Seven-membered silicon heterocyclic compound as well as preparation method and application thereof
Through a synergistic catalytic system of bienenyl functionalized silicon heteroquaternary compounds, metal palladium catalysts and phosphine ligands, a variety of seven-membered silicon heterocyclic compounds have been synthesized under mild conditions, solving the problems of high synthesis costs and narrow application scope of substrates in the prior art, and broadening their application in drug synthesis.
Patent Information
- Application Number
- CN202510778052.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-11
- Publication Date
- 2025-07-29
AI Technical Summary
It is difficult to efficiently and at low cost to synthesize seven-membered silicon heterocyclic compounds with specific structures and substituents. Traditional methods require high temperature, high pressure or strong acid and strong alkali conditions, and the application range of substrates is narrow, which limits their application in the fields of drug synthesis and other fields.
Two different types of 7-membered silicon heterocyclic compounds were mixed with metal palladium catalyst and phosphine ligand under an inert gas atmosphere. Through intramolecular cycloaddition and elimination reactions, two different types of seven-membered silicon heterocyclic compounds were synthesized. The reaction conditions were mild and commercial reagents were used to complete at 20-60 °C. The crude product was purified by flash chromatography on silica gel.
It has achieved low-cost and easy-to-get seven-membered silicon heterocyclic compound synthesis, with high yield and wide application range, and is suitable for the field of medicinal chemistry.
Smart Images
Figure CN120383622A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of organic chemistry, and particularly to a seven-membered silicon heterocyclic compound, a preparation method thereof, and an application thereof. Background Art
[0002] Silicon-centered chiral organosilicon compounds have shown unique values and application prospects in the fields of synthetic chemistry, materials chemistry, pharmaceutical chemistry, etc. due to their unique structures and properties. For example, chiral organosilanes can be used as chiral auxiliaries in organic synthesis to achieve the transfer from carbon chirality to silicon chirality. In addition, they can also be used as chiral reagents to achieve metallization reactions, oxidation reactions, Brook rearrangements, and reverse Brook rearrangement reactions of silicon-stereosilanes. Since silicon-containing molecules have low toxicity and good metabolic properties and can be complementary to carbon analogs, silicon-based substitution has received increasing attention in pharmaceutical chemistry. Among them, the silicon heterocyclic structure, due to its special structure, makes organosilicon molecules containing silicon heterocyclic structures not only exhibit better biological activities but also occupy great advantages in the fields of luminescent materials, etc. Therefore, the efficient synthesis of silicon heterocyclic organosilicon compounds has always been of concern to scientific researchers. In recent years, the method of intermolecular or intramolecular cyclization catalyzed by transition metals is one of the most common and effective methods for constructing silicon heterocycles.
[0003] As an important means for developing new drug active molecules, the silicon substitution strategy has significant potential application value. As the core structural unit in the silicon-containing functional molecular system, silicon heterocyclic compounds play an important role in the field of pharmaceutical chemistry. However, currently, there are key challenges in constructing the structural diversity of silicon heterocyclic compounds, and there are significant methodological limitations in the efficient synthesis strategies of silicon heterocycles, which directly restricts the development process of functional organosilicon molecules.
[0004] In the field of drug synthesis, seven-membered silicon heterocyclic compounds, as drug synthesis precursors, are of great significance for developing new drugs. However, due to the limitations of existing synthesis methods, it is difficult to obtain seven-membered silicon heterocyclic compounds with specific structures and substituents efficiently and at low cost. For example, some synthetic routes require the use of expensive special reagents, and the reaction process needs to be carried out under extreme conditions such as high temperature, high pressure, or strong acids and bases, which not only increases the production cost but also reduces the safety and operability of the reaction. Moreover, the substrate scope of traditional methods is relatively narrow, and it is difficult to synthesize seven-membered silicon heterocyclic compounds with different substituents, restricting their wide application in the fields of drug synthesis, etc.
[0005] Therefore, developing a seven-membered silicon heterocyclic compound with low raw material cost, easy availability, simple synthesis process, and a wide substrate expansion range, as well as a preparation method thereof, has become an urgent technical problem to be solved in this field. Summary of the Invention
[0006] The object of the present invention is to provide a heptasilacycle compound, a preparation method and an application thereof in view of the deficiencies of the prior art. The raw materials required by the present invention are low in cost and easy to obtain, and the synthesis process is simple and has the advantage of a wide range of substrate expansion.
[0007] The present invention is achieved by the following technical solutions: In the first aspect, the present invention provides a heptasilacycle compound, and the compound has a structural formula shown in the following formula (I) or formula (II): In the formula, R 1 is hydrogen or a halogen; R 2 is a cycloalkyl group, a phenyl group or a substituted phenyl group; the substitution is selected from one of C 1-4 alkyl, aryl, benzyloxy or halogen.
[0008] In the second aspect, the present invention provides a preparation method of the above-mentioned heptasilacycle compound. The reaction conditions are mild, the method is simple, and heptasilacycle compounds with various different substituents can be obtained. The preparation method is to synthesize two different heptasilacycle compounds by intramolecular cycloaddition and elimination reactions of an allenyl-functionalized silatetrameter compound. The reaction formula is shown as follows: The specific reaction steps are as follows: Under an inert gas atmosphere, a phosphine ligand, a palladium metal catalyst and a solvent are mixed, and then an allenyl-functionalized silatetrameter compound 1 is added. After the reaction is completed, the solvent is removed under vacuum, and the heptasilacycle compound is obtained after purification.
[0009] Preferably, the concentration of the reactant allenyl-functionalized silatetrameter compound is 0.1 mol / L. The allenyl-functionalized silatetrameter compound as a reactant directly undergoes intramolecular cycloaddition and elimination reactions under the action of a complex formed by a metal catalyst and a phosphine ligand. The reaction conditions are mild, the method is simple, and the crude product obtained can be purified by silica gel flash chromatography to obtain a pure product.
[0010] Preferably, the palladium metal catalyst is palladium acetate, and the usage amount is 3%-6% of the molar amount of the allenyl-functionalized silatetrameter compound 1.
[0011] Preferably, the phosphine ligand is tris(o-tolyl)phosphine or tris(pentafluorophenyl)phosphine.
[0012] Preferably, the usage amount of the phosphine ligand is 5%-7% of the molar amount of the allenyl-functionalized silatetrameter compound 1.
[0013] Preferably, the solvent is selected from one of toluene and m-xylene.
