A catalytic synthesis method of chiral polysubstituted hydrogenated quinolines

Abstract

The application discloses a catalytic synthesis method of chiral polysubstituted hydrogenated quinoline compounds, and belongs to the field of organic synthesis. The application comprises the following steps: at 0-40 DEG C, alcohol or halogenated alkane is used as a solvent, a copper metal catalyst and a chiral ligand are added, and reaction is carried out under nitrogen protection for 0.5-2 hours; the temperature is lowered to-60-0 DEG C; then, o-aminophenyl nitrone, propargyl alcohol ester and alkali are sequentially added; and reaction is carried out for 6-48 hours, so as to obtain a chiral polysubstituted hydrogenated quinoline compound shown in formula 1 or 2. The application realizes, for the first time, synthesis of chiral polysubstituted hydrogenated quinoline compounds by using o-aminophenyl nitrone and propargyl alcohol ester as reactants, and by using a cheap copper metal catalyst and a chiral ligand, the method is simple in operation, low in cost, and has excellent enantioselectivity and diastereoselectivity.

Description

Technical Field

[0001] This invention relates to a method for synthesizing chiral polysubstituted hydrogenated quinoline compounds, belonging to the field of organic synthesis. Background Technology

[0002] Chiral polysubstituted hydrogenated quinoline compounds are widely found in pesticides, pharmaceuticals, natural products and their derivatives. As one of the most important nitrogen heterocyclic skeletons in natural alkaloids, they have attracted widespread attention from researchers.

[0003] Chirality is one of the most important properties in nature, and the configuration of chiral drugs directly affects the pharmacology, efficacy, and toxicity of drug molecules. Asymmetric catalysis is the most direct and effective method for obtaining chiral molecules. With the development of the field of asymmetric catalysis, more and more methods for synthesizing chiral hydrogenated quinoline compounds have been developed, with the vast majority of research focusing on the asymmetric Povarov reaction and the asymmetric hydrogenation of quinoline compounds. The asymmetric Povarov reaction typically requires expensive chiral phosphoric acid catalysts or noble metal catalysts, while asymmetric hydrogenation requires noble metal catalysts or high-pressure hydrogen gas. Therefore, developing a simple, efficient, and low-cost method to obtain chiral polysubstituted hydrogenated quinoline compounds is of great value.

[0004] In 2011, Géraldine Masson's group reported a chiral phosphoric acid-catalyzed three-component Povarov reaction of aldehydes, anilines, and enamines to generate trisubstituted tetrahydroquinolines with three consecutive stereocenters (Dagousset, G.; Zhu, J.; Masson, G. Chiral phosphoric acid-catalyzed enantioselective three-component Povarov reaction using enecarbamates as dienophiles: highly diastereo-andenantioselective synthesis of substituted 4-aminotetrahydroquinolines. J. Am. Chem. Soc. 2011, 133, 14804-14813.). This reaction features a broad substrate range, high yield, and high diastereoselectivity and enantioselectivity, but it requires expensive chiral phosphoric acid catalysts.

[0005]

[0006] In 2021, Liu Qiang's research group reported a method for the asymmetric hydrogenation of quinolines catalyzed by inexpensive manganese metal (Liu, C.; Wang, M.; Liu, S.; Wang, Y.; Peng, Y.; Lan, Y.; Liu, Q. Manganese catalyzed asymmetric hydrogenation of quinolines enabled by π-π interaction. Angew. Chem. Int. Ed. 2021, 60, 5108-5113.). This method employs a novel ligand and achieves excellent yields and good enantioselectivity even with catalyst loadings as low as 0.025 mol%. Furthermore, the reaction exhibits a broad substrate scope, good selectivity (halogen tolerance), high yield, and good enantioselectivity, making it competitive with noble metal catalysis. However, it still requires high-pressure hydrogen, and the novel ligand used in this reaction is expensive.

[0007] Summary of the Invention

[0008] To address the aforementioned problems in the existing technology, the purpose of this invention is to provide a method for synthesizing polysubstituted hydrogenated quinoline compounds via a divergent asymmetric reaction catalyzed by an inexpensive metallic copper catalyst and a commercially available, inexpensive chiral ligand.

[0009] This invention yields two products by proceeding through different reaction pathways in different solvents. First, a copper allene intermediate I is generated by reacting with a copper catalyst, a chiral ligand, and a base. Then, it reacts with a nitroketone to generate a cyclization intermediate II. Following this, ring-opening occurs to generate a highly reactive allene ketone intermediate III and an imine intermediate IV. In an alcohol solvent, the two intermediates undergo a [4+2] cyclization / addition / elimination reaction tandem to yield product 1. In a haloalkane solvent, the two intermediates undergo a [4+2] cyclization / CH functionalization reaction tandem to yield product 2. This invention represents the first catalytic asymmetric reaction involving allene ketone intermediates. By controlling the solvent, two chiral polysubstituted hydrogenated quinoline compounds with different skeletons can be obtained. Furthermore, this method is simple, inexpensive, and exhibits excellent enantioselectivity and diastereoselectivity.

[0010]

[0011] To achieve the above-mentioned objectives, the technical solution adopted by this invention is as follows:

[0012] A catalytic synthesis method for chiral polysubstituted hydrogenated quinoline compounds includes the following steps: At 0-40°C, using an alcohol or a haloalkane as a solvent, a copper catalyst and a chiral ligand are added, and the reaction is carried out under nitrogen protection for 0.5-2 hours. The temperature is then lowered to -60-0°C, and then o-aminophenyl nitrone, propargyl ester, and a base are added sequentially. The reaction is carried out for 6-48 hours to obtain the chiral polysubstituted hydrogenated quinoline compound shown in Formula 1 or 2.

