A 4,5-azulenyl alkyne precursor, a method for preparing the same and a method for synthesizing azulene compounds

Abstract

This invention discloses a 4,5-azynylene precursor, its preparation method, and a method for synthesizing azurite compounds. The preparation method uses 2-bromo-3-(1,3-dioxolane-2-yl)phenol as a raw material and follows these steps: Step 1, reacting with sodium hydride, triethylchlorosilane, lithium halide exchange, and di-tert-butyl dicarbonate to obtain compound 2; Step 2, reacting compound 2 at low temperature with 1-diazo-1-(triethylsilyl)-2-propanone, diisopropylamine, di-tert-butyl dicarbonate, 2,6-dimethylpyridine, and 4-dimethylaminopyridine to obtain compound 3; Step 3, reacting compound 3 with bis[(A,A,A′,A′-tetramethyl-1,3-phenylenediol)rhodium] oxidation, methylmagnesium bromide, and boron trifluoride diethyl ether to obtain compound 4; Step 4, reacting compound 4 with trimethylsilyl trifluoromethanesulfonate, trifluoromethanesulfonic anhydride, and triethylamine to obtain 4,5-azynylene precursor 1. This invention solves the problem of introducing substituent groups into the seven-membered ring of azurite.

Description

Technical Field

[0001] This invention belongs to the technical field of organic chemistry, specifically relating to a 4,5-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 4,5-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 4,5-azynyne is one of its important regioisomers. However, there are currently no reports on the original formation of 4,5-azynyne. Therefore, researching and developing a stable, readily available, and efficient precursor for the formation of 4,5-azynyne, and establishing a wide range of syntheses based on 4,5-azynyne, is of urgent need and significant value.

[0004] Terminology: Yield refers to the ratio of raw material quantity to product quantity. Summary of the Invention

[0005] To address the problems existing in the prior art, the technical problem to be solved by this invention is to provide a 4,5-azynylene precursor that is stable, easy to synthesize, and can be converted into a highly reactive aazynylene intermediate, thus solving the problem of introducing substituent groups into the seven-membered ring of azurite. This invention also provides a method for preparing the 4,5-azynylene precursor, which is easy to implement. Furthermore, this invention provides a method for synthesizing azurite compounds that enables diverse substitution at the 4,5-site of the seven-membered ring, selective introduction of functional groups at predetermined sites, and controllable construction of fused-ring systems.

[0006] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows:

[0007] In a first aspect, a 4,5-azynylene precursor is provided, having the structure of formula (I): In formula (I), a trialkylsilyl-SiR3 and a leaving group L are attached to the 4- and 5-positions of the azurite ring, respectively, thereby forming a Kobayashi-type precursor that generates 4,5-azynylene via fluoride ion-induced elimination.

[0008] Specifically, the leaving group L is a sulfonate group or a halogen, such as -OTs, -OTf (trifluoromethanesulfonate), Br, or Cl; R in the trialkylsilyl-SiR3 1 R 2 R 3 All are C1-C6 alkyl groups.

[0009] Preferably, the leaving group L is p-toluenesulfonate group -OTs, and the trialkylsilyl-SiR3 is triethylsilyl-TES, that is, R in trialkylsilyl-SiR3. 1 R 2 R 2 All are ethyl; the structural formula of 4,5-azutyne precursor 1 is: In the structural formula, Me represents a methyl group.

[0010] In a second aspect, a method for preparing the above-mentioned 4,5-azynylene precursor according to the present invention includes the following steps:

[0011] Step 1: Using 2-bromo-3-(1,3-dioxolane-2-yl)phenol as a starting material, it was reacted sequentially with sodium hydride, triethylchlorosilane, lithium halide exchange, and di-tert-butyl dicarbonate to prepare compound 2.

[0012] Step 2: Compound 2 is reacted at low temperature with 1-diazo-1-(triethylsilyl)-2-propanone and diisopropylamine, and then with di-tert-butyl dicarbonate, 2,6-dimethylpyridine, and 4-dimethylaminopyridine to obtain compound 3. The low temperature is -100 °C to -55 °C;

[0013] Step 3: Compound 3 is oxidized with bis[(A,A,A′,A′-tetramethyl-1,3-phenylenedipropionic acid)rhodium], and then reacted with methylmagnesium bromide and boron trifluoride diethyl ether to obtain compound 4:

[0014] Step 4: Compound 4 is reacted with trimethylsilyl trifluoromethanesulfonate, and then with trifluoromethanesulfonic anhydride and triethylamine to obtain 4,5-azynylene precursor 1: .

