Chiral boron-nitrogen heterocyclic compound as well as preparation method and application thereof

Abstract

The invention discloses a chiral boron-nitrogen heterocyclic compound and a preparation method and application thereof.A chiral boron-nitrogen skeleton is constructed by adopting a desymmetry strategy, and the chiral boron-nitrogen heterocyclic compound is obtained by introducing heteroatoms into a conjugated system, adjusting the geometric configuration of molecules, introducing different donor and receptor units and regulating and controlling the electron energy level, electron cloud distribution and accumulation behaviors of the molecules. Structural diversity and luminescence property optimization are realized, and the chiral boron-nitrogen heterocyclic compound with emission wavelength red shift, high fluorescence quantum yield and strong circular polarization luminescence signals is obtained. According to the preparation method provided by the invention, the isoquinolinone compound is used as a raw material, a denitrification cyclization strategy is adopted, catalytic cyclization is performed in an organic solvent, a catalyst and imidazoline ligand system, and the target compound is efficiently and highly selectively synthesized; the method has the advantages of mild reaction conditions, wide substrate application, excellent atom economy, simplicity and convenience in operation, good functional group compatibility and stereoselectivity and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, in particular to a chiral boron-nitrogen heterocyclic compound and a preparation method and application thereof. BACKGROUND

[0002] As a kind of novel structure, unique performance chiral organic functional molecules, chiral boron-nitrogen (B / N) light-emitting molecules, with its excellent characteristics in electronic structure, optical properties, etc., in the design of chiral materials, optical device preparation, biological and pharmaceutical research and development, etc. It shows unique theoretical research value and practical application potential. The traditional preparation method mainly depends on chiral high performance liquid chromatography (HPLC) separation technology or chemical resolution technology. This kind of method has obvious limitations: on the one hand, chiral boron-nitrogen compounds generally have complex structure and special molecular configuration, which greatly affects the separation and purification efficiency due to their poor solubility in common solvents; On the other hand, chemical resolution process often needs to use a large amount of expensive chiral resolution reagent, and this method also has the problems of complicated steps, low atom economy, high environmental pollution risk, etc., which seriously restricts the scale preparation and application expansion of chiral boron-nitrogen compounds.

[0003] In recent years, asymmetric catalytic synthesis technology has provided a new solution for the preparation of chiral compounds due to its high efficiency, high selectivity and good atom economy. However, due to the construction of chiral boron-nitrogen skeleton involving special chemical bond formation and stereochemical control, the asymmetric catalytic synthesis method for chiral boron-nitrogen compounds is still in the initial exploration stage. The existing technology generally has the problems of narrow applicability of catalytic system, insufficient reaction selectivity, poor product stability and complex synthesis process, and has not formed an efficient, universal and environmentally friendly synthesis technology system that can meet the actual application needs. SUMMARY

[0004] In order to solve the technical problems of narrow applicability, insufficient selectivity, and unsatisfactory product performance and process of the existing asymmetric catalytic synthesis technology, the present application provides a chiral boron-nitrogen heterocyclic compound and a preparation method and application thereof. The chiral boron-nitrogen heterocyclic compound has stable structure, excellent optical performance, and the preparation method is efficient, highly selective, simple to operate, and environmentally friendly.

[0005] The present application is realized by the following technical solutions:

[0006] The first aspect of the present application provides a chiral boron-nitrogen heterocyclic compound, which has the following general structure:

[0007] ;

[0008] Among them, A is a benzene ring or a thiophene ring; B is a benzene ring, a naphthalene ring, a benzothiophene ring or a pyrrole ring; Z is C or N.

[0009] R 1 one or more of hydrogen, alkyl, alkoxy, morpholinyl, trifluoromethyl, ester, halogen, phenyl and substituted phenyl, the substituents of the substituted phenyl being selected from one or more of alkyl, alkoxy, ester and thienyl;

[0010] R 2 one or more of hydrogen, alkyl, alkoxy, morpholinyl, trifluoromethyl, ester, halogen, phenyl and substituted phenyl, the substituents of the substituted phenyl being selected from one or more of alkyl, alkoxy, ester and thienyl;

[0011] R 3 one or more of alkyl, benzyl, phenyl or substituted phenyl, the substituents of the substituted phenyl being selected from one or more of alkyl, alkoxy, trifluoromethyl, ester and halogen;

[0012] R 4 one or more of hydrogen, alkyl, benzyl, phenyl or substituted phenyl, the substituents of the substituted phenyl being selected from one or more of alkyl, alkoxy, trifluoromethyl, ester and halogen;

[0013] R 5 one or more of ethyl, alkynyl, substituted alkynyl, allenyl, triazolyl, substituted triazolyl, isoxazolyl or substituted isoxazolyl, the substituents of the substituted alkynyl being selected from alkyl, pyrenyl, phenyl or substituted phenyl, the substituents of the substituted phenyl being selected from alkoxy, trifluoromethyl, the substituents of the substituted triazolyl being benzyl, the substituents of the substituted isoxazolyl being phenyl;

[0014] R 6 one or more of hydrogen, alkyl, halogen and phenyl.

[0015] further R 1 one or more of hydrogen, methyl, alkoxy, morpholinyl and methoxycarbonyl.

[0016] further R 2 selected from hydrogen or methyl.

[0017] further R 3 one or more of benzyl, phenyl or substituted phenyl, the substituents of the substituted phenyl being selected from one or more of methyl, tert-butyl, alkoxy, trifluoromethyl and ester.

[0018] further R 4 one or more of hydrogen, phenyl or substituted phenyl, the substituents of the substituted phenyl being selected from one or more of alkoxy and trifluoromethyl.

[0019] further R 5The substituted group is selected from ethyl, alkynyl, substituted alkynyl, allenyl, substituted triazolyl or substituted isoxazolyl, wherein the substituent of the substituted alkynyl is selected from pyrene, phenyl or substituted phenyl, the substituent of the substituted phenyl is selected from alkoxy or trifluoromethyl, the substituent of the substituted triazolyl is benzyl, and the substituent of the substituted isoxazolyl is phenyl.

[0020] Furthermore, R 6 It is selected from one or more of hydrogen, methyl, isopropyl, halogen and phenyl.

[0021] Furthermore, the chiral boron-nitrogen heterocyclic compound is selected from compounds with the following structures, or their enantiomers and diastereomers:

[0022]

[0023] .

[0024] A second aspect of this invention provides a method for preparing chiral boron-nitrogen heterocyclic compounds, comprising the following steps:

[0025] Isoquinolinone compounds and The reaction was carried out in the presence of a nickel catalyst, an imidazoline ligand and an organic solvent to obtain the chiral boron-nitrogen heterocyclic compound shown in Formula I.

[0026] The structural formula of the isoquinolinone compound is as follows: ;

[0027] The structural formula of the imidazoline ligand is as follows: ;

[0028] The structural formula of the chiral boron-nitrogen heterocyclic compound represented by Formula I is as follows: ;

[0029] Where A is a benzene ring or a thiophene ring; B is a benzene ring, a naphthylene ring, a benzothiophene ring, or a pyrrole ring; Z is C or N;

[0030] R 1 The substituent is selected from one or more of hydrogen, alkyl, alkoxy, morpholino, trifluoromethyl, ester, halogen, phenyl and substituted phenyl, wherein the substituent of the substituted phenyl is selected from one or more of alkyl, alkoxy, ester and thiophene.

[0031] R 2 The substituent is selected from one or more of hydrogen, alkyl, alkoxy, morpholino, trifluoromethyl, ester, halogen, phenyl and substituted phenyl, wherein the substituent of the substituted phenyl is selected from one or more of alkyl, alkoxy, ester and thiophene groups;

[0032] R 3The phenyl group is selected from alkyl, benzyl, phenyl or substituted phenyl groups, wherein the substituents of the substituted phenyl group are selected from one or more of alkyl, alkoxy, trifluoromethyl, ester and halogen groups;

[0033] R 4 The phenyl group is selected from hydrogen, alkyl, phenyl or substituted phenyl, wherein the substituent of the substituted phenyl group is selected from one or more of alkyl, alkoxy, trifluoromethyl, ester and halogen groups;

[0034] R 5 The alkynyl group is selected from alkynyl or substituted alkynyl groups, wherein the substituent of the substituted alkynyl group is selected from alkyl, phenyl or substituted phenyl groups, and the substituent of the substituted phenyl group is selected from alkoxy or trifluoromethyl groups;

[0035] R 6 It is selected from one or more of hydrogen, alkyl, halogen and phenyl.

[0036] The preparation method provided by this invention adopts a denitrification cyclization strategy, using isoquinolinone compounds as raw materials, and imidazoline compounds as ligands in an organic solvent and catalyst system to efficiently and selectively synthesize chiral boron-nitrogen heterocyclic compounds through catalytic cyclization reaction. It has the technical characteristics of mild reaction conditions, wide substrate applicability, excellent atom economy, and simple and easy operation, while also having the advantages of good functional group compatibility and outstanding stereoselectivity.

[0037] Furthermore, the nickel catalyst is bis-(1,5-cyclooctadiene)nickel (Ni(cod)2).

[0038] Furthermore, the amount of nickel catalyst used is 5-15 mol of the isoquinolinone compound.

[0039] Furthermore, the amount of the imidazoline ligand used is 10-15 mol of the amount of the isoquinolinone compound.

[0040] Further, the preparation method of the imidazoline ligand includes the following steps: dissolving dimethyl oxalate and L(+)-leucine in toluene, stirring at 70-90 °C for 10-15 h, filtering and washing with petroleum ether to obtain a diol intermediate; dissolving the diol intermediate in toluene, adding sulfoxide at 60-80 °C, stirring at 65-75 °C for 20-40 min, then heating to 85-95 °C for 3-5 h, removing the solvent under reduced pressure, filtering with petroleum ether to obtain a dichloro intermediate; under a nitrogen atmosphere, dissolving the dichloro intermediate and phosphorus pentachloride in toluene, stirring at 80-90 °C for 4-5 h, removing the solvent under reduced pressure to obtain a tetrachloro intermediate; under a nitrogen atmosphere, dissolving the tetrachloro intermediate, triethylamine and aromatic amine in acetonitrile, heating under reflux at 80-90 °C for 30-40 h to obtain the imidazoline ligand.

[0041] Furthermore, the organic solvent is cyclopentylmethyl ether (CPME).

[0042] Furthermore, the reaction temperature is 20-40 °C.

[0043] Furthermore, the reaction time is 10-15 h.

[0044] In a specific embodiment, the reaction equation for preparing the chiral boron-nitrogen heterocyclic compound shown in Formula I is as follows:

[0045] .

[0046] Further, the chiral boron-nitrogen heterocyclic compound shown in Formula I was reacted in the presence of a catalyst, 1-bromopyrene, and an organic solvent to obtain the chiral boron-nitrogen heterocyclic compound shown in Formula II; the catalyst was tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) and cuprous iodide (CuI);

[0047] The structural formula of the chiral boron-nitrogen heterocyclic compound represented by Formula II is as follows: .

[0048] Furthermore, the amount of the catalyst is 25-35 mol% of the amount of the chiral boron-nitrogen heterocyclic compound shown in Formula I, and the molar ratio of tetra(triphenylphosphine)palladium to cuprous iodide is 1:(1.5-2.5).

[0049] Furthermore, the molar ratio of 1-bromopyrene to the chiral boron-nitrogen heterocyclic compound shown in Formula I is (1-1.5):1.

[0050] Furthermore, the organic solvent is a mixture of tetrahydrofuran (THF) and triethylamine (TEA); the volume ratio of tetrahydrofuran to triethylamine is (0.5-1.5):1.

[0051] Furthermore, the reaction is carried out at a temperature of 50-70 °C for 5-10 h.

[0052] Furthermore, the chiral boron-nitrogen heterocyclic compound shown in Formula I is reacted in the presence of a catalyst and an organic solvent to obtain the chiral boron-nitrogen heterocyclic compound shown in Formula III; the catalyst is palladium on carbon (Pd / C).

[0053] The structural formula of the chiral boron-nitrogen heterocyclic compound represented by Formula III is as follows: .

[0054] Furthermore, the amount of the catalyst used is 5-15 mol of the chiral boron-nitrogen heterocyclic compound represented by Formula I.

[0055] Furthermore, the organic solvent is methanol.

[0056] Furthermore, the reaction is carried out at a temperature of 20-40 °C for a time of 20-30 h.

[0057] Furthermore, the chiral boron-nitrogen heterocyclic compound shown in Formula I is reacted in the presence of a catalyst, paraformaldehyde, diisopropylamine, and an organic solvent to obtain the chiral boron-nitrogen heterocyclic compound shown in Formula IV; the catalyst is cuprous iodide.

[0058] The structural formula of the chiral boron-nitrogen heterocyclic compound represented by Formula IV is as follows: .

[0059] Further, the molar ratio of the catalyst to the chiral boron-nitrogen heterocyclic compound shown in Formula I is (0.7-0.8):1; the molar ratio of the paraformaldehyde to the chiral boron-nitrogen heterocyclic compound shown in Formula I is (1.5-1.7):1; and the molar ratio of the diisopropylamine to the chiral boron-nitrogen heterocyclic compound shown in Formula I is (1.3-1.5):1.

[0060] Furthermore, the chemical formula of the paraformaldehyde is (CH2O). n n is 6-50.

