Chiral 2-aminobenzopyran derivatives, processes for their preparation and uses thereof

Abstract

The present application relates to a kind of chiral 2-amino benzopyran derivatives with bactericidal activity, and its preparation method and purposes.The chiral 2-amino benzopyran derivatives of the present application have the structure shown in general formula I, and the synthesis process of the present application is simple, and has certain inhibitory effect on plant pathogenic fungi.

Description

Technical Field

[0001] This invention belongs to the field of pesticide technology, specifically relating to a chiral 2-aminobenzopyran derivative with bactericidal activity, its preparation method, and its uses. Background Technology

[0002] In the process of grain production, diseases, pests, weeds, and other harmful organisms are the main factors affecting crop production and reducing grain yield and quality. Therefore, controlling the occurrence of crop diseases is the key to increasing grain yield. Among these, pesticides are a powerful means of suppressing diseases.

[0003] Fungicides, as a member of the pesticide family, are a class of agents used to control plant diseases caused by various pathogenic microorganisms. They are a collective term for agents that kill or inhibit the growth of pathogens without hindering normal plant growth, and constitute an important type of pesticide. However, with the widespread use of fungicides, pathogens are increasingly developing resistance to these agents, thus necessitating the research of more novel fungicides to address this problem.

[0004] Benzopyrans are a very important class of oxygen-containing heterocyclic compounds, widely found in synthetic chemistry and natural products, exhibiting a wide range of biological activities, including but not limited to antitumor, antibacterial, antituberculosis, and antifungal activities, as well as Bcl-2 inhibitors. As potential drug candidate skeletons, benzopyrans are attracting increasing attention, and these compounds possess enormous research and development potential.

[0005] Currently, there are few reports on the application of benzopyran compounds in the field of pesticides. However, they have the characteristics of high efficiency, low toxicity, safety for non-target organisms, easy degradation in the environment, and low resistance to harmful organisms. Therefore, benzopyran compounds have the potential to be used as agricultural fungicides. Summary of the Invention

[0006] In a first aspect, the present invention provides a chiral 2-aminobenzopyran derivative having bactericidal activity as shown in general formula (I):

[0007]

[0008] in:

[0009] R 1 Selected from hydrogen, C 1-8 Alkyl, nitro, fluorine, chlorine, bromine, substituted or unsubstituted C 1-8 Alkoxy, C 1-8 Halogenated alkyl, hydroxyl, amino, methylamino, dimethylamino, C-substituted 1-8 The substituents of the alkoxy group are selected from halogens, or R 1Ringing with linked atoms;

[0010] R 2 Selected from nitro, cyano, ester, trifluoromethyl, trifluoroacetyl (-COCF3), C 1-6 Alkyl group, C 1-6 alkyl-formyl, C 1-6 Alkyl-methanesulfonyl or trifluoromethanesulfonyl (-SO2CF3);

[0011] R 3 Selected from substituted or unsubstituted C 1-8 Alkyl, substituted or unsubstituted C 3-8 cycloalkyl, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted C 1-4 Alkylene-C 6-10 Aryl, substituted or unsubstituted five- or six-membered heterocyclic groups containing nitrogen, oxygen and / or sulfur, where substitution refers to having one or more substituents selected from the group consisting of: C 1-6 Alkyl, nitro, fluorine, chlorine, bromine, C 1-6 Alkoxy, C 1-6 Halogenated alkyl, hydroxyl, amino, methylamino, dimethylamino, or, R 3 It forms a ring with the atoms it connects to.

[0012] In another preferred embodiment, R 1 Preferably selected from hydrogen, nitro, fluorine, chlorine, bromine, substituted or unsubstituted alkoxy, haloalkyl, hydroxyl, and amino groups.

[0013] In another preferred embodiment, R 2 Preferably selected from nitro, cyano, and ester groups.

[0014] In another preferred embodiment, R 3 Preferably selected from substituted or unsubstituted C 1-4 Alkyl, substituted or unsubstituted C 3-5 Cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted C1 alkylene-phenyl, substituted or unsubstituted five- or six-membered heterocyclic groups containing nitrogen, oxygen and / or sulfur, where substitution refers to having one or more substituents selected from the group consisting of: C 1-6 Alkyl, nitro, fluorine, chlorine, bromine, C 1-6 Alkoxy, C 1-6 The alkyl, hydroxyl, amino, methylamino, dimethylamino, or two substituents form a ring with the attached atom.

[0015] In another preferred embodiment, the compound has the structure shown in general formula (II):

[0016]

[0017] In the formula, R1 and R 3 As defined above.

[0018] Preferably, the compounds are selected from the following compounds

[0019]

[0020]

[0021] A second aspect of the present invention provides an agricultural composition comprising:

[0022] The first aspect provides compounds having the structure shown in general formula (I) or general formula (II) or pesticide-acceptable salts thereof; and

[0023] Pesticide-acceptable carriers and / or excipients.

[0024] In another preferred embodiment, the agricultural composition comprises 0.001-99.999% by mass of the above-described compound or a pesticide-acceptable salt thereof.

[0025] In another preferred embodiment, the concentration of the compound having the structure shown in general formula (I) or general formula (II) or its pesticide-acceptable salt is 10-1000 mg / L, more preferably 100-500 mg / L.

[0026] In another preferred embodiment, the pesticide composition is in the form of various conventional pesticide formulations, such as bait.

[0027] A third aspect of the present invention provides a method for preparing the compound described in the first aspect, comprising the steps of:

[0028] The compounds shown in formula a and formula b react under conditions of solvent, acid catalyst, metal catalyst, and ligand to give a compound having the structure shown in general formula I:

[0029]

[0030] In the above formula, the solvent used is selected from one or more of the following, with a water content of less than 10 ppm: acetonitrile (CH3CN), tetrahydrofuran (THF), toluene, trifluorotoluene, 1,2-dichloroethane (DCE), dichloromethane (CH2Cl2), 1,4-dioxane, methyl tert-butyl ether, cyclopentyl methyl ether, N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, preferably dichloromethane (CH2Cl2).

[0031] In the above formula, the metal catalyst used is a complex of iridium, palladium, rhodium, ruthenium, and cobalt, preferably a 1,5-cyclooctadiene iridium chloride dimer.

[0032] In the above formula, the ligand is selected from one of the following phosphoramidite ligands L1 to L12, preferably L1;

[0033]

[0034] In the above formula, the molar ratio of metal catalyst to ligand is 1%:4% or 2%:8% or 4%:16%, preferably 4%:16%, and in particular, the molar ratio of iridium metal catalyst to ligand is 4%:16%.

[0035] In the above formula, the acid catalyst used in the reaction is a protic acid or Lewis acid, selected from one or more of the following: o-nitrobenzoic acid, m-nitrobenzoic acid, diphenyl phosphate, diphenylsulfonamide, trifluoroacetic acid, trichloroacetic acid, acetic acid, phosphoric acid, boron trifluoride diethyl ether complex, iron trifluoromethanesulfonate, scandium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, ytterbium trifluoromethanesulfonate, lanthanum trifluoromethanesulfonate, cerium trifluoromethanesulfonate, neodymium trifluoromethanesulfonate, europium trifluoromethanesulfonate, dysprosium trifluoromethanesulfonate, lutetium trifluoromethanesulfonate, erbium trifluoromethanesulfonate, gadolinium trifluoromethanesulfonate, preferably cerium trifluoromethanesulfonate, ytterbium trifluoromethanesulfonate, or lanthanum trifluoromethanesulfonate, more preferably cerium trifluoromethanesulfonate;

[0036] In the above formula, the reaction temperature is -20 to 35℃, preferably 25℃.

[0037] In the above formula, the reaction time is 1-48 hours, preferably 24 hours.

[0038] This invention provides a method for preparing the compound, comprising the following specific steps: under nitrogen protection, a metal catalyst, such as 1,5-cyclooctadiene iridium chloride dimer, and a ligand, such as L1, are added to a dry reaction tube. After adding a solvent, such as CH2Cl2, the mixture is stirred at room temperature for 10 to 20 minutes. Then, compound b is added, followed by compound a and an acid catalyst, such as cerium trifluoromethanesulfonate, in sequence. Under TLC monitoring, the mixture is stirred at room temperature until the reaction is complete, and then the reaction is stopped. The product is obtained by purification by thin-layer chromatography.

[0039] The molar ratio of compound a to compound b is 1:2.5 to 1:3.5, preferably 1:3; the molar ratio of compound a to acid catalyst is 1:0.15 to 1:0.25, preferably 1:0.2; the molar ratio of compound a to metal catalyst is 1:0.035 to 1:0.045, preferably 1:0.04.

[0040] Based on the preparation method of the present invention, chiral 2-aminobenzopyran compounds can be synthesized in one step using simple and readily available raw materials. The operation is simple, the yield is high, the enantioselectivity is excellent, and the substrate range is broad.

[0041] Within the scope of this invention, the various technical details described above and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, further details will not be elaborated here.

