CN109354583B - Chiral 3, 4-dihydro-2 (1H) -quinolinone compound and preparation method thereof - Google Patents
Chiral 3, 4-dihydro-2 (1H) -quinolinone compound and preparation method thereof Download PDFInfo
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Abstract
A chiral 3, 4-dihydro-2 (1H) -quinolinone compound and a preparation method thereof belong to the technical field of compound preparation. The preparation method specifically comprises the steps of taking vinyl benzoxazinone and oxazolone as synthetic building blocks, adding a metal palladium catalyst, a phosphorus-containing ligand and an acid-base additive, and reacting at room temperature to obtain a product. The preparation method has the advantages of mild reaction conditions, high reaction speed, simple post-treatment and wide substrate range. The method is a brand-new and efficient diastereoselective synthesis method of 3, 4-dihydro-2 (1H) -quinolinone with wide physiological and pharmacological activities such as potential anti-tumor, anti-hypertension, anti-tuberculosis, pain relief and the like.
Description
Technical Field
The invention relates to a chiral 3, 4-dihydro-2 (1H) -quinolinone compound and a preparation method thereof, belonging to the technical field of compound preparation.
Background
3, 4-dihydro-2 (1H) -quinolinone is an important benzo nitrogen-containing heterocyclic compound, and is used as an advantageous drug skeleton structure and widely exists in active natural products and drug molecular structures. The 3, 4-dihydro-2 (1H) -quinolinone compounds with chemical structure complexity and stereochemical structure diversity have wide physiological and pharmacological activities of resisting tumors, hypertension, tuberculosis, pain and the like, and have important application and research values in the aspects of medicine, pharmacy and the like. At present, the stereoselective synthesis of chiral 3, 4-dihydro-2 (1H) -quinolinone has been reported in related literatures; however, the synthetic methods reported in these documents still have many shortcomings and limitations in terms of high efficiency, simplicity, stereochemical selectivity, and the like. Therefore, the synthesis method which is simple and efficient in construction, mild in condition, environment-friendly and simple and convenient to operate is used for constructing the 3, 4-dihydro-2 (1H) -quinolinone compounds with complex and diverse structures, and is a subject with important research value and practical application significance.
The vinyl benzoxazinone is an important organic synthesis building block and is widely applied to synthesis of various nitrogen heterocyclic compounds with complex and various structures. Under the synergistic catalytic action of palladium and a phosphorus-containing ligand, the vinyl benzoxazinone is easy to undergo intramolecular decarboxylation reaction to generate the allyl palladium zwitterion with high reaction activity. The reaction intermediate with high activity generated in situ can be used as a four-atom synthon to perform various cycloaddition reactions with electron-deficient olefin, thioylide, isatin, olefine aldehyde and the like, and is used for constructing various nitrogen heterocyclic systems with complex and various structures. Meanwhile, oxazolone as a synthetic building block with abundant chemical properties also has very wide and important application in cycloaddition reaction. The invention takes vinyl benzoxazinone and oxazolone which are easily available as reaction substrates, and realizes diastereoselective synthesis of 3, 4-dihydro-2 (1H) -quinolinone with reasonable chemical yield by constructing concise and efficient [4+2] cycloaddition reaction under mild conditions under the catalytic action of palladium and phosphorus ligands. The 3, 4-dihydro-2 (1H) -quinolinone contains a plurality of functional groups and two continuous chiral centers, has extremely strong drug-like chemical structure and spatial structure, and has potential biological activity and medicinal value in the aspects of resisting tumors, hypertension, tuberculosis, pain and the like.
Disclosure of Invention
The invention aims to provide a preparation method of a chiral 3, 4-dihydro-2 (1H) -quinolinone compound.
In order to achieve the purpose of the invention, the technical scheme adopted by the invention is as follows:
A preparation method of chiral 3, 4-dihydro-2 (1H) -quinolinone compounds comprises the following steps: taking vinyl benzoxazinone compounds and oxazolone compounds as reactants, adding a metal palladium catalyst, a phosphorus-containing ligand and an acid-base additive, and reacting in an organic solvent with the polarity of 2-6 at room temperature to obtain a chiral 3, 4-dihydro-2 (1H) -quinolinone compound; preferably, the mol ratio of the vinyl benzoxazinone compound to the oxazolone compound is 1: 1.2;
The structural formula of the 3, 4-dihydro-2 (1H) -quinolinone compound is as follows:
Wherein R is 1Is hydrogen One of fluorine, chlorine, bromine, nitro, alkyl and aryl; r 2Is one of hydrogen, alkyl, sulfonyl, arylsulfonyl, tert-butyloxycarbonyl and p-methoxybenzyl; r 3Is hydrogen or alkyl; r 4Is one of alkyl, pyridyl, imidazolyl or aryl, R 5Is hydrogen, benzyl, alkyl or aryl; the above aryl group means a phenyl group or a substituted phenyl group.
