Silicon-containing chiral ester-modified 1, 4-dihydrobenzo silazane compound as well as preparation method and application of silicon-containing chiral ester-modified 1, 4-dihydrobenzo silazane compound

Abstract

The invention discloses a silicon-containing chiral ester-modified 1, 4-dihydrobenzo silacyclohexane compound as well as a preparation method and application thereof, and the compound has a structural formula as shown in a formula (I). The preparation method comprises the following steps: in an inert gas atmosphere, mixing a phosphine ligand, a metal palladium catalyst and a reaction medium, stirring, sequentially adding a phenylpropynyl ester compound and benzo silazane, removing a solvent after reaction, and separating and purifying to obtain the silicon-containing chiral ester-modified 1, 4-dihydrobenzo silazane compound. According to the method disclosed by the invention, various benzo-silacyclohexane compounds with different substituent groups, which cannot be prepared by a traditional method, can be obtained, and the obtained compounds and derivatives can be widely applied to the fields of material chemistry and medicinal chemistry. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the field of organic chemistry, and particularly to a silicon-containing chiral 1,4-dihydrobenzotrisilacyclohexane compound with ester modification, and its preparation method and application. Background Art

[0002] In recent years, chiral organosilanes have shown unique value in the fields of asymmetric catalysis, functional materials, and bioactive molecules. Especially the benzotrisilacyclohexane skeleton, due to its rigid structure and the controllability of silicon-centered chirality, has become a key pharmacophore for constructing chiral silicon drug molecules. However, there are still significant defects in the precise construction of such structures by existing synthetic technologies.

[0003] In traditional methods, the ring-opening and ring-expansion reaction of silacyclobutane (SCB) is considered the most promising synthetic route. By the [2+2] cycloaddition reaction of SCB with unsaturated hydrocarbons catalyzed by transition metals (such as Rh, Pt), the silacycle hexane skeleton can be constructed. But this method has three limitations: (1) it is difficult to control chemical selectivity, especially when the substrate contains polar functional groups such as ketone carbonyl, the incidence of side reactions increases significantly; (2) the construction efficiency of silicon chiral centers is low, and the enantioselectivity of existing asymmetric catalytic systems is generally low; (3) the product structure is single, and it is difficult to introduce key modification groups such as ester groups, which severely restricts subsequent medicinal chemistry modifications.

[0004] Recent studies have tried to construct such skeletons through hydrosilylation reactions, but they face bottlenecks such as harsh reaction conditions and narrow substrate scope (only electron-deficient alkenes). It is particularly noteworthy that in the 1,4-dihydrobenzotrisilacyclohexane derivatives synthesized by existing methods, the esterification modification at the α-position of the silicon center is still blank - and this structural unit is exactly the key pharmacodynamic element to enhance molecular membrane penetration and regulate the logP value.

[0005] Although the Sommer-Baum system pioneered the SCB chemistry, its derivative methods face fundamental challenges in constructing ester-modified silicon chiral centers: ① strong nucleophilic organometallic reagents are prone to side reactions with ester carbonyls; ② existing catalysts are difficult to simultaneously control the activation selectivity of Si-C bonds and the compatibility of ester groups. This results in a generally low separation yield of the target product and complete failure of chiral control.

[0006] Therefore, developing a general method that can efficiently construct ester-modified chiral benzotrisilacyclohexanes will not only fill the technical gap in organosilicon chemistry, but also provide key structural modules for the design of targeted molecules such as central nervous system drugs and anti-tumor agents. Summary of the Invention

[0007] The object of the present invention is to solve the problems that the conventional synthesis methods are inefficient and it is difficult to obtain benzosilacyclohexane compounds with different substituents, etc., and to provide a 1,4-dihydrobenzosilacyclohexane compound containing silicon chirality and having an ester modification, a preparation method and an application thereof.

[0008] The present invention is achieved by the following technical solutions: In the first aspect, the present invention provides a 1,4-dihydrobenzosilacyclohexane compound containing silicon chirality and having an ester modification, and the compound has a structural formula shown in the following formula (I): In the formula, R1 is one of hydrogen, alkyl, halogen, haloalkyl, alkoxy or phenyl, and R is alkyl.

[0009] In the second aspect, the present invention provides a preparation method of the above-mentioned 1,4-dihydrobenzosilacyclohexane compound containing silicon chirality and having an ester modification. The reaction conditions are mild and the method is simple, and high-yield benzosilacyclohexane compounds with various different substituents can be obtained in one step. The preparation method is to synthesize a class of 1,4-dihydrobenzosilacyclohexane compounds containing silicon chirality and having an ester modification through the cycloaddition silanization reaction of benzosilacyclobutane and phenylpropiolate. 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 reaction medium are added to a reaction tube, and after stirring for 10 - 20 min, phenylpropiolate compound 2 and benzosilacyclobutane 1 are added in sequence. After the reaction is completed, the solvent is evaporated to obtain a crude product, and the crude product is separated and purified to obtain the 1,4-dihydrobenzosilacyclohexane compound containing silicon chirality and having an ester modification; wherein the definitions of R and R1 are as described above.

[0010] Preferably, the molar ratio of the phenylpropiolate compound 2 to the benzosilacyclobutane 1 is 1:4 - 1:5.

[0011] Preferably, the palladium metal catalyst is palladium acetate, and the usage amount is 3 - 5% of the molar amount of the phenylpropiolate compound 2.

[0012] Preferably, the structural formula of the phosphine ligand is: .

[0013] Preferably, the usage amount of the phosphine ligand is 8 - 12% of the molar amount of the phenylpropiolate compound. A complex formed by the metal catalyst and the phosphine ligand is used as a catalyst precursor, and the catalytic efficiency is good, and a high-yield target product can be obtained.

[0014] Preferably, the reaction solvent is selected from one or more of 2-methyltetrahydrofuran, tetrahydrofuran, and toluene. More preferably, it is 2-methyltetrahydrofuran.

[0015] Preferably, the reaction temperature is 30-40 °C and the reaction time is 12-24 h.

[0016] In a third aspect, the present invention provides the application of the above-mentioned 1,4-dihydrobenzotrisilacyclohexane compound containing silicon chirality and having ester modification as a luminescent material, wherein the silole structure provides a new direction for the research and development of luminescent materials due to its unique electronic properties.