[0014] Preferably, the reaction temperature is 20 - 60 °C and the reaction time is 10 - 24 h.
[0015] In a third aspect, the present invention provides the use of the above-mentioned seven-membered silicon heterocyclic compound as a drug synthesis precursor.
[0016] The above-mentioned seven-membered silicon heterocyclic compound can be used as a drug intermediate or a drug itself, or as an important intermediate in organic synthesis, and has broad application prospects in the field of organic synthesis. For example, derivatives shown in the following formula can be applied to the field of medicinal chemistry: .
[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: The present invention uses an easily prepared allenyl-functionalized silicon heterotetrameric compound as a raw material, constructs a synergistic catalytic system of a metal catalyst and a phosphine ligand, and realizes β precise regulation of -H elimination and reductive elimination, and a target product with a high yield can be obtained. Two different types of seven-membered silicon heterocyclic compounds are synthesized through intramolecular cycloaddition and selective elimination reactions. The catalyst is a commercially available reagent, and the reaction can be completed by stirring at 20 - 60 °C. The method is simple, and the crude product obtained can be purified by silica gel flash chromatography to obtain a pure product. It can be applied to the field of medicinal chemistry. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 1H NMR spectrum of the seven-membered silicon heterocyclic compound prepared in Example 3; Figure 2 13C NMR spectrum of the seven-membered silicon heterocyclic compound prepared in Example 3; Figure 3 1H NMR spectrum of the seven-membered silicon heterocyclic compound prepared in Example 15; Figure 4 13C NMR spectrum of the seven-membered silicon heterocyclic compound prepared in Example 15. DETAILED DESCRIPTION OF THE INVENTION
[0019] The present invention will be further described below in conjunction with specific examples, but the present invention is not limited to the following examples. Unless otherwise specified, the raw materials used in the examples can be purchased commercially or prepared by conventional methods.
[0020] Example 1: General method for preparing allenyl-functionalized silicon heterotetrameric compound 1 Add S1 (1.0 equiv), S2 (1.2 equiv), S3 (1.2 equiv), CuBr2 (0.4 equiv) and 1,4-Dioxane solution to a dry flask equipped with a stir bar and a rubber septum. Stir at 70 °C for 21 h. After completion, quench the reaction mixture with saturated NH4Cl solution, extract with EtOAc, concentrate in vacuo, and purify the residue by silica gel chromatography to obtain S4.
[0021] Mix S4 (1.0 equiv), p -TsOH•H2O (0.2 equiv) and MeOH solution, and stir overnight at 40 °C. After completion, quench with saturated NaHCO3, extract with EtOAc, concentrate in vacuo, and purify the residue by silica gel chromatography to obtain S5.
[0022] Mix S5 (1.1 equiv), S7 (1.0 equiv), PPh3 (1.0 equiv) and THF solution, add diisopropyl azodicarboxylate DIAD (1.1 equiv) dropwise with stirring, and then stir the reaction mixture overnight at room temperature. After completion, concentrate the reaction mixture in vacuo and purify directly by flash silica gel chromatography to obtain S6; At 0 °C, i -PrMgCl•LiCl (1.3 equiv) was added dropwise to a THF solution of S6 (1.0 equiv), and stirred at 0 °C for 1 h. Magnesium (1.5 equiv), 5 mL of a solution of S8 (1.0 equiv) in THF and a grain of iodine were heated to initiate the Grignard reaction. The remaining S6 solution was added dropwise within 1 h, and refluxed for 4 h, then the reaction mixture was cooled to room temperature. At 0 °C, 1-chloro-1-methylsilane was added dropwise to the solution of the Grignard reagent derived from S6, and the reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was quenched with saturated NH4Cl solution, extracted with EtOAc, concentrated in vacuo, and the residue was purified by silica gel chromatography to obtain Compound 1.
[0023] In the above synthetic route, R 1 、R 2 are defined as described above.
[0024] Example 2: General method for preparing the compound shown in formula (I) Add Pd(OAc)2 (2.26 mg, 0.01 mmol, 5.0 mol%) and Ligand 1 (3.65 mg, 0.012 mmol, 6.0 mol%) to a dry Schlenk tube equipped with a septum and a magnetic stir bar. Evacuate the tube under high vacuum and refill it with nitrogen (3 times). Introduce toluene (2.0 mL) into the tube and add Compound 1 (0.2 mmol, 1.0 equiv, 0.1 M) dropwise. Stir the reaction tube at 30 °C for 12 h. After completion, remove the solvent under vacuum and purify the residue by flash column chromatography on silica gel to obtain Product Ⅰ.
[0025] In the above synthetic route, R 1 and R 2 are defined as described above.
[0026] In addition, in the general method described in Example 2, the amounts of the relevant compounds can be adjusted according to actual needs. For example, the amount of Pd(OAc)2 used can be 3% - 6% of 1 molar equivalent of the allenylic-functionalized silyl quaternary compound, the amount of Ligand1 used is 5% - 7% of 1 molar equivalent of the allenylic-functionalized silyl quaternary compound, the reaction temperature is 20 - 60 °C, and the reaction time is 10 - 24 h. One can freely choose within the above ranges and will not be elaborated here.
[0027] Example 3: Prepare Compound Ⅰa: Prepared according to the method in Example 2, and Compound Ⅰa (37.9 mg, yield 62%) was obtained by silica gel column chromatography as a yellow oil. Its 1H NMR spectrum is as Figure 1 shown, and its 13C NMR spectrum is as Figure 2 shown.
[0028] 1 1H NMR (400 MHz, CDCl3) δ 7.37 (dd, J J = 7.2, 1.8 Hz, 1H), 7.29–7.23 (m,3H), 7.18–7.13 (m, 3H), 7.06–7.01 (m, 1H), 6.93–6.87 (m, 2H), 5.80–5.67 (m,1H), 4.87–4.77 (m, 2H), 4.30–4.24 (m, 1H), 4.01–3.94 (m, 1H), 2.94–2.86 (m,1H), 2.76–2.68 (m, 1H), 1.95–1.90 (m, 2H), 0.43 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.8, 139.9, 138.8, 138.1, 135.2, 134.5, 131.3, 129.2, 129.0, 128.3, 127.1, 123.6, 120.7, 114.0, 74.6, 33.4, 23.0, -5.2. HRMS (ESI) m / z: [M+Na] + calculated for C 20 H 22 OSi:329.1332, found: 329.1328. Example 4: Preparation of Compound Ib: Prepared according to the method in Example 2, and Compound Ib (31.7 mg, yield 49%) was obtained by silica gel column chromatography as a yellow oil.