The substituents on the above phenyl groups are selected from: one of methyl, methoxy, bromine, chlorine, nitro or trifluoromethyl.
The alkyl group is selected from methyl, ethyl, propyl, butyl, and the like.
In the above technical scheme, the organic solvent is dichloromethane, tetrahydrofuran, 1, 2-dichloroethane, toluene, acetonitrile or chloroform.
In the above technical scheme, the palladium catalyst is selected from tetrakis (triphenylphosphine) palladium, palladium acetate, bis (triphenylphosphine) palladium dichloride, tris (dibenzylideneacetone) dipalladium or tris (dibenzylideneacetone) dipalladium-chloroform adduct.
In the above technical solution, the phosphorus-containing ligand is selected from: one or more of tricyclohexylphosphine, triphenylphosphine, 1' -bis (diphenylphosphino) ferrocene, 1, 4-bis (diphenylphosphino) butane, 1, 3-bis (diphenylphosphino) propane and 1, 2-bis (diphenylphosphino) benzene.
In the above technical scheme, the acid-base additive is selected from: one or more of trimethylchlorosilane, triethylamine, ytterbium trifluoromethanesulfonate, trifluoroacetic acid, benzoic acid, glacial acetic acid, stearic acid, p-nitrobenzoic acid and p-toluenesulfonic acid.
In the technical scheme, the reaction time is 2-6 hours.
In the technical scheme, the dosage of the palladium catalyst is 2.5-15% of the molar weight of the vinyl benzoxazinone compound.
In the technical scheme, the dosage of the phosphorus-containing ligand is 5-30% of the molar weight of the vinyl benzoxazinone compound.
in the technical scheme, the reaction process comprises the steps of adding a vinyl benzoxazinone compound, an oxazolone compound, a metal palladium catalyst and a phosphorus-containing ligand into a reaction bottle, adding an organic solvent for reaction at room temperature, detecting the reaction process by using a TLC (liquid chromatography), and obtaining a target product by simple column chromatography (eluent is selected from ethyl acetate/petroleum ether mixed solution with the volume ratio of 1: 1-2) of a crude product after the reaction is finished.
The preparation method of the vinyl benzoxazinone compound belongs to the prior art, and the structural formula is as follows:
The preparation method of the oxazolone compound belongs to the prior art, and the structural formula is as follows:
The reaction process disclosed by the invention is as follows:
Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages:
1. The invention provides a method for preparing chiral 3, 4-dihydro-2 (1H) -quinolinone compounds by taking vinyl benzoxazinone compounds and oxazolone compounds as reactants and adding a metal palladium catalyst and a phosphorus-containing ligand for the first time; the method has the advantages of simple operation, mild reaction conditions and short time.
2. The preparation method disclosed by the invention has the advantages of small catalyst consumption and simple post-treatment.
3. The method disclosed by the invention has wide substrate application range.
4. The raw materials related by the invention are convenient and easy to obtain, and have no pollution.
Detailed Description
The present invention will be further described with reference to the following examples, but the present invention is not limited to the following examples.
Example 1:
1a (17.5mg, 0.1mmol), 2a (19.2mg, 0.12mmol), palladium catalyst (5.2mg, 0.005mmol) and ligand PPh were weighed out 3(2.6mg, 0.01mmol) is dissolved in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) is added and stirred for 4 hours (detection reaction by TLC), after the reaction is completed, the crude product is subjected to column chromatography (eluent is selected as petroleum ether/ethyl acetate mixed solution with volume ratio of 1: 1) to obtain the target product 3aa (23.9mg), and the yield is 82%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):8.72(s,1H),7.84–7.82(m,2H),7.55–7.50(m,1H),7.46–7.42(m,2H),7.23-7.20(m,2H),7.09-7.05(m,1H),6.95(d,J＝8.2,1H),6.87-6.85(m 1H),6.04-5.95(m,1H),5.38(dd,J＝10.0Hz,1H),5.26(dd,J＝17.2Hz,1H),5.00(dd,J＝13.2 1H),3.69(dd,J＝13.2 1H)ppm；HRMS(ESI)m/z：C18H16N2O2[M+H]+Theoretical calculation 293.1285, found 293.1288.