[0042] In a fourth aspect, the present invention provides the use of the above-mentioned compound as an agricultural composition in an agricultural fungicide, wherein the fungicide controls the following pathogens: Fusarium head blight of wheat, sheath blight of rice, gray mold of cucumber, sclerotinia sclerotinia of rapeseed, take-all pathogen of wheat, gray mold of tomato, late blight of potato, Phytophthora in pepper, early blight of tomato, bakanae disease of rice, dry rot of potato, anthracnose of cucumber, and rice blast fungus, preferably Fusarium head blight of wheat, sheath blight of rice, gray mold of cucumber, and sclerotinia sclerotinia of rapeseed. Detailed Implementation

[0043] Group definition

[0044] As used in this article, the term "C" 1-8 "Alkyl" refers to a straight or branched alkyl group having 1 to 8 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, or similar groups.

[0045] Term "C" 2-8 "Alkoxy" refers to a straight-chain or branched alkoxy group with 2-8 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, or similar groups.

[0046] The term "halogen" refers to fluorine, chlorine, bromine, or iodine. The term "halogenated" refers to a group substituted with one or more of the same or different halogen atoms, such as p-chlorophenyl, trifluoromethyl, or 1,2-dichloroethyl.

[0047] The term "five- or six-membered heterocyclic group" refers to a five- or six-membered heterocycle containing one or more atoms selected from nitrogen, oxygen, sulfur or other heteroatoms, such as pyridinyl, thiophene, thiazolyl, pyrimidinyl, tetrahydrofuranyl or oxazolyl.

[0048] Preparation method of the compound of the present invention

[0049] The target compound of the present invention can be obtained by reaction of the compounds shown in Formula a and Formula b. The conditions of the method, such as raw materials, solvent, temperature, catalyst, acid, base, ratio, and reaction time, are not limited to the following examples.

[0050]

[0051] The invention is further illustrated below with reference to specific embodiments. Experimental methods not specified in the following embodiments are generally performed under conventional conditions. Unless otherwise stated, percentages and parts are by weight.

[0052] The target products in Examples 1 to 58 below were confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0053] Example 1: Synthesis of (S)-3-nitro-N-phenyl-4-vinyl-4H-chromene-2-amine

[0054]

[0055] After placing a magnetic stir bar in a 10 mL Schlenk reaction tube and drying the tube, 1,5-cyclooctadiene iridium chloride dimer (2.7 mg, 0.004 mmol) and L1 ligand (8.2 mg, 0.016 mmol) were added to the Schlenk tube under nitrogen protection. Redistilled CH2Cl2 (1.5 mL) was added, and stirring was started at room temperature for 15 minutes. Then, o-hydroxyphenyl allyl alcohol (45.0 mg, 0.3 mmol) was added, followed by a nitroenamine compound (21.0 mg, 0.1 mmol) and cerium trifluoromethanesulfonate (11.7 mg, 0.02 mmol). The mixture was stirred at room temperature until complete under TLC monitoring, and the reaction was stopped. The product was purified by thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate). The target product was confirmed by NMR spectroscopy and high-resolution mass spectrometry.

[0056] Its physicochemical properties are as follows: yellow powder, yield 94%, 96% ee (enantiomer excess percentage). 1 H NMR (400MHz, CDCl3) δ12.26(brs,1H),7.45–7.42(m,4H),7.32–7.25(m,3H),7.24–7.19(m,1H),7.08(d,J=8.0Hz ,1H),5.92(ddd,J=16.7,10.0,6.6Hz,1H),5.10(d,J=9.8Hz,1H),5.04(d,J=16.8Hz,1H),5.02(d,J=6.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ156.9,148.1,137.2,135.2,129.7,129.5(2C),128.6,126.6, 126.1,123.3(1),123.3(0)(2C),116.3,115.8,108.2,39.6.HRMS(EI-TOF)m / z:[M] + calcd for C 17 H 14N2O3:294.0999,found:294.1006;[α] D 25 =+19.0 (c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flowrate=1.0mL / min, λ=220nm)t R =8.466min(minor),15.350min(major).

[0057] The metal complexes, ligands, acid catalysts, and solvents used in this reaction were screened, and the corresponding yields and enantiomeric excess percentages are shown in Table 1 below.

[0058] Table 1

[0059]

[0060]

[0061] Example 2: Synthesis of (S)-N-(3-fluorophenyl)-3-nitro-4-vinyl-4H-chromene-2-amine

[0062]

[0063] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 83%, 95% ee. 1 HNMR(400MHz, CDCl3)δ12.26(brs,1H),7.45–7.35(m,1H),7.33–7.24(m,4H),7.17(d,J=8.0Hz,1H ),7.12(d,J=7.9Hz,1H),7.02–6.97(m,1H),5.91(ddd,J=16.8,10.0,6.6Hz,1H),5.12(d,J=10.0Hz 1H), 5.07 (d, J = 17.1Hz, 1H), 5.01 (d, J = 6.6Hz, 1H). 13 C NMR (100MHz, CDCl3) δ 163.1 (d, 1 J C-F =246.9Hz),156.6 148.0,137.1,136.8(d, 3 J C-F =10.4Hz), 130.7(d, 3 J C-F =9.2Hz),129.8,128.7,126.3,123.2,118.7(d,4 J C-F =3.2Hz), 116.1(d, 2 J C-F =32.8Hz), 113.3(d, 2 J C-F =21.3Hz),110.6,110.4,108.7,39.5. 19 F NMR(376MHz, CDCl3)δ-110.48–-110.55(m).HRMS(EI-TOF)m / z:[M] + calcd for C 17 H 13 FN2O3:312.0905,found:312.0912;[α] D 25 =+22.9(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =7.218min(minor),13.914min(major).

[0064] Example 3: Synthesis of (S)-N-(3-chlorophenyl)-3-nitro-4-vinyl-4H-chromene-2-amine

[0065]

[0066] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 78%, 89% ee. 1 HNMR(400MHz, CDCl3)δ12.18(brs,1H),7.49(s,1H),7.39–7.35(m,1H),7.33–7.20(m,5H),7.09(d,J=7.8Hz,1 H),5.90(ddd,J=16.7,10.0,6.6Hz,1H),5.10(d,J=10.3Hz,1H),5.04(d,J=17.2Hz,1H),5.00(d,J=6.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ156.6,147.9,137.1,136.5,135.1,130.5,129.7,128.7,126 .5,126.3,123.3,123.2,121.2,116.3,115.9,108.7,39.5.HRMS(EI-TOF)m / z:[M] +calcd for C 17 H 13 35 ClN2O3:328.0610,found:328.0612;C 17 H 13 37 ClN2O3:330.0580,found:330.0585;[α] D 25 =+30.2(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =7.182min(minor),12.817min(major).

[0067] Example 4: Synthesis of (S)-N-(4-fluorophenyl)-3-nitro-4-vinyl-4H-chromene-2-amine

[0068]

[0069] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 95%, 90% ee. 1 HNMR(400MHz, CDCl3)δ12.17(brs,1H),7.40(dd,J=9.0,4.7Hz,2H),7.32–7.24(m,3H),7.17–7.13(m,2H),7.04(d,J=8 .2Hz,1H),5.91(ddd,J=16.8,10.0,6.6Hz,1H),5.10(d,J=10.0Hz,1H),5.06(d,J=16.4Hz,1H),5.01(d,J=6.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ 161.0 (d, 1 J C-F =247.2Hz),156.9,148.1,137.1,131.1(d, 4 J C-F =3.2Hz),129.8,128.6,126.2,125.4(d, 3 J C-F =8.4Hz)(2C),123.3,116.5,116.3(d, 2 J C-F =8.6Hz)(2C),115.9,108.2,39.6. 19F NMR(376MHz, CDCl3)δ-114.62–-114.68(m).HRMS(EI-TOF)m / z:[M] + calcdfor C 17 H 13 FN2O3:312.0905,found:312.0908;[α] D 25 =+21.7(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =10.287min(minor),21.105min(major).

[0070] Example 5: Synthesis of (S)-N-(4-chlorophenyl)-3-nitro-4-vinyl-4H-chromene-2-amine

[0071]

[0072] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 89%, 94% ee. 1 HNMR(400MHz, CDCl3)δ12.20(brs,1H),7.42–7.35(m,4H),7.29–7.27(m,2H),7.25–7.18(m,1H),7.07(d,J=7.8H z,1H),5.90(ddd,J=16.7,10.0,6.6Hz,1H),5.09(d,J=9.8Hz,1H),5.04(d,J=16.8Hz,1H),4.99(d,J=6.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ156.6,147.9,137.1,133.8,132.0,129.7,129.6(2C),128 .6,126.2,124.5(2C),123.1,116.2,115.9,108.4,39.5.HRMS(EI-TOF)m / z:[M] + calcd for C 17 H 13 35 ClN2O3:328.0610,found:328.0613;C 17 H 13 37 ClN2O3:330.0580,found:330.0579;[α]D 25 =+29.7(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =9.144min(minor),19.878min(major).