[0017] In a fourth aspect, the present invention provides the application of the above-mentioned 1,4-dihydrobenzotrisilacyclohexane compound containing silicon chirality and having ester modification as a drug synthesis precursor.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows: The present invention uses an asymmetric phenylpropargyl ester which is easy to prepare as a raw material, and a complex formed by a metal catalyst palladium salt and a phosphine ligand as a catalyst precursor. The catalyst precursor participates in the catalytic cycle system, and the catalytic efficiency is relatively high. An additive is used to control the chemoselectivity of the product, and a target product with extremely high yield and high enantioselectivity can be obtained. A series of 1,4-dihydrobenzotrisilacyclohexane compounds containing silicon chirality and having ester modification are efficiently synthesized through an intermolecular cycloaddition silanization reaction. The catalyst precursor is a commercial reagent, and the reaction can be completed by stirring at a relatively low temperature. The operation is simple and the yield is relatively high. The crude product can be concentrated under reduced pressure after removing impurities by flash column chromatography, and the post-treatment is convenient.

[0019] In summary, the present invention provides a method that is more direct and effective compared with the traditional chain-like silane cyclization reaction for synthesizing silacyclic compounds, and can obtain benzotrisilacyclohexane compounds with various different substituents that cannot be prepared by traditional methods. The obtained compounds and subsequent derivatives can be widely applied in the fields of materials chemistry and pharmaceutical chemistry. For example, the derivatives shown in the following formula can be widely applied in the fields of materials chemistry and pharmaceutical chemistry: . Description of the Drawings

[0020] Figure 1 1H NMR spectrum of the 1,4-dihydrobenzotrisilacyclohexane compound containing silicon chirality and having ester modification prepared in Example 1; Figure 2 13C NMR spectrum of the 1,4-dihydrobenzotrisilacyclohexane compound containing silicon chirality and having ester modification prepared in Example 1; Figure 3 1H NMR spectrum of the 1,4-dihydrobenzotrisilacyclohexane compound containing silicon chirality and having ester modification prepared in Example 2; Figure 413C NMR spectrum of the silicon-containing chiral 1,4-dihydrobenzodisilacyclohexane compound with ester modification prepared in Example 2. Detailed implementation mode

[0021] The present invention will be further described in detail below with reference to examples. All raw materials used in the examples can be purchased commercially or prepared by conventional methods.

[0022] As described above, the present invention provides a method for preparing a class of silicon-containing chiral 1,4-dihydrobenzodisilacyclohexane compounds with ester modification through Pd-catalyzed highly selective cycloaddition silylation of phenylpropiolate. Using phenylpropiolate compounds and benzodisilacyclobutane as reactants, a selective cycloaddition silylation reaction is directly carried out under the action of a complex formed by a metal catalyst and a phosphine ligand. The reaction is easy to synthesize, the operation is simple, and the obtained crude product can be concentrated under reduced pressure after removing impurities by flash column chromatography, and the post-treatment is convenient. In addition, the present invention also provides an extension of the scope of phenylpropiolate derivatives. Its disilacyclohexane structure is similar to drugs such as silteplase-vincamine, and it has important application value in reducing drug toxicity and drug sustained release. It also provides a feasible solution for the application of the silteplase strategy of other drug molecules with cyclohexane skeletons.

[0023] Specifically, the structural formula of the silicon-containing chiral 1,4-dihydrobenzodisilacyclohexane compound with ester modification is shown as follows: Wherein R1 is one of hydrogen, alkyl, halogen, haloalkyl, alkoxy or phenyl, and R is alkyl.

[0024] The silicon-containing chiral 1,4-dihydrobenzodisilacyclohexane compound with ester modification is prepared by the following method: Under an inert gas atmosphere, a phosphine ligand, palladium acetate as a metal palladium catalyst, and a reaction medium are added to a reaction tube. After stirring for 10-20 min, phenylpropiolate compound 1 and benzodisilacyclobutane 2 with a molar ratio of 1:4-1:5 are added in sequence. After reacting at 30-40 °C for 12-24 h, sodium borohydride is directly added for reduction. After the reaction is completed, the solvent is evaporated to obtain a crude product, and the crude product is separated and purified to obtain the silicon-containing chiral 1,4-dihydrobenzodisilacyclohexane compound with ester modification.

[0025] Among them, the concentration of phenylpropiolate compound 2 is 0.1 mol / L; the reaction medium can be selected from one or more of 2-methyltetrahydrofuran, tetrahydrofuran, and toluene; the usage amount of palladium acetate as the metal palladium catalyst is 3%-5% of the molar amount of phenylpropiolate compound 2; the usage amount of the phosphine ligand is 8%-12% of the molar amount of phenylpropiolate compound, and ligand L1 is used, and the structural formula is as follows: The present invention will be further described below in conjunction with specific embodiments.