Example 2:
1b (19.3mg, 0.1mmol), 2a (19.2mg, 0.12mmol), palladium catalyst (5.2mg, 0.005mmol) and ligand PPh were weighed out 3(2.6mg, 0.01mmol) in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) was added and stirred for 4 hours (detection of the reaction with TLC), after completion of the reaction the crude product was subjected to column chromatography (eluent was selected as body) Petroleum ether/ethyl acetate mixed solution with a volume ratio of 1: 1) to obtain the target product 3ba (21.7mg) with a yield of 70%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):8.86(s,1H),7.85-7.83(m,2H),7.56-7.51(m,1H),7.49-7.44(m,2H),7.20-7.16(m,1H),6.86(d,J＝8.0,1H),6.77(td,J＝8.4,1H),6.63(dd,J＝9.2,1H),6.01-5.92(m,1H),5.40(dd,J＝10.0Hz,1H),5.28(d,J＝17.2Hz,1H),4.99(m,1H),3.66(dd,J＝13.2 1H)ppm；HRMS(ESI)m/z：C18H15FN2O2[M+H]+Theoretical calculation 311.1190, found 311.1196.
Example 3:
1c (20.9mg, 0.1mmol), 2a (19.2mg, 0.12mmol), palladium catalyst (5.2mg, 0.005mmol) and ligand PPh were weighed out 3(2.6mg, 0.01mmol) is dissolved in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) is added and stirred for 4 hours (detection reaction is carried out by TLC), after the reaction is completed, the crude product is subjected to column chromatography (eluent is selected as petroleum ether/ethyl acetate mixed solution with volume ratio of 1: 1) to obtain the target product 3ca (17.9mg), and the yield is 55%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):8.62(s,1H),7.83(d,J＝7.6,2H),7.56-7.52(m,1H),7.50-7.44(m,2H),7.17(d,J＝8.0 1H),7.07(d,J＝7.21H),6.90(s,1H),6.81(d J＝8.0 1H),6.02-5.93(m,1H),5.43(d,J＝10.0Hz,1H),5.00(dd,J＝17.2Hz,1H),5.05-4.98(m,1H),3.70-3.65(m,1H)ppm；HRMS(ESI)m/z：C18H15ClN2O2[M+H]+Theoretical calculation 327.0895, found 327.0899.
Example 4:
1d (20.9mg, 0.1mmol), 2a (19.2mg, 0.12mmol) and palladium catalyst (5.2mg, 0.0 mmol) were weighed out 05mmol) and the ligand PPh 3(2.6mg, 0.01mmol) is dissolved in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) is added and stirred for 4 hours (detection reaction by TLC), after the reaction is completed, the crude product is subjected to column chromatography (eluent is selected as petroleum ether/ethyl acetate mixed solution with volume ratio of 1: 1) to obtain the target product 3da (17.9mg), and the yield is 55%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):8.54(s,1H),7.85-7.83(m,2H),7.54-7.44(m,3H),7.38-7.37(m,2H),6.77(d,J＝8.4 2H),6.03-5.94(m 1H),5.45(dd,J＝10,1H),5.30(d,J＝16.4Hz,1H),5.02-4.96(m,1H),3.72(dd,J＝13.2 1H)ppm；HRMS(ESI)m/z：C18H15ClN2O2[M+H]+Theoretical calculation 327.0895, found 327.0902.
Example 5:
1e (25.3mg, 0.1mmol), 2a (19.2mg, 0.12mmol), palladium catalyst (5.2mg, 0.005mmol) and ligand PPh were weighed out 3(2.6mg, 0.01mmol) is dissolved in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) is added and stirred for 4 hours (detection reaction by TLC), after the reaction is completed, the crude product is subjected to column chromatography (eluent is selected as petroleum ether/ethyl acetate mixed solution with volume ratio of 1: 1) to obtain the target product 3ea (20.0mg), and the yield is 54%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):9.05(s,1H),7.82(d,J＝7.2,2H),7.44(t,J＝7.6 2H),7.15-7.10(m,2H),6.98(d,J＝8.4,1H)6.76(d,J＝8.4,1H),5.95-5.86(m 1H),6.04-5.95(m,1H),5.41(dd,J＝10.0Hz,1H),5.28(d,J＝16.8Hz,1H),4.96-4.91(m,1H),3.70-3.65(m,1H)ppm；HRMS(ESI)m/z：C18H15BrN2O2[M+H]+Theoretical calculation 371.0390, found 371.0399.