[0013]

[0014] Wherein, R is selected from one of phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 2-naphthyl, and 2-thiophene; R 1 Selected from one of hydrogen, 5-methyl, 5-bromo, 4-methyl, 4-fluoro, 4-chloro, 4-bromo, 4-trifluoromethyl, and 4-methoxy; R 2 Selected from one of methyl, ethyl, isopropyl, 2,2,2-trifluoroethyl, and 1,1,1,3,3,3-hexafluoro-2-propyl; R 3 Selected from one of phenyl, 2-chlorophenyl, 2-methylphenyl, 3-chlorophenyl, 3-methylphenyl, 4-chlorophenyl, 4-methylphenyl, 4-fluorophenyl, 4-bromophenyl, 4-iodophenyl, 4-methoxyphenyl, 3,5-dimethylphenyl, 1-naphthyl, 2-naphthyl, 2-thienyl, 2-furanyl, 3-thienyl, and 3-furanyl; R 4 It is selected from one of hydrogen, 4-fluoro, 4-chloro, 4-bromine, 3-fluoro, 3-chloro, and 2-methyl.

[0015] The copper catalyst includes, but is not limited to, divalent or monovalent copper salts; the divalent or monovalent copper salt is one of copper trifluoromethanesulfonate, copper acetate, copper perchlorate, cuprous iodide, cuprous thiophene-2-carboxylate, and cuprous tetraacetonitrile hexafluorophosphate.

[0016] The chiral ligands include, but are not limited to, chiral Box ligands, chiral PyBox ligands, chiral PHOX ligands, and chiral Phos ligands; the base is an inorganic or organic base, including but not limited to sodium carbonate, sodium bicarbonate, potassium carbonate, triethylamine, diisopropylethylamine, and 1-methylpiperidine.

[0017] In molar amounts, the amount of the copper catalyst is 5-20% of o-aminophenyl nitrone; the amount of the chiral ligand is 5-25% of o-aminophenyl nitrone; the amount of propargyl ester is 1-3 times that of o-aminophenyl nitrone; and the amount of the base is 1-3 times that of o-aminophenyl nitrone.

[0018] The haloalkane solvents include, but are not limited to, dichloromethane, 1,2-dichloroethane, or chloroform.

[0019] The alcohol solvents include, but are not limited to, methanol, ethanol, isopropanol, 2,2,2-trifluoroethanol, and 1,1,1,3,3,3-hexafluoro-2-propanol.

[0020] The chemical structural formula of the o-aminophenyl nitrone is as follows: Wherein R is selected from one of phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 2-naphthyl, and 2-thienyl; R 1 Selected from one of hydrogen, 5-methyl, 5-bromo, 4-methyl, 4-fluoro, 4-chloro, 4-bromo, 4-trifluoromethyl, and 4-methoxy; R 4 It is selected from one of hydrogen, 4-fluoro, 4-chloro, 4-bromine, 3-fluoro, 3-chloro, and 2-methyl.

[0021] The chemical structural formula of the propargyl alcohol ester is as follows: Where R 3 Selected from one of phenyl, 2-chlorophenyl, 2-methylphenyl, 3-chlorophenyl, 3-methylphenyl, 4-chlorophenyl, 4-methylphenyl, 4-fluorophenyl, 4-bromophenyl, 4-iodophenyl, 4-methoxyphenyl, 3,5-dimethylphenyl, 1-naphthyl, 2-naphthyl, 2-thienyl, 2-furanyl, 3-thienyl, and 3-furanyl; R 5 It is selected from one of acetyl, benzoyl, 3,5-dinitrobenzoyl, and tert-butoxycarbonyl (Boc).

[0022] In a preferred embodiment, the amount of the copper catalyst is 10% of the amount of o-aminophenylnitrone, measured in molar amounts.

[0023] In a preferred embodiment, the amount of the chiral ligand is 12% of o-aminophenylnitrone, measured in molar amounts.

[0024] In a preferred embodiment, the amount of propargyl ester used is 2.0 times that of o-aminophenyl nitrone, measured in molar amounts.

[0025] In a preferred embodiment, the amount of alkali used is 2.0 times that of o-aminophenyl nitrone, measured in molar amounts.

[0026] In the preferred embodiment, the chemical structures of the chiral Box ligand, chiral PyBox ligand, chiral PHOX ligand, and chiral Phos ligand are shown below:

[0027]

[0028] In the above technical solution, after the reaction is completed, the product can be separated by simple column chromatography (the eluent is preferably petroleum ether: ethyl acetate: dichloromethane = 20:1:1 to 5:1:1).

[0029] The above reaction process is shown below:

[0030]

[0031] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0032] 1. This invention is the first to realize the synthesis of chiral polysubstituted hydrogenated quinoline compounds using o-aminophenyl nitrone and propargyl ester as reactants, catalyzed by inexpensive metallic copper catalyst and chiral ligand. The method is simple to operate, low in cost, and has excellent enantioselectivity and diastereoselectivity.

[0033] 2. The method of this invention does not involve a kinetic separation process; it is a series reaction. By controlling the solvent used in the reaction, two products can be obtained separately.

[0034] 3. The compounds synthesized in this invention have potential pharmaceutical activity, wherein the skeleton of product 2 is the first asymmetric synthesis. Detailed Implementation

[0035] The present invention will be further described below with reference to specific embodiments.

[0036] Example 1:

[0037]

[0038] Copper trifluoromethanesulfonate (3.6 mg, 0.01 mmol), a chiral ligand (4.0 mg, 0.012 mmol), and methanol (2 mL) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -20°C, and o-aminophenyl nitrone 1a (36.6 mg, 0.1 mmol), propargyl ester 2a (46.4 mg, 0.2 mmol), and diisopropylethylamine (25.8 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 12 hours. After the reaction, the product was subjected to simple column chromatography (preferably using petroleum ether: ethyl acetate: dichloromethane = 20:1:1 to 10:1:1) to obtain the target product 3a (34 mg), with a yield of 81% and ee = 91%. The analysis results of product 3a are as follows: Column Daicel Chiracel IC; iPrOH / Hexane = 30 / 70; flow rate = 1.0 mL / min; t R1 = 9.56 min, 95.5%; t R2 =12.82 min, 4.5%; 1H NMR (400MHz, CDCl3): δ7.68(d,J=8.1Hz,1H),7.33(t,J=7.7Hz,1H),7.29(d,J=8.3Hz, 2H),7.25-7.13(m,8H),7.07(d,J=8.0Hz,2H),6.51(s,1H),3.74(s,3H),2.35(s,3H). 13 C NMR (101MHz, CDCl3): δ165.1,143.8,137.2,135.6,134.0,133.7,130.8,129.1,1 28.4,128.3,128.1,128.0,127.3,127.3,127.2,126.9,126.8,55.8,52.1,21.5.

