The invention relates to axially chiral N, Napos based on C2 symmetry. Synthesis method of-dipyrrole skeleton chiral oxazoline ligand compound

Abstract

The invention discloses a synthesis method of an axially chiral N, N '-dipyrrole skeleton chiral oxazoline ligand compound based on C2 symmetry, and the synthesis method comprises the following steps: (1) dissolving chiral 2, 2'-dialdehyde-3, 3 '-diethoxycarbonyl-5, 5'-diphenyl-N, N '-dipyrrole, stirring with sodium hydrogen phosphate, sodium chlorite and 2-methylbutadiene to react to obtain 3, 3'-diethoxycarbonyl-5, 5 '-diphenyl-N, N'-dipyrrole, and reacting with sodium hydrogen phosphate, sodium chlorite and 2-methylbutadiene to obtain a chiral 2, 2 '-dialdehyde-3, 3'-diethoxycarbonyl-5, 5 '-diphenyl-N, N'-dipyrrole skeleton chiral oxazoline ligand compound; the solvent is 5, 5 '-diphenyl-N, N'-dipyrrole-2, 2 '-dicarboxylic acid; (2) dissolving 3, 3 '-diethoxycarbonyl-5, 5'-diphenyl-N, N '-dipyrrole-2, 2'-dicarboxylic acid in thionyl chloride, then refluxing at 60 DEG C for 3 hours, then introducing nitrogen to blow-dry thionyl chloride, and then dropwise adding chiral amino alcohol to react to obtain a product; and (3) reacting the obtained product with a burge reagent, and purifying to obtain the chiral N, N '-dipyrrole skeleton chiral oxazoline ligand compound.

Description

Technical Field

[0001] The present invention belongs to the technical field of fine chemical engineering, and particularly relates to a method for synthesizing a chiral oxazoline ligand compound based on a C2-symmetric axially chiral N,N'-bipyrrole skeleton. Background Art

[0002] Asymmetric catalysis is one of the most active research fields in synthetic chemistry today and is the most direct and effective method for obtaining chiral compounds. This technology has significant advantages such as chiral amplification, high enantioselectivity, economy, and easy industrialization. However, achieving highly efficient and highly selective asymmetric catalytic reactions remains a major challenge in the field of synthetic chemistry. One of the core scientific issues lies in the development of new and efficient chiral ligands and their catalysts. Although significant progress has been made in the design and synthesis of chiral ligands, many excellent chiral bisoxazoline ligands have been successfully developed and some have been applied in industrial production, but the existing ligands still have problems such as limited scope of application and high dependence on reaction substrates. Currently, there is no chiral ligand that can be universally applicable to all reactions. Therefore, exploring chiral ligands with novel skeletons has always been the core theme in the research of asymmetric catalytic synthesis.

[0003] The design and synthesis of chiral ligands are the key to improving catalytic activity and enantioselectivity, and the core lies in optimizing electronic factors and structural factors (such as dihedral angle, steric effect, and backbone rigidity, etc.). Research shows that the dihedral angle has a particularly significant impact on enantioselectivity in asymmetric catalysis (see related literature: Acc. Chem. Res. 2007, 40, 1385–1393; Tetrahedron: Asymmetry 2004, 15, 2185–2188; J. Org. Chem.1999, 65, 6223). By precisely regulating the geometric configuration and electronic distribution of the ligand, the performance of the catalyst can be effectively improved, thereby achieving efficient control and high enantioselectivity of the reaction.

