Method for efficiently synthesizing silylated indole compound

Abstract

The invention discloses a method for efficiently synthesizing a silylated indole compound, which comprises the following steps of: sequentially adding 1-(2-iodophenyl)-1H-indole and hexamethyldisilane in a reaction container according to a molar ratio of 1: 4, then adding a solvent, then adding a catalyst Pd (OAc) 2 and alkali K2CO3 which respectively account for 10.0% and 200% of the molar weight of the 1-(2-iodophenyl)-1H-indole, and 5 mL of N, N-dimethylformamide; reacting for 12 hours in an air atmosphere and an oil bath condition of 100 DEG C, cooling to room temperature, adding water, extracting with ethyl acetate for three times, combining organic layers, concentrating under reduced pressure, and purifying the product by column chromatography to obtain the product silicon-based indole compound. The reaction substrate is wide in source, commercially available, good in yield, good in selectivity, easy to separate and purify, less in pollution and simple in operation step, a coupling reaction among molecules of raw materials can be avoided, and the generated silylated indole compound is widely applicable to organic synthesis design of organic chemical reaction, bioactive intermediates and electronic materials.

Description

Technical Field

[0001] The invention relates to the synthesis of organic matter, and in particular to a method for efficiently synthesizing silylated indole compounds. Background Art

[0002] Organosilicon compounds have a wide range of applications in the following areas due to their unique biological, physical and chemical properties: 1. Organosilicon compounds are important pharmaceutical intermediates and can be used in the synthesis of many drugs, such as doxylamine, loratadine, Sila-dimetracrine, amsilarotene, silaproline, TMS-alanine and camptothecin. 2. Organosilicon compounds are also important intermediates in organic chemistry, which modify the molecular skeleton. 3. Their derivatives are also widely used in polymers, semiconductor materials, drug design and other fields. Since organosilicon compounds have broad application prospects and special biological activities, such as important physiological and pharmacological activities, and other biological activities such as anti-inflammatory and antibacterial, people are increasingly studying them. There are three main methods for synthesizing organosilicon compounds: 1. Synthesis method using halosilanes as silicon sources (Org. Lett. 2000, 2, 565, J. Org. Chem. 2003, 68, 9384, Org. Lett. 2000, 2, 3221, Org. Lett. 2003, 5, 1899, Org. Lett. 2006, 8, 765, J. Org. Chem. 2004, 69, 8305). This method mainly synthesizes organosilicon compounds by coupling reaction of organolithium reagents or Grignard reagents with halosilanes. The advantage of this method is that the synthesis route is simple, but the requirements for reaction conditions are relatively harsh. The reaction must be carried out under anhydrous and oxygen-free conditions. In addition, this method has poor tolerance to many functional groups, and the expansion of the substrate range is subject to certain restrictions. Therefore, the application of this synthesis route in organic synthesis is greatly limited. 2. A synthesis method using hydrosilane as a silicon source (J.Am.Chem.Soc.2003,125,13640, J.Am.Chem.Soc.2003,125,30, Org.Lett.2015,17,4538, ACS Catal.2018,8,5896, Org.Lett.2018,20,5357, Chem.Rev.2018,118,6516). This method has good selectivity, but hydrosilane is expensive, highly toxic, unstable and difficult to synthesize, which also limits the practical application of this method.3. A synthesis method using hexamethyldisilane as a silicon source (Chem. Commun. 2000, 1895, Organometallics, 2006, 25, 4665, Org. Lett. 2007, 9, 3785, J. Am. Chem. Soc. 2006, 128, 8152, J. Am. Chem. Soc. 2008, 130, 15982, J. Org. Chem. 1996, 61, 5779, Org. Lett. 2009, 12, 28, J. Am. Chem. Soc. 2008, 130, 16382, J. Am. Chem. Soc. 2010, 133, 409, Org. Lett. 2000, 2, 3877) This method has the advantages of high efficiency and good functional group tolerance. Hexamethyldisilane is a commercially available, stable, low-toxic disilane reagent that is widely used in the synthesis of silicon-based compounds. Compared with hydrosilane reagents, hexamethyldisilane has the advantages of low price, insensitivity to air and water, relatively stable properties, and easy storage. In recent years, organosilicon compounds have played an important role in the creation of new drugs, and the research on their synthesis methods has also made great progress. In 2008, Chatani and his colleagues developed a pyridine-directed Rh-catalyzed ortho-silylation reaction of aromatic CH bonds with hexamethyldisilane (Chem. Asian J. 2008, 3, 1585), thereby synthesizing organosilicon compounds. Although this method has a high yield, it has poor selectivity and the product is a mixture of monosilane and disilane. In 2014, Motomu Kanai's research group used 8-aminoquinoline as a directing group and palladium-catalyzed C(sp) of benzamides and carboxylic acid amides. 2 )-H and C(sp 3 )-H bond regioselective activation, followed by coupling with disilane to synthesize the silylation reaction of organosilanes (Org. Lett. 2014, 16, 1968). The reaction has good tolerance to functional groups, but the substrate needs to be pre-functionalized and the raw materials are not easy to synthesize. In 2015, Yingsheng Zhao's research group conducted a palladium-catalyzed direct ortho-silylation reaction of oxamide-protected benzylamine and phenylethylamine with hexamethyldisilane (Org. Lett. 2015, 17, 3646). This method has good selectivity, but requires protection of the amino group and the steps are cumbersome. In 2017, Debabrata MaitiThe research group has realized a palladium-catalyzed selective silylation reaction strategy for meta-CH bonds (Organometallics, 2017, 36, 2418). This method has good selectivity, but the substrate is not easy to synthesize. In 2016, Bing-Feng Shi's research group realized the Pd(II)-catalyzed intermolecular silylation reaction of CH bonds of a-amino acids and simple fatty acids (Angew. Chem. Int. Ed. 2016, 55, 13859), and synthesized various β-silyl-a-amino acids. This method has excellent regioselectivity and stereoselectivity, but it requires the removal of auxiliary groups, which increases the reaction steps. In 2018, Yanghui Zhang's research group developed a palladium-catalyzed method for the efficient synthesis of disilylation products from halogenated aromatics (Angew. Chem. Int. Ed. 2018, 57, 3233). This method has a high yield, but a narrow substrate range. The above-mentioned synthesis methods have many disadvantages: harsh reaction conditions, difficult substrate synthesis, difficult separation, inert gas protection during the reaction process, and high requirements for equipment. Summary of the invention

