A 5,6-oxafulvene precursor, a method for preparing the same and a method for synthesizing oxepin compounds

Abstract

The application discloses a 5,6-azulene yne precursor, a preparation method thereof and a method for synthesizing azulene compounds. The preparation method takes 3,4-dibromothiophene as raw material and comprises the following steps: 1, halogen-lithium exchange, reaction with alkyl borate, and then oxidation reaction and sulfonylation reaction; 2, reaction with an alkyl lithium reagent and halosilane to obtain a silicon-based compound 3a; 3, oxidation with a TFAA / TfOH / H2O2 system; and 4, reaction with 6-(dimethylamino)fulvene in an inert solvent to obtain the structural formula (I) of the 5,6-azulene yne precursor. The method for synthesizing azulene compounds comprises the following steps: in the presence of a fluorine ion source, treating the 5,6-azulene yne precursor in an inert atmosphere and in an organic solvent to generate a 5,6-azulene yne intermediate; and reacting the 5,6-azulene yne intermediate with a capturing agent to synthesize a seven-membered ring substituted azulene compound. The application solves the problem of introducing a substituent group into a seven-membered ring of azulene.

Description

Technical Field

[0001] This invention belongs to the technical field of organic chemistry, specifically relating to a 5,6-azynylene precursor and its preparation method, as well as a method for synthesizing polysubstituted azurites and polycyclic aromatic hydrocarbons by using the azuynylene intermediate generated from the 5,6-azynylene precursor to achieve the seven-membered ring functionalization of azurite. Background Technology

[0002] Azulene is a non-benzene aromatic hydrocarbon with unique photoelectric properties, but its selective functionalization, especially the modification of the seven-membered ring with low electron cloud density, remains a technical challenge in this field. Traditional methods, such as direct functionalization or de novo assembly, suffer from drawbacks such as site limitations, poor functional group compatibility, and low modularity.

[0003] Benzyne, as a classic strained cyclic alkyne, can achieve ortho-bifunctionalization of the benzene ring in one step and is widely used in the synthesis of substituted benzenes. Theoretically, azurite also has a similar highly reactive intermediate, "azynyne," among which 5,6-azynyne is one of its important regioisomers.

[0004] The literature "Bond Alternation in Azulenes", Yingchun Lu, David M. Lemal and Jerry P. Jasinski, Journal of the American Chemical Society, Vol. 122, No. 11, pp. 2440-2445, January 2000, records: "Treatment of dibromide 20 with phenyllithium-generated azulyne 12, which in the presence of excess furan gave the desired adduct 21 as a bluish-purple, microcrystalline powder after chromatography and sublimation. Evaporation of a methylene chloride solution of 21 yielded nearly black chunk crystals suitable for X-ray structure determination." The in-situ formation of 5,6-azuthylene from 5,6-dibromoazine and its reaction with furan is as follows:

[0005]

[0006] Although the 5,6-dibromoazine precursor can generate the 5,6-azynylene intermediate, it requires a strong base such as phenyllithium, and the activation conditions are very demanding.

[0007] Because lithium phenylene is not only a strong base but also a strong nucleophile, it may act as a nucleophile to react with the generated azuryne intermediate, consuming the intermediate and reducing the yield of the [4+2] reaction. This also limits the reaction of substrates containing electrophilic functional groups with azuryne under these conditions, such as those containing carbonyl, nitrile, or halogen groups, thus restricting the applicable substrate range. Therefore, the technique described in this literature only allows the generated 5,6-azyne intermediate to undergo a [4+2] reaction, resulting in a highly limited reaction mode and low efficiency. The reaction efficiency, expressed as a yield of only 22%, refers to the ratio of reactant quantity to product.

[0008] Therefore, an innovative and stable 5,6-azynylene precursor and a method for its efficient preparation have been developed. This method enables the 5,6-azynylene precursor to be activated under mild conditions to generate an azuynylene intermediate. Through reactions similar to benzylene, such as nucleophilic reactions, cycloaddition reactions, and transition metal catalytic reactions, different groups are introduced onto the seven-membered ring of azuyn, solving the problem of traditional methods that are difficult to introduce substituent groups into the seven-membered ring of azuyn. Summary of the Invention

[0009] To address the problems existing in the prior art, the technical problem to be solved by this invention is to provide a 5,6-azynylene precursor that can be activated under mild conditions to generate an azuynylene intermediate, thus solving the problem of introducing substituent groups into the seven-membered ring of azuyn with high reaction efficiency and mild, controllable modification. This invention also provides a method for preparing the 5,6-azynylene precursor, which uses mild reaction conditions and exhibits excellent acceptance of the seven-membered ring of azuyn. Furthermore, this invention provides a method for synthesizing azuyn-like compounds that enables diverse substitution at the 5,6-site of the seven-membered ring, selective introduction of functional groups at predetermined sites, and controllable construction of fused-ring systems.

[0010] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows:

[0011] In a first aspect, a 5,6-azynylene precursor is provided, having the structure of formula (I): In formula (I), a trialkylsilyl-SiR3 and a leaving group L are connected at the 5- and 6-positions of the azurite ring, respectively, and a substituent R is located at the 7-position of the azurite ring. 1 .

[0012] Specifically, the leaving group L is a sulfonate group or a halogen; the leaving group L is preferably -OTs, -OTf, Br or Cl;

[0013] R in the trialkylsilyl-SiR3 2 R 3 R 4 All are C1-C6 alkyl groups; The substituent R 1 It can be hydrogen, alkyl, cycloalkyl, or aryl.

[0014] Preferably, the leaving group L is p-toluenesulfonate group -OTs, and the trialkylsilyl-SiR3 is trimethylsilyl-TMS, that is, R in trialkylsilyl-SiR3. 2 R 3 R 4 All are methyl groups; including 5,6-azynylene precursor 1a, with the following structural formula:

[0015] 5,6-Azeetylene precursor 1b has the following structural formula:

[0016] 5,6-Azeetene precursor 1c has the following structural formula:

[0017] 5,6-Azetylene precursor 1d has the following structural formula: .

[0018] Secondly, a method for preparing the above-mentioned 5,6-azynylene precursor according to the present invention is characterized by comprising the following steps:

[0019] Step 1: Using 3,4-dibromothiophene as a raw material, compound 2 was prepared by lithium halide exchange, reaction with alkyl borate ester, followed by oxidation and sulfonation.

[0020] Step 2: Compound 2 reacts with an alkyllithium reagent at low temperature, and then with a halosilane to introduce a trialkylsilane group, yielding the silanized compound 3a: The low temperature is -100 °C to -78 °C;

[0021] Determine the substituent R introduced at a specified position on the thiophene ring. 1 Is it hydrogen? If yes, proceed to step 3; otherwise, proceed to step 2.1.

[0022] Step 2.1: After the lithiation step of compound 3a, iodomethane or iodoethane is added to obtain -R, respectively. 1 Compounds 3b and 3c are methyl or ethyl compounds; Me stands for methyl, and Et represents ethyl;

[0023] Following the lithiation step of compound 3a, acetone is added, followed by a reduction reaction to obtain compound 3d: Pr stands for isopropyl;

[0024] Step 3: Oxidize any one of compounds 3a, 3b, 3c, or 3d using a trifluoroacetic anhydride (TFAA) / trifluoromethanesulfonic acid (TfOH) / hydrogen peroxide (H2O2) system to obtain the corresponding thiophene dioxide compounds 4a, 4b, 4c, and 4d.

[0025] Step 4: React any one of thiophene dioxide compounds 4a, 4b, 4c, and 4d with 6-(dimethylamino)fulne in an inert solvent at room temperature or upon heating, resulting in a [4+6] cycloaddition accompanied by aromatization, and isolate the 5,6-azynylene precursors 1a, 1b, 1c, and 1d: .