[0073] Example 6 Synthesis of 5(S)-N-(4-bromophenyl)-3-nitro-4-vinyl-4H-chromene-2-amine

[0074]

[0075] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 89%, 98% ee. 1 HNMR(400MHz, CDCl3)δ12.19(brs,1H),7.57(d,J=8.7Hz,2H),7.33–7.25(m,5H),7.07(d,J=7.7Hz,1H),5 .91(ddd,J=16.8,10.0,6.6Hz,1H),5.10(d,J=10.7Hz,1H),5.05(d,J=17.6Hz,1H),5.01(d,J=6.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ156.7,148.1,137.1,134.4,132.7(2C),129.8,128.7,126 .3,124.9(2C),123.2,119.9,116.3,115.9,108.6,39.6.HRMS(EI-TOF)m / z:[M] + calcd for C 17 H 13 79 BrN2O3:372.0104,found:372.0111;C 17 H 13 81 BrN2O3:374.0084,found:374.0090;[α] D 25 =+19.8(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R=9.542min(minor),23.178min(major).

[0076] Example 7 Synthesis of (S)-3-nitro-N-(p-tolyl)-4-vinyl-4H-chromene-2-amine

[0077]

[0078] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 98%, 85% ee. 1 HNMR(400MHz, CDCl3)δ12.25(brs,1H),7.31–7.18(m,7H),7.05(d,J=9.4Hz,1H ),5.91(ddd,J=16.6,9.9,5.9Hz,1H),5.08(d,J=9.8Hz,1H),5.03(d,J=16.4Hz 1H), 4.99 (d, J = 6.6Hz, 1H), 2.38 (s, 3H). 13 CNMR(100MHz,CDCl3)δ156.8,148.1,137.1,136.6,132.5,129.9(2C),129.6,128.5 ,125.9,123.20,123.1(2C),116.2,115.6,107.9,39.5,21.1.HRMS(EI-TOF)m / z:[M] + calcd for C 18 H 16 N2O3:308.1155,found:308.1158;[α] D 25 =+24.5(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =9.176min(minor),14.421min(major).

[0079] Example 8: Synthesis of (S)-N-(3-chloro-4-methylphenyl)-3-nitro-4-vinyl-4H-chromene-2-amine

[0080]

[0081] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 89%, 93% ee. 1HNMR (400MHz, CDCl3) δ12.17(brs,1H),7.50(d,J=2.2Hz,1H),7.33–7.25(m,3H),7.24(d,J=5.3Hz,1H),7.23–7.16(m,1H),7.12–7 .05(m,1H),5.91(ddd,J=16.8,10.0,6.6Hz,1H),5.10(d,J=9.9Hz,1H),5.04(d,J=18.8Hz,1H),5.01(d,J=6.5Hz,1H),2.41(s,3H). 13 CNMR (100MHz, CDCl3) δ156.7,148.0,137.1,134.9,134.5,133.9,131.5,129.7,128.7 ,126.2,123.8,123.2,121.5,116.3,115.9,108.4,39.5,19.8.HRMS(EI-TOF)m / z:[M] + calcdfor C 18 H 15 35 ClN2O3:342.0766,found:342.0769; C 18 H 15 37 ClN2O3:344.0737,found:344.0749; [α] D 25 =+27.9 (c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flowrate=1.0mL / min, λ=220nm)t R =6.863min(minor),11.101min(major).

[0082] Example 9: Synthesis of (S)-N-(2-methoxyphenyl)-3-nitro-4-vinyl-4H-chromene-2-amine

[0083]

[0084] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 95%, 50% ee. 1HNMR(400MHz, CDCl3)δ12.61(brs,1H),7.82(d,J=8.0Hz,1H),7.33–7.24(m,2H),7.26–7.17(m,2H),7.1 7–7.10(m,1H),7.08–6.96(m,2H),5.93(ddd,J=16.7,10.8,6.5Hz,1H),5.12–4.99(m,3H),3.94(s,3H). 13 C NMR (100MHz, CDCl3) δ156.7,150.6,148.2,137.4,129.7,128.5,126.6,126.0,125.3 ,123.5,122.4,120.9,116.3,115.6,111.2,108.3,56.2,39.7.HRMS(EI-TOF)m / z:[M] + calcd for C 18 H 16 N2O4:324.1105,found:324.1112;[α] D 25 =+16.3(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =8.152min(minor),16.787min(major).

[0085] Example 10: Synthesis of (S)-N-benzyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0086]

[0087] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 80%, 92% ee. 1 HNMR(400MHz, CDCl3)δ10.75(brs,1H),7.43–7.30(m,5H),7.30–7.22(m,2H),7.24–7.14(m,1H),7.08–7.01(m,1H),5.88 (ddd,J=16.7,10.0,6.5Hz,1H),5.06(d,J=10.1Hz,1H),5.02(d,J=16.9Hz,1H),4.95(d,J=6.5Hz,1H),4.85–4.69(m,2H). 13C NMR (100MHz, CDCl3) δ159.2,148.2,137.4,136.4,129.8,129.2(2C),128.5,128.3 ,127.6(2C),125.9,123.5,116.1,115.5,107.4,45.6,39.6.HRMS(EI-TOF)m / z:[M] + calcd for C 18 H 16 N2O3:308.1155,found:308.1165;[α] D 25 =+3.2(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =13.326min(minor),39.044min(major).

[0088] Example 11 Synthesis of (S)-N-((6-chloropyridin-3-yl)methyl)-3-nitro-4-vinyl-4H-chromene-2-amine

[0089]

[0090] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 65%, 96% ee. 1 HNMR (400MHz, CDCl3) δ10.72(brs,1H),8.46(d,J=2.5Hz,1H),7.71(dd,J=8.3,2.5Hz,1H),7.36(d,J=8.2Hz,1H),7.27–7.16(m,3H),7.03(dd,J =7.8,1.9Hz,1H),5.85(ddd,J=16.7,10.0,6.6Hz,1H),5.06(d,J=10.0Hz,1H),5.01(d,J=17.0Hz,1H),4.92(d,J=6.6Hz,1H),4.85–4.70(m,2H). 13 C NMR (100MHz, CDCl3) δ159.1,151.4,149.1,147.9,138.2,137.2,131.5,129.8,12 8.7,126.1,124.8,123.2,115.9,115.7,107.8,42.3,39.5.HRMS(EI-TOF)m / z:[M] + calcd for C17 H 14 35 ClN3O3:343.0719,found:343.0727; C 17 H 14 37 ClN3O3:345.0689,found:345.0695;[α] D 25 =+22.4(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =18.847min(minor),48.310min(major).

[0091] Example 12 Synthesis of (S)-N-(furan-2-ylmethyl)-3-nitro-4-vinyl-4H-chromene-2-amine

[0092]

[0093] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 98%, 91% ee. 1 HNMR(400MHz, CDCl3)δ10.58(brs,1H),7.40(dd,J=1.8,0.9Hz,1H),7.32–7.26(m,2H),7.22(d,J=6.7Hz,1H),7.13(d,J=6.7Hz,1H),6.37 –6.34(m,2H),5.87(ddd,J=16.7,10.0,6.5Hz,1H),5.06(d,J=11.8Hz,1H),5.00(d,J=16.8,1H),4.94(d,J=6.6Hz,1H),4.82–4.69(m,2H). 13 C NMR (100MHz, CDCl3) δ158.9,149.3,148.2,143.1,137.4,129.8,128.5,125.9 ,123.5,116.2,115.5,110.8,108.6,107.6,39.6,38.4.HRMS(EI-TOF)m / z:[M] + calcdfor C 16 H 14 N2O4:298.0948,found:298.0951;[α] D 25=+6.3(c 0.20, CH2Cl2); HPLC (ChiralpakAS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =13.716min(minor),42.619min(major).

[0094] Example 13 Synthesis of (S)-N-methyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0095]

[0096] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 96%, 82% ee. 1 HNMR(400MHz, CDCl3)δ10.48(brs,1H),7.32–7.24(m,2H),7.22–7.18(m 1H),7.15–7.09(m,1H),5.88(ddd,J=16.7,9.9,6.4Hz,1H),5.05(d,J=10.0H z, 1H), 5.00 (d, J = 16.9Hz, 1H), 4.94 (d, J = 6.4Hz, 1H), 3.22 (d, J = 5.2Hz, 3H). 13 C NMR(100MHz, CDCl3)δ159.9,148.2,137.4,129.8,128.5,125.9,123.4,116.2,115.3,107.2,39.6,27.9.HRMS(EI-TOF)m / z:[M] + calcd for C 12 H 12 N2O3:232.0842,found:232.0845;[α] D 25 =+19.3(c 0.20, CH2Cl2); HPLC (Chiralpak IC, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =28.767min(major),36.700min(minor).

