. The mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 0.793 g of a white solid, compound I-2, in 70% yield. 1 H NMR (400MHz, CDCl3) δ7.89-7.75(m,2H),7.11-6.96(m,3H),6.92-6.87(m,1H),6.63-6.47(m,5H),5.05(d,J=6 .2Hz,1H),4.87(d,J=6.2Hz,1H),3.67-3.57(m,2H),3.32-3.04(m,8H),2.99-2.93(m,1H),2.90-2.70(m,4H). 13 C NMR (100MHz, CDCl3) δ165.3 (d, J = 251.0Hz), 159.2, 147.6, 140.1, 139.3, 137.9, 137.6 (d, J = 8.2Hz), 133.4 ,133.1,131.5,130.8,130.5,128.5,114.8(d,J=20.0Hz),99.4,71.5,69.3,59.0,37.0,35.6,34.5,32.1. 19 F NMR (376MHz, CDCl3) δ -108.61. 11 B NMR(128MHz,CDCl3)δ44.7(brs).HRMS(ESI)m / z:[M+H] + Calcd forC 26 H 29 BFO4435.2142; Found:435.2166.

[0194] Example 3: Synthesis of compound formula I-3

[0195]

[0196] Under nitrogen protection, compound a1 (0.700 g, 2 mmol), potassium carbonate (1.382 g, 10 mmol), and 10 mL of acetone were added to a 100 mL reaction flask. The reaction was carried out at 0 °C for 30 minutes. Then, compound b3 (0.59 mL, 5 mmol) was added, and the reaction was carried out at room temperature for 8 hours. After adding 10 mL of water, the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 0.713 g of a yellow solid, which was compound c3, in 81% yield. Subsequently, compound C3 (0.881 g, 2 mmol) was added to a 50 mL reaction flask under nitrogen protection, followed by 10 mL of anhydrous diethyl ether. Then, n-butyllithium (1.2 mL, 3 mmol) was added at 0 °C. After stirring for 1 hour, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl)fluorobenzene D1 (0.63 mL, 3 mmol) was added. After reacting at 0 °C for 18 hours, 10 mL of saturated ammonium chloride solution was added and stirred for 30 minutes. The mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 0.546 g of a white solid, compound I-3, with a yield of 63%. 1 H NMR (400MHz, CDCl3) δ7.82-7.71(m,2H),7.65-7.58(m,1H),7.35-7.22(m,5H),7.09-6.99(m,2H),6.95-6.88(m,1H),6.67-6.4 5(m,5H),4.78(dd,J=11.2,1.8Hz,1H),4.57(dd,J=11.1,1.9Hz,1H),3.44-3.36(m,1H),3.23-3.06(m,2H),2.99-2.64(m,5H). 13 C NMR (100MHz, CDCl3) δ165.1(d,J=250.3Hz),161.4,148.6,140.0,139.2,137.9,137.4(d,J=8.1Hz),136.7,1 33.4,132.9,131.9,131.1,130.8,128.7,128.6,128.5,128.3,114.7(d,J=19.9Hz),37.2,35.7,34.7,31.8. 19 F NMR (376MHz, CDCl3) δ-109.02. 11 B NMR(128MHz,CDCl3)δ46.4(brs).HRMS(ESI)m / z:[M+H] +Calcdfor C 29 H 27 BFO2437.2088; Found:437.2092.

[0197] Example 4: Synthesis of Compound II-1

[0198]