[0026] Preferably, in step 1, The halolithium exchange is performed by dissolving 3,4-dibromothiophene in diethyl ether, cooling it to below -78 °C, and then adding n-butyllithium dropwise. The reaction with alkyl borate esters is as follows: isopropanol pinacol borate ester is added dropwise, the reaction is carried out at room temperature, and the reaction is quenched with HCl to obtain the first crude product; The oxidation reaction is as follows: the first crude product is dissolved in ethanol, boric acid is added at room temperature, and then hydrogen peroxide (H2O2) is added dropwise to react and obtain the second crude product; The sulfonation reaction is as follows: the second crude product is dissolved in dichloromethane, cooled to below -30 °C, p-toluenesulfonyl chloride p-TsCl is added, followed by the dropwise addition of triethylamine Et3N until complete conversion.

[0027] Preferably, in step 2, compound 2 is dissolved in tetrahydrofuran and cooled to a low temperature, wherein the alkyllithium reagent is n-butyllithium; and the halosilane is trimethylchlorosilane (TMSCl).

[0028] Preferably, in step 2.1, Compound 3b was prepared as follows: To a solution of compound 3a in anhydrous tetrahydrofuran (THF), n-butyllithium was added dropwise under an inert atmosphere at low temperature with stirring. Iodomethane (MeI) was then added, and the reaction mixture was slowly heated to room temperature with stirring. After the reaction was complete, the reaction was quenched with a saturated ammonium chloride aqueous solution and extracted with ethyl acetate. The combined organic layers were washed with saturated brine, dried with anhydrous sodium sulfate, filtered, and concentrated. The mixture was purified by petroleum ether-ethyl acetate chromatography to obtain compound 3b. The preparation of compound 3c differs from the preparation of compound 3b in that iodomethane MeI is replaced with iodoethane EtI. The preparation of compound 3d differs from the preparation of compound 3b in that: (1) Replace iodomethane MeI with acetone, and then purify the product by silica gel column chromatography. (2) Dissolve AlCl3 in diethyl ether, cool to 0 °C, add LiAlH4 in portions, and react for at least 5 minutes; (3) Dissolve the product obtained in (1) in diethyl ether and add it dropwise to the suspension obtained in (2). Raise the temperature to room temperature and react. After post-treatment, purify the product by silica gel chromatography column to obtain compound 3d.

[0029] Preferably, in step 3, trifluoroacetic anhydride (TFAA) and trifluoromethanesulfonic acid (TfOH) are added to a reaction flask, cooled to below -20 °C, and hydrogen peroxide (H2O2) is slowly added dropwise. The mixture is then raised to room temperature to obtain a mixed solution. Compounds 3a, 3b, 3c, and 3d are dissolved in dichloromethane (DCM) and added to the mixed solution. The reaction is carried out for at least 12 hours, and the mixture is purified to obtain compounds 4a, 4b, 4c, and 4d.

[0030] Preferably, in step 4, the inert solvent is toluene or tert-butyl methyl ether.

[0031] Thirdly, a method for synthesizing azurite compounds from the above-mentioned 5,6-azynylene precursor according to the present invention involves treating the 5,6-azynylene precursor in an inert atmosphere in the presence of a fluoride ion source in an organic solvent to generate a 5,6-azynylene intermediate; the 5,6-azynylene intermediate reacts with a scavenging agent to synthesize a seven-membered ring substituted azurite compound (hereinafter referred to as "azrite compound").

[0032] Preferably, the fluoride ion source is selected from cesium fluoride (CsF), the organic solvent is acetonitrile, and the reaction temperature is 0 °C to 110 °C (under catalysis).

[0033] Preferably, the trapping agent is selected from conjugated dienes, nucleophiles, reagents capable of σ-bond insertion, coupling agents in the presence of transition metal catalysts, and 1,3-dipoles.

[0034] The conjugated diene is selected from furan, substituted furan, pyrrole, anthracene or rich ene derivatives; The nucleophile is selected from morpholine, imidazole, phenoxy anion, phosphonate or sulfonyl anion; The reagent for σ-bond insertion is selected from diphenyl diselenyl ether, cyano ketone, or malonate derivatives; The transition metal catalyst is a palladium catalyst, and the coupling agent is a 5,6-azynylene precursor (the 5,6-azynylene precursor reacts with itself), or an aryl iodide; The 1,3-dipolar is selected from diazoacetic acid ester, azide, nitrone, or iodonium ylide.

[0035] The capturing agent is o-hydroxychalcone.

[0036] The technical effects of this invention are:

[0037] 1. The 5,6-azynylene precursor of the present invention can mildly generate aazynylene intermediates and undergo corresponding reactions under the action of fluoride ions, and the reaction efficiency is high, with yields mostly above 70%, thus solving the technical problem of the difficulty in obtaining aazynylene intermediates.

[0038] 2. The 5,6-azynylene precursor of the present invention has a high conversion rate and substrate (referring to reactants for the synthesis of azurite compounds) compatibility. It can be compatible with more than six common benzynylene reactions and can accurately introduce structurally diverse functional groups into the 5,6-position of the azurite ring, realizing diversified modification of the azurite core, especially its seven-membered ring. This solves the problem that it is not easy to introduce substituents into the seven-membered ring of azurite and realizes the efficient functionalization of the seven-membered ring of azurite.

[0039] 3. The 5,6-azynylene precursor of the present invention has strong synthetic capabilities, and can directly and efficiently synthesize azurite derivatives with complex substitution patterns at the 5,6-position that are difficult to obtain by traditional methods. It can also conveniently construct linearly arranged azurite-fused-ring aromatic systems (such as compound 28), which greatly expands the chemical space of azurite compounds.

[0040] 4. The preparation method of the present invention is carried out under mild conditions, the seven-membered ring of azurite has good acceptability, the preparation is simple and practical. Detailed Implementation

[0041] The present invention will be further described below with reference to embodiments: Example 1

[0042] 5,6-Azeetene precursor 1a (R 1 Synthesis of H)

[0043] Step 1: Synthesize compound 2

[0044] Halogenated lithium exchange: 3,4-Dibromothiophene (9.6 g, 40.0 mmol, 1.0 equiv) was dissolved in diethyl ether (80 mL), cooled to -78 °C, and n-butyllithium (2.5 M n-hexane solution, n-BuLi) (16 mL, 40.0 mmol, 1.0 equiv) was added dropwise, and the reaction was carried out for 1 hour;

[0045] Reaction with alkyl borate esters: Isopropanol pinacol borate ester (8.2 g, 44.0 mmol, 1.1 equiv) was added dropwise, and the reaction was carried out at room temperature for 2 hours. The reaction was quenched (i.e., the reaction was terminated) by adding HCl (10% by mass, 80 mL), and the first crude product was obtained after post-treatment.

[0046] Oxidation: The first crude product was dissolved in ethanol (100 mL), and boric acid (247.3 mg, 4.0 mmol, 0.1 equiv) was added at room temperature. Then hydrogen peroxide (H2O2) (20.4 mL, 30% by mass, 200 mmol, 5.0 equiv) was added dropwise. After reacting for 2 hours, the second crude product was obtained by post-processing.

[0047] Sulfonation: The second crude product was dissolved in dichloromethane (100 mL), cooled to -30 °C, and p-toluenesulfonyl chloride (p-TsCl) (11.4 g, 60.0 mmol, 1.5 equiv) was added, followed by the dropwise addition of triethylamine (Et3N) (8.1 g, 80.0 mmol, 2.0 equiv) until complete conversion. The reaction was quenched with water, and the product was post-processed to obtain the third crude product, which was purified by silica gel column chromatography to give 9.0 g of compound 2. Melting point (Mp): 122-124 °C; 1 H NMR (400 MHz, CDCl3) δ 7.77(d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.15-7.11 (m, 2H), 2.44 (s,3H) ppm; 13 C NMR (100 MHz, CDCl3) δ 146.0, 142.8, 132.1, 130.0, 128.9, 122.5,114.7, 106.0, 21.9 ppm; IR (thin film) 3116, 2921, 1595, 1513, 1490, 1418,1375, 1298, 1195, 1184, 1170, 1158, 1119, 1092, 1016, 998, 882, 823, 806 (cm -1 ); HRMS (ESI) m / z: calcd for C 11 H9BrO3S2 [M + H] + , 332.9249; found, 332.9249.