[0003] In view of the defects of the existing methods for synthesizing organosilicon compounds, the present invention provides a method for synthesizing silylated indole compounds which is simple to operate, cheap in raw materials and efficient.

[0004] The technical solution adopted by the present invention is: a method for efficiently synthesizing a silylated indole compound, comprising the following steps:

[0005] In a reaction vessel, 1-(2-iodophenyl)-1H-indole and hexamethyldisilane were added in a molar ratio of 1:4, 5 mL of solvent was added according to the ratio of 0.5 mmol of 1-(2-iodophenyl)-1H-indole, and then the catalyst Pd(OAc)2 and the base K2CO3 were added, and the added amounts were 10.0% and 200% of the molar amount of 1-(2-iodophenyl)-1H-indole, respectively, DMF 5 mL, air atmosphere, 100 ° C oil bath conditions for 12 hours, cooled to room temperature, added water, extracted with ethyl acetate three times, combined the organic layers, concentrated under reduced pressure, and the product was purified by column chromatography to obtain the product silylated indole compound. The general reaction formula of the synthesis method is:

[0006]

[0007] A silylated indole compound, the general chemical structure of which is as follows:

[0008]

[0009] Among them, R1 is a hydrogen group or a methyl group; R2 is a hydrogen group, a methyl group or a methoxy group; R3 is a hydrogen group, a methyl group, a methoxy group, a cyano group or a benzyloxy group; R4 is a hydrogen group, a methoxy group or a chloro group; R5 is a hydrogen group, a methyl group or a methoxy group.

