A method for preparing a chiral dihydroquinolone compound

Abstract

The application belongs to the technical field of organic synthesis, and particularly relates to a preparation method of a chiral dihydroquinolone compound. The application utilizes N-heterocyclic carbene (NHC) as a catalyst, and generates the chiral dihydroquinolone through a nitrogen hetero-diene Diels-Alder reaction of a chloroaldehyde and an azo-ortho-benzoquinone precursor under the action of NHC and an alkaline reagent. The preparation method of the application does not need to use a transition metal as a catalyst, can perform a reaction under relatively mild conditions, and has the advantages of green environmental protection, low cost, wide substrate selectivity, mild reaction conditions and the like. In addition, by optimizing the reaction conditions of the preparation method, the product has high yield, high purity, unique cis selectivity and excellent enantioselectivity. The application provides a new route and new idea for the chiral dihydroquinolone compound, can play an important role in the fields of drug intermediates and the like, and has good application value and potential.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology. More specifically, it relates to a method for preparing chiral dihydroquinolone compounds. Background Technology

[0002] The quinolone skeleton is one of the important skeletons of natural products and is known as a superior skeleton in the pharmaceutical field. Due to its unique structure and excellent activity, this class of compounds has become an important member of the vast database of bioactive molecules. Among them, dihydroquinolone drugs are important representatives of quinolone compounds, widely found in natural products and marketed drugs, exhibiting significant biological activity. For example, aripiprazole (an antipsychotic), carteolol hydrochloride (a non-selective beta-blocker), vesinalinone (a cardiotonic), and cilostazol (a phosphodiesterase-3 inhibitor) are all natural products useful for drugs or medicine, and all contain the dihydroquinolone motif. In addition, dihydroquinolone drugs may also serve as multifunctional intermediates, which can be further converted into several other common heterocycles, such as tetrahydroquinoline or other quinolone drugs, showing promising application prospects.

[0003]

[0004] Currently, the synthesis of chiral dihydroquinolones is mainly based on two strategies: 1) asymmetric intermolecular 1,4-addition of quinolones via organometallic reagents; and 2) aza-Michael addition of aminochalcones. While both strategies are effective, they require demanding reaction conditions and involve lengthy steps. For example, Chinese patent application CN112239456A discloses a method for substituting 2,3-... The method for preparing dihydroquinolone compounds involves reacting N-pyridinesulfonyl-o-iodoaniline with an olefin, using a complex of palladium salt and ligand as a catalyst, and requiring the addition of reaction aids and oxidants. The reaction can only be completed at 100–120°C in the reaction medium. The process is cumbersome, requires a large number of reagents, and is costly. Furthermore, there is still room for improvement in selectivity. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to overcome the defects and shortcomings of the existing dihydroquinolone synthesis methods, such as cumbersome process, high requirements for reaction conditions, high cost, and limited yield and selectivity. The present invention provides a green, environmentally friendly, low-cost, mild reaction condition, simple reaction, and high yield and selectivity method for preparing chiral dihydroquinolone compounds.

[0006] Another object of the present invention is to provide the application of the preparation method in the preparation of drugs containing dihydroquinolone structural units, tetrahydroquinoline or quinolone drugs.

[0007] The above-mentioned objective of this invention is achieved through the following technical solution:

[0008] This invention protects a method for preparing a chiral dihydroquinolone compound. The specific preparation method is as follows: Compound 1, Compound 2, catalyst NHC, alkaline reagent and Lewis acid are reacted completely in an organic solvent under inert gas protection at 20-35°C. After separation and purification, Compound 3 (a chiral dihydroquinolone compound) is obtained.

[0009] The synthesis route is as follows:

[0010]

[0011] Where R represents a double substitution, and each substitution is independently C. 1～5 Alkoxy, or methylenedioxy, wherein the two alkoxy groups of the methylenedioxy group are respectively attached to two adjacent carbon atoms on the benzene ring; Ar is an aryl or substituted aryl, wherein the substituent in the substituted aryl group is C. 1～12 Alkyl or C 1～5 One or more of the alkoxy groups; R 1 Selected from C 1～12 One of alkyl, aryl, or substituted aryl, wherein the substituent in the substituted aryl group is selected from C10. 1～12 Alkyl, C 1～5 Alkoxy, C 1～3 One of the following: alkyl halogroups or halogens;

[0012] The aryl group has 5 to 10 carbon atoms.

[0013] This invention uses N-heterocyclic carbene (NHC) as a catalyst. Chlorinated aldehydes react with aza-o-benzoquinone precursors via a Diels-Alder reaction in the presence of NHC, a basic reagent, and a Lewis acid to generate chiral dihydroquinones. The reaction mechanism is as follows:

[0014] The chiral NHC catalyst first chemically selectively attacks the favorable carbonyl carbon to generate an enol; then, it forms intermediate III with aziridine in the presence of a Lewis acid, promoting the Diels-Alder reaction; finally, intermediate IV generates a chiral dihydroquinone as the target product via intramolecular electron transfer, while the NHC catalyst is released to continue catalytic cycling. The lithium ions in the added Lewis acid form lithium bonds with both the enol and aziridine intermediates, enhancing the reactivity and improving product yield, regioselectivity, and enantioselectivity.

[0015] Preferably, R is a disubstituted compound, each of which is independently C. 1～5Alkoxy, or methylenedioxy, wherein the two alkoxy groups of the methylenedioxy group are respectively attached to two adjacent carbon atoms on the benzene ring; Ar is selected from phenyl or substituted phenyl, naphthyl, wherein the substituent in the substituted phenyl is C. 1～8 Alkyl or C 1～4 One or more of the alkoxy groups; R 1 Selected from C 1～12 One of alkyl, phenyl or substituted phenyl, naphthyl, furanyl, wherein the substituent in the substituted phenyl is selected from C 1～8 Alkyl, C 1～4 Alkoxy, C 1～3 One of the following: alkyl halogroups and halogens.