[0004] In 2022, we achieved the asymmetric catalytic synthesis of a series of C2-symmetric N,N'-bipyrrole skeletons through chiral phosphoric acid catalysis (see related literature: Angew. Chem. Int. Ed. 2022, 61, e202200371). However, the price of chiral phosphoric acid is very high, and the preparation cost of the chiral skeleton is relatively high, which affects its practicality. Summary of the Invention

[0005] In order to overcome the above technical problems, the object of the present invention is to provide a method for synthesizing a class of chiral oxazoline ligands based on a C2-symmetric axially chiral N,N'-bipyrrole skeleton. Starting from a relatively inexpensive chiral bipyrrole skeleton, a chiral oxazoline ligand compound based on a C2-symmetric axially chiral N,N'-bipyrrole skeleton can be easily obtained by using three simple and efficient reactions.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions: A method for preparing a class of chiral oxazoline ligands based on a C2-symmetric axially chiral N,N'-bipyrrole skeleton, the preparation method of the compound comprising the following steps: (1) After dissolving chiral 2,2'-dialdehyde-3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole, stirring and reacting with sodium hydrogen phosphate, sodium chlorite and 2-methylbutadiene, extracting with ethyl acetate, drying, filtering, concentrating under reduced pressure, and recrystallizing with ethyl acetate to obtain chiral 5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid; (2) Dissolving the 3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid obtained in step (1) in thionyl chloride, refluxing at 60 °C for 3 hours first, then blowing dry thionyl chloride with nitrogen, and then dropping chiral amino alcohol to react. After completion, extract with ethyl acetate, dry with a water removing agent, filter, concentrate under reduced pressure, and purify by silica gel column chromatography to obtain the product; (3) Reacting the product obtained in step (2) with Burgess reagent, after completion, extracting with ethyl acetate, drying with a water removing agent, filtering, concentrating under reduced pressure, and purifying by silica gel column chromatography to obtain a chiral N,N'-bipyrrole skeleton chiral oxazoline ligand compound; The structural formula of the chiral oxazoline ligand compound is as follows: .

[0007] Further, in step (1), the mass ratio of 2,2'-dialdehyde-3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole, sodium hydrogen phosphate, sodium chlorite and 2-methylbutadiene is 0.969 g: 1.95 g: 1.81 g: 1.6 g.

[0008] Further, in step (1), 2,2'-dialdehyde-3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole is dissolved in a tetrahydrofuran / tert-butanol / water solution, and the volume ratio of tetrahydrofuran, tert-butanol and water is 1:1:1, and the stirring reaction time is 12 h.

[0009] Further, in step (2), the dosage ratio of 3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid to thionyl chloride is 1 mol: 3 mL.

[0010] Further, in step (2), the chiral amino alcohol is dissolved in ultradry dichloromethane and then added dropwise. The reaction time is 12 h, and the molar ratio to 3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid is 3:1. The chiral amino alcohol is L-(+)-valinol or S -tert-leucinol.

[0011] Further, in step (3), the molar ratio of diol to Burgess reagent is 1:1.

[0012] Further, in step (3), the reaction time is 12 h and the reaction temperature is 60 °C.

[0013] The beneficial effects of the present invention are as follows: The synthetic method route of the compound synthesized by the present invention is simple and green, without the need for high temperature and high pressure. The highest temperature of the route is only 60 °C, and the intermediate substances in the route have very good stability and can be exposed to air for a long time. The prices of the various drugs in the route are relatively low and environmentally friendly. The yield of the route is relatively high, and it is an efficient method for obtaining a C2-symmetric axially chiral N,N'-bipyrrole framework chiral oxazoline ligand compound. Description of the Drawings

[0014] Figure 1 is the S H NMR spectrum of ( S )-2,2'-bis(( 1 )-4-isopropyl-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl.

[0015] Figure 2 is the S C NMR spectrum of ( S )-2,2'-bis(( 13 )-4-isopropyl-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl.

[0016] Figure 3 is the R H NMR spectrum of ( S )-2,2'-bis(( 1 )-4-isopropyl-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl.

[0017] Figure 4 For R )-2,2'-bis(( S )-4-isopropyl-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl 13 13C NMR spectrum.

[0018] Figure 5 For S )-2,2'-bis(( S )-4-(tert-butyl)-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl 1 1H NMR spectrum.

[0019] Figure 6 For S )-2,2'-bis(( S )-4-(tert-butyl)-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl 13 13C NMR spectrum.

[0020] Figure 7 For R )-2,2'-bis(( S )-4-(tert-butyl)-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl 1 1H NMR spectrum.