[0026] Example 1: Under a nitrogen atmosphere, add the phosphine ligand L1 (6.7 mg, 0.02 mmol) and the metal catalyst palladium acetate (2.2 mg, 0.01 mmol) to a Schlenk reaction tube, then add 2.0 mL of toluene solvent. After pre-stirring at 30 °C for 10 min, add the phenylpropiolate compound 2a (0.20 mmol). After stirring for 15 min, add benzosilacyclobutane (0.80 mmol), and continue stirring and reacting at 30 °C for 12 h. After monitoring the reaction by TLC until it is completed, then filter, extract, concentrate the filtrate, and purify it by silica gel column chromatography to obtain 64 mg of a pale yellow oily liquid product 3a with a yield of 86%, 90% ee , and its 1H NMR spectrum is as Figure 1 shown, and its 13C NMR spectrum is as Figure 2 shown. The physical and chemical indexes of this product: Enantiomeric excess was determined by HPLC with achiralcel OX column (hexanes: 2-propanol = 97:3, 0.8 mL / min, 254 nm, 95:5 er ); major enantiomer tr = 7.23 min, minor enantiomer tr = 6.84 min. 1 H NMR (400 MHz, CDCl3) δ 7.52 – 7.46 (m, 3H), 7.31 – 7.24 (m, 6H), 7.23 – 7.15 (m, 5H), 3.93 (dd, J J = 28.4, 21.6 Hz, 2H), 3.32 (s, 3H), 0.67 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 169.7, 160.0, 142.8, 142.6, 134.7, 133.6, 132.9, 130.7, 128.5, 128.4, 127.2, 127.0, 126.8, 125.7, 125.1, 50.1, 41.9, -5.0. HRMS (ESI) m / z: [M+Na] + calculated for C 24 H 22 NaO2Si: 393.1281, found: 393.1285. Example 2: Under a nitrogen atmosphere, phosphine ligand L1 (8.0 mg, 0.024 mmol) and metal catalyst palladium acetate (2.2 mg, 0.01 mmol) were added to a Schlenk reaction tube, and then 2.0 mL of methyltetrahydrofuran solvent was added. After pre-stirring at 30 °C for 10 min, propargyl benzoate compound 2a (0.20 mmol) was added. After stirring for 15 min, benzosilacyclobutane (1.00 mmol) was added, and the reaction was continued to stir at 40 °C for 16 h. After the reaction was monitored by TLC and completed, it was filtered, extracted, the filtrate was concentrated, and purified by silica gel column chromatography to obtain 62 mg of a pale yellow oily liquid product 3b with a yield of 81%, 86% ee , and its 1H NMR spectrum is as Figure 3 shown, and its 13C NMR spectrum is as Figure 4 shown. The physical and chemical indexes of this product: Enantiomeric excess was determined by HPLC with achiralcel OX column (hexanes: 2 - propanol = 99:1, 0.8 mL / min, 254 nm, 93:7 er ); major enantiomer tr = 10.82 min, minor enantiomer tr = 9.65 min. 1 1H NMR (400 MHz, CDCl3) δ 7.54 – 7.44 (m, 3H), 7.33 – 7.17 (m, 6H), 7.15 – 7.05 (m, 4H), 3.91 (dd, J J = 26.4, 21.2 Hz, 2H), 3.35 (s, 3H), 2.28 (s, 3H), 0.66 (s, 3H). 1313C NMR (101 MHz, CDCl3) δ 169.9, 160.1, 142.9, 139.7, 136.7, 134.8, 133.6, 132.9, 130.8, 128.4, 127.9, 127.0, 126.8, 125.7, 125.1, 50.1, 42.0, 20.2, -5.0. HRMS (ESI) m / z: [M+Na] + calculated for C 25 H 24 NaO2Si: 407.1438, found: 407.1443. Example 3: Under a nitrogen atmosphere, the phosphine ligand L1 (6.7 mg, 0.02 mmol) and the metal catalyst palladium acetate (2.0 mg, 0.008 mmol) were added to a Schlenk reaction tube, and then 2.0 mL of 2-methyltetrahydrofuran solvent was added. After pre-stirring at 30 °C for 10 min, the propargyl benzoate compound 2c (0.20 mmol) was added. After stirring for 15 min, benzosilacyclobutane (0.80 mmol) was added, and the reaction was continued to stir at 30 °C for 24 h. After monitoring the reaction by TLC until completion, it was then filtered, extracted, the filtrate was concentrated, and purified by silica gel column chromatography to obtain 66 mg of a pale yellow oily liquid product 3c, with a yield of 85%, 90% ee . The physical and chemical indices of this product: Enantiomeric excess was determined by HPLC with achiralcel OX column (hexanes: 2-propanol = 99.5:0.5, 0.8 mL / min, 254 nm, 95:5 er ); major enantiomer tr = 17.58 min, minor enantiomer tr = 15.19 min. 1 1H NMR (400 MHz, CDCl3) δ 7.54 – 7.40 (m, 3H), 7.33 – 7.23 (m, 4H), 7.22 – 7.12 (m, 4H), 7.00 – 6.90 (m, 2H), 3.90 (dd, J= 31.2, 21.2 Hz, 2H), 3.34 (s, 3H), 0.67 (s, 3H). 19 19F NMR (376 MHz, CDCl3) δ -113.82. 13 13C NMR (101 MHz, CDCl3) δ 169.6, 161.3 (d, J J = 247.1 Hz), 158.7, 142.6, 138.5 (d, J J = 3.6 Hz), 134.5, 133.6, 133.0, 130.6, 129.0, 128.5, 127.5 (d, J J = 8.1 Hz), 127.0, 126.9, 114.2 (d, J J = 21.6 Hz), 50.2, 42.0, -5.0. HRMS (ESI) m / z: [M+Na] + calculated for C 24 H 21 NaFO2Si: 411.1187, found: 411.1185. Example 4: Under a nitrogen atmosphere, add the phosphine ligand L1 (6.7 mg, 0.02 mmol) and the metal catalyst palladium acetate (2.2 mg, 0.01 mmol) to a Schlenk reaction tube, then add 2.0 mL of 2-methyltetrahydrofuran solvent. After pre-stirring at 30 °C for 10 min, add the phenylpropiolate compound 2d (0.20 mmol). After stirring for 15 min, add benzosilacyclobutane (0.80 mmol). Continue stirring the reaction at 30 °C for 24 h. After monitoring the reaction by TLC until it is completed, then filter, extract, concentrate the filtrate, and purify it by silica gel column chromatography to obtain 64 mg of a pale yellow oily liquid product 3d with a yield of 73%, 93% ee . The physical and chemical indexes of this product: Enantiomeric excess was determined by HPLC with achiralcel OX column (hexanes: 2-propanol = 99.5:0.5, 0.8 mL / min, 254 nm, 96.5:3.5 er); major enantiomer tr = 9.10 min, minor enantiomer tr = 8.01 min. 1 H NMR (400 MHz, CDCl3) δ 7.60 – 7.45 (m, 5H), 7.35 – 7.25 (m, 6H), 7.25 – 7.14 (m, 2H), 3.91 (dd, J J = 35.6, 21.2 Hz, 2H), 3.34 (s, 3H), 0.69 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ -62.45. 