[0016] More preferably, R is a disubstituted compound, each being either methoxy or methylenedioxy, wherein the two alkoxy groups of the methylenedioxy compound are respectively bonded to two adjacent carbon atoms on the benzene ring; Ar is selected from phenyl or substituted phenyl, naphthyl, wherein the substituent in the substituted phenyl is one or more of methyl or methoxy; R 1 It is selected from one of pentyl, decyl, phenyl or substituted phenyl, naphthyl, furanyl, wherein the substituent in the substituted phenyl is selected from one of methyl, methoxy, trifluoromethyl, halogen.

[0017] Furthermore, the catalyst NHC is selected from any of the following structures:

[0018]

[0019] Furthermore, the alkaline reagent is selected from one or more of 1,8-diazabicycloundec-7-ene, potassium tert-butoxide, and cesium carbonate.

[0020] Preferably, the alkaline reagent is selected from one or both of cesium carbonate or potassium tert-butoxide.

[0021] Furthermore, the organic solvent is selected from one of dichloromethane, tetrahydrofuran, toluene, methyl tert-butyl ether, and acetonitrile.

[0022] Preferably, the organic solvent is selected from dichloromethane or toluene.

[0023] Preferably, the Lewis acid is lithium fluoride or lithium chloride.

[0024] Furthermore, the reaction time is 12–24 hours.

[0025] Furthermore, the inert gas is nitrogen or argon.

[0026] Further, the molar ratio of compound 1, compound 2, catalyst N-heterocyclic carbene, basic reagent, and Lewis acid is (0.5-1):(1-2):(0.1-0.2):(1.5-3):(0.25-0.5).

[0027] Preferably, the molar ratio of compound 1, compound 2, catalyst N-heterocyclic carbene, basic reagent, and Lewis acid is 1:2:0.2:3:0.5.

[0028] The chiral dihydroquinolone compounds prepared according to the preparation method described in this invention can be easily processed to remove the p-toluenesulfonyl protecting group to obtain free lactams, or can be easily converted into chiral tetrahydroquinolinones and quinolinone derivatives.

[0029] In addition, the present invention also protects the use of the method for preparing the chiral dihydroquinolone compound in the preparation of drugs containing dihydroquinolone structural units, tetrahydroquinoline or quinolone.

[0030] The present invention has the following beneficial effects:

[0031] This invention provides a method for preparing chiral dihydroquinolones. Using NHC as a catalyst, the method involves reacting chloroaldehydes, azidoquinone precursors, a basic reagent, and lithium fluoride in an organic solvent under inert gas protection at 20–35°C, via a Diels-Alder reaction to generate chiral dihydroquinolones. This method eliminates the need for transition metal catalysts, allows for reactions under milder conditions, and offers advantages such as being environmentally friendly, low-cost, having broad substrate selectivity (both aromatic and aliphatic α-chloroaldehydes show good synthetic results), and mild reaction conditions. Furthermore, optimizing the reaction conditions of this method can result in high yields, high purity, and unique cis-selectivity and excellent enantioselectivity of the product. This invention provides a novel route and approach for chiral dihydroquinolones, which has significant potential and application value in pharmaceutical intermediates and other fields. Attached Figure Description

[0032] Figure 1 This is a diagram illustrating the reaction mechanism of chiral dihydroquinolones.

[0033] Figure 2 The 1H spectrum is shown for the chiral dihydroquinolone compound 3a prepared in Example 1.

[0034] Figure 3 The C-ray spectroscopy spectrum of chiral dihydroquinolone compound 3a prepared in Example 1 is shown.

[0035] Figure 4The HPLC chromatograms of chiral dihydroquinolone compound 3a prepared in Example 1 are shown below; where A is the HPLC chromatogram of racemic dihydroquinolone compound 3a and B is the HPLC chromatogram of chiral dihydroquinolone compound 3a.

[0036] Figure 5 The structural formulas and related data diagrams of compounds 3a to 3o are shown.

[0037] Figure 6 The structural formulas and related data diagrams for compounds 3p to 3u are shown. Detailed Implementation

[0038] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0039] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0040] The NHC catalyst structure used in the embodiments of the present invention is any one of the following:

[0041]

[0042] The reaction mechanism diagram for the preparation of chiral dihydroquinolones in this invention is shown below. Figure 1 As shown. Specifically, under alkaline conditions, the chiral NHC catalyst first chemically selectively attacks the favorable carbonyl carbon (compound 2) to generate an enol (intermediate II), then reacts with azido-o-methylenebenzoquinone (intermediate I formed by the loss of TsH from compound 1) in the presence of a Lewis acid to form intermediate III, which promotes the Diels-Alder reaction; finally, intermediate IV generates a chiral dihydroquinone as the target product via intramolecular electron transfer, while the NHC catalyst is released to continue its catalytic cycle.

[0043] Preparation methods of chiral dihydroquinolone 3a in Examples 1-9 and Comparative Examples 1-7

[0044]

[0045] The preparation method of the chiral dihydroquinolone 3a includes the following steps:

[0046] Chiral catalyst NHC (251.4 mg, 0.6 mmol), aza-o-benzoquinone precursor 1a (1.6950 g, 3 mmol), α-chlorophenylpropionaldehyde 2a (1.0080 g, 6 mmol), basic reagent (2.9250 g, 9 mmol), and Lewis acid (38.9 mg, 1.5 mmol) were added to a 120 mL dry Schlenk tube equipped with a magnetic stir bar. The tube was sealed with a diaphragm, evacuated, and refilled with nitrogen (3 cycles). Solvent (40 mL, 0.1 M) was added, and the reaction mixture was stirred at 25 °C (oil bath temperature). After 1a was completely consumed (monitored by TLC), the reaction mixture was concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography using petroleum ether / EtOAc (v / v) = 10 / 1 as the eluent to obtain chiral dihydroquinolone 3a.

[0047] Table 1 details the chiral catalyst (NHC type), basic reagent type, Lewis acid type, solvent type, and stirring reaction time used in the preparation processes of Examples 1-9 and Comparative Examples 1-7. Table 1 also details the yield, dr value, and ee value of the prepared chiral dihydroquinolone 3a.

