A bipyrrole axially chiral phase transfer catalyst and its preparation method
By designing a quaternary ammonium salt phase transfer catalyst with an axially chiral bipyrrole framework, the problem of the single framework structure of existing catalysts has been solved, enabling more precise chiral control and enhanced catalytic activity, and providing a novel and efficient phase transfer catalytic system.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- FUZHOU UNIV
- Filing Date
- 2026-04-13
- Publication Date
- 2026-05-26
AI Technical Summary
Existing quaternary ammonium salt phase transfer catalysts have simple framework structures, limited chiral control capabilities and substrate applicability, and insufficient innovative research on axial chiral phase transfer catalysts, resulting in insufficient catalytic activity.
A quaternary ammonium salt phase transfer catalyst with an axially chiral bipyrrole framework was designed by introducing a C2-symmetric bipyrrole framework. The catalyst utilizes the reaction of bromide with a tertiary amine to generate the quaternary ammonium salt, without producing carbocation intermediates during the reaction, thus improving catalytic activity.
This study expands the types of catalyst frameworks, optimizes the catalytic chiral environment, enhances catalytic activity, and provides a highly efficient design strategy for phase transfer catalytic systems.
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of axially chiral phase transfer catalysis technology, specifically relating to a bipyrrole axially chiral phase transfer catalyst, its preparation method, and its application. Background Technology
[0002] Phase transfer catalysts are a class of catalysts with significant application value in organic synthesis. Their core mechanism of action is to promote the efficient transfer of reactant molecules between two immiscible phases, thereby significantly improving reaction rates and target product yields, providing a feasible pathway for the efficient synthesis of complex organic molecules. Phase transfer catalysts can mediate cross-phase transfer of reactants between aqueous and organic phases, achieving dual optimization of reaction rates and product yields. Furthermore, the reactants can be efficiently separated from the system after reaction by washing or extraction. Among them, quaternary ammonium salt phase transfer catalysts are widely used in organic synthesis due to their good thermal stability, low cost, simple preparation, low toxicity, and excellent catalytic performance. Asymmetric catalysis is a key means of constructing chiral compounds, and the development of economical, green, and efficient asymmetric phase transfer catalysts is of significant research value. However, the existing catalyst framework structures are relatively simple, and there are still certain limitations in terms of chiral control ability and substrate applicability. In addition, current innovative research on axial chiral phase transfer catalysts is still relatively limited, and many challenges remain in expanding framework types, optimizing chiral environments, and improving catalytic activity. Therefore, designing and developing axially chiral phase transfer catalysts with novel framework structures that enable more precise chiral control is of great significance for promoting the further development of asymmetric catalysis technology. Summary of the Invention
[0003] The purpose of this invention is to provide a quaternary ammonium salt phase transfer catalyst with an axially chiral bipyrrole framework, its preparation method and application. Its core structure is based on the axially chiral bipyrrole framework. By introducing a bipyrrole framework with C2 symmetry, the types of quaternary ammonium salt phase transfer catalyst frameworks are expanded, providing a new approach to optimizing the catalytic chiral environment and enhancing the catalytic activity of quaternary ammonium salt phase transfer catalysts.
[0004] To achieve the above objectives, the present invention adopts the following technical solution: A method for preparing a quaternary ammonium salt phase-transfer catalyst with an axially chiral bipyrrole framework, comprising compound 1 ( S )-1,9-diphenyl-5-(( S Diethyl 1-(1-phenylethyl)-5,6-dihydro-4H-dipyrrolo[1,2-b:2',1'-g][1,2,5]triazacyclohepta-3,7-dicarboxylate is used as a key precursor. This precursor acts as a nucleophile, attacking the carbon atom with lower electron cloud density in the bromide (R-Br) to replace the bromide ion and generate a quaternary ammonium salt. The synthetic route is shown below: .