[0048] The “post-treatment” refers to: extraction three times with ethyl acetate (EtOAc, 30 mL), combining the organic phases, washing the organic phases with saturated NaCl aqueous solution (30 mL), drying with anhydrous sodium sulfate, filtering, and concentrating the filtrate.

[0049] Step 2: Synthesize compound 3a

[0050] Reaction with alkyllithium reagent: Compound 2 (4.5 g, 13.5 mmol, 1.0 equiv) was dissolved in tetrahydrofuran (400 mL), cooled to -100°C, and n-butyllithium (2.5 M n-hexane solution, n-BuLi) (5.4 mL, 13.5 mmol, 1.0 equiv) was rapidly added;

[0051] Reaction with halosilanes: Trimethylsilyl chloride (TMSCl) (1.6 g, 15.4 mmol, 1.1 equiv) was immediately and rapidly added to the reaction solution, and the reaction was allowed to proceed for 5 minutes. Post-treatment yielded a crude product, which was purified by silica gel column chromatography to give 3.4 g of compound 3a (77% yield). Melting point (Mp): 45-47 °C; 1 H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.4Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 3.2 Hz, 1H), 6.93 (d, J = 3.2Hz, 1H), 2.44 (s, 3H), 0.21 (s, 9H) ppm; 13 C NMR (100 MHz, CDCl3) δ 149.7,145.6, 135.0, 132.9, 131.5, 130.0, 128.6, 111.8, 21.8, -0.8 ppm; IR (thinfilm) 3426, 2956, 1599, 1496, 1376, 1338, 1250, 1193, 1180, 1137, 1094, 1029,883, 843, 756, 706, 663, 625, 568 (cm -1 ); HRMS (ESI) m / z: calcd for C 14 H 18 O3S2Si[M + H] + , 327.0539; found, 327.0537.

[0052] Step 3: Synthesize compound 4a

[0053] Trifluoroacetic anhydride (TFAA) (6.4 g, 30.5 mmol, 5.0 equiv) and trifluoromethanesulfonic acid (TfOH) (0.9 g, 6.1 mmol, 1.0 equiv) were added to a reaction flask, cooled to -20 °C, and hydrogen peroxide (H₂O₂) (4.4 mL, 30% by mass, 42.7 mmol, 7.0 equiv) was slowly added dropwise. The mixture was then heated to room temperature and reacted for 15 minutes to obtain a mixed solution. Compound 3a (2.0 g, 6.1 mmol, 1.0 equiv) was dissolved in dichloromethane (DCM) and added to the mixed solution. The reaction was carried out for 12 hours, and the crude product was obtained after post-processing. Purification by silica gel column chromatography yielded 1.1 g of compound 4a (50% yield). Melting point (Mp): 110-112 °C; 1 H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4Hz, 2H), 6.52 (d, J = 2.0 Hz, 1H), 6.39 (d, J = 2.0 Hz, 1H), 2.49 (s, 3H),0.19 (s, 9H) ppm; 13 C NMR (100 MHz, CDCl3) δ 153.4, 147.4, 143.0, 138.8,131.2, 130.6, 128.6, 108.8, 22.0, -1.8 ppm; IR (thin film) 3094, 1602, 1393,1307, 1263, 1200, 1180, 1148, 1081, 1014, 894, 849, 816, 767, 740, 662, 597,571, 548 (cm -1 ); HRMS (ESI) m / z: calcd for C 14 H 18 O5S2Si [M + H] + , 359.0438;found, 359.0437.

[0054] Step 4: Synthesis of azeyn precursor 1a

[0055] Compound 4a (1.1 g, 3.0 mmol, 1.0 equiv) was dissolved in toluene (15 mL) with 6-(dimethylamino)fulne (435.6 mg, 3.6 mmol, 1.2 equiv) at room temperature for 30 min. The solvent was evaporated under reduced pressure, and the solution was purified by silica gel column chromatography to give 777.2 mg of 5,6-azynylene precursor 1a as a blue solid (70% yield). ¹H NMR, ¹³C NMR, and HRMS data were consistent with the structure. Melting point (Mp): 99–101 °C; 1 H NMR (400 MHz, CDCl3) δ 8.47 (s, 1H), 8.12 (d, J =10.8 Hz, 1H), 7.90 (d, J = 8.4 Hz, 2H), 7.84 (t, J = 3.6 Hz, 1H), 7.42-7.36(m, 4H), 7.14 (d, J = 10.8 Hz, 1H), 2.48 (s, 3H), 0.38 (s, 9H) ppm; 13 C NMR(100 MHz, CDCl3) δ 161.6, 145.7, 141.3, 138.7, 138.1, 136.7, 135.3, 134.3,130.1, 128.5, 127.3, 121.0, 119.9, 114.6, 21.9, 0.4 ppm; IR (thin film) 2953,2899, 1596, 1569, 1508, 1459, 1437, 1409, 1374, 1293, 1250, 1192, 1179, 1088,1061, 988, 846, 823, 757, 672 (cm -1 ); HRMS (ESI) m / z: calcd for C 20 H 22 O3SSi [M+ H] + , 371.1132; found, 371.1131.

[0056] The 5,6-azynylene precursor 1a was cultured into single crystals and its structure was characterized using a single-crystal diffractometer. The single-crystal structure is as follows: Example 2

[0057] 5,6-Azeetene precursor 1b (R 1= Me) or 5,6-azynylene precursor 1c (R 1 Synthesis of Et) For the synthesis of compound 3a, see steps 1 and 2 in Example 1.

[0058] Step 2.1: Synthesize compound 3b or compound 3c.

[0059] Compound 3a (2.0 g, 6.1 mmol, 1.0 equiv) was added dropwise to an anhydrous tetrahydrofuran (THF) solution (40 mL) at -78°C under an inert atmosphere with n-butyllithium (n-BuLi) (2.7 mL, 6.6 mmol, 1.1 equiv). After stirring at -78°C for 30 min, methyl iodide (MeI) (952.1 mg, 6.7 mmol, 1.1 equiv) was added. The reaction mixture was then slowly heated to room temperature and stirred for two hours. After the reaction was complete, the reaction was quenched with a saturated ammonium chloride aqueous solution (20 mL) and extracted with ethyl acetate (10 mL × 3). The combined organic layers were washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by rapid column chromatography (petroleum ether:ethyl acetate = 50:1) gave compound 3b (1.7 g, 83% yield) as a white solid. Melting point (MP): 83-85 °C; 1 H NMR (400 MHz, CDCl3) δ 7.82 (d, J =8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.10 (s, 1H), 2.47 (s, 3H), 1.85 (s,3H), 0.30 (s, 9H) ppm; 13 C NMR (100 MHz, CDCl3) δ 145.5, 145.4, 137.1, 133.7,130.0, 128.7, 128.6, 128.4, 21.9, 11.5, -0.2 ppm; IR (thin film) 2955, 2925,1597, 1537, 1494, 1415, 1375, 1324, 1250, 1196, 1175, 1077, 948, 863, 844,819, 749, 719, 665, 559 (cm -1 ); HRMS (ESI) m / z: calcd for C 15 H 20 O3S2Si [M + Na]+ , 363.0515; found, 363.0522.

[0060] Compound 3a (3.9 g, 12.0 mmol, 1.0 equiv) was added dropwise to anhydrous THF (40 mL) at -78°C under an inert atmosphere with n-butyllithium (n-BuLi) (5.3 mL, 13.2 mmol, 1.1 equiv). After stirring at -78°C for 30 min, ethane iodoform (EtI) (2.1 g, 13.2 mmol, 1.1 equiv) was added. The reaction mixture was slowly heated to room temperature and stirred for two hours. After the reaction was complete, the reaction was quenched with saturated ammonium chloride aqueous solution (40 mL) and extracted with ethyl acetate (10 mL × 3). The combined organic layers were washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by rapid column chromatography (petroleum ether:ethyl acetate = 50:1) gave compound 3c (2.4 g, 56% yield) as a colorless oil. 1 H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.4 Hz, 2H), 7.36 (d, J =8.4 Hz, 2H), 7.15 (s, 1H), 2.46 (s, 3H), 2.32 (q, J = 7.6 Hz, 2H), 1.06 (t, J= 7.6 Hz, 3H), 0.31 (s, 9H) ppm; 13 C NMR (100 MHz, CDCl3) δ 145.4, 144.2,136.8, 136.7, 133.8, 129.9, 128.4, 21.8, 19.8, 15.5, -0.1 ppm; IR (thin film)2958, 1597, 1527, 1494, 1457, 1415, 1375, 1325, 1249, 1195, 1175, 1089, 999,944, 869, 843, 819, 756, 665, 628, 559 (cm -1 ); HRMS (ESI) m / z: calcd forC 16 H 22 O3S2Si [M + H] + , 355.0852; found, 355.0860.