[0015] Preferably, in step 1, The reaction with sodium hydride is as follows: 2-bromo-3-(1,3-dioxolane-2-yl)phenol is dissolved in tetrahydrofuran, cooled to below 0°C, and sodium hydride is added dropwise to react; The reaction with triethylchlorosilane is as follows: triethylchlorosilane is added dropwise, and the reaction is carried out at room temperature; The halolithium exchange process involves cooling the temperature to below -78 °C and then adding n-butyllithium dropwise. The reaction with di-tert-butyl dicarbonate is described as follows: di-tert-butyl dicarbonate is added dropwise slowly, and the reaction is carried out at room temperature.

[0016] Preferably, in step 2, the following steps are performed: (1) Under an inert gas atmosphere, 1-diazo-1-(triethylsilyl)-2-propanone was dissolved in tetrahydrofuran, cooled to below -55°C, and diisopropylamine was added dropwise to react. The reaction was then cooled to below -100°C, and compound 2 dissolved in tetrahydrofuran was added dropwise to react. After post-treatment, it was dissolved in methanol, stirred at room temperature, and the first crude product was obtained. (2) The first crude product was dissolved in dichloromethane, and 2,6-dimethylpyridine, ditert-butyl dicarbonate and 4-dimethylaminopyridine were added to react. After post-treatment, the first crude product was obtained, and compound 3 was obtained by silica gel column chromatography.

[0017] Preferably, in step 3, the following steps are performed: (1) Under an inert gas atmosphere, compound 3 was dissolved in dichloromethane, and the resulting solution was divided into multiple syringes. Each syringe was slowly added dropwise to the corresponding dichloromethane solution containing bis[(A,A,A′,A′-tetramethyl-1,3-phenylpropionic acid)rhodium] to react. All reaction solutions were combined, and the solvent was removed by vacuum evaporation to obtain the second crude product. (2) Dissolve the second crude product in anhydrous tetrahydrofuran and cool it to below -55°C. Add methyl magnesium bromide dropwise to treat the reaction solution and obtain the third crude product. (3) The third crude product was dissolved in dichloromethane and cooled to below -30°C. Boron trifluoride diethyl ether complex was added, and the second crude product was obtained after post-treatment. Compound 4 was obtained by silica gel column chromatography.

[0018] Preferably, in step 4, compound 4 is dissolved in dichloromethane, cooled to below 0°C, and trimethylsilyl trifluoromethanesulfonate is added dropwise. The reaction is then cooled to below -30°C and triethylamine and trifluoromethanesulfonic anhydride are added dropwise. After post-treatment, a third crude product is obtained, which is then subjected to silica gel chromatography to obtain a blue solid 4,5-azynylene precursor 1.

[0019] Thirdly, a method for synthesizing azurite compounds from the above-mentioned 4,5-azynylene precursor of the present invention involves treating the 4,5-azynylene precursor 1 in an organic solvent in the presence of a fluoride ion source under an inert atmosphere to generate a 4,5-azynylene intermediate; the 4,5-azynylene intermediate reacts with a scavenging agent to synthesize a seven-membered ring substituted azurite compound (hereinafter referred to as "azrite compound").

[0020] Preferably, the fluoride ion source is selected from cesium fluoride (CsF) or tetrabutylammonium fluoride (TBAF), and the organic solvent is acetonitrile.

[0021] Preferably, the trapping agent is selected from conjugated dienes, nucleophiles, reagents capable of σ-bond insertion, or coupling agents in the presence of transition metal catalysts.

[0022] The conjugated diene is selected from 2,5-dimethylfuran; The nucleophile is either 4-methyl-N-phenylbenzenesulfonamide or methyl 3-oxo-2-(phenyl-λ³-iodoalkyl)butyrate. The reagent used for σ-bond insertion is 2-oxocyclopentane-1-carboxynitrile; The transition metal catalyst is a palladium catalyst, and the coupling agent is 4,5-azynylene precursor 1 (4,5-azynylene precursor 1 reacts with itself).