[0097] Example 14 Synthesis of (S)-N-ethyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0098]

[0099] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 98%, 65% ee. 1 HNMR (400MHz, CDCl3) δ10.50(brs,1H),7.30–7.25(m,2H),7.21(d,J=7.1Hz,1H),7.10(d,J=6.0Hz,1H),5.88(ddd,J=16.9,9. 9,6.1Hz,1H),5.05(d,J=9.6Hz,1H),4.99(d,J=16.6Hz,1H),4.95(d,J=7.0Hz,1H),3.71–3.59(m,2H),1.38(t,J=7.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ159.3,148.3,137.4,129.8,128.5,125.8,123.5,116.1,115.3,106.9,39.6,36.7,15.2.HRMS(EI-TOF)m / z:[M] + calcd for C 13 H 14 N2O3:246.0999,found:246.1001;[α] D 25 =+16.9(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =8.319min(minor),36.278min(major).

[0100] Example 15 Synthesis of (S)-3-nitro-N-propyl-4-vinyl-4H-chromene-2-amine

[0101]

[0102] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 95%, 69% ee. 1HNMR (400MHz, CDCl3) δ10.59(brs,1H),7.26(d,J=6.8Hz,2H),7.21(d,J=7.4Hz,1H),7.11(d,J=8.1Hz,1H),5.92–5.84(m,1H),5.0 5(d,J=10.0Hz,1H),5.00(d,J=17.0Hz,1H),4.95(d,J=6.3Hz,1H),3.58(t,J=6.3Hz,2H),1.80–1.71(m,2H),1.05(t,J=7.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ159.4,148.2,137.3,129.7,128.4,125.8,123.4,116.1,115.3,106.9,43.3,39.6,23.1,11.5.HRMS(EI-TOF)m / z:[M] + calcd for C 14 H 16 N2O3:260.1155,found:260.1159;[α] D 25 =+5.4(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =7.287min(minor),18.508min(major).

[0103] Example 16 Synthesis of (S)-3-nitro-N-n-butyl-4-vinyl-4H-chromene-2-amine

[0104]

[0105] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 90%, 75% ee. 1HNMR (400MHz, CDCl3) δ10.57(brs,1H),7.30–7.26(m,2H),7.22–7.18(m,1H),7.10(dd,J=8.2,1.3Hz,1H),5.88(ddd,J=16.7,10.0,6.4Hz,1H),5.0 5(d,J=10.0Hz,1H),5.00(d,J=16.9Hz,1H),4.95(d,J=6.6Hz,1H),3.65– 3.57(m,2H),1.77–1.65(m,2H),1.54–1.40(m,2H),0.99(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ159.4,148.3,137.4,129.8,128.5,125.8,123.5,116.1,115.3,107.0,41.4,39.6,31.8,20.1,13.8.HRMS(EI-TOF)m / z:[M] + calcd for C 15 H 18 N2O3:274.1312,found:274.1315;[α] D 25 =+13.5(c0.20,CH2Cl2);HPLC(Chiralpak AS-H,n-hexane / ethanol=80 / 20, flow rate=1.0mL / min,λ=220nm)t R =6.707min(minor),13.253min(major).

[0106] Example 17 Synthesis of (S)-N-isopropyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0107]

[0108] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 88%, 72% ee. 1HNMR (400MHz, CDCl3) δ10.46(brs,1H),7.31–7.26(m,2H),7.20(d,J=7.9Hz,1H),7.11(d,J=8.6Hz,1H),5.88(ddd,J=16.7,10.0,6.4Hz,1 H),5.05(d,J=10.0Hz,1H),4.99(d,J=17.0Hz,2H),4.95(d,J=6.3Hz,1H),4.38–4.22(m,1H),1.41(d,J=6.6Hz,3H),1.38(d,J=6.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ158.6,148.3,137.4,129.7,128.4,125.8,123.5,116.1,115.3,106.8,44.5,39.6,23.4,23.2.HRMS(EI-TOF)m / z:[M] + calcd for C 14 H 16 N2O3:260.1155,found:260.1158;[α] D 25 =+14.1(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =5.879min(minor),20.802min(major).

[0109] Example 18 Synthesis of (S)-N-(3-chloropropyl)-3-nitro-4-vinyl-4H-chromene-2-amine

[0110]

[0111] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 62%, 77% ee. 1HNMR (400MHz, CDCl3) δ10.54(brs,1H),7.33–7.26(m,2H),7.24–7.19(m,1H),7.14(dd,J=8.1,1.3Hz,1H),5.87(ddd,J=16.8,10.0,6.5Hz ,1H),5.06(d,J=10.0Hz,1H),5.01(d,J=17.0Hz,1H),4.94(d,J=6.5Hz,1H),3.88–3.75(m,2H),3.67(t,J=6.0Hz,2H),2.23–2.16(m,2H). 13 C NMR (100MHz, CDCl3) δ159.4,148.1,137.3,129.7,128.5,125.9,123.3,116.2,115.5,107.3,41.8,39.6,38.7,32.5.HRMS(EI-TOF)m / z:[M] + calcd for C 14 H 15 35 ClN2O3:294.0766, found:294.0766; C 14 H 15 37 ClN2O3:296.0737,found:296.0748; [α] D 25 =+18.5 (c0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =12.271min(minor),28.732min(major).

[0112] Example 19 Synthesis of (S)-N-cyclopropyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0113]

[0114] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 93%, 60% ee. 1HNMR (400MHz, CDCl3) δ10.35(brs,1H),7.35–7.23(m,2H),7.21(d,J=7.4Hz,1H),7.15(d,J=8.1Hz,1H),5.91–5.83(m,1H),5.05(d ,J=10.0Hz,1H),5.00(d,J=17.0Hz,1H),4.93(d,J=6.4Hz,1H),3.03(tt,J=7.8,3.9Hz,1H),0.95–1.00(m,2H),0.87–0.74(m,2H). 13 C NMR (100MHz, CDCl3) δ160.88,148.28,137.34,129.72,128.48,125.83,123. 33,116.33,115.42,107.37,39.55,23.94,7.41(2C).HRMS(EI-TOF)m / z:[M] + calcd for C 14 H 14 N2O3:258.0999,found:258.1007;[α] D 25 =+2.4(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =7.778min(minor),27.845min(major).

[0115] Example 20: Synthesis of (S)-N-cyclopentyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0116]

[0117] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 91%, 69% ee. 1HNMR (400MHz, CDCl3) δ10.59(brs,1H),7.30–7.25(m,2H),7.22–7.17(m,1H),7.11(dd,J=8.1,1.3Hz,1H),5.88(ddd,J=16.7,10.0,6.4Hz,1H),5 .05(d,J=9.9Hz,1H),4.99(d,J=16.9Hz,1H),4.94(d,J=6.3Hz,1H),4.4 3–4.35(m,1H),2.22–2.07(m,2H),1.90–1.79(m,2H),1.78–1.67(m,4H). 13 C NMR (100MHz, CDCl3) δ158.9,148.3,137.4,129.8,128.4,125.8,123.5,116.1,115.3,106.9,53.6,39.6,34.0,33.8,23.9,23.9.HRMS(EI-TOF)m / z:[M] + calcd for C 16 H 18 N2O3:286.1312,found:286.1314;[α] D 25 =+10.9(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =6.577min(minor),16.542min(major).

[0118] Example 21: Synthesis of (S)-6-fluoro-3-nitro-N-phenyl-4-vinyl-4H-chromene-2-amine

[0119]

[0120] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 98%, 87% ee. 1HNMR (400MHz, CDCl3) δ12.18(brs,1H),7.47–7.40(m,4H),7.32–7.29(m,1H),7.05(dd,J=8.7,4.5Hz,1H),6.99(d,J= 8.1Hz,2H),5.90(ddd,J=16.6,9.9,6.6Hz,1H),5.14(d,J=9.2Hz,1H),5.10(d,J=15.6Hz,1H),4.99(d,J=6.7Hz,1H). 13 C NMR (100MHz, CDCl3) δ 160.0 (d, 1 J C-F =245.6Hz),156.7,144.2,136.6,135.1,129.6(2C),126.8,125.3(d, 3 J C-F =7.9Hz), 123.4(2C), 117.8(d, 3 J C-F =8.4Hz), 116.4, 115.9 (d, 2 J C-F =23.9Hz), 115.7(d, 2 J C-F =24.1Hz), 107.6, 39.9. 19 F NMR(376MHz, CDCl3)δ-115.76–-115.82(m).HRMS(EI-TOF)m / z:[M] + calcd for C 17 H 13 FN2O3:312.0905,found:312.0909; [α] D 25 =+23.8(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =8.241min(minor),13.449min(major).