[0061] Step 3: Synthesize compound 4b or compound 4c.

[0062] At -20 °C, 30% H2O2 (3.6 mL, 35.0 mmol, 7.0 equiv) was slowly added to a mixture of TFAA (5.3 g, 25.0 mmol, 5.0 equiv) and TfOH (750.4 mg, 5.0 mmol, 1.0 equiv). The reaction mixture was then heated to room temperature and stirred for 15 minutes. Subsequently, a DCM solution (10 mL) of compound 3b (1.7 g, 5.0 mmol, 1.0 equiv) was added dropwise to the reaction mixture. The reaction was stirred overnight, quenched with water (30 mL), and extracted with DCM (20 mL × 3). The combined organic layers were washed with saturated brine (50 mL), dried over Na2SO4, filtered, and concentrated. Purification by rapid column chromatography (petroleum ether:EtOAc = 10:1) gave compound 4b (1.4 g, 75% yield) as a white solid. Melting point (MP): 168-170 °C; 1 H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.4 Hz, 2H), 7.42 (d, J =8.4 Hz, 2H), 6.60 (s, 1H), 2.50 (s, 3H), 1.66 (s, 3H), 0.23 (s, 9H) ppm; 13 CNMR (100 MHz, CDCl3) δ 146.9, 146.5, 146.4, 136.5, 132.7, 130.5, 128.6,126.4, 22.0, 6.7, -1.1 ppm; IR (thin film) 3084, 2040, 1652, 1597, 1377,1295, 1254, 1239, 1180, 1088, 1071, 934, 882, 851, 811, 766, 685, 534 (cm -1 );HRMS (ESI) m / z: calcd for C 15 H 20 O5S2Si [M + Na] + , 395.0414; found, 395.0407.

[0063] At -20 °C, 30% H₂O₂ (4.9 mL, 47.6 mmol, 7.0 equiv) was slowly added dropwise to a mixture of TFAA (7.1 g, 34.0 mmol, 5.0 equiv) and TfOH (1.0 g, 6.8 mmol, 1.0 equiv). The reaction mixture was then brought to room temperature and stirred for 15 min. A solution of compound 3c (2.4 g, 6.8 mmol, 1.0 equiv) dissolved in DCM (10 mL) was then slowly added dropwise to the reaction mixture. The reaction was stirred overnight, quenched with water (30 mL), and extracted with DCM (20 mL × 3). The combined organic phases were washed with saturated brine (50 mL), dried over Na₂SO₄, filtered, and concentrated. Purification by rapid column chromatography (petroleum ether: EtOAc = 10:1) gave compound 4c (1.3 g, 50% yield) as a white solid. Melting point (MP): 90-92 °C; 1 H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 6.56 (s, 1H), 2.49 (s, 3H), 2.20 (q, J = 7.6 Hz, 2H), 1.10 (t, J = 7.6 Hz, 3H), 0.23 (s, 9H) ppm; 13 C NMR (100 MHz, CDCl3) δ146.8, 146.2, 146.0, 136.8, 132.9, 131.4, 130.4, 128.4, 21.9, 16.7, 11.1, -1.1 ppm; IR (thin film) 2941, 1634, 1597, 1458, 1382, 1303, 1255, 1234, 1203,1176, 1104, 1088, 930, 846, 815, 738, 689, 572, 550, 467 (cm -1 ); HRMS (ESI) m / z: calcd for C 16 H 22 O5S2Si [M + Na] + , 409.0570; found, 409.0569.

[0064] Step 4: Synthesize 5,6-azynylene precursor 1b or 5,6-azynylene precursor 1c.

[0065] Compound 4b (1.4 g, 3.7 mmol, 1.0 equiv) and 6-(dimethylamino)fulne (537.2 mg, 4.4 mmol, 1.2 equiv) were dissolved in methyl tert-butyl ether (15 mL) and stirred at 50 °C. After the reaction was complete, the mixture was concentrated under reduced pressure. Purification by rapid column chromatography (petroleum ether: ethyl acetate = 20:1) gave 5,6-azynylene precursor 1b (blue solid, 1.2 g, 83% yield). Melting point (Mp): 116–118 °C; 1 H NMR (400 MHz, CDCl3) δ 8.46(s, 1H), 8.10 (s, 1H), 7.87 (t, J = 3.6 Hz, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 1.6 Hz, 1H), 7.29 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 2.4 Hz, 1H), 2.46 (s, 3H), 2.10 (s, 3H), 0.48 (s, 9H) ppm; 13 C NMR (100 MHz, CDCl3) δ156.9, 145.5, 139.6, 138.5, 138.1, 137.6, 133.8, 131.0, 129.8, 128.7, 126.9,118.6, 118.0, 23.0, 21.9, 1.8 ppm; IR (thin film) 2954, 2040, 1597, 1565,1418, 1375, 1250, 1192, 1179, 1127, 1097, 1049, 971, 874, 837, 818, 764, 675,591, 560 (cm -1 ); HRMS (ESI) m / z: calcd for C 21 H 24 O3SSi [M + H] + , 385.1288;found, 385.1292.

[0066] Compound 4c (1.3 g, 3.3 mmol, 1.0 equiv) and 6-(dimethylamino)fulne (484 mg, 4.0 mmol, 1.2 equiv) were dissolved in methyl tert-butyl ether (15 mL) and stirred at 80 °C. After the reaction was complete, the mixture was concentrated under reduced pressure. Purification by rapid column chromatography (petroleum ether: ethyl acetate = 20:1) gave 5,6-azynylene precursor 1c (blue solid, 998.5 mg, 76% yield). Melting point (Mp): 96–98 °C; 1 H NMR (400 MHz, CDCl3) δ 8.47 (s, 1H),8.11 (s, 1H), 7.87 (t, J = 3.6 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.35 (d, J= 3.6 Hz, 1H), 7.29-7.25 (m, 3H), 2.45 (s, 3H), 2.38 (q, J = 7.6 Hz, 2H), 1.06 (t, J = 7.6 Hz, 3H), 0.50 (s, 9H) ppm; 13 C NMR (100 MHz, CDCl3) δ 156.4,145.5, 139.5, 138.9, 138.2, 137.5, 133.4, 133.2, 131.4, 129.7, 128.8, 118.6,118.2, 29.0, 21.8, 16.0, 1.8 ppm; IR (thin film) 2960, 1597, 1567, 1455,1417, 1375, 1250, 1191, 1096, 1065, 1045, 984, 928, 862, 841, 809, 765, 677,549 (cm -1 ); HRMS (ESI) m / z: calcd for C 22 H 26 O3SSi [M + H] + , 399.1445; found, 399.1446.

[0067] 5,6-Azynylene precursor 1b was characterized by NMR mass spectrometry. The structure of 5,6-Azynylene precursor 1c was confirmed by the NOESY experiment, and the observed relevant signals are as follows: Example 3

[0068] 5,6-Azetylene precursor 1d (R 1 Synthesis of (i-Pr) For the synthesis of compound 3a, see steps 1 and 2 in Example 1.