[0061] Furthermore, the organic solvent is 1,4-dioxane.

[0062] Furthermore, the reaction is carried out at a temperature of 100-120 °C for a time of 10-20 h.

[0063] Further, the chiral boron-nitrogen heterocyclic compound shown in Formula I was reacted in the presence of a catalyst, benzyl azide and an organic solvent to obtain the chiral boron-nitrogen heterocyclic compound shown in Formula V; the catalyst was copper tetraacetonitrile hexafluorophosphate (Cu(CH3CN)4PF6).

[0064] The structural formula of the chiral boron-nitrogen heterocyclic compound represented by Formula V is as follows: .

[0065] Furthermore, the amount of the catalyst used is 5-15 mol% of the amount of the chiral boron-nitrogen heterocyclic compound shown in Formula I; the molar ratio of the benzyl azide to the chiral boron-nitrogen heterocyclic compound shown in Formula I is (1.8-2.2):1.

[0066] Furthermore, the organic solvent is tetrahydrofuran.

[0067] Furthermore, the reaction is carried out at a temperature of 40-60 °C for a time of 15-25 h.

[0068] Further, the chiral boron-nitrogen heterocyclic compound shown in Formula I was reacted in the presence of a catalyst, potassium bicarbonate, sodium citrate, (Z)-N-hydroxybenzylimine chloride, and a solvent to obtain the chiral boron-nitrogen heterocyclic compound shown in Formula VI; the catalyst was copper sulfate pentahydrate (CuSO4·5H2O).

[0069] The structural formula of the chiral boron-nitrogen heterocyclic compound represented by Formula VI is as follows: .

[0070] Further, the amount of the catalyst is 5-15 mol% of the amount of the chiral boron-nitrogen heterocyclic compound shown in Formula I; the molar ratio of potassium bicarbonate to the chiral boron-nitrogen heterocyclic compound shown in Formula I is (3.8-4.2):1; the molar ratio of sodium citrate to the chiral boron-nitrogen heterocyclic compound shown in Formula I is (0.4-0.6):1; and the molar ratio of (Z)-N-hydroxybenzylimine chloride to the chiral boron-nitrogen heterocyclic compound shown in Formula I is (1.4-1.6):1.

[0071] Furthermore, the solvent is a mixture of tetrahydrofuran and water; the volume ratio of the solvent to water is (0.5-1.5):1.

[0072] Furthermore, the reaction is carried out at a temperature of 100-120 °C for a time of 10-20 h.

[0073] The third aspect of this invention provides the application of the chiral boron-nitrogen heterocyclic compound described in the first aspect or the chiral boron-nitrogen heterocyclic compound prepared by the preparation method described in the second aspect in the preparation of fluorescent probes.

[0074] Compared with the prior art, the above-described technical solution of the present invention has the following advantages:

[0075] This invention constructs a chiral boron-nitrogen framework by employing a desymmetry strategy, introduces heteroatoms into the conjugated system to regulate the molecular electronic energy levels and stacking behavior, thereby optimizing its fluorescence performance; at the same time, it achieves structural diversity by adjusting the molecular geometry to regulate the electron cloud distribution and stacking mode, and introduces different donor and acceptor units to regulate the luminescence properties, ultimately achieving a redshift in emission wavelength and obtaining high fluorescence quantum yield and strong circularly polarized luminescence signal. Attached Figure Description

[0076] Figure 1The images show the spectra of the chiral boron-nitrogen heterocyclic compounds prepared in Examples 17-22; wherein, (a) is the UV-Vis absorption spectrum of the chiral boron-nitrogen heterocyclic compounds prepared in Examples 17-22, (b) is the fluorescence emission spectrum of the chiral boron-nitrogen heterocyclic compounds prepared in Examples 17-22, (c) is the circular dichroism spectrum of the chiral boron-nitrogen heterocyclic compounds and their enantiomers prepared in Example 20, and (d) is the circularly polarized emission spectrum of the chiral boron-nitrogen heterocyclic compounds and their enantiomers prepared in Example 20.

[0077] Figure 2 The graph shows the biosafety test results of the chiral boron-nitrogen heterocyclic compound prepared in Example 23.

[0078] Figure 3 The graph shows the lysosomal targeting test results of commercial lysosomal dyes and the chiral boron-nitrogen heterocyclic compound prepared in Example 23; where (a) is the staining image of HeLa cells by commercial lysosomal dyes (scale bar is 20 μm), (b) is the staining image of HeLa cells by the chiral boron-nitrogen heterocyclic compound prepared in Example 23 (scale bar is 20 μm), (c) is the staining overlap image of (a) and (b) (scale bar is 20 μm), and (d) is the overlap coefficient analysis graph. Detailed Implementation

[0079] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0080] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments described are not intended to limit the present invention.

[0081] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, and the materials and reagents used are commercially available.

[0082] The structural formula of the imidazoline ligand (L*) in the following examples is as follows: It is prepared by the following method:

[0083]

[0084] Step 1: Dimethyl oxalate (1.180 g, 10 mmol, 1.0 equivalent) and L(+)-leucine (2.340 g, 20.0 mmol, 2.0 equivalent) shown in S1 were dissolved in toluene (60 mL) and heated to 80 °C. The reaction was stirred for 12 h and then cooled to room temperature. The product precipitated from the solution as a white solid. After filtration and washing with petroleum ether, the diol intermediate shown in S2 (2.793 g, 97%, white solid) was obtained.

[0085] Step 2: The diol intermediate shown in S2 (2.793 g, 9.7 mmol) was dissolved in toluene (60 mL), heated to 70 °C, and then thionyl chloride (1.54 mL, 21.3 mmol, 2.2 equivalents) was added. The reaction was stirred at 70 °C for 30 min, and then heated to 90 °C for 4 h. After the reaction was complete, it was cooled to room temperature, toluene was removed by vacuum distillation, a large amount of petroleum ether was added, and the product precipitated out. After filtration, the dichloro intermediate shown in S3 (2.733 g, 87%, white solid) was obtained.

[0086] Step 3: Under a nitrogen atmosphere, add the dichloro intermediate (2.733 g, 8.44 mmol) and phosphorus pentachloride (4.213 g, 20.3 mmol, 2.4 equivalents) shown in S3 to 60 mL of toluene in a flame-dried double-necked flask. Stir the reaction at 85 °C for 4.5 h, then cool to room temperature. Remove the toluene by vacuum distillation to obtain the tetrachloro intermediate (3.351 g, 81%, yellow liquid) shown in S4.

[0087] Step 4: Under a nitrogen atmosphere, add the tetrachloro intermediate (6.84 mmol, 3.351 g, 1.0 equivalent), triethylamine (5.709 mL, 41 mmol, 6.0 equivalent), and aromatic amine (41.0 mmol, 6.0 equivalent) shown in S4 to a flame-dried 50 mL round-bottom flask, followed by 60 mL of acetonitrile. Then, reflux the reaction mixture at 85 °C for 36 h under nitrogen protection. After cooling to room temperature, remove volatile components using a rotary evaporator. Dilute the residue with dichloromethane and wash with saturated ammonium chloride solution (100 mL × 3 times) and water, respectively. Dry the organic layer with anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue by rapid column chromatography and recrystallize from n-hexane and ethyl acetate to obtain the imidazoline ligand.

[0088] The characterization data for L* are: mp = 117-120 °C. 1H NMR (400 MHz, CDCl3) δ 6.67 (d, J = 8.8 Hz, 4H), 6.53 (d, J = 9.2 Hz, 4H), 4.22-4.12 (m, 2H), 3.69 (t, J = 9.2Hz, 2H), 3.24 (t, J = 8.8 Hz, 2H), 2.89 (s, 12H), 1.92-1.81 (m, 2H), 1.72-1.64 (m, 2H), 1.34-1.25 (m, 2H), 0.95 (d, J = 6.8 Hz, 6H), 0.92 (d, J = 6.8Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 154.1, 147.4, 130.0, 122.2, 112.4, 62.5,57.4, 45.3, 40.7, 24.6, 22.7, 22.2. HRMS (ESI) m / z: [M + H] + Calcd for C 30 H 45 N6 + 489.3700; Found 489.3696. [α] D 21.8 = -28.2 (c = 0.01, CH2Cl2).

[0089] Example 1

[0090] A chiral boron-nitrogen heterocyclic compound represented by formula I-01 ( The preparation method of ) includes the following steps:

[0091] In an argon-filled glove box, Ni(cod)₂ (4 mg, 10% mol) and L* (6 mg, 12% mol) were charged into a 10 mL reaction tube. Then, anhydrous solvent CPME (2.0 mL) was added, and the mixture was stirred at room temperature for 30 minutes. Next, 1,2,3-benzotriazine-4(3H)-one (26 mg, 0.10 mmol, 1.0 equivalent) and 6,6-diethynyl-7,10-dimethyl-6H-5λ were added to the resulting solution. 4 ,6λ 4-Benzo[3,4][1,2]azaboranecyclopentano[1,5-a]pyridine (24 mg, 0.10 mmol, 1.0 equivalent). The reaction tube was then sealed with hermetically sealed electrical tape, removed from the glove box, and stirred at 500 rpm for 12 hours at room temperature (monitored by TLC). The mixture was then concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-01 in 96% yield with an ee value of 93%.

[0092] The characterization data for product I-01 are: mp = 294-298 ℃. 1 H NMR (400 MHz, CDCl3) δ8.54-8.41 (m, 2H), 8.24 (d, J = 8.3 Hz, 2H), 8.08-7.98 (m, 1H), 7.57 (t, J =6.8 Hz, 4H), 7.29 (t, J = 6.6 Hz, 1H), 7.23 (t, J = 7.6 Hz, 1H), 7.12 (s,3H), 6.44 (s, 1H), 2.79 (s, 3H), 2.28 (s, 3H), 2.20 (s, 1H), 1.53-1.37 (m,9H). 13 C NMR (101 MHz, CDCl3) δ 162.5, 158.8, 150.3, 143.7, 141.4, 140.4,139.4, 139.0, 138.2, 134.2, 132.4, 132.3, 131.5, 130.6, 128.3, 126.5, 126.3,126.0, 125.4, 125.1, 121.9, 121.7, 85.0, 34.61, 31.3, 21.9, 19.9. HRMS (ESI)m / z: [M + H] + C 34 H 32 BN2O + Calculated value: 495.2602; Measured value: 495.2602. HPLC: 3.5:96.5. Determined by analytical HPLC, Daicel CHIRALPAK. ® AD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t minor = 16.0 min, t major= 22.8 min. [α] D 20 = -30.6 (c = 0.01, CH2Cl2).

[0093] Example 2

[0094] A chiral boron-nitrogen heterocyclic compound represented by formula I-02 ( The preparation method of ) is basically the same as that in Example 1, except that 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of 3-phenylbenzo[d][1,2,3]triazine-4(3H)-one.

[0095] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-02 in 92% yield with an ee value of 92%.

[0096] The characterization data for product I-02 are: mp = 288-292 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.50(d, J = 5.6 Hz, 1H), 8.45 (d, J = 8.0 Hz, 1H), 8.34-8.09 (m, 2H), 8.07 (t, J= 8.0 Hz, 1H), 7.61 (d, J = 6.8 Hz, 2H), 7.56 (t, J = 7.6 Hz, 2H), 7.44 (t, J= 7.2 Hz, 1H), 7.33 (t, J = 6.4 Hz, 1H), 7.26-7.19 (m, 1H), 7.12 (s, 2H), 7.06 (brs, 1H), 6.40 (s, 1H), 2.80 (s, 3H), 2.27 (s, 3H), 2.19 (s, 1H). 13 CNMR (101 MHz, CDCl3) δ 162.3, 158.6, 143.6, 142.0, 141.4, 140.3, 138.8,138.1, 134.1, 132.3, 131.6, 130.5, 129.0, 128.2, 127.5, 126.9, 126.3, 125.5,125.1, 121.9, 121.7, 85.0, 21.9, 19.9. HRMS (ESI) m / z: [M + H] + C 30 H 24BN2O + Calculated value: 439.1976; Measured value: 439.1979. HPLC: 4.96. Determined by analytical HPLC, Daicel Chiralpak. ® AD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254nm, t minor = 14.6 min, t major = 16.1 min. [α] D 24.2 = -44.5 (c = 0.01, CH2Cl2).

[0097] Example 3

[0098] A chiral boron-nitrogen heterocyclic compound represented by formula I-03 ( The preparation method of ) is basically the same as that in Example 1, except that 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of 3-benzylbenzo[d][1,2,3]triazine-4(3H)-one.

[0099] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3 / 1) to give product I-03 in 93% yield with an ee value of 96%.

