A method for synthesizing quinoline-substituted homoallylamine compounds

Abstract

The invention discloses a method for synthesizing quinoline-substituted homoallylamine compounds. 2-allylquinoline is used as an allylation reagent. In the presence of a catalyst, a base, and a solvent, allylation of the 2-allylquinoline with an N-aryl imine is achieved by cross-coupling. The system is stirred in an air atmosphere at room temperature for 6 hours to yield a high product yield, thereby synthesizing quinoline-substituted homoallylamine compounds. This method does not require the introduction of metals, has mild reaction conditions, is easy to operate, has good functional group compatibility, and reacts rapidly, making it an excellent strategy for synthesizing quinoline-substituted homoallylamine compounds.

Description

Technical Field

[0001] The invention belongs to the technical field of synthesis and application of organic compounds, and particularly relates to a method for synthesizing a quinoline-substituted homoallylamine compound. Background Art

[0002] Numerous reports have been published on the study of homoallylamines, which can be used to synthesize various pharmaceuticals and biologically active natural substances. Their synthetic pathways are crucial. Due to the high reactivity and shelf stability of N-aryliminines, their allylation is a relatively direct and efficient strategy for synthesizing these compounds. However, allylation has always been a challenging research topic in organic synthesis, and reports on the allylation of N-aryliminines are even rarer. Most methods involve coupling reactions of allyl metal reagents with imines and three-component reactions involving 1,3-butadiene. These methods suffer from environmental concerns, poor functional group tolerance, and high raw material costs. Therefore, developing a milder method for the allylation of N-aryliminines is of great significance.

[0003] At present, there are some literature reports on the allylation method of N-aryl imine, but these methods all have some deficiencies and shortcomings. For example, in 1999, the Journal of Organic Chemistry (J.Org.Chem.1999,64,4233.) reported the cross-coupling reaction of allyl silicon reagents with N-aryl imines. This method uses tetrabutylammonium fluoride as a catalyst and adds a small amount of molecular sieves to the system. The reaction can harvest a high product yield and the substrate has a wide range of uses. However, the nucleophilic reagent used in the reaction needs to be isolated from the air for preparation and use. The operation is not simple enough and the inhibition in large-scale reactions is also large, so the practicality is not high. In 2017, the American Chemical Society (J.Am.Chem.Soc.2017,139,4362.) reported the cross-coupling reaction of bis(trimethylsilyl)amino The sodium-promoted cross-coupling reaction of allylbenzene and N-aryl imine uses dioxane as solvent and can produce a product yield of 96% at room temperature, but the system used is not mild enough. The strong base sodium bistrimethylsilylamide needs to be added to the system. Various acidic functional groups cannot be well tolerated in this system, and the substrate range is greatly limited; in 2020, "American Chemical Society" (J.Am.Chem.Soc.2020,142,10337.) also reported the reductive coupling reaction of N-aryl imine and allyl bromide reagent catalyzed by divalent metal samarium. The reaction also achieved a high yield, but the metal catalyst used is relatively expensive and its practical value is not high.

[0004] Not only can two-component cross-coupling reactions achieve the allylation of N-aryliminides, but three-component reactions involving some 1,3-butadiene can also achieve this transformation. Both Organic Letters (Org. Lett. 2007, 9, 1871) and Organometallics (Organometallics) describe allylation reactions involving aryl nucleophiles and 1,3-butadiene. The former uses diphenylzinc as the nucleophile, a combination of Ni(acac)2 and 3-hexene as the catalyst, and THF as the solvent. The system completes the reaction after three hours of stirring at 30°C, achieving good yields. The latter uses a relatively weaker nucleophilic arylboronic acid as the nucleophile, a combination of Ni(cod)2 and 3-hexyne as the catalyst, and THF as the solvent. The reaction achieves near-100% yield after six hours of stirring at room temperature. Furthermore, the system is applicable to a wide range of substrates, demonstrating its practical value. However, both reactions require nickel catalysis and anhydrous and oxygen-free reaction conditions and atmosphere. These operations are not simple, and the high cost of metal catalysts hinders widespread application and hinders their widespread adoption. Therefore, developing a safe and reliable method for the allylation of N-arylimines, characterized by readily available raw materials, good selectivity, and a wide range of applications, remains of great significance.