[0069] Step 2.1, Synthesize compound 3d

[0070] i. Compound 3a (5.9 g, 18.1 mmol, 1.0 equiv) was dissolved in tetrahydrofuran (60 mL), cooled to -78 °C, and n-butyllithium (2.5 M n-hexane solution, n-BuLi) (8 mL, 19.9 mmol, 1.1 equiv) was slowly added dropwise. The reaction was allowed to proceed for 30 minutes, followed by the addition of acetone. The mixture was then slowly brought to room temperature and reacted for 5 hours. The product was post-processed and purified by silica gel column chromatography to yield 5.4 g of product. Melting point (Mp): 102–104 °C; 1 H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.4Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 7.22 (s, 1H), 3.90 (s, 1H), 2.49 (s, 3H),1.67 (s, 6H), 0.27 (s, 9H) ppm; 13 C NMR (100 MHz, CDCl3) δ 145.9, 141.9,141.2, 138.2, 133.0, 130.1, 129.1, 128.4, 70.6, 32.1, 21.9, 0.1 ppm; IR (thinfilm) 3526, 2976, 1597, 1500, 1458, 1349, 1317, 1249, 1193, 1179,1095, 1065,1014, 982, 948, 842, 820, 744, 703, 664, 628, 555 (cm -1 ); HRMS (ESI) m / z:calcd for C 17 H 24 O4S2Si [M + Na] + , 407.0777; found, 407.0779.

[0071] ii. AlCl3 (7.5 g, 56 mmol, 4.0 equiv) was suspended in diethyl ether (30 mL), cooled to 0 °C, and LiAlH4 (1.1 g, 28 mmol, 2.0 equiv) was added in portions. The reaction was allowed to proceed for 5 minutes. 5.4 g of the product from the previous step was dissolved in diethyl ether (20 mL) and added dropwise to the suspension. The mixture was brought to room temperature and reacted for 15 minutes. Post-treatment followed by purification by silica gel column chromatography yielded compound 3d (4.2 g, 80% yield). Melting point (Mp): 72-74 °C; 1 H NMR (400 MHz, CDCl3 ) δ 7.84(d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.15 (s, 1H), 2.83 (sept, J =6.8 Hz, 1H), 2.46 (s, 3H), 1.05 (d, J = 6.8 Hz, 6H), 0.29 (s, 9H) ppm; 13 C NMR (100 MHz, CDCl3) δ 145.3, 143.1, 142.8, 136.6, 133.9, 129.9, 128.4, 128.3,27.0, 24.9, 21.8, -0.1 ppm; IR (thin film) 2962, 2927, 2869, 1726, 1598,1523, 1494, 1457, 1413, 1375, 1329, 1308, 1250, 1192, 1179, 1095, 1055, 975,893, 844, 818, 744, 721, 665, 627, 558 (cm -1 ); HRMS (ESI) m / z: calcd forC 17 H 24 O3S2Si [M + Na] + , 391.0828; found, 391.0831.

[0072] Step 3, Synthesize compound 4d

[0073] Trifluoroacetic anhydride (TFAA) (12.0 g, 57.0 mmol, 5.0 equiv) and trifluoromethanesulfonic acid (TfOH) (1.7 g, 11.4 mmol, 1.0 equiv) were added to a reaction flask. The mixture was cooled to -20 °C, and hydrogen peroxide (H2O2) (8.2 mL, 30% by mass, 79.8 mmol, 7.0 equiv) was slowly added dropwise. The mixture was then heated to room temperature and reacted for 15 minutes. Compound 3d (4.2 g, 11.4 mmol, 1.0 equiv) was dissolved in dichloromethane (DCM) and added to the mixed solution. The reaction was allowed to proceed for 12 hours. Post-processing yielded a crude product, which was purified by silica gel column chromatography to obtain compound 4d (2.9 g, 63% yield). Melting point (Mp): 131-133 °C; 1 HNMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 6.50 (s, 1H), 2.60 (sept, J = 7.2 Hz, 1H), 2.49 (s, 3H), 1.15 (d, J = 7.2 Hz, 6H), 0.27 (s, 9H) ppm; 13 C NMR (100 MHz, CDCl3) δ 146.7, 145.8, 145.5, 137.4,135.7, 133.0, 130.4, 128.5, 26.8, 21.9, 19.9, -0.8 ppm; IR (thin film) 3081,2974, 1622, 1596, 1381, 1324, 1305, 1297, 1257, 1240, 1215, 1193, 1176, 1108,1088, 1048, 944, 852, 769, 705, 692, 550 (cm -1 ); HRMS (ESI) m / z: calcd forC 17 H 24 O5S2Si [M + H] + , 401.0907; found, 401.0908.

[0074] Step 4: Synthesis of 5,6-azynylene precursor 1 day

[0075] Compound 4d (1 g, 2.5 mmol, 1.0 equiv) was dissolved in methyl tert-butyl ether with 6-(dimethylamino)fulne (363 mg, 3.0 mmol, 1.2 equiv). The mixture was heated to 70 °C and reacted for 12 hours. The solvent was evaporated under reduced pressure, and the solution was purified by silica gel column chromatography to give a blue solid 5,6-azynylene precursor 1d (587 mg, 57% yield). Melting point (Mp): 84-86 °C; 1 H NMR (400MHz, CDCl3) δ 8.45 (s, 1H), 8.17 (s, 1H), 7.86 (t, J = 3.6 Hz, 1H), 7.60 (d,J = 8.4 Hz, 2H), 7.34 (d, J = 3.6 Hz, 1H), 7.30-7.26 (m, 3H), 3.23 (sept, J =6.8 Hz, 1H), 2.43 (s, 3H), 0.98 (d, J = 6.8 Hz, 6H), 0.47 (s, 9H) ppm; 13 C NMR(100 MHz, CDCl3) δ 155.8, 145.4, 139.6, 139.3, 138.2, 137.3, 137.0, 133.9,133.3, 131.5, 129.8, 128.8, 118.5, 118.3, 31.1, 23.7, 21.8, 1.9 ppm; IR (thinfilm) 2957, 2870, 1597, 1576, 1494, 1463, 1404, 1374, 1249, 1192, 1179, 1084,1031, 843, 769, 706, 679, 554 (cm -1 ); HRMS (ESI) m / z: calcd for C 23 H 28 O3SSi [M+ H] + , 413.1601; found, 413.1610. Example 4

[0076] The [4+2] cycloaddition of the 5,6-azynylene precursor with furan yields compound 5 (a seven-membered ring-substituted azulene compound).

[0077] Furan was used as the trapping agent. Under nitrogen atmosphere, 111.0 mg (111.0 mg, 0.3 mmol, 1.0 equiv) of 5,6-azine precursor 1a, 136.7 mg (0.9 mmol, 3.0 equiv) of cesium fluoride (CsF), and 30.6 mg (0.45 mmol, 1.5 equiv) of furan were weighed into a round-bottom flask, and 3.0 mL of acetonitrile (MeCN) was added. The mixture was heated to 50°C and stirred. The reaction was monitored by TLC. After the reaction was complete, the acetonitrile was removed, and the crude product was directly purified by silica gel column chromatography to give 47.2 mg of purple solid compound 5, with a yield of 81%.

[0078] Melting point (MP): 130-132 °C; 1 H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 8.09 (d,J = 8.8 Hz, 1H), 7.70 (t, J = 3.2 Hz, 1H), 7.23-7.18 (m, 3H), 7.10 (dd, J1 =5.6 Hz, J2 = 2.0 Hz, 1H), 6.99 (dd, J1 = 5.6 Hz, J2 = 2.0 Hz, 1H), 5.78 (s,1H), 5.70 (s, 1H) ppm; 13 C NMR (100 MHz, CDCl3) δ 155.5, 143.2, 141.5, 140.5,139.2, 136.2, 135.7, 135.5, 127.5, 119.7, 119.4, 116.6, 86.1, 85.4 ppm; IR(thin film) 3014, 2924, 2360, 1613, 1589, 1504, 1377, 1339, 1276, 1239, 1199,1178, 1132, 1056, 998, 883, 854, 839, 760, 721, 595, 572, 545 (cm -1 ); HRMS(ESI) m / z: calcd for C 14 H 10 O [M + H] + , 195.0804; found, 195.0807.