[0100] The characterization data for product I-03 are: mp = 246-247 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.41(d, J = 8.0 Hz, 1H), 8.37 (d, J = 6.0 Hz, 1H), 8.24 (d, J = 8.4 Hz, 1H), 8.14(brs, 1H), 8.07-8.01 (m, 1H), 7.43 (d, J = 7.6 Hz, 2H), 7.36 (t, J = 7.6 Hz,2H), 7.32-7.27 (m, 2H), 7.20 (t, J = 7.6 Hz, 1H), 7.14-7.06 (m, 2H), 7.02(brs, 1H), 6.38 (brs, 1H), 5.47-5.37 (m, 1H), 5.36-5.18 (s, 1H), 2.79 (s,3H), 2.22 (s, 1H), 2.16 (s, 3H).13 C NMR (101 MHz, CDCl3) δ 162.6, 158.8,143.7, 141.3, 140.4, 138.8, 138.2, 137.7, 134.2, 132.4, 132.3, 131.2, 130.6,128.6, 128.1, 127.9, 127.4, 126.3, 125.2, 125.2, 121.9, 121.7, 84.9, 52.1,22.0, 19.8. HRMS (ESI) m / z: [M + H] + C 31 H 25 BN2O + Calculated value: 453.2133; Measured value: 453.2130. HPLC: 2:98. Measured by analytical HPLC, Daicel CHIRALPAK. ® AD-Hcolumn, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 210 nm, t minor = 14.0 min,t major = 21.9 min. [α] D 21.7 = -26.7 (c = 0.01, CH2Cl2).

[0101] Example 4

[0102] A chiral boron-nitrogen heterocyclic compound represented by formula I-04 ( The preparation method of ) is basically the same as that in Example 1, except that 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of 3-(4-methoxyphenyl)benzo[d][1,2,3]triazine-4(3H)-one.

[0103] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3 / 1) to give product I-04 in 90% yield with an ee value of 90%.

[0104] The characterization data for product I-04 are: mp = 255-260 ℃. 1H NMR (400 MHz, CDCl3) δ 8.49(d, J = 5.6 Hz, 1H), 8.43 (d, J = 6.4 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.18(s, 1H), 8.10-8.04 (m, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.33 (t, J = 6.0 Hz,1H), 7.22 (t, J = 7.6 Hz, 1H), 7.12 (s, 2H), 7.07 (d, J = 8.8 Hz, 3H), 6.39(brs, 1H), 3.89 (s, 3H), 2.80 (s, 3H), 2.26 (s, 3H), 2.18 (s, 1H). 13 C NMR(101 MHz, CDCl3) δ 162.5, 158.7, 158.6, 143.6, 141.4, 140.3, 139.1, 138.1,135.0, 134.1, 132.3, 131.4, 130.5, 128.2, 127.9, 126.3, 125.4, 125.2, 121.8,121.7, 114.2, 84.9, 55.4, 21.9, 19.9. HRMS (ESI) m / z: [M + H] + C 31 H 26 BN2O2 + Calculated value: 469.2082; Measured value: 469.2082. HPLC: 5:95. Measured by analytical HPLC, Daicel CHIRALPAK. ® AD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254nm, t minor = 30.8 min, t major = 38.5 min. [α] D 23.1 = -31.7 (c = 0.01, CH2Cl2).

[0105] Example 5

[0106] A chiral boron-nitrogen heterocyclic compound represented by formula I-05 ( The preparation method of ) is basically the same as that of Example 1, except that 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of 3-(4-(trifluoromethyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one.

[0107] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3 / 1) to give product I-05 in 83% yield with an ee value of 83%.

[0108] The characterization data for product I-05 are: mp = 253-255 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.46(d, J = 5.6 Hz, 1H), 8.41 (d, J = 8.0 Hz, 1H), 8.21 (d, J = 8.4 Hz, 2H), 8.03-7.97 (m, 1H), 7.85-7.68 (m, 4H), 7.26 (t, J = 6.4 Hz, 1H), 7.23-7.16 (m,1H), 7.09 (s, 2H), 7.05 (brs, 1H), 6.39 (brs, 1H), 2.75 (s, 3H), 2.24 (s,3H), 2.19 (s, 1H). 13 C NMR (101 MHz, CDCl3) δ 162.2, 158.8, 144.9, 143.6,141.5, 140.2, 138.0, 137.8, 134.2, 132.4, 132.4, 131.9, 130.6, 129.4 (q, J C-F = 32.3 Hz), 128.3, 127.3, 126.2, 126.2, 125.8, 125.2 (d, J C-F = 5.1 Hz), 122.5, 121.8 (d, J C-F = 18.2 Hz), 85.2, 21.9, 19.9. 19 F NMR (376 MHz, CDCl3) δ-62.4. HRMS (ESI) m / z: [M + H] + C 31 H 23 BF3N2O +Calculated value: 507.1850; Measured value: 507.1854. HPLC: 8.5:91.5. Analyzed by analytical HPLC, Daicel CHIRALPAK. ® AD-Hcolumn, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t minor = 20.3 min,t major = 26.2 min. [α] D 22.8 = -40.8 (c = 0.01, CH2Cl2).

[0109] Example 6

[0110] A chiral boron-nitrogen heterocyclic compound represented by formula I-06 ( The preparation method of ) is basically the same as that in Example 1, except that 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of 3-(4-(tert-butyl)phenyl)-6-methoxybenzo[d][1,2,3]triazine-4(3H)-one.

[0111] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-06 in 94% yield with an ee value of 92%.

[0112] The characterization data for product I-06 are: mp = 176-179 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.49(d, J = 5.6 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 8.14 (brs, 1H), 8.01 (t, J =7.6 Hz, 1H), 7.91 (d, J = 2.8 Hz, 1H), 7.68-7.52 (m, 4H), 7.28 (d, J = 7.6Hz, 1H), 7.16-7.07 (m, 2H), 6.71 (brs, 1H), 6.38 (brs, 1H), 3.79 (s, 3H), 2.77 (s, 3H), 2.29 (s, 3H), 2.20 (s, 1H), 1.42 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 162.0, 158.7, 157.5, 150.2, 143.6, 141.3, 139.5, 138.1, 136.9,134.4, 134.1, 132.3, 132.3, 130.5, 127.6, 126.7, 126.3, 126.2, 125.9, 121.8,121.7, 121.5, 108.3, 84.8, 55.2, 34.6, 31.3, 21.9, 19.8. HRMS (ESI) m / z: [M +H] + C 35 H 34 BN2O2 + Calculated value: 525.2708; Measured value: 525.2703. HPLC: 4:96. Analyzed by analytical HPLC, Daicel CHIRALPAK. ® AD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t minor = 13.8 min, t major = 20.9 min. [α] D 22.4 = -101.0 (c = 0.01, CH2Cl2).

[0113] Example 7

[0114] A chiral boron-nitrogen heterocyclic compound represented by formula I-07 ( The preparation method of ) is basically the same as that in Example 1, except that 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of methyl 3-(4-(tert-butyl)phenyl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-7-carboxylate.

[0115] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-07 in 82% yield with an ee value of 98%.

[0116] The characterization data for product I-07 are: mp = 277-280 ℃. 1H NMR (400 MHz, CDCl3) δ 8.50(d, J = 5.6 Hz, 1H), 8.46 (d, J = 8.4 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.24(brs, 1H), 8.07 (t, J = 8.0 Hz, 1H), 7.79 (dd, J = 8.4, 1.6 Hz, 1H), 7.58 (d,J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.32 (t, J = 6.8 Hz, 1H), 7.24 -7.02 (m, 3H), 3.70 (s, 3H), 2.84 (s, 3H), 2.28 (s, 3H), 2.25 (s, 1H), 1.41 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 166.3, 161.9, 159.1, 150.6, 143.7, 141.5,139.9, 139.5, 139.1, 138.1, 134.5, 132.6, 132.2, 130.5, 129.4, 128.5, 127.6,126.2, 126.1, 125.4, 122.0, 121.8, 85.4, 51.8, 34.7, 31.3, 21.9, 19.9. HRMS(ESI) m / z: [M + H] + C 36 H 34 BN2O3 + Calculated value: 553.2657; Measured value: 553.2654. HPLC: 99:1, determined by analytical HPLC, Daicel CHIRALPAK. ® IA column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t major = 11.9 min, t minor = 16.2 min. [α] D 22.8 =-1.4 (c = 0.01, CH2Cl2).

[0117] Example 8

[0118] A chiral boron-nitrogen heterocyclic compound represented by formula I-08 ( The preparation method of ) is basically the same as that of Example 1, except that 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of 8-methyl-3-(p-tolyl)benzo[d][1,2,3]triazine-4(3H)-one.

[0119] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-08 in 66% yield with an ee value of 90%.

[0120] The characterization data for product I-08 are: mp = 258-260 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.76(s, 1H), 8.56 (d, J = 5.6 Hz, 1H), 8.48 (d, J = 6.0 Hz, 1H), 8.24 (d, J = 8.4Hz, 1H), 8.11 (t, J = 7.2 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.40 (t, J = 6.0Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.21 (t, J = 7.6 Hz, 1H), 7.11 - 7.03 (m,3H), 2.75 (s, 3H), 2.45 (s, 3H), 2.12 (s, 3H), 2.06 (s, 1H), 1.23 (s, 3H). 13 CNMR (101 MHz, CDCl3) δ 162.5, 159.0, 143.6, 142.9, 141.4, 141.0, 139.5,137.3, 137.2, 135.1, 135.0, 134.3, 132.6, 132.5, 130.2, 129.7, 127.9, 126.9,126.6, 125.3, 122.2, 121.7, 83.9, 22.0, 21.5, 21.2, 20.0. HRMS (ESI) m / z: [M+ H] + C 32 H 28 BN2O + Calculated value: 467.2289; Measured value: 467.2286. HPLC: 95:5. Analyzed by analytical HPLC, Daicel CHIRALPAK.® OD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t major = 15.4 min, t minor = 20.5 min. [α] D 22.3 = -42.3 (c = 0.01, CH2Cl2).

[0121] Example 9

[0122] A chiral boron-nitrogen heterocyclic compound represented by formula I-09 ( The preparation method of ) is basically the same as that of Example 1, except that 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of 3-(4-(tert-butyl)phenyl)thiopheno[3,2-d][1,2,3]triazine-4(3H)-one.

[0123] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-09 in 92% yield with an ee value of 92%.

[0124] The characterization data for product I-09 are: mp = 295-297 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.50(d, J = 5.6 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.10 - 8.00 (m, 2H), 7.59 -7.51 (m, 4H), 7.34 - 7.30 (m, 1H), 7.21 (d, J = 5.2 Hz, 1H), 7.14 - 7.09 (m,2H), 6.03 (brs, 1H), 2.76 (s, 3H), 2.29 (s, 3H), 2.24 (s, 1H), 1.40 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 158.9, 158.7, 150.6, 149.0, 144.0, 141.7, 139.4,138.9, 138.5, 134.6, 132.5, 132.5, 132.3, 130.9, 130.3, 126.5, 126.1, 124.4,122.0, 121.8, 85.4, 34.8, 31.5, 22.0, 20.1. HRMS (ESI) m / z: [M + H] + C 32 H 30 BN2OS + Calculated value: 501.2166; Measured value: 501.2163. HPLC: 4:96. Analyzed by analytical HPLC, Daicel CHIRALPAK. ® AD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t minor = 9.4 min, t major = 14.5 min. [α] D 21.9 = -38.3 (c = 0.01, CH2Cl2).

[0125] Example 10

[0126] A chiral boron-nitrogen heterocyclic compound represented by Formula I-10 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 10-chloro-6,6-diethynyl-7-methyl-6H-5λ. 4 ,6λ 4 -Benzo[3,4][1,2]nitroborono[1,5-a]pyridine.

[0127] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-10 in 80% yield with an ee value of 96%.

[0128] The characterization data for product I-10 are: mp = 289-293 ℃. 1H NMR (400 MHz, CDCl3) δ 8.55(d, J = 5.6 Hz, 1H), 8.46 (d, J = 8.0 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.22- 7.99 (m, 2H), 7.60 - 7.49 (m, 4H), 7.41 - 7.37 (m, 1H), 7.31 - 7.26 (m,1H), 7.22 (t, J = 7.6 Hz, 1H), 7.15 (d, J = 8.0 Hz, 1H), 7.07 (brs, 1H), 6.37(brs, 1H), 2.80 (s, 3H), 2.23 (s, 1H), 1.40 (s, 9H). 13 C NMR (101 MHz, CDCl3)δ 162.4, 157.3, 150.3, 144.1, 141.8, 140.3, 139.7, 139.4, 136.0, 135.0,133.8, 132.1, 131.9, 131.5, 128.50, 126.6, 126.4, 126.0 125.3, 124.7, 122.7,122.2, 85.1, 34.6, 31.4, 21.8. HRMS (ESI) m / z: [M + H] + C 33 H 29 BClN2O + Calculated value: 515.2056; Measured value: 515.2051. HPLC: 2:98. Analyzed by analytical HPLC, Daicel Chiralpak. ® AD-H column, 25 ℃, Hexane / i-PrOH = 70:30, 1.0 mL / min, 254nm, t minor = 12.8 min, t major = 21.1 min. [α] D 22.9 = -7.7 (c = 0.01, CH2Cl2).

[0129] Example 11

[0130] A chiral boron-nitrogen heterocyclic compound represented by Formula I-11 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 7-chloro-6,6-diethynyl-10-fluoro-6H-5λ. 4 ,6λ 4 -Benzo[3,4][1,2]nitroborono[1,5-a]pyridine.

[0131] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 1 / 1) to give product I-11 in 90% yield with an ee value of 97%.