[0005] In summary, it is of great significance to select a more stable and easy-to-prepare allylation reagent and develop a mild method to cross-couple it with N-aryl imines to synthesize highly allylic amine compounds, further improving the product yield, rate, functional group tolerance, economy and operability of the reaction. Summary of the Invention

[0006] As mentioned above, although there are many methods for allylating N-arylimines, each method has its limitations. The present invention is directed to the deficiencies in the above-mentioned prior art, and provides a synthetic method for a quinoline-substituted homoallylamine compound, wherein the allylation of the latter is achieved by a cross-coupling method of 2-allylquinoline and N-arylimine. The present invention uses cheap and readily available 2-allylquinoline as an allylation reagent, promotes the coupling reaction of the two by boron trifluoride etherate and triethylamine, and reacts to produce the corresponding allylated product in a very good yield under room temperature and air conditions. The reaction conditions are mild, simple to operate, and has good functional group tolerance, making it an excellent solution for synthesizing various types of homoallylamine compounds.

[0007] The invention discloses a method for synthesizing quinoline-substituted homoallylamine compounds. Allylquinoline and allylquinoline with partial substituents are used as allylation reagents. In the presence of a catalyst, a base and a solvent, 2-allylquinoline and N-aryl imine are cross-coupled to achieve allylation of the latter. The system is placed in an air atmosphere at room temperature and stirred for reaction for 6 hours to obtain a high product yield, thereby synthesizing the quinoline-substituted homoallylamine compounds.

[0008] The substituents in the partially substituted allylquinoline are selected from one of hydrogen, methoxy, phenoxy, methyl, hydroxyl, fluorine, chlorine, bromine, nitro, trifluoromethyl and the like.

[0009] The N-aryl imine is selected from N-p-methoxyphenyl aryl imine, N-p-tolyl aryl imine, N-phenyl-p-methoxyphenyl imine, N-phenyl-p-tolyl imine, N-phenyl-p-chlorophenyl imine, N-phenyl-p-bromophenyl imine, etc., and the general structural formula is shown below:

[0010]

[0011] In the above general formula, R1 and R2 are independently selected from one of hydrogen, methoxy, phenoxy, methyl, hydroxy, fluorine, chlorine, bromine, nitro and trifluoromethyl.

[0012] The solvent is selected from dichloroethane, toluene, methanol, etc., preferably methanol.

[0013] The catalyst is boron trifluoride ethyl ether or ferric chloride, preferably boron trifluoride ethyl ether.

[0014] The base is selected from sodium methoxide, sodium tert-butoxide, triethylamine, etc., preferably triethylamine.

[0015] In the present invention, the molar ratio of the N-aryl imine, allylquinoline, catalyst and base is 1.0:2.0-2.5:0.5:0.5, and the preferred molar ratio is 1.0:2.0:0.5:0.5.

[0016] The reaction scheme of the present invention is shown as follows:

[0017]

[0018] R1, R2, and R3 are each independently selected from one of hydrogen, methoxy, phenoxy, methyl, hydroxy, fluorine, chlorine, bromine, nitro, and trifluoromethyl.

[0019] In the present invention, the nucleophilic raw material is prepared by the most common coupling method, that is, cross-coupling of allylmagnesium bromide and 2-bromoquinoline is carried out under nitrogen protection. That is, 5.0 mmol of 2-bromoquinoline and its derivatives are first added to a Schlenk flask under nitrogen protection, 10.0 mL of THF is added as a reaction solvent, and then allylmagnesium bromide (7.5 mmol) is added. After stirring the reaction for 4 hours, water is added dropwise to quench the reaction. Finally, the raw material allylquinoline is separated and purified by column chromatography (eluent: petroleum ether / ethyl acetate = 20 / 1, V / V).