[0079] The [4+2] cycloaddition reaction: the trapping agent is a conjugated diene, including but not limited to furan, substituted furan, pyrrole, anthracene, and olefinic derivatives, to generate an azuron-bridged ring compound.

[0080]

[0081] Note: During the reaction of the 5,6-azynylene precursor, the generated 5,6-azynylene intermediate is unstable and is immediately captured to obtain the product. Therefore, the 5,6-azynylene precursor, fluoride ion activating agent, and capturing agent are added together. Example 5

[0082] The regioselective nucleophilic addition of 5,6-azutyne precursor 1d with morpholine yielded compound 20 (a seven-membered ring-substituted azulene compound).

[0083] Morpholine was used as the capture agent. Under nitrogen atmosphere, 123.6 mg (123.6 mg, 0.3 mmol, 1.0 equiv) of the 5,6-azine ring precursor 1d, 136.7 mg (0.9 mmol, 3.0 equiv) of cesium fluoride (CsF) and 39.2 mg (0.45 mmol, 1.5 equiv) of morpholine were weighed into a round-bottom flask, and 3.0 mL of acetonitrile (MeCN) was added. The mixture was stirred at room temperature (rt). TLC monitoring was performed. After the reaction was complete, the acetonitrile was removed, and the crude product was directly purified by silica gel column chromatography to give 67.4 mg of a blue solid compound 20, with a yield of 88%. ¹H NMR and ¹³C NMR showed a single regioisomer, confirming that the nucleophilic attack occurred entirely at the sterically less sterically hindered 5-position.

[0084] Melting point (MP): 128-130 °C; 1 H NMR (400 MHz, CDCl3) δ 8.13 (s, 1H), 8.11 (s,1H), 7.81 (t, J = 3.6 Hz, 1H), 7.33 (s, 1H), 7.15 (t, J = 3.6 Hz, 2H), 3.94-3.91 (m, 4H), 3.20-3.17 (m, 4H), 3.07 (sept, J = 6.8 Hz, 1H), 1.37 (d, J =6.8 Hz, 6H) ppm; 13IR (thin) film)2958, 2854, 1601, 1449, 1400, 1299, 1263, 1200, 1119, 1040, 973, 889, 749(cm -1 ); HRMS (ESI) m / z: calcd for C 17 H 21 NO [M + H] + , 256.1696; found, 256.1705.

[0085] The nucleophilic addition reaction involves a scavenging agent that is a nucleophile, including but not limited to amines (such as morpholine and imidazole), phenoxy anions, phosphonates, and sulfonyl anions, introducing a heteroatom functional group at the 5- or 6-position of the azurite ring. Specifically, when R in general formula (I) 1 When the group is large (such as isopropyl), nucleophilic addition occurs with high selectivity at the sterically less hindrance position 5.

[0086] Example 6

[0087] Compound 25 (a seven-membered ring-substituted azulene compound) was generated by inserting the 5,6-azynylene precursor 1d into the C-C σ-bond of 2-oxocyclopentane-1-carboxylonitrile.

[0088] The trapping agent was 2-oxocyclopentane-1-carboxynitrile. Under nitrogen atmosphere, 123.6 mg (0.3 mmol, 1.0 equiv) of 5,6-azine ring precursor 1d, 136.7 mg (0.9 mmol, 3.0 equiv) of cesium fluoride (CsF) and 49.1 mg (0.45 mmol, 1.5 equiv) of 2-oxocyclopentane-1-carboxynitrile were weighed into a round-bottom flask, and 3.0 mL of acetonitrile (MeCN) was added. The mixture was stirred at room temperature (rt). TLC monitoring was performed. After the reaction was complete, the acetonitrile was removed, and the crude product was directly purified by silica gel column chromatography to give 67.3 mg of blue solid compound 25, with a yield of 81%. The reaction formed a [5,7,7] tricyclic system as a single regioisomer. The structure was confirmed by NMR, HRMS, and NOESY.

[0089] Melting point (MP): 235-237 °C; 1 H NMR (400 MHz, CDCl3) δ 8.61 (brs, 1H), 8.40(s, 1H), 7.97 (t, J = 3.6 Hz, 1H), 7.46 (d, J = 2.8 Hz, 1H), 7.37 (d, J = 3.6Hz, 1H), 4.13 (dd, J1 = 11.6 Hz, J2 = 5.2 Hz, 1H), 2.89 (sept, J = 6.8 Hz,1H), 2.70 (dd, J1 = 8.4 Hz, J2 = 4.0 Hz, 2H), 2.42-2.35 (m, 1H), 2.15-2.05 (m,1H), 2.03-1.89 (m, 1H), 1.76 (brs, 1H), 1.38 (d, J = 6.8 Hz, 3H), 1.33 (d, J= 6.8 Hz, 3H) ppm; 13 C NMR (100 MHz, CDCl3) δ 211.0, 146.1, 141.2, 139.6,137.5, 137.2, 136.0, 133.3, 120.7, 120.3, 120.1, 119.1, 42.4, 36.4, 34.6,32.2, 24.7, 24.3, 21.1 ppm; IR (thin film) 3855, , 3677, 2950, ​​2361, 2342,2241, 1697, 1591, 1459, 1417, 1406, 1236, 1192, 1177, 1052, 926, 774, 761,512 (cm -1 ); HRMS (ESI) m / z: calcd for C 19 H 19 NO [M + Na] + , 300.1359; found, 300.1365.

[0090] The σ-bond insertion reaction: the trapping agent is a reagent capable of σ-bond insertion, including but not limited to diphenyldiselenes (inserting Se-Se bonds), or compounds with active methylene groups such as cyanoketones and malonic acid ester derivatives (inserting CC bonds), to efficiently construct quaternary carbon centers and fused ring systems.

[0091] Example 7

[0092] The palladium-catalyzed reaction of 5,6-azynylene precursor 1a yields compounds 28a and 28b (seven-membered ring-substituted azulene compounds).

[0093] The transition metal catalyst used was tetratetraphenylphosphine palladium (Pd(PPh3)4), and the coupling agent was a 5,6-azynylene precursor. Under nitrogen atmosphere, 5,6-azynylene precursor 1a (111.0 mg, 0.3 mmol, 1.0 equiv), cesium fluoride (CsF) (136.7 mg, 0.9 mmol, 3.0 equiv), and tetratetraphenylphosphine palladium (Pd(PPh3)4) (34.7 mg, 0.03 mmol, 0.1 equiv) were weighed into a round-bottom flask, and acetonitrile (MeCN) (3.0 mL) was added. The mixture was heated to 50°C and stirred. TLC monitoring was performed. After the reaction was complete, the acetonitrile was removed, and the crude product was directly purified by silica gel column chromatography to obtain trimers 28a and 28b (ratio 1:2.9), with an overall yield of 70%. The structure of 28b was confirmed by single-crystal X-ray diffraction (CCDC 2499530).