[0023] The technical effects of this invention are: 1. The 4,5-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 50%, thus solving the technical problem that aazynylene intermediates are not easy to obtain. 2. The 4,5-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 four common benzynylene reactions and can accurately introduce structurally diverse functional groups into the 4,5-position of the azurite ring, realizing diversified modification of the azurite core, especially its seven-membered ring. It 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. 3. The 4,5-azynylene precursor of the present invention has strong synthetic capabilities, and can directly and efficiently synthesize azurite derivatives with complex substitution patterns at the 4,5-position that are difficult to obtain by existing technologies. It can also conveniently construct linearly arranged azurite-fused-ring aromatic systems (such as compound 8), which greatly expands the chemical space of azurite compounds. 4. The preparation method of the present invention involves the reaction for preparing the 4,5-azynylene precursor under mild conditions, which allows for good acceptance of the seven-membered ring of azurite, making the preparation simple and practical. Detailed Implementation

[0024] The present invention will be further described below with reference to embodiments: Example 1

[0025] Synthesis of 4,5-Azeonium precursor 1

[0026] Step 1: Synthesize compound 2

[0027] Under an inert atmosphere (commonly nitrogen), 2-bromo-3-(1,3-dioxolane-2-yl)phenol (4.9 g, 20.0 mmol, 1.0 equiv) was dissolved in tetrahydrofuran (50 mL), cooled to 0°C, and sodium hydride (60% dispersion in mineral oil, NaH) (1.0 g, 26.0 mmol, 1.3 equiv) was added in portions (200 mg / time), and the reaction was allowed to proceed for 30 minutes.

[0028] Add triethylchlorosilane (TESCl) (3.6 g, 24.0 mmol, 1.2 equiv) dropwise and react at room temperature for 30 minutes;

[0029] Cool to -78°C, and slowly add n-butyllithium (2.5 M n-hexane solution, n-BuLi) (12 mL, 30 mmol, 1.5 equiv), react for 1 hour;

[0030] Di-tert-butyl dicarbonate (Boc2O) (6.5 g, 30.0 mmol, 1.5 equiv) was slowly added dropwise, and the reaction was allowed to proceed to room temperature for 1 hour. The reaction was quenched (i.e. terminated) with HCl (10% by mass, 40 mL), and the product was post-processed to give 5.0 g (75% yield) of compound 2. 1 H NMR (400 MHz, CDCl3) δ 10.30 (s, 1H), 7.83 (dd, J1= 7.6 Hz, J2 = 0.8 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), 7.32 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 1.55 (s, 9H), 0.92-0.97 (m, 15H) ppm; 13 C NMR (100 MHz, CDCl3) δ 193.0, 157.2, 152.1, 144.4, 132.2, 130.5, 127.7, 126.8, 83.8, 27.8,7.8, 6.0 ppm; IR (thin film) 2957, 2876, 1760, 1697, 1588, 1560, 1458, 1441,1395, 1371, 1257, 1221, 1147, 1050, 1002, 871, 781, 735 (cm -1 ); HRMS (ESI) m / z: calcd for C 18 H 28O4Si [M + Na] + , 359.1649; found, 359.1653.

[0031] 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.

[0032] Step 2, Synthesize compound 3

[0033] i. Under an inert atmosphere, 1-diazo-1-(triethylsilyl)-2-propanone (4.4 g, 22.4 mmol, 1.5 equiv) was dissolved in tetrahydrofuran (80 mL), cooled to -55°C, and diisopropylamine (2.0 M n-hexane solution, LDA) (59.6 mL, 29.8 mmol, 2.0 equiv) was slowly added dropwise, and the reaction was allowed to proceed for 30 minutes. Subsequently, the reaction was cooled to -100°C, and compound 2 (5.0 g, 14.9 mmol, 1.0 equiv) dissolved in tetrahydrofuran (40 mL) was slowly added dropwise, and the reaction was allowed to proceed for 1 hour. After post-treatment, the compound was dissolved in methanol, stirred at room temperature for one day, and then further post-treated to obtain the first crude product.

[0034] ii. The first crude product was dissolved in dichloromethane (40 mL), and 2,6-dimethylpyridine (1.6 g, 14.9 mmol, 1.0 equiv), di-tert-butyl dicarbonate (4.9 g, 22.4 mmol, 1.5 equiv), and 4-dimethylaminopyridine were added. The reaction was carried out overnight, and the product was post-processed to obtain the first crude product. The first crude product was purified by silica gel column chromatography to give 3.2 g (yield 41%) of compound 3.

