CN112341444A - 3- (2, 3-dihydropyrrole) indole compound and preparation method thereof - Google Patents
3- (2, 3-dihydropyrrole) indole compound and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to the field of organic chemical medicines, and particularly relates to a 3- (2, 3-dihydropyrrole) indole compound and a preparation method thereof. The method provided by the invention comprises the steps of taking a 3-vinyl indole derivative and an aryl triazole compound as raw materials, taking rhodium salt as a catalyst, adding a proper amount of solvent, stirring and reacting at 40-100 ℃ for a certain time, extracting a reaction system for 3 times by using ethyl acetate after the reaction is finished, combining organic phases, and drying by using anhydrous sodium sulfate. Filtering, evaporating the solvent under reduced pressure, adsorbing with silica gel, and separating by column chromatography or recrystallization to obtain the target product; realizes the reaction of 3-vinyl indole and aryl triazole under mild conditions to generate the 3- (2, 3-dihydropyrrole) indole compound.
Description
Technical Field
The invention belongs to the field of organic chemical medicines, and particularly relates to a method for generating a 3- (2, 3-dihydropyrrole) indole compound by reacting 3-vinyl indole with aryl triazole.
Background
The nitrogen-containing heterocycle is widely existed in a plurality of natural products and drug intermediates with high biological activity, wherein the substituted indole is taken as an important nitrogen-containing heterocycle, has wide biological activity and pharmacological activity, and can be used for treating cancers, AIDS and the like. Indole and dihydropyrrole are important alkaloids, and alkaloids containing the two nitrogen-containing heterocycles, such as nertase, peptazine [ Tian.et al, nat. Commun.,2018,9(1):4428 ], have pyrrole and indole structures. All the natural products have quite high biological activity and practical value.
Indole compounds are an extremely important heterocyclic chemical raw material due to unique structures, and a plurality of methods for synthesizing simpler substituted indoles [ Yu Z K et al, Tetrahedron Lett., (2015), 56, 296-.
Alkenyl indole is a very important synthon, and the special structural characteristics of the alkenyl indole enable the compounds to participate in organic reaction in multiple roles. In the asymmetric synthesis methodology, the reactions in which alkenyl indoles participate as diolefins, dienophiles and electrophiles have been reported more often, and the reaction which mainly occurs is an electrocyclic reaction. In 2019, Guo [ Yang X, Zhou Y H, Yang H, et al [ J ]. Organic Letters,2019,21(4):1161-1164 ] and the like report an asymmetric Diels-Alder reaction of 3-alkenyl indole and nitroolefin catalyzed by chiral thiourea, and aryl or alkyl nitroolefin has good adaptability in the reaction. The reaction gave enantioselectivities of up to 93%, but only moderate yields.
The azole compound has wide biological activity and better drug property, so the azole compound becomes an important branch in the medicine. Wherein, the triazole compounds have different biological activities under the condition of having different side chains. The different modifications of the side chains have different effects on the resistance to fungi, both safety and bioavailability.
Disclosure of Invention
In order to further enrich the variety of indole derivatives and screen out more indole ring-containing functional molecules with an opportunity, the invention provides a simple and efficient method for synthesizing a 3- (2, 3-dihydropyrrole) indole product, which adopts a 3-vinyl indole compound and an aryl triazole compound as substrates, can quickly and straightly synthesize the indole product in an organic solvent at 40-100 ℃ under the catalysis of rhodium saltSynthesizing 3- (2, 3-dihydropyrrole) indole compound. All products have the structure1H NMR、13C NMR and ESI-MS. The reaction condition is mild, the substrate adaptability is wide, and indole alkaloid compounds are enriched. And only nitrogen is discharged in the reaction, so that the atom economy is high, the method is environment-friendly and meets the requirement of green chemistry.
The technical scheme of the invention is as follows: 3-vinyl indole compounds and aryl triazole compounds are used as substrates, rhodium salt is used as a catalyst under the condition of argon, finally, a solvent is added to dissolve the rhodium salt to form a reactant solution, and the reactant solution is stirred and reacts at a certain temperature, so that the 3- (2, 3-dihydropyrrole) indole product is obtained by taking the 3-vinyl indole compounds and the aryl triazole compounds as raw materials.
Purifying by a column chromatography separation method after reaction, and purifying the product by taking a mixed solvent of petroleum ether and ethyl acetate as an eluent or an ethyl acetate/petroleum ether system as a recrystallization solvent to obtain a pure 3- (2, 3-dihydropyrrole) indole product.
The synthesis method of the 3- (2, 3-dihydropyrrole) indole comprises the following steps:
wherein R is1Is methyl, methoxy, chlorine or bromine; r2Is hydrogen, benzyl or C2CO2Me; ar is 4-phenyl-1-tolyl, 4- (4-propylphenyl) -1-tolyl, 4- (4- (tert-butyl) phenyl) -1-tolyl, 4- (4-ethoxyphenyl) -1-tolyl, 4- (4-chlorophenyl) -1-tolyl, 4- (4-bromophenyl) -1-tolyl, 1-tosyl-4- (4- (trifluoromethyl) phenyl) -1-tolyl, 4- (3-bromophenyl) -1-tolyl, 4- (m-tolyl) -1-tolyl, 4- (benzo [ d ] d][1,3]Dioxa-5-yl) -1-tosyl, 4- (thiophen-2-yl) -1-tosyl.