[0021] Figure 8 For R )-2,2'-bis(( S )-4-(tert-butyl)-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl 13 13C NMR spectrum. Detailed implementation manners

[0022] In order to make the objectives, technical solutions and advantages of the present invention clearer and more understandable, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0023] The structural formula of the chiral N,N'-bipyrrole framework chiral oxazoline ligand in the following embodiments is as follows: .

[0024] Example 1:( S )-2,2'-Bis(( S )-4-Isopropyl-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl The reaction formula is as follows: ; S1: Dissolve chiral 2,2'-diformyl-3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole (1a, 2 mmol, 969.02 mg) with S configuration in 24 mL of tetrahydrofuran / tert-butanol / aqueous solution (volume ratio 1:1:1), then add 8 equivalents of sodium hydrogen phosphate (1.95 g) and sodium chlorite (1.81 g), and 20 equivalents of 2-methylbutadiene (1.6 g, 4.72 mL). Stir at room temperature for 12 h. After completion, extract with ethyl acetate, dry, filter, concentrate under reduced pressure, and recrystallize with ethyl acetate to obtain S chiral 3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid (1b, 836.7 mg, yield 81%) with configuration; S )-2,2'-Bis((( S )-1-Hydroxy-3-methylbutan-2-yl)carbamoyl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl (1c, 401.26 mg, yield 60%).

[0025] S3: In ( S )-2,2'-Bis((( S)-(1-Hydroxy-3-methylbutan-2-yl)carbamoyl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl (1c, 2.2 mmol, 1.41 g) was added with Burgess reagent (516.9 mg) and 5 mL of ultradry tetrahydrofuran solvent, and the reaction was carried out at 60 °C for 12 h. After completion, it was extracted with ethyl acetate, dried with a water scavenger, filtered, and concentrated under reduced pressure. The water scavenger can be selected from anhydrous sodium sulfate and anhydrous magnesium sulfate. Purification by silica gel column chromatography (elution system: PE / EA = 10 / 1 by volume) gave ( S )-2,2'-Bis(( S )-4-Isopropyl-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl (1d, 1.259 g, yield 88%). The NMR data are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.16 (d, J = 7.5 Hz, 2H), 7.08 (t, J = 7.5 Hz, 4H), 6.87 (d, J = 7.9 Hz, 4H), 6.58 (s, 2H), 4.38 – 4.29 (m, 6H), 4.00 (t, J = 7.8 Hz, 2H), 3.91 (q, J = 9.1 Hz, 2H), 1.55 (d, J = 7.0 Hz, 2H), 1.35 (t, J = 7.1 Hz, 6H), 0.78 (d, J = 6.6 Hz, 6H), 0.74 (d, J = 5.8 Hz, 6H); 13 C NMR (126 MHz, CDCl3) δ 163.4, 154.9, 137.1, 129.3, 128.2, 128.2, 128.2, 125.4, 116.7, 108.1, 73.7, 71.0, 60.6, 33.2, 19.0, 19.0, 14.4.

[0026] Example 2 ( R )-2,2'-Bis(( S )-4-Isopropyl-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl The reaction scheme is as follows:

[0027] S1: Add RThe 2,2'-dialdehyde-3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole (2a, 2 mmol, 969.02 mg) of the configuration was dissolved in 24 mL of a tetrahydrofuran / tert-butanol / water solution (volume ratio 1:1:1), then 8 equivalents of sodium hydrogen phosphate (1.95 g), sodium chlorite (1.81 g), and 20 equivalents of 2-methylbutadiene (1.6 g, 4.72 mL) were added, and the mixture was stirred at room temperature for 12 h. After completion, it was extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and recrystallized from ethyl acetate to obtain R The chiral 3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid (2b, 774.7 mg, yield 75%); S2: 3 mL of thionyl chloride was placed in a dry two-necked round-bottom flask, and then 3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid (2b, 1 mol, 516.5 mg) was added. The mixture was refluxed at 60 °C for 3 h, and then the thionyl chloride was blown dry with nitrogen. L-(+)-valinol (309.5 mg) was dissolved in ultra-dry dichloromethane and slowly added dropwise under nitrogen protection, and the reaction was carried out at room temperature for 12 h. After completion, it was extracted with ethyl acetate, dried with a water removing agent, filtered, concentrated under reduced pressure, and the water removing agent can be selected from anhydrous sodium sulfate and anhydrous magnesium sulfate. Purification by silica gel column chromatography (elution system: PE / EA = 1 / 1 by volume) gave the product ( R )-2,2'-bis((( S )-1-hydroxy-3-methylbutan-2-yl)carbamoyl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl (2c, 354.4 mg, yield 53%).