[0035] Melting point (MP): 79-81 °C; 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 1.6 Hz, 1H), 7.38 (s, 1H), 7.05 (dd, J1 = 5.2 Hz, J2 = 3.6 Hz, 1H), 6.29 (dd, J1 =10.4 Hz, J2 = 3.2 Hz, 1H), 5.23 (s, 1H), 2.81 (t, J = 13.2 Hz, 1H), 2.57 (dd,J1 = 15.6 Hz, J2 = 2.8 Hz, 1H), 1.54 (s, 9H), 1.42 (s, 9H), 0.99-0.94 (m, 15H)ppm; 13 C NMR (100 MHz, CDCl3) δ 190.3, 156.4, 152.2, 152.1, 148.5, 130.5,127.2, 123.2, 121.9, 83.4, 82.5, 73.6, 55.6, 49.1, 27.9, 27.8, 8.0, 5.2 ppm;IR (thin film) 3100, 2957, 2876, 2105, 1757, 1645, 1596, 1564, 1457, 1370,1332, 1279, 1255, 1215, 1147, 1101, 1000, 875, 783, 730 (cm -1 ); HRMS (ESI) m / z: calcd for C 26 H 40 N₂O₇Si[M + Na] + , 543.2497; found, 543.2505.

[0036] Step 3: Synthesize compound 4

[0037] Under an inert atmosphere, compound 3 (832.4 mg, 1.6 mmol, 1.0 equivalent) was dissolved in dichloromethane (24 mL), and the resulting solution was aliquoted into eight syringes (each containing 0.2 mmol). This solution was then slowly added dropwise using a syringe pump to each of eight parallel dichloromethane solutions containing bis[(A,A,A′,A′-tetramethyl-1,3-phenylenediol)rhodium] (Rh2(esp)2) (0.8 mg, 0.001 mmol, 0.005 equivalent), over a period of 2 hours. After the addition was complete, the reaction mixture was allowed to react for another 5 minutes. All reaction mixtures were then combined, and the solvent was removed under reduced pressure to obtain the second crude product.

[0038] The second crude product was dissolved in anhydrous tetrahydrofuran (10 mL) and cooled to -55°C. Methyl magnesium bromide (MeMgBr) (4.8 mL, 4.8 mmol, 3.0 equiv) was slowly added dropwise. After the addition was complete, water was added to terminate the reaction, and the third crude product was obtained after post-treatment.

[0039] The third crude product was dissolved in dichloromethane (15 mL) and cooled to -30°C, followed by the addition of boron trifluoride diethyl ether complex (BF3·Et2O) (60.6 μL, 0.48 mmol, 0.3 equiv). Post-treatment yielded the second crude product, which was purified by silica gel column chromatography to give 285 mg (48% yield) of compound 4. 1 H NMR (400 MHz, CDCl3) δ 8.15 (d, J =9.2 Hz, 1H), 7.71 (d, J = 3.6 Hz, 1H), 7.65 (d, J = 3.6 Hz, 1H), 7.28-7.25(m, 1H), 6.99 (dd, J1 = 10.8 Hz, J2 = 9.6 Hz, 1H), 2.64 (s, 3H), 1.56 (s, 9H), 1.20-1.03 (m, 6H), 0.99 (t, J = 7.2 Hz, 9H) ppm; 13C NMR (100 MHz, CDCl3) δ153.2, 149.4, 142.2, 140.5, 138.2, 137.9, 132.3, 131.8, 125.7, 119.6, 118.5,83.3, 27.9, 13.0, 8.1, 6.8 ppm; IR (thin film) 3535, 2956, 2875, 2361, 2342,1754, 1459, 1420, 1370, 1273, 1253, 1151, 1118, 1003, 925, 881, 836, 783,728, 648 (cm -1 ); HRMS (ESI) m / z: calcd for C 22 H 32 O3Si [M + Na] + , 395.2013;found, 398.2021.