The rhodium salt is preferably Rh2(OAc)4、Rh2(PTPA)4、Rh2(cap)4、[Cp*RhCl2]2、Rh2(esp)2Or Rh2(Oct)4The dosage of the one of the (1) and the (b) is 2 to 10 percent of the mole number of the 3-vinyl indole.
The 3-vinyl indole compound comprises the compound with the following structure
The aryl triazole compound comprises a compound with the following structure
The molar number of the aryltriazole compounds is 1-2.5 times of that of the 3-vinyl indole compounds.
The stirring reaction temperature is 40-100 ℃; the stirring reaction time is 3-24 hours.
The reaction solvent is an organic solvent. The organic solvent is preferably one of chloroform, carbon tetrachloride, toluene, dichloromethane, tetrahydrofuran, 1, 4-dioxane, n-hexane or 1, 2-dichloroethane.
The concentration of the 3-vinyl indole in the solution is 0.0125 mol/L-0.1 mol/L.
The 3- (2, 3-dihydropyrrole) indole synthesized by the invention enriches the structure of alkaloid.
Has the advantages that:
1) the method is a novel method for synthesizing 3- (2, 3-dihydropyrrole) indole.
2) The method has mild reaction conditions and small catalyst consumption.
3) The reaction of the invention only releases nitrogen, and the atom economy is high.
Drawings
FIG. 1 is a schematic diagram of the reaction process of example 1.
Detailed Description
The present invention is further described below with reference to examples, but is not limited thereto.
Example 1
Adding 0.1mmol of 1-benzyl-3-vinyl indole 1a and 0.2mmol of 4-phenyl-1-tolyltriazole 2a into a sealed pressure-resistant tube, then adding 0.002mmol of catalyst rhodium acetate, and measuring 2mL of DCE as a solvent to be added into the reaction tube. Placed in an oil bath under the protection of argon and heated to 40 ℃ and stirred for 3 hours, and the TLC point plate is tracked until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times, combining organic phases, drying by using anhydrous sodium sulfate, filtering, removing the solvent from the filtrate by reduced pressure evaporation, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 18mg of yellow solid with the yield of 35%; m.p.112-113 ℃;1H NMR(300MHz,CDCl3)δ:7.47(d,J＝8.3Hz,2H),7.40(d,J＝7.9Hz,1H),7.36～7.27(m,7H),7.24～7.06(m,7H),7.03～6.89(m,3H),5.33(dd,J＝11.0,6.2Hz,1H),5.26(s,2H),3.35(ddd,J＝15.7,11.0,2.0Hz,1H),3.14(ddd,J＝15.8,6.2,1.5Hz,1H),2.27(s,3H)；13C NMR(75MHz,CDCl3)δ:143.2,137.3,137.1,134.7,134.0,129.2,128.8,128.7,127.8,127.1,127.0,126.9,125.8,125.4,124.7,122.4,121.8,119.7,119.5,115.7,109.9,57.6,50.2,39.4,21.5；HRMS(ESI)m/z:calcd for C32H29N2O2S{[M+H]+}505.1944,found 505.1942.
example 2
0.1mmol of 1-benzyl-3-vinyl indole 1a and 0.25mmol of 4-phenyl-1-tolyltriazole 2a are added into a sealed pressure-resistant tube, then 0.010mmol of catalyst rhodium acetate is added, and 2mL of toluene is measured as a solvent and added into the reaction tube. Placed in an oil bath under the protection of argon and heated to 100 ℃ and stirred for 24 hours, and a TLC point plate tracks the reaction to be complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to give 3aa 35mg of a yellow solid with a yield of 70%,
example 3
Adding 0.1mmol of 1-benzyl-3-vinyl indole 1a and 0.1mmol of 4-phenyl-1-tolyltriazole 2a into a sealed pressure-resistant tube, then adding 0.0025mmol of rhodium acetate serving as a catalyst, and measuring 10mL of chloroform serving as a solvent to be added into a reaction tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 21mg of a yellow solid with a yield of 41%.
Example 4
0.1mmol of 1a and 0.12mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 80 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 37mg of a yellow solid with a yield of 75%.
Example 5
0.1mmol of 1a and 0.12mmol of 2a are introduced into a closed pressure vessel, followed by 0.0025mmol of the catalyst Rh2(PTPA)4Then, 2mL of DCE was measured as a solvent and added to the reaction tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 80 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 13mg of a yellow solid in a yield of 27%.
Example 6
0.1mmol of 1a and 0.12mmol of 2a are introduced into a closed pressure vessel, followed by 0.0025mmol of the catalyst Rh2(cap)4Then, 2mL of DCE was measured as a solvent and added to the reaction tube. Placing in an oil bath pan under the protection of argon, heating to 80 deg.C, stirring for 6 hrTLC could track the product to 3aa, but the yield was less than 5%.
Example 7
0.1mmol of 1a and 0.12mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 38mg of a yellow solid in a yield of 77%.
Example 8
0.1mmol of 1a and 0.12mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. Placed in an oil bath under the protection of argon and heated to 100 ℃ and stirred for 6 hours, and a TLC point plate tracks the reaction to be complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 35mg of a yellow solid with a yield of 69%.
Example 9
Adding 0.1mmol of 1a and 0.12mmol of 2a into a sealed pressure-resistant tube, then adding 0.0025mmol of rhodium acetate of catalyst, and measuring 2mL of toluene as solvent to be added into the reaction tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 35.5mg of a yellow solid with a yield of 71%.