[0199] Under nitrogen protection, compound e1 (1.073 g, 4 mmol) was added to a 100 mL reaction flask, followed by 15 mL of anhydrous diethyl ether. Then, n-butyllithium (5 mL, 8 mmol) and N,N,N',N'-tetramethylethylenediamine (1.2 mL, 8 mmol) were added at 0 °C. After stirring for 3 hours, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)fluorobenzene d1 (1.3 mL, 6 mmol) was added. After reacting at 0 °C for 18 hours, 10 mL of saturated ammonium chloride solution was added and stirred for 30 minutes. The mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 0.967 g of a white solid, compound II-1, in 61% yield. 1 H NMR (400MHz, CDCl3) δ7.87-7.78(m,2H),7.08-6.99(m,3H),6.93-6.88(m,1H),6.62-6.49(m,5H),4.93(d,J=6 .0Hz,1H),4.79(d,J=5.9Hz,1H),3.36-3.26(m,4H),3.20-3.05(m,2H),3.00-2.93(m,1H),2.90-2.71(m,4H). 13 C NMR (100MHz, CDCl3) δ165.33 (d, J = 251.0Hz), 159.3, 147.8, 140.2, 139.4, 137.8, 137.6 (d, J = 8.1Hz), 133.4,131.6,130.8,130.6,128.6,128.6,114.9(d,J=20.0Hz),100.3,57.8,37.0,35.6,34.6,32.1. 19 F NMR (376MHz, CDCl3) δ -108.72. 11 BNMR(128MHz,CDCl3)46.4(brs).HRMS(ESI)m / z:[M+H] + Calcd for C 24 H 25 BFO2391.1880; Found:391.1873.

[0200] Example 5: Synthesis of Compound II-2

[0201]

[0202] Under nitrogen protection, compound e1 (0.537 g, 2 mmol) was added to a 100 mL reaction flask, followed by 7 mL of anhydrous diethyl ether. Then, n-butyllithium (1.1 mL, 2.6 mmol) and N,N,N',N'-tetramethylethylenediamine (0.39 mL, 2.6 mmol) were added at 0 °C. After stirring for 3 hours, (4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)benzene d2 (0.531 g, 2.6 mmol) was added. After reacting at room temperature for 18 hours, 10 mL of saturated ammonium chloride solution was added and stirred for 30 minutes. The mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 0.412 g of a white solid, compound II-2, in 55% yield. 1 H NMR (400MHz, CDCl3) δ7.93-7.71(m,2H),7.53-7.43(m,1H),7.42-7.31(m,2H),7.14(s,1H),6.97-6.89(m,1H),6.68-6.47(m,5H),4.95 (d,J=5.9Hz,1H),4.80(d,J=5.9Hz,1H),3.42-3.24(m,4H),3.22-3.06(m,2H),3.00-2.93(m,1H),2.90-2.82(m,2H),2.82-2.72(m,2H). 13 C NMR (100MHz, CDCl3) δ159.3,148.1,140.1,139.4,137.7,135.1,133.4,133.1, 131.7,131.3,130.7,130.5,128.6,127.8,100.3,57.8,37.1,35.6,34.6,32.1. 11 B NMR(128MHz,CDCl3)45.9(brs).HRMS(ESI)m / z:[M+H] + Calcd for C 24 H 26 BO3373.1974; Found:373.2001.

[0203] Example 6: Synthesis of Compound II-3

[0204]

[0205] Under nitrogen protection, compound e1 (0.537 g, 2 mmol) was added to a 100 mL reaction flask, followed by 7 mL of anhydrous diethyl ether. Then, n-butyllithium (1.1 mL, 2.6 mmol) and N,N,N',N'-tetramethylethylenediamine (0.39 mL, 2.6 mmol) were added at 0 °C. After stirring for 3 hours, pinacol 4-methoxyphenylboronic acid ester d3 (0.609 g, 2.6 mmol) was added. The reaction was carried out at room temperature for 18 hours, followed by stirring in 10 mL of saturated ammonium chloride solution for 30 minutes. The mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 0.496 g of a white solid, compound II-3, in 62% yield. 1 H NMR (400MHz, CDCl3) δ7.86-7.71(m,2H),6.94-6.83(m,4H),6.63-6.49(m,5H),4.91(d,J=5.9Hz,1H),4.79 (d,J=6.0Hz,1H),3.84(s,3H),3.37-3.27(m,4H),3.21-3.05(m,2H),3.00-2.86(m,3H),2.81-2.71(m,2H). 13 CNMR (100MHz, CDCl3) δ162.4,159.1,147.8,140.1,139.4,137.5,137.3,133.3,13 3.1,131.6,130.6,130.5,128.6,113.3,100.2,57.8,55.2,37.0,35.6,34.6,32.1. 11 B NMR(128MHz,CDCl3)45.1(brs).HRMS(ESI)m / z:[M+H] + Calcd for C 25 H 28 BO4403.2080; Found: 403.2096.