[0005] Furthermore, the reaction was performed using the Schlenk technique to ensure the absence of water and oxygen in the system. Compound 1 was dissolved in acetonitrile as the organic solvent, and compound 2 was added at room temperature. The mixture was then heated to 60°C to react. The reaction was monitored by thin-layer chromatography (TLC). After the reaction was complete, the reaction solution was concentrated under reduced pressure using a rotary evaporator. The concentrated crude product was then separated and purified using silica gel column chromatography to obtain compound 3.
[0006] The quaternary ammonium salt phase-transfer catalyst with an axially chiral bipyrrole skeleton prepared by the above method was used in the [3+2] cycloaddition reaction of 2-(morpholine-4-carbonyl)allyl benzenesulfinate with phenylacryloylbenzene.
[0007] The beneficial effects of this invention are as follows: It utilizes the reaction of bromide with a tertiary amine, a bimolecular nucleophilic substitution reaction. The nucleophile attacks the carbon atom with its lone pair electrons, and the leaving group simultaneously detaches, without generating a carbocation intermediate during the reaction. Electrons transfer from the nucleophile to the carbon-halogen bond, and the leaving group gradually detaches from the central carbon atom. The catalyst prepared by this method exhibits excellent catalytic performance in specific catalytic reactions, effectively overcoming the shortcomings of traditional phase-transfer catalysts in specific reactions, and providing a novel design strategy for developing highly efficient phase-transfer catalytic systems. Detailed Implementation
[0008] To make the content of this invention easier to understand, the technical solution of this invention will be further described below with reference to specific embodiments, but this invention is not limited thereto.
[0009] The synthesis process of compound 1 in this application is described in Org. Biomol. Chem., 2023, 21, 6484-6487 and Angew. Chem. Int. Ed. 2022, 61 According to document e202200371, the quaternary ammonium salt phase transfer catalyst with axial chiral bipyrrole skeleton prepared in this invention is represented by four specific substances in the examples, namely compounds 3a-3d described in Examples 1-4.
[0010] Example 1; Synthesis of Compound 3a: Compound 1 (5 mmol, 1 equiv.) and Compound 2a (75 mmol, 15 equiv.) were added sequentially to a pressure-resistant tube equipped with a magnetic stirrer. Acetonitrile was used as the solvent to dissolve the starting materials. Under a nitrogen atmosphere, the reaction temperature was raised to 60 °C and the mixture was continuously stirred for 24 hours. The reaction was monitored by TLC. Once a concentrated product spot was observed, the reaction was considered complete. Most of the acetonitrile was removed by vacuum concentration using a rotary evaporator. The concentrated crude product was then separated and purified using silica gel chromatography (dichloromethane / methanol = 20 / 1) to obtain the target compound 3a (yield 40%).
[0011] 1 H NMR (500 MHz, Chloroform- d ) δ 7.81 (d, J = 6.8 Hz, 4H), 7.47 (d, J= 6.7 Hz, 6H), 7.10 (t, J = 7.5 Hz, 2H), 6.98 (t, J = 7.6 Hz, 4H), 6.67 (s,2H), 6.49 (d, J = 7.6 Hz, 4H), 5.44 (d, J = 14.1 Hz, 2H), 5.23 (d, J = 13.5Hz, 2H), 5.06 (d, J = 14.1 Hz, 2H), 4.83 (d, J = 13.5 Hz, 2H), 4.38 (td, J =8.7, 5.4 Hz, 4H), 1.34 (t, J = 7.1 Hz, 6H). 13 C NMR (126 MHz, Chloroform- d ) δ 163.65, 135.40, 133.36, 131.15,129.63, 128.36, 128.28, 127.14, 127.12, 122.40, 117.47, 109.55, 64.93, 61.47,55.62, 14.40. The specific synthesis process is as follows:
[0012] Example 2; Synthesis of Compound 3b: Compound 1 (5 mmol, 1 equiv.) and Compound 2b (75 mmol, 15 equiv.) were added sequentially to a pressure-resistant tube equipped with a magnetic stirrer. Acetonitrile was used as the solvent to dissolve the starting materials. Under a nitrogen atmosphere, the reaction temperature was raised to 60 °C and the mixture was continuously stirred for 24 hours. The reaction was monitored by TLC. Once a concentrated product spot was observed, the reaction was considered complete. Most of the acetonitrile was removed by vacuum concentration using a rotary evaporator. The concentrated crude product was then separated and purified using silica gel chromatography (dichloromethane / methanol = 20 / 1) to obtain the target compound 3b (yield 40%).