13 C NMR (101 MHz, CDCl3) δ 169.0, 158.7, 146.3, 142.3, 134.3, 133.6, 133.1, 130.5, 129.7, 128.6, 127.0, 126.9, 126.1, 125.8 (q, J J = 270.0 Hz), 125.3, 124.2 (q, J J = 3.8 Hz), 50.3, 41.9, -4.9. HRMS (ESI) m / z: [M+Na] + calculated for C 25 H 21 NaF3O2Si: 461.1155, found: 461.1154. Example 5: Under a nitrogen atmosphere, add the phosphine ligand L1 (6.7 mg, 0.02 mmol) and the metal catalyst palladium acetate (2.2 mg, 0.01 mmol) to a Schlenk reaction tube, then add 2.0 mL of 2-methyltetrahydrofuran solvent. After pre-stirring at 30 °C for 10 min, add the phenylpropiolate compound 2e (0.20 mmol). After stirring for 15 min, add benzosilacyclobutane (0.80 mmol). Continue stirring the reaction at 30 °C for 24 h. After monitoring the reaction by TLC until it is completed, then filter, extract, concentrate the filtrate, and purify it by silica gel column chromatography to obtain 70 mg of a pale yellow oily liquid product 3e with a yield of 91%, 85% ee . Physicochemical properties of the product: Enantiomeric excess was determined by HPLC with achiralcel OX column (hexanes: 2-propanol = 99:1, 1.0 mL / min, 254 nm, 92.5:7.5 er ); retention time of the major enantiomer tr = 19.19 min, retention time of the minor enantiomer tr = 11.07 min. 1 1H NMR (400 MHz, CDCl3) δ 7.51 – 7.46 (m, 3H), 7.30 – 7.23 (m, 4H), 7.20 – 7.14 (m, 3H), 7.06 – 6.99 (m, 3H), 3.92 (dd, J J = 27.6, 21.6 Hz, 2H), 3.33 (s, 3H), 2.27 (s, 3H), 0.67 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 169.8, 160.1, 142.9, 142.6, 136.8, 134.7, 133.6, 132.9, 130.8, 128.4, 128.4, 127.6, 127.1, 127.0, 126.8, 126.2, 125.1, 122.9, 50.1, 41.9, 20.4, -5.0. HRMS (ESI) m / z: [M+Na] + calculated for C 25 H 24 NaO2Si: 407.1438, found: 407.1439. Example 6: Under a nitrogen atmosphere, phosphine ligand L1 (6.7 mg, 0.02 mmol) and metal catalyst palladium acetate (2.2 mg, 0.01 mmol) were added to a Schlenk reaction tube. Then, 2.0 mL of 2-methyltetrahydrofuran solvent was added. After pre-stirring at 30 °C for 10 min, propargyl benzoate 2f (0.20 mmol) was added. After stirring for 15 min, benzosilacyclobutane (0.80 mmol) was added, and the reaction was continued to stir at 30 °C for 24 h. After monitoring the reaction by TLC until completion, it was filtered, extracted, the filtrate was concentrated, and purified by silica gel column chromatography to obtain 64 mg of a pale yellow oily liquid product 3f with a yield of 82%, 90% ee . The physical and chemical indexes of this product: Enantiomeric excess was determined by HPLC with achiralcel OX column (hexanes: 2-propanol = 99:1, 0.8 mL / min, 254 nm, 95:5 er ); major enantiomer tr = 13.21 min, minor enantiomer tr = 12.48 min. 1 H NMR (400 MHz, CDCl3) δ 7.52 – 7.44 (m, 3H), 7.31 – 7.21 (m, 5H), 7.21 – 7.13 (m, 2H), 7.00 – 6.88 (m, 3H), 3.90 (dd, J J = 32.0, 21.6 Hz, 2H), 3.34 (s, 3H), 0.67 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ -112.89. 13 C NMR (101 MHz, CDCl3) δ 169.3, 161.5 (d, J J = 246.5 Hz), 158.3 (d, J J = 1.9 Hz), 144.7 (d, J J = 7.2 Hz), 142.5, 134.4, 133.6, 133.0, 130.5, 129.3, 128.8 (d, J= 8.3 Hz), 128.6, 127.0, 126.9, 125.2, 121.5 (d, J = 2.9 Hz), 113.7 (d, J =21.1 Hz), 112.8 (d, J = 22.0 Hz), 50.2, 41.7, -5.0. HRMS (ESI) m / z: [M+Na] + calculated for C 24 H 21 NaFO2Si: 411.1187, found:411.1189. Example 7: Under a nitrogen atmosphere, add phosphine ligand L1 (6.7 mg, 0.02 mmol) and metal catalyst palladium acetate (2.2 mg, 0.01 mmol) to a Schlenk reaction tube, then add 2.0 mL of 2-methyltetrahydrofuran solvent. After pre-stirring at 30 °C for 10 min, add propargyl benzoate compound 2g (0.20 mmol). After stirring for 15 min, add benzosilacyclobutane (0.80 mmol), and continue stirring the reaction at 30 °C for 24 h. After monitoring the reaction by TLC until it is completed, filter, extract, concentrate the filtrate, and purify it by silica gel column chromatography to obtain 72 mg of pale yellow oily liquid product 3g, with a yield of 90%, 85% ee . The physical and chemical indexes of this product: Enantiomeric excess was determined by HPLC with achiralcel AD column (hexanes: 2-propanol = 99:1, 1.0 mL / min, 254 nm, 92.5:7.5 er ); major enantiomer tr = 32.77 min, minor enantiomer tr = 19.18 min. 1 1H NMR (400 MHz, CDCl3) δ 7.55 – 7.44 (m, 3H), 7.33 – 7.23 (m, 4H),7.22 – 7.13 (m, 3H), 6.85 – 6.72 (m, 3H), 3.92 (dd, J= 28.4, 21.2 Hz, 2H), 3.71 (s, 3H), 3.34 (s, 3H), 0.67 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 169.7, 159.4, 158.3, 144.0, 142.8, 134.6, 133.6, 132.9, 130.7, 128.5, 128.3, 127.0, 126.8, 125.1, 118.2, 112.4, 111.3, 54.2, 50.2, 41.8, -5.0. HRMS (ESI) m / z: [M+Na] + calculated for C 25 H 24 NaO3Si: 423.1387, found: 423.1389. Example 8: Under a nitrogen atmosphere, the phosphine ligand L1 (6.7 mg, 0.02 mmol) and the metal catalyst palladium acetate (2.2 mg, 0.01 mmol) were added to a Schlenk reaction tube, and then 2.0 mL of 2-methyltetrahydrofuran solvent was added. After pre-stirring at 30 °C for 10 min, the propargyl benzoate compound 2h (0.20 mmol) was added. After stirring for 15 min, benzosilacyclobutane (0.80 mmol) was added, and the reaction was continued to stir at 30 °C for 24 h. After monitoring the reaction by TLC until completion, it was then filtered, extracted, the filtrate was concentrated, and purified by silica gel column chromatography to obtain 64 mg of a pale yellow oily liquid product 3h, with a yield of 79%, 90% ee 。 