Example 6:
1f (18.9mg, 0.1mmol), 2a (19.2mg, 0.12mmol), palladium catalyst (5.2mg, 0.005mmol) and ligand PPh were weighed out 3(2.6mg, 0.01mmol) is dissolved in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) is added and stirred for 4 hours (detection reaction by TLC), after the reaction is completed, the crude product is subjected to column chromatography (eluent is selected as petroleum ether/ethyl acetate mixed solution with volume ratio of 1: 1) to obtain the target product 3fa (21.4mg), and the yield is 70%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):8.72(s,1H),7.83(d,J＝8.0 2H),7.54–7.50(m,1H),7.48–7.42(m,2H),7.03(d,J＝7.6 2H),6.94(d,J＝8.01H),6.74(d,J＝8.0,1H),6.03-5.94(m,1H),5.39-5.37(m,1H),5.26(d,J＝16.8Hz,1H),4.98(dd,J＝13.2 1H),3.66(dd,J＝13.2 1H)2.32(s,3H)ppm；HRMS(ESI)m/z：C19H18N2O2[M+H]+Theoretical calculation 307.1441, found 307.1447.
Example 7:
1a (17.5mg, 0.1mmol), 2b (21.0mg, 0.12mmol), palladium catalyst (5.2mg, 0.005mmol) and ligand PPh were weighed out 3(2.6mg, 0.01mmol) is dissolved in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) is added and stirred for 4 hours (detection reaction is carried out by using TL C), after the reaction is completed, the crude product is subjected to column chromatography (eluent is selected as petroleum ether/ethyl acetate mixed solution with the volume ratio of 1: 1) to obtain the target product 3ab (22.0mg), and the yield is 72%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):8.86(s,1H),7.73(d,J＝8.0 2H),7.27-7.20(m,4H),7.09-7.05(m,1H),6.89(d,J＝8.0Hz,1H),6.86(d,J＝7.6Hz,1H),6.03-5.94(m,1H),5.38-5.35(m,1H),5.24(d,J＝16.8Hz,1H),5.02-4.97(m,1H),3.71-3.65(m 1H),2.41(s,3H)ppm；HRMS(ESI)m/z：C19H18N2O2[M+H]+Theoretical calculation value 307.1441, found value 3 07.1447。
Example 8:
1b (19.3mg, 0.1mmol), 2b (21.0mg, 0.12mmol), palladium catalyst (5.2mg, 0.005mmol) and ligand PPh were weighed out 3(2.6mg, 0.01mmol) is dissolved in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) is added and stirred for 4 hours (detection reaction is carried out by TLC), after the reaction is completed, the crude product is subjected to column chromatography (eluent is selected as petroleum ether/ethyl acetate mixed solution with volume ratio of 1: 1) to obtain the target product 3bb (25.3mg), and the yield is 78%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):8.48(s,1H),7.73(d,J＝8.0 2H),7.28-7.25(m,4H),6.77-6.71(m,2H),6.02-5.93(m 1H),5.43(d,J＝10.4Hz,1H),5.29(d,J＝17.2Hz,1H),4.98(dd,J＝13.2Hz 1H),3.70(dd,J＝13.2 1H),2.42(s,3H)ppm；HRMS(ESI)m/z：C19H17FN2O2[M+H]+Theoretical calculation 325.1347, found 325.1355.