[0132] The characterization data for product I-11 are: mp = 299-301 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.51(d, J = 5.2 Hz, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.33 (d, J = 8.0 Hz, 1H), 8.27- 8.05 (m, 2H), 7.59 - 7.48 (m, 4H), 7.42 (t, J = 7.2 Hz, 1H), 7.36 (dd, J =8.4, 4.0 Hz, 1H), 7.24 (d, J = 7.6 Hz, 1H), 7.13 (brs, 1H), 7.09 - 7.01 (m,1H), 6.35 (brs, 1H), 2.27 (s, 1H), 1.40 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ162.3, 158.9 (d, J C-F = 257.6 Hz), 153.6 (d, J C-F = 5.1 Hz), 150.3, 143.7,142.4, 140.1, 139.8, 139.2, 133.8 (d, J C-F = 8.1 Hz), 131.9, 131.9, 131.6,128.6, 126.5, 126.3, 126.0, 125.5, 124.5 (d, J C-F = 10.1 Hz), 123.6, 122.8 (d,J C-F = 10.1 Hz), 116.0 (d, JC-F = 21.2 Hz), 85.7, 34.6, 31.3. 19 F NMR (376 MHz, CDCl3) δ -119.3. HRMS (ESI) m / z: [M + H] + C 32 H 26 BClFN2O + Calculated value: 519.1809; Measured value: 519.1802. HPLC: 1.5:98.5. Measured by analytical HPLC, Daicel CHIRALPAK. ® AD-H column, 25 ℃, Hexane / i-PrOH = 70:30, 1.0 mL / min, 254 nm, t minor = 11.8min, t major = 30.1 min. [α] D 23.0 = -24.6 (c = 0.01, CH2Cl2).

[0133] Example 12

[0134] A chiral boron-nitrogen heterocyclic compound represented by Formula I-12 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 6,6-diethynyl-9,10-dimethyl-6H-5λ. 4 ,6λ 4 -Benzo[3,4][1,2]nitroborono[1,5-a]pyridine.

[0135] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-12 in 70% yield with an ee value of 88%.

[0136] The characterization data for product I-12 are: mp = 280-283 ℃. 1H NMR (400 MHz, CDCl3) δ 8.51(d, J = 5.6 Hz, 1H), 8.43 (d, J = 9.6 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.04(t, J = 8.8 Hz, 1H), 7.95 (s, 1H), 7.54 - 7.45 (m, 4H), 7.40 (d, J = 7.2 Hz,1H), 7.33 - 7.27 (m, 1H), 7.25 - 7.17 (m, 2H), 7.10 (t, J = 7.6 Hz, 1H), 6.66(brs, 1H), 2.71 (s, 3H), 2.40 (s, 3H), 2.20 (s, 1H), 1.37 (s, 9H). 13 C NMR(101 MHz, CDCl3) δ 162.4, 158.9, 150.3, 144.1, 141.4, 140.3, 139.4, 138.4,135.7, 134.9, 134.0, 133.9, 131.4, 128.3, 127.2, 126.6, 126.3, 126.0, 125.7,125.4, 122.3, 121.7, 85.1, 34.6, 31.3, 20.5, 17.1. HRMS (ESI) m / z: [M + H] + C 34 H 32 BN2O + Calculated value: 495.2602; Measured value: 495.2598. HPLC: 94:6. Analyzed by analytical HPLC, Daicel CHIRALPAK. ® AD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t major = 14.3 min, t minor = 20.9 min. [α] D 22.8 = -12.4 (c = 0.01, CH2Cl2).

[0137] Example 13

[0138] A chiral boron-nitrogen heterocyclic compound represented by Formula I-13 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 6,6-diethynyl-3-methyl-6H-5λ. 4 ,6λ 4 -Benzo[3,4][1,2]nitroborono[1,5-a]pyridine.

[0139] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-13 in 77% yield with an ee value of 94%.

[0140] The characterization data for product I-13 are: mp = 298-300 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.45(d, J = 8.0 Hz, 1H), 8.22 (s, 1H), 7.99 (d, J = 5.2 Hz, 2H), 7.93 (d, J = 7.2Hz, 1H), 7.62 - 7.49 (m, 5H), 7.39 (p, J = 7.2 Hz, 2H), 7.21 (t, J = 7.6 Hz,1H), 7.13 (brs, 1H), 7.01 (t, J = 7.6 Hz, 1H), 6.23 (d, J = 8.4 Hz, 1H), 2.70(s, 3H), 2.24 (s, 1H), 1.41 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 162.5, 158.8,157.4, 150.4, 141.6, 140.2, 139.5, 138.8, 136.1, 131.9, 131.5, 129.8, 128.5,127.0, 126.4, 126.1, 125.5, 124.8, 124.4, 122.0, 116.1, 85.7, 34.7, 31.5,21.3. HRMS (ESI) m / z: [M + H] + C 33 H 30 BN2O +Calculated value: 481.2446; Measured value: 481.2443. HPLC: 97:3. Measured by analytical HPLC, Daicel CHIRALPAK. ® AD-H column,25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t major = 17.2 min, t minor =28.8 min. [α] D 23.7 = +4.5 (c = 0.01, CH2Cl2).

[0141] Example 14

[0142] A chiral boron-nitrogen heterocyclic compound represented by Formula I-14 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 6,6-diethynyl-1-methyl-6H-5λ. 4 ,6λ 4 -Benzo[3,4][1,2]nitroborono[1,5-a]pyridine.

[0143] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-14 in 94% yield with an ee value of 90%.

[0144] The characterization data for product I-14 are: mp = 259-262 ℃. 1H NMR (400 MHz, CDCl3) δ 8.24(d, J = 8.0 Hz, 1H), 8.20 (d, J = 5.6 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.76(brs, 1H), 7.65 (d, J = 7.6 Hz, 1H), 7.50 (d, J = 6.4 Hz, 1H), 7.34 - 7.27(m, 4H), 7.25 - 7.20 (m, 1H), 7.09 - 7.00 (m, 3H), 6.89 (t, J = 7.6 Hz, 1H), 6.44 (brs, 1H), 2.71 (s, 3H), 2.02 (s, 1H), 1.18 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 162.4, 156.0, 150.3, 144.0, 141.6, 140.3, 139.4, 138.4, 137.5, 132.4, 131.4, 131.2, 130.1, 128.4, 126.9, 126.6, 126.3, 126.0, 125.9, 125.7,125.4, 122.1, 85.3, 34.6, 31.3, 21.2. HRMS (ESI) m / z: [M + H] + C 33 H 30 BN2O + Calculated value: 481.2446; Measured value: 481.2441. HPLC: 5:95. Measured by analytical HPLC, Daicel Chiralpak. ® AD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254nm, t minor = 22.0 min, t major = 27.2 min. [α] D 22.7 = -46.4 (c = 0.01, CH2Cl2).

[0145] Example 15

[0146] A chiral boron-nitrogen heterocyclic compound represented by Formula I-15 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 12,12-diethynyl-12H-11λ. 4 ,12λ 4 -naphtho[1',2':3,4][1,2]nitroborono[1,5-a]pyridine.

[0147] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-15 in 88% yield with an ee value of 86%.

[0148] The characterization data for product I-15 are: mp = 293-295 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.57- 8.27 (m, 3H), 8.20 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 8.05 -8.00 (m, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.86 (d, J= 8.0 Hz, 1H), 7.61 (s, 4H), 7.52 - 7.46 (m, 1H), 7.46 - 7.40 (m, 1H), 7.30 -7.26 (m, 1H), 7.17 (t, J = 7.8 Hz, 1H), 6.97 (brs, 1H), 6.47 (brs, 1H), 2.25 (s, 1H), 1.43 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 162.5, 158.4, 150.4, 143.5,141.7, 140.4, 139.4, 139.1, 134.9, 134.3, 132.8, 131.6, 129.2, 128.5, 128.4,128.3, 127.7, 126.6, 126.5, 126.3, 126.1, 125.5, 125.1, 122.0, 118.8, 118.3,85.8, 34.7, 31.4. DaicelCHIRALPAK ® AD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 0.8 mL / min, 254 nm,t major = 31.6 min, t minor = 34.5 min. HRMS (ESI) m / z: [M + H] + C 36 H 30 BN2O + Calculated value: 517.2446; Test value: 517.2441. [α] D 22.9 = +81.0 (c = 0.01, CH2Cl2).

[0149] Example 16

[0150] A chiral boron-nitrogen heterocyclic compound represented by Formula I-16 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 6,6-diethynyl-6H-5λ. 4 ,6λ 4 -Benzo[4',5']thieno[3',2':3,4][1,2]niboranecyclopentano[1,5-a]pyridine.

[0151] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-16 in 70% yield with an ee value of 74%.

[0152] The characterization data for product I-16 are: mp = 230-232 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.50- 8.40 (m, 2H), 8.10 (brs, 1H), 8.07 - 8.00 (m, 1H), 7.92 (d, J = 8.0 Hz,1H), 7.88 (d, J = 7.2 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.58 - 7.48 (m, 4H), 7.40 - 7.36 (m, 1H), 7.36 - 7.32 (m, 1H), 7.32 - 7.26 (m, 1H), 7.25 - 7.21(m, 1H), 7.13 (t, J = 7.6 Hz, 1H), 6.90 (brs, 1H), 2.22 (s, 1H), 1.39 (s,9H). 13 C NMR (101 MHz, CDCl3) δ 162.4, 154.5, 150.4, 146.3, 144.0, 142.0,140.4, 139.5, 139.3, 139.0, 135.9, 131.8, 128.4, 126.5, 126.5, 126.3, 126.1,125.6, 125.1, 125.0, 123.3, 121.1, 118.5, 85.4, 34.7, 31.4. HRMS (ESI) m / z:[M + H] + C 34 H 28 BN2OS + Calculated value: 523.2010; Measured value: 523.2003. HPLC: 87:13. Determined by analytical HPLC, Daicel CHIRALPAK. ® AD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t major = 13.5 min, t minor = 16.9 min. [α] D 22.7 = +51.6 (c = 0.01, CH2Cl2).

[0153] Example 17

[0154] A chiral boron-nitrogen heterocyclic compound represented by Formula I-17 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 5,5-diethynyl-1,3-dimethyl-5H-5λ. 4 ,6λ 4 -pyrrolo[1',2':3,4][1,3,2]diazoborane[1,5-a]pyridine.

[0155] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-17 in 72% yield with an ee value of 90%.

[0156] The characterization data for product I-17 are: mp = 268-270 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.50(d, J = 9.6 Hz, 1H), 8.12 (brs, 1H), 7.99 (d, J = 6.0 Hz, 1H), 7.73 (t, J =8.0 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.54 - 7.45 (m, 3H), 7.31 (q, J = 7.2Hz, 2H), 6.84 (t, J = 6.8 Hz, 1H), 6.64 (brs, 1H), 5.96 (s, 1H), 2.45 (s,3H), 2.27 (s, 1H), 2.11 (s, 3H), 1.41 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ162.5, 150.5, 149.4, 141.3, 141.0, 139.7, 139.2, 138.0, 132.1, 128.4, 126.9,126.5, 126.2, 126.1, 125.8, 124.8, 123.0, 117.1, 115.8, 115.8, 85.4, 34.6,31.3, 13.0, 12.3. HRMS (ESI) m / z: [M + H] + C 32 H 31 BN3O +Calculated value: 484.2555; Measured value: 484.2556. HPLC: 5:95. Measured by analytical HPLC, Daicel CHIRALPAK. ® AD-Hcolumn, 25 ℃, Hexane / i-PrOH = 85:15, 1.0 mL / min, 254 nm, t minor = 19.3 min,t major = 22.6 min. [α] D 23.2 = -28.7 (c = 0.01, CH2Cl2).

[0157] Example 18

[0158] A chiral boron-nitrogen heterocyclic compound represented by Formula I-18 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 5,5-diethynyl-1,3-diisopropyl-5H-5λ. 4 ,6λ 4 -pyrrolo[1',2':3,4][1,3,2]diazoborane[1,5-a]pyridine.

[0159] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-18 in 88% yield with an ee value of 92%.

[0160] The characterization data for product I-18 are: mp = 230-233 ℃. 11H NMR (400 MHz, CDCl3) δ 8.46 (d, J = 9.6 Hz, 1H), 8.18 (brs, 1H), 7.98 (d, J = 6.0 Hz, 1H), 7.73 (t, J = 8.8 Hz, 1H), 7.57 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.23 - 7.14 (m, 1H), 6.83 (t, J = 7.2 Hz, 1H), 6.33 (brs, 1H), 6.07 (s, 1H), 3.32 (p, J = 6.8 Hz, 1H), 2.84 (p, J = 6.8 Hz, 1H), 2.29 (s, 1H), 1.41 (s, 9H), 1.38 (d, J = 2.4 Hz, 6H), 1.25 (d, J = 6.8 Hz, 3H), 0.81 (d, J = 6.8 Hz, 3H). 13 13C NMR (101 MHz, CDCl3) δ 162.6, 150.5, 149.6, 149.3, 141.4, 141.1, 139.74, 139.3, 136.5, 132.0, 128.5, 126.5, 126.3, 126.1, 125.8, 125.0, 124.9, 117.0, 116.1, 107.7, 85.8, 34.7, 31.4, 27.7, 26.6, 24.4, 23.4, 23.1, 22.7. HRMS (ESI) m / z: [M + H] + C 36 H 39 BN3O + Calculated: 540.3181; Found: 540.3185. HPLC: 96:4 er determined by analytical HPLC, Daicel CHIRALPAK ® AD - H column, 25 °C, Hexane / i - PrOH = 90:10, 1.0 mL / min, 254 nm, t major = 7.0 min, t minor = 12.9 min. [α] D21.8 = -244.4 (c = 0.01, CH2Cl2).