The physical and chemical indexes of this product: Enantiomeric excess was determined by HPLC with achiralcel AD column (hexanes: 2-propanol = 99:1, 1.0 mL / min, 254 nm, 95:5 er ); major enantiomer tr = 20.57 min, minor enantiomer tr = 10.80 min. 11H NMR (400 MHz, CDCl3) δ 7.52 – 7.44 (m, 3H), 7.30 – 7.24 (m, 4H),7.23 – 7.17 (m, 5H), 7.12 – 7.03 (m, 1H), 3.87 (dd, J J = 32.0, 21.2 Hz, 2H),3.35 (s, 3H), 0.67 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 169.2, 158.3, 144.3, 142.4, 134.4, 133.6,133.1, 133.0, 130.5, 129.4, 128.6, 128.5, 127.0, 126.9, 125.8, 125.2, 124.0,50.3, 41.85, -5.0. HRMS (ESI) m / z: [M+Na] + calculated for C 24 19 21 H13NaClO2Si: 427.0892, found:427.0893. Example 9: Under a nitrogen atmosphere, add the phosphine ligand L1 (6.0 mg, 0.016 mmol) and the metal catalyst palladium acetate (2.2 mg, 0.01 mmol) to a Schlenk reaction tube, then add 2.0 mL of 2-methyltetrahydrofuran solvent. After pre-stirring at 30 °C for 10 min, add the phenylpropiolate compound 2i (0.20 mmol). After stirring for 15 min, add benzosilacyclobutane (0.80 mmol). Continue stirring the reaction at 40 °C for 14 h. After monitoring the reaction by TLC until it is completed, filter, extract, concentrate the filtrate, and purify it by silica gel column chromatography to obtain 56 mg of a pale yellow oily liquid product 3i with a yield of 63%, 91% ee . The physical and chemical indexes of this product: Enantiomeric excess was determined by HPLC with achiralcel OD column (hexanes: 2-propanol = 99.5:0.5, 0.7 mL / min, 254 nm, 95.5:4.5 er); major enantiomer tr = 14.16 min, minor enantiomer tr = 13.52 min. 1 H NMR (400 MHz, CDCl3) δ 7.51 – 7.45 (m, 3H), 7.39 – 7.35 (m, 2H), 7.32 – 7.26 (m, 4H), 7.21 – 7.12 (m, 4H), 3.89 (dd, J J = 32.0, 21.6 Hz, 2H), 3.37 (s, 3H), 0.68 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 169.2, 158.2, 144.6, 142.4, 134.4, 133.6, 133.0, 130.5, 129.8, 129.5, 128.8, 128.6, 127.0, 126.9, 125.2, 121.2, 50.3, 41.8, -5.0. HRMS (ESI) m / z: [M+Na] + calculated for C 24 H 21 NaBrO2Si: 471.0386, found: 471.0387. Example 10: Under a nitrogen atmosphere, add the phosphine ligand L1 (6.7 mg, 0.02 mmol) and the metal catalyst palladium acetate (2.2 mg, 0.01 mmol) to a Schlenk reaction tube, then add 2.0 mL of tetrahydrofuran solvent. After pre-stirring at 30 °C for 10 min, add the phenylpropiolate compound 2j (0.20 mmol). After stirring for 15 min, add benzosilacyclobutane (0.80 mmol), and continue stirring the reaction at 30 °C for 18 h. After monitoring the reaction by TLC until it is completed, then filter, extract, concentrate the filtrate, and purify it by silica gel column chromatography to obtain 72 mg of a pale yellow oily liquid product 3j, with a yield of 82%, 91% ee . Physicochemical indices of the product: Enantiomeric excess was determined by HPLC with achiralcel AD column (hexanes: 2-propanol = 99:1, 1.0 mL / min, 254 nm, 94.5:5.5 er ); major enantiomer tr = 14.36 min, minor enantiomer tr = 7.42 min. 1 1H NMR (400 MHz, CDCl3) δ 7.52 – 7.44 (m, 5H), 7.38 (d, J J = 4.6 Hz, 2H),7.30 – 7.23 (m, 4H), 7.18 (t, J J = 7.3 Hz, 2H), 3.91 (dd, J J = 35.6, 21.2 Hz, 2H),3.32 (s, 3H), 0.68 (s, 3H). 19 19F NMR (376 MHz, CDCl3) δ -62.43. 13 13C NMR (101 MHz, CDCl3) δ 169.1, 158.1, 143.3, 142.3, 134.3, 133.6,133.1, 130.4, 130.1, 129.7, 129.4, 129.1, 128.6 (d, J J = 1.7 Hz), 127.7, 127.0,126.9, 125.3, 123.5 (q, J J = 3.2 Hz), 123.0 (q, J J = 271.0 Hz),122.6 (q, J J = 3.9 Hz),50.2, 41.7, -4.9. HRMS (ESI) m / z: [M+Na] + calculated for C 25 H 21 NaF3O2Si: 461.1155, found:461.1156. Example 11: Under a nitrogen atmosphere, add the phosphine ligand L1 (6.7 mg, 0.02 mmol) and the metal catalyst palladium acetate (2.2 mg, 0.01 mmol) to a Schlenk reaction tube. Then add 2.0 mL of 2-methyltetrahydrofuran solvent. After pre-stirring at 30 °C for 10 min, add the propargyl benzoate compound 2k (0.20 mmol). After stirring for 15 min, add benzosilacyclobutane (0.80 mmol). Continue stirring the reaction at 30 °C for 16 h. After monitoring the reaction by TLC until it is completed, filter, extract, concentrate the filtrate, and purify it by silica gel column chromatography to obtain 74 mg of a pale yellow oily liquid product 3k with a yield of 86%, 90% ee 。 The physical and chemical indicators of this product: Enantiomeric excess was determined by UPLC with an achiralcel INA column (hexanes: 2-propanol = 98:2, 0.8 mL / min, 211 nm, 95:5 er ); major enantiomer tr = 10.45 min, minor enantiomer tr = 7.56 min. 1 H NMR (400 MHz, CDCl3) δ 7.94 – 7.87 (m, 2H), 7.53 – 7.45 (m, 3H), 7.40 – 7.33 (m, 2H), 7.31 – 7.24 (m, 4H), 7.22 – 7.16 (m, 2H), 3.93 (dd, J = 34.0, 21.2 Hz, 2H), 3.82 (s, 3H), 3.32 (s, 3H), 0.68 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 169.2, 165.8, 159.2, 142.9, 142.4, 133.6, 133.0, 132.4, 130.6, 130.3, 129.1, 128.6, 127.9, 127.4, 127.3, 127.0, 126.9, 126.7, 125.2, 51.2, 50.2, 41.9, -4.9. HRMS (ESI) m / z: [M+Na] +Calculated for C 26 H 24 NaO4Si: 451.1336, found: 451.1336. Example 12: Under a nitrogen atmosphere, add the phosphine ligand L1 (6.7 mg, 0.02 mmol) and the metal catalyst palladium acetate (2.2 mg, 0.01 mmol) to a Schlenk reaction tube, then add 2.0 mL of 2-methyltetrahydrofuran solvent. After pre-stirring at 30 °C for 10 min, add the phenylpropiolate compound 2l (0.20 mmol). After stirring for 15 min, add benzosilacyclobutane (0.80 mmol). Continue stirring the reaction at 30 °C for 24 h. After monitoring the reaction by TLC until it is completed, filter, extract, concentrate the filtrate, and purify it by silica gel column chromatography to obtain 64 mg of a pale yellow oily liquid product 3l, with a yield of 80%, 82% ee . The physical and chemical indexes of this product: Enantiomeric excess was determined by HPLC with achiralcel AD column (hexanes: 2-propanol = 99:1, 1.0 mL / min, 254 nm, 91:9 er ); major enantiomer tr = 15.58 min, minor enantiomer tr = 7.89 min. 1 H NMR (400 MHz, CDCl3) δ 7.51 – 7.45 (m, 3H), 7.30 – 7.23 (m, 4H), 7.18 (t, J J = 7.6 Hz, 2H), 6.87 (s, 1H), 6.83 (s, 2H), 3.91 (dd, J J = 26.8, 21.2 Hz, 2H), 3.35 (s, 3H), 2.23 (s, 6H), 0.66 (s, 3H). 