[0048] Table 1. Conditions and yields for the preparation of chiral dihydroquinolone 3a in Examples 1-9 and Comparative Examples 1-7.

[0049]

[0050] Note: "-" indicates none; yield is determined by separation of product; trace indicates trace amount; np indicates no product; dr value is determined by coarse NMR spectrum; ee value is determined by high performance liquid chromatography. DBU is 1,8-diazabicycloundec-7-ene, TEA is triethylamine, DABCO is 1,4-diazabicyclo[2.2.2]octane, THF is tetrahydrofuran, MTBE is methyl tert-butyl ether, and Toluene is toluene.

[0051] As shown in Table 1, the yield and selectivity were higher when cesium carbonate and potassium tert-butoxide were used as the basic reagents; dichloromethane and toluene were suitable solvents. The yields were lower in Comparative Examples 1–4 without the addition of Lewis acids; in Comparative Examples 5–7, the basic reagents added were sodium acetate, tetrahydrofuran, and 1,4-diazabicyclo[2.2.2]octane, but compound 3a could not be obtained.

[0052] The H spectrum of compound 3a was determined (see details). Figure 2 The chemical shift of the proton NMR peak of compound 3a can be seen from the figure. 1H NMR(300MHz,Chloroform-d)δ8.02(d,J=8.4Hz,2H),7.42(s,1H),7.37(d,J=8.1Hz ,2H),7.28(d,J=6.6Hz,1H),7.26-7.16(m,2H),7.04(d,J=6.3Hz,2H),6.87(d,J=8. 7Hz,2H),6.69(d,J=8.7Hz,2H),6.59(s,1H),5.95(d,J=4.7Hz,2H),3.77(s,3H),3 .73(d,J=5.7Hz,1H),3.35(dd,J=14.7,4.2Hz,1H),3.24-2.99(m,1H),2.49(s,4H);

[0053] The carbon spectrum of compound 3a was obtained (see details). Figure 3 The chemical shifts of the carbon spectrum peaks of compound 3a can be seen from the figure. 13 C NMR(75MHz,Chloroform-d)δ171.88,158.72,146.58,145.49,145.11,138.80,136.36,129.45,129.42,129.35,129 .07,128.93,128.63,128.54,127.36,126.50,114.15,107.81,105.05,101.74,55.20,49.44,44.34,32.35,21.77;

[0054] HRMS(ESI,m / z):calcd.for C 31 H 27 NO6S[M+H] + 542.1632, found 542.1631.

[0055] High-performance liquid chromatography (HPLC) analysis data: 99% ee, [chiral column IB N-5; flow rate 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 28.4 min (semi-retention), 26.6 min (major)]. The HPLC spectrum of compound 3a was obtained as follows: Figure 4 As shown.

[0056] Examples 9-27: Preparation of chiral dihydroquinolones 3b-3u

[0057] The specific synthesis process is as follows:

[0058]

[0059] For specific preparation steps, refer to the preparation method of chiral dihydroquinolone 3a described above.

[0060] In chiral dihydroquinolones 3b-3o, the R substituent is 3,4-methylenedioxy and the Ar substituent is 4-methoxyphenyl; wherein, when R 1 When the substituent is 2-methylphenyl, compound 3b is prepared; when R 1 When the substituent is 2-bromophenyl, compound 3c is prepared; when R 1 When the substituent is 2-trifluoromethylphenyl, compound 3d is prepared; when R 1 When the substituent is 3-chlorophenyl, compound 3e is prepared; when R 1 When the substituent is 3-methoxyphenyl, compound 3f is prepared; when R 1 When the substituent is 4-fluorophenyl, 3g of compound is prepared; when R 1 When the substituent is 4-chlorophenyl, compound 3h is prepared; when R 1 When the substituent is 4-bromophenyl, compound 3i is prepared; when R 1 When the substituent is 4-methylphenyl, compound 3j is prepared; when R 1 When the substituent is 4-methoxyphenyl, compound 3k is prepared; when R 1 When the substituent is naphthyl, compound 3l is prepared; when R 1 When the substituent is furanyl, compound 3m is prepared; when R 1 When the substituent is pentyl, compound 3n is prepared; when R 1 When the substituent is nonyl, compound 3o is prepared. The structural formulas, yields, dr values, and ee values ​​of compounds 3a to 3o are as follows: Figure 5 As shown.

[0061] R in chiral dihydroquinolone 3p-3u compounds 1 The substituents are phenyl; wherein, when R is 3,4-methylenedioxy and Ar is phenyl, compound 3p is prepared; when R is 3,4-methylenedioxy and Ar is 3-methylphenyl, compound 3q is prepared; when R is 3,4-methylenedioxy and Ar is 4-methylphenyl, compound 3r is prepared; when R is 3,4-methylenedioxy and Ar is 2-methyl-4-methoxyphenyl, compound 3s is prepared; when R is 3,4-methylenedioxy and Ar is 2-naphthyl, compound 3t is prepared; and when R is 3,4-dimethoxy and Ar is 4-methoxyphenyl, compound 3u is prepared. The structural formulas, yields, dr values, and ee values ​​of compounds 3p–3u are as follows: Figure 6 As shown.

[0062] The structure of the compound is characterized as follows:

[0063] Compound 3b: 1 H NMR(300MHz,Chloroform-d)δ8.02(d,J=8.1Hz,2H),7.43-7.33(m,3H),7.17-7.04(m,3H),6.89(dd,J=16.6,7.6Hz,3H),6.69(d,J=8.5Hz,2H),6.64(s,1H ),5.95(d,J=6.9Hz,2H),3.78(s,4H),3.33(dd,J=14.9,4.1Hz,1H),3.13(dt, J=10.0,5.0Hz,1H),2.61(dd,J=15.0,10.0Hz,1H),2.50(s,3H),2.10(s,3H); 13 C NMR(75MHz,Chloroform-d)δ172.09,158.68,146.56,145.52,145.12,136.81,136.55,136.32,130.65,129.50,129.44,129.31 ,129.18,129.05,128.38,127.40,126.58,125.99,114.24,107.74,105.14,101.77,55.22,47.64,44.36,29.42,21.79,19.50;

[0064] HRMS(ESI,m / z):calcd.for C 32 H 29 NO6S[M+H] + 556.1789, found 556.1786; HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 23.9 min (secondary peak), 21.0 min (main peak)].