[0028] S3: Burgess reagent (516.9 mg) and 5 mL of ultra-dry tetrahydrofuran solvent were added to ( R )-2,2'-bis((( S )-1-hydroxy-3-methylbutan-2-yl)carbamoyl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl (2c, 2.2 mmol, 1.41 g), and the reaction was carried out at 60 °C for 12 h. After completion, it was extracted with ethyl acetate, dried with a water removing agent, filtered, concentrated under reduced pressure, and the water removing agent can be selected from anhydrous sodium sulfate and anhydrous magnesium sulfate. Purification by silica gel column chromatography (elution system: PE / EA = 10 / 1 by volume) gave ( R )-2,2'-bis(( S )-4-isopropyl-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl (1.316 g, yield 92%). The NMR data are as follows: 1 1H NMR (500 MHz, CDCl3) δ 7.21 - 7.16 (m, 2H), 7.11 (t, J = 7.2 Hz, 4H), 6.90 (d, J = 7.8 Hz, 4H), 6.61 (s, 2H), 4.35 - 4.25 (m, 6H), 3.92 (t, J = 8.6 Hz, 2H), 3.83 (q, J = 8.5 Hz, 2H), 1.68 (t, J = 6.8 Hz, 2H), 1.35 (t, J = 7.2 Hz, 6H), 0.88 (d, J = 7.3 Hz, 6H), 0.82 (d, J = 6.8 Hz, 6H); 13 13C NMR (126 MHz, CDCl3) δ 163.6, 154.6, 137.0, 129.4, 128.3, 128.2, 128.0, 125.4, 116.8, 108.3, 73.5, 70.5, 60.6, 32.8, 19.3, 18.6, 14.4。

[0029] Example 3:( S )-2,2'-Bis(( S )-4-(tert-Butyl)-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethylcarbonyloxy The reaction formula is as follows:

[0030] S1: Dissolve the chiral 2,2'-dialdehyde-3,3'-diethylcarbonyloxy-5,5'-diphenyl-N,N'-bipyrrole (1a, 2 mmol, 969.02 mg) of S configuration in 24 mL of a tetrahydrofuran / tert-butanol / water solution (volume ratio 1:1:1), then add 8 equivalents of sodium hydrogen phosphate (1.95 g), sodium chlorite (1.81 g), and 20 equivalents of 2-methylbutadiene (1.6 g, 4.72 mL), and stir at room temperature for 12 h. After completion, extract with ethyl acetate, dry, filter, concentrate under reduced pressure, and recrystallize with ethyl acetate to obtain S the chiral 3,3'-diethylcarbonyloxy-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid (1b, 836.7 mg, yield 81%) of S2: Take 3 mL of thionyl chloride in a dry two-necked round-bottom flask and then add SThe chiral 3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid (1b, 1 mol, 516.5 mg) of the configuration was refluxed at 60 °C for 3 hours, and then the thionyl chloride was blown dry by passing nitrogen. It was then dissolved in ultradry dichloromethane. S -tert-Leucinol (351.57 mg) was slowly added dropwise under nitrogen protection, and the reaction was carried out at room temperature for 12 hours. After completion, it was extracted with ethyl acetate, dried with a water-removing agent, filtered, concentrated under reduced pressure, and the water-removing agent can be selected from anhydrous sodium sulfate and anhydrous magnesium sulfate. The product was purified by silica gel column chromatography (elution system: volume ratio PE / EA = 1 / 1) to obtain S ()-2,2'-bis((( S )-1-hydroxy-3,3-dimethylbutan-2-yl)carbamoyl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl (3c, 371.43 mg, yield 53%).