[0040] Step 4: Synthesis of 4,5-Azeyn precursor 1

[0041] Compound 4 (818 mg, 2.2 mmol, 1.0 equiv) was dissolved in dichloromethane (10 mL), cooled to 0°C, and trimethylsilyl trifluoromethanesulfonate was added dropwise. The reaction was then cooled to -30°C, and triethylamine (445 mg, 4.4 mmol, 2.0 equiv) and trifluoromethanesulfonic anhydride (1.2 g, 4.4 mmol, 2.0 equiv) were added dropwise. The reaction was then processed to obtain a third crude product. The third crude product was subjected to silica gel column chromatography to obtain 809 mg (91% yield) of blue solid 4,5-azynylene precursor 1. 1 H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 9.2 Hz, 1H), 7.81 (d, J = 4.0 Hz, 1H), 7.73 (d, J = 4.0Hz, 1H), 7.43 (d, J = 10.8 Hz, 1H), 6.97 (dd, J1 = 10.8 Hz, J2 = 9.6 Hz, 1H), 2.67 (s, 3H), 1.18 (q, J = 8.0 Hz, 6H), 0.99 (t, J = 8.0 Hz, 9H) ppm; 13C NMR(100 MHz, CDCl3) δ 148.2, 143.5, 140.5, 139.3, 137.4, 133.5, 129.0, 128.2,120.8, 118.8 (q, J = 318.6 Hz, C), 118.7, 13.0, 8.0, 7.2 ppm; IR (thin film)2958, 2878, 1591, 1543, 1459, 1415, 1244, 1210, 1140, 1053, 1033, 954, 908,873, 785, 760, 733, 693, 606, 515 (cm -1 ); HRMS (ESI) m / z: calcd forC 18 H 23 F3O3SSi [M + H] + , 405.1162; found, 405.1169. Example 2

[0042] Compound 5 (a seven-membered ring-substituted azulene compound) was obtained by cycloaddition of 4,5-azynylene precursor 1 with 2,5-dimethylfuran via a [4+2] cycloaddition.

[0043] The trapping agent used was 2,5-dimethylfuran. Under nitrogen atmosphere, 2,5-dimethylfuran (57.6 mg, 0.6 mmol, 3.0 equiv), 4,5-azynylene precursor 1 (80.8 mg, 0.2 mmol, 1.0 equiv), and cesium fluoride (CsF) (91.1 mg, 0.6 mmol, 3.0 equiv) were weighed into a round-bottom flask, and acetonitrile (3.0 mL) was added. The mixture was stirred at room temperature. 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 26.9 mg of blue oily compound 5 (yield 57%).

[0044] 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 10.4 Hz, 1H), 7.64 (d, J = 4.4Hz, 1H), 7.38 (d, J = 4.4 Hz, 1H), 7.29 (d, J = 8.8 Hz, 1H), 6.85-6.75 (m,2H), 6.69 (d, J = 5.2 Hz, 1H), 2.59 (s, 3H), 2.26 (s, 3H), 1.98 (s, 3H) ppm; 13 C NMR (100 MHz, CDCl3) δ 156.9, 146.2, 143.8, 143.3, 139.0, 134.4, 134.2,131.0, 128.9, 125.2, 118.0, 112.3, 90.9, 89.3, 19.7, 16.0, 13.0 ppm; IR (thinfilm) 3446, 2977, 2934, 1690, 1591, 1451, 1383, 1360, 1303, 1231, 1161, 1133,1075, 1020, 963, 894, 867, 740, 726, 663, 617 (cm -1 ); HRMS (ESI) m / z: calcdfor C 17 H 16 O [M + H] + , 237.1274; found, 237.1277.

[0045] Note: During the reaction of 4,5-azynyne precursor 1, the generated 4,5-azynyne intermediate is unstable and is immediately captured to obtain the product. Therefore, 4,5-azynyne precursor 1, fluoride ion activating reagent and capturing reagent are added together. Example 3

[0046] Compound 6 (a seven-membered ring-substituted azulene compound) was obtained by regioselective nucleophilic addition of 4,5-azynylene precursor 1 to 4-methyl-N-phenylbenzenesulfonamide.

[0047] The trapping agent was 4-methyl-N-phenylbenzenesulfonamide. Under nitrogen atmosphere, 4-methyl-N-phenylbenzenesulfonamide (148.4 mg, 0.6 mmol, 3.0 equiv), tetrabutylammonium fluoride (TBAF) (0.4 mL, 0.4 mmol, 2.0 equiv, 1.0 M tetrahydrofuran solution), and acetonitrile (2 mL) were added to the reaction flask. At room temperature, an acetonitrile solution (80.9 mg, 0.2 mmol, 1.0 equiv) of 4,5-azynylene precursor 1 (2 mL) was slowly added dropwise to the above mixture over 1 hour using a syringe pump. After the reaction was complete, the crude product was obtained and purified by silica gel column chromatography to give 49.6 mg of blue solid compound 6 (64% yield).