[0206] Example 7: Synthesis of Compound III-1

[0207]

[0208] Under nitrogen protection, compound a1 (1.761 g, 5 mmol), potassium tert-butoxide (0.617 g, 55.5 mmol), and 20 mL of tetrahydrofuran were added to a 100 mL reaction flask. The reaction was carried out at 0 °C for 30 min, followed by the addition of compound f1 (2.581 g, 6 mmol) and the reaction was continued at room temperature for 10 h. After adding 10 mL of water, the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 1.213 g of a yellow solid, compound g1, in 57% yield. Subsequently, compound g1 (0.881 g, 2 mmol) was added to a 50 mL reaction flask under nitrogen protection, followed by 5 mL of anhydrous diethyl ether. Then, n-butyllithium (0.74 mL, 1.2 mmol) was added at 0 °C. After stirring for 1 hour, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)fluorobenzene d1 (0.25 mL, 1.2 mmol) was added. After reacting at 0 °C for 18 hours, 10 mL of saturated ammonium chloride solution was added and stirred for 30 minutes. The mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 0.065 g of a white solid, compound III-1, in 20% yield. 1 H NMR (400MHz, CDCl3) δ7.80-7.71(m,2H),7.18-7.08(m,4H),7.02-6.95(m,2H),6.93-6.87(m,1H),6.82-6. 74(m,2H),6.69-6.58(m,4H),6.56-6.51(m,1H),3.16-3.07(m,2H),3.04-2.76(m,5H),2.62-2.54(m,1H). 13 C NMR (100MHz, CDCl3) δ165.3(d,J=251.0Hz),157.9,156.1,148.7,140.1,139.3,138.2,137.5(d,J=8.3Hz),1 33.6,133.3,131.9,131.5,131.3,129.6,128.5,122.1,115.7,114.8(d,J=20.0Hz),37.1,35.6,34.3,32.0. 19 F NMR (376MHz, CDCl3) δ -108.53. 11 BNMR(128MHz,CDCl3)δ47.0(brs).HRMS(ESI)m / z:[M+H] + Calcd for C 28 H 25 BFO2423.1931; Found:423.1936.

[0209] Example 8: Synthesis of compound IV-1

[0210]

[0211] Under nitrogen protection, compound h1 (1.093 g, 3 mmol), sodium hydride (0.180 g, 4.5 mmol), and 10 mL of tetrahydrofuran were added to a 100 mL reaction flask. The reaction was carried out at 0 °C for 60 min. Then, compound b1 (0.28 mL, 4.5 mmol) was added, and the reaction was carried out at room temperature for 16 h. After adding 10 mL of water, the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 0.942 g of a white solid, which was compound i1, in 83% yield. Subsequently, compound i1 (0.942 g, 2.4 mmol) was added to a 50 mL reaction flask under nitrogen protection, followed by 10 mL of anhydrous diethyl ether. Then, n-butyllithium (2.2 mL, 3.6 mmol) was added at 0 °C. After stirring for 1 hour, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaboron-2-yl)fluorobenzene d1 (0.76 mL, 3.6 mmol) was added. The reaction was carried out at room temperature for 16 hours, followed by the addition of 10 mL of saturated ammonium chloride solution and stirring for 30 minutes. The mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 0.257 g of a white solid, compound IV-1, with a yield of 29%. 1 H NMR (400MHz, CDCl3) δ7.63-7.29(m,2H),7.07-6.85(m,2H),6.75-6.42(m,6H),4.83(s,1H),4.49(q,J=11.2Hz,2H),3.35(s,3H),3.17-2.92(m,8H). 13 C NMR (100MHz, CDCl3) δ163.8 (d, J = 247.2Hz), 142.9, 140.2, 139.2, 138.1, 135.1 (d, J = 7.7Hz), 134.5, 134.3, 133.5, 133.3, 132.9, 131.2, 128.8, 114.4 (d, J = 19.6Hz), 74.2, 57.3, 35.6, 35.1, 34.5, 32.4. 19 F NMR (376MHz, CDCl3) δ -112.56. 11 B NMR(128MHz,CDCl3)δ32.89(brs).HRMS(ESI)m / z:[M+H] + CalcdforC 24 H 25 BFO2375.1930; Found:375.1925.