1313C NMR (101 MHz, CDCl3) δ 169.9, 160.3, 143.0, 142.6, 136.7, 134.8, 133.6, 132.9, 130.8, 128.6, 128.4, 128.4, 127.9, 127.0, 126.8, 125.0, 123.4, 50.1, 41.9, 20.3, -5.0. HRMS (ESI) m / z: [M+Na] + calculated for C 26 H 26 NaO2Si: 421.1594, found: 421.1595. Example 13: Under a nitrogen atmosphere, the phosphine ligand L1 (6.7 mg, 0.02 mmol) and the metal catalyst palladium acetate (2.2 mg, 0.01 mmol) were added to a Schlenk reaction tube, and then 2.0 mL of 2-methyltetrahydrofuran solvent was added. After pre-stirring at 30 °C for 10 min, the phenylpropiolate compound 2m (0.20 mmol) was added. After stirring for 15 min, benzosilacyclobutane (0.80 mmol) was added, and the reaction was continued to stir at 30 °C for 24 h. After monitoring the reaction by TLC until completion, it was then filtered, extracted, the filtrate was concentrated, and purified by silica gel column chromatography to obtain 56 mg of a pale yellow oily liquid product 3m, with a yield of 69%, 91% ee . The physical and chemical indicators of this product: Enantiomeric excess was determined by HPLC with achiralcel OX column (hexanes: 2-propanol = 99.5:0.5, 0.8 mL / min, 254 nm, 95.5:4.5 er ); major enantiomer tr = 9.53 min, minor enantiomer tr = 9.01 min. 1 1H NMR (400 MHz, CDCl3) δ 7.51 – 7.42 (m, 3H), 7.33 – 7.24 (m, 4H), 7.22 – 7.14 (m, 2H), 6.79 – 6.63 (m, 3H), 3.87 (dd, J= 34.0, 21.6 Hz, 2H), 3.39 (s, 2H), 0.67 (s, 3H). 19 19F NMR (376 MHz, CDCl3) δ -109.51. 13 13C NMR (101 MHz, CDCl3) δ 168.9, 161.9 (d, J J = 247.0 Hz), 161.7 (d, J J = 248.0 Hz), 157.1, 145.7 (d, J J = 8.9 Hz), 142.1, 134.1, 133.6, 133.1, 130.3, 130.2, 128.7, 127.0 (d, J J = 12.8 Hz), 125.3, 108.908 (d, J J = 11.7 Hz), 108.907 (d, J J = 25.6 Hz), 102.4, 102.1, 101.87, 50.4, 41.5, -5.0. HRMS (ESI) m / z: [M+Na] + calculated for C 24 H 20 NaF2O2Si: 429.1093, found: 429.1093. Example 14: Under a nitrogen atmosphere, add the phosphine ligand L1 (6.7 mg, 0.02 mmol) and the metal catalyst palladium acetate (2.2 mg, 0.01 mmol) to a Schlenk reaction tube, then add 2.0 mL of 2-methyltetrahydrofuran solvent. After pre-stirring at 30 °C for 10 min, add the phenylpropiolate compound 2n (0.20 mmol). After stirring for 15 min, add benzosilacyclobutane (0.80 mmol). Continue stirring the reaction at 30 °C for 24 h. After monitoring the reaction by TLC until it is completed, then filter, extract, concentrate the filtrate, and purify it by silica gel column chromatography to obtain 46 mg of a pale yellow oily liquid product 3n with a yield of 69%, 90% ee . Physicochemical indices of the product: Enantiomeric excess was determined by UPLC with achiralcel MD column (hexanes: 2-propanol = 99.5:0.5, 0.8 mL / min, 210 nm, 95:5 er ); retention time of the major enantiomer tr = 5.22 min, retention time of the minor enantiomer tr = 4.69 min. 1 1H NMR (400 MHz, CDCl3) δ 7.50 – 7.44 (m, 3H), 7.34 – 7.26 (m, 4H), 7.25 – 7.22 (m, 2H), 7.20 – 7.16 (m, 1H), 7.09 (d, J J = 1.9 Hz, 2H), 3.87 (d, J J = 34.8, 21.6 Hz, 2H), 3.41 (s, 3H), 0.68 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 169.8, 158.0, 146.4, 143.1, 135.2, 134.8, 134.7, 134.2, 131.4, 131.4, 129.8, 129.7, 128.1, 128.0, 127.8, 126.4, 125.3, 51.5, 42.7, -3.9. HRMS (ESI) m / z: [M+Na] + calculated for C 24 H 20 NaCl2O2Si: 461.0502, found: 461.0504. Example 15: Under a nitrogen atmosphere, phosphine ligand L1 (6.7 mg, 0.02 mmol) and palladium acetate (2.2 mg, 0.01 mmol) as the metal catalyst were added to a Schlenk reaction tube. Then, 2.0 mL of 2-methyltetrahydrofuran solvent was added. After pre-stirring at 30 °C for 10 min, propargyl benzoate 2o (0.20 mmol) was added. After stirring for 15 min, benzosilacyclobutane (0.80 mmol) was added, and the reaction was continued to stir at 30 °C for 24 h. After monitoring the reaction by TLC until completion, the mixture was filtered, extracted, and the filtrate was concentrated. The residue was purified by silica gel column chromatography to obtain 74 mg of the product 3o as a pale yellow oily liquid, with a yield of 73%, 94% ee . The physical and chemical indexes of this product: Enantiomeric excess was determined by UPLC with achiralcel MD column (hexanes: 2-propanol = 99.5:0.5, 0.8 mL / min, 211 nm, 97:3 er ); major enantiomer tr = 3.76 min, minor enantiomer tr = 6.29 min. 1 H NMR (400 MHz, CDCl3) δ 7.75 (s, 1H), 7.64 (s, 2H), 7.51 – 7.44 (m,3H), 7.34 – 7.18 (m, 6H), 3.93 (q, J = 21.5 Hz, 2H), 3.36 (s, 3H), 0.70 (s,3H). 19 F NMR (376 MHz, CDCl3) δ -62.71. 13 C NMR (101 MHz, CDCl3) δ 168.5, 156.4, 144.5, 141.8, 133.9, 133.7,133.2, 131.6, 130.5 (q, J = 33.3 Hz), 130.1, 128.80, 128.78, 127.1, 127.0,126.1 (d, J = 3.9 Hz), 125.5, 122.2 (q, J= 272.8 Hz), 120.5 (q, J = 4.0 Hz), 50.4, 41.6, -4.9. HRMS (ESI) m / z: [M+Na] + calculated for C 26 H 20 NaF6O2Si: 529.1029, found: 529.1026. Example 16: Under a nitrogen atmosphere, the phosphine ligand L1 (6.7 mg, 0.02 mmol) and the metal catalyst palladium acetate (2.2 mg, 0.01 mmol) were added to a Schlenk reaction tube, and then 2.0 mL of 2-methyltetrahydrofuran solvent was added. After pre-stirring at 30 °C for 10 min, the phenylpropiolate compound 2p (0.20 mmol) was added. After stirring for 15 min, benzosilacyclobutane (0.80 mmol) was added, and the reaction was continued to stir at 30 °C for 24 h. After monitoring the reaction by TLC until completion, the mixture was filtered, extracted, the filtrate was concentrated, and purified by silica gel column chromatography to obtain 78 mg of a pale yellow oily liquid product 3p, with a yield of 92%, 86% ee 。 