[0048] Melting point (MP): 92-94 °C; 1 H NMR (400 MHz, CDCl3) δ 8.21-8.12 (m, 2H), 7.75 (d, J = 3.6 Hz, 1H), 7.68-7.61 (m, 2H), 7.52 (dd, J1 = 10.8 Hz, J2 = 2.4 Hz, 1H), 7.38-7.33 (m, 2H), 7.33-7.27 (m, 5H), 7.23-7.19 (m, 1H), 6.94 (t, J =10.0 Hz, 1H), 2.65 (s, 3H), 2.45 (s, 3H) ppm; 13 C NMR (100 MHz, CDCl3) δ143.8, 142.4, 139.6, 139.2, 138.4, 137.8, 137.7, 136.4, 134.0, 133.9, 129.8,129.4, 128.4, 128.1, 127.2, 127.0, 119.5, 119.1, 21.7, 12.8 ppm; IR (thinfilm) 3736, 3023, 2917, 2361, 2342, 1573, 1488, 1445, 1391, 1347, 1242, 1160,1117, 1090, 1005, 907, 810, 770, 695, 579, 554 (cm -1 ); HRMS (ESI) m / z: calcdfor C 24 H 21 NO2S [M + H] + , 388.1366; found, 388.1374. Example 4

[0049] The regioselective nucleophilic addition of 4,5-azynylene precursor 1 with methyl 3-oxo-2-(phenyl-λ³-iodoalkyl)butyrate yielded compound 7 (a seven-membered ring-substituted azulene compound).

[0050] The trapping agent was methyl 3-oxo-2-(phenyl-λ³-iodoalkyl)butyrate. Under nitrogen atmosphere, methyl 3-oxo-2-(phenyl-λ³-iodoalkyl)butyrate (127.2 mg, 0.4 mmol, 2.0 equiv), 4,5-azynylene precursor 1 (80.9 mg, 0.2 mmol, 1.0 equiv), and cesium fluoride (CsF) (91.1 mg, 0.6 mmol, 3.0 equiv) were weighed into a round-bottom flask, and acetonitrile (MeCN) (3.0 mL) was added. The mixture was stirred at room temperature. 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 17.3 mg of green solid compound 7 (yield 34%).

[0051] Melting point (MPa): 104-106 °C; 1 H NMR (400 MHz, CDCl3) δ 8.59 (d, J = 10.8 Hz,1H), 8.23 ​​(d, J = 9.6 Hz, 1H), 7.60 (d, J = 3.2 Hz, 1H), 7.49 (d, J = 3.2 Hz,1H), 7.20 (dd, J1 = 10.4 Hz, J2 = 9.6 Hz, 1H), 3.98 (s, 3H), 2.83 (s, 3H), 2.66 (s, 3H) ppm; 13 C NMR (100 MHz, CDCl3) δ 164.8, 162.6, 154.6, 139.6,135.4, 132.6, 129.9, 124.7, 122.1, 121.7, 119.4, 111.4, 109.4, 51.7, 15.1,12.7 ppm; IR (thin film) 3735, 2952, 2917, 2360, 2342, 1705, 1601, 1528,1438, 1382, 1311, 1279, 1213, 1139, 1088, 924, 725, 679 (cm-1 ); HRMS (ESI) m / z: calcd for C 16 H 14 O3 [M + H] + , 255.1016; found, 255.1025. Example 5

[0052] Compound 8 (a seven-membered ring-substituted azulene compound) was obtained by inserting the 4,5-azynylene precursor 1 into the C-C σ-bond of 2-oxocyclopentane-1-carboxynitrile.

[0053] The trapping agent was 2-oxocyclopentane-1-carboxylonitrile. Under nitrogen atmosphere, 65.4 mg (0.6 mmol, 3.0 equiv) of 2-oxocyclopentane-1-carboxylonitrile, 80.9 mg (0.2 mmol, 1.0 equiv) of 4,5-azynylene precursor 1, and 91.1 mg (0.6 mmol, 3.0 equiv) of cesium fluoride (CsF) were weighed into a round-bottom flask, and 3.0 mL of acetonitrile (MeCN) was added. The mixture was stirred at room temperature. 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 42.3 mg of green solid compound 8 (85% yield). The reaction formed a [5,7,7] tricyclic system as a single regioisomer. The structure was confirmed by NMR, HRMS, and NOESY.

