Tetra-substituted axially chiral alkenyl amide quinolinone and synthesis method thereof

Abstract

The invention discloses tetra-substituted axially chiral alkenyl amide quinolinone and a synthesis method thereof. According to the method, MBH carbonate and quinolin-2 (1H)-ketone derivatives are used as raw materials, (DHQD) 2PYR is used as a catalyst, DME is used as a solvent, central chiral alkenyl amide quinolinone is synthesized, DBU is used as alkali, toluene is used as a solvent, and enantiomer-enriched tetra-substituted axially chiral alkenyl amide quinolinone is obtained. The method has the advantages of mild reaction conditions, easily available raw materials, high enantioselectivity of the product and excellent yield, and provides a simple and efficient way for the preparation of the alkenyl amide axially chiral compound.

Description

Technical Field

[0001] The invention relates to a method for synthesizing tetrasubstituted axial chiral enamide quinolinone, belonging to the technical field of organic synthetic chemistry. Background Art

[0002] Quinolinones are a class of N-heterocyclic carbonyl compounds with various biological properties, which have attracted considerable attention due to their widespread presence in natural products and bioactive compounds, such as antimalarial, anticancer, antitumor and herbicidal activities. Due to their wide range of biological and pharmacological significance, the synthesis of N-heterocyclic carbonyl compounds has always been the focus of chemists.

[0003] In this regard, axially chiral arylquinolinones show very excellent structural properties, because these skeletons constitute a variety of small molecule drugs and bioactive molecules. Although the reported methods have been demonstrated in many aspects, it is still desirable to develop general, efficient, simple and sustainable methods. In recent years, organic chemists have proposed the construction of axially chiral compounds through center-axial chirality transformation. (Latchipatula, BR; Chinnabattigalla, S.; Dakoju, RK2022, 127, 133093.; Osamu Kitagawa. Acc. Chem. Res. 2021, 54, 3, 719–730.; Chao Sun, Xiao-LongMin, Xue-Dan Bai. Chem. Sci. 2020, 11, 10119.; Xing-Feng Bai, Yu-Ming Cui, Jian Cao, Li-Wen Xu. Acc. Chem. Res. 2022, 55, 18, 2545–2561.; Yong-Bin Wang, Bin Tan, Acc. Chem. Res. 2018, 51, 2, 534–547.; Hui Yang, Jie Chen, Ling Zhou. ChemAsian J. 2020, 15, 2939-2951.). Summary of the invention

[0004] The purpose of the present invention is to provide a method for synthesizing tetrasubstituted axial chiral enamide quinolinone. The method uses MBH carbonate and quinoline-2(1H)-one derivative as raw materials, and further isomerizes to obtain the synthesized tetrasubstituted axial chiral enamide quinolinone.

[0005] The technical solution to achieve the purpose of the present invention is as follows: a tetrasubstituted axial chiral enamide quinolinone, the structural formula of which is as follows:

[0006]

[0007] The synthesis method of the tetrasubstituted axial chiral enamide quinolinone comprises:

[0008] (1) Using MBH carbonate 1 and quinoline-2(1H)-one derivative 2 as reaction raw materials, hydrogenated quinine-2,5-diphenyl-4,6-pyrimidine dimethyl ether ((DHQD)2PYR) as catalyst, and ethylene glycol dimethyl ether (DME) as solvent, the steps of synthesizing central chiral enamide quinolinone 3,

[0009]

[0010] (2) The steps of synthesizing tetrasubstituted axial chiral enamide quinolinone 4 using central chiral enamide quinolinone 3 as a reaction raw material, 1,8-diazabicycloundec-7-ene (DBU) as a base, and toluene as a solvent,

[0011]

[0012] Among them, when R 1 When R is selected from hydrogen, methyl or bromine, 2 is selected from hydrogen; R 1 When selected from hydrogen, R 2 is selected from hydrogen, methyl or bromine.

[0013] Preferably, in step (1), the molar ratio of MBH carbonate to quinoline-2(1H)-one derivative is 3:1.

[0014] Preferably, in step (1), the molar amount of the (DHQD)2PYR catalyst is 20% of the molar amount of the quinoline-2(1H)-one derivative.

[0015] Preferably, in step (1), the reaction temperature is room temperature.

[0016] Preferably, in step (2), the amount of DBU used is twice the molar amount of the central chiral enamide quinolinone.