Example 10
0.1mmol of 1a and 0.12mmol of 2a are added to a sealed pressure resistant tube, followed by 0.0025mmol of rhodium acetate as a catalyst, and 2mL of DCM is added as a solvent to the reaction tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 14.5mg of a yellow solid with a yield of 29%.
Example 11
0.1mmol of 1a and 0.15mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 38.5mg of a yellow solid in a yield of 77%.
Example 12
0.1mmol of 1a and 0.2mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 40.5mg of a yellow solid with a yield of 81%.
Example 13
0.1mmol of 1a and 0.25mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 37.5mg of a yellow solid with a yield of 75%.
Example 14
Adding 0.1mmol of 1-benzyl-3-vinyl indole 1a and 0.2mmol of 4-phenyl-1-tolyltriazole 2a into a sealed pressure-resistant tube, then adding 0.0025mmol of rhodium acetate serving as a catalyst, and measuring 1mL of dichloromethane serving as a solvent to be added into the reaction tube. Placed in an oil bath under the protection of argon and heated to 40 ℃ and stirred for 6 hours, and the TLC point plate is tracked until the reaction is complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 10mg of a yellow solid with a yield of 21%.
Example 15
Adding 0.1mmol of 1-benzyl-3-vinyl indole 1a and 0.2mmol of 4-phenyl-1-tolyltriazole 2a into a sealed pressure-resistant tube, then adding 0.010mmol of catalyst rhodium acetate, and measuring 2mL of carbon tetrachloride as a solvent to be added into the reaction tube. Placed in an oil bath under the protection of argon and heated to 80 ℃ and stirred for 16 hours, and the TLC point plate is tracked until the reaction is complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 23mg of a yellow solid with a yield of 45%.
Example 16
Adding 0.1mmol of 1-benzyl-3-vinyl indole 1a and 0.2mmol of 4-phenyl-1-tolyl triazole 2a into a sealed pressure-resistant pipe, and adding 0.010mmol of catalyst Rh2(PTPA)4Then, 2mL of DCE was measured as a solvent and added to the reaction tube. Placed in an oil bath under the protection of argon and heated to 100 ℃ and stirred for 24 hours, and a TLC point plate tracks the reaction to be complete. Cooling to room temperature after reaction, sequentially adding EA for extraction for 3 times, combining organic phases, drying with anhydrous sodium sulfate, filtering, and filtering to obtain filtrateThe solvent was evaporated under pressure and the residue was isolated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to give 3aa 12mg of a yellow solid in 23% yield.
Example 17
Adding 0.1mmol of 1-benzyl-3-vinyl indole 1a and 0.2mmol of 4-phenyl-1-tolyl triazole 2a into a sealed pressure-resistant pipe, and adding 0.010mmol of catalyst Rh2(esp)2Then, 2mL of DCE was measured as a solvent and added to the reaction tube. Placed in an oil bath under the protection of argon and heated to 100 ℃ and stirred for 24 hours, and a TLC point plate tracks the reaction to be complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 15mg of a yellow solid with a yield of 29%.
Example 18
Adding 0.1mmol of 1-benzyl-3-vinyl indole 1a and 0.2mmol of 4-phenyl-1-tolyl triazole 2a into a sealed pressure-resistant pipe, and adding 0.010mmol of catalyst Rh2(Oct)4Then, 2mL of DCE was measured as a solvent and added to the reaction tube. Placed in an oil bath under the protection of argon and heated to 100 ℃ and stirred for 24 hours, and a TLC point plate tracks the reaction to be complete. After the reaction was completed, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3aa 14mg of a yellow solid in a yield of 27%.
Example 19
0.1mmol of 1-benzyl-3-vinyl indole 1a and 0.2mmol of 4- (4-propylphenyl) -1-tolyl-1, 2, 3-triazole 2b were added to a sealed pressure-resistant tube, followed by addition of 0.0025mmol of rhodium acetate as a catalyst, and then 2mL of DCE was added as a solvent to the reaction tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times, combining organic phases, drying with anhydrous sodium sulfate, filtering, removing the solvent from the filtrate through reduced pressure evaporation, and obtaining a residueSeparating by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain yellow solid 3ab 29mg, yield 54%, m.p.100-101 deg.C;1H NMR(400MHz,CDCl3)δ:7.51(d,J＝8.1Hz,2H),7.43(d,J＝7.9Hz,1H),7.38～7.26(m,5H),7.24～7.16(m,5H),7.15～7.08(m,3H),7.02(d,J＝8.1Hz,2H),7.00～6.93(m,1H),5.35～5.31(m,1H),5.28(s,2H),3.33(dd,J＝13.9,11.3Hz,1H),3.13(dd,J＝15.8,5.8Hz,1H),2.59(t,J＝7.6Hz,2H),2.30(s,3H),1.66(dd,J＝15.0,7.5Hz,2H),0.97(t,J＝7.3Hz,3H)；13C NMR(75MHz,CDCl3)δ:143.2,141.7,137.3,137.1,134.6,131.3,129.2,128.8,128.75,127.72,127.1,127.0,125.8,124.6,122.7,121.8,119.7,119.5,115.9,109.9,57.6,50.1,39.5,37.8,24.6,21.5,13.9；HRMS(ESI)m/z:calcd for C35H35N2O2S{[M+H]+}547.2414,found 547.2415.