[0013] 1 H NMR (500 MHz, CDCl3) δ 7.67 (d, J = 8.1 Hz, 4H), 7.47 (d, J = 8.1Hz, 4H), 7.10 (t, J = 7.5 Hz, 2H), 6.99 (t, J = 7.6 Hz, 4H), 6.69 (s, 2H), 6.52 (d, J = 7.6 Hz, 4H), 5.35 (d, J = 14.3 Hz, 2H), 4.99 (dd, J = 31.8, 13.9Hz, 4H), 4.80 (d, J = 13.6 Hz, 2H), 4.35 (p, J = 7.2 Hz, 4H), 1.32 (m, 24H). 13 C NMR (126 MHz, CDCl3) δ 163.65, 154.34, 135.33, 133.12, 128.40,128.37, 128.25, 127.19, 126.64, 124.10, 122.64, 117.38, 109.56, 77.41, 76.91,64.31, 61.44, 55.50, 34.95, 31.20, 14.33. The specific synthesis process is as follows:
[0014] Example 3: Compound 1 (5 mmol, 1 equiv.) and compound 2c (75 mmol, 15 equiv.) were added sequentially to a pressure-resistant tube equipped with a magnetic stirrer. Acetonitrile was used as the solvent to dissolve the raw materials. Under a nitrogen atmosphere, the reaction temperature was raised to 60 °C and the mixture was continuously stirred for 24 hours. The reaction was monitored by TLC plate. Once a concentrated product spot was observed, the reaction was considered complete. Most of the acetonitrile was removed by vacuum concentration using a rotary evaporator. The concentrated crude product was then separated and purified using silica gel chromatography (dichloromethane / methanol = 20 / 1) to obtain the target compound 3c (yield 11%).
[0015] 1H NMR (500 MHz, CDCl3) δ 7.86 (d, J = 7.9 Hz, 4H), 7.65 (d, J = 7.9Hz, 4H), 7.57 (d, J = 7.5 Hz, 4H), 7.44 (t, J = 7.5 Hz, 4H), 7.37 (t, J = 7.4Hz, 2H), 7.10 (t, J = 7.5 Hz, 2H), 6.99 (t, J = 7.6 Hz, 4H), 6.67 (s, 2H), 6.49 (d, J = 7.8 Hz, 4H), 5.60 (d, J = 14.2 Hz, 2H), 5.34 (d, J = 13.6 Hz,2H), 5.04 (d, J = 14.2 Hz, 2H), 4.94 (d, J = 13.5 Hz, 2H), 4.51 – 4.34 (m,4H), 1.34 (t, J = 7.1 Hz, 6H). 13C NMR (126 MHz, CDCl3) δ 163.51, 143.49, 139.70, 135.08, 133.87,128.90, 128.32, 128.27, 128.14, 127.99, 127.94, 127.19, 126.94, 126.10,122.53, 117.48, 109.45, 65.48, 61.54, 55.41, 14.35. The specific synthesis process is as follows:
[0016] Example 4; Synthesis of Compound 3d: Compound 1 (5 mmol, 1 equiv.) and Compound 2d (75 mmol, 15 equiv.) were added sequentially to a pressure-resistant tube equipped with a magnetic stirrer. Acetonitrile was used as the solvent to dissolve the starting materials. Under a nitrogen atmosphere, the reaction temperature was raised to 60 °C and the mixture was continuously stirred for 24 hours. The reaction was monitored by TLC. Once a concentrated product spot was observed, the reaction was considered complete. Most of the acetonitrile was removed by vacuum concentration using a rotary evaporator. The concentrated crude product was then separated and purified using silica gel chromatography (dichloromethane / methanol = 20 / 1) to obtain the target compound 3d (yield 11%).