[0121] Example 22 Synthesis of (S)-6-fluoro-N-methyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0122]

[0123] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 98%, 88% ee. 1 HNMR(400MHz, CDCl3)δ10.42(brs,1H),7.11(dd,J=8.7,4.5Hz,1H),7.03–6.93(m,2H),5.85(ddd,J=16.7,10 .0,6.6Hz,1H),5.09(d,J=10.0Hz,1H),5.04(d,J=16.9Hz,1H),4.91(d,J=6.5Hz,1H),3.22(d,J=5.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ 160.4 (d, 1 J C-F =140.8Hz),158.6,144.3,136.8,125.3(d, 3 J C-F =8.0Hz), 117.7(d, 3 J C-F =8.7Hz), 115.9(d, 2 J C-F =12.7Hz), 115.7(d, 2 J C-F =15.7Hz),115.4,106.6,39.9,28.0. 19 F NMR(376MHz, CDCl3)δ-116.21–-116.24(m).HRMS(EI-TOF)m / z:[M] + calcd for C 12 H 11 FN2O3:250.0748,found:250.0752;[α] D 25 =+16.9(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =11.028min(minor),55.533min(major).

[0124] Example 23 Synthesis of (S)-6-fluoro-N-isopropyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0125]

[0126] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 90%, 79% ee. 1 HNMR(400MHz, CDCl3)δ10.39(brs,1H),7.09(dd,J=8.6,4.5Hz,1H),7.01–6.95(m,2H),5.86(ddd,J=16.8,10.0,6.5Hz,1H),5.09 (d,J=10.0Hz,1H),5.03(d,J=16.9Hz,1H),4.92(d,J=6.6Hz,1H),4.32–4.24(m,1H),1.40(d,J=6.5Hz,3H),1.37(d,J=6.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ 159.8 (d, 1 J C-F =245.2Hz), 158.4, 144.3 (d, 4 J C-F =2.6Hz), 136.8, 125.4 (d, 3 J C-F =8.0Hz), 117.5(d, 3 J C-F =8.6Hz), 115.9(d, 2 J C-F =17.5Hz), 115.8, 115.5(d, 2 J C-F =24.1Hz),106.2,44.5,39.8,23.4,23.2. 19 F NMR(376MHz, CDCl3)δ-116.29–-116.40(m).HRMS(EI-TOF)m / z:[M] + calcd for C 14 H 15 FN2O3:278.1061,found:278.1064;[α] D 25 =+10.6(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =5.905min(minor),17.752min(major).

[0127] Example 24 Synthesis of (S)-6-chloro-3-nitro-N-phenyl-4-vinyl-4H-chromene-2-amine

[0128]

[0129] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 98%, 96% ee. 1 HNMR(400MHz, CDCl3)δ12.18(brs,1H),7.47–7.39(m,4H),7.31(d,J=7.2Hz,1H),7.28–7.22(m,2H),7.02(d,J=8.5 Hz,1H),5.88(ddd,J=16.8,10.0,6.7Hz,1H),5.14(d,J=10.0Hz,1H),5.11(d,J=16.8Hz,1H),4.97(d,J=6.7Hz,1H). 13 C NMR (100MHz, CDCl3) δ156.5,146.6,136.6,134.9,131.2,129.6(2C),129.4,128 .7,126.8,125.1,123.4(2C),117.7,116.4,107.7,39.6.HRMS(EI-TOF)m / z:[M] + calcd for C 17 H 13 35 ClN2O3:328.0610,found:328.0611;C 17 H 13 37 ClN2O3:330.0580,found:328.0589; [α] D 25 =+23.9 (c0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =8.652min(minor),11.454min(major).

[0130] Example 25 Synthesis of (S)-6-chloro-N-methyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0131]

[0132] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 99%, 86% ee. 1HNMR(400MHz, CDCl3)δ10.41(brs,1H),7.29–7.22(m,2H),7.11–7.04(m,1H),5.83(ddd,J=16.8,10.0,6 .6Hz,1H),5.09(d,J=10.0Hz,1H),5.04(d,J=16.9Hz,1H),4.89(d,J=6.6Hz,1H),3.22(d,J=5.2Hz,3H). 13 C NMR(100MHz, CDCl3)δ159.5,146.7,136.8,130.9,129.5,128.6,125.2,117.6,116.0,106.7,39.6,28.1.HRMS(EI-TOF)m / z:[M] + calcd forC 12 H 11 35 ClN2O3:266.0453,found:266.0457; C 12 H 11 37 ClN2O3:268.0424,found:268.0427;[α] D 25 =+27.6(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flowrate=1.0mL / min, λ=220nm)t R =10.521min(minor),21.262min(major).

[0133] Example 26 Synthesis of (S)-6-chloro-N-isopropyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0134]

[0135] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 85%, 90% ee. 1HNMR (400MHz, CDCl3) δ10.37(brs,1H),7.25(d,J=7.6Hz,2H),7.10–7.03(m,1H),5.84(ddd,J=16.8,10.0,6.6Hz,1H),5.08(d ,J=9.9Hz,1H),5.04(d,J=16.9Hz,1H),4.89(d,J=6.7Hz,1H),4.33–4.24(m,1H),1.40(d,J=6.6Hz,3H),1.38(d,J=6.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ158.2,146.7,136.7,130.8,129.3,128.5,125.2,117.5,115.9,106.2,44.5,39.5,23.3,23.2.HRMS(EI-TOF)m / z:[M] + calcd for C 14 H 15 35 ClN2O3:294.0766, found:294.0774; C 14 H 15 37 ClN2O3:296.0737,found:294.0743;[α] D 25 =-0.1 (c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =6.428min(minor),16.698min(major).

[0136] Example 27 Synthesis of (S)-6-bromo-3-nitro-N-phenyl-4-vinyl-4H-chromene-2-amine

[0137]

[0138] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 99%, 95% ee. 1HNMR(400MHz, CDCl3)δ12.18(brs,1H),7.52–7.35(m,6H),7.35–7.26(m,1H),6.96(d,J=8.7Hz,1H),5. 88(ddd,J=16.8,10.0,6.7Hz,1H),5.14(d,J=7.2Hz,1H),5.11(d,J=14.1Hz,1H),4.97(d,J=6.8Hz,1H). 13 C NMR (100MHz, CDCl3) δ156.5,147.1,136.6,134.9,132.4,131.6,129.6(2C),126 .8,125.5,123.4(2C),118.7,118.1,116.5,107.7,39.5.HRMS(EI-TOF)m / z:[M] + calcd for C 17 H 13 79 BrN2O3:372.0105, found:372.0112; C 17 H 13 81 BrN2O3:374.0084,found:374.0085;[α] D 25 =+18.2(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =8.859min(minor),11.241min(major).

[0139] Example 28 Synthesis of (S)-6-bromo-N-methyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0140]

[0141] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 98%, 78% ee. 1HNMR(400MHz, CDCl3)δ10.41(brs,1H),7.43–7.36(m,2H),7.06–6.99(m,1H),5.83(ddd,J=16.8,9.9,6 .7Hz,1H),5.09(d,J=10.0Hz,1H),5.04(d,J=16.9Hz,1H),4.88(d,J=6.7Hz,1H),3.22(d,J=5.3Hz,3H). 13 C NMR(100MHz, CDCl3)δ159.4,147.2,136.8,132.4,131.5,125.6,118.4,117.9,116.0,106.6,39.5,28.1.HRMS(EI-TOF)m / z:[M] + calcd forC 12 H 11 79 BrN2O3:309.9948, found:309.9957; C 12 H 11 81 BrN2O3:311.9928,found:311.9934;[α] D 25 =+20.9(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flowrate=1.0mL / min, λ=220nm)t R =10.335min(minor),17.279min(major).

[0142] Example 29 Synthesis of (S)-6-bromo-N-isopropyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0143]

[0144] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 88%, 84% ee. 1HNMR(400MHz, CDCl3)δ10.38(brs,1H),7.41–7.38(m,2H),7.00(d,J=9.2Hz,1H),5.84(ddd,J=16.8,10.0,6.6Hz,1H),5.09(d, J=10.0Hz,1H),5.04(d,J=17.0Hz,1H),4.90(d,J=6.6Hz,1H),4.33–4.20(m,1H),1.40(d,J=6.6Hz,3H),1.37(d,J=6.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ158.2,147.4,136.8,132.4,131.5,125.8,118.4,117.9,116.0,106.3,44.6,39.5,23.4,23.3.HRMS(EI-TOF)m / z:[M] + calcd for C 14 H 15 79 BrN2O3:338.0261, found:338.0265; C 14 H 15 81 BrN2O3:340.0241,found:340.0248;[α] D 25 =+8.3 (c0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =6.076min(minor),12.532min(major).

[0145] Example 30: Synthesis of (S)-6-methyl-3-nitro-N-phenyl-4-vinyl-4H-chromene-2-amine

[0146]

[0147] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 98%, 89% ee. 1HNMR (400MHz, CDCl3) δ12.31(brs,1H),7.46–7.41(m,4H),7.31–7.26(m,1H),7.06(dd,J=5.7,2.4Hz,2H),6.96(d,J=8.9Hz ,1H),5.90(ddd,J=17.4,9.5,6.6Hz,1H),5.11(d,J=10Hz,1H),5.07(d,J=16.8Hz,1H),4.95(d,J=6.6Hz,1H),2.34(s,3H). 13 C NMR (100MHz, CDCl3) δ157.0,146.0,137.2,135.9,135.2,129.8,129.5(2C),129.2 ,126.5,123.2(2C),122.9,115.9,115.7,108.2,39.6,20.9.HRMS(EI-TOF)m / z:[M] + calcd for C 18 H 16 N2O3:308.1155,found:308.1158;[α] D 25 =+22.1(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =8.094min(minor),14.282min(major).