[0029] 1 H NMR (400 MHz, CDCl3) δ 7.45 (dd, J J = 7.3, 1.8 Hz, 1H), 7.33 (td, J J = 7.6, 1.8 Hz, 1H), 7.19 – 7.09 (m, 5H), 6.99 (d, J J = 7.9 Hz, 1H), 6.95 – 6.92 (m, 1H), 5.89 – 5.74 (m, 1H), 4.96 – 4.84 (m, 2H), 4.39 – 4.32 (m, 1H), 4.10 – 4.02 (m, 1H), 3.04 – 2.95 (m, 1H), 2.85 – 2.77 (m, 1H), 2.36 (s, 3H), 2.03 – 1.96 (m, 2H), 0.50 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.8, 139.8, 138.0, 136.8, 135.2, 135.1, 134.6, 131.2, 129.2, 129.0, 123.5, 120.7, 113.9, 33.4, 23.1, 21.3, -5.1. HRMS (ESI) m / z: [M+Na] + calculated for C 21 H 24 OSi: 343.1489, found: 343.1489. Example 5: Compound Ⅰc was prepared according to the method in Example 2 and obtained by silica gel column chromatography as a yellow oil (42.2 mg, yield 65%).
[0030] 1 H NMR (400 MHz, CDCl3) δ 7.44 (dd, J J = 7.3, 1.8 Hz, 1H), 7.34 (td, J J = 7.7, 1.8 Hz, 1H), 7.22–7.16 (m, 2H), 7.14–7.09 (m, 1H), 7.06–6.97 (m, 3H), 6.91(s, 1H), 5.87–5.75 (m, 1H), 4.96–4.85 (m, 2H), 4.39–4.31 (m, 1H), 4.11–4.02(m, 1H), 2.99–2.90 (m, 1H), 2.82–2.73 (m, 1H), 2.04–1.95 (m, 2H), 0.50 (s,3H). 13 C NMR (100 MHz, CDCl3) δ 165.8, 161.78 (d, J J = 245.0 Hz), 138.9, 138.7,135.2, 134.01 (d, J J = 3.0 Hz), 134.0, 131.3, 130.7, 130.6, 128.8, 123.6, 120.7,115.3, 115.1, 114.0, 74.5, 33.4, 23.0, -5.1. 19 F NMR (376 MHz, CDCl3) δ -115.0. HRMS (ESI) m / z: [M+Na] + calculated for C 20 H21 FOSi: 347.1238, found: 347.1234. Example 6: Preparation of Compound Id: Prepared according to the method in Example 2, and Compound Id (38.5 mg, yield 56%) was obtained by silica gel column chromatography as a yellow oil.
[0031] 1 H NMR (400 MHz, CDCl3) δ 7.44 (dd, J J = 7.3, 1.8 Hz, 1H), 7.37 – 7.29 (m, 3H), 7.17 – 7.10 (m, 3H), 6.99 (d, J J = 8.0 Hz, 1H), 6.89 (s, 1H), 5.87 – 5.74 (m, 1H), 4.95 – 4.85 (m, 2H), 4.38 – 4.30 (m, 1H), 4.09 – 4.01 (m, 1H), 2.97 – 2.88 (m, 1H), 2.82 – 2.73 (m, 1H), 2.02 – 1.96 (m, 2H), 0.50 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.7, 139.9, 138.5, 136.4, 135.2, 134.4, 132.8, 131.4, 130.3, 128.8, 128.5, 123.6, 120.7, 114.1, 74.4, 33.4, 23.0, -5.2. HRMS (ESI) m / z: [M+Na] + calculated for C 20 H 21 ClOSi: 363.0942, found: 363.0947. Example 7: Preparation of Compound Ie: Prepared according to the method in Example 2, and Compound Ie (52.7 mg, yield 63%) was obtained by silica gel column chromatography as a yellow oil.
[0032] 1 H NMR (400 MHz, CDCl3) δ7.38 – 7.33 (m, 3H), 7.30 (t, J = 7.2 Hz, 2H),7.27 – 7.21 (m, 2H), 7.10 (d, J = 8.3 Hz, 2H), 7.02 (t, J = 7.3 Hz, 1H), 6.92 –6.84 (m, 3H), 6.80 (s, 1H), 5.80 – 5.66 (m, 1H), 4.98 (s, 2H), 4.87 – 4.75(m, 2H), 4.32 – 4.22 (m, 1H), 4.05 – 3.95 (m, 1H), 2.98 – 2.86 (m, 1H), 2.78– 2.67 (m, 1H), 1.95 – 1.85 (m, 2H), 0.41 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.8, 157.8, 139.4, 137.1, 137.0, 135.2,134.6, 131.2, 130.9, 130.4, 129.0, 128.7, 128.1, 127.6, 123.4, 120.6, 114.6,113.9, 74.6, 70.1, 33.5, 23.2, 1.2, -5.0. HRMS (ESI) m / z: [M+Na] + calculated for C 27 H 28 O2Si: 435.1751, found:435.1752. Example 8: Compound If was prepared according to the method in Example 2 and obtained by silica gel column chromatography as a yellow oil (52.2 mg, yield 72%).
[0033] 1 H NMR (400 MHz, CDCl3) δ 7.36 (dd, J = 7.3, 1.7 Hz, 1H), 7.30 – 7.26 (m,2H), 7.23 (dd, J = 7.7, 1.8 Hz, 1H), 7.10 (d,J = 8.2 Hz, 2H), 7.03 (td, J = 7.2,1.1 Hz, 1H), 6.93 – 6.89 (m, 1H), 6.84 (s, 1H), 5.79 – 5.66 (m, 1H), 4.86 –4.74 (m, 2H), 4.32 – 4.23 (m, 1H), 4.03 – 3.92 (m, 1H), 2.98 – 2.89 (m, 1H),2.79 – 2.69 (m, 1H), 1.96 – 1.84 (m, 2H), 1.24 (s, 9H), 0.41 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.8, 150.1, 139.7, 138.0, 135.2, 135.1,134.6, 131.2, 129.2, 128.8, 125.2, 123.5, 120.7, 113.9, 74.7, 34.7, 33.5,31.4, 23.1, 1.2, -5.1. HRMS (ESI) m / z: [M+Na] + calculated for C 24 H 30 OSi: 385.1958, found:385.1954. Example 9: Compound Ig was prepared according to the method in Example 2, and compound Ig (48.7 mg, yield 63%) was obtained by silica gel column chromatography as a white solid (m.p. = 64 - 67 °C).