The physical and chemical indexes of this product: Enantiomeric excess was determined by UPLC with achiralcel MD column (hexanes: 2-propanol = 99:1, 0.8 mL / min, 254 nm, 93:7 er ); major enantiomer tr = 4.50 min, minor enantiomer tr = 4.11 min. 1 1H NMR (400 MHz, CDCl3) δ 7.53 – 7.45 (m, 3H), 7.32 – 7.22 (m, 6H), 7.20 – 7.11 (m, 4H), 3.92 (dd, J = 25.6, 21.6 Hz, 2H), 3.32 (s, 3H), 1.24 (s, 9H), 0.66 (s, 3H). 1313C NMR (101 MHz, CDCl3) δ 170.0, 159.7, 149.8, 143.0, 139.5, 134.7, 133.6, 132.9, 130.9, 128.4, 128.0, 127.0, 126.8, 125.5, 125.1, 124.0, 50.1, 41.8, 33.6, 30.3, -5.1. HRMS (ESI) m / z: [M+Na] + calculated for C 28 H 30 NaO2Si: 449.1907, found: 449.1912. Example 17: Under a nitrogen atmosphere, the phosphine ligand L1 (6.7 mg, 0.02 mmol) and the metal catalyst palladium acetate (2.2 mg, 0.01 mmol) were added to a Schlenk reaction tube, and then 2.0 mL of 2-methyltetrahydrofuran solvent was added. After pre-stirring at 30 °C for 10 min, the propargyl benzoate compound 2q (0.20 mmol) was added. After stirring for 15 min, benzosilacyclobutane (0.80 mmol) was added, and the reaction was continued to stir at 30 °C for 24 h. After monitoring the reaction by TLC until completion, it was then filtered, extracted, the filtrate was concentrated, and purified by silica gel column chromatography to obtain 76 mg of a pale yellow oily liquid product 3q with a yield of 90%, 80% ee . The physical and chemical indexes of this product: Enantiomeric excess was determined by UPLC with achiralcel MD column (hexanes: 2-propanol = 99:1, 0.8 mL / min, 254 nm, 90:10 er ); major enantiomer tr = 11.79 min, minor enantiomer tr = 7.70 min. 1 1H NMR (400 MHz, CDCl3) δ 7.78 – 7.71 (m, 3H), 7.69 – 7.65 (m, 1H), 7.55 – 7.47 (m, 3H), 7.41 – 7.25 (m, 7H), 7.25 – 7.16 (m, 2H), 4.01 (dd,J = 27.2, 6.0 Hz, 2H), 3.27 (s, 3H), 0.70 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 169.8, 159.8, 134.6, 133.7, 133.0, 132.1, 131.7, 130.7, 128.9, 128.5, 127.1, 127.0, 126.9, 126.8, 126.7, 125.3, 125.2, 124.4, 124.2, 50.2, 42.0, -5.0. HRMS (ESI) m / z: [M+Na] + calculated for C 28 H 24 NaO2Si: 443.1438, found: 443.1439. Example 18: Under a nitrogen atmosphere, phosphine ligand L1 (6.7 mg, 0.02 mmol) and metal catalyst palladium acetate (2.2 mg, 0.01 mmol) were added to a Schlenk reaction tube. Then, 2.0 mL of 2-methyltetrahydrofuran solvent was added. After pre-stirring at 30 °C for 10 min, propargyl benzoate compound 2r (0.20 mmol) was added. After stirring for 15 min, benzosilacyclobutane (0.80 mmol) was added. The reaction was continued to stir at 30 °C for 24 h. After monitoring the reaction by TLC until completion, it was then filtered, extracted, and the filtrate was concentrated. After purification by silica gel column chromatography, 68 mg of a pale yellow oily liquid product 3r was obtained with a yield of 89%, 90% ee . The physical and chemical indexes of this product: Enantiomeric excess was determined by HPLC with achiralcel AD column (hexanes: 2-propanol = 99:1, 1.0 mL / min, 254 nm, 95:5 er ); major enantiomer tr = 17.92 min, minor enantiomer tr = 12.37 min. 1H NMR (400 MHz, CDCl3) δ 7.56 – 7.45 (m, 3H), 7.32 – 7.24 (m, 6H), 7.23 – 7.15 (m, 4H), 3.93 (dd, J J = 28.0, 21.2 Hz, 2H), 3.78 (q, J J = 7.2 Hz, 1H), 0.77 (t, J J = 7.1 Hz, 1H), 0.68 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 169.2, 159.8, 142.8, 142.8, 134.8, 133.7, 133.0, 130.8, 128.4, 127.1, 127.0, 126.8, 126.7, 125.8, 125.4, 59.0, 42.0, 12.7, -4.9. HRMS (ESI) m / z: [M+Na]+ calculated for C25H24NaO2Si: 407.1438, found: 407.1439. Example 19: Under a nitrogen atmosphere, add phosphine ligand L1 (6.7 mg, 0.02 mmol) and metal catalyst palladium acetate (2.2 mg, 0.01 mmol) to a Schlenk reaction tube, then add 2.0 mL of 2-methyltetrahydrofuran solvent. After pre-stirring at 30 °C for 10 min, add propargyl benzoate compound 2s (0.20 mmol). After stirring for 15 min, add benzosilacyclobutane (0.80 mmol), and continue stirring the reaction at 30 °C for 24 h. After monitoring the reaction by TLC until it is completed, then filter, extract, concentrate the filtrate, and purify it by silica gel column chromatography to obtain 64 mg of a pale yellow oily liquid product 3s, with a yield of 80%, 90% ee . The physical and chemical indexes of this product: Enantiomeric excess was determined by HPLC with achiralcel AD column (hexanes: 2-propanol = 99:1, 1.0 mL / min, 254 nm, 95:5 er); retention time of the major enantiomer = 14.42 min, retention time of the minor enantiomer = 11.50 min. 1 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J J = 7.8 Hz, 2H), 7.47 (d, J J = 7.2 Hz,1H), 7.30 – 7.15 (m, 11H), 4.72 – 4.61 (m, 1H), 3.94 (dd, J J = 28.8, 21.6 Hz,2H), 0.76 (t, J J = 6.0 Hz, 6H), 0.68 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 168.8, 158.8, 142.9, 142.7, 134.7, 133.8,133.0, 130.8, 129.1, 128.42, 128.40, 127.1, 127.0, 126.7, 126.7, 125.9,125.0, 66.4, 41.8, 20.3, 20.3, -4.8. HRMS (ESI) m / z: [M+Na] + calculated for C 26 H 26 NaO2Si: 421.1594, found:421.1597. In summary, the above are only the preferred embodiments of the present invention. All equivalent changes and modifications made according to the scope of the patent application of the present invention shall fall within the scope of the patent of the present invention.