[0020] Preparation of 6-methoxyallylquinoline and 4,8-dimethylallylquinoline: Under nitrogen, add substituted 2-chloroquinoline (81.8 mg, 5.0 mmol) to a Schlenk flask, then add 10 mol% Co(acac)2 (89.0 mg, 0.25 mmol), 10.0 mL of tetrahydrofuran, and finally allylmagnesium bromide (7.5 mmol). Stir the reaction for 4 hours, then quench with water dropwise. The organic phase is separated and purified by column chromatography (eluent: petroleum ether / ethyl acetate = 20 / 1, v / v) to obtain the raw material allylquinoline. (Chem. Lett. 2004, 33, 1240.)

[0021] N-aryliminines, due to the special carbon-nitrogen double bond in their molecular structure, are highly reactive and are electrophilic raw materials that can be stably present and have great reactivity among amine compounds. N-benzylideneaniline is commercially available, but its imine derivatives with substituents on the biphenyl group need to be prepared in-house. The preparation method is relatively simple: simply add 1 equivalent of aryl formaldehyde and 1.2 equivalents of aniline compounds to a flask at room temperature. Add a small amount of magnesium chloride and molecular sieves to the system, then add 10mL of methanol and gently heat under reflux. After the reaction stops, filter with suction, cool and concentrate the filtrate, and recrystallize to obtain the target product.

[0022] In the present invention, methanol does not need to be dehydrated and purified, and the reaction can be completed by placing the system in air at room temperature.

[0023] The present invention is a method for allylating N-arylimine, and the specific preparation process is described as follows:

[0024] N-aryl imine (18.0 mg, 0.1 mmol) was weighed and added to a 10 mL round-bottom flask equipped with a stirrer. Triethylamine (7.0 μL, 0.05 mmol), boron trifluoride etherate (7.1 mg, 0.05 mmol) and 3 mL of methanol were added respectively. Allyl quinoline (33.8 mg, 0.2 mmol) was added under stirring. The mixture was stirred at room temperature for 6 hours, concentrated in vacuo, and then separated and purified by silica gel column chromatography and preparative thin layer chromatography (eluent: petroleum ether / ethyl acetate = 5 / 1, V / V) to obtain the corresponding product.

[0025] Compared with the existing reaction method for allylation of N-aryl imine, the present invention has the following advantages:

[0026] 1. Mild reaction conditions; 2. Excellent yield; 3. Simple and rapid reaction; 4. Inexpensive and environmentally friendly system; 5. Wide range of applicable reaction substrates; 6. Provides an excellent solution for the synthesis of quinoline-substituted homoallylamine compounds. DETAILED DESCRIPTION

[0027] The technical solution of the present invention is further analyzed and explained below in conjunction with specific embodiments.

[0028] Example 1:

[0029]

[0030] N-Benzylaniline (18.0 mg, 0.1 mmol) was weighed and placed in a 10 mL round-bottom flask equipped with a stirrer. Triethylamine (7.0 μL, 0.05 mmol), boron trifluoride etherate (7.1 mg, 0.05 mmol), and 3 mL of methanol were added. 2-Allylquinoline (33.8 mg, 0.2 mmol) was added with stirring and the mixture was stirred at room temperature for 6 hours. The mixture was concentrated in vacuo and then purified by silica gel column chromatography and preparative thin-layer chromatography (eluent: petroleum ether / ethyl acetate = 5 / 1) to obtain the product.

[0031] 1 H NMR (400MHz, CDCl3) δ8.07 (dd, J=13.0, 8.5Hz, 2H), 7.77 (d, J=8.1Hz, 1H), 7.74 (t, 1H), 7.55 –7.47(m,2H),7.43(d,J=7.1Hz,2H),7.36(t,J=7.5Hz,2H),7.31–7.23(m,1H),7.08(t,J=7. 7Hz,2H),6.89(d,J=15.9Hz,1H),6.80–6.70(m,1H),6.69–6.62(m,1H),6.53(d,J=8.0Hz,2H ),4.58(dd,J=8.2,5.0Hz,1H),4.23(t,J=6.5Hz,1H),2.94–2.85(m,1H),2.85–2.74(m,1H). 13C NMR (101MHz, CDCl3) δ155.70,148.01,147.21,143.38,136.58,134.34,133.15,129.90,129.21,129.18, 128.87,127.62,127.41,127.32,126.41,126.36,118.73,117.56,113.60,57.51,42.64.HRMS(ESI):m / z 351.1861[M+H] + ,calcd.for C 25 H 23 N2351.1861.