[0034] 1 H NMR (400 MHz, CDCl3) δ 7.65–7.58 (m, 4H), 7.50–7.44 (m, 3H), 7.39–7.32 (m, 4H), 7.15 (td, J= 7.4, 1.1 Hz, 1H), 7.05–7.00 (m, 2H), 5.95–5.78 (m,1H), 5.03–4.87 (m, 2H), 4.47–4.34 (m, 1H), 4.16–4.06 (m, 1H), 3.13–3.02 (m,1H), 2.95–2.83 (m, 1H), 2.08–1.99 (m, 2H), 0.55 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.8, 140.8, 139.8, 139.4, 139.2, 137.0,135.2, 134.5, 131.3, 129.5, 129.0, 128.9, 127.5, 127.1, 127.0, 123.6, 120.7,114.0, 74.6, 33.5, 23.1, 1.2, -5.1. HRMS (ESI) m / z: [M+Na] + calculated for C 26 H 26 OSi: 421.1385, found:421.1387. Example 10: Preparation of Compound Ih: Prepared according to the method in Example 2, and Compound Ih (48.7 mg, yield 63%) was obtained by silica gel column chromatography as a yellow oil.
[0035] 1 H NMR (400 MHz, CDCl3) δ 7.65 – 7.58 (m, 4H), 7.50 – 7.44 (m, 3H), 7.39– 7.32 (m, 4H), 7.15 (td, J = 7.4, 1.1 Hz, 1H), 7.05 – 7.00 (m, 2H), 5.95 –5.78 (m, 1H), 5.03 – 4.87 (m, 2H), 4.47 – 4.34 (m, 1H), 4.16 – 4.06 (m, 1H),3.13 – 3.02 (m, 1H), 2.95 – 2.83 (m, 1H), 2.08 – 1.99 (m, 2H), 0.55 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 165.8, 140.8, 139.8, 139.4, 139.2, 137.0, 135.2, 134.5, 131.3, 129.5, 129.0, 128.9, 127.5, 127.1, 127.0, 123.6, 120.7, 114.0, 74.6, 33.5, 23.1, 1.2, -5.1. HRMS (ESI) m / z: [M+Na] + calculated for C 26 H 26 OSi: 421.1385, found: 421.1387. Example 11: Compound Ii was prepared according to the method in Example 2 and obtained by silica gel column chromatography as a yellow oil (43.0 mg, yield 67%).
[0036] 1 1H NMR (400 MHz, CDCl3) δ 7.39 – 7.34 (m, 1H), 7.28 – 7.22 (m, 1H), 7.17 – 7.12 (m, 1H), 7.06 – 7.00 (m, 1H), 7.00 – 6.88 (m, 4H), 6.85 (s, 1H), 5.80 – 5.67 (m, 1H), 4.87 – 4.76 (m, 2H), 4.31 – 4.22 (m, 1H), 4.01 – 3.92 (m, 1H), 2.95 – 2.85 (m, 1H), 2.76 – 2.67 (m, 1H), 2.27 (s, 3H), 1.97 – 1.86 (m, 2H), 0.42 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 165.7, 140.0, 138.5, 138.0, 137.8, 135.2, 134.5, 131.3, 129.7, 129.2, 128.1, 127.8, 126.0, 123.6, 120.7, 113.9, 74.7, 33.4, 23.0, 21.6, 1.2, -5.2. HRMS (ESI) m / z: [M+Na] + calculated for C 21 H 24 OSi: 321.1669, found: 321.1666. Example 12: Preparation of Compound Ⅰj: Prepared according to the method in Example 2, and Compound Ⅰj (31.8 mg, yield 38%) was obtained by silica gel column chromatography as a yellow oil.
[0037] 1 H NMR (400 MHz, CDCl3) δ 7.49–7.44 (m, 1H), 7.37–7.31 (m, 2H), 7.16–7.10 (m, 1H), 7.09–7.04 (m, 2H), 7.03–6.98 (m, 2H), 5.90–5.77 (m, 1H), 4.98 –4.85 (m, 2H), 4.42–4.34 (m, 1H), 4.12–4.04 (m, 1H), 3.07–2.96 (m, 1H), 2.90 –2.78 (m, 1H), 2.02 (d, J = 8.0 Hz, 2H), 1.33 (s, 18H), 0.52 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.7, 150.6, 141.0, 137.8, 137.1, 135.2, 134.6, 131.3, 129.4, 123.6, 123.3, 121.1, 120.7, 113.9, 74.8, 34.9, 33.5, 31.7, 31.6, 23.0, 1.2. HRMS (ESI) m / z: [M+Na] + calculated for C 28 H 38 OSi: 441.2584, found: 441.2588. Example 13: Preparation of compound Ik: Prepared according to the method in Example 2, compound Ik (35.0 mg, yield 53%) was obtained by silica gel column chromatography as a yellow oil.
[0038] 1 H NMR (400 MHz, CDCl3) δ 7.29 – 7.24 (m, 2H), 7.19 – 7.16 (m, 1H), 7.15– 7.12 (m, 2H), 7.00 (dd, J = 8.1, 2.9 Hz, 1H), 6.94 – 6.84 (m, 3H), 5.79 –5.65 (m, 1H), 4.88 – 4.77 (m, 2H), 4.26 – 4.17 (m, 1H), 3.93 – 3.84 (m, 1H),2.89 – 2.80 (m, 1H), 2.75 – 2.64 (m, 1H), 1.95 – 1.88 (m, 2H), 0.41 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 161.3, 161.3, 160.4, 158.0, 140.2, 138.1,137.9, 134.1, 132.2, 132.1, 128.9, 128.3, 127.2, 122.3, 122.2, 120.8, 120.6,117.8, 117.6, 114.3, 75.0, 33.1, 22.5, 1.2, -5.5. 19 F NMR (376 MHz, CDCl3) δ -120.3. HRMS (ESI) m / z: [M+Na] + calculated for C 20 H 21 FOSi: 347.1238, found:347.1233. Example 14: General method for preparing compounds represented by formula (II) Add Pd(OAc)2 (2.26 mg, 0.01 mmol, 5.0 mol%) and Ligand 2 (6.38 mg, 0.012 mmol, 6.0 mol%) to a dry Schlenk tube equipped with a septum and a magnetic stir bar. Evacuate the tube under high vacuum and refill it with nitrogen (3 times). Introduce m-Xylene (2.0 mL) into the tube and add Compound 1 (0.2 mmol, 1.0 equiv, 0.1 M) dropwise. Stir the reaction tube at 50 °C for 12 hours. After completion, remove the solvent under vacuum and purify the residue by flash column chromatography on silica gel to obtain Product II.