[0148] Example 31: Synthesis of (S)-N,6-dimethyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0149]

[0150] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 98%, 64% ee. 1 HNMR(400MHz, CDCl3)δ10.49(brs,1H),7.14–6.95(m,3H),5.85(ddd,J=16.8,10.0,6.6Hz,1H),5.04 (d,J=10.0Hz,1H),5.01(d,J=16.4Hz,1H),4.87(d,J=6.7Hz,1H),3.21(d,J=5.2Hz,3H),2.34(s,3H). 13CNMR(100MHz, CDCl3)δ160.0,146.1,137.4,135.6,129.8,129.0,122.9,115.9,115.2,107.2,39.6,27.9,20.8.HRMS(EI-TOF)m / z:[M] + calcd forC 13 H 14 N2O3:246.0999,found:246.1006;[α] D 25 =+22.6(c 0.20, CH2Cl2); HPLC (ChiralpakAS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =9.497min(minor),29.834min(major).

[0151] Example 32 Synthesis of (S)-N-isopropyl-6-methyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0152]

[0153] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 98%, 64% ee. 1 HNMR (400MHz, CDCl3) δ10.48(brs,1H),7.06(d,J=8.1Hz,1H),7.04(s,1H),6.99(d,J=8.2Hz,1H),5.86(ddd,J=16.7,10.0,6.5Hz,1H),5.05( d,J=8.8Hz,1H),5.01(d,J=15.8Hz,1H),4.89(d,J=6.4Hz,1H),4.32–4.24(m,1H),2.34(s,3H),1.39(d,J=6.6Hz,3H),1.37(d,J=6.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ158.8,146.3,137.4,135.6,129.9,129.0,123.1,115.8,115.2,106.9,44.4,39.7,23.4,23.2,20.9.HRMS(EI-TOF)m / z:[M] + calcd for C 15 H 18N2O3:274.1312,found:274.1320;[α] D 25 =+15.8(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =5.824min(minor),22.793min(major).

[0154] Example 33 Synthesis of (S)-6-methoxy-3-nitro-N-phenyl-4-vinyl-4H-chromene-2-amine

[0155]

[0156] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 97%, 99% ee. 1 HNMR(400MHz, CDCl3)δ12.29(brs,1H),7.49–7.38(m,4H),7.33–7.27(m,1H),7.01(d,J=8.9Hz,1H),6.84–6.73(m,2H) ,5.91(ddd,J=16.7,9.7,6.6Hz,1H),5.12(d,J=9.6Hz,1H),5.09(d,J=17.2Hz,1H),4.98(d,J=6.6Hz,1H),3.81(s,3H). 13 C NMR (100MHz, CDCl3) δ157.4,157.0,142.1,136.9,135.2,129.5(2C),126.5,124.2 ,123.2(2C),117.2,115.9,114.5,113.5,107.9,55.9,40.0.HRMS(EI-TOF)m / z:[M] + calcd for C 18 H 16 N2O4:324.1105,found:324.1113;[α] D 25 =+14.5(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =12.304min(minor),19.211min(major).

[0157] Example 34 Synthesis of (S)-6-methoxy-N-methyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0158]

[0159] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 80%, 52% ee. 1 HNMR (400MHz, CDCl3) δ10.47(brs,1H),7.05(d,J=8.9Hz,1H),6.81(d,J=9.1Hz,1H),6.73(s,1H),5.86(ddd,J=15.8,8. 7,6.6Hz,1H),5.06(d,J=8.0Hz,1H),5.03(d,J=15.3Hz,1H),4.89(d,J=6.6Hz,1H),3.80(s,3H),3.20(d,J=5.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ160.0,157.2,142.2,137.2,124.3,117.1,115.4,114.4,113.5,106.9,55.8,39.9,27.9.HRMS(EI-TOF)m / z:[M] + calcd for C 13 H 14 N2O4:262.0948,found:262.0951;[α] D 25 =+15.7(c 0.20, CH2Cl2); HPLC (Chiralpak IC-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =35.147min(major),47.328min(minor).

[0160] Example 35 Synthesis of (S)-N-isopropyl-6-methoxy-3-nitro-4-vinyl-4H-chromene-2-amine

[0161]

[0162] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 86%, 79% ee. 1HNMR (400MHz, CDCl3) δ10.45(brs,1H),7.03(d,J=8.9Hz,1H),6.81(dd,J=8.9,3.0Hz,1H),6.74(d,J=3.0Hz,1H),5.87(ddd,J=16.5,10.3,6.2Hz,1H) .,5.06(d,J=8.8Hz,1H),5.03(d,J=14.6Hz,1H),4.90(d,J=6.4Hz,1H),4. 32–4.23(m,1H),3.80(s,3H),1.39(d,J=6.6Hz,3H),1.37(d,J=6.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ158.8,157.1,142.3,137.1,124.4,116.9,115.4,114.4,113.5,106.6,55.8,44.4,39.9,23.3,23.2.HRMS(EI-TOF)m / z:[M] + calcd for C 15 H 18 N2O4:290.1261,found:290.1265;[α] D 25 =+4.8(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =7.312min(minor),26.847min(major).

[0163] Example 36 Synthesis of (S)-3-nitro-N-phenyl-6-(trifluoromethoxy)-4-vinyl-4H-chromene-2-amine

[0164]

[0165] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 97%, 90% ee. 1HNMR(400MHz, CDCl3)δ12.16(brs,1H),7.48–7.44(m,2H),7.43–7.38(m,2H),7.34–7.29(m,1H),7.17–7.09(m, 3H), 5.90 (ddd, J=16.8, 10.0, 6.7Hz, 1H), 5.15 (d, J=10.0Hz, 1H), 5.11 (d, J=16.9Hz, 1H), 5.02 (d, J=6.6Hz, 1H). 13 C NMR (100MHz, CDCl3) δ156.5,146.5,146.3136.5,134.9,129.6(2C),126.9,125.2,123.5(2C),122.2,121.5,120.5(q, 1 J C-F =256.5Hz),117.8,116.5,107.5,39.7. 19 F NMR(376MHz, CDCl3)δ-58.23(s).HRMS(EI-TOF)m / z:[M] + calcd for C 18 H 13 F3N2O4:378.0822,found:378.0824;[α] D 25 =+16.2(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =5.547min(minor),7.354min(major).

[0166] Example 37 Synthesis of (S)-N-methyl-3-nitro-6-(trifluoromethoxy)-4-vinyl-4H-chromene-2-amine

[0167]

[0168] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 98%, 77% ee. 1HNMR(400MHz, CDCl3)δ10.40(brs,1H),7.19–7.16(m,2H),7.13(s),5.85(ddd,J=16.7,10.0,6.5H z,1H),5.10(d,J=9.9Hz,1H),5.03(d,J=16.9Hz,1H),4.93(d,J=6.6Hz,1H),3.23(d,J=5.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ159.5,146.4,146.3,136.7,125.3,122.2,121.3,120.5(q, 1 J C-F =256.3Hz),117.7,116.0,106.5,39.7,28.1. 19 F NMR(376MHz, CDCl3)δ-58.25(s).HRMS(EI-TOF)m / z:[M] + calcd for C 13 H 11 F3N2O4:316.0665,found:316.0673;[α] D 25 =+16.1(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =7.580min(minor),10.998min(major).

[0169] Example 38 Synthesis of (S)-N-isopropyl-3-nitro-6-(trifluoromethoxy)-4-vinyl-4H-chromene-2-amine

[0170]

[0171] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 92%, 84% ee. 1HNMR (400MHz, CDCl3) δ10.37(brs,1H),7.17–7.12(m,3H),5.86(ddd,J=16.8,10.0,6.4Hz,1H),5.10(d,J=9.7Hz,1 H),5.03(d,J=16.8Hz,1H),4.95(d,J=6.7Hz,1H),4.32–4.24(m,1H),1.41(d,J=6.2Hz,3H),1.38(d,J=6.6Hz,3H). 13 C NMR (100MHz, CDCl3) δ158.3,146.5,146.3,136.7,125.4,122.3,121.4,120.5(q, 1 J C-F =247.2Hz),117.5,116.1,106.1,44.6,39.8,23.4,23.3. 19 F NMR(376MHz, CDCl3)δ-58.25(s).HRMS(EI-TOF)m / z:[M] + calcd forC 15 H 15 F3N2O4:344.0978,found:344.0986;[α] D 25 =+10.9(c 0.20, CH2Cl2); HPLC (ChiralpakAS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =4.586min(minor),8.490min(major).