example 20
0.1mmol of 1a and 0.2mmol of 4- (4- (tert-butyl) phenyl) -1-tolyl-1, 2, 3-triazole 2c were added to a closed pressure-resistant tube, followed by 0.0025mmol of rhodium acetate as a catalyst, and 2mL of DCE was added as a solvent to the reaction tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times, combining organic phases, drying by using anhydrous sodium sulfate, filtering, removing the solvent from the filtrate by reduced pressure evaporation, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3ac 33mg of yellow solid, wherein the yield is 59 percent, and the m.p.90-91 ℃;1H NMR(400MHz,CDCl3)δ:7.56(dd,J＝8.1,2.0Hz,2H),7.48(dd,J＝7.7,3.2Hz,1H),7.44～7.39(m,2H),7.38～7.30(m,5H),7.28～7.20(m,4H),7.16(s,2H),7.08～6.98(m,3H),5.40～5.32(m,1H),5.30(s,2H),3.37(m,1H),3.23～3.12(m,1H),2.33(s,3H),1.38(s,9H)；13C NMR(75MHz,CDCl3)δ:150.2,143.2,137.3,137.1,134.6,131.1,129.2,128.8,127.7,127.2,127.04,127.01,125.8,125.6,124.8,124.5,122.6,121.9,119.8,119.5,115.9,109.9,57.6,50.2,39.5,34.6,31.3,21.5；HRMS(ESI)m/z:calcd for C36H37N2O2S{[M+H]+}561.2570,found 561.2568.
example 21
0.1mmol of 1a and 0.2mmol of 4- (4-ethoxyphenyl) -1-tolyl-1, 2, 3-triazole 2d were added to a closed pressure-resistant tube, followed by 0.0025mmol of rhodium acetate as a catalyst, and 2mL of DCE was added as a solvent to the reaction tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times, combining organic phases, drying by using anhydrous sodium sulfate, filtering, removing the solvent from the filtrate by reduced pressure evaporation, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain yellow solid 3ad 23mg, the yield is 42%, and m.p.106-108 ℃;1H NMR(400MHz,CDCl3)δ:7.49(d,J＝8.1Hz,2H),7.41(d,J＝7.9Hz,1H),7.33～7.27(m,2H),7.26～7.19(m,4H),7.19(m,3H),7.09～7.12(t,J＝7.6Hz,1H),7.02～6.90(m,4H),6.83(d,J＝8.6Hz,2H),5.27(dd,J＝10.9,5.9Hz,1H),5.22(s,2H),4.09～3.91(m,2H),3.26(dd,J＝14.7,12.0Hz,1H),3.06(dd,J＝15.7,5.8Hz,1H),2.26(s,3H),1.39(t,J＝7.0Hz,3H)；13C NMR(75MHz,CDCl3)δ:158.2 143.2,137.4,137.1,134.6,129.2,128.8,127.7,127.2,127.1,127.0,126.4,126.0,125.8,123.5,122.7,121.9,119.7,119.5,116.0,114.7,110.0,63.6,57.5,50.2,39.6,21.5,14.9；HRMS(ESI)m/z:calcd for C34H33N2O2S{[M+H]+}549.2206,found 549.2207.
example 22
0.1mmol of 1a and 0.2mmol of 4- (4-chlorophenyl) -1-tolyl-1, 2, 3-triazole 2e were added to a sealed pressure-resistant tube, followed by 0.0025mmol of rhodium acetate as a catalyst, and 2mL of DCE was added as a solvent to the reaction tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times in sequence, combining organic phases, drying by using anhydrous sodium sulfate, filtering, removing the solvent from the filtrate by reduced pressure evaporation, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3ae 41mg of yellow solid, wherein the yield is 76%, and m.p.117-118 ℃;1H NMR(400MHz,CDCl3)δ:7.49(d,J＝8.1Hz,2H),7.42～7.30(m,6H),7.28(s,2H),7.25～7.12(m,6H),6.99(d,J＝8.1Hz,3H),5.41(dd,J＝11.1,6.2Hz,1H),5.28(s,2H),3.44～3.29(m,1H),3.15(dd,J＝15.7,6.1Hz,1H),2.30(s,3H)；13C NMR(75MHz,CDCl3)δ:143.3,137.3,137.1,134.8,132.5,132.4,129.2,128.9,128.8,127.8,127.2,127.07,127.05,126.1,125.9,125.7,121.9,121.0,119.7,119.6,115.4,110.0,57.8,50.2,39.4,21.5；HRMS(ESI)m/z:calcd for C32H28 35ClN2O2S{[M+H]+}539.1555,found 539.1557.
example 23
0.1mmol of 1a and 0.2mmol of 4- (4-bromophenyl) -1-tolyl-1, 2, 3-triazole 2f were added to a closed pressure-resistant tube, followed by 0.0025mmol of rhodium acetate as a catalyst, and 2mL of DCE was measured as a solvent and added to the reaction tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times in sequence, combining organic phases, drying by using anhydrous sodium sulfate, filtering, evaporating the solvent from the filtrate under reduced pressure, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain yellow solid 3af 40mg, the yield is 69%, and m.p.124-125 ℃;1H NMR(300MHz,CDCl3)δ:7.46-7.39(m,3H),7.34～7.24(m,7H),7.23～7.18(m,2H),7.15～7.08(m,4H),7.00(d,J＝8.7Hz,1H),6.95(d,J＝8.0Hz,2H),5.26(dd,J＝11.0,6.6Hz,1H),5.18(s,2H),3.30(ddd,J＝15.7,11.0,2.0Hz,1H),3.01(ddd,J＝15.8,6.7,1.6Hz,1H),2.24(s,3H)；13C NMR(75MHz,CDCl3)δ:143.4,136.8,135.7,134.7,133.8,129.3,129.0,128.7,128.4,128.0,127.5,127.1,127.0,125.5,124.74,124.69,122.3,122.2,115.2,113.0,111.5,57.5,50.4,39.7,21.5；HRMS(ESI)m/z:calcd for C32H28 79BrN2O2S{[M+H]+}583.1049,found 539.1050.