[0039] In the above synthetic route, R 1 and R 2 are defined as described above.
[0040] In addition, in the general method described in Example 14, the amounts of the relevant compounds can be adjusted according to actual needs. For example, the amount of Pd(OAc)2 used can be 3% - 6% of 1 molar amount of the allenylic-functionalized silyl quaternary compound, the amount of Ligand 2 used is 5% - 7% of 1 molar amount of the allenylic-functionalized silyl quaternary compound, the reaction temperature is 20 - 60 °C, and the reaction time is 10 - 24 h. One can choose within the above ranges and will not be elaborated here.
[0041] Example 15: Prepare Compound IIa: Prepared according to the method in Example 14, Compound IIa (38.5 mg, yield 63%) was obtained by silica gel column chromatography as a yellow oil. Its 1H NMR spectrum is as Figure 3 shown, and its 13C NMR spectrum is as Figure 4 shown.
[0042] 1 1H NMR (400 MHz, CDCl3) δ 7.41–7.34 (m, 2H), 7.32–7.28 (m, 2H), 7.23 –7.19 (m, 1H), 7.17–7.11 (m, 3H), 7.00 (d, J= 7.9 Hz, 1H), 5.28–5.25 (m, 1H),4.70–4.63 (m, 1H), 4.35–4.29 (m, 1H), 3.52–3.47 (m, 1H), 2.30–2.23 (m, 1H),2.03–1.97 (m, 1H), 1.83–1.68 (m, 2H), 1.29–1.25 (m, 2H), 1.02 (td, J = 13.8,5.2 Hz, 1H), 0.50 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.6, 144.6, 143.0, 137.4, 134.0, 132.0,131.6, 128.9, 128.4, 126.2, 124.1, 120.5, 73.6, 52.8, 37.0, 23.9, 13.0, -2.2. HRMS (ESI) m / z: [M+Na] + calculated for C 20 H 22 OSi: 329.1332, found:329.1327. Example 16: Compound Ⅱb was prepared as follows: Prepared according to the method in Example 14, and compound Ⅱb (47.2 mg, yield 73%) was obtained by silica gel column chromatography as a white solid (m.p. = 74 - 78 °C).
[0043] 1 H NMR (400 MHz, CDCl3) δ 7.40 – 7.33 (m, 2H), 7.17 – 7.11 (m, 3H), 7.04– 6.99 (m, 3H), 5.34 – 5.28 (m, 1H), 4.72 – 4.63 (m, 1H), 4.37 – 4.30 (m,1H), 3.51 – 3.43 (m, 1H), 2.34 (s, 3H), 2.30 – 2.22 (m, 1H), 2.02 – 1.96 (m,1H), 1.83 – 1.63 (m, 2H), 1.30 – 1.24 (m, 1H), 1.02 (td, J= 13.8, 5.2 Hz, 1H), 0.50 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.6, 143.1, 141.5, 137.3, 135.6, 134.0, 132.1, 131.5, 129.1, 128.7, 124.1, 120.5, 73.7, 52.4, 37.1, 23.9, 21.2, 13.0, -2.2. HRMS (ESI) m / z: [M+Na] + calculated for C 21 H 24 OSi:343.1489,found:343.1489. Example 17: Compound Ⅱc was prepared according to the method in Example 14. Compound Ⅱc (47.2 mg, yield 73%) was obtained by silica gel column chromatography as a white solid (m.p. = 74 - 78 °C).
[0044] 1 H NMR (400 MHz, CDCl3) δ 7.40–7.33 (m, 2H), 7.18–7.12 (m, 1H), 7.11–7.04 (m, 2H), 7.03–6.96 (m, 3H), 5.27–5.22 (m, 1H), 4.73–4.63 (m, 1H), 4.37–4.29 (m, 1H), 3.52–3.44 (m, 1H), 2.31–2.22 (m, 1H), 2.02–1.93 (m, 1H), 1.85–1.73 (m, 1H), 1.72–1.63 (m, 1H), 1.30–1.23 (m, 1H), 1.01 (td, J = 14.0, 5.3 Hz, 1H), 0.50 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.6, 161.39 (d, J = 242.1 Hz), 143.0, 140.22(d, J= 3.5 Hz), 137.5, 134.0, 131.9, 131.6, 130.2, 130.1, 124.2, 120.5, 115.2, 115.0, 73.6, 52.1, 37.2, 23.8, 13.0, 1.2, -2.2. 19 19F NMR (376 MHz, CDCl3) δ -117.2. HRMS (ESI) m / z: [M+Na] + calculated for C 20 H 21 FOSi: 347.1238, found: 347.1237. Example 18: Compound Ⅱd was prepared according to the method in Example 14. Compound Ⅱd (44.5 mg, yield 65%) was obtained by silica gel column chromatography as a yellow oil.
[0045] 1 1H NMR (400 MHz, CDCl3) δ 7.30–7.25 (m, 2H), 7.20–7.17 (m, 2H), 7.09–7.04 (m, 1H), 6.99–6.95 (m, 2H), 6.93–6.90 (m, 1H), 5.18–5.14 (m, 1H), 4.63–4.55 (m, 1H), 4.28–4.20 (m, 1H), 3.42–3.36 (m, 1H), 2.22–2.13 (m, 1H), 1.91–1.85 (m, 1H), 1.73–1.67 (m, 1H), 1.62–1.54 (m, 1H), 1.19–1.15 (m, 1H), 0.93(td, J = 14.0, 5.3 Hz, 1H), 0.41 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ165.6, 143.1, 142.7, 137.6, 134.0, 131.9, 131.8, 131.6, 130.2, 128.5, 128.5, 124.2, 120.5, 73.6, 52.2, 47.8, 37.0, 26.8, 23.8, 20.3, 15.1, 13.3, 12.9, 1.2, 0.6, -0.3, -2.2. HRMS (ESI) m / z: [M+H] + calculated for C 20 H 21 ClOSi: 341.1123, found: 341.1127. Example 19: Compound IIe was prepared according to the method in Example 14. Compound IIe (47.2 mg, yield 73%) was obtained by silica gel column chromatography as a white solid (m.p. = 113 - 116 °C).