Example 9:
1c (20.9mg, 0.1mmol), 2b (21.0mg, 0.12mmol), palladium catalyst (5.2mg, 0.005mmol) and ligand PPh were weighed out 3(2.6mg, 0.01mmol) is dissolved in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) is added and stirred for 4 hours (detection reaction by TLC), after the reaction is completed, the crude product is subjected to column chromatography (eluent is selected as petroleum ether/ethyl acetate mixed solution with volume ratio of 1: 1) to obtain the target product 3cb (17.0mg), and the yield is 50%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):8.38(s,1H),7.73(d,J＝8.0,2H),7.28-7.24(m,4H),6.77-6.71(m,2H),6.02-5.93(m,1H),5.43(d,J＝10.4,1H),5.29(d J＝17.2,1H),4.98(dd,J＝13.2Hz,1H),3.70(dd,J＝13.21H)2.42(s,3H)ppm；HRMS(ESI)m/z：C19H17ClN2O2[M+H]+Theoretical calculation 341.1051, found 341.1057.
Example 10:
1d (20.9mg, 0.1mmol), 2b (21.0mg, 0.12mmol), palladium catalyst (5.2mg, 0.005mmol) and ligand PPh were weighed out 3(2.6mg, 0.01mmol) is dissolved in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) is added and stirred for 4 hours (detection reaction by TLC), after the reaction is completed, the crude product is subjected to column chromatography (eluent is selected as petroleum ether/ethyl acetate mixed solution with volume ratio of 1: 1) to obtain the target product 3db (17.0mg), and the yield is 50%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):8.40(s,1H),7.73(d,J＝8.0 2H),7.25(d,J＝8.0 2H),7.16(d,J＝8.0 1H),7.06(d,J＝8.4 1H),6.88(s,1H),7.76(d,J＝7.6,1H),6.01-5.92(m 1H),5.40(d,J＝10,1H),5.27(d,J＝16.8Hz,1H),5.00-4.94(m,1H),3.65(dd,J＝13.2 1H),3.42(s,3H)ppm；HRMS(ESI)m/z：C19H17ClN2O2[M+H]+Theoretical calculation 341.1051, found 341.1056.
Example 11:
1e (25.3mg, 0.1mmol), 2b (21.0mg, 0.12mmol), palladium catalyst (5.2mg, 0.005mmol) and ligand PPh were weighed out 3(2.6mg, 0.01mmol) is dissolved in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) is added and stirred for 4 hours (detection reaction is carried out by TLC), after the reaction is completed, the crude product is subjected to column chromatography (eluent is selected as petroleum ether/ethyl acetate mixed solution with volume ratio of 1: 1) to obtain the target product 3eb (20.7mg), and the yield is 54%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):8.13(s,1H),7.74(d,J＝8.0 2H),7.28-7.23(m,4H),6.80(d,J＝8.8 1H),6.70(d,J＝8.0 1H),6.03-5.94(m1H),5.44-5.42(m,1H),5.28(d,J＝16.8Hz,1H),4.98(dd,J＝13.2Hz1H),3.68(dd,J＝13.21H),2.43(s,3H)ppm；HRMS(ESI)m/z：C19H17BrN2O2[M+H]+Theoretical calculation 385.0546, found 385.0555.
Example 12:
1f (18.9mg, 0.1mmol), 2b (21.0mg, 0.12mmol), palladium catalyst (5.2mg, 0.005mmol) and ligand PPh were weighed out 3(2.6mg, 0.01mmol) is dissolved in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) is added and stirred for 4 hours (detection reaction by TLC), after the reaction is completed, the crude product is subjected to column chromatography (eluent is selected as petroleum ether/ethyl acetate mixed solution with volume ratio of 1: 1) to obtain the target product 3fb (21.8mg), and the yield is 68%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):8.38(s,1H),7.75-7.73(d,J＝8.0Hz,2H),7.24(d,J＝8.0Hz,2H),7.07-7.04(m,2H),6.78(dd,J＝14.0Hz,2H),6.05-5.96(m,1H),5.38(dd,J＝10.0,1H),5.25(dd,J＝16.8,1H),4.99(dd,J＝13.2 1H),3.69-3.63(m,1H)2.41(s,3H)2.34(s,3H)ppm；HRMS(ESI)m/z：C20H20N2O2[M+H]+Theoretical calculation 321.1598, found 321.1607.
Example 13:
1a (17.5mg, 0.1mmol), 2c (30.1mg, 0.12mmol), palladium catalyst (5.2mg, 0.005mmol) and ligand PPh were weighed out 3(2.6mg, 0.01mmol) is dissolved in 1.0m L dichloromethane, benzoic acid (2.4mg, 0.02mmol) is added and stirred for 4 hours (detection reaction is carried out by TLC), after the reaction is completed, the crude product is subjected to column chromatography (eluent is selected as petroleum ether/ethyl acetate mixed solution with volume ratio of 1: 1) to obtain the target product 3ac (13.4mg), The yield was 35%.