[0094] Compound 28a: Melting point (Mp): 191-193 °C; 1 H NMR (400 MHz, CDCl3) δ 9.13 (s,3H), 8.38 (d, J = 10.8 Hz, 3H), 7.86 (t, J = 3.6 Hz, 3H), 7.63 (d, J = 3.6Hz, 3H), 7.54 (d, J = 3.6 Hz, 3H), 7.51 (d, J = 10.8 Hz, 3H) ppm; 13 C NMR (100MHz, CDCl3) δ 159.0, 138.3, 135.4, 134.6, 133.5, 127.4, 121.5, 121.1, 120.1,108.4 ppm; IR (thin film) 3904, 3854, 3752, 3736, 3712, 3630, 3620, 3588,3005, 2360, 2342, 1735, 1654, 1637, 1541, 1508, 1275, 1260, 1167, 750, 678,551 (cm -1); HRMS (ESI) m / z: calcd for C 30 H 18 [M + H] + , 379.1481; found, 379.1491。

[0095] Compound 28b: Melting point (Mp): 263 - 265 °C; 1 H NMR (400 MHz, CDCl3) δ 9.42 (s,1H), 9.40 (s, 1H), 9.39 (s, 1H), 8.39 (d, J = 4.8 Hz, 1H), 8.36 (d, J = 4.8Hz, 1H), 8.34 (d, J = 11.2 Hz, 1H), 8.08 - 8.04 (m, 2H), 8.02 (d, J = 3.6 Hz,1H), 7.96 - 7.90 (m, 3H), 7.62 - 7.58 (m, 3H), 7.49 - 7.43 (m, 3H), ppm; 13 C NMR(100 MHz, CDCl3) δ 141.7, 141.4, 140.8, 140.5, 140.4, 139.4, 138.2, 137.9,137.1, 136.6, 136.0, 135.8, 135.7, 135.6, 135.5, 133.5, 132.9, 132.4, 130.9,130.2, 129.1, 122.4, 122.3, 122.2, 121.4, 121.3, 121.2, 120.6, 119.8, 119.7ppm; IR (thin film) 3871, 3854, 3839, 3751, 3711, 3690, 3676, 3649, 3629,3567, 3005, 2360, 2342, 1559, 1541, 1508, 1275, 1260, 765, 750, 688, 550, 474(cm -1 ); HRMS (ESI) m / z: calcd for C 30 H 18 [M + H] + , 40B.1301; found, 333.1390。 It should be noted that there may be an error in the original text where "40B.1301" should probably be "401.1301". This translation is based on the provided text with this possible correction in mind for the English rendering.

[0096] Transition metal catalytic reaction: In the presence of a palladium catalyst, the coupling agent is an aryl iodide, which realizes the coupling, trimerization and other reactions of azuryne to construct complex linear azurofused aromatic hydrocarbons.

[0097] The transition metal catalysts used were bis(dibenzylacetone)palladium(0) (Pd(dba)2) and bis(dibenzylacetone)palladium(0) (P(o-Tol)3), with 2-iodobiphenyl as the coupling agent. 5,6-Azynylene precursor 1a (111.0 mg, 0.3 mmol, 1.0 equiv), 2-iodobiphenyl (252.0 mg, 0.9 mmol, 3.0 equiv), CsF (136.7 mg, 0.9 mmol, 3.0 equiv), Pd(dba)2 (8.6 mg, 0.015 mmol, 0.05 equiv), and P(o-Tol)3 (4.6 mg, 0.015 mmol, 0.05 equiv) were dissolved in anhydrous acetonitrile (1 mL) and anhydrous toluene (2 mL), placed in an inert gas-sealed tube, and stirred at 110°C. After the reaction was complete, the mixture was concentrated under reduced pressure and separated by rapid column chromatography to obtain a blue solid product (52.6 mg, yield 63%).

[0098] Melting point (MPa): 153-155 °C; 1 H NMR (400 MHz, CDCl3) δ 9.72 (s, 1H), 8.75-8.6 (m, 4H), 8.45 (d, J = 11.6 Hz, 1H), 8.39 (d, J = 11.6 Hz, 1H), 7.89 (t, J= 4.0 Hz, 1H), 7.83-7.62 (m, 4H), 7.58 (d, J = 4.0 Hz, 1H), 7.43 (d, J = 2.8Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 140.9, 137.2, 136.7, 135.7, 134.5,132.8, 132.7, 132.1, 131.8, 130.1, 128.6, 127.8, 127.6, 127.1, 126.6, 125.5,125.4, 123.4, 123.3, 120.8, 119.3, 119.0 ppm; IR (thin film) 1592, 1530,1490, 1446, 1424, 1385, 1180, 1052, 1385, 1180, 1052, 997, 921, 834, 754,751, 581 (cm -1 ); HRMS (ESI) m / z: calcd for C 22 H 14 [M + H] + , 279.1168; found, 279.1172. Example 8

[0099] [3+2] Cycloaddition reaction: The scavenger is a 1,3-dipolar, including but not limited to diazonium acetate, azide, nitrone, and iodonium ylide, to generate azuron five-membered heterocyclic compounds (seven-membered ring substituted azuron compounds).

[0100] The trapping agent was methyl 3-oxo-2-(phenyl-13-iodoethylene)butyrate. Under nitrogen protection, 5,6-azynylene precursor 1d (123.8 mg, 0.3 mmol, 1.0 equiv), methyl 3-oxo-2-(phenyl-13-iodoethylene)butyrate (143.1 mg, 0.45 mmol, 1.5 equiv), and CsF (136.7 mg, 0.9 mmol, 3.0 equiv) were dissolved in anhydrous acetonitrile (3 mL) and stirred at 50°C. After the reaction was complete, the mixture was concentrated under reduced pressure and separated by rapid column chromatography to give a blue solid compound 17 (44.9 mg, 53% yield). Melting point (Mp): 99-101 °C; 1H NMR (400 MHz, CDCl3) δ 9.40 (s,1H), 8.25 (s, 1H), 7.77 (t, J = 4.0 Hz, 1H), 7.41 (d, J = 4.4 Hz, 1H), 7.35(d, J = 2.4 Hz, 1H), 4.02 (s, 3H), 3.83 (sept, J = 6.8 Hz, 1H), 2.82 (s, 3H), 1.44 (d, J = 6.8 Hz, 6H) ppm; 13 C NMR (100 MHz, CDCl3) δ 164.8, 160.5, 155.9,138.4, 135.3, 134.3, 130.0, 129.4, 128.7, 121.1, 118.6, 117.9, 112.1, 51.8,30.2, 23.4, 15.1 ppm; IR (thin film) 3398, 2949, 2875, 1712, 1613, 1588,1450, 1382, 1272, 1248, 1157, 1142, 1088, 1058, 937, 904, 744, 697 (cm -1 );HRMS (ESI) m / z: calcd for C 18 H 18 O3 [M + H] + , 283.1329; found, 283.1337.

[0101] Example 9

[0102] Serial reaction: The trapping agent is a molecule that has both a nucleophilic site and a subsequent reaction site, such as o-hydroxychalcone, which initiates intramolecular Michael addition and other cyclization through nucleophilic addition, forming a fused ring structure in one step (azurite compounds with seven-membered ring substitution).

[0103] The trapping agent was (E)-4-(2-hydroxyphenyl)but-3-en-2-one. Under nitrogen protection, 5,6-azynylene precursor 1d (123.8 mg, 0.3 mmol, 1.0 equiv), (E)-4-(2-hydroxyphenyl)but-3-en-2-one (73.0 mg, 0.45 mmol, 1.5 equiv), CsF (136.7 mg, 0.9 mmol, 3.0 equiv), and Cs₂CO₃ (195.5 mg, 0.6 mmol, 2.0 equiv) (as a base to remove hydrogen from phenol to improve reaction efficiency) were dissolved in anhydrous acetonitrile (MeCN) (3 mL) and stirred at room temperature. After the reaction was complete, the mixture was concentrated under reduced pressure and separated by rapid column chromatography to give compound 27 (67.4 mg, 68% yield) as a blue solid. Melting point (Mp): 90-92 °C; 1 H NMR (400 MHz, CDCl3) δ 8.43 (s, 1H),8.38 (s, 1H), 7.88 (t, J = 4.0 Hz, 1H), 7.42 (d, J = 7.2 Hz, 1H), 7.30-7.24(m, 2H), 7.23-7.19 (m, 2H), 7.10 (t, J = 7.2 Hz, 1H), 5.18 (dd, J1 = 10.8 Hz, J2= 2.8 Hz, 1H), 3.63 (sept, J = 6.8 Hz, 1H), 3.06 (dd, J1 = 16.8 Hz, J2=10.8 Hz, 1H), 2.50 (dd, J1 = 16.8 Hz, J2= 2.8 Hz, 1H), 1.95 (s, 3H), 1.49 (d,J = 6.8 Hz, 3H), 1.40 (d,J = 6.8 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ206.3, 153.7, 149.5, 138.7, 138.6, 137.7, 137.0, 135.1, 132.0, 128.6, 128.2,128.1, 127.0, 123.8, 116.1, 116.0, 115.5, 50.0, 36.0, 31.9, 31.2, 25.5, 23.9ppm; IR (thin film) 2961, 1715, 1661, 1602, 1489, 1461, 1410, 1357, 1319,1242, 1109, 1050, 945, 753, 589, 475 (cm -1 ); HRMS (ESI) m / z: calcd for C 23 H 22 O2[M + H] + , 331.1693; found, 331.1702。

Claims

1. A 5,6-azynylene precursor, characterized in that, It has a structure of (I): In formula (I), a trialkylsilyl-SiR3 and a leaving group L are connected at the 5- and 6-positions of the azurite ring, respectively, and a substituent R is located at the 7-position of the azurite ring. 1 .