[0065] Compound 3c: 1H NMR(300MHz,Chloroform-d)δ7.99(d,J=8.4Hz,2H),7.48(dd,J=7.8,1.4Hz,1H),7.41- 7.31(m,3H),7.19-7.11(m,1H),7.05(ddd,J=10.2,8.2,2.0Hz,2H),6.98-6.85(m,2H), 6.75-6.61(m,3H),6.02-5.89(m,2H),3.80(d,J=5.6Hz,1H),3.77(s,3H),3.35(dd,J=1 3.8,5.8Hz,1H),3.26(dt,J=7.4,5.7Hz,1H),2.76(dd,J=13.9,7.3Hz,1H),2.48(s,3H); 13 C NMR(75MHz,Chloroform-d)δ171.64,158.71,146.56,145.53,145.03,138.35,136.29,132.90,132.05,129.45,129.40 ,129.29,129.15,128.40,128.30,127.32,124.61,114.24,107.67,105.24,101.75,55.21,47.38,45.46,33.77,21.76;

[0066] HRMS(ESI,m / z):calcd.for C 31 H 26 BrNO6S[M+Na] + 642.0557, found 642.0542; HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 25.3 min (secondary peak), 23.1 min (main peak)].

[0067] Compound 3d: 1H NMR(300MHz,Chloroform-d)δ7.96(d,J=8.1Hz,2H),7.59(d,J=7.7Hz,1H),7.54-7.21(m,6H),6.91(d,J=8.4Hz,2H),6.67(d,J=6.6Hz,3H),5.94(d ,J=3.8Hz,2H),3.89(d,J=5.5Hz,1H),3.76(s,3H),3.47(dd,J=14.8,5.9 Hz,1H),3.09(q,J=6.1Hz,1H),2.87(dd,J=14.8,6.8Hz,1H),2.47(s,3H); 13 C NMR(75MHz,Chloroform-d)δ171.61,158.73,146.62,145.62,145.08,137.85,136.20,132.16,131.84,129.46,129.40 ,129.12,129.03,128.42,127.38,126.74,126.37,114.26,107.59,105.35,101.80,55.19,49.02,45.58,29.98,21.74;

[0068] HRMS(ESI,m / z):calcd.for C 35 H 29 F3NO6S[M+H] + ,found 556.1786;

[0069] HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 20.5 min (secondary peak), 18.1 min (main peak)].

[0070] Compound 3e: 1 H NMR(300MHz,Chloroform-d)δ8.02(d,J=8.1Hz,2H),7.43(s,1H),7.37(d,J=8.1Hz,2H),7.18(d,J=4.7Hz,2H),7.03(s,1H),6.96-6.85(m,3H),6.7 1(d,2H),6.60(s,1H),5.93(d,J=5.9,1.4Hz,2H),3.76(s,3H),3.73(d,J= 5.7Hz,1H),3.30(dd,J=14.6,4.6Hz,1H),3.18-3.05(m,1H),2.48(s,4H); 13C NMR(75MHz,Chloroform-d)δ171.53,158.84,146.67,145.58,145.23,141.04,136.28,134.31,129.91,129.47,129.42,129 .29,129.01,128.91,128.46,127.24,127.09,126.76,114.26,107.84,105.06,101.83,55.22,49.28,44.74,32.38,21.77;

[0071] HRMS(ESI,m / z):calcd.for C 31 H 26 ClNO6S[M+Na] + 598.1062, found 598.1068; HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 29.7 min (secondary peak), 26.4 min (main peak)].

[0072] Compound 3f: 1 H NMR(300MHz,Chloroform-d)δ8.01(d,J=8.0Hz,2H),7.36(d,J=8.5Hz,3H),7.28(s,1H),6.95(d,J=8.5Hz,2H),6.76-6.63(m,3 H),6.54(s,1H),5.97(d,J=6.7Hz,2H),3.77(s,4H),3.70(s,3H),3.33-3.18(m,2H),2.73(dt,J=12.1,5.7Hz,1H),2.49(s,3H); 13 C NMR(75MHz,Chloroform-d)δ171.72,158.86,153.38,146.66,145.62,145.14,136.36,136.13,130.28,129.43,129.31,129.25 ,129.14,128.25,127.05,125.15,121.30,115.48,114.30,107.66,105.12,101.79,56.22,55.25,46.97,45.76,31.95,21.75;

[0073] HRMS(ESI,m / z):calcd.for C 32 H 29 NO7S[M+H]+ ,found 556.1786;

[0074] HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 39.6 min (secondary peak), 29.4 min (main peak)].

[0075] Compound 3g: 1 H NMR(300MHz,Chloroform-d)δ8.01(d,J=8.4Hz,2H),7.41(s,1H),7.36(d,J=8.2Hz,2H),7.00-6.90(m,4H),6.86(d,J=8.7Hz,2H),6.72-6.6 4(m,2H),6.60(s,1H),6.00-5.91(m,2H),3.77(s,3H),3.70(d,J=5.8Hz,1H),3.28(dd,J=14.6,4.6Hz,1H),3.14-3.01(m,1H),2.49(s,4H); 13 C NMR(101MHz,Chloroform-d)δ171.72,161.55(d,J=242.9Hz),158.76,146.62,145.54,145.16,136.30,134.35(d,J=3.3Hz),130.34(d,J=7.8Hz ),129.43,129.25,129.07,128.96,128.47,127.19,115.41(d,J=21.0H z),114.20,107.77,105.06,101.77,55.21,49.52,44.52,31.75,21.77;

[0076] HRMS(ESI,m / z):calcd.for C 31 H 26 FNO6S[M+Na] + 582.1358, found 582.1348; HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 32.9 min (secondary peak), 26.5 min (main peak)].