[0010] The 1-(2-iodophenyl)-1H-indole is replaced with 1-(2-iodophenyl)-3-methyl-1H-indole, 1-(2-iodophenyl)-4-methoxy-1H-indole, 1-(2-iodophenyl)-4-methyl-1H-indole, 1-(2-iodophenyl)-5-methoxy-1H-indole, 1-(2-iodophenyl)-5-methyl-1H-indole, 1-(2-iodophenyl)-5-cyano-1H-indole, 1-(2-iodophenyl)-5-(benzyloxy)-1H-indole 1-(2-iodophenyl)-6-methoxy-1H-indole, 1-(2-iodophenyl)-6-chloro-1H-indole, 1-(2-iodophenyl)-7-methoxy-1H-indole or 1-(2-iodophenyl)-7-methyl-1H-indole.

[0011] According to the above-mentioned method for synthesizing the silylated indole compound, the solvent is N,N-dimethylformamide.

[0012] According to the above-mentioned synthesis method of silylated indole compound, the column chromatography conditions are: 200-300 mesh silica gel column, and the eluent is petroleum ether.

[0013] The present invention adopts a method for efficiently synthesizing silylated indole compounds designed by the above technical scheme, which has the following beneficial effects:

[0014] 1. The present invention utilizes 1-(2-iodophenyl)-1H-indole to replace the use of traditional raw materials, halogenated aromatic hydrocarbons and substrates containing directing groups. The reaction operation is relatively simple, the reaction substrate is simple and has a wide source, and is suitable for indoles substituted with various functional groups. The steric hindrance effect has little effect on the reaction.

[0015] 2. The reaction substrate of the present invention is cheap, has high yield, good selectivity, is easy to separate and purify, has little pollution, and has simple steps. The protection and deprotection synthesis steps of functional groups can be omitted. The target product silylated indole compound is widely applicable to organic intermediates of organic chemical reactions, pharmaceutical intermediates and electronic device materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 The nuclear magnetic hydrogen spectrum of Example 1 of the present invention is shown;

[0017] Figure 2 The NMR carbon spectrum of Example 1 of the present invention is shown;

[0018] Figure 3 The nuclear magnetic hydrogen spectrum of Example 2 of the present invention is shown;

[0019] Figure 4 The NMR carbon spectrum of Example 2 of the present invention is shown. DETAILED DESCRIPTION

[0020] The following is a detailed description of a method for efficiently synthesizing silylated indole compounds according to the present invention in conjunction with examples.

[0021] Example 1

[0022] A method for synthesizing 2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2a) comprises the following steps:

[0023] In a 25 mL Schlenk reaction tube, 0.2 mmol (63.6 mg) of 1-(2-iodophenyl)-1H-indole, 0.8 mmol of hexamethyldisilane (116.8 mg), 4.5 mg of palladium acetate, 55.2 mg of potassium carbonate, and 2 ml of N,N-dimethylformamide were added, and the mixture was stirred at 100° C. for 12 hours. After the reaction (monitored by TLC), the mixture was cooled to room temperature, the reaction solution was filtered, and the organic layer was dried under reduced pressure using a rotary evaporator. Finally, the crude product was purified by column chromatography (petroleum ether unless otherwise specified) to obtain 61 mg of the desired target product (2a) as a colorless oily liquid. After drying under vacuum conditions, the yield was calculated to be 90% and the purity was 99.9%. 1 H NMR (500MHz, CDCl3, δppm) δδ8.12 (dd, J=7.16Hz, 1.96Hz, 1H), 8.09-8.06 (m, 1H), 7.93-7 .85(m,2H),7.63-7.61(m,1H),7.55-7.50(m,2H),7.28(s,2H),0.50(s,9H),0.25(s,9H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ144.4,142.1,142.0,140.7,135.6,130.1,129.5,128.1,128.0,122.0,120.3,119.4,112.3,110.8,-0.2,-0.7.