example 24
0.1mmol of 1a and 0.2mmol of 1-tosyl 4- (4- (trifluoromethyl) phenyl) -1-tolyl-1, 2, 3-triazole are added to a pressure-tight tube, 2g is added, 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured as a solvent and added to the reactionA tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction, the reaction mixture was cooled to room temperature, EA was sequentially added thereto and extracted 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the solvent was removed from the filtrate by evaporation under reduced pressure, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:30) to give 49mg of brown liquid 3ag with a yield of 86%,1H NMR(300MHz,CDCl3)δ:7.43(d,J＝8.3Hz,2H),7.37～7.30(m,2H),7.29～7.27(m,2H),7.25～7.22(m,3H),7.21～7.05(m,7H),6.96～6.88(m,3H),5.35(dd,J＝11.1,6.2Hz,1H),5.22(s,2H),3.37～3.25(m,1H),3.14～3.05(m,1H),2.24(s,3H)；13C NMR(75MHz,CDCl3)δ:143.3,137.6,137.2,137.1,134.9,129.1,128.9,128.6,128.2,127.8,127.75,127.3,127.1,126.9,125.7,125.6,124.6,121.9,120.2,119.6,115.0,110.0,57.9,50.2,39.2,21.4；HRMS(ESI)m/z:calcd for C33H28F3N2O2S{[M+H]+}573.1818,found 539.1821.
example 25
0.1mmol of 1a and 0.2mmol of 4- (1-tolyl-1, 2, 3-triazol-4-yl) benzonitrile were added to a closed pressure vessel for 2h, followed by addition of 0.0025mmol of rhodium acetate as a catalyst, and 2mL of DCE was added as a solvent to the reaction vessel. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, sequentially adding EA for extraction for 3 times, combining organic phases, drying by using anhydrous sodium sulfate, filtering, evaporating the solvent from the filtrate under reduced pressure, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether: 1:20) to obtain a yellow solid 3ah 44mg with the yield of 83 percent and the yield of 112-;1H NMR(300MHz,CDCl3)δ:7.62～7.53(m,2H),7.44～7.28(m,8H),7.27～7.21(m,2H),7.20～7.15(m,3H),7.11～7.04(m,1H),6.92～6.78(m,3H),5.44(dd,J＝11.3,6.6Hz,1H),5.24(s,2H),3.40(ddd,J＝15.6,11.3,1.8Hz,1H),3.16(ddd,J＝15.7,6.6,1.5Hz,1H),2.21(s,3H)；13C NMR(75MHz,CDCl3)δ:143.3,138.8,137.08,137.1,134.9,132.9,132.4,130.6,129.0,128.9,127.9,127.4,127.1,126.8,126.5,125.6,124.7,122.0,119.6,119.4,114.6,110.0,109.5,58.0,50.2,39.0,21.4；HRMS(ESI)m/z:calcd for C33H28N3O2S{[M+H]+}530.1897,found 530.1899.
example 26
0.1mmol of 1a and 0.2mmol of 4- (3-bromophenyl) -1-tolyl-1, 2, 3-triazole 2i were added to a closed pressure-resistant tube, followed by 0.0025mmol of rhodium acetate as a catalyst, and 2mL of DCE was measured as a solvent and added to the reaction tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times in sequence, combining organic phases, drying by using anhydrous sodium sulfate, filtering, removing the solvent from the filtrate by reduced pressure evaporation, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain yellow solid 3ai 45mg, the yield is 77%, and m.p. is.125-126 ℃;1H NMR(300MHz,CDCl3)δ:7.45～7.37(m,3H),7.35～7.24(m,5H),7.23～7.12(m,7H),7.11～7.03(m,1H),6.98～6.85(m,3H),5.34(dd,J＝11.1,6.3Hz,1H),5.20(s,2H),3.29(ddd,J＝15.7,11.1,2.0Hz,1H),3.07(ddd,J＝15.8,6.3,1.5Hz,1H),2.21(s,3H)；13C NMR(75MHz,CDCl3)δ:143.3,137.3,137.1,136.3,134.8,130.2,129.6,129.2,128.9,127.8,127.5,127.3,127.1,127.0,126.8,125.7,123.1,122.9,122.0,120.5,119.7,119.6,115.3,110.0,57.8,50.2,39.3,21.5；HRMS(ESI)m/z:calcd for C32H28BrN2O2S{[M+H]+}583.1049,found 583.1050.