[0017] Compared with the prior art, the present invention has the following advantages:

[0018] The invention uses stable and easily available MBH carbonate and quinoline-2(1H)-one as raw materials, realizes the transfer of central chirality to axial chirality under simple and easy reaction conditions, has mild reaction conditions, high enantioselectivity of the product and excellent yield. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is the hydrogen spectrum of methyl 2-(2-oxoquinolin-1(2H)-yl)(pyridin-2-yl)methyl)acrylate 3a prepared in Example 4.

[0020] Figure 2This is the carbon spectrum of methyl 2-(2-oxoquinolin-1(2H)-yl)(pyridin-2-yl)methyl)acrylate 3a prepared in Example 4.

[0021] Figure 3 This is the hydrogen spectrum of methyl (E)-2-methyl-3-(2-oxoquinolin-1(2H)-yl)-3-(pyridin-2-yl)acrylate 4a prepared in Example 4.

[0022] Figure 4 This is the carbon spectrum of (E)-methyl 2-methyl-3-(2-oxoquinolin-1(2H)-yl)-3-(pyridin-2-yl)acrylate 4a prepared in Example 4.

[0023] Figure 5 This is the hydrogen spectrum of methyl 2-((5-bromopyridin-2-yl)(2-oxoquinolin-1(2H)-yl)methyl)acrylate 3b prepared in Example 5.

[0024] Figure 6 This is the carbon spectrum of methyl 2-((5-bromopyridin-2-yl)(2-oxoquinolin-1(2H)-yl)methyl)acrylate 3b prepared in Example 5.

[0025] Figure 7 This is the hydrogen spectrum of methyl (E)-3-(5-bromopyridin-2-yl)-2-methyl-3-(2-oxoquinolin-1(2H)-yl)acrylate 4b prepared in Example 5.

[0026] Figure 8 This is the carbon spectrum of methyl (E)-3-(5-bromopyridin-2-yl)-2-methyl-3-(2-oxoquinolin-1(2H)-yl)acrylate 4b prepared in Example 5.

[0027] Fig. 9 This is the hydrogen spectrum of methyl 2-((4-methylpyridin-2-yl)(2-oxoquinolin-1(2H)-yl)methyl)acrylate 3c prepared in Example 6.

[0028] Fig.10 This is the carbon spectrum of methyl 2-((4-methylpyridin-2-yl)(2-oxoquinolin-1(2H)-yl)methyl)acrylate 3c prepared in Example 6.

[0029] Fig.11 Hydrogen spectrum of methyl (E)-2-methyl-3-(4-methylpyridin-2-yl)-3-(2-oxoquinolin-1(2H)-yl)acrylate 4c prepared in Example 6.

[0030] Fig.12 This is the carbon spectrum of methyl (E)-2-methyl-3-(4-methylpyridin-2-yl)-3-(2-oxoquinolin-1(2H)-yl)acrylate 4c prepared in Example 6.

[0031] Fig.13 This is the hydrogen spectrum of (7-bromo-2-oxoquinolin-1(2H)-yl)methylpicolyl ester 3d prepared in Example 7.

[0032] Fig.14 This is the carbon spectrum of (7-bromo-2-oxoquinolin-1(2H)-yl)methylpicolyl ester 3d prepared in Example 7.

[0033] Fig.15 This is the hydrogen spectrum of methyl (E)-3-(7-bromo-2-oxoquinolin-1(2H)yl)-2-methyl-3-(pyridin-2-yl)acrylate 4d prepared in Example 7.

[0034] Fig.16 This is the 4d carbon spectrum of methyl (E)-3-(7-bromo-2-oxoquinolin-1(2H)yl)-2-methyl-3-(pyridin-2-yl)acrylate prepared in Example 7.

[0035] Fig.17 This is the hydrogen spectrum of (S)-2-(4-methyl-2-oxoquinolin-1(2H)-yl)picolylmethacrylate 3e prepared in Example 8.

[0036] Fig.18 This is the carbon spectrum of (S)-2-(4-methyl-2-oxoquinolin-1(2H)-yl)pyridine methyl methacrylate 3e prepared in Example 8.

[0037] Fig.19 This is the hydrogen spectrum of (E)-2-methyl-3-(4-methyl-2-oxoquinolyl)-3-(2H)pyridineacrylate methyl ester 4e prepared in Example 8.

[0038] Fig. 20 This is the carbon spectrum of (E)-2-methyl-3-(4-methyl-2-oxoquinolyl)-3-(2H)pyridineacrylate methyl ester 4e prepared in Example 8. DETAILED DESCRIPTION

[0039] The present invention is described in detail below through specific embodiments, but the use and purpose of these examples are only used to illustrate the present invention, and do not constitute any form of limitation on the actual protection scope of the present invention, nor limit the protection scope of the present invention to these.