[0172] Example 39 Synthesis of (S)-7-bromo-3-nitro-N-phenyl-4-vinyl-4H-chromene-2-amine

[0173]

[0174] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 99%, 95% ee. 1HNMR(400MHz, CDCl3)δ12.16(brs,1H),7.48–7.44(m,2H),7.39(d,J=7.9Hz,2H),7.37–7.29(m,2H),7.24(s),7.16(d,J =8.2Hz,1H),5.89(ddd,J=16.8,10.0,6.6Hz,1H),5.12(d,J=10.0Hz,1H),5.07(d,J=16.9Hz,1H),4.97(d,J=6.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ156.5,148.4,136.8,134.9,130.9,129.6(2C),129.3,126 .9,123.5(2C),122.5,121.3,119.6,116.2,107.9,39.29.HRMS(EI-TOF)m / z:[M] + calcd for C 17 H 13 79 BrN2O3:372.0105, found:372.0115; C 17 H 13 81 BrN2O3:374.0084,found:374.0085;[α] D 25 =+12.8 (c0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =8.658min(minor),12.162min(major).

[0175] Example 40 Synthesis of (S)-7-bromo-N-methyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0176]

[0177] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 97%, 74% ee. 1HNMR (400MHz, CDCl3) δ10.41(brs,1H),7.34–7.32(m,2H),7.14(d,J=8.5Hz,1H),5.84(ddd,J=16.7,10.0 ,6.5Hz,1H),5.06(d,J=10.0Hz,1H),5.00(d,J=17.0Hz,1H),4.88(d,J=6.4Hz,1H),3.22(d,J=5.2Hz,3H). 13 C NMR(100MHz, CDCl3)δ159.4,148.4,136.9,130.9,128.9,122.5,121.1,119.5,115.8,106.8,39.2,28.1.HRMS(EI-TOF)m / z:[M] + calcd forC 12 H 11 79 BrN2O3:309.9948, found:309.9952; C 12 H 11 81 BrN2O3:311.9928,found:311.9934;[α] D 25 =+9.8(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flowrate=1.0mL / min, λ=220nm)t R =12.740min(minor),34.731min(major).

[0178] Example 41: Synthesis of (S)-7-bromo-N-isopropyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0179]

[0180] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 92%, 64% ee. 1HNMR(400MHz, CDCl3)δ10.38(brs,1H),7.35–7.29(m,2H),7.14(d,J=8.2Hz,1H),5.85(ddd,J=16.7,10.0,6.4Hz,1H),5.07(d, J=10.0Hz,1H),5.00(d,J=16.9Hz,1H),4.90(d,J=6.4Hz,1H),4.35–4.18(m,1H),1.40(d,J=6.6Hz,3H),1.37(d,J=6.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ158.2,148.6,136.9,131.0,128.9,122.7,121.2,119.5,115.8,106.5,44.6,39.3,23.4,23.3.HRMS(EI-TOF)m / z:[M] + calcd for C 14 H 15 79 BrN2O3:338.0261, found:338.0262; C 14 H 15 81 BrN2O3:340.0241,found:340.0249;[α] D 25 =+5.0 (c0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =6.125min(minor),13.359min(major).

[0181] Example 42 Synthesis of (S)-7-chloro-3-nitro-N-phenyl-4-vinyl-4H-chromene-2-amine

[0182]

[0183] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 96%, 88% ee. 1HNMR(400MHz, CDCl3)δ12.16(brs,1H),7.48–7.44(m,2H),7.39(d,J=7.8Hz,2H),7.33–7.30(m,1H),7.24–7.19(m,2H),7.09 (d,J=1.9Hz,1H),5.89(ddd,J=16.7,10.0,6.6Hz,1H),5.12(d,J=9.8Hz,1H),5.07(d,J=17.2Hz,1H),4.98(d,J=6.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ156.5,148.3,136.9,134.9,133.9,130.7,129.6(2C),126 .9,126.4,123.5(2C),121.9,116.7,116.2,107.9,39.2.HRMS(EI-TOF)m / z:[M] + calcd for C 17 H 13 35 ClN2O3:328.0610,found:328.0612;C 17 H 13 37 ClN2O3:330.0580,found:328.0583;[α] D 25 =+21.6 (c0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =8.275min(minor),11.256min(major).

[0184] Example 43 Synthesis of (S)-7-chloro-N-methyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0185]

[0186] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 87%, 75% ee. 1HNMR (400MHz, CDCl3) δ10.42(brs,1H),7.19(d,J=1.6Hz,2H),7.17(s,1H),5.84(ddd,J=16.7,10.0,6. 5Hz,1H),5.07(d,J=10.0Hz,1H),5.00(d,J=16.9Hz,1H),4.90(d,J=6.6Hz,1H),3.22(d,J=5.2Hz,3H). 13 C NMR(100MHz, CDCl3)δ159.4,148.4,137.0,133.7,130.7,126.1,122.0,116.7,115.8,106.9,39.2,28.1.HRMS(EI-TOF)m / z:[M] + calcd forC 12 H 11 35 ClN2O3:266.0453, found:266.0454; C 12 H 11 37 ClN2O3:268.0424,found:268.0430; [α] D 25 =-9.7 (c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flowrate=1.0mL / min, λ=220nm)t R =10.726min(minor),25.968min(major).

[0187] Example 44 Synthesis of (S)-7-chloro-N-isopropyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0188]

[0189] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 78%, 78% ee. 1HNMR (400MHz, CDCl3) δ10.39(brs,1H),7.22–7.19(m,2H),7.15(d,J=1.7Hz,1H),5.85(ddd,J=16.7,10.0,6.5Hz,1H),5.07(d, J=10.0Hz,1H),5.00(d,J=17.0Hz,1H),4.91(d,J=6.4Hz,1H),4.34–4.21(m,1H),1.40(d,J=6.6Hz,3H),1.38(d,J=6.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ158.2,148.5,136.9,133.7,130.7,126.1,122.1,116.6,115.7,106.5,44.6,39.2,23.4,23.2.HRMS(EI-TOF)m / z:[M] + calcd for C 14 H 15 35 ClN2O3:294.0766, found:294.0773; C 14 H 15 37 ClN2O3:296.0737,found:294.0739;[α] D 25 =+33.3(c0.20,CH2Cl2); HPLC(Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =6.020min(minor),12.457min(major).

[0190] Example 45 Synthesis of (S)-7-chloro-N-cyclopropyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0191]

[0192] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 86%, 69% ee. 1HNMR (400MHz, CDCl3) δ10.27(brs,1H),7.21–7.17(m,3H),5.84(ddd,J=16.7,10.0,6.6Hz,1H),5.07(d,J=10.0 Hz,1H),5.01(d,J=16.9Hz,1H),4.89(d,J=6.6Hz,1H),2.97–3.03(m,1H),1.02–0.97(m,2H),0.91–0.72(m,2H). 13 C NMR (100MHz, CDCl3) δ160.5,148.5,137.1,133.8,130.7,126.1,122.1,116.8,115.9,107.2,39.2,24.0,7.5,7.5.HRMS(EI-TOF)m / z:[M] + calcd for C 14 H 13 35 ClN2O3:292.0610,found:292.0611;C 14 H 13 37 ClN2O3:294.0580,found:294.0586; [α] D 25 =+7.7(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =7.562min(minor),16.631min(major).

[0193] Example 46 Synthesis of (S)-7-chloro-3-nitro-N-propyl-4-vinyl-4H-chromene-2-amine

[0194]

[0195] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 90%, 58% ee. 1HNMR (400MHz, CDCl3) δ10.51(brs,1H),7.19(d,J=2.4Hz,2H),7.15(s,1H),5.85(ddd,J=16.7,9.9,6.4Hz,1H),5.07(d,J =10.0Hz,1H),5.00(d,J=17.0Hz,1H),4.91(d,J=6.4Hz,1H),3.60–3.51(m,2H),1.80–1.71(m,2H),1.05(t,J=7.4Hz,3H). 13 C NMR (100MHz, CDCl3) δ158.9,148.4,137.0,133.7,130.7,126.1,122.1,116.6,115.7,106.7,43.4,39.2,23.1,11.5.HRMS(EI-TOF)m / z:[M] + calcd for C 14 H 15 35 ClN2O3:294.0766, found:294.0768; C 14 H 15 37 ClN2O3:296.0737; found:296.0735,[α] D 25 =+10.7(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =7.017min(minor),12.371min(major).

[0196] Example 47 Synthesis of (S)-5-chloro-3-nitro-N-phenyl-4-vinyl-4H-chromene-2-amine

[0197]

[0198] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 84%, 99% ee. 1HNMR(400MHz, CDCl3)δ12.09(brs,1H),7.48–7.39(m,4H),7.34–7.24(m,3H),7.02(d,J=8.0Hz,1H),5.9 8(ddd,J=16.6,10.1,5.9Hz,1H),5.30(d,J=5.8Hz,1H),5.15(d,J=10.0Hz,1H),5.01(d,J=17.1Hz,1H). 13 C NMR (100MHz, CDCl3) δ156.8,149.4,135.0,134.3,134.1,129.6(2C),128.9,127 .0,126.8,123.4(2C),122.7,116.3,115.0,108.4,37.4.HRMS(EI-TOF)m / z:[M] + calcd for C 17 H 13 35 ClN2O3:328.0610,found:328.0620; C 17 H 13 37 ClN2O3:330.0580,found:330.0588;[α] D 25 =+29.2(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =8.431min(minor),11.118min(major).