[0039] Example 2:

[0040]

[0041] Anhydrous copper acetate (1.8 mg, 0.01 mmol), a chiral ligand (4.0 mg, 0.012 mmol), and chloroform (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -20°C, and o-aminophenyl nitrone 1a (36.6 mg, 0.1 mmol), propargyl ester 2a (46.4 mg, 0.2 mmol), and diisopropylethylamine (25.8 mg, 0.2 mmol) were added sequentially. The reaction was continued at this temperature for 8 hours. After the reaction was completed, the product was subjected to simple column chromatography (preferably using petroleum ether: ethyl acetate: dichloromethane = 10:1:1 to 5:1:1) to obtain the target product 4a (29 mg), with a yield of 60% and ee = 91%. The analysis results of product 4a are as follows: Column Daicel Chiracel IC; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =20.81 min, 95.5%; t R2 =22.91 min, 4.5%; 1H NMR (400MHz, DMSO-d6): δ7.97(d,J=8.3Hz,2H),7.70(d,J=3.8Hz,1H),7.58( d,J=6.7Hz,1H),7.46-7.36(m,6H),7.34-7.25(m,4H),7.10(t,J=8.0Hz,1H) ,6.92(t,J=7.5Hz,1H),6.80(d,J=8.2Hz,1H),6.58(t,J=7.2Hz,1H),6.46(d ,J=3.5Hz,1H),4.24-4.17(m,1H),3.63(dd,J=6.1,3.6Hz,1H),2.35(s,3H). 13 CNMR (101MHz, DMSO-d6): δ190.6,150.8,144.8,141.9,137.9,136.9,136.2,130.2,129.3,128.9,12 8.7,127.9,127.5,127.3,126.1,125.4,122.9,117.8,117.6,117.3,116.9,57.6,49.8,47.8,21.5.

[0042] Example 3:

[0043]

[0044] Cuprous iodide (1.9 mg, 0.01 mmol), a chiral ligand (7.0 mg, 0.012 mmol), and methanol (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -10°C, and o-aminophenyl nitrone 1b (35.2 mg, 0.1 mmol), propargyl ester 2a (46.4 mg, 0.2 mmol), and diisopropylethylamine (25.8 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 8 hours. After the reaction was completed, the product was subjected to simple column chromatography (petroleum ether: ethyl acetate: dichloromethane = 20:1:1 to 10:1:1) to obtain the target product 3b (30 mg), with a yield of 74% and ee = 92%. The analysis results of product 3b are as follows: Column Daicel Chiracel IC; i PrOH / Hexane=30 / 70; flow rate=1.0mL / min; t R1 =7.79min, 96.0%; t R2 =10.26 min, 4.0%; 1H NMR (400MHz, CDCl3): δ7.69 (d, J = 8.1Hz, 1H), 7.50-7.45 (m, 1H), 7.43-7.39 (m, 2H), 7.37-7.32 (m, 1 H),7.29(d,J=7.5Hz,2H),7.26-7.18(m,7H),7.15(dd,J=7.6,1.6Hz,1H),6.52(s,1H),3.73(s,3H). 13 C NMR (101MHz, CDCl3): δ165.0,138.4,137.0,133.9,133.6,133.0,130.8,1 28.5,128.4,128.3,128.1,128.1,127.3,127.2,126.9,126.9,55.9,52.1.

[0045] Example 4:

[0046]

[0047] Copper perchlorate (3.7 mg, 0.01 mmol), a chiral ligand (7.0 mg, 0.012 mmol), and dichloromethane (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -40°C, and o-aminophenyl nitrone 5b (43.0 mg, 0.1 mmol), propargyl ester 2a (46.4 mg, 0.2 mmol), and triethylamine (20.2 mg, 0.2 mmol) were added sequentially. The reaction was continued at this temperature for 40 hours. After the reaction was completed, the product was subjected to simple column chromatography (preferably using petroleum ether: ethyl acetate: dichloromethane = 10:1:1 to 5:1:1) to obtain the target product 4b (30 mg), with a yield of 55% and ee = 91%. The analysis results of product 4b are as follows: Column Daicel Chiracel IA; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =12.79min, 4.4%; t R2 =14.04 min, 95.6%; 1H NMR (400MHz, CDCl3): δ7.91(d,J=2.3Hz,1H),7.85(d,J=8.1Hz,1H),7.70-7.64(m,2H),7.57-7.52(m,1H),7.43-7.26(m,7H),7.21-7.1 6(m,3H),7.13-7.08(m,1H),6.27(d,J=8.7Hz,1H),5.68(d,J=7.7Hz,1H),4.47-4.39(m,1H),4.01(s,1H),2.97(dd,J=7.7,3.9Hz,1H). 13 C NMR (101MHz, CDCl3): δ189.0,148.0,141.6,139.2,138.0,137.2,132.8,130.5,130.0,128.8,1 28.7,127.8,127.7,127.5,127.2,126.3,124.7,123.3,119.0,117.8,111.0,58.0,53.7,51.9.