[0040] Example 1:

[0041] MBH carbonate 1, quinolinone 2, catalyst (20 mol%), solvent (1.5 mL) and stirring bar were added to a 4 ml reaction bottle and stirred at room temperature for 72 h. After the reaction was completed by TLC monitoring, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate) to obtain the central chiral enamide quinolinone 3.

[0042] Example 2:

[0043] Other conditions were the same as in Example 1. The effects of different catalysts on the reaction were examined. The experimental results are shown in Table 1.

[0044] Table 1 Effect of different catalysts on the reaction

[0045]

[0046] From the above results, it can be seen that the catalyst is preferably (DHQD)2PYR (No. 1).

[0047] Example 3:

[0048] The other conditions were the same as in Example 1. The effects of different solvents on the reaction were examined. The experimental results are shown in Table 2.

[0049] Table 2 Effect of different solvents on the reaction

[0050]

[0051] From the above results, it can be seen that DME (No. 4) is preferably used as the solvent.

[0052] Example 4:

[0053] Methyl 2-(2-oxoquinolin-1(2H)-yl)(pyridin-2-yl)methyl)acrylate

[0054]

[0055] The specific steps are as follows:

[0056] Step 1, MBH carbonate (263.8 mg, 0.9 mmol), quinoline-2(1H)-one (43.5 mg, 0.3 mmol), catalyst (DHQD) 2PYR (52.9 mg, 0.06 mmol), and reaction solvent ethylene glycol dimethyl ether (1.5 mL) were added to a 4 mL reaction bottle equipped with a stirrer, and the mixture was reacted at room temperature and monitored by TLC spot plate. After the reaction was complete, the crude product was purified by silica gel column chromatography to obtain central chiral enamide quinolinone 3a with a yield of 78% and an ee value of 95%. The hydrogen and carbon spectra of the obtained 3a are shown as follows: Figure 1 and Figure 2 shown.

[0057] 1H NMR(500MHz,Chloroform-d)δ8.56(d,J=4.9Hz,1H),8.01(s,1H),7.74(d,J=9.4Hz,1H),7.54–7.50(m,2H),7.30(d,J =10.4Hz,2H),7.19(t,J=8.0Hz,1H),7.13–7.07(m,3H),6.81(d,J=9.4Hz,1H),6.36(s,1H),5.30(s,1H),3.75(s,3H). 13 C NMR(126MHz,Chloroform-d)δ167.26,162.58,157.96,148.56,140.27,138.81,136.91,136. 67,129.88,128.80,125.07,122.93,122.34,122.29,121.36,121.31,118.03,58.55,52.17..

[0058] (E)-2-methyl-3-(2-oxoquinolin-1(2H)-yl)-3-(pyridin-2-yl)acrylate

[0059]

[0060] Step 2, 3a (0.1 mmol), DBU (30.4 mg, 0.2 mmol), and solvent toluene (1 mL) were added to a 4 mL reaction bottle equipped with a stirrer and reacted at room temperature. After the reaction, the crude product was purified by silica gel column chromatography to obtain tetrasubstituted axial chiral enamide quinolinone 4a with a yield of 96% and an ee value of 95%. The hydrogen and carbon spectra of the obtained 4a are shown as follows: Figure 3 and Figure 4 shown.

[0061] 1 H NMR (500MHz, Chloroform-d) δ8.58(d,J=5.0Hz,1H),7.82(d,J=9.5Hz,1H),7.61(d,J=7.5Hz,1H),7.53(t,J=7.6Hz,1H),7.44(t ,J=7.6Hz,1H),7.29–7.23(m,2H),7.17–7.15(m,1H),6.96(d,J=7.8Hz,1H),6.79(d,J=9.5Hz,1H),3.78(s,3H),1.85(s,3H). 13C NMR(126MHz,Chloroform-d)δ170.30,161.05,152.38,149.09,140.46,139.11,136.85,135. 04,134.73,131.22,128.68,123.21,123.00,122.13,120.93,120.47,115.48,52.16,16.81.