[0031] S3: Burgess reagent (516.9 mg) and 5 mL of ultradry tetrahydrofuran solvent were added to ( S )-2,2'-bis((( S )-1-hydroxy-3,3-dimethylbutan-2-yl)carbamoyl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl (3c, 2.2 mmol, 1.54 g), and the reaction was carried out at 60 °C for 12 h. After completion, it was extracted with ethyl acetate, dried with a water-removing agent, filtered, concentrated under reduced pressure, and the water-removing agent can be selected from anhydrous sodium sulfate and anhydrous magnesium sulfate. The product was purified by silica gel column chromatography (elution system: volume ratio PE / EA = 10 / 1) to obtain S )-2,2'-bis(( S )-4-(tert-butyl)-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl (3d, 1.343 g, yield 90%). The NMR data are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.18 (d, J = 7.3 Hz, 2H), 7.11 (t, J = 7.6Hz, 4H), 6.90 (d, J = 7.1 Hz, 4H), 6.58 (s, 2H), 4.35 – 4.29(m, 4H), 4.23(td, J = 10.5, 2.7 Hz, 2H), 4.05 (t, J = 8.8 Hz, 2H), 3.87 – 3.82 (m, 2H),1.35 (t, J = 7.1 Hz, 6H), 0.80 (s, 18H); 13 13C NMR (126 MHz, CDCl3) δ 162.57, 153.54, 136.04, 128.38, 127.06, 127.02, 126.95, 124.22, 115.67, 107.17, 67.35, 59.42, 32.41, 24.84, 13.29。

[0032] Example 4:( R )-2,2'-Bis(( S )-4-(tert-Butyl)-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethyl carbonyloxy The reaction formula is as follows:

[0033] S1: Dissolve the chiral 2,2'-dialdehyde-3,3'-diethyl carbonyloxy-5,5'-diphenyl-N,N'-bipyrrole (2a, 2 mmol, 969.02 mg) with R configuration in 24 mL of a tetrahydrofuran / tert-butanol / water solution (volume ratio 1:1:1), then add 8 equivalents of sodium hydrogen phosphate (1.95 g) and sodium chlorite (1.81 g), as well as 20 equivalents of 2-methylbutadiene (1.6 g, 4.72 mL), and stir at room temperature for 12 h. After completion, extract with ethyl acetate, dry, filter, concentrate under reduced pressure, and recrystallize with ethyl acetate to obtain R chiral 3,3'-diethyl carbonyloxy-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid (2b, 774.7 mg, yield 75%); S2: Take 3 mL of thionyl chloride in a dry two-necked round-bottom flask, then add 3,3'-diethyl carbonyloxy-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid (2b, 1 mol, 516.5 mg), reflux at 60 °C for 3 h, and then blow dry the thionyl chloride with nitrogen. Then dissolve S -tert-leucinol (351.57 mg) and slowly add dropwise under nitrogen protection, and react at room temperature for 12 h. After completion, extract with ethyl acetate, dry with a water scavenger, filter, concentrate under reduced pressure, and the water scavenger can be anhydrous sodium sulfate and anhydrous magnesium sulfate. Purify by silica gel column chromatography (elution system: PE / EA = 1 / 1 by volume) to obtain the product ( R )-2,2'-Bis((( S)-1-Hydroxy-3,3-dimethylbutan-2-yl)carbamoyl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl (4c, 441.51 mg, yield 63%).