[0077] Compound 3h: 1H NMR(300MHz,Chloroform-d)δ8.01(d,J=8.4Hz,2H),7.44-7.31(m,3H),7.25-7.18(m,2H),6.95(d,J=8.4Hz,2H),6.89-6.81(m,2H),6.73-6.63(m ,2H),6.60(s,1H),5.96(dd,J=6.2,1.4Hz,2H),3.77(s,3H),3.69(d,J=5 .8Hz,1H),3.27(dd,J=14.6,4.6Hz,1H),3.14-3.02(m,1H),2.49(s,4H); 13 C NMR(75MHz,Chloroform-d)δ171.60,158.79,146.64,145.16,137.28,136.30,132.26,130.28,129.42,129 .25,128.88,128.72,128.45,127.11,114.21,107.77,105.05,101.78,55.21,49.34,44.57,31.96,21.77;

[0078] HRMS(ESI,m / z):calcd.for C 31 H 26 ClNO6S[M+Na] + 598.1062, found 598.1048; HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 41.8 min (secondary peak), 33.7 min (main peak)].

[0079] Compound 3i: 1 H NMR(300MHz,Chloroform-d)δ8.01(d,J=8.4Hz,2H),7.44-7.31(m,5H),6.94-6.81(m,4H),6.75-6.64(m,2H),6.60(s,1 H),6.00-5.91(m,2H),3.76(s,3H),3.70(d,J=5.7Hz,1H),3.25(dd,J=14.6,4.6Hz,1H),3.14-3.02(m,1H),2.48(s,4H); 13CNMR(75MHz,Chloroform-d)δ171.59,158.80,146.65,145.57,145.20,137.85,136.28,131.68,130.71,129.45,12 9.42,129.27,128.88,128.46,127.11,120.31,114.22,107.80,105.05,101.80,55.21,49.27,44.61,32.08,21.78;

[0080] HRMS(ESI,m / z):calcd.for C 31 H 26 BrNO6S[M+Na] + 642.0557, found 642.0541; HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 45.8 min (secondary peak), 34.2 min (main peak)].

[0081] Compound 3j: 1 H NMR(300MHz,Chloroform-d)δ8.02(d,J=8.4Hz,2H),7.42(s,1H),7.37(d,J=8.2Hz,2H),7.07(d,J=7.8Hz,2H),6.97-6.83(m,4H),6.69(d,J =8.7Hz,2H),6.59(s,1H),5.99-5.91(m,2H),3.77(s,4H),3.31(dd,J=14.7,4.2Hz,1H),3.17-3.05(m,1H),2.54-2.39(m,4H),2.32(s,3H); 13 C NMR(75MHz,Chloroform-d)δ171.95,158.70,146.55,145.47,145.08,136.40,136.02,135.61,129.44,129.40,129.37 ,129.31,129.12,128.79,128.57,127.44,114.12,107.82,105.04,101.73,55.20,49.51,44.22,31.85,21.76,21.05;

[0082] HRMS(ESI,m / z):calcd.for C 32 H 29 NO6S[M+Na] +578.1608, found 578.1594; HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 26.8 min (secondary peak), 25.1 min (main peak)].

[0083] Compound 3k: 1 H NMR(300MHz,Chloroform-d)δ8.02(d,J=8.4Hz,2H),7.42(s,1H),7.36(d,J=8. 2Hz,2H),6.97-6.85(m,4H),6.80(d,J=8.6Hz,2H),6.68(d,J=8.7Hz,2H),6.59 (s,1H),5.95(d,J=4.9Hz,2H),3.77(d,J=4.0Hz,6H),3.73(d,J=5.7Hz,1H),3. 28(dd,J=14.6,4.3Hz,1H),3.14-3.01(m,1H),2.48(s,3H),2.47-2.35(m,1H); 13 C NMR(75MHz,Chloroform-d)δ171.97,158.70,158.20,146.55,145.48,145.09,136.38,130.62,129.88,129.43,129.41 ,129.34,129.14,128.54,127.43,114.13,114.01,107.81,105.04,101.74,55.27,55.20,49.62,44.26,31.46,21.77;

[0084] HRMS(ESI,m / z):calcd.for C 37 H 29 NO7S[M+Na] + 594.1557, found 594.1546; HPLC analysis: 99% ee, [chiral IA column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 30 / 70; retention time: 55.4 min (secondary peak), 31.7 min (main peak)].

[0085] Compound 3l: 1H NMR(300MHz,Chloroform-d)δ8.30(d,J=8.4Hz,1H),8.04(d,J=8.1Hz,2H),7.82 (d,J=8.4Hz,1H),7.67-7.30(m,7H),6.93(dd,J=15.5,8.0Hz,3H),6.71(d,J=8.2 Hz,2H),6.54(s,1H),5.90(s,2H),3.89(dd,J=14.7,3.7Hz,1H),3.80(s,3H),3.6 8(d,J=5.8Hz,1H),3.28-3.16(m,1H),2.92(dd,J=14.8,9.8Hz,1H),2.52(s,3H); 13 CNMR(75MHz,Chloroform-d)δ171.83,158.77,146.54,145.48,145.24,136.21,134.07,132.66,131.14,131.07,129.58,129.47,129.22 ,129.17,128.14,127.26,127.02,126.83,125.59,125.44,123.88,114.37,107.68,105.05,101.74,55.25,48.06,44.67,29.34,21.81;

[0086] HRMS(ESI,m / z):calcd.for C 35 H 29 NO6S[M+H] + 592.1789, found 592.1799; HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 35.2 min (secondary peak), 29.5 min (main peak)].