Claims

1. A silicon-containing chiral 1,4-dihydrobenzodisilacyclohexane compound with ester modification, characterized in that, The compound has a structural formula shown in the following formula (I): In the formula, R1 is one of hydrogen, alkyl, halogen, haloalkyl, alkoxy or phenyl, and R is alkyl.

2. A method for preparing a silicon-containing chiral 1,4-dihydrobenzodisilacyclohexane compound with ester modification as described in claim 1, characterized in that, The preparation method includes the following steps: Under an inert gas atmosphere, a phosphine ligand, a palladium metal catalyst and a reaction medium are mixed. After stirring for 10 - 20 min, a propargyl ester compound 2 and a benzosilacyclobutane 1 are added successively. After the reaction is completed and the solvent is removed, the silicon-containing chiral 1,4-dihydrobenzosilacyclohexane compound with an ester modification is obtained by separation and purification.

3. The preparation method according to claim 2, characterized in that, The molar ratio of the propargyl ester compound 2 to the benzosilacyclobutane 1 is 1:4 - 5.

4. The preparation method according to claim 2, characterized in that, The palladium metal catalyst is palladium acetate.

5. The preparation method according to claim 4, characterized in that, The usage amount of the palladium metal catalyst is 3 - 5% of the molar amount of the propargyl ester compound.

6. The preparation method according to claim 2, characterized in that, The structural formula of the phosphine ligand is: 。 7. The preparation method according to claim 6, characterized in that, The usage amount of the phosphine ligand is 8 - 12% of the molar amount of the propargyl ester compound.

8. The preparation method according to claim 2, characterized in that, The reaction medium is selected from one or more of 2-methyltetrahydrofuran, tetrahydrofuran, and toluene.

9. Use of the silicon-containing chiral 1,4-dihydrobenzosilacyclohexane compound with an ester modification as described in claim 1 as a luminescent material.

10. Use of the silicon-containing chiral 1,4-dihydrobenzosilacyclohexane compound with an ester modification as described in claim 1 as a pharmaceutical synthesis precursor.

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