[0034] S3: In ( R )-2,2'-Bis((( S )-1-Hydroxy-3,3-dimethylbutan-2-yl)carbamoyl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl (4c, 2.2 mmol, 1.54 g), add Burgess reagent (516.9 mg), 5 mL of ultra-dry tetrahydrofuran solvent, react at 60 °C for 12 h. After completion, extract with ethyl acetate, dry with a water scavenger, filter, concentrate under reduced pressure. The water scavenger can be anhydrous sodium sulfate and anhydrous magnesium sulfate. Purify by silica gel column chromatography (elution system: PE / EA = 10 / 1 by volume) to obtain ( S )-2,2'-Bis(( S )-4-(tert-Butyl)-4,5-dihydrooxazol-2-yl)-5,5'-diphenyl-[1,1'-bipyrrole]-3,3'-diethoxycarbonyl (4d, 1.387 g, yield 93%). The NMR data are as follows: 1 H NMR (500 MHz, CDCl3) δ 7.18 (t, J J = 7.1 Hz, 2H), 7.10 (t, J J = 7.5 Hz, 4H), 6.93 (d, J J = 7.0 Hz, 4H), 6.57 (s, 2H), 4.32 (dqd, J J = 21.3, 7.0, 3.7 Hz, 6H), 4.08 – 4.03 (m, 2H), 3.98 (t, J J = 10.0 Hz, 2H), 1.34 (t, J J = 7.2 Hz, 6H), 0.73 (s, 18H); 13 C NMR (126 MHz, CDCl3) δ 163.42, 155.28, 137.18, 129.35, 128.29, 128.22, 128.14, 125.90, 116.81, 108.11, 77.41, 77.16, 76.91, 68.88, 60.55, 33.50, 25.95, 14.43, 1.16.

[0035] Those skilled in the art can easily understand that the above are only the preferred examples of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, and improvements made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for synthesizing a C2-symmetric axially chiral N,N'-bipyrrole framework chiral oxazoline ligand compound, characterized in that: The steps include: (1) Chiral 2,2'-dialdehyde-3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole is dissolved and reacted with sodium hydrogen phosphate, sodium chlorite and 2-methylbutadiene by stirring, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and recrystallized with ethyl acetate to obtain chiral 3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid; (2) dissolving the 3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid obtained in step (1) in thionyl chloride and refluxing at 60°C for 3 hours, then blowing the thionyl chloride dry with nitrogen, then adding chiral amino alcohol dropwise to react, extracting with ethyl acetate, drying with a dehydrating agent, filtering, concentrating under reduced pressure, and purifying by silica gel column chromatography to obtain the product; (3) reacting the product obtained in step (2) with a burgess reagent, extracting with ethyl acetate, drying with a dehydrating agent, filtering, concentrating under reduced pressure, and purifying by silica gel column chromatography to obtain a chiral N,N'-bipyrrole skeleton chiral oxazoline ligand compound; The structural formula of the chiral oxazoline ligand compound is as follows: 。 2. The synthesis method according to claim 1, characterized in that: In step (1), the mass ratio of 2,2'-dialdehyde-3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole, sodium hydrogen phosphate, sodium chlorite and 2-methylbutadiene is 0.969 g:1.95 g:1.81 g:1.6 g.

3. The synthesis method according to claim 1, characterized in that: In step (1), 2,2'-dialdehyde-3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole is dissolved in tetrahydrofuran / tert-butyl alcohol / water solution, the volume ratio of tetrahydrofuran, tert-butyl alcohol and water is 1:1:1, and the stirring reaction time is 12 hours.

4. The synthesis method according to claim 1, characterized in that: In step (2), the ratio of 3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid to thionyl chloride is 1 mol:3 mL.

5. The synthesis method according to claim 1, characterized in that: In step (2), the molar ratio of the chiral amino alcohol to 3,3'-diethoxycarbonyl-5,5'-diphenyl-N,N'-bipyrrole-2,2'-dicarboxylic acid is 3:1, and the reaction time is 12 hours. The chiral amino alcohol is L-(+)-valinol or S -tert-leucinol.

6. The synthesis method according to claim 1, characterized in that: The molar ratio of the product to the burgess reagent in step (3) is 1:

1.

7. The synthesis method according to claim 1, characterized in that: The reaction time in step (3) is 12 h and the reaction temperature is 60°C.

Images