[0024] The general chemical structure of 2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2a) is:

[0025]

[0026] Example 2

[0027] A method for synthesizing 3-methyl-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2b) comprises the following steps:

[0028] In a 25 mL Schlenk reaction tube, 0.2 mmol (66.6 mg) of 1-(2-iodophenyl)-1H-indole, 0.8 mmol of hexamethyldisilane (116.8 mg), 4.5 mg of palladium acetate, 55.2 mg of potassium carbonate, and 2 ml of N,N-dimethylformamide were added, and the mixture was stirred at 100° C. for 12 hours. After the reaction (monitored by TLC), the mixture was cooled to room temperature, the reaction solution was filtered, and the organic layer was dried under reduced pressure using a rotary evaporator. Finally, the crude product was purified by column chromatography (petroleum ether unless otherwise specified) to obtain 58 mg of the desired target product (2b) as a colorless oily liquid. After drying under vacuum conditions, the yield was calculated to be 83% and the purity was 99.9%. 1 H NMR (500MHz, CDCl3, δppm) δ7.72 (dd, J=7.36Hz, 1.72Hz, 1H), 7.67-7.63 (m, 1H), 7.51-7. 44(m,2H),7.16-7.12(m,3H),6.80-6.78(m,1H),2.56(s,3H),0.09(s,9H),-0.08(s,9H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ145.4,141.4,140.6,137.1,135.5,130.2,129.7,128.9,127.9,122.0,121.2,118.8,118.2,111.0,10.9,0.5,-0.5.

[0029] The general chemical structure of 3-methyl-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2b) is:

[0030]

[0031] Example 3

[0032] A method for synthesizing 4-methoxy-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2c) comprises the following steps:

[0033] In a 25 mL Schlenk reaction tube, 0.2 mmol (69.6 mg) of 1-(2-iodophenyl)-1H-indole, 0.8 mmol hexamethyldisilane (116.8 mg), 4.5 mg palladium acetate, 55.2 mg potassium carbonate, and 2 ml N,N-dimethylformamide were added, and the mixture was stirred at 100° C. for 12 hours. After the reaction (monitored by TLC), the mixture was cooled to room temperature, the reaction solution was filtered, and the organic layer was dried under reduced pressure using a rotary evaporator. Finally, the crude product was purified by column chromatography (petroleum ether unless otherwise specified) to obtain 65 mg of the desired target product (2c) as a colorless oily liquid. After drying under vacuum conditions, the yield was calculated to be 88% and the purity was 99.9%. 1 H NMR (500MHz, CDCl3, δppm) δ7.71-7.68(m,1H),7.51-7.44(m,2H),7.20-7.18(m,1H),7.05( t,J=7.76Hz,1H),6.97(s,1H),6.52-6.47(m,2H),4.01(s,3H),0.06(s,9H),-0.16(s,9H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ152.8,144.5,143.4,140.7,140.7,135.6,130.0,129.5,128.1,122.8,118.7,109.3,104.5,98.9,55.2,-0.2,-0.7.

[0034] The chemical structure of 4-methoxy-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2c) is as follows:

[0035]

[0036] Example 4

[0037] A method for synthesizing 4-methyl-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2d) comprises the following steps:

[0038] In a 25 mL Schlenk reaction tube, 0.2 mmol (66.6 mg) of 1-(2-iodophenyl)-1H-indole, 0.8 mmol hexamethyldisilane (116.8 mg), 4.5 mg palladium acetate, 55.2 mg potassium carbonate, and 2 ml N,N-dimethylformamide were added, and the mixture was stirred at 100° C. for 12 hours. After the reaction (monitored by TLC), the mixture was cooled to room temperature, the reaction solution was filtered, and the organic layer was dried under reduced pressure using a rotary evaporator. Finally, the crude product was purified by column chromatography (petroleum ether unless otherwise specified) to obtain 60 mg of the desired target product (2d) as a colorless oily liquid. After drying under vacuum conditions, the yield was calculated to be 86% and the purity was 99.9%. 1 H NMR (500MHz, CDCl3, δppm) δ7.75 (dd, J=7.25Hz, 1.87Hz, 1H), 7.55-7.48 (m, 2H), 7.25-7.23 (m, 1H), 7.08 (t, J=7. 71Hz,1H),6.95(d,J=6.90Hz,1H),6.92(s,1H),6.73(d,J=8.18Hz,1H),2.68(s,3H),0.14(s,9H),-0.11(s,9H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ144.6,141.8,141.3,140.7,135.5,130.1,129.8,128.5,128.0,127.9,122.2,119.6,110.8,108.6,18.8,-0.1,-0.7.