[0032] The reaction conditions optimization process is as follows:

[0033]

[0034]

[0035] Example 2:

[0036]

[0037] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent (v:v=5:1) as the eluent. The product yield was 87%, and the product was a yellow-brown liquid.

[0038] 1 H NMR(400MHz, CDCl3)δ8.06(dd,J=11.6,8.5Hz,2H),7.77(d,J=8.1,1.4Hz,1H),7.72–7.67(m,1H),7.54–7.46(m,2H),7.34(d,2H),7.09(t ,2H),6.95–6.82(m,3H),6.79–6.61(m,2H),6.53(d,2H),4.54(dd,J=7.9,5.3Hz,1H),3.80(s,3H),2.90–2.82(m,1H),2.82–2.73(m,1H). 13 C NMR (101MHz, CDCl3) δ158.80,155.77,148.02,147.29,136.55,135.33,134.24,133.28,129.88,129.20 ,127.61,127.48,127.41,126.33,118.72,117.52,114.22,113.64,56.96,55.37,42.66.HRMS(ESI):m / z 381.1961[M+H]+ ,calcd.forC 31 H 27 N2O 381.1967.

[0039] Example 3:

[0040]

[0041] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent (v:v=5:1) as the eluent. The product yield was 90%, and the product was a yellow liquid.

[0042] 1 H NMR (400MHz, CDCl3) δ7.98 (dd, J=13.7, 8.5Hz, 2H), 7.70 (d, J=8.1, 1.4Hz, 1H) ,7.66–7.57(m,3H),7.47–7.35(m,2H),7.27–7.15(m,3H),7.10(d,2H),7.06– 6.94(m,4H),6.89(d,2H),6.84–6.73(m,2H),6.71–6.54(m,2H),6.44(d,2H), 4.47(dd,J=8.0,5.1Hz,2H),2.85–2.76(m,1H),2.71(dt,J=14.8,7.7Hz,1H). 13 C NMR (101MHz, CDCl3) δ157.60,157.26,155.65,148.09,147.04,145.72,136.56,134.51,132.75,130.23,129.90,129.84,129 .26,129.22,127.62,127.44,126.38,123.26,121.35,118.82,118.79,117.72,117.05,113.70,57.38,42.46.HRMS(ESI):m / z 443.2125[M+H] + ,calcd.for C 31 H 27 N2O443.2123.

[0043] Example 4:

[0044]

[0045] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent (v:v=5:1) as the eluent. The product yield was 94%, and the product was a yellow liquid.

[0046] 1H NMR (400MHz, CDCl3) δ8.08(d,J=8.6Hz,1H),8.04(d,J=8.5Hz,1H),7.77(d,J=8.1Hz,1H),7. 69(t,J=8.6,6.8,1.5Hz,1H),7.57–7.44(m,2H),7.31(d,J=7.8Hz,2H),7.16(d,J=7.7Hz,2H ),7.07(t,2H),6.88(d,J=16.0Hz,1H),6.80–6.69(m,1H),6.64(t,J=7.4Hz,1H),6.52(d,J= 8.0Hz,2H),4.55(dd,J=8.1,5.2Hz,1H),2.92–2.83(m,1H),2.83–2.73(m,1H),2.34(s,3H). 13 C NMR (126MHz, CDCl3) δ155.76,147.99,147.30,140.34,136.88,136.59,134.24,133.37,129.91,129.56,129 .21,129.18,127.62,127.41,126.36,126.32,118.72,117.50,113.59,57.25,42.67,21.24.HRMS(ESI):m / z 365.2013[M+H] + ,calcd.for C 26 H 25 N2365.2018.