[0062] Example 5:

[0063] Methyl 2-((5-bromopyridin-2-yl)(2-oxoquinolin-1(2H)-yl)methyl)acrylate

[0064]

[0065] Step 1, MBH carbonate (333.9 mg, 0.9 mmol), quinoline-2(1H)-one (43.5 mg, 0.3 mmol), catalyst (DHQD) 2PYR (52.9 mg, 0.06 mmol), and reaction solvent ethylene glycol dimethyl ether (1.5 mL) were added to a 4 mL reaction bottle equipped with a stirrer, and the mixture was reacted at room temperature and monitored by TLC spot plate. After the reaction was complete, the crude product was purified by silica gel column chromatography to obtain central chiral enamide quinolinone 3b with a yield of 73% and an ee value of 93%. The hydrogen and carbon spectra of the obtained 3b are shown as follows: Figure 5 and Figure 6 shown.

[0066] 1 H NMR(500MHz,Chloroform-d)δ8.60(d,J=2.4Hz,1H),7.90(s,1H),7.74(d,J=9.5Hz,1H),7.65(dd,J=8.4,2.4Hz,1H),7.52(d,J=7.7Hz, 1H),7.27(d,J=5.2Hz,2H),7.13(t,J=7.2Hz,1H),7.04(d,J=8.5Hz,1H),6.78(d,J=9.5Hz,1H),6.38(s,1H),5.35(s,1H),3.76(s,3H). 13 C NMR(126MHz,Chloroform-d)δ166.97,162.43,156.60,149.57,140.36,139.58,138.71,136. 03,130.11,128.96,125.78,124.32,122.53,121.37,121.35,119.40,117.56,58.09,52.28..

[0067] (E)-methyl 3-(5-bromopyridin-2-yl)-2-methyl-3-(2-oxoquinolin-1(2H)-yl)acrylate

[0068]

[0069] Step 2, add 3b (0.1 mmol), DBU (30.4 mg, 0.2 mmol), and solvent toluene (1 mL) to a 4 mL reaction bottle equipped with a stirrer, and react at room temperature. After the reaction, the crude product was purified by silica gel column chromatography to obtain tetrasubstituted axial chiral enamide quinolinone 4b with a yield of 91% and an ee value of 94%. The hydrogen and carbon spectra of the obtained 4b are as follows: Figure 7 and Figure 8 shown.

[0070] 1 H NMR(500MHz,Chloroform-d)δ8.62(d,J=2.3Hz,1H),7.82(d,J=9.6Hz,1H),7.66(dd,J=8.5,2.4Hz,1H),7.62(d,J=7.8H z,1H),7.46(t,J=7.9Hz,1H),7.27–7.24(m,2H),6.87(d,J=8.5Hz,1H),6.78(d,J=9.5Hz,1H),3.79(s,3H),1.83(s,3H). 13 CNMR(126MHz,Chloroform-d)δ169.87,160.99,151.02,150.20,140.61,139.43,138.95,135. 38,134.40,131.33,128.81,123.17,122.34,122.05,120.48,120.47,115.26,52.29,16.90.

[0071] Example 6:

[0072] Methyl 2-((4-methylpyridin-2-yl)(2-oxoquinolin-1(2H)-yl)methacrylate

[0073]

[0074] Step 1, MBH carbonate (276.4 mg, 0.9 mmol), quinoline-2(1H)-one (43.5 mg, 0.3 mmol), catalyst (DHQD) 2PYR (52.9 mg, 0.06 mmol), and reaction solvent ethylene glycol dimethyl ether (1.5 mL) were added to a 4 mL reaction bottle equipped with a stirrer, and the mixture was reacted at room temperature and monitored by TLC spot plate. After the reaction was complete, the crude product was purified by silica gel column chromatography to obtain central chiral enamide quinolinone 3c with a yield of 58% and an ee value of 90%. The hydrogen and carbon spectra of the obtained 3c are shown as follows: Fig. 9 and Fig.10 shown.

[0075] 1 H NMR(500MHz,Chloroform-d)δ8.40(d,J=5.1Hz,1H),7.99(s,1H),7.73(d,J=9.5Hz,1H),7.50(d,J=7.7Hz,1H),7.40(d,J=8.6Hz,1H),7. 21(t,J=8.1Hz,1H),7.09(t,J=7.5Hz,1H),6.95–6.93(m,2H),6.82(d,J=9.4Hz,1H),6.33(s,1H),5.26(s,1H),3.74(s,3H),2.19(s,3H). 13 C NMR(126MHz,Chloroform-d)δ167.28,162.63,157.72,148.18,140.22,138.89,136.80,129.89, 128.73,124.82,123.80,123.49,122.31,122.31,121.34,121.32,118.18,58.33,52.11,21.02.