[0161] Example 19

[0162] A chiral boron-nitrogen heterocyclic compound represented by Formula I-19 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 1,3-di-tert-butyl-5,5-dieethynyl-5H-5λ. 4 ,6λ 4 -pyrrolo[1',2':3,4][1,3,2]diazoborane[1,5-a]pyridine.

[0163] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-19 in 90% yield with an ee value of 90%.

[0164] The characterization data for product I-19 are: mp = 308-310 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.44(d, J = 8.0 Hz, 1H), 8.24 (s, 1H), 7.98 (d, J = 5.6 Hz, 1H), 7.81 - 7.70 (m,2H), 7.63 - 7.55 (m, 2H), 7.51 (d, J = 8.8 Hz, 2H), 7.30 - 7.23 (m, 1H), 7.16 (t, J = 7.6 Hz, 1H), 6.86 - 6.81 (m, 1H), 6.31 (d, J = 8.4 Hz, 1H), 6.18 (s,1H), 2.30 (s, 1H), 1.53 (s, 9H), 1.41 (s, 9H), 1.18 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 162.5, 151.3, 150.6, 148.4, 141.4, 140.5, 139.8, 139.6, 139.6,139.3, 132.0, 128.4, 126.9, 126.6, 126.4, 126.2, 125.8, 125.0, 117.7, 116.8,111.7, 86.1, 34.8, 33.3, 31.5, 31.5, 30.9, 30.8. HRMS (ESI) m / z: [M + H] + C 38 H 43 BN3O + Calculated value: 568.3494; Measured value: 568.3497. HPLC: 95:5. Analyzed by analytical HPLC, Daicel CHIRALPAK. ® OD-H column, 25 ℃, Hexane / i-PrOH = 90:10, 1.0 mL / min, 254 nm, t major = 6.7 min, t minor = 13.6 min. [α] D 23.9 = -16.9 (c = 0.01, CH2Cl2).

[0165] Example 20

[0166] A chiral boron-nitrogen heterocyclic compound represented by Formula I-20 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 5,5-diethynyl-1,3-diphenyl-5H-5λ. 4 ,6λ 4 -pyrrolo[1',2':3,4][1,3,2]diazoborane[1,5-a]pyridine.

[0167] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-20 in 92% yield with an ee value of 94%.

[0168] The characterization data for product I-20 are: mp = 252-254 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.42(d, J = 8.8 Hz, 1H), 8.14 (d, J = 5.6 Hz, 2H), 7.89 (d, J = 7.6 Hz, 2H), 7.79(d, J = 8.4 Hz, 1H), 7.77 - 7.70 (m, 3H), 7.62 (d, J = 8.0 Hz, 2H), 7.57 (t,J = 7.6 Hz, 2H), 7.46 (t, J = 7.6 Hz, 3H), 7.30 - 7.23 (m, 4H), 7.22 (d, J =7.2 Hz, 1H), 6.79 (t, J = 6.0 Hz, 1H), 6.52 (s, 1H), 6.52 (brs, 1H), 2.45 (s,1H), 1.46 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 162.3, 150.5, 148.6, 142.0,141.4, 141.3, 140.6, 139.4, 139.1, 135.4, 132.6, 132.0, 129.8, 128.8, HRMS (ESI) m / z: [M + H] + C 42 H 35 BN3O + Calculated value: 608.2868; Measured value: 608.2871. HPLC: 97:3. Determined by analytical HPLC, Daicel Chiralpak. ® OD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254nm, t major = 10.1 min, t minor = 20.6 min. [α] D 23.2 = +27.4 (c = 0.01, CH2Cl2).

[0169] Example 21

[0170] A chiral boron-nitrogen heterocyclic compound represented by formula I-21 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 5,5-diethynyl-1-methyl-3-phenyl-5H-5λ. 4 ,6λ 4 -pyrrolo[1',2':3,4][1,3,2]diazoborane[1,5-a]pyridine.

[0171] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-21 in 92% yield with an ee value of 91%.

[0172] The characterization data for product I-21 are: mp = 288-290 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.43- 8.35 (m, 1H), 8.06 (d, J = 6.0 Hz, 2H), 7.83 - 7.75 (m, 3H), 7.58 (dd, J =11.2, 8.4 Hz, 3H), 7.39 (d, J = 8.0 Hz, 2H), 7.30 - 7.17 (m, 5H), 7.13 (t, J= 7.6 Hz, 1H), 6.92 (t, J = 6.4 Hz, 1H), 6.55 (s, 1H), 2.54 (s, 3H), 2.34 (s,1H), 1.41 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 162.5, 150.6, 148.8, 141.5,141.4, 141.3, 140.3, 139.6, 139.3, 132.9, 132.1, 130.0, 128.4, 127.8, 127.2,126.9, 126.5, 126.4, 126.2, 125.8, 124.8, 123.6, 118.1, 116.3, 116.1, 86.3,34.8, 31.5, 12.4. HRMS (ESI) m / z: [M + H] + C37 H 33 BN3O + Calculated value: 546.2711; Measured value: 546.2717. HPLC: 95.5:4.5. Measured by analytical HPLC, Daicel CHIRALPAK. ® AD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t major = 11.2min, t minor = 22.4 min. [α] D 23.7 = -2.4 (c = 0.01, CH2Cl2).

[0173] Example 22

[0174] A chiral boron-nitrogen heterocyclic compound represented by formula I-22 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 5,5-diethynyl-1,2,3-trimethyl-5H-5λ. 4 ,6λ 4 -pyrrolo[1',2':3,4][1,3,2]diazoborane[1,5-a]pyridine.

[0175] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-22 in 85% yield with an ee value of 80%.

[0176] The characterization data for product I-22 are: mp = 275-278 ℃. 1H NMR (400 MHz, CDCl3) δ 8.47(d, J = 8.0 Hz, 1H), 8.10 (brs, 1H), 7.93 (d, J = 6.0 Hz, 1H), 7.71 (t, J =7.6 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.52 - 7.45 (m, 3H), 7.34 - 7.28 (m,1H), 7.28 - 7.23 (m, 1H), 6.79 (t, J = 6.8 Hz, 1H), 6.63 (brs, 1H), 2.37 (s,3H), 2.24 (s, 1H), 2.04 (s, 3H), 1.96 (s, 3H), 1.40 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 162.6, 150.5, 149.5, 141.3, 141.0, 139.8, 139.3, 135.8, 132.1,128.5, 126.6, 126.3, 126.1, 126.0, 125.8, 125.1, 122.1, 121.4, 116.6, 115.6,85.2, 34.7, 31.4, 11.4, 10.7, 9.3. HRMS (ESI) m / z: [M + H] + C 33 H 33 BN3O + Calculated value: 498.2711; Measured value: 498.2715. HPLC: 90:10. Analyzed by analytical HPLC, Daicel Chiralpak. ® AD-H column, 25 ℃, Hexane / i-PrOH = 90:10, 1.0 mL / min, 254nm, t major = 23.5 min, t minor = 28.8 min. [α] D 22.7 = -28.2 (c = 0.01, CH2Cl2).

[0177] Example 23

[0178] A chiral boron-nitrogen heterocyclic compound represented by formula I-23 ( The preparation method of ) is basically the same as that in Example 1, except that: 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of 3-(4-(tert-butyl)phenyl)-6-morpholinobenzo[d][1,2,3]triazine-4(3H)-one, and 6,6-diethynyl-7,10-dimethyl-6H-5λ 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 5,5-diethynyl-1-methyl-3-phenyl-5H-5λ. 4 ,6λ 4 -pyrrolo[1',2':3,4][1,3,2]diazoborane[1,5-a]pyridine.

[0179] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-23 in 94% yield with an ee value of 84%.

[0180] The characterization data for product I-23 are: mp = 244-246 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.12(d, J = 6.0 Hz, 1H), 8.04 - 7.79 (m, 3H), 7.80 - 7.63 (m, 5H), 7.53 (t, J =7.6 Hz, 2H), 7.42 (t, J = 7.6 Hz, 1H), 7.38 - 7.26 (m, 4H), 7.22 (t, J = 7.6Hz, 2H), 7.18 - 7.13 (m, 1H), 6.99 (td, J = 6.0, 2.0 Hz, 1H), 6.89 (brs, 1H), 6.75 (s, 1H), 6.41 (brs, 1H), 3.78 (d, J = 4.8 Hz, 4H), 3.13 (d, J = 4.8 Hz, 4H), 2.46 (s, 3H), 2.37 (s, 1H). 13C NMR (101 MHz, CDCl3) δ 162.3, 148.9,148.6, 142.0, 141.5, 141.2, 139.6, 138.1, 137.5, 135.5, 132.6, 132.4, 129.7,129.6, HRMS (ESI) m / z: [M + H] + C 43 H 36 BN4O2 + Calculated value: 651.2926; Measured value: 651.2922. HPLC: 8:92. Analyzed by analytical HPLC, Daicel CHIRALPAK. ® AD-H column, 25 ℃, Hexane / i-PrOH = 70:30, 1.0 mL / min, 254 nm, t minor = 11.9 min, t major = 50.4 min. [α] D 22.3 = -42.4 (c = 0.01, CH2Cl2).

[0181] Example 24

[0182] A chiral boron-nitrogen heterocyclic compound represented by Formula I-24 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 7-chloro-10-fluoro-6,6-bis(phenethynyl)-6H-5λ. 4 ,6λ 4 -Benzo[3,4][1,2]nitroborono[1,5-a]pyridine.

[0183] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-24 in 60% yield with an ee value of 74%.

[0184] The characterization data for product I-24 are: mp = 261-263 ℃. 1 H NMR (400 MHz, CDCl3) δ10.05 (d, J = 8.4 Hz, 1H), 8.70 (d, J = 5.6 Hz, 1H), 8.60 (d, J = 8.0 Hz,1H), 7.92 (t, J = 8.0 Hz, 1H), 7.81 (t, J = 7.6 Hz, 1H), 7.72 (d, J = 8.0 Hz,1H), 7.55 (t, J = 7.6 Hz, 1H), 7.44 (t, J = 6.8 Hz, 1H), 7.30 - 7.26 (m, 2H),7.24 - 7.20 (m, 1H), 7.20 - 7.14 (m, 3H), 7.03 - 6.95 (d, J = 9.2 Hz, 2H), 6.73 (t, J = 9.2 Hz, 2H), 6.66 (d, J = 8.0 Hz, 1H), 6.64 - 6.55 (m, 1H), 6.36- 6.28 (m, 2H), 6.24 (t, J = 7.6 Hz, 1H), 5.67 (d, J = 7.6 Hz, 1H), 1.11 (s,9H). 13 C NMR (101 MHz, CDCl3) δ 163.1, 158.4 (d, J C-F = 254.5 Hz), 153.7,149.6, 146.4, 143.6, 142.4, 141.0, 137.0, 135.5, 132.8 (d, J C-F = 7.1 Hz),131.7, 131.2, 131.0, 130.8, 129.7, 129.0, 128.8, 127.9, 127.8, 127.0, 126.3,126.2, 126.1, 125.7 (d, J C-F = 5.1 Hz), 125.3, 125.0, 124.8, 124.0 (d, J C-F =10.1 Hz), 123.0, 122.6 (d, J C-F = 10.1 Hz), 114.4 (d, J C-F = 22.2 Hz), 99.4, 34.2, 31.1. 19F NMR (376 MHz, CDCl3) δ -120.9. HRMS (ESI) m / z: [M + H] + C 44 H 34 BClFN2O + Calculated value: 671.2431; Measured value: 671.2427. HPLC: 13:87. Analyzed by analytical HPLC, Daicel CHIRALPAK. ® IA column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t minor = 14.0 min, t major = 33.1 min. [α] D 22.8 = -3.1 (c = 0.01, CH2Cl2).

[0185] Example 25

[0186] A chiral boron-nitrogen heterocyclic compound represented by Formula I-25 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 7-chloro-10-fluoro-6,6-bis((4-methoxyphenyl)ethynyl)-6H-5λ. 4 ,6λ 4 -Benzo[3,4][1,2]nitroborono[1,5-a]pyridine.

[0187] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-25 in 44% yield with an ee value of 74%.

[0188] The characterization data for product I-25 are: mp = 266-269 ℃. 1H NMR (400 MHz, CDCl3) δ 10.03(d, J = 8.4 Hz, 1H), 8.69 (d, J = 5.6 Hz, 1H), 8.59 (d, J = 7.2 Hz, 1H), 7.93(t, J = 7.6 Hz, 1H), 7.79 (t, J = 8.0 Hz, 2H), 7.54 (t, J = 7.6 Hz, 1H), 7.42(t, J = 6.8 Hz, 1H), 7.24 - 7.18 (m, 3H), 7.07 - 6.96 (m, 2H), 6.76 - 6.70(m, 4H), 6.66 (d, J = 8.4 Hz, 1H), 6.24 (d, J = 6.4 Hz, 1H), 5.84 (dd, J =8.4, 2.8 Hz, 1H), 5.77 (dd, J = 8.4, 2.8 Hz, 1H), 5.55 (dd, J = 8.4, 2.0 Hz,1H), 3.74 (s, 3H), 3.54 (s, 3H), 1.12 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ163.2, 158.7, 158.5 (d, J C-F = 256.5 Hz), 157.7, 153.7, 149.5, 146.1, 143.7,142.5, 141.0, 137.2, 133.0, 132.9, 132.6, 131.0, 130.9, 130.1, 129.8, 128.9(d, J C-F = 13.1 Hz), 128.4, 127.8, 126.4, 125.7, 125.1 (d, J C-F = 22.2 Hz),124.1, 123.1, 122.6 (d, J C-F = 11.1 Hz), 117.8, 114.2 (d, J C-F = 22.2 Hz),113.6, 112.3, 110.8, 99.2, 55.2, 55.1, 34.3, 31.2. 19 F NMR (376 MHz, CDCl3) δ-121.2. HRMS (ESI) m / z: [M + H] + C 46 H 38BClFN2O3 + Calculated value: 731.2643; Measured value: 731.2636. HPLC: 27:73. Measured by analytical HPLC, Daicel CHIRALPAK. ® IAcolumn, 25 ℃, Hexane / i-PrOH = 70:30, 1.0 mL / min, 254 nm, t minor = 15.9 min,t major = 38.6 min. [α] D 23.5 = -16.1 (c = 0.01, CH2Cl2).