[0047] Example 5:

[0048]

[0049] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent (v:v=5:1) as the eluent. The product yield was 94%, and the product was a yellow liquid.

[0050] 1H NMR (400MHz, CDCl3) δ8.11(d,J=8.5Hz,1H),8.06(d,J=8.5Hz,1H),7.78(d,J=8.1Hz,1H ),7.74–7.68(m,1H),7.61(d,J=8.1Hz,2H),7.55(d,J=8.1Hz,2H),7.51(t,J=7.5Hz,2H) ,7.15–7.03(m,2H),6.90(d,J=15.9Hz,1H),6.78–6.70(m,1H),6.67(t,J=7.3Hz,1H),6 .48(d,J=7.5Hz,2H),4.63(dd,J=8.2,4.9Hz,1H),2.95–2.85(m,1H),2.83–2.73(m,1H). 13 C NMR (101MHz, CDCl3) δ155.42,148.09,147.69,146.78,136.67,134.88,132.10,129.97,129.31,129.30 (q, J=32.01Hz) 129 .27,127.65,127.50,126.80,126.47,125.92(q,J=4.2Hz),124.31(q,J=271.87Hz),118.85,118.04,113.65,57.26,42.44. 19 FNMR(376MHz,CDCl3)δ-62.06.HRMS(ESI):m / z 419.1732[M+H] + ,calcd.forC 26 H 22 F3N2419.1730.

[0051] Example 6:

[0052]

[0053] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent (v:v=5:1) as the eluent. The product yield was 85%, and the product was a yellow-white liquid.

[0054] 1H NMR (400MHz, CDCl3) δ8.25–8.19(m,2H),8.10(d,J=8.6Hz,1H),8.03(d,J=8.5Hz ,1H),7.78(d,1H),7.73–7.67(m,1H),7.61(dd,J=8.7,1.5Hz,2H),7.55–7.45(m, 2H),7.12–7.05(m,2H),6.88(d,J=15.6Hz,1H),6.77–6.65(m,2H),6.45(d,2H),4 .66(dd,J=8.2,5.1Hz,1H),4.31(brs,1H),2.95–2.85(m,1H),2.84–2.73(m,1H). 13 C NMR (101MHz, CDCl3) δ155.19,151.33,148.10,147.40,146.47,136.72,135.19,131.42,130.01,129.37, 129.28,127.66,127.53,127.36,126.54,124.27,118.91,118.34,113.66,57.24,42.22.HRMS(ESI):m / z 396.1700[M+H] + ,calcd.for C 25 H 22 N3O2396.1712.

[0055] Example 7:

[0056]

[0057] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent (v:v=5:1) as the eluent. The product yield was 93%, and the product was a yellow liquid.

[0058] 1H NMR (400MHz, CDCl3) δ8.09(d,J=8.6Hz,1H),8.05(d,J=8.5Hz,1H),7.77(d,J=8.2, 1.5Hz,1H),7.73–7.66(m,1H),7.54–7.46(m,2H),7.43–7.34(m,2H),7.09(dd,J=8 .6,7.3Hz,2H),7.04(t,J=8.7Hz,2H),6.87(d,1H),6.78–6.63(m,2H),6.51(d,J=7 .0,1.5Hz,2H),4.56(dd,J=8.1,5.1Hz,1H),2.90–2.81(m,1H),2.81–2.71(m,1H). 13 C NMR(101MHz, CDCl3)δ162.07(d,J=244.4Hz),155.57,148.03,147.03,139.04(d,J=2.9Hz),136.64,134.52,132.72,129.95, 129.25, 129.22, 127.94 (d, J = 8.0Hz), 127.63, 127.46, 126.42, 118.79, 117.80, 115.72 (d, J = 21.3Hz), 113.67, 56.95, 42.69. 19 F NMR(376MHz, CDCl3)δ-115.70.HRMS(ESI):m / z 367.1769[M+H] + ,calcd.for C 25 H 22 FN2369.1767.