[0212] Example 9: Synthesis of compound IV-2

[0213]

[0214] Under nitrogen protection, compound J1 (1.448 g, 4 mmol), 10 mL of tetrahydrofuran, and compound K1 (2.67 mL, 8 mmol) were added dropwise to a 100 mL reaction flask at 0 °C. The reaction was carried out at room temperature for 16 hours. The pH was adjusted to 6 with 1 N hydrochloric acid, 10 mL of water was added, and the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Column chromatography yielded 0.678 g of a white solid, compound L1, in a 45% yield. Under nitrogen protection, compound L1 (0.678 g, 1.8 mmol), sodium hydride (0.204 g, 5.1 mmol), and 15 mL of tetrahydrofuran were added to a 100 mL reaction flask. The reaction was carried out at 0 °C for 30 minutes, and compound B1 (0.53 mL, 8.5 mmol) was added. The reaction was carried out at 70 °C for 2 hours. 10 mL of water was added, and the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and subjected to column chromatography under reduced pressure to obtain 0.653 g of a white solid, which was compound m1, with a yield of 98%. Subsequently, compound m1 (0.653 g, 1.6 mmol) was added to a 50 mL reaction flask under nitrogen protection, followed by 10 mL of tetrahydrofuran. Then, 1.5 mL of n-butyllithium (2.4 mmol) was added at 0 °C, and the mixture was stirred for 1 hour. Then, 0.51 mL of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)fluorobenzene d1 (2.4 mmol) was added. The mixture was reacted at 0 °C for 16 hours, followed by the addition of 10 mL of saturated ammonium chloride solution and stirring for 30 minutes. The mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and subjected to column chromatography under reduced pressure to obtain 0.221 g of a white solid, which was compound IV-2, with a yield of 36%. 1 H NMR (400MHz, CDCl3) δ7.51-7.38(m,2H),7.00-6.88(m,2H),6.71-6.63(m,2H),6.54-6.49(m,1H),6 .46-6.34(m,3H),4.66(q,J=6.6Hz,1H),3.69(brs,1H),3.22-2.78(m,11H),1.94(d,J=6.6Hz,3H). 13 C NMR (100MHz, CDCl3) δ163.5 (d, J = 246.3Hz), 143.0, 140.6, 140.3, 138.7, 135.3, 135.0 (d, J = 7.5Hz) ,133.2,133.1,132.9,131.7,131.1,114.3(d,J=19.6Hz),81.7,54.9,35.5,35.4,34.6,33.0,21.7.19 F NMR (376MHz, CDCl3) δ -113.55. 11 B NMR(128MHz,CDCl3)δ30.24(brs).HRMS(ESI)m / z:[M+H] + Calcd forC 24 H 25 BFO2389.2087; Found:389.2094.

[0215] Application Example 1: Desymmetry reaction of diols

[0216]

[0217] Under nitrogen protection, compound II-1 (3.9 mg, 0.01 mmol), compound 4 (15.2 mg, 0.1 mmol), compound 5 (19.0 mg, 0.15 mmol), potassium carbonate (23.5 mg, 0.17 mmol), and potassium iodide (16.6 mg, 0.1 mmol) prepared in Example 4 were dissolved in 1.0 mL of acetonitrile and stirred at 30 °C in the dark for 48 hours. The solvent was removed under reduced pressure, and column chromatography was used to obtain compound 6, a white solid, 23.0 mg, yield 95%, 83.6% ee. 1 H NMR (400MHz, CDCl3) δ7.40-7.15(m,10H),4.54(s,2H),4.06-3.93(m,1H),3.92-3.73(m,3H),3.26-3.14(m,1H),2.50(t,J=5.2Hz,1H). 13 C10 NMR (100MHz, CDCl3) δ 139.7, 137.9, 128.8, 128.6, 128.1, 127.9, 127.8, 127.2, 73.7, 73.6, 66.6, 47.9. HPLC: Chiralcel OJ-H column, 210nm, 30℃, n-hexane / isopropanol = 60 / 40, flow rate = 0.7mL / min, retention time 10.1min (main peak) and 11.7min.