[0076] (E)-2-methyl-3-(4-methylpyridin-2-yl)-3-(2-oxoquinolin-1(2H)-yl)acrylate

[0077]

[0078] Step 2, add 3c (0.1 mmol), DBU (30.4 mg, 0.2 mmol), and solvent toluene (1 mL) to a 4 mL reaction bottle equipped with a stirrer, and react at room temperature. After the reaction, the crude product was purified by silica gel column chromatography to obtain tetrasubstituted axial chiral enamide quinolinone 4c with a yield of 94% and an ee value of 89%. The hydrogen and carbon spectra of the obtained 4c are as follows: Fig.11 and Fig.12 shown.

[0079] 1 H NMR(500MHz,Chloroform-d)δ8.57(dd,J=4.8,1.6Hz,1H),7.74(d,J=8.2Hz,1H),7.52(td,J=7.8,1.7Hz,1H),7.43(ddd,J=8.5,7.3,1 .5Hz,1H),7.30–7.24(m,2H),7.15(dd,J=7.6,4.8Hz,1H),6.95(d,J=7.9Hz,1H),6.68(s,1H),3.78(s,3H),2.55(s,3H),1.84(s,3H). 13 C NMR(126MHz,Chloroform-d)δ170.37,160.76,152.54,149.02,148.20,138.75,136.82,135.06, 134.73,131.03,125.22,123.14,122.80,121.35,121.22,120.96,115.74,52.10,19.29,16.81..

[0080] Example 7:

[0081] (7-Bromo-2-oxoquinolin-1(2H)-yl)methylpicolinate 3d:

[0082]

[0083] Step 1, MBH carbonate (263.8 mg, 0.9 mmol), quinoline-2(1H)-one (66.9 mg, 0.3 mmol), catalyst (DHQD) 2PYR (52.9 mg, 0.06 mmol), and reaction solvent ethylene glycol dimethyl ether (1.5 mL) were added to a 4 mL reaction bottle equipped with a stirrer, and the mixture was reacted at room temperature and monitored by TLC spot plate. After the reaction was complete, the crude product was purified by silica gel column chromatography to obtain central chiral enamide quinolinone 3d with a yield of 69% and an ee value of 94%. The hydrogen and carbon spectra of the obtained 3d are shown as follows: Fig.13 and Fig.14 shown.

[0084] 1H NMR(500MHz,Chloroform-d)δ8.58(d,J=4.9Hz,1H),7.86(s,1H),7.67(d,J=9.5Hz,1H),7.58–7.54(m,2H),7.35(d,J=8.3Hz,1 H),7.21(d,J=8.3Hz,1H),7.15(dd,J=14.6,8.1Hz,2H),6.78(d,J=9.5Hz,1H),6.42(d,J=2.0Hz,1H),5.35(s,1H),3.74(s,3H). 13 C NMR(126MHz,Chloroform-d)δ166.84,162.19,157.33,148.73,139.78,139.61,136.95,136. 38,129.81,125.71,125.58,124.39,123.03,122.55,121.68,120.71,120.08,58.94,52.19..

[0085] (E)-3-(7-bromo-2-oxoquinolin-1(2H)yl)-2-methyl-3-(pyridin-2-yl)

[0086]

[0087] Step 2, add 3d (0.1 mmol), DBU (30.4 mg, 0.2 mmol), and solvent toluene (1 mL) to a 4 mL reaction bottle equipped with a stirrer, and react at room temperature. After the reaction, the crude product was purified by silica gel column chromatography to obtain tetrasubstituted axial chiral enamide quinolinone 4d with a yield of 96% and an ee value of 93%. The hydrogen and carbon spectra of the obtained 4d are as follows: Fig.15 and Fig.16 shown.

[0088] 1 H NMR(500MHz,Chloroform-d)δ8.59(d,J=4.8Hz,1H),7.76(d,J=9.5Hz,1H),7.57–7.54(m,1H),7.47–7.43(m,2H),7.35(dt,J =8.2,1.6Hz,1H),7.18(dd,J=7.6,4.8Hz,1H),6.96(d,J=8.0Hz,1H),6.78(dd,J=9.6,1.3Hz,1H),3.78(s,3H),1.86(s,3H). 13C NMR(126MHz,Chloroform-d)δ169.95,160.64,152.09,149.26,140.12,139.87,136.84,134. 98,134.88,129.86,126.46,125.76,123.36,122.39,120.97,119.24,118.16,52.21,16.86.