[0046] 1 H NMR (400 MHz, CDCl3) δ 7.48 (d, J J = 7.5 Hz, 3H), 7.44–7.39 (m, 3H), 7.39–7.33 (m, 2H), 7.17 (t, J J = 7.3 Hz, 1H), 7.08 (d, J J = 8.2 Hz, 2H), 7.03 (d, J J = 7.9 Hz, 1H), 6.97 (d, J J = 8.2 Hz, 2H), 5.39–5.32 (m, 1H), 5.07 (s, 2H), 4.78–4.65 (m, 1H), 4.41–4.31 (m, 1H), 3.53–3.45 (m, 1H), 2.35–2.22 (m, 1H), 2.01 (d, J J = 12.8 Hz, 1H), 1.86–1.66 (m, 2H), 1.29 (d, J = 14.0 Hz, 1H), 1.04 (td, J J = 13.9, 5.2 Hz, 1H), 0.53 (s, 3H). 1313C NMR (100 MHz, CDCl3) δ 165.6, 157.2, 143.3, 137.3, 137.3, 137.0, 134.0, 132.0, 131.5, 129.7, 128.7, 128.1, 128.0, 127.7, 127.6, 124.1, 120.5, 114.6, 73.6, 70.1, 52.0, 37.2, 23.9, 13.0, 1.2, -2.2. HRMS (ESI) m / z: [M+Na] + calculated for C 27 H 28 O2Si: 435.1751, found: 435.1755. Example 20: Preparation of Compound Ⅱf: Prepared according to the method in Example 14, and Compound Ⅱf (60.9 mg, yield 74%) was obtained by silica gel column chromatography as a white solid (m.p. = 145 - 147 °C).
[0047] 1 1H NMR (400 MHz, CDCl3) δ 7.31–7.21 (m, 4H), 7.06 (t, J J = 7.3 Hz, 1H), 6.96 (d, J J = 8.0 Hz, 2H), 6.91 (d, J J = 7.9 Hz, 1H), 5.25–5.19 (m, 1H), 4.63–4.55 (m, 1H), 4.28–4.20 (m, 1H), 3.43–3.34 (m, 1H), 2.22–2.12 (m, 1H), 1.95–1.86 (m, 1H), 1.74–1.55 (m, 2H), 1.24 (s, 9H), 1.19–1.15 (m, 1H), 0.93 (td, J J = 13.8, 5.2 Hz, 1H), 0.41 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ165.6, 148.9, 143.1, 141.4, 137.3, 134.0, 132.0, 131.5, 128.4, 125.2, 124.1, 120.5, 73.6, 52.3, 37.0, 34.5, 31.6, 23.9, 13.0, 1.2, -2.1. HRMS (ESI) m / z: [M+Na] + calculated for C 24 H 30 OSi: 385.1958, found: 385.1961. Example 21: Compound Ⅱg was prepared according to the method in Example 14. Compound Ⅱg (67.1 mg, yield 87%) was obtained by silica gel column chromatography as a white solid (m.p. = 95 - 99 °C).
[0048] 1 H NMR (400 MHz, CDCl3) δ 7.61–7.58 (m, 2H), 7.54 (d, J = 8.2 Hz, 2H), 7.44 –7.39 (m, 2H), 7.38–7.29 (m, 3H), 7.21–7.17 (m, 2H), 7.14 (td, J = 7.2, 1.0 Hz, 1H), 6.99 (d, J = 7.8 Hz, 1H), 5.37 –5.33 (m, 1H), 4.72–4.64 (m, 1H), 4.37–4.29 (m, 1H), 3.58–3.49 (m, 1H), 2.32–2.23 (m, 1H), 1.85–1.69 (m, 2H), 1.31–1.21 (m, 2H), 1.03 (td, J = 13.8, 5.2 Hz, 1H), 0.51 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ165.6, 143.7, 142.9, 141.1, 139.0, 137.6, 134.0, 132.0, 131.6, 129.3, 128.8, 127.2, 127.1, 127.1, 127.0, 124.2, 120.5, 73.7, 52.5, 37.0, 23.9, 13.0, 1.2, -2.1. HRMS (ESI) m / z: [M+Na] + calculated for C 26 H 26 OSi: 405.1645, found: 405.1649. Example 22: Compound Ⅱh was prepared according to the method in Example 14. Compound Ⅱh (55.8 mg, yield 87%) was obtained by silica gel column chromatography as a white solid (m.p. = 64 - 67 °C).
[0049] 1 H NMR (400 MHz, CDCl3) δ 7.31–7.23 (m, 2H), 7.15–7.03 (m, 2H), 6.96–6.89 (m, 2H), 6.88–6.81 (m, 2H), 5.25–5.16 (m, 1H), 4.63–4.53 (m, 1H), 4.30–4.20 (m, 1H), 3.42–3.30 (m, 1H), 2.24 (s, 3H), 2.21–2.13 (m, 1H), 1.94–1.85 (m, 1H), 1.75–1.55 (m, 2H), 1.21–1.14 (m, 1H), 0.93 (td, J = 13.8, 5.2 Hz, 1H), 0.41 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.6, 144.5, 143.0, 137.8, 137.4, 134.0, 132.0, 131.5, 129.7, 129.6, 128.2, 126.9, 125.9, 124.1, 120.5, 73.7, 52.8, 37.0, 23.9, 21.6, 13.0, 1.2, -2.2. HRMS (ESI) m / z: [M+Na] + calculated for C 21 H 24 OSi: 343.1489, found: 343.1485. Example 23: Preparation of Compound Ⅱi: Prepared according to the method in Example 14, and Compound Ⅱi (52.8 mg, yield 79%) was obtained by silica gel column chromatography as a white solid (m.p. = 118 - 121 °C).