[0048] Example 5:

[0049]

[0050] Cuprous thiophene-2-carboxylate (1.9 mg, 0.01 mmol), a chiral ligand (6.1 mg, 0.012 mmol), and methanol (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -60°C, and o-aminophenyl nitrone 1c (38.0 mg, 0.1 mmol), propargyl ester 2a (46.4 mg, 0.2 mmol), and sodium carbonate (21.2 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 48 hours. After the reaction was completed, the product was subjected to simple column chromatography (preferably petroleum ether: ethyl acetate: dichloromethane = 20:1:1 to 10:1:1) to obtain the target product 3c (32 mg), with a yield of 74% and ee = 90%. The analysis results of product 3c are as follows: Column Daicel Chiracel IC; i PrOH / Hexane=30 / 70; flow rate=1.0mL / min; t R1 =10.55min, 94.8%; t R2 =13.75 min, 5.2%; 1H NMR (400MHz, CDCl3): δ7.56(d,J=8.2Hz,1H),7.29(d,J=8.3Hz,2H),7.26-7.23(m,2H),7.21-7.17(m,4H),7.13(dd, J=8.2,1.6Hz,1H),7.07(d,J=8.1Hz,2H),6.94(d,J=1.6Hz,1H),6.48(s,1H),3.73(s,3H),2.35(s,3H),2.30(s,3H). 13 C NMR (101MHz, CDCl3): δ165.2,143.7,137.3,136.7,135.7,134.0,131.7,131.5,129 .1,128.7,128.4,128.0,127.8,127.2,127.1,127.1,127.0,55.9,52.1,21.5,20.9.

[0051] Example 6:

[0052]

[0053] Cuprous thiophene-2-carboxylate (1.9 mg, 0.01 mmol), a chiral ligand (6.1 mg, 0.012 mmol), and chloroform (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -60°C, and o-aminophenyl nitrone 5c (45.8 mg, 0.1 mmol), propargyl ester 2a (46.4 mg, 0.2 mmol), and sodium carbonate (21.2 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 48 hours. After the reaction was completed, the product was subjected to simple column chromatography (preferably using petroleum ether: ethyl acetate: dichloromethane = 10:1:1 to 5:1:1) to obtain the target product 4c (35 mg), with a yield of 61% and ee = 88%. The analysis results of product 4c are as follows: Column Daicel Chiracel ID; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =16.57min, 94.1%; t R2 =19.07 min, 5.9%; 1H NMR (400MHz, CDCl3): δ7.91(d,J=2.3Hz,1H),7.74(d,J=8.4Hz,1H),7.53(d, J=8.3Hz,2H),7.36(dd,J=8.7,2.4Hz,1H),7.33-7.25(m,4H),7.20-7.15(m,5 H),6.98-6.95(m,1H),6.22(d,J=8.7Hz,1H),5.58(d,J=8.0Hz,1H),4.43-4.3 7(m,1H),3.92(s,1H),2.92(dd,J=7.9,3.7Hz,1H),2.41(s,3H),2.30(s,3H). 13 C NMR (101MHz, CDCl3): δ189.2,148.1,143.4,141.8,137.9,136.3,134.6,134.5,130.7,130.5,129.4, 128.7,128.1,127.8,127.7,127.1,126.4,123.5,118.9,117.6,110.9,57.9,53.9,52.1,21.6,20.7.

[0054] Example 7:

[0055]

[0056] Copper trifluoroacetate (2.9 mg, 0.01 mmol), a chiral ligand (6.2 mg, 0.012 mmol), and methanol (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -30°C, and o-aminophenyl nitrone 1d (44.4 mg, 0.1 mmol), propargyl ester 2a (46.4 mg, 0.2 mmol), and potassium carbonate (27.8 mg, 0.2 mmol) were added sequentially. The reaction was continued at this temperature for 30 hours. After the reaction was completed, the product was subjected to simple column chromatography (preferably using petroleum ether: ethyl acetate: dichloromethane = 20:1:1 to 10:1:1) to obtain the target product 3d (39 mg), with a yield of 78% and ee = 87%. The analysis results of product 3d are as follows: Column Daicel Chiracel IC; i PrOH / Hexane=30 / 70; flow rate=1.0mL / min; t R1 =7.74min, 93.6%; t R2 =9.82 min, 6.4%; 1H NMR (400MHz, CDCl3): δ7.56(d,J=8.6Hz,1H),7.43(dd,J=8.6,2.3Hz,1H),7.32(d,J=8.3Hz,2H),7.29(d,J =2.3Hz,1H),7.24-7.20(m,5H),7.17(s,1H),7.10(d,J=8.0Hz,2H),6.51(s,1H),3.74(s,3H),2.36(s,3H). 13 C NMR (101MHz, CDCl3): δ164.7,144.2,136.7,135.5,133.5,133.1,132.3,130.7,1 29.5,129.3,128.9,128.7,128.5,128.3,127.1,126.9,120.1,55.9,52.3,21.5.

[0057] Example 8:

[0058]

[0059] Copper trifluoroacetate (2.9 mg, 0.01 mmol), a chiral ligand (6.2 mg, 0.012 mmol), and dichloromethane (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -30°C, and o-aminophenyl nitrone 5d (52.1 mg, 0.1 mmol), propargyl ester 2a (46.4 mg, 0.2 mmol), and potassium carbonate (27.8 mg, 0.2 mmol) were added sequentially. The reaction was continued at this temperature for 30 hours. After the reaction was completed, the product was subjected to simple column chromatography (preferably using petroleum ether: ethyl acetate: dichloromethane = 10:1:1 to 5:1:1) to obtain the target product 4d (44 mg), with a yield of 69% and ee = 85%. The analysis results of product 4d are as follows: Column Daicel Chiracel IA; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =11.98min, 7.5%; t R2 =13.17min, 92.5%; 1H NMR (400MHz, CDCl3): δ7.90(d,J=2.3Hz,1H),7.71(d,J=8.3Hz,2H),7.66(d,J=8.9Hz,1H),7.39-7.36(m,2H),7.33-7.30(m,3H),7.28-7.26( m,1H),7.25-7.23(m,1H),7.23-7.19(m,3H),6.36(d,J=8.7Hz,1H),5. 96(d,J=6.3Hz,1H),4.45-4.35(m,2H),3.12-3.06(m,1H),2.41(s,3H). 13 C NMR (101MHz, CDCl3): δ188.6,147.6,144.1,141.2,138.2,136.7,136.0,132.5,130.4,129.8,129 .6,128.9,128.0,127.9,127.8,126.0,123.1,119.2,117.8,116.9,111.1,57.8,52.2,50.3,21.6.