[0089] Example 8:

[0090] (S)-2-(4-Methyl-2-oxoquinolin-1(2H)-yl)pyridine methyl methacrylate

[0091]

[0092] Step 1, MBH carbonate (263.8 mg, 0.9 mmol), quinoline-2(1H)-one (47.7 mg, 0.3 mmol), catalyst (DHQD) 2PYR (52.9 mg, 0.06 mmol), and reaction solvent ethylene glycol dimethyl ether (1.5 mL) were added to a 4 mL reaction bottle equipped with a stirrer, and the mixture was reacted at room temperature and monitored by TLC spot plate. After the reaction was complete, the crude product was purified by silica gel column chromatography to obtain central chiral enamide quinolinone 3e with a yield of 72% and an ee value of 95%. The hydrogen and carbon spectra of the obtained 3e are shown as follows: Fig.17 and Fig.18 shown.

[0093] 1 H NMR(500MHz,Chloroform-d)δ8.55(d,J=4.9Hz,1H),8.04(s,1H),7.65(d,J=7.9Hz,1H),7.50(t,J=7.8Hz,1H),7.30(d,J=8.6 Hz,1H),7.19(t,J=7.9Hz,1H),7.11(td,J=8.8,5.5Hz,3H),6.71(s,1H),6.34(s,1H),5.30(s,1H),3.75(s,3H),2.50(s,3H). 13 CNMR(126MHz,Chloroform-d)δ167.31,162.27,158.18,148.51,147.70,138.45,136.85,129.66, 125.13,125.00,122.88,122.88,122.19,122.14,122.06,120.70,118.31,58.29,52.11,19.21..

[0094] (E)-2-Methyl-3-(4-methyl-2-oxoquinolinyl)-3-(2H)pyridine acrylate

[0095]

[0096] Step 2, add 3d (0.1 mmol), DBU (30.4 mg, 0.2 mmol), and solvent toluene (1 mL) to a 4 mL reaction bottle equipped with a stirrer, and react at room temperature. After the reaction, the crude product was purified by silica gel column chromatography to obtain tetrasubstituted axial chiral enamide quinolinone 4e with a yield of 92% and an ee value of 94%. The hydrogen and carbon spectra of the obtained 4e are as follows: Fig.19 and Fig. 20 shown.

[0097] 1 H NMR(500MHz,Chloroform-d)δ8.57(d,J=4.6Hz,1H),7.74(d,J=7.9Hz,1H),7.52(td,J=7.8,1.8Hz,1H),7.45–7.41(m,1H), 7.30–7.24(m,2H),7.15(dd,J=7.5,4.8Hz,1H),6.96(d,J=7.9Hz,1H),6.68(s,1H),3.78(s,3H),2.55(s,3H),1.84(s,3H). 13 CNMR(126MHz,Chloroform-d)δ170.34,160.76,152.51,148.99,148.23,138.74,136.86,135.04, 134.75,131.04,125.23,123.16,122.82,121.33,121.21,120.98,115.73,52.10,19.29,16.81..

Claims

1. A tetrasubstituted axial chiral enamide quinolinone, characterized in that: Its structural formula is as follows:

2. A method for synthesizing a tetrasubstituted axial chiral enamide quinolinone, characterized in that: include: (1) The steps of synthesizing central chiral enamide quinolinone 3 using MBH carbonate 1 and quinolin-2(1H)-one derivative 2 as reaction raw materials, (DHQD)2PYR catalyst, and DME as solvent, (2) The step of synthesizing a tetrasubstituted axial chiral enamide quinolinone 4 using a central chiral enamide quinolinone 3 as a reaction raw material, DBU as a base, and toluene as a solvent, Among them, when R 1 When R is selected from hydrogen, methyl or bromine, 2 is selected from hydrogen; R 1 When selected from hydrogen, R 2 is selected from hydrogen, methyl or bromine.

3. The method according to claim 1, characterized in that In step (1), the molar ratio of MBH carbonate to quinoline-2(1H)-one derivative is 3:

1.

4. The method according to claim 1, characterized in that In step (1), the molar amount of the (DHQD)2PYR catalyst is 20% of the molar amount of the quinoline-2(1H)-one derivative.

5. The method according to claim 1, characterized in that In step (1), the reaction temperature is room temperature.

6. The method according to claim 1, characterized in that In step (2), the amount of DBU used is twice the molar amount of the central chiral enamide quinolinone.

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