[0218] The above description is merely a few embodiments of this application and is not intended to limit this application in any way. Although this application discloses preferred embodiments as described above, it is not intended to limit this application. Any changes or modifications made by those skilled in the art without departing from the scope of the technical solution of this application using the disclosed technical content are equivalent to equivalent implementation cases and fall within the scope of the technical solution.

Claims

1. A class of planar chiral boric acid compounds, characterized in that, The planar chiral boric acid compound has the structure shown in Formula I. In Formula I: R 1 Selected from one of C1-C8 alkyl, C1-C8 alkoxy, and C1-C20 aryloxy groups; R 2 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl. Preferably, the planar chiral boric acid compound has a structure shown in formula Ia, Ib, Ic, Id, or Ie. R 3 It is selected from one of C1-C8 alkyl, C1-C8 alkoxy, and C1-C20 aryl groups; R 3 'Selected from one of C1-C7 alkyl, C1-C7 alkoxy, and C1-C19 aryl; R 3 "Selected from one of C1-C7 alkyl, C1-C7 alkoxy, and C1-C19 aryl; R 4 It is selected from one of hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, and isopropyl; R 6 It is selected from one of the C1-C6 alkyl groups and the C1-C18 aryl groups.

2. The planar chiral compound according to claim 1, characterized in that, The planar chiral boric acid compound is selected from one of Formula 1-1, Formula 1-2, Formula 1-3, Formula 2-1, Formula 2-2, Formula 2-3, Formula 3-1, Formula 4-1, and Formula 5-1; Preferably, the planar chiral compound is in the R configuration or the S configuration.

3. The method for preparing the planar chiral boric acid compound according to claim 1 or 2, characterized in that, Prepared using Method 1; the reaction formula is shown in Formula II; The method is as follows: a mixture containing compounds a and b as shown in Formula II and a solvent undergoes a substitution reaction in an inactive atmosphere to obtain compound c; then compound c undergoes a lithiation and boronization reaction under the conditions of solvent, lithium reagent and boron reagent d to obtain the compound shown in Formula Ia. In formula II, R 2 The definition is the same as that in claim 1; In Formula II, R4 is defined as in claim 1; In Formula II, X is selected from at least one of iodine, bromine, and chlorine.

4. The preparation method according to claim 3, characterized in that, In method one: The molar ratio of compound a to compound b in the reaction formula II is 1:1.1 to 1:3; the reaction conditions for the substitution reaction are: temperature 0 to 70°C and time 6 to 48 hours. The inactive atmosphere in the substitution reaction is selected from at least one of nitrogen and argon. The solvent in the substitution reaction is selected from at least one of acetone and tetrahydrofuran; The substitution reaction is carried out under alkaline conditions, and the base is selected from at least one of potassium carbonate and sodium hydride. In the reaction shown in Formula II, the molar ratio of compound a to the base is 1:1.1 to 1:5; In the reaction shown in Formula II, the molar ratio of compound c to compound d is 1:1.1 to 1:1.5; The molar ratio of compound c shown in Formula II to the lithium reagent is 1:1.1 to 1:2; The reaction conditions for the lithiation and boronization reaction are: temperature from 0°C to room temperature, and time from 12 to 18 hours. The lithium reagent in the lithiation boronization reaction is at least one of n-butyllithium, sec-butyllithium, tert-butyllithium or diisopropylaminolithium; The lithiation and boronization reaction is carried out in an inactive atmosphere, which is selected from at least one of nitrogen and argon. The solvent in the lithiation boronization reaction is either diethyl ether or tetrahydrofuran.