[0039] Wherein, the chemical structure of 4-methyl-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2d) is as follows:

[0040]

[0041] Example 5

[0042] A method for synthesizing 5-methoxy-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2e) comprises the following steps:

[0043] In a 25 mL Schlenk reaction tube, 0.2 mmol (69.6 mg) of 1-(2-iodophenyl)-1H-indole, 0.8 mmol hexamethyldisilane (116.8 mg), 4.5 mg palladium acetate, 55.2 mg potassium carbonate, and 2 ml N,N-dimethylformamide were added. The mixture was stirred at 100° C. for 12 hours. After the reaction (monitored by TLC), the mixture was cooled to room temperature, the reaction solution was filtered, and the organic layer was dried under reduced pressure using a rotary evaporator. Finally, the crude product was purified by column chromatography (petroleum ether unless otherwise specified) to obtain 65 mg of the desired target product (2e) as a colorless oily liquid. After drying under vacuum conditions, the yield was calculated to be 88% and the purity was 99.9%. 1 H NMR (500MHz, CDCl3, δppm) δ7.80 (dd, J=7.23Hz, 1.92Hz, 1H), 7.59-7.52 (m, 3H), 7.30-7.28 (m, 1H), 7 .06(d,J=8.38Hz,1H),6.89(s,1H),6.86(d,J=8.38Hz,1H),2.57(s,3H),0.18(s,9H),-0.03(s,9H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ144.6,142.1,140.7,140.6,135.5,130.2,129.5,128.5,128.3,128.0,123.8,119.8,111.8,110.5,21.4,-0.2,-0.7.

[0044] The general chemical structure of 5-methoxy-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2e) is:

[0045]

[0046] Example 6

[0047] A method for synthesizing 5-methyl-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2f) comprises the following steps:

[0048] In a 25 mL Schlenk reaction tube, 0.2 mmol (66.6 mg) of 1-(2-iodophenyl)-1H-indole, 0.8 mmol hexamethyldisilane (116.8 mg), 4.5 mg palladium acetate, 55.2 mg potassium carbonate, and 2 ml N,N-dimethylformamide were added, and the mixture was stirred at 100° C. for 12 hours. After the reaction (monitored by TLC), the mixture was cooled to room temperature, the reaction solution was filtered, and the organic layer was dried under reduced pressure using a rotary evaporator. Finally, the crude product was purified by column chromatography (petroleum ether unless otherwise specified) to obtain 57 mg of the desired target product (2f) as a colorless oily liquid. After drying under vacuum conditions, the yield was calculated to be 81% and the purity was 99.9%. 1 H NMR (500MHz, CDCl3, δppm) δ7.76-7.74(m,1H),7.55-7.50(m,3H),7.24(d,J=7.33Hz,1H),7.01( d,J=8.37Hz,1H),6.84(s,1H),6.80(d,J=8.37Hz,1H),2.52(s,3H),0.13(s,9H),-0.09(s,9H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ144.6,142.1,140.7,140.6,135.5,130.2,129.5,128.5,128.3,128.0,123.8,119.8,111.8,110.5,21.4,-0.2,-0.7.