[0189] Example 26

[0190] A chiral boron-nitrogen heterocyclic compound represented by Formula I-26 ( The preparation method of ) is basically the same as that in Example 1, except that: 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 7-chloro-10-fluoro-6,6-bis((4-(trifluoromethyl)phenyl)ethynyl)-6H-5λ 4 ,6λ 4 -Benzo[3,4][1,2]nitroborono[1,5-a]pyridine.

[0191] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-26 in 72% yield with an ee value of 54%.

[0192] The characterization data for product I-26 are: mp = 329-331 ℃. 1H NMR (600 MHz, CDCl3) δ 9.93(d, J = 8.4 Hz, 1H), 8.76 (d, J = 6.0 Hz, 1H), 8.61 (d, J = 8.0 Hz, 1H), 8.05(t, J = 7.6 Hz, 1H), 7.85 - 7.78 (m, 2H), 7.59 (t, J = 7.6 Hz, 1H), 7.52 (t,J = 6.8 Hz, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.23(dd, J = 8.8, 3.6 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 6.95 (d, J = 8.4 Hz,1H), 6.82 - 6.74 (m, 2H), 6.61 - 6.51 (m, 4H), 5.80 (d, J = 8.0 Hz, 1H), 1.09(s, 9H). 13 C NMR (151 MHz, CDCl3) δ 162.8, 158.3 (d, J C-F = 256.8 Hz), 153.8(d, J C-F = 4.8 Hz), 150.3, 144.9, 143.8, 141.9, 141.7, 139.2, 136.5, 133.2 (d,J C-F = 7.0 Hz), 132.1, 131.4, 131.4, 130.9, 130.7, 129.4 (d, J C-F = 9.3 Hz),129.1, 128.9, 128.7, 128.7, 128.5 (d, J C-F = 32.6 Hz), 128.1, 126.4 (q, J C-F =32.7 Hz), 125.2 (d, J C-F = 28.3 Hz), 124.9 (q, J C-F = 3.7 Hz), 123.8 (d, J C-F =9.6 Hz), 123.7 (d, J C-F = 183.7 Hz), 123.4, 122.8 (d, J C-F = 10.7 Hz), 122.7(d, JC-F = 3.9 Hz), 122.5, 122.5 (d, J C-F = 3.7 Hz), 115.0 (d, J C-F = 22.1 Hz), 98.6, 34.3, 31.0. 19 F NMR (376 MHz, CDCl3) δ -62.6, -63.6, -120.2. HRMS (ESI)m / z: [M + H] + C 46 H 32 BClF7N2O + Calculated value: 807.2179; Measured value: 807.2169. HPLC: 23:77. Determined by analytical HPLC, Daicel CHIRALPAK. ® IB column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t minor = 18.9 min, t major = 27.8 min. [α] D 22.6 =-26.0 (c = 0.01, CH2Cl2).

[0193] Example 27

[0194] A chiral boron-nitrogen heterocyclic compound represented by Formula I-27 ( The preparation method of ) is basically the same as that in Example 1, except that: 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of (E)-2-methoxy-4-((8-methylnon-6-enamido)methyl)phenyl-4-(4-oxobenzo[d][1,2,3]triazine-3(4H)-yl)benzoate, and 6,6-diethynyl-7,10-dimethyl-6H-5λ 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 5,5-diethynyl-1-methyl-3-phenyl-5H-5λ. 4 ,6λ 4 -pyrrolo[1',2':3,4][1,3,2]diazoborane[1,5-a]pyridine.

[0195] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 4 / 1) to give product I-27 in 86% yield with an ee value of 90%.

[0196] The characterization data for product I-27 are: mp = 128-130 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.37(t, J = 8.8 Hz, 3H), 8.25 - 7.90 (m, 3H), 7.85 (d, J = 7.6 Hz, 2H), 7.79-7.73(m, 2H), 7.70 (d, J = 8.4 Hz, 2H), 7.62-7.49 (m, 4H), 7.43 (t, J = 7.2 Hz,1H), 7.35-7.26 (m, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 7.2Hz, 1H), 7.14 (d, J = 8.0 Hz, 1H), 7.00 (t, J = 6.4 Hz, 1H), 6.96 (s, 1H), 6.90 (d, J= 8.0 Hz, 1H), 6.74 (s, 1H), 6.52 (brs, 1H), 6.07 (t, J = 6.0 Hz, 1H), 5.41-5.31 (m, 1H), 4.44 (d, J = 5.7 Hz, 2H), 3.82 (s, 3H), 2.45 (s, 1H), 2.23 (t,J = 7.7 Hz, 2H), 2.02-1.98 (m, 1H), 1.72-1.63 (m, 2H), 1.57-1.38 (m, 2H),1.34-1.25 (m, 3H), 1.22-1.11 (m, 1H), 0.98-0.82 (m, 6H). 13C NMR (101 MHz, CDCl3) δ 173.1, 173.0, 164.1, 162.0, 151.3, 148.7, 146.2, 142.0, 141.5,139.3, 139.1, 138.0, 137.6, 135.3, 132.7, 132.4, 131.3, 129.9, 128.8, 128.6,128.5, 128.5, 128.4, 127.7, 127.4, 127.3, 127.2, 127.1, 126.4, 126.2, 126.1,124.6, 122.9, 120.0, 119.2, 116.4, 115.1, 112.1, 86.8, 55.9, 43.3, 36.6,32.2, 30.9, 29.3, 25.2, 22.6. HRMS (ESI) m / z: [M + H] + C 57 H 52 BN4O5 + Calculated value: 883.4025; Measured value: 883.4017. HPLC: 95:5. Analyzed by analytical HPLC, Daicel Chiralpak. ® AD-H column, 25 ℃, Hexane / i-PrOH = 70:30, 1.0 mL / min, 254nm, t major = 7.3 min, t minor = 10.4 min. [α] D 21.5 = +93.7 (c = 0.01, CH2Cl2).

[0197] Example 28

[0198] A chiral boron-nitrogen heterocyclic compound represented by formula I-28 ( The preparation method of ) is basically the same as that in Example 1, except that: 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of (S)-3,7-dimethyloct-6-en-1-yl-4-(4-oxobenzo[d][1,2,3]triazine-3(4H)-yl)benzoate, and the compound 6,6-diethynyl-7,10-dimethyl-6H-5λ is replaced with benzoate. 4 ,6λ 4The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 5,5-diethynyl-1-methyl-3-phenyl-5H-5λ. 4 ,6λ 4 -pyrrolo[1',2':3,4][1,3,2]diazoborane[1,5-a]pyridine.

[0199] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10 / 1) to give product I-28 in 92% yield and de value of 93%.

[0200] The characterization data for product I-28 are: mp = 110-112 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.36(d, J = 6.4 Hz, 1H), 8.22 (d, J = 8.0 Hz, 2H), 8.13 (d, J = 6.0 Hz, 1H), 8.01(brs, 1H), 7.83 (d, J = 7.6 Hz, 2H), 7.79-7.73 (m, 2H), 7.73-7.66 (m, 2H),7.54 (t, J = 7.6 Hz, 4H), 7.42 (t, J = 7.6 Hz, 1H), 7.29-7.14 (m, 5H), 7.01(td, J = 6.0, 2.0 Hz, 1H), 6.73 (s, 1H), 6.53 (brs, 1H), 5.19-5.07 (m, 1H), 4.51-4.36 (m, 2H), 2.43 (s, 1H), 2.14-1.94 (m, 2H), 1.93-1.80 (m, 1H), 1.71(s, 3H), 1.69-1.63 (m, 2H), 1.64 (s, 3 H), 1.50-1.38 (m, 1H), 1.31-1.27 (m,1H), 1.01 (d, J = 6.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 166.0, 162.1, 148.8,145.7, 142.1, 141.5, 141.4, 139.3, 135.4, 132.7, 132.4, 131.4, 130.5, 130.0,129.7, 128.9, 128.6, 128.5, 127.8, 127.5, 127.4, 127.2, 126.9, 126.3, 126.0,124.6, 119.2, 116.5, 115.1, 86.8, 63.8, 37.0, 35.5, 29.5, 25.7, 25.4, 19.5,17.7. HPLC: 89:11 dr determined by analytical HPLC, Daicel CHIRALPAK ® AD-Hcolumn, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t major = 9.3 min,t minor = 13.0 min. HRMS (ESI) m / z: [M + H] + C 49 H 45 BN3O3 + Calculated value: 734.3548; Test value: 734.3541. [α] D 21.8 = -27.9 (c = 0.01, CH2Cl2).

[0201] Example 29

[0202] A chiral boron-nitrogen heterocyclic compound represented by Formula I-29 ( The preparation method of ) is basically the same as that of Example 1, except that: 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of ((3aR,5R,5aS,8aS,8bR)-2,2,7,7-tetramethyltetrahydro-5H-bis([1,3]dioxacyclopentene)[4,5-b:4',5'-d]pyran-5-yl)methyl-4-(4-oxobenzo[d][1,2,3]triazine-3(4H)-yl)benzoate, and the compound 6,6-diethynyl-7,10-dimethyl-6H-5λ is replaced with benzoate. 4 ,6λ 4The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 5,5-diethynyl-1-methyl-3-phenyl-5H-5λ. 4 ,6λ 4 -pyrrolo[1',2':3,4][1,3,2]diazoborane[1,5-a]pyridine.

[0203] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5 / 1) to give product I-29 in 88% yield with a de value of 90%.

[0204] The characterization data for product I-29 are: mp = 134-136 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.35(d, J = 6.0 Hz, 1H), 8.24 (d, J = 8.0 Hz, 2H), 8.13 (d, J = 5.6 Hz, 1H), 8.03(brs, 1H), 7.83 (d, J = 7.6 Hz, 2H), 7.79-7.70 (m, 2H), 7.68 (d, J = 7.6 Hz, 2H), 7.52 (t, J = 7.6 Hz, 4H), 7.41 (t, J = 7.4 Hz, 1H), 7.28-7.14 (m, 5H), 7.02-6.94 (m, 1H), 6.73 (s, 1H), 6.52 (brs, 1H), 5.60 (d, J = 4.8 Hz, 1H), 4.69 (dd, J = 8.0, 2.4 Hz, 1H), 4.60 (dd, J = 12.0, 4.8 Hz, 1H), 4.54-4.44(m, 1H), 4.42-4.34 (m, 2H), 4.28-4.21 (m, 1H), 2.45 (s, 1H), 1.57 (s, 3H), 1.52 (s, 3H), 1.39 (s, 3H), 1.36 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 165.7,162.0, 148.7, 145.8, 142.0, 141.4, 139.3, 135.4, 132.6, 132.3, 130.7, 129.8,129.2, 128.8, 128.6, 128.5, 128.4, 127.7, 127.4, 127.3, 127.2, 126.9, 126.3,126.0, 124.5, 119.2, 116.4, 115.0, 109.7, 108.8, 96.3, 86.8, 71.1, 70.7,70.5, 66.1, 64.1, 26.0, 25.9, 24.9, 24.5. HRMS (ESI) m / z: [M + H] + C 51 H 45 BN3O8 + Calculated value: 838.3294; ​​Measured value: 838.3285. HPLC: 95:5 dr determined by analytical HPLC, Daicel CHIRALPAK ® OD-H column, 25 ℃, Hexane / i-PrOH = 70:30, 1.0 mL / min, 254 nm, t major = 15.8 min, t minor = 26.8 min. [α] D 22.7 = -1.1 (c = 0.01, CH2Cl2).

[0205] Example 30

[0206] A chiral boron-nitrogen heterocyclic compound represented by Formula I-30 ( The preparation method of ) is basically the same as that in Example 1, except that: 3-(4-(tert-butyl)phenyl)benzo[d][1,2,3]triazine-4(3H)-one is replaced with an equimolar amount of the compound 4-(4-oxobenzo[d][1,2,3]triazine-3(4H)-yl)phenyl-(S)-2-(4-isobutylphenyl)propionate, and 6,6-diethynyl-7,10-dimethyl-6H-5λ is used. 4 ,6λ 4 The benzo[3,4][1,2]azaborane[1,5-a]pyridine is replaced with an equimolar amount of 5,5-diethynyl-1-methyl-3-phenyl-5H-5λ. 4 ,6λ4 -pyrrolo[1',2':3,4][1,3,2]diazoborane[1,5-a]pyridine.