[0059] Example 8:

[0060]

[0061] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent (v:v=5:1) as the eluent. The product yield was 85%, and the product was a white liquid.

[0062] 1H NMR (500MHz, CDCl3) δ8.09(d,J=8.5Hz,1H),8.04(d,J=8.5Hz,1H),7.77(d,J=8.1Hz, 1H),7.70(t,J=7.7Hz,1H),7.56–7.45(m,2H),7.40–7.34(m,2H),7.34–7.29(m,2H), 7.08(t,J=7.7Hz,2H),6.87(d,J=15.9Hz,1H),6.77–6.62(m,2H),6.49(d,J=8.0Hz,2 H),4.55(dd,J=8.1,5.0Hz,1H),4.26(brs,1H),2.90–2.81(m,1H),2.81–2.71(m,1H). 13 CNMR(101MHz, CDCl3)δ155.53,148.09,146.93,141.97,136.62,134.69,132.91,132.43,129.93,129 .27,129.05,127.84,127.63,127.47,126.42,118.81,117.88,113.66,57.01,42.53.HRMS(ESI):m / z 385.1466[M+H] + ,calcd.for C 25 H 22 ClN2385.1472.

[0063] Example 9:

[0064]

[0065] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent as the eluent (v:v=5:1). The product yield was 86%, and the product was a yellow liquid.

[0066] 1 H NMR (400MHz, CDCl3) δ8.09(d,J=8.6Hz,1H),8.04(d,J=8.5Hz,1H),7.77(dd ,J=8.0,1.4Hz,1H),7.73–7.67(m,1H),7.54–7.42(m,4H),7.31(d,2H),7.12 –7.03(m,2H),6.87(d,J=16.0Hz,1H),6.77–6.59(m,2H),6.48(d,2H),4.53 (dd,J=8.0,5.1Hz,1H),4.23(brs,1H),2.90–2.81(m,1H),2.81–2.71(m,1H)13 C NMR (101MHz, CDCl3) δ155.52,148.10,146.90,142.53,136.62,134.72,132.39,132.00,129.94,129 .27,128.24,127.64,127.48,126.43,121.01,118.82,117.91,113.67,57.07,42.48.HRMS(ESI):m / z 429.0965[M+H] + ,calcd.for C 25 H 22 BrN2429.0966.

[0067] Example 10:

[0068]

[0069] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent (v:v=5:1) as the eluent. The product yield was 74%, and the product was a yellow-white liquid.

[0070] 1 H NMR (400MHz, CDCl3) δ8.08(d,J=8.6Hz,1H),8.05(d,J=8.6Hz,1H),7.77(d,J=6.7 Hz,1H),7.73–7.66(m,1H),7.55–7.47(m,2H),7.42(d,J=6.8Hz,2H),7.35(t,J=7. 6Hz,2H),7.30–7.27(m,0H),6.88(d,J=16.2Hz,1H),6.79–6.73(m,1H),6.69–6.64 (m,2H),6.47(d,J=8.9Hz,2H),4.54–4.45(m,1H),3.68(s,3H),2.92–2.72(m,2H). 13 C NMR (101MHz, CDCl3) δ155.77,152.12,147.99,143.67,141.50,136.61,134.22,133.40,129.92,129.15 ,128.85,127.62,127.43,127.28,126.49,126.36,118.76,114.84,58.33,55.84,42.72.HRMS(ESI):m / z 381.1957[M+H] + ,calcd.for C 26 H 25 N2O 381.1967.

[0071] Example 11:

[0072]

[0073] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent (v:v=1:1) as the eluent. The product yield was 72%, and the product was a yellow-brown solid.