[0060] Example 9:

[0061]

[0062] Cuprous thiophene-2-carboxylate (1.9 mg, 0.01 mmol), a chiral ligand (6.1 mg, 0.012 mmol), and methanol (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -60°C, and o-aminophenyl nitrone 1e (38.0 mg, 0.1 mmol), propargyl ester 2a (46.4 mg, 0.2 mmol), and sodium bicarbonate (16.8 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 48 hours. After the reaction was completed, the product was subjected to simple column chromatography (petroleum ether: ethyl acetate: dichloromethane = 20:1:1 to 10:1:1) to obtain the target product 3e (32 mg), with a yield of 74% and ee = 95%. The analysis results of product 3e are as follows: Column Daicel Chiracel IC; i PrOH / Hexane=30 / 70; flow rate=1.0mL / min; t R1 =8.97 min, 97.5%; t R2 =12.72 min, 2.5%; 1H NMR (400MHz, CDCl3): δ7.50 (s, 1H), 7.30 (d, J = 8.3Hz, 2H), 7.28-7.24 (m, 2H), 7.23-7.1 7(m,4H),7.09-7.02(m,3H),7.02-6.98(m,1H),6.48(s,1H),3.72(s,3H),2.35(m,6H). 13 C NMR (101MHz, CDCl3): δ165.2,143.8,141.5,137.4,135.7,133.9,133.9,129.0,128 .5,128.4,128.1,128.0,127.7,127.2,127.0,126.0,124.8,55.9,52.0,21.8,21.5.

[0063] Example 10:

[0064]

[0065]

[0066] Cuprous thiophene-2-carboxylate (1.9 mg, 0.01 mmol), a chiral ligand (6.1 mg, 0.012 mmol), and dichloromethane (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -60°C, and o-aminophenyl nitrone 5e (45.8 mg, 0.1 mmol), propargyl ester 2a (46.4 mg, 0.2 mmol), and sodium bicarbonate (16.8 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 48 hours. After the reaction was completed, the product was subjected to simple column chromatography (petroleum ether: ethyl acetate: dichloromethane = 10:1:1 to 5:1:1) to obtain the target product 4e (34 mg), with a yield of 59% and ee = 93%. The analysis results of product 4e are as follows: Column Daicel Chiracel IA; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =10.27min, 96.5%; t R2 =13.24min, 3.5%; 1H NMR (400MHz, CDCl3): δ7.90(d,J=2.3Hz,1H),7.67(s,1H),7.59(d,J=8.3Hz ,2H),7.37-7.26(m,4H),7.22-7.17(m,4H),7.04(d,J=7.7Hz,1H),6.90(d, J=7.7Hz,1H),6.25(d,J=8.7Hz,1H),5.70(d,J=7.5Hz,1H),4.40(d,J=3.3H z,1H),4.04(s,1H),2.95(dd,J=7.5,4.1Hz,1H),2.41(s,3H),2.35(s,3H). 13 C NMR (101MHz, CDCl3): δ189.2,148.0,143.6,141.7,140.0,137.9,137.1,136.3,130.5,129.4,128.7, 127.9,127.6,127.2,126.3,125.2,123.8,123.6,119.0,117.7,110.8,57.9,53.5,51.4,21.6,21.6.

[0067] Example 11:

[0068]

[0069] Cuprous hexafluorophosphate tetraacetonitrile (3.7 mg, 0.01 mmol), a chiral ligand (4.3 mg, 0.012 mmol), and methanol (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to 0°C, and o-aminophenyl nitrone 1a (36.6 mg, 0.1 mmol), propargyl ester 2b (53.2 mg, 0.2 mmol), and 1-methylpiperidine (19.8 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 6 hours. After the reaction was completed, the product was subjected to simple column chromatography (petroleum ether: ethyl acetate: dichloromethane = 20:1:1 to 10:1:1) to obtain the target product 3f (30 mg), with a yield of 66% and ee = 81%. The analysis results of product 3f are as follows: Column Daicel Chiracel IC; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =7.65min, 90.5%; t R2 =9.77 min, 9.5%; 1H NMR (400MHz, CDCl3): δ7.70 (d, J = 8.1Hz, 1H), 7.38-7.33 (m, 1H), 7.29-7.25 (m, 3H), 7.24-7. 19(m,2H),7.18-7.12(m,4H),7.07(d,J=8.0Hz,2H),6.47(s,1H),3.75(s,3H),2.34(s,3H). 13 C NMR (101MHz, CDCl3): δ164.8,144.0,139.4,135.4,134.3,134.1,133.8,131.0,129.7,1 29.1,128.5,128.3,128.0,127.3,127.1,127.0,126.9,126.5,125.5,55.3,52.2,21.5.

[0070] Example 12:

[0071]

[0072] Cuprous hexafluorophosphate tetraacetonitrile (3.7 mg, 0.01 mmol), a chiral ligand (4.3 mg, 0.012 mmol), and 1,2-dichloroethane (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to 0°C, and o-aminophenyl nitrone 5a (44.4 mg, 0.1 mmol), propargyl ester 2b (53.2 mg, 0.2 mmol), and 1-methylpiperidine (19.8 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 6 hours. After the reaction was completed, the product was subjected to simple column chromatography (petroleum ether: ethyl acetate: dichloromethane = 10:1:1 to 5:1:1) to obtain the target product 4f (30 mg), with a yield of 51% and ee = 86%. The analysis results of product 4f are as follows: Column Daicel Chiracel IA; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =10.50min, 7.0%; t R2 =13.96 min, 93.0%; 1HNMR (400MHz, CDCl3): δ7.93-7.84(m,2H),7.53(d,J=8.1Hz,2H),7.41-7.36(m,2H),7.24(d,J=4.7Hz,2H),7.21-7.10(m,5H),7 .08-7.04(m,1H),6.23(d,J=8.7Hz,1H),5.55(d,J=8.0Hz,1H),4.48-4.40(m,1H),3.94(s,1H),2.94-2.88(m,1H),2.42(s,3H). 13 C NMR (101MHz, CDCl3): δ188.7,148.0,143.8(2C),138.0,136.9,135.9,134.5,130.5,130.1,129.9,129. 5,128.0,127.8,127.6,127.0,126.5,124.9,124.8,123.6,118.7,117.7,111.0,57.5,53.6,51.9,21.6.