[0049] Wherein, the chemical structure formula of 5-methyl-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2f) is:

[0050]

[0051] Example 7

[0052] A method for synthesizing 2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole-5-carbonitrile (2 g) comprises the following steps:

[0053] In a 25 mL Schlenk reaction tube, 0.2 mmol (68.6 mg) of 1-(2-iodophenyl)-1H-indole, 0.8 mmol hexamethyldisilane (116.8 mg), 4.5 mg palladium acetate, 55.2 mg potassium carbonate, and 2 ml N,N-dimethylformamide were added, and the mixture was stirred at 100° C. for 12 hours. After the reaction (monitored by TLC), the mixture was cooled to room temperature, the reaction solution was filtered, and the organic layer was dried under reduced pressure using a rotary evaporator. Finally, the crude product was purified by column chromatography (petroleum ether unless otherwise specified) to obtain 45 mg of the desired target product (2 g) as a colorless oily liquid. After drying under vacuum conditions, the yield was calculated to be 62% and the purity was 99.9%. 1 H NMR (500MHz, CDCl3, δppm) δ7.99 (s, 1H), 7.72-7.70 (m, 1H), 7.55-7.47 (m, 2H), 7.32 (d, J = 8.40H z,1H),7.16(d,J=7.32Hz,1H),6.89(s,1H),6.87(d,J=8.61Hz,1H),0.07(s,9H),-0.20(s,9H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ145.6,143.2,143.0,140.5,135.9,129.8,129.7,128.7,126.1,124.8,120.9,112.9,111.6,102.5,-0.5,-0.8.

[0054] Wherein, the chemical structure formula of 2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole-5-carbonitrile (2g) is:

[0055]

[0056] Example 8

[0057] A method for synthesizing 5-(benzyloxy)-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2h) comprises the following steps:

[0058] In a 25 mL Schlenk reaction tube, 0.2 mmol (85 mg) of 1-(2-iodophenyl)-1H-indole, 0.8 mmol of hexamethyldisilane (116.8 mg), 4.5 mg of palladium acetate, 55.2 mg of potassium carbonate, and 2 ml of N,N-dimethylformamide were added, and the mixture was stirred at 100° C. for 12 hours. After the reaction (monitored by TLC), the mixture was cooled to room temperature, the reaction solution was filtered, and the organic layer was dried under reduced pressure using a rotary evaporator. Finally, the crude product was purified by column chromatography (petroleum ether unless otherwise specified) to obtain 71 mg of the desired target product (2h) as a colorless oily liquid. After drying under vacuum conditions, the yield was calculated to be 80% and the purity was 99.9%. 1 H NMR(500MHz, CDCl3, δppm) δ7.70(d,J=6.79Hz,1H),7.52-7.47(m,4H),7.41(t,J=7.51Hz,2H),7.36-7.32(m,1H),7 .20(d,J=6.08Hz,2H),6.89(dd,J=8.76Hz,2.09Hz,1H),6.78-6.75(m,2H),5.14(s,2H),0.08(s,9H),-0.14(s,9H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ153.2,144.4,142.8,140.7,137.8,137.7,135.6,130.1,129 .5,128.5,128.2,128.0,127.7,127.6,113.3,111.7,111.5,102.9,70.8,-0.2,-0.7.

[0059] Wherein, the chemical structure of 5-(benzyloxy)-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2h) is as follows:

[0060]

[0061] Example 9

[0062] A method for synthesizing 6-methoxy-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2i) comprises the following steps:

[0063] In a 25 mL Schlenk reaction tube, 0.2 mmol (69.6 mg) of 1-(2-iodophenyl)-1H-indole, 0.8 mmol hexamethyldisilane (116.8 mg), 4.5 mg palladium acetate, 55.2 mg potassium carbonate, and 2 ml N,N-dimethylformamide were added, and the mixture was stirred at 100° C. for 12 hours. After the reaction (monitored by TLC), the mixture was cooled to room temperature, the reaction solution was filtered, and the organic layer was dried under reduced pressure using a rotary evaporator. Finally, the crude product was purified by column chromatography (petroleum ether unless otherwise specified) to obtain 65 mg of the desired target product (2i) as a colorless oily liquid. After drying under vacuum conditions, the yield was calculated to be 89% and the purity was 99.9%. 1 H NMR (500MHz, CDCl3, δppm) δ7.71 (d, J = 6.56Hz, 1H), 7.53-7.47 (m, 3H), 7.21 (d, J = 7. 29Hz,1H),6.79-6.77(m,2H),6.29(s,1H),3.72(s,3H),0.06(s,9H),-0.13(s,9H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ156.6,144.4,142.7,140.9,140.7,135.7,130.2,129.6,128.1,122.4,120.9,112.4,110.1,93.4,55.4,-0.2,-0.7.