example 27
0.1mmol of 1a and 0.2mmol of 4- (m-tolyl) -1-tolyl-1, 2, 3-triazole 2j were added to a pressure-tight tube, followed by 0.0025mmol of rhodium acetate as a catalyst, and 2mL of DCE was added as a solvent to the reaction tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times in sequence, combining organic phases, drying by using anhydrous sodium sulfate, filtering, removing the solvent from the filtrate by reduced pressure evaporation, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain yellow solid 3aj 29mg, the yield is 56%, and m.p. is 101-102 ℃;1H NMR(400MHz,CDCl3)δ:7.47(d,J＝8.1Hz,2H),7.39(d,J＝7.9Hz,1H),7.36～7.25(m,3H),7.22～7.14(m,5H),7.13～7.06(m,4H),7.03(d,J＝7.4Hz,1H),7.00～6.91(m,3H),5.31(dd,J＝11.0,6.0Hz,1H),5.24(s,2H),3.32(dd,J＝14.7,12.1Hz,1H),3.11(dd,J＝15.8,6.0Hz,1H),2.33(s,3H),2.26(s,3H)；13C NMR(75MHz,CDCl3)δ:143.2,138.2,137.3,137.1,134.7,133.9,129.2,128.8,128.6,127.8,127.7,127.11,127.08,127.0,125.8,125.4,125.3,122.6,121.9,121.8,119.7,119.5,115.8,110.0,57.6,50.2,39.5,21.5,21.4；HRMS(ESI)m/z:calcd for C33H31N2O2S{[M+H]+}519.2101,found 519.2102.
example 28
0.1mmol of 1a and 0.2mmol of 2k are added into a sealed pressure-resistant tube, then 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times in sequence, combining organic phases, drying by using anhydrous sodium sulfate, filtering, removing the solvent from the filtrate by reduced pressure evaporation, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain yellow solid 3ak 28mg, the yield is 51%, and m.p.117-118 ℃;1H NMR(300MHz,CDCl3)δ:7.47(d,J＝8.3Hz,2H),7.38(d,J＝7.9Hz,1H),7.32～7.29(m,1H),7.29～7.27(m,1H),7.22(s,1H),7.19(s,1H),7.17～7.08(m,4H),7.00～6.91(m,4H),6.85(d,J＝1.5Hz,1H),6.76～6.64(m,2H),5.94(s,2H),5.28(dd,J＝11.0,6.1Hz,1H),5.23(s,2H),3.25(ddd,J＝15.6,11.0,2.0Hz,1H),3.13～2.94(ddd,J＝15.7,6.1,1.4Hz,1H),2.26(s,3H)；13C NMR(75MHz,CDCl3)δ:148.0,146.8,143.2,137.3,137.1,134.6,129.2,128.8,128.2,127.8,127.14,127.09,127.02,125.8,124.2,122.6,121.9,119.7,119.5,118.4,115.8,110.0,108.4,105.1,101.2,57.6,50.2,39.7,21.5；HRMS(ESI)m/z:calcd for C33H29N2O4S{[M+H]+}549.1843,found 549.1845.
example 29
Adding 0.1mmol of 1a and 0 in a sealed pressure-resistant pipe2l of 2mmol of rhodium acetate catalyst were added in a subsequent 0.0025mmol and 2mL of DCE were metered in as solvent into the reaction tube. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times in sequence, combining organic phases, drying by using anhydrous sodium sulfate, filtering, evaporating the solvent from the filtrate under reduced pressure, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3al 33mg of yellow solid, wherein the yield is 65 percent, and the m.p.104-105 ℃;1H NMR(300MHz,CDCl3)δ:7.47(d,J＝8.3Hz,2H),7.39(d,J＝7.9Hz,1H),7.32～7.25(m,3H),7.25～7.19(m,2H),7.17(d,J＝7.3Hz,3H),7.14～7.04(m,2H),7.00～6.91(m,4H),6.86(dd,J＝2.7,1.0Hz,1H),5.27(dd,J＝11.0,6.2Hz,1H),5.22(s,2H),3.28(ddd,J＝15.6,11.0,2.0Hz,1H),3.06(ddd,J＝15.7,6.2,1.4Hz,1H),2.26(s,3H)；13C NMR(75MHz,CDCl3)δ:143.3,137.3,137.1,135.6,134.7,129.3,128.9,127.7,127.2,127.1,127.0,126.4,125.8,125.1,124.9,121.9,119.7,119.5,119.3,118.9,115.7,110.0,57.5,50.2,40.0,21.5；HRMS(ESI)m/z:calcd for C30H27N2O2S2{[M+H]+}511.1508,found 511.1507.
example 30
0.1mmol of 1-benzyl-5-methoxy-3-vinyl indole 1b and 0.2mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of catalyst rhodium acetate is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times in sequence, combining organic phases, drying by using anhydrous sodium sulfate, filtering, evaporating the solvent from the filtrate under reduced pressure, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3ba 21mg of yellow solid, wherein the yield is 40%, and the m.p.106-107 ℃;1H NMR(300MHz,CDCl3)δ:7.44(d,J＝8.3Hz,2H),7.36～7.27(m,7H),7.25～7.20(m,1H),7.19(s,2H),7.17～7.13(m,2H),7.05(d,J＝8.8Hz,1H),6.93(d,J＝8.0Hz,2H),6.79(d,J＝2.3Hz,1H),6.73(dd,J＝8.9,2.4Hz,1H),5.36(dd,J＝11.0,5.6Hz,1H),5.21(s,2H),3.58(s,3H),3.43～3.29(m,1H),3.18～3.06(m,1H),2.26(s,3H)；13C NMR(75MHz,CDCl3)δ:153.8,143.1,137.3,135.1,133.9,132.3,129.1,128.8,128.7,127.82,127.76,127.99,126.96,126.1,125.4,124.6,122.4,115.0,111.9,110.7,101.7,57.8,55.5,50.4,39.1,21.4；HRMS(ESI)m/z:calcd for C33H31N2O2S{[M+H]+}535.2050,found 535.2051.