[0073] Example 13:

[0074]

[0075] Copper trifluoromethanesulfonate (3.6 mg, 0.01 mmol), a chiral ligand (5.8 mg, 0.012 mmol), and methanol (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -20°C, and o-aminophenyl nitrone 1a (36.6 mg, 0.1 mmol), propargyl ester 2c (49.2 mg, 0.2 mmol), and 1-methylpiperidine (19.8 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 12 hours. After the reaction was completed, the product was subjected to simple column chromatography (petroleum ether: ethyl acetate: dichloromethane = 20:1:1 to 10:1:1) to obtain 3 g (35 mg) of the target product, with a yield of 81% and ee = 91%. The analysis results of the 3 g product are as follows: Column Daicel Chiracel IC; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =10.33min, 95.7%; t R2 =15.04 min, 4.3%; 1H NMR (400MHz, CDCl3): δ7.67(d,J=8.1Hz,1H),7.35-7.27(m,3H),7.24(s,1H),7.22-7.15(m,2H),7.13(d,J=7 .9Hz,2H),7.06(d,J=8.0Hz,2H),7.01(d,J=8.0Hz,2H),6.48(s,1H),3.73(s,3H),2.34(s,3H),2.24(s,3H). 13 CNMR (101MHz, CDCl3): δ165.1,143.8,137.8,135.7,134.1,134.0,133.6,130.7,129 .1,129.1,128.3,128.0,127.4,127.4,127.1,126.9,126.7,55.7,52.1,21.5,21.0.

[0076] Example 14:

[0077]

[0078] Copper trifluoromethanesulfonate (3.6 mg, 0.01 mmol), a chiral ligand (5.8 mg, 0.012 mmol), and dichloromethane (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -20°C, and o-aminophenyl nitrone 5a (44.4 mg, 0.1 mmol), propargyl ester 2c (49.2 mg, 0.2 mmol), and 1-methylpiperidine (19.8 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 12 hours. After the reaction was completed, the product was subjected to simple column chromatography (petroleum ether: ethyl acetate: dichloromethane = 10:1:1 to 5:1:1) to obtain 4 g (39 mg) of the target product, with a yield of 68% and ee = 94%. The analysis results of the 4 g product are as follows: Column Daicel Chiracel ID; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =16.89min, 97.0%; t R2 =18.90 min, 3.0%; 1H NMR (400MHz, CDCl3): δ7.90(d,J=2.1Hz,1H),7.83(d,J=8.3Hz,1H),7.57(d,J=8.1Hz,2H),7.37-7.32(m,2H),7.20-7.15(m,3H),7.1 4-7.05(m,5H),6.25(d,J=8.7Hz,1H),5.65(d,J=7.6Hz,1H),4.48-4.40(m,1H),4.06(s,1H),2.96(m,1H),2.41(s,3H),2.31(s,3H). 13 C NMR (101MHz, CDCl3): δ189.1,148.0,143.6,138.7,137.9,137.3,136.3,130.5,129.8,129.4,129 .4,127.8,127.4,126.9,126.2,124.4,123.1,119.0,117.7,110.8,57.7,53.6,51.7,21.6,21.1.

[0079] Example 15:

[0080]

[0081] Copper trifluoromethanesulfonate (3.6 mg, 0.01 mmol), a chiral ligand (4.0 mg, 0.012 mmol), and methanol (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -20°C, and o-aminophenyl nitrone 1a (36.6 mg, 0.1 mmol), propargyl ester 2d (56.4 mg, 0.2 mmol), and 1-methylpiperidine (19.8 mg, 0.2 mmol) were added sequentially. The reaction was continued at this temperature for 12 hours. After the reaction was completed, the product was subjected to simple column chromatography (preferably using petroleum ether: ethyl acetate: dichloromethane = 20:1:1 to 10:1:1) to obtain the target product 3h (26 mg), with a yield of 55% and ee = 90%. The product 3h was analyzed, and the results are as follows: Column Daicel Chiracel IC; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =10.07min, 5.1%; t R2 =11.09 min, 94.9%; 1H NMR (400MHz, CDCl3): δ7.78-7.72(m,2H),7.69-7.64(m,2H),7.61(dd,J=8.6,1.8Hz,1H),7.49(s,1H),7.43-7. 37(m,2H),7.36-7.27(m,4H),7.21-7.16(m,2H),7.09(d,J=8.0Hz,2H),6.68(s,1H),3.75(s,3H),2.36(s,3H). 13 C NMR (101MHz, CDCl3): δ165.1,143.9,135.6,134.4,134.1,133.9,133.0,132.8,130.8,129.1,128. 4,128.3,128.0,127.5,127.4,127.1,127.0,126.9,126.1,126.0,125.9,125.7,56.0,52.2,21.5.