[0017] 1 H NMR (500 MHz, Methanol- d 4) δ 8.01 (d, J = 7.9 Hz, 4H), 7.85 (d, J =8.0 Hz, 4H), 7.13 (t, J = 7.4 Hz, 2H), 7.00 (t, J = 7.6 Hz, 4H), 6.75 (d, J =3.7 Hz, 2H), 6.58 (d, J = 7.5 Hz, 4H), 5.14 (d, J = 14.1 Hz, 2H), 4.94 (d, J = 14.0 Hz, 2H), 4.78 (d, J = 13.9 Hz, 2H), 4.59 (d, J = 7.1 Hz, 2H), 4.32 –4.23 (m, 4H), 1.24 (t, J = 7.1 Hz, 6H). 13 C NMR (126 MHz, Methanol- d 4) δ 164.78, 136.84, 135.32, 132.65,129.83, 129.51, 129.49, 128.25, 127.50, 127.47, 127.44, 123.83, 118.67,110.16, 64.41, 62.32, 57.22, 14.48. The specific synthesis process is as follows:
[0018] Application example: The catalysts 3a to 3d prepared in Examples 1-4 were applied to the [3+2] cycloaddition reaction of 2-(morpholino-4-carbonyl)allyl benzenesulfinate (0.05 mmol, 1 equiv.) and phenylacryloylbenzene (0.06 mmol, 1.2 equiv.).
[0019] Using 3a as catalyst, compound 4 (0.05 mmol, 1 equiv.) and compound 5 (0.06 mmol, 1.2 equiv.) were added sequentially to a reaction tube equipped with a magnetic stirrer. The starting materials were dissolved in THF. The reaction was carried out under nitrogen atmosphere and stirred continuously at room temperature for 12 hours. The reaction was monitored by TLC plate. Once the starting material spot disappeared, the reaction was considered complete. Most of the THF was removed by vacuum concentration using a rotary evaporator. The concentrated crude product was then separated and purified by silica gel chromatography (petroleum ether / ethyl acetate = 2 / 1) to obtain the target compound 6 (58% yield). The specific reaction process is as follows:
[0020]
[0021] The above description is only a preferred embodiment of the present invention. All equivalent changes and modifications made within the scope of the claims of the present invention should be included in the scope of the present invention.
Claims
1. A method for preparing a bipyrrole-based chiral phase transfer catalyst, characterized in that: The axially chiral compound (S)-1,9-diphenyl-5-((S)-1-phenylethyl)-5,6-dihydro-4H-dipyrrolo[1,2-b:2',1'-g][1,2,5]triazacycloheptane-3,7-dicarboxylic acid diethyl ester of compound 1 was dissolved in acetonitrile, and compound 2 bromide was added at room temperature. The mixture was heated to 60°C to generate the bipyrrole-based axially chiral phase transfer catalyst described above. The synthetic route is shown below: 。 2. The method according to claim 1, characterized in that: The reaction system was kept free of water and oxygen. The reaction was monitored by thin-layer chromatography (TLC). After the reaction was completed, the mixture was concentrated by rotary evaporation under reduced pressure, purified by silica gel column chromatography, and then recrystallized to obtain compounds 3a-3d.
3. A bipyrrole-based axially chiral phase transfer catalyst prepared by the method according to any one of claims 1-2.
4. The application of a bipyrrole axially chiral phase transfer catalyst prepared by the method according to any one of claims 1-2 in asymmetric [3+2] cycloaddition reactions.