2. The 5,6-azynylene precursor according to claim 1, characterized in that: The leaving group L is a sulfonate group or a halogen; R in the trialkylsilyl-SiR3 2 R 3 R 4 All are C1-C6 alkyl groups; the substituent R 1 It can be hydrogen, alkyl, cycloalkyl or aryl.

3. The 5,6-azynylene precursor according to claim 2, characterized in that: The leaving group L is p-toluenesulfonate group -OTs, and the trialkylsilyl-SiR3 is trimethylsilyl-TMS, comprising: 5,6-Azeetene precursor 1a has the following structural formula: 5,6-Azeetylene precursor 1b has the following structural formula: 5,6-Azeetene precursor 1c has the following structural formula: 5,6-Azetylene precursor 1d has the following structural formula: 。 4. A method for preparing the 5,6-azynylene precursor according to any one of claims 1-3, comprising the following steps: Step 1: Using 3,4-dibromothiophene as a raw material, compound 2 was obtained through lithium halide exchange, reaction with alkyl borate ester, followed by oxidation and sulfonation. Step 2: Compound 2 reacts with an alkyllithium reagent at low temperature, and then with a halosilane to introduce a trialkylsilane group, yielding the silanized compound 3a: The low temperature is -100 °C to -78 °C; Determine the substituent R introduced at a specified position on the thiophene ring. 1 Is it hydrogen? If so, proceed to step 3; otherwise, proceed to step 2.

1. Step 2.1: After the lithiation step of compound 3a, iodomethane or iodoethane is added to obtain -R, respectively. 1 Compounds 3b and 3c are methyl or ethyl compounds; Me stands for methyl, and Et represents ethyl; Following the lithiation step of compound 3a, acetone is added, followed by a reduction reaction to obtain compound 3d: Pr stands for isopropyl; Step 3: Oxidize any one of compounds 3a, 3b, 3c, or 3d using a trifluoroacetic anhydride (TFAA) / trifluoromethanesulfonic acid (TfOH) / hydrogen peroxide (H2O2) system to obtain the corresponding thiophene dioxide compounds 4a, 4b, 4c, and 4d. Step 4: React any one of thiophene dioxide compounds 4a, 4b, 4c, and 4d with 6-(dimethylamino)fulne in an inert solvent at room temperature or upon heating, resulting in a [4+6] cycloaddition accompanied by aromatization, and isolate the 5,6-azynylene precursors 1a, 1b, 1c, and 1d: 。 5. The method for preparing the 5,6-azynylene precursor according to claim 4, characterized in that: in In step 1, The halolithium exchange is performed by dissolving 3,4-dibromothiophene in diethyl ether, cooling it to below -78 °C, and then adding n-butyllithium dropwise. The reaction with alkyl borate esters is as follows: isopropanol pinacol borate ester is added dropwise, the reaction is carried out at room temperature, and the reaction is quenched with HCl to obtain the first crude product; The oxidation reaction is as follows: the first crude product is dissolved in ethanol, boric acid is added at room temperature, and then hydrogen peroxide (H2O2) is added dropwise to react and obtain the second crude product; The sulfonation reaction is as follows: the second crude product is dissolved in dichloromethane, cooled to below -30 °C, p-toluenesulfonyl chloride p-TsCl is added, followed by the dropwise addition of triethylamine Et3N until complete conversion.

6. The method for preparing the 5,6-azynylene precursor according to claim 5, characterized in that: in In step 2, compound 2 is dissolved in tetrahydrofuran and cooled to a low temperature. The alkyllithium reagent is n-butyllithium; the halosilane is trimethylchlorosilane (TMSCl).

7. The method for preparing the 5,6-azynylene precursor according to claim 6, characterized in that: in In step 2.1, Compound 3b was prepared as follows: To a solution of compound 3a in anhydrous tetrahydrofuran (THF), n-butyllithium was added dropwise under an inert atmosphere at low temperature with stirring. Iodomethane (MeI) was then added, and the reaction mixture was slowly heated to room temperature with stirring. After the reaction was complete, the reaction was quenched with a saturated ammonium chloride aqueous solution and extracted with ethyl acetate. The combined organic layers were washed with saturated brine, dried with anhydrous sodium sulfate, filtered, and concentrated. The mixture was purified by petroleum ether-ethyl acetate chromatography to obtain compound 3b. The preparation of compound 3c differs from that of compound 3b in that iodomethane MeI is replaced with iodoethane EtI. The preparation of compound 3d differs from the preparation of compound 3b in that: (1) Replace iodomethane MeI with acetone, and then purify the product by silica gel column chromatography. (2) Dissolve AlCl3 in diethyl ether, cool to 0 °C, add LiAlH4 in portions, and react for at least 5 minutes; (3) Dissolve the product obtained in (1) in diethyl ether and add it dropwise to the suspension obtained in (2). Raise the temperature to room temperature and react. After post-treatment, purify the product by silica gel chromatography column to obtain compound 3d.

8. The method for preparing the 5,6-azynylene precursor according to claim 6 or 7, characterized in that: in In step 3, trifluoroacetic anhydride (TFAA) and trifluoromethanesulfonic acid (TfOH) were added to the reaction flask, cooled to below -20 °C, and hydrogen peroxide (H2O2) was slowly added dropwise. The mixture was then raised to room temperature to obtain a mixed solution. Compounds 3a, 3b, 3c, and 3d were dissolved in dichloromethane (DCM) and added to the mixed solution. The reaction was carried out for at least 12 hours, and the compounds 4a, 4b, 4c, and 4d were obtained after purification.

9. The method for preparing the 5,6-azynylene precursor according to claim 8, characterized in that: In step 4, the inert solvent is toluene or tert-butyl methyl ether.

10. A method for synthesizing azurite compounds from the 5,6-azynylene precursor of any one of claims 1-3, characterized in that: The 5,6-azynyne precursor was treated in an organic solvent in the presence of a fluoride ion source under an inert atmosphere to generate a 5,6-azynyne intermediate; the 5,6-azynyne intermediate was reacted with a scavenging agent to synthesize a seven-membered ring substituted azurite compound.

11. The method for synthesizing azurite compounds from the 5,6-azynylene precursor according to claim 10, characterized in that: The fluoride ion source is selected from cesium fluoride (CsF), the organic solvent is acetonitrile, and the reaction temperature is 0 °C to 110 °C.

12. The method for synthesizing azurite compounds from the 5,6-azynylene precursor according to claim 10 or 11, characterized in that: The trapping agent is selected from conjugated dienes, nucleophiles, reagents capable of σ-bond insertion, coupling agents in the presence of transition metal catalysts, or 1,3-dipoles.

13. The method for synthesizing azurite compounds from the 5,6-azynylene precursor according to claim 12, characterized in that: The conjugated diene is selected from furan, substituted furan, pyrrole, anthracene or rich ene derivatives; The nucleophile is selected from morpholine, imidazole, phenoxy anion, phosphonate or sulfonyl anion; The reagent for σ-bond insertion is selected from diphenyl diselenyl ether, cyano ketone, or malonate derivatives; The transition metal catalyst is a palladium catalyst, and the coupling agent is a 5,6-azynylene precursor, or an aryl iodide. The 1,3-dipolar is selected from diazoacetic acid ester, azide, nitrone, or iodonium ylide.

14. The method for synthesizing azurite compounds from the 5,6-azynylene precursor according to claim 10 or 11, characterized in that: The capturing agent is o-hydroxychalcone.

Images