[0087] Compound 3m: 1H NMR(300MHz,Chloroform-d)δ8.03(d,J=8.4Hz,2H),7.44(s,1H),7.35(d,J=8.0Hz,2H),7.31(d,J=1.9Hz,1H),7.00-6.89(m,2H),6.75-6.66(m,2H) ,6.64(s,1H),6.29(dd,J=3.2,1.9Hz,1H),6.05-5.92(m,3H),3.87(d,J=5 .3Hz,1H),3.75(s,3H),3.30-3.14(m,2H),2.64-2.52(m,1H),2.47(s,3H); 13 C NMR(75MHz,Chloroform-d)δ171.14,158.83,152.71,146.70,145.57,145.11,141.52,136.45,129.61,129.42,129 .31,128.85,128.56,127.07,114.08,110.33,107.98,107.07,105.01,101.77,55.18,47.45,44.62,25.15,21.73;

[0088] HRMS(ESI,m / z):calcd.for C 29 H 25 NO7S[M+Na] + 554.1244, found 554.1249; HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 27.2 min (secondary peak), 24.3 min (main peak)].

[0089] Compound 3n: Yield: 34 mg (63%), white solid; 1 H NMR(300MHz,Chloroform-d)δ7.96(d,J=8.4Hz,2H),7.43(s,1H),7.31(d,J=7.9Hz,2H),6.97-6.83(m,2H),6.70(s,1H),6.69-6.60(m,2H),6.04-5. 83(m,2H),3.93(d,J=5.5Hz,1H),3.74(s,3H),2.77-2.60(m,1H),2.45(s, 3H),1.89-1.74(m,1H),1.41-1.30(m,3H),1.24(m,6H),0.89-0.79(m,3H);13 C NMR(75MHz,Chloroform-d)δ172.22,158.66,146.55,145.50,144.88,136.52,129.32,129.29,129.08,128.89, 127.42,114.00,107.73,105.21,101.74,55.17,48.42,45.21,31.59,29.18,27.41,26.67,22.57,21.71,14.04;

[0090] HRMS(ESI,m / z):calcd.for C 30 H 33 NO6S[M+Na] + ,found 578.1594;

[0091] HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 26.0 min (secondary peak), 18.0 min (main peak)].

[0092] Compound 3o: 1 H NMR(300MHz,Chloroform-d)δ7.96(d,J=8.4Hz,2H),7.43(s,1H),7.31(d,J=8.2Hz,2H),6.95-6.81(m,2H),6.74-6.60(m,3H),6.02-5.93(m,2 H),3.93(d,J=5.6Hz,1H),3.74(s,3H),2.69(q,J=6.6,5.9Hz,1H),2.45(s,3H),1.86-1.74(m,1H),1.31-1.18(m,17H),0.88(d,J=6.5Hz,3H); 13 C NMR(75MHz,Chloroform-d)δ172.22,158.65,146.55,145.50,144.87,136.52,129.32,129.28,129.07,128.88,127.42,11 4.00,107.73,105.22,101.73,55.16,48.42,45.18,31.90,29.56,29.50,29.39,29.31,27.43,26.64,22.68,21.71,14.12;

[0093] HRMS(ESI,m / z):calcd.for C 34 H41 NO6S[M+Na] + 614.2547, found 614.2533; HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 23.7 min (secondary peak), 16.1 min (main peak)].

[0094] Compound 3q: 1 H NMR(300MHz,Chloroform-d)δ8.03(d,J=8.4Hz,2H),7.28(d,J=6.6Hz,1H),7.25-7.18(m,2H),7.08-7.00(m,4H),6.97(s,1H),6.76-6.69(m,1H),6 .62(s,1H),6.00-5.91(m,2H),3.76(d,J=5.8Hz,1H),3.37(dd,J=14.7,4 .2Hz,1H),3.20-3.07(m,1H),2.53(dd,J=14.7,10.1Hz,1H),2.48(s,3H); 13 C NMR(75MHz,Chloroform-d)δ171.91,146.62,145.46,145.05,138.87,138.59,136.93,136.62,129.47,129.27,129 .18,128.95,128.61,128.18,127.19,126.49,125.10,107.91,104.94,101.74,49.41,44.97,32.40,21.76,21.41;

[0095] HRMS(ESI,m / z):calcd.for C 31 H 27 NO5S[M+Na] + 548.1503, found 548.1493;

[0096] HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 17.2 min (secondary peak), 14.8 min (main peak)].

[0097] Compound 3r: 1H NMR(300MHz,Chloroform-d)δ8.01(d,J=8.4Hz,2H),7.42(s,1H),7.36(d,J=8.1Hz ,2H),7.28(t,J=2.0Hz,1H),7.26-7.19(m,2H),7.07-6.99(m,2H),6.95(d,J=8.0H z,2H),6.84(d,J=8.2Hz,2H),6.60(s,1H),6.02-5.80(m,2H),3.74(d,J=5.7Hz,1H ),3.35(dd,J=14.6,4.2Hz,1H),3.20-3.07(m,1H),2.60-2.40(m,4H),2.29(s,3H); 13 C NMR(75MHz,Chloroform-d)δ171.84,146.58,145.47,145.05,138.86,136.94,136.37,134.00,129.46,129 .38,128.94,128.61,128.09,127.25,126.48,107.83,105.04,101.72,49.37,44.71,32.35,21.75,21.04;

[0098] HRMS(ESI,m / z):calcd.for C 31 H 27 NO5S[M+Na] + 548.1503, found 548.1494;

[0099] HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 22.5 min (secondary peak), 20.7 min (main peak)].

[0100] Compound 3s: 1H NMR(300MHz,Chloroform-d)δ8.08(d,J=8.4Hz,2H),7.44-7.37(m,3H),7.20(d,J=7. 0Hz,3H),6.89-6.82(m,2H),6.73(d,J=8.6Hz,1H),6.68(d,J=2.8Hz,1H),6.60(s,1H ),6.42(dd,J=8.6,2.9Hz,1H),5.94(dd,J=9.7,1.4Hz,2H),3.97(d,J=6.3Hz,1H),3. 76(s,4H),3.28(dd,J=14.2,4.6Hz,1H),3.22-3.13(m,1H),2.51(s,3H),2.03(s,3H); 13 C NMR(75MHz,Chloroform-d)δ172.51,158.18,146.36,145.39,145.20,138.49,137.78,136.34,129.54,129.46,128.79,12 8.58,128.24,127.95,126.92,126.49,116.89,111.71,107.70,105.08,101.70,55.08,49.21,39.10,32.46,21.78,20.68;

[0101] HRMS(ESI,m / z):calcd.for C 32 H 29 NO6S[M+Na] + 578.1608, found 578.1600;

[0102] HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 24.8 min (secondary peak), 22.8 min (main peak)].