[0054] Melting point (MP): 43-45 °C; 1 H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 9.6 Hz, 1H), 7.86 (d, J = 10.0 Hz, 1H), 7.82 (d, J = 4.0 Hz, 1H), 7.15 (t, J = 10.0Hz, 1H), 7.11 (d, J = 4.0 Hz, 1H), 4.11 (dd, J1 = 11.6 Hz, J2 = 5.6 Hz, 1H), 2.84 (dt, J1 = 17.6 Hz, J2 = 4.4 Hz, 1H), 2.73 (dd, J1 = 12.4 Hz, J2 = 3.6 Hz, 1H), 2.68 (s, 3H), 2.40-2.30 (m, 1H), 2.15-2.05 (m, 1H), 1.99-1.88 (m, 1H), 1.80-1.65 (m, 1H) ppm;13 C NMR (100 MHz, CDCl3) δ 208.1, 145.4, 140.7, 137.3,135.4, 134.0, 133.8, 129.5, 121.4, 120.8, 119.9, 116.7, 41.3, 36.4, 31.8,20.9, 12.9 ppm; IR (thin film) 3389, 2930, 2243, 1703, 1555, 1443, 1400,1384, 1362, 1233, 1180, 1079, 942, 905, 782, 729, 581 (cm -1 ); HRMS (ESI) m / z:calcd for C 17 H 15 NO [M + Na] + , 272.1046; found, 272.1056. Example 6

[0055] The palladium-catalyzed dimerization of 4,5-azynylene precursor 1 yielded compound 9 (a seven-membered ring-substituted azulene compound).

[0056] Under nitrogen atmosphere, azeynylene precursor 1 (80.9 mg, 0.2 mmol, 1.0 equiv), tetratetraphenylphosphine palladium (Pd(PPh3)4) (23.1 mg, 0.02 mmol, 0.1 equiv), and cesium fluoride (CsF) (91.1 mg, 0.6 mmol, 3.0 equiv) were weighed into a round-bottom flask, and acetonitrile (2.0 mL) was added. The mixture was stirred at room temperature. 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 19.9 mg of dimer compound 9 (71% yield). The structure of dimer compound 9 was confirmed by single-crystal X-ray diffraction (CCDC 2499528).

[0057] Melting point (Mp): 197-199 °C; 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 10.8 Hz,2H), 7.46 (d, J = 4.4 Hz, 2H), 7.44 (d, J = 4.4 Hz, 2H), 7.01 (d, J = 8.8 Hz,2H), 6.65 (t,J = 10.0 Hz, 2H), 2.46 (s, 6H) ppm; 13 C NMR (100 MHz, CDCl3) δ151.7, 145.4, 142.9, 136.9, 134.6, 131.9, 129.1, 121.8, 121.6, 116.3, 13.0ppm; IR (thin film) 1576, 1492, 1414, 1381, 1359, 1043, 899, 784, 756, 699,601, 579 (cm -1 ); HRMS (ESI) m / z: calcd for C 22 H 16 [M] •+ , 280.1247; found,280.1255。

Claims

1. A 4,5-oxyl alkyn 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 4- and 5-positions of the azurite ring, respectively.

2. The 4,5-azolyl yne precursor of claim 1, characterized by: The leaving group L is a sulfonate group or a halogen; the trialkylsilyl group -SiR3in which R 1 , R 2 , R 3 are each a C1-C6 alkyl group.

3. The 4,5-azolyl yne precursor of claim 2, characterized by: The leaving group L is p-toluenesulfonate group -OTs, and the trialkylsilyl-SiR3 is triethylsilyl-TES, with the following structural formula: In the structural formula, Me represents a methyl group.

4. A method for preparing the 4,5-azolyl yne precursor according to any one of claims 1 to 3, characterized in that, Includes the following steps: Step 1: Using 2-bromo-3-(1,3-dioxolane-2-yl)phenol as a starting material, it was reacted sequentially with sodium hydride, triethylchlorosilane, lithium halide exchange, and di-tert-butyl dicarbonate to prepare compound 2. Step 2: Compound 2 is reacted at low temperature with 1-diazo-1-(triethylsilyl)-2-propanone and diisopropylamine, and then with di-tert-butyl dicarbonate, 2,6-dimethylpyridine, and 4-dimethylaminopyridine to obtain compound 3. The low temperature is -55 °C to -100 °C; Step 3: Compound 3 is oxidized with bis[(A,A,A′,A′-tetramethyl-1,3-phenylenedipropionic acid)rhodium], and then reacted with methylmagnesium bromide and boron trifluoride diethyl ether to obtain compound 4: Step 4: Compound 4 is reacted with trimethylsilyl trifluoromethanesulfonate, and then with trifluoromethanesulfonic anhydride and triethylamine to obtain 4,5-azynylene precursor 1: 。 5. The method for preparing the 4,5-azynylene precursor according to claim 4, characterized in that: in In step 1, The reaction with sodium hydride is as follows: 2-bromo-3-(1,3-dioxolane-2-yl)phenol is dissolved in tetrahydrofuran, cooled to below 0°C, and sodium hydride is added dropwise to react; The reaction with triethylchlorosilane is as follows: triethylchlorosilane is added dropwise, and the reaction is carried out at room temperature; The halolithium exchange process involves cooling the temperature to below -78 °C and then adding n-butyllithium dropwise. The reaction with di-tert-butyl dicarbonate is described as follows: di-tert-butyl dicarbonate is added dropwise slowly, and the reaction is carried out at room temperature.