[0064] The general chemical structure of 6-methoxy-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2i) is:

[0065]

[0066] Example 10

[0067] A method for synthesizing 6-chloro-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2j) comprises the following steps:

[0068] In a 25 mL Schlenk reaction tube, 0.2 mmol (70.4 mg) of 1-(2-iodophenyl)-1H-indole, 0.8 mmol of hexamethyldisilane (116.8 mg), 4.5 mg of palladium acetate, 55.2 mg of potassium carbonate, and 2 ml of N,N-dimethylformamide were added, and the mixture was stirred at 100° C. for 12 hours. After the reaction (monitored by TLC), the mixture was cooled to room temperature, the reaction solution was filtered, and the organic layer was dried under reduced pressure using a rotary evaporator. Finally, the crude product was purified by column chromatography (petroleum ether unless otherwise specified) to obtain 53 mg of the desired target product (2j) as a colorless oily liquid. After drying under vacuum conditions, the yield was calculated to be 71% and the purity was 99.9%. 1 H NMR (500MHz, CDCl3, δppm) δ7.71 (dd, J=7.21Hz, 1.72Hz, 1H), 7.55-7.46 (m, 3H), 7.20-7.1 7(m,1H),7.06(dd,J=8.36Hz,1.72Hz,1H),6.83-6.81(m,2H),0.07(s,9H),-0.16(s,9H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ143.7,143.3,142.2,140.6,135.8,130.0,129.7,128.4,128.1,126.6,121.1,120.2,112.3,110.7,-0.3,-0.8.

[0069] The general chemical structure of 6-chloro-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2j) is:

[0070]

[0071] Embodiment 11

[0072] A method for synthesizing 7-methoxy-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2k) comprises the following steps:

[0073] In a 25 mL Schlenk reaction tube, 0.2 mmol (69.6 mg) of 1-(2-iodophenyl)-1H-indole, 0.8 mmol hexamethyldisilane (116.8 mg), 4.5 mg palladium acetate, 55.2 mg potassium carbonate, and 2 ml N,N-dimethylformamide were added, and the mixture was stirred at 100° C. for 12 hours. After the reaction (monitored by TLC), the mixture was cooled to room temperature, the reaction solution was filtered, and the organic layer was dried under reduced pressure using a rotary evaporator. Finally, the crude product was purified by column chromatography (petroleum ether unless otherwise specified) to obtain 57 mg of the desired target product (2k) as a colorless oily liquid. After drying under vacuum conditions, the yield was calculated to be 77% and the purity was 99.9%. 1 H NMR (500MHz, CDCl3, δppm) δ8.04 (d, J = 7.29Hz, 1H), 7.89-7.79 (m, 2H), 7.70 (t, J = 8.30Hz, 2H), 7. 46(t,J=7.79Hz,1H),7.26(s,1H),6.97(d,J=7.54Hz,2H),3.93(s,3H),0.49(s,9H),0.30(s,9H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ147.3,147.2,142.7,140.3,134.3,131.1,130.3,129.5,128.1,127.3,119.9,113.2,112.6,102.6,54.7,-0.1,-0.9.