Characterization and analysis of the target: a yellow solid, which is a solid, 1H NMR(400MHz,CDCl3):8.68(s,1H),7.65-7.63(m,2H),7.51–7.48(m,1H),7.40(t,J＝7.60 2H),7.25-7.17(m,7H),7.07-7.04(m,1H),6.79(d,J＝7.60,1H),6.29(s 1H),6.27-6.18(m,1H),5.51(dd,J＝10.0Hz,1H),5.38(d,J＝16.8Hz,1H),4.90(d,J＝9.6 1H),3.30(d,J＝14.4 1H)3.17(d,J＝14.0 1H)ppm；HRMS(ESI)m/z：C25H22N2O2[M+H]+Theoretical calculation 383.1754, found 383.1770.
The results show that the preparation method disclosed by the invention has the advantages of mild reaction conditions, high reaction speed and simple post-treatment.
Claims (5)
1. A preparation method of chiral 3, 4-dihydro-2 (1H) -quinolinone compounds is characterized in that vinyl benzoxazinone compounds and oxazolone compounds are used as reactants, and a metal palladium catalyst, a phosphorus-containing ligand and an acid-base additive are added to react in a polar organic solvent at room temperature to obtain the chiral 3, 4-dihydro-2 (1H) -quinolinone compounds; the mol ratio of the vinyl benzoxazinone compound to the oxazolone compound is 1: 1.2;
The structural formula of the 3, 4-dihydro-2 (1H) -quinolinone compound is as follows:
The structural formula of the vinyl benzoxazinone compound is shown as follows:
The structural formula of the oxazolone compound is shown as follows:
Wherein R is 1Is one of hydrogen, fluorine, chlorine, bromine, nitryl, alkyl and aryl; r 2Is one of hydrogen, alkyl, sulfonyl, arylsulfonyl, tert-butyloxycarbonyl and p-methoxybenzyl; r 3Is hydrogen or alkyl; r 4Is one of alkyl, pyridyl, imidazolyl or aryl, R 5Is hydrogen, benzyl, alkyl or aryl; the above aryl group means a phenyl group or a substituted phenyl group; the palladium catalyst is selected from tetrakis (triphenylphosphine) palladium, palladium acetate, bis (triphenylphosphine) palladium dichloride, tris (dibenzylideneacetone) dipalladium or tris (dibenzylideneacetone) dipalladium-chloroform adduct; the phosphorus-containing ligand is selected from: one or more of tricyclohexylphosphine, triphenylphosphine, 1' -bis (diphenylphosphino) ferrocene, 1, 4-bis (diphenylphosphino) butane, 1, 3-bis (diphenylphosphino) propane and 1, 2-bis (diphenylphosphino) benzene; the acid-base additive is selected from: one or more of trimethylchlorosilane, triethylamine, ytterbium trifluoromethanesulfonate, trifluoroacetic acid, benzoic acid, glacial acetic acid, stearic acid, p-nitrobenzoic acid and p-toluenesulfonic acid;
The substituents on the phenyl group are selected from: one of methyl, methoxy, bromine, chlorine, nitro or trifluoromethyl;
The organic solvent is selected from dichloromethane, tetrahydrofuran, 1, 2-dichloroethane, toluene, acetonitrile or trichloromethane.
2. The process according to claim 1, wherein the alkyl group is selected from the group consisting of methyl, ethyl, propyl, and butyl.
3. The method for preparing chiral 3, 4-dihydro-2 (1H) -quinolinone compounds according to claim 1, wherein the amount of the palladium catalyst is 2.5-15% of the molar amount of the vinyl benzoxazinone compounds.
4. The method for preparing chiral 3, 4-dihydro-2 (1H) -quinolinone compounds according to claim 1, wherein the phosphorus-containing ligand is used in an amount of 5-30% by mole based on the vinyl benzoxazinone compound.
5. The preparation method of the chiral 3, 4-dihydro-2 (1H) -quinolinone compound according to claim 1, wherein the crude product is subjected to simple column chromatography to obtain a target product, and the eluent is selected from a mixed solution of ethyl acetate and petroleum ether in a volume ratio of 1: 1-2.
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