[0074] 1 H NMR (400MHz, CDCl3) δ8.09(d,J=8.5Hz,2H),7.76(dd,J=8.1Hz,1H),7.66(td,1H ),7.52–7.45(m,2H),7.39–7.34(m,2H),7.31(t,J=7.5Hz,2H),7.23(t,J=7.1Hz ,1H),6.87(d,J=16.2Hz,1H),6.77–6.66(m,1H),6.61(d,J=8.9Hz,2H),6.33(d, J=8.8Hz,2H),4.40(dd,J=8.0,5.0Hz,1H),2.84–2.75(m,1H),2.75–2.65(m,1H). 13 C NMR (101MHz, CDCl3) δ155.70,148.48,147.55,143.73,140.99,137.05,134.12,133.67,130.20,128 .78,128.63,127.62,127.43,127.19,126.49,118.92,116.29,115.15,58.29,42.66.HRMS(ESI):m / z 389.1632[M+Na] + ,calcd.for C 25 H 22 N2ONa 389.1630.

[0075] Example 12:

[0076]

[0077] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent (v:v=5:1) as the eluent. The product yield was 83%, and the product was a yellow liquid.

[0078] 1H NMR (400MHz, CDCl3) δ8.07(t,J=8.3Hz,2H),7.77(d,J=8.1Hz,1H),7.70(td,J= 6.9Hz,1H),7.51(d,J=8.4Hz,2H),7.43(d,J=6.9Hz,2H),7.36(t,J=7.6Hz,2H), 7.30–7.22(m,1H),6.94–6.84(m,3H),6.80–6.69(m,1H),6.45(d,J=8.4Hz,2H), 4.55(dd,J=8.2,5.0Hz,1H),2.94–2.84(m,1H),2.83–2.72(m,1H),2.18(s,3H). 13 C NMR (101MHz, CDCl3) δ155.76,148.01,144.97,143.59,136.57,134.25,133.33,129.89,129.71,129.18,128 .84,127.61,127.42,127.25,126.74,126.44,126.34,118.74,113.72,57.78,42.65,20.46.HRMS(ESI):m / z 365.2019[M+H] + ,calcd.for C 26 H 25 N2365.2018.

[0079] Example 13:

[0080]

[0081] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent as the eluent (v:v=5:1). The product yield was 63%, and the product was a yellow liquid.

[0082] 1H NMR(500MHz, CDCl3)δ7.98–7.90(m,2H),7.42(d,J=8.7Hz,1H),7.40–7.36(m,1H),7 .34(d,J=7.5Hz,2H),7.32–7.25(m,3H),7.18(d,J=5.0Hz,1H),7.00(t,J=7.7Hz,2H) ,6.76(d,J=15.9Hz,1H),6.70–6.61(m,1H),6.57(t,J=7.3Hz,1H),6.44(d,J=8.0Hz ,2H),4.49(t,J=8.2,5.1Hz,1H),4.16(s,1H),2.85–2.76(m,1H),2.76–2.64(m,1H). 13 C NMR (126MHz, CDCl3) δ160.38 (d, J = 247.5Hz), 155.15, 147.20, 145.17, 143.35, 135.84 (d, J = 5.4Hz), 134.05, 133.09, 131.67 (d, J = 9.1Hz), 1 29.23, 128.88, 127.93 (d, J = 10.0Hz), 127.34, 126.41, 119.96 (d, J = 25.5Hz), 119.56, 117.61, 113.61, 110.74 (d, J = 21.4Hz), 57.53, 42.58. 19 F NMR(471MHz, CDCl3)δ-113.78.HRMS(ESI):m / z 367.1769[M+H] + ,calcd.for C 25 H 22 FN2369.1766.

[0083] Example 14:

[0084]

[0085] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent as the eluent (v:v=5:1). The product yield was 64%, and the product was a yellow liquid.

[0086] 1H NMR (400MHz, CDCl3) δ7.97(d,J=8.7Hz,1H),7.94(d,J=9.3Hz,1H),7.46(d,J=8 .6Hz,1H),7.44–7.40(m,2H),7.37(d,J=3.0Hz,1H),7.36–7.32(m,2H),7.29–7 .23(m,1H),7.10–7.03(m,3H),6.85(d,J=15.7,1.3Hz,1H),6.70–6.60(m,2H), 6.55–6.49(m,2H),4.56(dd,J=8.1,5.0Hz,1H),3.93(s,3H),2.92–2.71(m,2H). 13 C NMR (101MHz, CDCl3) δ157.78,153.49,147.30,144.03,143.50,135.34,134.32,131.80,130.64,129.21,128 .87,128.41,127.29,126.45,122.46,119.05,117.56,113.65,105.36,57.60,55.68,42.64.HRMS(ESI):m / z 403.1780[M+Na] + ,calcd.for C 26 H 24 N2ONa 403.1786.