[0074] The general chemical structure of 7-methoxy-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (2k) is:

[0075]

[0076] Example 12

[0077] A method for synthesizing 7-methyl-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (21) comprises the following steps:

[0078] In a 25 mL Schlenk reaction tube, 0.2 mmol (69.6 mg) of 1-(2-iodophenyl)-1H-indole, 0.8 mmol hexamethyldisilane (116.8 mg), 4.5 mg palladium acetate, 55.2 mg potassium carbonate, and 2 ml N,N-dimethylformamide were added, and the mixture was stirred at 100° C. for 12 hours. After the reaction (monitored by TLC), the mixture was cooled to room temperature, the reaction solution was filtered, and the organic layer was dried under reduced pressure using a rotary evaporator. Finally, the crude product was purified by column chromatography (petroleum ether unless otherwise specified) to obtain 51 mg of the desired target product (21) as a colorless oily liquid. After drying under vacuum conditions, the yield was calculated to be 72% and the purity was 99.9%. 1 H NMR (500MHz, CDCl3, δppm) δ7.65 (d, J=7.48Hz, 1H), 7.55 (t, J=8.00Hz, 1H), 7.53-7.49 (m, 1H), 7.4 7-7.41(m,2H),7.03(t,J=7.22Hz,1H),7.00-6.86(m,2H),1.85(s,3H),0.06(s,9H),-0.14(s,9H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ147.0,142.7,141.5,139.7,135.0,130.7,128.8,128.6,128.1,124.9,121.5,119.6,118.7,112.5,19.0,-0.1,-0.8.

[0079] Wherein, the chemical structure formula of 7-methyl-2-(trimethylsilyl)-1-(2-(trimethylsilyl)phenyl)-1H-indole (21) is:

[0080]

Claims

1. A method for efficiently synthesizing a silylated indole compound, characterized in that The following steps are involved: In a reaction vessel, 1-(2-iodophenyl)-1H-indole and hexamethyldisilane were added in a molar ratio of 1:4, 5 mL of solvent was added according to the ratio of 0.5 mmol of 1-(2-iodophenyl)-1H-indole, and then the catalyst Pd(OAc)2 and the base K2CO3 were added, and the added amounts were 10.0% and 200% of the molar amount of 1-(2-iodophenyl)-1H-indole, respectively, DMF 5 mL, air atmosphere, 100 ° C oil bath conditions for 12 hours, cooled to room temperature, added water, extracted with ethyl acetate three times, combined the organic layers, concentrated under reduced pressure, and the product was purified by column chromatography to obtain the product silylated indole compound. The general reaction formula of the synthesis method is: A silylated indole compound, the general chemical structure of which is as follows: Among them, R1 is a hydrogen group or a methyl group; R2 is a hydrogen group, a methyl group or a methoxy group; R3 is a hydrogen group, a methyl group, a methoxy group, a cyano group or a benzyloxy group; R4 is a hydrogen group, a methoxy group or a chloro group; R5 is a hydrogen group, a methyl group or a methoxy group.

2. A method for efficiently synthesizing silylated indole compounds according to claim 1, characterized in that The 1-(2-iodophenyl)-1H-indole is replaced with 1-(2-iodophenyl)-3-methyl-1H-indole, 1-(2-iodophenyl)-4-methoxy-1H-indole, 1-(2-iodophenyl)-4-methyl-1H-indole, 1-(2-iodophenyl)-5-methoxy-1H-indole, 1-(2-iodophenyl)-5-methyl-1H-indole, 1-(2-iodophenyl)-5-cyano-1H-indole, 1-(2-iodophenyl)-5-(benzyloxy)-1H-indole 1-(2-iodophenyl)-6-methoxy-1H-indole, 1-(2-iodophenyl)-6-chloro-1H-indole, 1-(2-iodophenyl)-7-methoxy-1H-indole or 1-(2-iodophenyl)-7-methyl-1H-indole.

3. A method for efficiently synthesizing a silylated indole compound according to claim 1, characterized in that The solvent is N,N-dimethylformamide.

4. The method for efficiently synthesizing a silylated indole compound according to claim 1, characterized in that The column chromatography conditions are: 200-300 mesh silica gel column, and the eluent is petroleum ether.

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