5. The method for preparing the planar chiral compound according to claim 1 or 2, characterized in that, Prepared using method two; the reaction formula is shown in formula III; Method 2 involves a mixture containing compound e and compound d of Formula III, a lithium reagent, N,N,N',N'-tetramethylethylenediamine, and a solvent, which undergoes a boron lithiation reaction in an inactive atmosphere to obtain the compound of Formula Ib. In Formula III, R 2 The definition is the same as in claim 1.

6. The preparation method according to claim 5, characterized in that, In method two: The molar ratio of compound e to compound d shown in Formula III is 1:1.1 to 1:1.5; The molar ratio of compound e shown in Formula III to the lithium reagent is 1:1.1 to 1:2; The molar ratio of lithium reagent to N,N,N',N'-tetramethylethylenediamine in the lithiation boronization reaction is 1:0.5 to 1:1.5; The lithium reagent in the lithiation boronization reaction is at least one of n-butyllithium, sec-butyllithium, tert-butyllithium or diisopropylaminolithium; The conditions for the lithiation and boronization reaction are: temperature from 0°C to room temperature, and time from 10 to 48 hours. The lithiation and boronization reaction is carried out in an inactive atmosphere, which is selected from at least one of nitrogen and argon. The solvent in the lithiation boronization reaction is either diethyl ether or tetrahydrofuran.

7. The method for preparing the planar chiral compound according to claim 1 or 2, characterized in that, Prepared using method three; the reaction formula is shown in formula IV; Method 3 involves a mixture containing compound e and compound f (shown in Formula IV) and a solvent undergoing a substitution reaction in an inactive atmosphere to obtain compound g; then, compound g undergoes a lithiation reaction with boron under the conditions of solvent, lithium reagent, and boron reagent d to obtain the compound shown in Formula Ic. In formula IV, R 2 The definition is the same as that in claim 1; In formula IV, R 4 The definition is the same as that in claim 1; In formula IV, R 5 Selected from hydrogen, fluorine, methyl, ethyl, methoxy, ester, nitro, phenyl, benzyl, tert-butyl, isopropyl, 2,4,6-tri-Ome; Preferably, in method three: In the reaction shown in Formula IV, the molar ratio of compound e to compound f is 1:1.1 to 1:2; The reaction conditions for the substitution reaction are: temperature 0–30°C, time 6–48 hours; The inactive atmosphere in the substitution reaction is selected from at least one of nitrogen and argon. The solvent in the substitution reaction is selected from at least one of acetone and tetrahydrofuran; The substitution reaction is carried out under alkaline conditions, and the base is selected from at least one of potassium carbonate, potassium tert-butoxide, and sodium hydride. In the reaction shown in Formula IV, the molar ratio of compound e to the base is 1:1.1 to 1:5; The molar ratio of compound e to compound d shown in Formula IV is 1:1.1 to 1:1.5; The molar ratio of compound e shown in Formula IV to the lithium reagent is 1:1.1 to 1:2; The lithium reagent in the lithiation boronization reaction is at least one of n-butyllithium, sec-butyllithium, tert-butyllithium or diisopropylaminolithium; The conditions for the lithiation and boronization reaction are: temperature from 0°C to room temperature, and time from 10 to 48 hours. The lithiation and boronization reaction is carried out in an inactive atmosphere, which is selected from at least one of nitrogen and argon. The solvent in the lithiation boronization reaction is either diethyl ether or tetrahydrofuran.