[0082] Example 16:

[0083]

[0084] Copper trifluoromethanesulfonate (3.6 mg, 0.01 mmol), a chiral ligand (4.0 mg, 0.012 mmol), and dichloromethane (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -20°C, and o-aminophenyl nitrone 5a (44.4 mg, 0.1 mmol), propargyl ester 2d (56.4 mg, 0.2 mmol), and 1-methylpiperidine (19.8 mg, 0.2 mmol) were added sequentially. The reaction was continued at this temperature for 12 hours. After the reaction was completed, the product was subjected to simple column chromatography (preferably using petroleum ether: ethyl acetate: dichloromethane = 10:1:1 to 5:1:1) to obtain the target product 4h (33 mg), with a yield of 54% and ee = 85%. The product 4h was analyzed, and the results are as follows: Column Daicel Chiracel IC; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =14.52min, 7.6%; t R2 =18.86 min, 92.4%; 1H NMR (400MHz, DMSO-d6): δ7.98-7.90 (m, 4H), 7.82 (d, J = 3.3Hz, 1H), 7.80-7.74 (m,2H),7.64(d,J=2.2Hz,1H),7.55(d,J=8.5Hz,1H),7.53-7.47(m,3H),7.45 -7.38(m,4H),7.20(t,J=7.8Hz,1H),6.99(t,J=7.5Hz,1H),6.80(d,J=8.9Hz, 1H), 6.48 (d, J = 3.7Hz, 1H), 4.37-4.29 (m, 1H), 3.79-3.70 (m, 1H), 2.36 (s, 3H). 13 C NMR (101MHz, DMSO-d6): δ189.6,149.9,144.8,139.5,138.5,137.9,136.7,133.2,132.8,130.3,129.2,129.1,129.0,12 8.6,128.3,128.1,127.6,127.1,126.7,125.2,125.1,124.2,123.2,119.5,118.7,118.5,108.6,57.8,49.6,48.1,21.5.

[0085] Example 17:

[0086]

[0087] Copper trifluoromethanesulfonate (3.6 mg, 0.01 mmol), a chiral ligand (4.0 mg, 0.012 mmol), and methanol (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -20°C, and o-aminophenyl nitrone 1a (36.6 mg, 0.1 mmol), propargyl ester 2e (44.4 mg, 0.2 mmol), and 1-methylpiperidine (19.8 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 12 hours. After the reaction was completed, the product was subjected to simple column chromatography (petroleum ether: ethyl acetate: dichloromethane = 20:1:1 to 10:1:1) to obtain the target product 3i (25 mg), with a yield of 61% and ee = 91%. The analysis results of product 3i are as follows: Column Daicel Chiracel IC; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =14.65min, 95.5%; t R2 =29.40 min, 4.5%; 1H NMR (400MHz, CDCl3): δ7.71 (d, J = 8.1Hz, 1H), 7.39-7.34 (m, 1H), 7.30-7.26 (m, 3H), 7.24-7.20 (m, 1H), 7.19-7.1 4(m,2H),7.05(d,J=8.0Hz,2H),6.60(s,1H),6.14-6.11(m,1H),5.97(d,J=3.3Hz,1H),3.75(s,3H),2.33(s,3H). 13 C NMR (101MHz, CDCl3): δ164.6,149.7,143.9,143.2,135.5,134.1,133.9,130.8,1 29.1,128.5,127.5,126.9,126.9,126.8,125.3,110.1,108.7,52.1,51.0,21.5.

[0088] Example 18:

[0089]

[0090]

[0091] Copper trifluoromethanesulfonate (3.6 mg, 0.01 mmol), a chiral ligand (4.0 mg, 0.012 mmol), and dichloromethane (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -20°C, and o-aminophenyl nitrone 5a (44.4 mg, 0.1 mmol), propargyl ester 2e (44.4 mg, 0.2 mmol), and 1-methylpiperidine (19.8 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 12 hours. After the reaction was completed, the product was subjected to simple column chromatography (petroleum ether: ethyl acetate: dichloromethane = 10:1:1 to 5:1:1) to obtain the target product 4i (29 mg), with a yield of 53% and ee = 84%. The analysis results of product 4i are as follows: Column Daicel Chiracel IA; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 =12.28min, 92.1%; t R2 =14.11 min, 7.9%; 1H NMR (400MHz, CDCl3): δ7.89(d,J=2.1Hz,1H),7.65(d,J=8.3Hz,1H),7.61(d,J=8.2Hz,2H),7.38-7.32(m,2H),7.25-7.15(m,4H),7. 08-7.02(m,1H),6.40-6.27(m,3H),5.98(d,J=6.9Hz,1H),4.60-4.51(m,1H),4.28(s,1H),3.40(dd,J=6.6,4.9Hz,1H),2.40(s,3H). 13 C NMR (101MHz, CDCl3): δ188.8,152.3,148.1,143.8,142.5,138.1,136.8,136.5,130.5,129.6,129 .5,127.9,127.1,126.3,124.3,122.5,119.0,117.7,110.9,110.6,108.9,51.9,51.4,49.3,21.6.

[0092] Example 19:

[0093]

[0094] Copper trifluoromethanesulfonate (3.6 mg, 0.01 mmol), a chiral ligand (4.0 mg, 0.012 mmol), and ethanol (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to -20°C, and o-aminophenyl nitrone 1a (36.6 mg, 0.1 mmol), propargyl ester 2a (46.6 mg, 0.2 mmol), and diisopropylethylamine (25.8 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 12 hours. After the reaction was completed, the product was subjected to simple column chromatography (petroleum ether: ethyl acetate: dichloromethane = 20:1:1 to 10:1:1) to obtain the target product 3j (26 mg), with a yield of 60% and ee = 84%. The analysis results of product 3j are as follows: Column Daicel Chiracel IC; i PrOH / Hexane=30 / 70; flow rate=1mL / min; t R1 = 9.66 min, 92.1%; t R2 =12.54 min, 7.9%; 1H NMR (400MHz, CDCl3): δ7.69 (d, J = 8.1Hz, 1H), 7.36-7.28 (m, 3H), 7.27-7.24 (m, 2H), 7.24-7.13 (m, 6H), 7.06 (d, J = 8.0Hz, 2H), 6.51 (s, 1H), 4.20 (q, J = 7.1Hz, 2H), 2.34 (s, 3H), 1.27 (t, J = 7.1Hz, 3H). 13 C NMR (101MHz, CDCl3): δ164.6,143.8,137.3,135.7,134.1,133.4,130.7,129.1,128 .4,128.3,128.1,128.0,127.8,127.4,127.2,126.9,126.8,60.9,55.8,21.5,14.3.