[0103] Compound 3t: 1H NMR(300MHz,Chloroform-d)δ7.94(d,J=8.4Hz,2H),7.83-7.73(m,1H),7.65(t,J=7.8Hz,2H) ,7.56-7.38(m,4H),7.28(d,J=6.4Hz,1H),7.25-7.22(m,2H),7.20(s,1H),7.15(dd,J=8.5,2 .0Hz,1H),7.08-7.00(m,2H),6.71(s,1H),5.97(dd,J=8.0,1.4Hz,2H),3.96(d,J=5.6Hz,1H) ,3.45(dd,J=14.6,4.3Hz,1H),3.31-3.14(m,1H),2.65(dd,J=14.7,10.1Hz,1H),2.43(s,3H); 13 C NMR(75MHz,Chloroform-d)δ171.92,146.74,145.55,145.00,138.82,136.45,134.55,133.33,132.48,129.40,129.17,128.93,128 .67,128.50,128.23,127.44,127.09,126.93,126.57,126.38,126.12,126.08,107.94,105.24,101.79,49.50,44.92,32.62,21.74;

[0104] HRMS(ESI,m / z):calcd.for C 34 H 27 NO5S[M+Na] + 584.1503, found 584.1496;

[0105] HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate: 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 26.5 min (secondary peak), 22.5 min (main peak)].

[0106] Compound 3u: 1H NMR(300MHz,Chloroform-d)δ8.01(d,J=8.4Hz,1H),7.56(s,1H),7.37(d,J=8.2Hz,2H),7.32-7.26(m,2H),7.26-7.16(m,3H),7.10-7.01(m,2H) ,6.83-6.72(m,2H),6.67-6.54(m,3H),3.95(s,3H),3.78(d,J=12.8Hz, 7H),3.33(dd,J=14.6,4.2Hz,1H),3.24-3.13(m,1H),2.52-2.36(m,4H); 13 C NMR(75MHz,Chloroform-d)δ171.78,158.66,147.54,146.98,145.07,138.89,136.29,129.57,129.42,129.36,129.3 1,129.01,128.62,128.14,126.45,125.65,114.07,110.69,107.76,56.35,56.05,55.17,49.57,44.32,32.31,21.76;

[0107] HRMS(ESI,m / z):calcd.for C 32 H 31 NO6S[M+Na] + 580.1756, found 580.1765;

[0108] HPLC analysis: 99% ee, [chiral IH column; flow rate 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 31.9 min (secondary peak), 42.1 min (main peak)].

[0109] Example 28: Preparation method of chiral dihydroquinolone derivative 4

[0110] Experimental materials: chiral dihydroquinolone 3a compounds prepared in any of Examples 1 to 8.

[0111] 0.4 mL of Na / naphthalene THF solution (5 mmol Na, 5 mmol naphthalene added to 2 mL of THF solution containing chiral dihydroquinolone 3a (108.2 mg, 0.20 mmol, 99% ee) was added, and the mixture was stirred at -78 °C for 10 min. The reaction was then quenched with 2 mL of H₂O, and the mixture was extracted with CH₂Cl₂ (1 mL × 2). The combined organic layer was dried over Na₂SO₄, filtered, and concentrated under reduced pressure at 40 °C. The residue was purified by silica gel (petroleum ether / ethyl acetate = 8:1–3:1) column chromatography to give the desired product 4 as a white solid (70.4 mg, 0.182 mmol, 91% yield, >20:1 dr, 99% ee).

[0112] The structural diagram of compound 4 is shown below:

[0113]

[0114] Compound 4: 1 H NMR(300MHz,Chloroform-d)δ8.48(s,1H),7.31(t,J=7.2Hz,2H),7.22(d,J=7 .5Hz,1H),7.17-7.08(m,2H),7.05-6.99(m,2H),6.85-6.71(m,2H),6.51(s,1 H),6.39(s,1H),5.85(dd,J=14.9,1.4Hz,2H),3.76(s,4H),3.47(dd,J=14.5, 4.5Hz,1H),3.29(ddd,J=10.6,6.5,4.3Hz,1H),2.44(dd,J=14.6,10.3Hz,1H); 13 C NMR(75MHz,Chloroform-d)δ172.06,158.76,147.07,143.50,139.74,132.02,130.16,129 .06,128.46,126.25,121.22,114.21,108.42,101.22,97.80,55.20,46.14,44.73,31.75;

[0115] HRMS(ESI,m / z):calcd.for C 24 H 21 NO4S[M+H] + 388.1544, found 388.1558;

[0116] HPLC analysis: 99% ee, [chiral IB N-5 column; flow rate 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 23.9 min (secondary peak), 18.0 min (main peak)].

[0117] Example 29: Preparation method of chiral dihydroquinolone derivative 5

[0118] Experimental materials: chiral dihydroquinolone 3a compounds prepared in any of Examples 1 to 8.

[0119] LiAlH4 (22.8 mg, 0.6 mmol, 3.0 equiv) was added to anhydrous THF (1 mL), and chiral dihydroquinolone 3a (108.2 mg, 0.20 mmol, 99% ee, 1.0 equiv) was slowly added under a N2 atmosphere at 0 °C. The reaction was stirred at 0 °C for 2 h, and then quenched with 0.1 M HCl solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by silica gel column chromatography (petroleum ether / ethyl acetate = 6:1) gave 5 (80.1 mg, 0.125 mmol, 76% yield, >20:1 dr, 99% ee).