8. The method for preparing the planar chiral compound according to claim 1 or 2, characterized in that, Preparation using method four: The reaction formula is shown in formula V; Method four involves a mixture containing compound h and compound b (shown in formula V) and a solvent undergoing a substitution reaction in an inactive atmosphere to obtain compound i; then, compound i undergoes a boron lithiation reaction under the conditions of a solvent, lithium reagent butyllithium, and boron reagent d to obtain the compound shown in formula Id. In formula V, R 2 The definition is the same as that in claim 1; In formula V, R 3 The definition of ' is the same as that in claim 1; In formula V, X is selected from at least one of iodine, bromine, and chlorine; Preferably, in method four: In the reaction shown in Formula V, the molar ratio of compound h to compound b is 1:1.1 to 1:2; The reaction conditions for the substitution reaction are a temperature of 0–70°C and a reaction time of 6–48 hours. The inactive atmosphere in the substitution reaction is selected from at least one of nitrogen and argon. The solvent in the substitution reaction is selected from at least one of acetone and tetrahydrofuran; The substitution reaction is carried out under alkaline conditions, and the base is selected from at least one of potassium carbonate and sodium hydride. In the reaction shown in Formula V, the molar ratio of compound h to the base is 1:1.1 to 1:5; In the reaction shown in formula V, the molar ratio of compound i to compound d is 1:1.1 to 1:1.5; The molar ratio of compound i to lithium reagent shown in formula V is 1:1.1 to 1:2; The reaction conditions for the lithiation and boronization reaction are: temperature from 0°C to room temperature, and time from 12 to 18 hours. The lithium reagent in the lithiation boronization reaction is at least one of n-butyllithium, sec-butyllithium, tert-butyllithium or diisopropylaminolithium; The lithiation and boronization reaction is carried out in an inactive atmosphere, which is selected from at least one of nitrogen and argon. The solvent in the lithiation boronization reaction is either diethyl ether or tetrahydrofuran.

9. The method for preparing the planar chiral compound according to claim 1 or 2, characterized in that, Prepared using method five; the reaction formula is shown in formula VI; Method 5 involves a mixture containing compound j (shown in Formula VI), compound k (shown in Formula VI), and a solvent, undergoing a substitution reaction a in an inactive atmosphere to obtain compound l; then, a mixture containing compound l, compound b (shown in Formula VI), and a solvent undergoes a substitution reaction b in an inactive atmosphere to obtain compound m; finally, compound m undergoes a lithiation reaction with boron in the presence of a solvent, lithium reagent butyllithium, and boron reagent d to obtain the compound shown in Formula Ie. In formula VI, R 2 The definition is the same as that in claim 1; In formula VI, R 3 The definition of "is the same as in claim 1; In Formula VI, R6 is defined as in claim 1; In formula VI, X is selected from at least one of iodine, bromine, and chlorine; Preferably, in method five: In the reaction shown in Formula VI, the molar ratio of compound j to compound k is 1:1.1 to 1:2; The reaction conditions for the substitution reaction a are a temperature of 0–70°C and a reaction time of 6–48 hours. The inactive atmosphere in the substitution reaction a is selected from at least one of nitrogen and argon; The solvent in the substitution reaction a is selected from at least one of acetone and tetrahydrofuran; In the reaction shown in Formula VI, the molar ratio of compound 1 to compound b is 1:1.1 to 1:2; The reaction conditions for the substitution reaction b are: temperature 0–70°C, time 6–48 hours; The inactive atmosphere in the substitution reaction b is selected from at least one of nitrogen and argon. The solvent in the substitution reaction b is selected from tetrahydrofuran, N,N-dimethylformamide, and diethyl ether. The substitution reaction is carried out under alkaline conditions, and the base is selected from at least one of potassium carbonate and sodium hydride. In the reaction shown in Formula VI, the molar ratio of compound i to the base is 1:1.1 to 1:5; In the reaction shown in Formula VI, the molar ratio of compound m to compound d is 1:1.1 to 1:1.5; The molar ratio of compound m and lithium reagent shown in Formula VI is 1:1.1 to 1:2; The reaction conditions for the lithiation and boronization reaction are 0°C to room temperature and 12 to 18 hours. The lithium reagent in the lithiation boronization reaction is at least one of n-butyllithium, sec-butyllithium, tert-butyllithium or diisopropylaminolithium; The lithiation and boronization reaction is carried out in an inactive atmosphere, which is selected from at least one of nitrogen and argon. The solvent in the lithiation boronization reaction is either diethyl ether or tetrahydrofuran.

10. The use of at least one of the chiral cycloaryl skeletal borate compounds according to claim 1 or 2, or the chiral cycloaryl skeletal borate compounds prepared by any one of claims 3 to 9, as a catalyst in the desymmetrization reaction of diols.

Images