[0050] 1 H NMR (400 MHz, CDCl3) δ 7.30–7.23 (m, 2H), 7.05 (td, J J = 7.3, 1.0 Hz, 1H), 6.93–6.89 (m, 1H), 6.77–6.75 (m, 1H), 6.69–6.64 (m, 2H), 5.26–5.22 (m, 1H), 4.63–4.56 (m, 1H), 4.29–4.21 (m, 1H), 3.37–3.31 (m, 1H), 2.20 (s, 6H), 2.18–2.13 (m, 1H), 1.93–1.85 (m, 1H), 1.72–1.57 (m, 2H), 1.18–1.12 (m, 1H), 0.92 (td, J J = 13.8, 5.2 Hz, 1H), 0.41 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.6, 144.5, 143.0, 137.7, 137.4, 134.0, 132.0, 131.5, 127.8, 126.8, 126.7, 124.1, 120.5, 73.7, 52.8, 37.0, 23.9, 21.5, 13.1, 1.2, -2.2. HRMS (ESI) m / z: [M+Na] + calculated for C 22 H 26 OSi: 357.1645, found: 357.1640. Example 24: Preparation of Compound Ⅱj: Prepared according to the method in Example 14, and Compound Ⅱj (48.5 mg, yield 57%) was obtained by silica gel column chromatography as a yellow oil.
[0051] 1 H NMR (400 MHz, CDCl3) δ 7.34 – 7.24 (m, 2H), 7.19 – 7.15 (m, 1H), 7.07(t, J = 7.2 Hz, 1H), 6.93 (d, J = 8.0 Hz, 1H), 6.89 – 6.83 (m, 2H), 5.25 – 5.16(m, 1H), 4.66 – 4.53 (m, 1H), 4.31 – 4.20 (m, 1H), 3.47 – 3.33 (m, 1H), 2.25– 2.11 (m, 1H), 1.97 – 1.88 (m, 1H), 1.77 – 1.58 (m, 2H), 1.23 (s, 18H), 1.19– 1.16 (m, 2H), 0.95 (td, J = 13.7, 5.0 Hz, 1H), 0.43 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.7, 150.5, 143.5, 142.8, 137.3, 134.0,132.4, 131.5, 124.2, 123.1, 120.6, 119.9, 73.9, 53.5, 37.2, 34.9, 31.7, 31.6,24.0, 13.1, 1.2. HRMS (ESI) m / z: [M+Na] + calculated for C 28 H 38 OSi: 441.2584, found:441.2582. Example 25: Preparation of Compound Ⅱk: Prepared according to the method in Example 14, and Compound Ⅱk (48.5 mg, yield 57%) was obtained by silica gel column chromatography as a white solid (m.p. = 86 - 88 ℃).
[0052] 1 1H NMR (400 MHz, CDCl3) δ 7.34 – 7.29 (m, 2H), 7.24 – 7.20 (m, 1H), 7.13(d, J J = 7.4 Hz, 2H), 7.05 – 6.94 (m, 3H), 5.27 – 5.22 (m, 1H), 4.69 – 4.61 (m,1H), 4.33 – 4.25 (m, 1H), 3.54 – 3.45 (m, 1H), 2.34 – 2.23 (m, 1H), 2.05 –1.99 (m, 1H), 1.85 – 1.68 (m, 2H), 1.27 – 1.20 (m, 1H), 1.01 (td, J J = 13.7, 5.2Hz, 1H), 0.51 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 161.4, 161.3, 160.8, 158.4, 144.5, 141.5,137.8, 135.0, 134.9, 128.9, 128.4, 128.3, 126.3, 122.1, 122.0, 119.7, 119.5,118.0, 117.8, 74.1, 52.8, 36.9, 23.7, 12.6, 1.2, -2.4. 19 19F NMR (376 MHz, CDCl3) δ -119.8. HRMS (ESI) m / z: [M+Na] + calculated for C 20 H 21 FOSi: 347.1238, found:347.1242. Example 26: Preparation of Compound Ⅱl: Prepared according to the method in Example 14, and Compound Ⅱl (33.8 mg, yield 54%) was obtained by silica gel column chromatography as a white solid (m.p. = 120 - 123 °C).
[0053] 1 1H NMR (400 MHz, CDCl3) δ7.37 – 7.31 (m, 2H), 7.14 – 7.08 (m, 1H), 7.01(d, J = 8.1 Hz, 1H), 6.09 – 6.03 (m, 1H), 4.88 – 4.81 (m, 1H), 4.56 – 4.49 (m,1H), 2.15 – 2.02 (m, 2H), 1.89 – 1.76 (m, 3H), 1.74 – 1.70 (m, 1H), 1.67 –1.63 (m, 1H), 1.62 – 1.52 (m, 2H), 1.38 – 1.22 (m, 4H), 1.19 – 1.12 (m, 2H),1.05 – 0.96 (m, 1H), 0.93 – 0.81 (m, 2H), 0.40 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 165.8, 143.0, 134.2, 132.8, 131.3, 131.1,123.7, 120.3, 73.3, 49.6, 38.5, 32.8, 30.7, 27.8, 27.4, 27.1, 26.8, 23.8,13.3, -2.1. HRMS (ESI) m / z: [M+H] + calculated for C 20 H 28 OSi:313.1982,found:313.1981. Example 27: Late-stage transformation of the compound shown in (Ia) Under a nitrogen atmosphere, a dry 25 mL sealed tube reactor equipped with a stir bar was charged with Ia (30.61 mg, 0.1 mmol, 1.0 equiv) in DCM (1.0 mL, 0.1 M), III (0.1 mmol, 1.0 equiv), and Grubbs II catalyst (4.2 mg, 0.005 mmol, 5 mol%). The mixture was stirred at 40 °C for 12 h. Once completed, the reaction solution was concentrated and purified by silica gel column chromatography to give the product IV.
[0054] Example 28: Preparation of Compound Ⅳa: Compound Ⅳa was prepared according to the same method as in Example 27. The stoichiometric ratio of reactants, reaction conditions and other parameters were the same as in Example 27. 21.8 mg of Compound Ⅳa was obtained with a yield of 59%, which was a colorless oil.
[0055] 1 H NMR (400 MHz, CDCl3) δ 7.36 – 7.27 (m, 4H), 7.21 – 7.18 (m, 1H), 7.16– 7.12 (m, 2H), 7.07 (td, J = 7.3, 1.1 Hz, 1H), 7.02 – 6.97 (m, 1H), 6.96 –6.93 (m, 1H), 6.89 (s, 1H), 5.67 – 5.60 (m, 1H), 4.32 – 4.23 (m, 1H), 3.96 –3.87 (m, 1H), 3.62 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 167.3, 165.5, 147.4, 140.6, 137.7, 134.9,131.8, 128.9, 128.6, 128.3, 127.2, 124.0, 121.0, 119.6, 74.7, 51.4, 33.2,23.2, -5.3. HRMS (ESI) m / z: [M+Na]+ calculated for C 22 H 24 O3Si:387.1387,found:387.1383. Example 29: Preparation of Compound Ⅳb: Compound Ⅳb was prepared according to the same method as in Example 27. The stoichiometric ratio of reactants, reaction conditions and other parameters were the same as in Example 27. 27.3 mg of Compound Ⅳb was obtained with a yield of 44%, which was a colorless oil.