[0120] The structural diagram of compound 5 is shown below:

[0121]

[0122] Compound 5: 1 H NMR(300MHz,Chloroform-d)δ7.78(d,J=8.3Hz,2H),7.33(d,J=8.1Hz,2H),7.28( d,J=7.4Hz,1H),7.24(s,1H),7.22-7.12(m,3H),6.83(s,1H),6.71(q,J=8.8Hz,4 H),6.57(s,1H),5.85(dd,J=10.3,1.4Hz,2H),4.05(d,J=11.7Hz,1H),3.77(s,3H ),3.49(d,J=10.9Hz,1H),3.15(d,J=12.0Hz,1H),2.75-2.60(m,2H),2.49(s,3H); 13CNMR(75MHz,Chloroform-d)δ158.03,146.64,145.93,143.51,140.77,137.97,134.46,133.12,129.93,129.3 9,128.95,128.50,127.47,127.43,126.07,113.94,107.71,101.42,60.23,55.23,46.03,45.27,34.77,21.63;

[0123] HRMS(ESI,m / z):calcd.for C 31 H 29 NO5S[M+H] + 528.1840, found 528.1824;

[0124] HPLC analysis: 99% ee; [Chiral IB N-5 column; flow rate 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 26.4 min (secondary peak), 24.2 min (main peak)].

[0125] Example 30: Preparation method of chiral dihydroquinolone derivative 6

[0126] Experimental materials: chiral dihydroquinolone 3a compounds prepared in any of Examples 1 to 8.

[0127] DDQ (45.4 mg, 0.20 mmol, 2.0 equiv) was added to a solution of 1,4-dioxane (1 mL) containing compound 3a (54.1 mg, 0.10 mmol, 99% ee, 1.0 equiv). The mixture was stirred at 100 °C for 12 h, then H₂O (2 mL) was added, and the mixture was extracted with ethyl acetate (2 mL × 2). The bound organic layer was dried over Na₂SO₄, filtered, and concentrated under reduced pressure at 40 °C until dry. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10:1–5:1) to give compound 6 (46.8 mg, 0.087 mmol, 87% yield) as a white solid.

[0128] The structural diagram of compound 6 is shown below:

[0129]

[0130] Compound 6: 1H NMR(300MHz,Chloroform-d)δ7.88(d,J=8.4Hz,2H),7.30(d,J=8.0Hz,2H),7.18-7.09(m,4H),7.07-7.01(m,2H), 7.00-6.93(m,2H),6.90(dd,J=7.4,2.1Hz,2H),6.62(s,1H),6.02(s,2H),3.93(s,2H),3.86(s,3H),2.44(s,3H); 13 C NMR(75MHz,Chloroform-d)δ159.52,154.16,150.72,150.46,147.73,144.80,142.57,139.71,134.81,130.43, 129.29,129.07,128.44,128.15,125.90,124.41,121.52,114.06,105.01,102.28,101.81,55.36,33.34,21.73;

[0131] HRMS(ESI,m / z):calcd.for C 31 H 25 NO6S[M+H] + 540.1476, found 540.1491;

[0132] HPLC analysis: 99% ee; [Chiral IB N-5 column; flow rate 0.5 mL / min; mobile phase: isopropanol / n-hexane = 20 / 80; retention time: 26.4 min (secondary peak), 24.2 min (main peak)].

[0133] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A method for preparing a chiral dihydroquinolone compound, characterized in that, The specific preparation method is to react compound 1, compound 2, catalyst N-heterocyclic carbene, basic reagent and Lewis acid in an organic solvent under nitrogen or argon protection at 20~35℃ until complete, separate and purify to obtain chiral dihydroquinolone compound 3. The synthesis route is shown below: Where R represents a double substitution, and each substitution is independently C. 1~5 Alkoxy, or methylenedioxy, wherein the two alkoxy groups of the methylenedioxy group are respectively attached to two adjacent carbon atoms on the benzene ring; Ar is an aryl or substituted aryl, wherein the substituent in the substituted aryl group is C. 1~12 Alkyl or C 1~5 One or more of the alkoxy groups; R 1 Selected from C 1~12 One of alkyl, aryl or substituted aryl, and furanyl, wherein the substituent in the substituted aryl group is selected from C10. 1~12 Alkyl, C 1~5 Alkoxy, C 1~3 One of the following: alkyl halogroups or halogens; The aryl group has 5 to 10 carbon atoms; The catalyst N-heterocyclic carbene is selected from the following structures: ； The alkaline reagent is selected from one or more of potassium tert-butoxide and cesium carbonate; The Lewis acid is lithium fluoride or lithium chloride; The organic solvent is selected from one of dichloromethane, tetrahydrofuran, toluene, methyl tert-butyl ether, and acetonitrile.

2. The preparation method according to claim 1, characterized in that, The R is a double substitution, each of which is independently C. 1~5 Alkoxy, or methylenedioxy, wherein the two alkoxy groups of the methylenedioxy group are respectively attached to two adjacent carbon atoms on the benzene ring; Ar is selected from phenyl or substituted phenyl, naphthyl, wherein the substituent in the substituted phenyl is C. 1~8 Alkyl or C 1~4 One or more of the alkoxy groups; R 1 Selected from C 1~12 One of alkyl, phenyl or substituted phenyl, naphthyl, furanyl, wherein the substituent in the substituted phenyl is selected from C 1~8 Alkyl, C 1~4 Alkoxy, C 1~3 One of the following: alkyl halogroups or halogens.

3. The preparation method according to claim 2, characterized in that, R is a disubstituted compound, each being either methoxy or methylenedioxy, wherein the two alkoxy groups of the methylenedioxy compound are respectively bonded to two adjacent carbon atoms on the benzene ring; Ar is selected from phenyl or substituted phenyl, naphthyl, wherein the substituent in the substituted phenyl compound is one or more of methyl or methoxy; R 1 It is selected from one of pentyl, decyl, phenyl or substituted phenyl, naphthyl, furanyl, wherein the substituent in the substituted phenyl is selected from one of methyl, methoxy, trifluoromethyl, halogen.

4. The preparation method according to claim 1, characterized in that, The reaction time is 12-24 h.

5. The use of the preparation method according to any one of claims 1 to 4 in the preparation of drugs containing dihydroquinolone structural units, tetrahydroquinoline, or quinolone drugs.

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