[0087] Example 15:

[0088]

[0089] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent (v:v=5:1) as the eluent. The product yield was 82%, and the product was a yellow liquid.

[0090] 1H NMR(400MHz, CDCl3)δ8.05(d,J=8.5Hz,1H),7.94(d,J=7.0Hz,1H),7.73–7.66(m, 1H),7.56–7.48(m,1H),7.43(d,J=9.6Hz,2H),7.37(d,3H),7.29–7.24(m,1H),7.0 8(dd,J=8.6,7.3Hz,2H),6.85(d,J=17.1Hz,1H),6.78–6.68(m,1H),6.65(t,1H),6 .52(d,J=6.3Hz,2H),4.57(dd,J=8.2,5.0Hz,1H),2.94–2.72(m,2H),2.68(s,3H). 13 C NMR (101MHz, CDCl3) δ155.32,147.74,147.28,144.78,143.46,134.34,133.01,129.65,129.22,128.88 ,127.57,127.31,126.44,126.17,123.79,119.36,117.58,113.65,57.58,42.68,19.00.HRMS(ESI):m / z 387.1832[M+Na] + ,calcd.for C 26 H 24 N2Na 387.1837.

[0091] Example 16:

[0092]

[0093] The experimental operation was carried out with reference to Example 1, using a petroleum ether / ethyl acetate mixed solvent (v:v=5:1) as the eluent. The product yield was 62%, and the product was a yellow liquid.

[0094] 1H NMR(400MHz,CDCl3)δ7.73(d,J=8.3Hz,1H),7.47(d,J=7.0Hz,1H),7.38(d,J=7.4Hz,2H),7.36–7.28(m,3H),7.25–7.18(m,2H),7.02(d,2H),6.80(d,J=16.0Hz,1H),6.76–6.67(m,1H),6.59(t,J=7.3,0.9Hz,1H),6.47(d,2H),4.52(dd,J=8.3,4.9Hz,1H),2.87–2.79(m,1H),2.76(s,3H),2.74–2.67(m,1H),2.61(d,J=0.9Hz,3H). 13 C NMR(101MHz,CDCl3)δ153.97,147.35,147.02,144.50,143.61,137.75,134.93,131.97,129.67,129.21,128.85,127.46,127.27,126.45,125.64,121.65,119.36,117.55,113.68,57.65,42.66,19.26,18.42.HRMS(ESI):m / z 401.1990[M+Na] + ,calcd.for C 27 H 26 N2Na401.1994.

Claims

1. A method for synthesizing a quinoline-substituted homoallylamine compound, characterized in that: Quinoline-substituted homoallylamine compounds are prepared by cross-coupling in the presence of a catalyst, a base, and a solvent in an air atmosphere at room temperature using an N-aryl imine shown in 1a as an electrophilic reagent and an allylquinoline or an allylquinoline with partial substituents shown in 2a as an allylation reagent. The reaction route is as follows: ； R1, R2, and R3 are each independently selected from one of hydrogen, methoxy, phenoxy, methyl, hydroxy, fluorine, chlorine, bromine, nitro, and trifluoromethyl; The catalyst is boron trifluoride etherate or ferric chloride; The solvent is methanol; The base is selected from sodium methoxide or triethylamine.

2. The synthesis method according to claim 1, wherein: The catalyst is boron trifluoride etherate.

3. The synthesis method according to claim 1, wherein: The base is triethylamine.

4. The synthesis method according to claim 1, wherein: The molar ratio of 1a, 2a, catalyst and base is 1.0: 2.0-2.5: 0.5: 0.5.

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