[0056] 1 H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.4 Hz, 1H), 7.58 – 7.53 (m, 1H),7.31 (dd, J= 7.3, 1.8 Hz, 1H), 7.26 – 7.23 (m, 2H), 7.22 – 7.16 (m, 3H), 7.15– 7.12 (m, 2H), 7.11 – 7.05 (m, 4H), 7.04 – 6.99 (m, 2H), 6.98 – 6.89 (m,2H), 6.86 (s, 1H), 5.64 – 5.57 (m, 1H), 5.09 (d, J = 4.0 Hz, 1H), 4.28 – 4.21(m, 1H), 3.90 – 3.83 (m, 1H), 2.89 – 2.81 (m, 1H), 2.73 – 2.63 (m, 1H), 2.22– 2.17 (m, 1H), 2.14 – 2.10 (m, 1H), 1.25 – 1.21 (m, 2H), 0.91 (dd, J = 8.1,3.0 Hz, 2H), 0.45 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 166.3, 165.5, 163.9, 162.4, 161.5, 148.1,147.7, 140.6, 137.6, 137.6, 134.9, 132.0, 132.0, 131.9, 131.5, 131.5, 131.39,131.37, 129.6, 129.1, 128.8, 128.5, 128.3, 127.3, 126.6, 126.2, 125.5, 124.8(d, J = 172.2 Hz), 121.0, 119.4, 115.57 (d, J = 21.6 Hz), 77.5, 74.7, 61.1, 33.2,23.3, 14.8, 9.7, 9.7, -5.2. HRMS (ESI) m / z: [M+Na]+ calculated for C 39 H 34 FNO3Si:634.2184,found:634.2182. Example 30: Preparation of Compound Ⅳc: Compound Ⅳc was prepared according to the method substantially the same as in Example 27. The stoichiometric ratio of reactants, reaction conditions and other parameters were the same as in Example 27. 26.6 mg of Compound Ⅳc was obtained with a yield of 36%, which was a colorless oil.
[0057] 1 H NMR (400 MHz, CDCl3) δ 7.34 (dd, J = 7.3, 1.8 Hz, 1H), 7.31 – 7.24 (m,3H), 7.19 – 7.17 (m, 1H), 7.16 – 7.12 (m, 2H), 7.09 – 7.04 (m, 1H), 7.02 –6.96 (m, 1H), 6.94 (d, J = 8.2 Hz, 1H), 6.87 (s, 1H), 5.61 (d, J = 15.3 Hz, 1H),5.33 – 5.25 (m, 1H), 4.61 – 4.51 (m, 1H), 4.31 – 4.21 (m, 1H), 3.97 – 3.87(m, 1H), 2.91 – 2.83 (m, 1H), 2.76 – 2.66 (m, 1H), 2.28 – 2.21 (m, 2H), 2.18– 2.06 (m, 2H), 1.97 – 1.87 (m, 2H), 1.82 – 1.74 (m, 3H), 1.50 – 1.38 (m,6H), 1.32 – 1.21 (m, 5H), 1.11 – 0.99 (m, 7H), 0.94 (s, 4H), 0.84 (d, J = 6.5Hz, 3H), 0.79 (dd, J = 6.6, 1.9 Hz, 6H), 0.60 (s, 3H), 0.47 (s, 3H). 1313C NMR (100 MHz, CDCl3) δ 166.2, 165.5, 146.8, 140.7, 140.0, 137.8, 137.7, 135.0, 131.8, 128.9, 128.7, 128.3, 127.2, 124.0, 122.6, 121.0, 120.5, 74.7, 73.5, 56.8, 56.2, 50.1, 42.4, 39.9, 39.6, 38.3, 37.1, 36.7, 36.3, 35.9, 33.2, 32.0, 31.98, 28.4, 28.2, 28.0, 24.4, 24.1, 23.1, 23.0, 22.7, 21.2, 19.5, 18.8, 12.0, -5.2. HRMS (ESI) m / z: [M+H]+ calculated for C 49 H 70 O3Si: 735.5167, found: 735.5175. As described above, it is only the specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention should be covered by the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.
Claims
1. A heptasilacycle compound, characterized in that, The compound has a structural formula shown in the following formula (I) or formula (II): Among them, R 1 is one of hydrogen and halogen; R 2 is a cycloalkyl group, a phenyl group or a substituted phenyl group; the substitution is selected from one of C 1-4 alkyl group, aryl group, benzyloxy group or halogen.
2. A method for preparing a seven-membered silicon heterocyclic compound as described in claim 1, characterized in that, The preparation method comprises the following steps: Under an inert gas atmosphere, a phosphine ligand, a palladium metal catalyst and a reaction medium are mixed, and an allenyl-functionalized silicon heterocyclic quaternary compound 1 is added. After the reaction is completed, the solvent is removed under vacuum, and the seven-membered silicon heterocyclic compound is obtained after purification; The synthesis route is as follows: 。 3. The preparation method according to claim 2, characterized in that, The palladium metal catalyst is palladium acetate.
4. The preparation method according to claim 3, characterized in that, The usage amount of the palladium metal catalyst is 3%-6% of the molar amount of the allenyl-functionalized silicon heterocyclic quaternary compound 1.
5. The preparation method according to claim 2, characterized in that, The phosphine ligand is tris(ortho-methylphenyl)phosphine or tris(pentafluorophenyl)phosphine.
6. The preparation method according to claim 5, wherein The usage amount of the phosphine ligand is 5%-7% of the molar amount of the allenyl-functionalized silicon heterocyclic quaternary compound 1.
7. The preparation method according to claim 2, characterized in that, The reaction medium is toluene or m-xylene.
8. The preparation method according to claim 2, characterized in that, The reaction temperature is 20-60 °C, and the reaction time is 10-24 h.
9. Use of the seven-membered silicon heterocyclic compound according to claim 1 as a pharmaceutical synthesis precursor.