6. The method for preparing the 4,5-azynylene precursor according to claim 5, characterized in that, In step 2, follow these steps: (1) Under an inert gas atmosphere, 1-diazo-1-(triethylsilyl)-2-propanone was dissolved in tetrahydrofuran, cooled to below -55°C, and diisopropylamine was added dropwise to react. The reaction was then cooled to below -100°C, and compound 2 dissolved in tetrahydrofuran was added dropwise to react. After post-treatment, it was dissolved in methanol, stirred at room temperature, and the first crude product was obtained. (2) The first crude product was dissolved in dichloromethane, and 2,6-dimethylpyridine, ditert-butyl dicarbonate and 4-dimethylaminopyridine were added to react. After post-treatment, the first crude product was obtained, and compound 3 was obtained by silica gel column chromatography.

7. The method for preparing the 4,5-azynylene precursor according to claim 6, characterized in that, In step 3, follow these steps: (1) Under an inert gas atmosphere, compound 3 was dissolved in dichloromethane, and the resulting solution was divided into multiple syringes. Each syringe was slowly added dropwise to the corresponding dichloromethane solution containing bis[(A,A,A′,A′-tetramethyl-1,3-phenylpropionic acid)rhodium] to react. All reaction solutions were combined, and the solvent was removed by vacuum evaporation to obtain the second crude product. (2) Dissolve the second crude product in anhydrous tetrahydrofuran and cool it to below -55°C. Add methyl magnesium bromide dropwise to treat the reaction solution and obtain the third crude product. (3) The third crude product was dissolved in dichloromethane and cooled to below -30°C. Boron trifluoride diethyl ether complex was added, and the second crude product was obtained after post-treatment. Compound 4 was obtained by silica gel column chromatography.

8. The method for preparing the 4,5-azynylene precursor according to claim 7, characterized in that: in In step 4, compound 4 was dissolved in dichloromethane, cooled to below 0°C, and trimethylsilyl trifluoromethanesulfonate was added dropwise. The reaction was then cooled to below -30°C and triethylamine and trifluoromethanesulfonic anhydride were added dropwise. After post-treatment, the third crude product was obtained, and the blue solid 4,5-azynylene precursor 1 was obtained by silica gel column chromatography.

9. A method for synthesizing azurite compounds from the 4,5-azynylene precursor according to any one of claims 1-3, characterized in that: The 4,5-azyn precursor was treated in an organic solvent in the presence of a fluoride ion source under an inert atmosphere to generate a 4,5-azyn intermediate; the 4,5-azyn intermediate was reacted with a scavenging agent to synthesize a seven-membered ring substituted azurite compound.

10. The method for synthesizing azurite compounds from the 4,5-azynylene precursor according to claim 9, characterized in that: The fluoride ion source is selected from cesium fluoride (CsF) or tetrabutylammonium fluoride (TBAF), and the organic solvent is acetonitrile.

11. The method for synthesizing azurite compounds from the 4,5-azynylene precursor according to claim 9 or 10, characterized in that: The trapping agent is selected from conjugated dienes, nucleophiles, reagents capable of σ-bond insertion, or coupling agents in the presence of transition metal catalysts.

12. The method for synthesizing azurite compounds from the 4,5-azynylene precursor according to claim 11, characterized in that: The conjugated diene is selected from 2,5-dimethylfuran; The nucleophile is either 4-methyl-N-phenylbenzenesulfonamide or methyl 3-oxo-2-(phenyl-λ³-iodoalkyl)butyrate. The reagent used for σ-bond insertion is 2-oxocyclopentane-1-carboxynitrile; The transition metal catalyst is a palladium catalyst, and the coupling agent is 4,5-azutyne precursor 1.

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