[0207] The mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product I-30 in 92% yield with a de value of 92%.

[0208] The characterization data for product I-30 are: mp = 98-100 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.42-8.35 (m, 1H), 8.23-7.95 (m, 2H), 7.87 (d, J = 7.6 Hz, 2H), 7.82-7.61 (m, 5H), 7.55 (t, J = 7.6 Hz, 2H), 7.51-7.41 (m, 3H), 7.39 (d, J = 8.0 Hz, 2H), 7.30-7.26 (m, 1H), 7.25-7.15 (m, 7H), 6.96 (t, J = 6.4 Hz, 1H), 6.76 (s, 1H), 6.55(brs, 1H), 4.04 (q, J = 7.2 Hz, 1H), 2.54 (d, J = 7.2 Hz, 2H), 2.45 (s, 1H), 2.03-1.86 (m, 1H), 1.69 (d, J = 7.2 Hz, 3H), 0.98 (d, J = 6.8 Hz, 6H). 13 C NMR(101 MHz, CDCl3) δ 173.1, 162.2, 149.9, 148.6, 141.9, 141.4, 141.3, 140.8,140.1, 139.3, 139.1, 137.0, 135.4, 132.6, 132.1, 129.7, 129.5, 128.7, 128.6,128.5, 128.5, 128.3, 127.9, 127.6, 127.3, 127.2, 127.1, 127.1, 126.2, 125.8,124.4, 122.0, 119.2, 116.3, 114.9, 86.8, 45.2, 44.9, 30.1, 22.3, 18.4. HPLC:96:4 dr determined by analytical HPLC, Daicel CHIRALPAK ®IA column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t major = 14.8 min, t minor = 25.3 min.HRMS (ESI) m / z: [M + H] + C 51 H 43 BN3O3 + Calculated value: 756.3392; Test value: 756.3386. [α] D 22.1 = +55.2 (c = 0.01, CH2Cl2).

[0209] Example 31

[0210] A chiral boron-nitrogen heterocyclic compound represented by formula II-01 ( The preparation method of ) includes the following steps:

[0211] In an argon-filled glove box, a 10.0 mL PTFE screw-cap test tube, dried in an oven, was filled with I-20 (60.7 mg, 0.10 mmol, 1.0 equiv.), 1-bromopyrene (0.12 mmol, 1.2 equiv.), Pd(PPh3)4 (11.6 mg, 10 mol%), CuI (3.8 mg, 20 mol%), and TEA / THF (1:1 mixed solvent, 2.0 mL). The tube was capped and removed from the glove box. The resulting mixture was placed in an aluminum block reactor preheated to 60 °C and stirred for 8 hours. After the reaction, the mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product II-01, with a yield of 79% and an ee value of 94%.

[0212] The characterization data for product II-01 are: mp = 249-251 ℃. 1H NMR (400 MHz, CDCl3) δ8.60-8.38 (m, 3H), 8.35 (brs, 1H), 8.20 - 8.14 (m, 2H), 8.08-7.92 (m, 8H),7.83 (d, J = 8.4 Hz, 1H), 7.79-7.71 (m, 3H), 7.61-7.41 (m, 7H), 7.32 (t, J =7.2 Hz, 4H), 7.28-7.21 (m, 1H), 7.08-7.01 (m, 1H), 6.83 (s, 1H), 6.68 (brs,1H), 1.34 (s, 9H). 13 C NMR (151 MHz, CDCl3) δ 162.5, 150.6, 148.9, 142.3,141.8, 141.4, 139.7, 139.3, 135.7, 133.0, 132.2, 132.1, 131.3, 131.0, 130.8,129.8, 129.7, 128.9, 128.9, 128.7, 128.6, 128.0, 128.0, 127.9, 127.7, 127.4,127.3, 127.2, 126.7, 126.3, 126.2, 126.2, 125.9, 125.7, 125.4, 125.3, 124.4,124.3, 119.4, 119.2, 116.6, 115.2, 97.9, 34.7, 31.4. HRMS (ESI) m / z: [M + H] + C 58 H 43 BN3O + Calculated value: 808.3494; Measured value: 808.3489. HPLC: 97:3. Analyzed by analytical HPLC, Daicel CHIRALPAK. ® OD-H column, 25 ℃, Hexane / i-PrOH = 80:20, 1.0 mL / min, 254 nm, t major = 20.2 min, t minor = 36.9 min. [α] D 21.3 = +125.3 (c =0.01, CH2Cl2).

[0213] Example 32

[0214] A chiral boron-nitrogen heterocyclic compound represented by formula III-01 ( The preparation method of ) includes the following steps:

[0215] Alkyne I-20 (60.7 mg, 0.1 mmol, 1.0 equivalent) and Pd / C (10.6 mg, 10 mol%) were added to a reaction flask. After three evacuation and nitrogen purging cycles, methanol (20 mL) was injected, followed by hydrogen purging through a balloon to displace the resulting suspension. The reaction was stirred at room temperature for 24 hours, then the solvent was removed under reduced pressure. The residue was purified by rapid silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 4 / 1) to give a yellow solid product III-01 (58.0 mg), with a yield of 95% and an ee value of 91%.

[0216] The characterization data for product Ⅲ-01 are: mp = 270-271 ℃. 1 H NMR (400 MHz, CDCl3) δ8.37 (d, J = 7.6 Hz, 1H), 7.76 (d, J = 5.6 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H),7.61 - 7.55 (m, 3H), 7.45 - 7.38 (m, 4H), 7.35 (s, 1H), 7.32 - 7.27 (m, 4H), 7.22 - 7.14 (m, 2H), 7.13 (d, J = 1.6 Hz, 2H), 7.07 - 7.02 (m, 3H), 6.89 -6.80 (m, 2H), 6.59 (s, 1H), 1.27 (s, 9H), 0.96 - 0.88 (m, 1H), 0.75 - 0.66 (m, 1H), 0.00 (t, J = 7.6 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 162.4, 150.7,149.2, 141.8, 140.5, 140.3, 139.4, 137.2, 136.0, 133.8, 132.28, 129.2, 128.7,128.6, HRMS (ESI) m / z: [M + H] + C 42 H 39 BN3O + Calculated value: 612.3181; Measured value: 612.3183. HPLC: 95.5:4.5. Analyzed by analytical HPLC, Daicel CHIRALPAK. ® AD-H column, 25 ℃, Hexane / i-PrOH = 70:30, 1.2 mL / min, 254 nm, t minor = 10.4 min, t major = 6.5 min. [α] D 22.9 = +4.7 (c =0.01, CH2Cl2).

[0217] Example 33

[0218] A chiral boron-nitrogen heterocyclic compound of formula IV-01 ( The preparation method of ) includes the following steps:

[0219] In an argon-filled glove box, CuI (2.0 mg, 0.075 mmol, 0.75 equiv.), paraformaldehyde (14.0 mg, 0.16 mmol, 1.6 equiv.), diisopropylamine (19 μL, 0.14 mmol, 1.4 equiv.), I-11 (51.8 mg, 0.10 mmol, 1.0 equiv.), and dioxane (2.0 mL) were added sequentially to an oven-dried 10.0 mL polytetrafluoroethylene screw-cap test tube. The resulting mixture was placed in an aluminum block reactor preheated to 110 °C and stirred for 15 hours. After the reaction was completed, the mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 4 / 1) to give product IV-01 in 70% yield with an ee value of 94%.

[0220] The characterization data for product Ⅳ-01 are: mp = 200-202 ℃. 1 H NMR (400 MHz, CDCl3) δ8.47 (d, J = 8.0 Hz, 1H), 8.37 (d, J = 8.0 Hz, 1H), 8.23 ​​(d, J = 5.6 Hz, 1H), 8.13 (t, J = 7.6 Hz, 1H), 7.73 - 7.60 (m, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.52- 7.41 (m, 3H), 7.34 (dd, J = 8.4, 4.0 Hz, 1H), 7.28 - 7.24 (m, 1H), 7.20 -7.08 (m, 1H), 7.04 (t, J = 7.6 Hz 1H), 6.43 (brs, 1H), 5.66 (t, J = 6.8 Hz, 1H), 4.12 (dd, J = 10.0, 6.8 Hz, 1H), 3.80 (dd, J = 10.0, 6.8 Hz, 1H), 1.40 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 207.3, 162.4, 159.2 (d, J C-F = 257.6 Hz), 152.8 (d, J C-F = 5.1 Hz), 150.5, 143.8, 141.4, 140.8, 139.4, 138.7, 133.1 (d,J C-F= 7.1 Hz), 131.6, 131.4, 128.5, 126.7, 126.4, 126.1, 125.5, 125.0, 124.0(d, J C-F = 10.1 Hz), 122.63, 122.60, 122.5, 115.3 (d, J C-F = 22.2 Hz), 68.5, 34.7, 31.4. 19 F NMR (376 MHz, CDCl3) δ -119.3. HRMS (ESI) m / z: [M + H] + C 33 H 28 BClFN2O + Calculated value: 533.1962; Measured value: 533.1957. HPLC: 3:97. Analyzed by analytical HPLC, Daicel CHIRALPAK. ® AD-H column, 25 ℃, Hexane / i-PrOH = 70:30, 1.0 mL / min, 254 nm, t minor = 9.9 min, t major = 24.7 min. [α] D 18.9 = -84.6 (c = 0.01, CH2Cl2).

[0221] Example 34

[0222] A chiral boron-nitrogen heterocyclic compound represented by formula V-01 ( The preparation method of ) includes the following steps:

[0223] In an argon-filled glove box, Cu(CH3CN)4PF6 (4.0 mg, 0.10 mmol, 10 mol%), I-11 (51.8 mg, 0.10 mmol), benzyl azide (26.6 mg, 0.2 mmol, 2.0 equiv.), and THF (2.0 mL) were added sequentially to a 10 mL polytetrafluoroethylene screw-cap test tube that had been dried in an oven. The reaction system was stirred at 50 °C for 20 hours. After the reaction was completed, the mixture was concentrated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 1 / 1) to give product V-01 in 88% yield with an ee value of 94%.

[0224] The characterization data for product V-01 are: mp = 223-225 ℃. 1 H NMR (400 MHz, CD3OD) δ8.88 (d, J = 5.6 Hz, 1H), 8.29 (dd, J = 12.7, 8.0 Hz, 2H), 8.19 (t, J = 7.6Hz, 1H), 7.88 (s, 1H), 7.65 (s, 1H), 7.50 (t, J = 6.8 Hz, 1H), 7.43 (d, J =8.0 Hz, 2H), 7.34 - 7.22 (m, 4H), 7.17 - 7.11 (m, 4H), 7.10 - 7.01 (m, 3H), 6.61 (brs, 1H), 5.40 (s, 2H), 1.31 (s, 9H). 13 C NMR (101 MHz, CD3OD) δ 164.1,160.5 (d, J C-F = 257.6 Hz), 154.1, 152.2, 146.0, 144.4, 142.1, 140.5, 140.5,137.0, 134.9 (d, J C-F = 8.1 Hz), 133.2, 132.7, 129.8, 129.2, 128.6, 127.4,127.3, 127.2, 126.7, 126.3 (d, J C-F = 9.1 Hz), 125.4, 124.2 (d, J C-F = 11.1Hz), 117.4 (d, J C-F = 23.2 Hz), 79.4, 54.3, 35.5, 31.8. 19 F NMR (376 MHz, CDCl3) δ -118.9. HRMS (ESI) m / z: [M + H] + C 39 H 33 BClFN5O + Calculated value: 652.2445; Measured value: 652.2440. HPLC: 3:97. Measured by analytical HPLC, Daicel CHIRALPAK. ®AD-Hcolumn, 25 ℃, Hexane / i-PrOH = 70:30, 1.2 mL / min, 254 nm, t minor = 43.7 min,t major = 82.7 min. [α] D 18.5 = -32.2 (c = 0.01, CH2Cl2).

[0225] Example 35

[0226] A chiral boron-nitrogen heterocyclic compound represented by formula VI-01 ( The preparation method of ) includes the following steps:

[0227] Under a nitrogen atmosphere, CuSO4·5H2O (2.5 mg, 0.010 mmol, 10 mol%), sodium citrate (12.9 mg, 0.05 mmol, 0.5 equiv.), and potassium bicarbonate (40.0 mg, 0.40 mmol, 4.0 equiv.) were added sequentially to a 10 mL PTFE screw-cap test tube that had been dried in an oven. A mixed solvent of THF and water (volume ratio = 1:1, 1.0 mL) was then added. The mixture was stirred at room temperature for 20 minutes, followed by the addition of a solution of I-11 (51.8 mg, 0.10 mmol, 1.0 equiv.) and (Z)-N-hydroxybenzylimine chloride (23.2 mg, 0.15 mmol, 1.5 equiv.) dissolved in the above mixed solvent (1.5 mL). The reaction system was stirred at 110 °C for 15 hours. The mixture was filtered through diatomaceous earth and washed with dichloromethane (15 mL × 3 times). The organic phases were combined and dried over anhydrous sodium sulfate. After vacuum concentration of the solvent, the product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2 / 1) to give product VI-01 in 89% yield with an ee value of 94%.