[0095] Example 20:

[0096]

[0097] Cuprous hexafluorophosphate tetraacetonitrile (3.7 mg, 0.01 mmol), a chiral ligand (4.3 mg, 0.012 mmol), and 1,2-dichloroethane (2 ml) were added sequentially to a nitrogen-protected reaction flask. After reacting at room temperature for 30 minutes, the temperature was lowered to 0°C, and o-aminophenyl nitrone 5f (40.0 mg, 0.1 mmol), propargyl ester 2a (46.4 mg, 0.2 mmol), and 1-methylpiperidine (19.8 mg, 0.2 mmol) were added sequentially. The reaction was carried out at this temperature for 6 hours. After the reaction was completed, the product was subjected to simple column chromatography (petroleum ether: ethyl acetate: dichloromethane = 10:1:1 to 5:1:1) to obtain the target product 4j (28 mg), with a yield of 54% and ee = 87%. The analysis results of product 4j are as follows: Column Daicel Chiracel IC; i PrOH / Hexane=30 / 70; flow rate=0.5mL / min; t R1 =37.77min, 6.6%; t R2 = 41.15 min, 93.4%; 1HNMR (400MHz, CDCl3): δ7.87(d,J=8.3Hz,1H),7.75(d,J=8.5Hz,1H),7.55(d,J= 8.3Hz,2H),7.40-7.36(m,1H),7.34-7.27(m,3H),7.22-7.16(m,5H),7.16-7.10 (m,1H),6.73(dd,J=8.5,1.8Hz,1H),6.30(d,J=1.8Hz,1H),5.59(d,J=7.9Hz,1H ),4.47(d,J=3.5Hz,1H),3.92(s,1H),2.96(dd,J=7.8,4.0Hz,1H),2.44(s,3H). 13 C NMR (101MHz, CDCl3): δ189.3,149.7,143.7,141.8,141.5,137.2,136.3,130.0,129.8,129.5,128 .7,127.8,127.7,127.5,127.2,126.3,124.7,123.7,119.3,116.1,115.4,58.0,54.0,52.0,21.6.

[0098] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A catalytic synthesis method for chiral polysubstituted hydrogenated quinoline compounds, characterized in that, Includes the following steps: At 0-40℃, using alcohols or haloalkanes as solvents, copper catalysts and chiral ligands were added, and the reaction was carried out under nitrogen protection for 0.5-2 hours. The temperature was then lowered to -60-0℃, and then o-aminophenylnitrone was added sequentially. propargyl ester Reacting with a base for 6-48 hours yields chiral polysubstituted hydrogenated quinoline compounds as shown in Formula 1 or 2: ； Wherein, R is selected from one of phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 2-naphthyl, and 2-thiophene; R 1 Selected from one of hydrogen, 5-methyl, 5-bromo, 4-methyl, 4-fluoro, 4-chloro, 4-bromo, 4-trifluoromethyl, and 4-methoxy; R 2 Selected from one of methyl, ethyl, isopropyl, 2,2,2-trifluoroethyl, and 1,1,1,3,3,3-hexafluoro-2-propyl; R 3 Selected from one of phenyl, 2-chlorophenyl, 2-methylphenyl, 3-chlorophenyl, 3-methylphenyl, 4-chlorophenyl, 4-methylphenyl, 4-fluorophenyl, 4-bromophenyl, 4-iodophenyl, 4-methoxyphenyl, 3,5-dimethylphenyl, 1-naphthyl, 2-naphthyl, 2-thienyl, 2-furanyl, 3-thienyl, and 3-furanyl; R 4 Selected from one of hydrogen, 4-fluoro, 4-chloro, 4-bromine, 3-fluoro, 3-chloro, and 2-methyl; R 5 It is selected from one of acetyl, benzoyl, 3,5-dinitrobenzoyl, and tert-butoxycarbonyl. The copper catalyst is one or more of divalent or monovalent copper salts; the chiral ligand is one or more of chiral Box ligand, chiral PyBox ligand, chiral PHOX ligand, and chiral Phos ligand. The haloalkane is one or more of dichloromethane, 1,2-dichloroethane, or chloroform; the alcohol is one or more of methanol, ethanol, isopropanol, 2,2,2-trifluoroethanol, and 1,1,1,3,3,3-hexafluoro-2-propanol.

2. The catalytic synthesis method for chiral polysubstituted hydrogenated quinoline compounds as described in claim 1, characterized in that: The base is one or more of sodium carbonate, sodium bicarbonate, potassium carbonate, triethylamine, diisopropylethylamine, and 1-methylpiperidine.

3. The catalytic synthesis method for chiral polysubstituted hydrogenated quinoline compounds as described in claim 1, characterized in that: The divalent or monovalent copper salt is one of copper trifluoromethanesulfonate, copper acetate, copper perchlorate, cuprous iodide, cuprous thiophene-2-carboxylate, and cuprous tetraacetonitrile hexafluorophosphate.

4. The catalytic synthesis method for chiral polysubstituted hydrogenated quinoline compounds as described in claim 1, characterized in that: In molar amounts, the amount of the copper catalyst is 5-20% of o-aminophenyl nitrone; the amount of the chiral ligand is 5-25% of o-aminophenyl nitrone; the amount of propargyl ester is 1-3 times that of o-aminophenyl nitrone; and the amount of the base is 1-3 times that of o-aminophenyl nitrone.

5. The catalytic synthesis method for chiral polysubstituted hydrogenated quinoline compounds as described in claim 1, characterized in that: After the reaction is complete, a column chromatography separation and purification step is also included.

6. The catalytic synthesis method for chiral polysubstituted hydrogenated quinoline compounds as described in claim 5, characterized in that: The eluent for the column chromatography was petroleum ether: ethyl acetate: dichloromethane = 20:1:1 to 5:1:1.

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