example 31
0.1mmol of 1-benzyl-5-bromo-3-vinyl indole 1c and 0.2mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times in sequence, combining organic phases, drying by using anhydrous sodium sulfate, filtering, evaporating the solvent from the filtrate under reduced pressure, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain yellow solid 3ca 39mg, the yield is 67%, and m.p.122-123 ℃;1H NMR(400MHz,CDCl3)δ7.37–7.30(m,2H),7.28–7.13(m,8H),7.13–7.07(m,4H),7.05–6.98(m,2H),6.88–6.79(m,3H),5.33–5.21(m,1H),5.17(s,2H),3.39–3.17(m,1H),3.07–2.97(m,1H),2.17(s,3H).；13C NMR(100MHz,CDCl3)δ142.7,136.8,136.6,134.2,133.5,128.7,128.3,128.2,127.3,126.6,126.53,126.45,125.3,125.0,124.2,121.9,121.4,119.2,119.0,115.2,109.4,57.2,49.7,38.9,21.0.HRMS(ESI)m/z:calcd for C32H28 79BrN2O2S{[M+H]+}582.0977，found 582.0978.
example 32
0.1mmol of 1-benzyl-6-methyl-3-vinyl indole 1d and 0.2mmol of 2a are added into a sealed pressure-resistant pipe, then 0.0025mmol of catalyst rhodium acetate is added, and 2mL of DCE is measured and added into a reaction pipe as a solvent. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA in sequence for extraction for 3 times, combining organic phases, and usingDried over sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove the solvent, and the residue was separated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to give 3da 29mg of a yellow solid, yield 56%, m.p.98-100 ℃;1H NMR(300MHz,CDCl3)δ:7.45(d,J＝8.3Hz,2H),7.34～7.25(m,7H),7.25～7.19(m,2H),7.18～7.08(m,4H),6.96(d,J＝7.8Hz,3H),6.75(dt,J＝13.5,6.8Hz,1H),5.29(dd,J＝11.0,6.2Hz,1H),5.20(s,2H),3.31(ddd,J＝15.7,11.0,2.0Hz,1H),3.11(ddd,J＝15.8,6.2,1.5Hz,1H),2.37(s,3H),2.26(s,3H)；13C NMR(75MHz,CDCl3)δ:143.2,137.6,137.5,134.8,134.0,131.8,129.2,128.8,128.7，127.7,127.1,127.0,126.9,126.5,125.5,124.7,123.6,122.3,121.3,119.4,115.6,109.8,57.7,49.9,39.4,21.9,21.5；HRMS(ESI)m/z:calcd for C33H31N2O2S{[M+H]+}519.2101,found 519.2102.
example 33
0.1mmol of 1-benzyl-6-chloro-3-vinyl indole 1e and 0.2mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of catalyst rhodium acetate is added, and 2mL of DCE is measured and added into a reaction tube as a solvent. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction is finished, cooling to room temperature, adding EA to extract for 3 times in sequence, combining organic phases, drying by using anhydrous sodium sulfate, filtering, evaporating the solvent from the filtrate under reduced pressure, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:20) to obtain 3EA 40mg of yellow solid, wherein the yield is 74%, and the m.p. is 121-122 ℃;1H NMR(300MHz,CDCl3)δ:7.40(d,J＝8.3Hz,2H),7.38～7.28(m,7H),7.26～7.24(m,1H),7.24～7.20(m,1H),7.19～7.14(m,4H),7.12(t,J＝1.7Hz,1H),6.93(d,J＝8.0Hz,2H),6.87(dd,J＝8.5,1.8Hz,1H),5.30(dd,J＝11.1,6.2Hz,1H),5.20(s,2H),3.35(ddd,J＝15.8,11.1,2.0Hz,1H),3.07(ddd,J＝15.8,6.2,1.6Hz,1H),2.27(s,3H)；13C NMR(75MHz,CDCl3)δ:143.3,137.5,136.6,134.8,133.8,129.1,129.0,128.7,128.03,128.01,127.9,127.0,126.95,125.4,124.6,124.4,122.0,120.7,120.2,115.8,109.8,57.4,50.2,39.4,21.4；HRMS(ESI)m/z:calcd for C32H2835ClN2O2S{[M+H]+}539.1555,found 539.1557.
example 34
0.1mmol of 1d and 0.2mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. Placing the mixture in an oil bath kettle under the protection of argon, heating the mixture to 60 ℃, stirring the mixture for 6 hours, and tracking the mixture by a TLC point plate until the reaction is complete. After the reaction, cooling to room temperature, adding EA sequentially to extract for 3 times, combining the organic phases, drying with anhydrous sodium sulfate, filtering, evaporating the solvent from the filtrate under reduced pressure, and separating the residue by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:30) to obtain 33mg of yellow solid 3la with a yield of 65%; 1H NMR (400MHz, CDCl3) δ 7.54(t, J ═ 8.1Hz,2H), 7.51-7.43 (m,3H), 7.42-7.32 (m,3H), 7.31-7.27 (m,3H), 7.25-7.16 (m,4H), 7.06-6.96 (m,3H),5.46(dd, J ═ 11.1,6.2Hz,1H),5.27(s,2H), 3.48-3.28 (m,1H), 3.22-3.13 (m,1H),2.31(s,3H).13C NMR (100MHz, CDCl3) δ 143.4,137.4,137.2,134.9,133.1,131.8,129.3,128.9,127.8,127.4,127.2,127.1,126.3126.2,125.8,122.0,121.0,120.5,119.8,119.7,115.4,110.1, 57.9,50.2,39.4, 21.5; HRMS (ESI) M/z calcd for C32H28N2O2S { [ M + H ] + }505.1944, found505.1945.