[0228] The characterization data for product VI-01 are: mp = 213-215 ℃. 1H NMR (400 MHz, CDCl3) δ8.88 (d, J = 5.6 Hz, 1H), 8.51 (d, J = 8.0 Hz, 1H), 8.37 (d, J = 8.0 Hz, 1H), 8.19 (t, J = 7.6 Hz, 1H), 7.74 (d, J = 7.6 Hz, 2H), 7.52 (t, J = 6.8 Hz, 1H),7.49 - 7.43 (m, 3H), 7.42 - 7.34 (m, 5H), 7.32 - 7.26 (m, 2H), 7.18 - 7.09(m, 2H), 6.56 (s, 1H), 6.43 (brs, 1H), 1.34 (s, 9H). 13 C NMR (101 MHz, CDCl3)δ 162.3, 161.1, 159.0 (d, J C-F = 257.6 Hz), 153.3 (d, J C-F = 4.0 Hz), 150.4,144.8, 142.5, 140.3, 139.3, 138.9, 134.0 (d, J C-F = 8.1 Hz), 131.8, 131.7,129.5, 129.4, 128.7, 128.6, 126.8, 126.1, 126.1, 125.7, 124.8 (d, J C-F = 10.1Hz), 124.6, 123.6, 122.8 (d, J C-F = 11.1 Hz), 116.3 (d, J C-F = 22.2 Hz), 107.2, 34.5, 31.2. 19 F NMR (376 MHz, CDCl3) δ -118.5. HRMS (ESI) m / z: [M + H] + C 39 H 31 BClFN3O2 + Calculated value: 638.2176; Measured value: 638.2173. HPLC: 3:97. Analyzed by analytical HPLC, Daicel CHIRALPAK. ®IA column, 25 ℃, Hexane / i-PrOH = 70:30, 1.2 mL / min, 210 nm, t minor = 17.7 min, t major = 21.0 min. [α] D 20.4 = +19.7 (c =0.01, CH2Cl2).

[0229] Test Example 1

[0230] To investigate the photophysical properties of chiral boron-nitrogen heterocyclic compounds, the chiral boron-nitrogen heterocyclic compounds prepared in Examples 17-22 were subjected to spectral analysis. The results are as follows:

[0231] like Figure 1 As shown in (a), the UV-Vis absorption spectra were measured using a Shimadzu-UV-2600 spectrometer. A 10 μM solution of chiral boron-nitrogen heterocyclic compounds (dichloromethane as solvent) was used as the test system. The maximum UV-Vis absorption peaks of the chiral boron-nitrogen heterocyclic compounds represented by formulas I-17, I-18, and I-19 were found to be at 400 nm, while the maximum absorption peaks of the chiral boron-nitrogen heterocyclic compounds represented by formulas I-20, I-21, and I-22 were at 410 nm. Figure 1 As shown in (b), the fluorescence emission spectra were measured using a Guangdong F-97 spectrometer. A 10 μM solution of chiral boron-nitrogen heterocyclic compounds (dichloromethane as solvent) was used as the test system. The maximum emission peaks of the chiral boron-nitrogen heterocyclic compounds represented by formulas I-17, I-18, and I-19 were located at 500 nm, while the maximum emission peaks of the chiral boron-nitrogen heterocyclic compounds represented by formulas I-20, I-21, and I-22 were located at 510 nm. Figure 1 As shown in (c), circular dichroism spectroscopy was performed using a Chirascan V100 spectrometer with a 10 μM solution of chiral boron-nitrogen heterocyclic compounds (dichloromethane as the solvent) as the test system. The chiral boron-nitrogen heterocyclic compounds and their enantiomers represented by Formula I-20 exhibited a significant Corton effect at 343 nm, indicating that they possess a significant chiral optical response; Figure 1 As shown in (d), the circularly polarized emission spectra were measured using a Jasco CPL-300 spectrometer. A 10 μM solution of a chiral boron-nitrogen heterocyclic compound (dichloromethane as solvent) was used as the test system. The chiral boron-nitrogen heterocyclic compound represented by Formula I-20 exhibits excellent circularly polarized emission activity in solution. The spectra of this chiral boron-nitrogen heterocyclic compound and its enantiomers show clear mirror symmetry. The measured emission asymmetry factor (g)... lum The values ​​are +2.62 × 10⁻⁶.-4 and -1.91 × 10 -4 The above results fully demonstrate that the chiral boron-nitrogen heterocyclic compounds provided by this invention exhibit rich and excellent photophysical behaviors in the fields of absorption, emission, and chiral optics. This characteristic makes them potentially valuable in multiple fields such as medicinal chemistry and biochemistry, and further expands their applications as chiral functional materials and chiral fluorescent probes.

[0232] Test Example 2

[0233] The chiral boron-nitrogen heterocyclic compound prepared in Example 23 was subjected to biosafety and lysosomal targeting tests.

[0234] The biocompatibility test method was as follows: Different concentrations of chiral boron-nitrogen heterocyclic compound solutions (using dimethyl sulfoxide as solvent) of Formula I-23 were co-incubated with HeLa cell models at 37 °C for 24 hours under dark conditions. The test results are as follows: Figure 2 As shown, even at a high concentration of 100 μM, no significant cytotoxicity was observed, confirming that the chiral boron-nitrogen heterocyclic compound represented by Formula I-23 possesses excellent biocompatibility.

[0235] The method for testing lysosomal targeting was as follows: a co-localization assay was performed, using a commercially available lysosomal dye (Lyso-Tracker) and a chiral boron-nitrogen heterocyclic compound as shown in Formula I-23 to co-stain HeLa cells (concentration: 0.5 μM). The test results are as follows: Figure 3 As shown, the cell imaging of the two exhibits a high degree of overlap, with a Pearson correlation coefficient of 0.90 and an overlap coefficient R of 0.92 ± 0.01, which fully demonstrates that this chiral boron-nitrogen heterocyclic compound has excellent lysosomal targeting performance as a chiral fluorescent molecule.

[0236] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art should understand that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively describe all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A chiral boron-nitrogen heterocyclic compound, characterized in that, It has the following general structural formula: ； Where A is a benzene ring or a thiophene ring; B is a benzene ring, a naphthylene ring, a benzothiophene ring, or a pyrrole ring; Z is C or N; R 1 The substituent is selected from one or more of hydrogen, alkyl, alkoxy, morpholino, trifluoromethyl, ester, halogen, phenyl and substituted phenyl, wherein the substituent of the substituted phenyl is selected from one or more of alkyl, alkoxy, ester and thiophene. R 2 The substituent is selected from one or more of hydrogen, alkyl, alkoxy, morpholino, trifluoromethyl, ester, halogen, phenyl and substituted phenyl, wherein the substituent of the substituted phenyl is selected from one or more of alkyl, alkoxy, ester and thiophene groups; R 3 The phenyl group is selected from alkyl, benzyl, phenyl or substituted phenyl groups, wherein the substituents of the substituted phenyl group are selected from one or more of alkyl, alkoxy, trifluoromethyl, ester and halogen groups; R 4 The phenyl group is selected from hydrogen, alkyl, phenyl or substituted phenyl, wherein the substituent of the substituted phenyl group is selected from one or more of alkyl, alkoxy, trifluoromethyl, ester and halogen groups; R 5 The substituted group is selected from ethyl, alkynyl, substituted alkynyl, allenyl, triazolyl, substituted triazolyl, isoxazolyl or substituted isoxazolyl, wherein the substituent of the substituted alkynyl is selected from alkyl, pyrene, phenyl or substituted phenyl, the substituent of the substituted phenyl is selected from alkoxy or trifluoromethyl, the substituent of the substituted triazolyl is benzyl, and the substituent of the substituted isoxazolyl is phenyl; R 6 It is selected from one or more of hydrogen, alkyl, halogen and phenyl.

2. The chiral boron-nitrogen heterocyclic compound according to claim 1, characterized in that, R 1 Selected from one or more of hydrogen, methyl, alkoxy, morpholino, and methoxycarbonyl; R 2 Selected from hydrogen or methyl; R 3 Selected from benzyl, phenyl, or substituted phenyl groups, wherein the substituents of the substituted phenyl group are selected from one or more of methyl, tert-butyl, alkoxy, trifluoromethyl, and ester groups; R 4 Selected from hydrogen, phenyl, or substituted phenyl groups, wherein the substituents of the substituted phenyl groups are selected from one or more of alkoxy and trifluoromethyl groups; R 5 The group is selected from ethyl, alkynyl, substituted alkynyl, allenyl, substituted triazolyl, or substituted isoxazolyl, wherein the substituent of the substituted alkynyl group is selected from pyrene, phenyl, or substituted phenyl, the substituent of the substituted phenyl group is selected from alkoxy or trifluoromethyl, the substituent of the substituted triazolyl group is benzyl, and the substituent of the substituted isoxazolyl group is phenyl; R 6 It is selected from one or more of hydrogen, methyl, isopropyl, halogen and phenyl.

3. The chiral boron-nitrogen heterocyclic compound according to claim 1 or 2, characterized in that, The chiral boron-nitrogen heterocyclic compounds are selected from compounds with the following structures, or their enantiomers and diastereomers: 。 4. A method for preparing a chiral boron-nitrogen heterocyclic compound, characterized in that, Includes the following steps: Isoquinolinone compounds and The reaction was carried out in the presence of a nickel catalyst, an imidazoline ligand and an organic solvent to obtain the chiral boron-nitrogen heterocyclic compound shown in Formula I. The structural formula of the isoquinolinone compound is as follows: ; The structural formula of the imidazoline ligand is as follows: ; The structural formula of the chiral boron-nitrogen heterocyclic compound represented by Formula I is as follows: ; Where A is a benzene ring or a thiophene ring; B is a benzene ring, a naphthylene ring, a benzothiophene ring, or a pyrrole ring; Z is C or N; R 1 The substituent is selected from one or more of hydrogen, alkyl, alkoxy, morpholino, trifluoromethyl, ester, halogen, phenyl and substituted phenyl, wherein the substituent of the substituted phenyl is selected from one or more of alkyl, alkoxy, ester and thiophene. R 2 The substituent is selected from one or more of hydrogen, alkyl, alkoxy, morpholino, trifluoromethyl, ester, halogen, phenyl and substituted phenyl, wherein the substituent of the substituted phenyl is selected from one or more of alkyl, alkoxy, ester and thiophene groups; R 3 The phenyl group is selected from alkyl, benzyl, phenyl or substituted phenyl groups, wherein the substituents of the substituted phenyl group are selected from one or more of alkyl, alkoxy, trifluoromethyl, ester and halogen groups; R 4 The phenyl group is selected from hydrogen, alkyl, phenyl or substituted phenyl, wherein the substituent of the substituted phenyl group is selected from one or more of alkyl, alkoxy, trifluoromethyl, ester and halogen groups; R 5 The alkynyl group is selected from alkynyl or substituted alkynyl groups, wherein the substituent of the substituted alkynyl group is selected from alkyl, phenyl or substituted phenyl groups, and the substituent of the substituted phenyl group is selected from alkoxy or trifluoromethyl groups; R 6 It is selected from one or more of hydrogen, alkyl, halogen and phenyl.

5. The preparation method according to claim 4, characterized in that, The chiral boron-nitrogen heterocyclic compound shown in Formula I was reacted in the presence of a catalyst, 1-bromopyrene, and an organic solvent to obtain the chiral boron-nitrogen heterocyclic compound shown in Formula II; the catalyst was tetra(triphenylphosphine)palladium and cuprous iodide. The structural formula of the chiral boron-nitrogen heterocyclic compound represented by Formula II is as follows: .

6. The preparation method according to claim 4, characterized in that, The chiral boron-nitrogen heterocyclic compound shown in Formula I was reacted in the presence of a catalyst and an organic solvent to obtain the chiral boron-nitrogen heterocyclic compound shown in Formula III; the catalyst was palladium on carbon. The structural formula of the chiral boron-nitrogen heterocyclic compound represented by Formula III is as follows: .

7. The preparation method according to claim 4, characterized in that, The chiral boron-nitrogen heterocyclic compound shown in Formula I was reacted in the presence of a catalyst, paraformaldehyde, diisopropylamine, and an organic solvent to obtain the chiral boron-nitrogen heterocyclic compound shown in Formula IV; the catalyst was cuprous iodide. The structural formula of the chiral boron-nitrogen heterocyclic compound represented by Formula IV is as follows: .

8. The preparation method according to claim 4, characterized in that, The chiral boron-nitrogen heterocyclic compound shown in Formula I was reacted in the presence of a catalyst, benzyl azide, and an organic solvent to obtain the chiral boron-nitrogen heterocyclic compound shown in Formula V; the catalyst was copper tetraacetonitrile hexafluorophosphate. The structural formula of the chiral boron-nitrogen heterocyclic compound represented by Formula V is as follows: .

9. The preparation method according to claim 4, characterized in that, The chiral boron-nitrogen heterocyclic compound shown in Formula I was reacted in the presence of a catalyst, potassium bicarbonate, sodium citrate, (Z)-N-hydroxybenzylimine chloride, and a solvent to obtain the chiral boron-nitrogen heterocyclic compound shown in Formula VI; the catalyst was copper sulfate pentahydrate. The structural formula of the chiral boron-nitrogen heterocyclic compound represented by formula VI is as follows: .

10. The application of a chiral boron-nitrogen heterocyclic compound according to any one of claims 1-3 or a chiral boron-nitrogen heterocyclic compound prepared by the preparation method according to any one of claims 4-9 in the preparation of fluorescent probes.

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