Example 35
0.1mmol of 1-benzyl-7-chloro-3-vinyl indole 1f and 0.2mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of catalyst rhodium acetate is added, and 2mL of DCE is measured and added into a reaction tube as a solvent. The product 3fa was followed by TLC with stirring for 6 hours under argon protection in an oil bath heated to 60 deg.C, but the yield was less than 5%.
Example 36
Adding 1g of 0.1mmol of 1-benzyl-7-methyl-3-vinyl indole and 0.2mmol of 2a into a sealed pressure-resistant tube, then adding 0.0025mmol of rhodium acetate serving as a catalyst, and measuring 2mL of DCE serving as a solvent to be added into the reaction tube. The product 3ga was followed by TLC heating to 60 ℃ under argon protection for 6 hours with stirring, but the yield was less than 5%.
Example 37
0.1mmol of 1h and 0.2mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. The product was stirred for 6 hours in an oil bath heated to 60 ℃ under argon blanket and the TLC tracked to 3ha, but the yield was less than 5%.
Example 38
0.1mmol of 1i and 0.2mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. The product 3ia was followed by TLC with stirring for 6 hours under argon protection in an oil bath heated to 60 deg.C, but the yield was less than 5%.
Example 39
0.1mmol of 1j and 0.2mmol of 2a are added into a sealed pressure-resistant tube, then 0.0025mmol of rhodium acetate catalyst is added, and 2mL of DCE is measured and added into the reaction tube as a solvent. The TLC was able to follow the product 3ja when placed in an oil bath under argon blanket and heated to 60 deg.C with stirring for 6 hours, but the yield was less than 5%.
Claims (10)
1. A 3- (2, 3-dihydropyrrole) indole compound characterized in that: the structural formula of the compound is shown as the following formula:
wherein R is1Is methyl, methoxy, chlorine or bromine; r2Is hydrogen, benzyl or C2CO2Me; ar is 4-phenyl-1-tolyl, 4- (4-propylphenyl) -1-tolyl, 4- (4- (tert-butyl) phenyl) -1-tolyl, 4- (4-ethoxyphenyl) -1-tolyl, 4- (4-chlorophenyl) -1-tolyl, 4- (4-bromophenyl) -1-tolyl, 1-tosyl-4- (4- (trifluoromethyl) phenyl) -1-tolyl, 4- (3-bromophenyl) -1-tolyl, 4- (m-tolyl) -1-tolyl, 4- (benzo [ d ] d][1,3]Dioxa-5-yl) -1-tosyl or 4- (thiophen-2-yl) -1-tosyl.
2. A process for preparing a 3- (2, 3-dihydropyrrole) indole compound according to claim 1, which comprises: the preparation method comprises the following steps: under the condition of argon, adding 3-vinyl indole compounds and aryl triazole compounds, adding rhodium salt catalyst, finally adding solvent, stirring for reaction, separating and purifying to obtain 3- (2, 3-dihydropyrrole) indole compounds.
3. A process for preparing a 3- (2, 3-dihydropyrrole) indole compound according to claim 2, which comprises: the molar number of the aryltriazole compounds is 1-2.5 times of that of the 3-vinyl indole compounds.
4. A process for preparing a 3- (2, 3-dihydropyrrole) indole compound according to claim 2, which comprises: the 3-vinyl indole compound comprises:
5. a process for preparing a 3- (2, 3-dihydropyrrole) indole compound according to claim 2, which comprises: the aryl triazole compound comprises:
6. a process for preparing a 3- (2, 3-dihydropyrrole) indole compound according to claim 2, which comprises: the rhodium salt catalyst is Rh2(OAc)4、Rh2(PTPA)4、Rh2(cap)4、[Cp*RhCl2]2、Rh2(esp)2Or Rh2(Oct)4The dosage of the one of the (1) and the (b) is 2 to 10 percent of the mole number of the 3-vinyl indole compound.
7. A process for preparing a 3- (2, 3-dihydropyrrole) indole compound according to claim 2, which comprises: the solvent is one of trichloromethane, carbon tetrachloride, toluene, dichloromethane, tetrahydrofuran, 1, 4-dioxane, n-hexane or 1, 2-dichloroethane.
8. A process for preparing a 3- (2, 3-dihydropyrrole) indole compound according to claim 2, which comprises: the stirring reaction temperature is 40-100 ℃; the stirring reaction time is 3-24 hours.
9. A process for preparing a 3- (2, 3-dihydropyrrole) indole compound according to claim 2, which comprises: the concentration of the 3-vinyl indole compound in the solution is 0.0125 mol/L-0.1 mol/L.
10. A process for preparing a 3- (2, 3-dihydropyrrole) indole compound according to claim 2, which comprises: the separation and purification method is column chromatography, thin layer chromatography or recrystallization; the eluent used for column chromatography is a mixed solution of ethyl acetate and petroleum ether.
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