[0199] Example 48 Synthesis of (S)-5-chloro-N-methyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0200]

[0201] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 92%, 92% ee. 1HNMR (400MHz, CDCl3) δ10.34(brs,1H),7.30–7.24(m,2H),7.08(dd,J=7.4,1.9Hz,1H),5.95(ddd,J=17.1,10 .0,5.8Hz,1H),5.22(d,J=5.8Hz,1H),5.10(d,J=10.0Hz,1H),4.93(d,J=17.1Hz,1H),3.23(d,J=5.2Hz,3H). 13 C NMR(100MHz, CDCl3)δ159.8,149.4,134.4,134.1,128.8,126.8,122.7,115.8,114.9,107.3,37.3,28.1.HRMS(EI-TOF)m / z:[M] + calcdfor C 12 H 11 35 ClN2O3:266.0453, found:266.0461; C 12 H 11 37 ClN2O3:268.0424,found:268.0432; [α] D 25 =+23.9(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flowrate=1.0mL / min, λ=220nm)t R =10.575min(minor),36.027min(major).

[0202] Example 49 Synthesis of (S)-5-chloro-N-isopropyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0203]

[0204] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 74%, 57% ee. 1HNMR (400MHz, CDCl3) δ10.30(brs,1H),7.28(d,J=7.2Hz,1H),7.23(d,J=8.0Hz,1H),7.05(dd,J=7.8,1.7Hz,1H),5.95(ddd,J=16.6,10.0,5.8 Hz,1H),5.24(d,J=5.8Hz,1H),5.10(d,J=10.0Hz,1H),4.93(d,J=18.1Hz,1H),4.32–4.24(m,1H),1.41(d,J=6.6Hz,3H),1.37(d,J=6.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ158.6,149.6,134.4,134.2,128.8,126.8,122.9,115.8,114.8,107.0,44.7,37.4,23.5,23.3.HRMS(EI-TOF)m / z:[M] + calcd forC 14 H 15 35 ClN2O3:294.0766, found:294.0770; C 14 H 15 37 ClN2O3:296.0737,found:294.0738;[α] D 25 =+13.9 (c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flowrate=1.0mL / min, λ=220nm)t R =5.864min(minor),15.092min(major).

[0205] Example 50 Synthesis of (S)-5-methoxy-3-nitro-N-phenyl-4-vinyl-4H-chromene-2-amine

[0206]

[0207] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 80%, 72% ee. 1HNMR(400MHz, CDCl3)δ12.25(brs,1H),7.43(d,J=5.8Hz,4H),7.34–7.19(m,2H),6.72(dd,J=13.3,8.3Hz,2H),6.02 (ddd,J=17.1,10.0,5.6Hz,1H),5.23(d,J=5.7Hz,1H),5.05(d,J=10.0Hz,1H),4.97(d,J=17.1Hz,1H),3.88(s,3H). 13 C NMR (100MHz, CDCl3) δ157.2,157.1,149.1,135.8,135.3,129.5(2C),128.7,126.5 ,123.2(2C),114.7,112.9,108.8,108.5,107.7,56.1,34.3.HRMS(EI-TOF)m / z:[M] + calcd for C 18 H 16 N2O4:324.1105,found:324.1111;[α] D 25 =+26.9(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =10.010min(minor),10.624min(major).

[0208] Example 51 Synthesis of (S)-5-methoxy-N-methyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0209]

[0210] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 61%, 70% ee. 1 HNMR(400MHz, CDCl3)δ10.46(brs,1H),7.28–7.19(m,1H),6.76–6.71(m,2H),5.99(ddd,J=17.2,10.0,5.5Hz, 1H), 5.17 (d, J = 5.5Hz, 1H), 5.00 (d, J = 10.1Hz, 1H), 4.89 (d, J = 17.1Hz, 1H), 3.86 (s, 3H), 3.21 (d, J = 5.2Hz, 3H). 13C NMR(100MHz, CDCl3)δ160.3,157.1,149.2,136.0,128.6,114.3,113.1,108.4,107.8,107.5,56.1,34.3,28.0.HRMS(EI-TOF)m / z:[M] + calcd for C 13 H 14 N2O4:262.0948,found:262.0956;[α] D 25 =+41.4(c 0.20, CH2Cl2); HPLC (Chiralpak IC-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =27.667min(major),42.084min(minor).

[0211] Example 52 Synthesis of (S)-5-methoxy-N-isopropyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0212]

[0213] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 77%, 90% ee. 1 HNMR (400MHz, CDCl3) δ10.43(brs,1H),7.25–7.21(m,1H),6.73(d,J=8.2Hz,2H),5.98(ddd,J=17.4,10.1,5.6Hz,1H),5.17(d,J=5.5 Hz,1H),5.00(d,J=10.1Hz,1H),4.89(d,J=17.2Hz,1H),4.35–4.20(m,1H),3.86(s,3H),1.40(d,J=6.5Hz,3H),1.37(d,J=6.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ159.0,157.1,149.3,135.9,128.6,114.2,113.2,108.3,107.4,107.4,56.1,44.5,34.3,23.4,23.2.HRMS(EI-TOF)m / z:[M] + calcd for C 15 H 18 N2O4:290.1261,found:290.1265;[α]D 25 =+19.2(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =6.278min(minor),8.570min(major).

[0214] Example 53 Synthesis of (S)-8-bromo-3-nitro-N-phenyl-4-vinyl-4H-chromene-2-amine

[0215]

[0216] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 96%, 97% ee. 1 HNMR(400MHz, CDCl3)δ12.31(brs,1H),7.58(d,J=7.9Hz,2H),7.54–7.40(m,3H),7.34–7.19(m,2H),7.10–7.07(m ,1H),5.89(ddd,J=16.7,10.0,6.6Hz,1H),5.13(d,J=10.8Hz,1H),5.08(d,J=17.6Hz,1H),5.03(d,J=6.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ156.5,145.5,136.9,134.7,132.6,129.4(2C),128.8,126 .9,126.8,125.3,123.9(2C),116.2,110.1,107.9,39.9.HRMS(EI-TOF)m / z:[M] + calcd for C 17 H 13 79 BrN2O3:372.0105, found:372.0108; C 17 H 13 81 BrN2O3:374.0084,found:372.0093;[α] D 25 =+18.0(c0.20,CH2Cl2);HPLC(ChiralpakAS-H,n-hexane / ethanol=80 / 20, flow rate=1.0mL / min,λ=220nm)t R=8.177min(minor),15.913min(major).

[0217] Example 54 Synthesis of (S)-8-bromo-N-methyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0218]

[0219] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 97%, 61% ee. 1 HNMR (400MHz, CDCl3) δ10.28(brs,1H),7.50(d,J=7.9Hz,1H),7.21(d,J=7.6Hz,1H),7.08(dd,J=8.0Hz,8.0Hz,1H),5.86(d dd,J=16.8,10.0,6.4Hz,1H),5.07(d,J=10.2Hz,1H),5.01(d,J=17.7Hz,1H),4.96(d,J=7.0Hz,1H),3.31(d,J=5.2Hz,3H). 13 C NMR(100MHz, CDCl3)δ159.5,145.1,136.9,132.1,128.7,126.5,125.4,115.7,110.3,106.9,39.9,28.5.HRMS(EI-TOF)m / z:[M] + calcd for C 12 H 11 79 BrN2O3:309.9948, found:309.9950; C 12 H 11 81 BrN2O3:311.9928,found:311.9937;[α] D 25 =+14.6(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =11.440min(minor),43.566min(major).

[0220] Example 55 Synthesis of (S)-8-bromo-N-isopropyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0221]

[0222] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 86%, 59% ee. 1 HNMR (400MHz, CDCl3) δ10.24(brs,1H),7.50(d,J=6.4Hz,1H),7.21(d,J=5.7Hz,1H),7.10–7.06(m,1H),5.86(ddd,J=16.7,10.0,6.4Hz,1 H),5.07(d,J=10.0Hz,1H),5.01(d,J=16.9Hz,1H),4.97(d,J=6.4Hz,1H),4.48–4.40(m,1H),1.44(d,J=6.6Hz,3H),1.42(d,J=6.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ158.2,145.3,136.9,132.1,128.8,126.5,125.5,115.7,110.3,106.5,45.1,39.9,23.3,23.1.HRMS(EI-TOF)m / z:[M] + calcd forC 14 H 15 79 BrN2O3:338.0261, found:338.0265; C 14 H 15 81 BrN2O3:340.0241,found:340.0247; [α] D 25 =+8.3(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flowrate=1.0mL / min, λ=220nm)t R =5.785min(minor),15.419min(major).

[0223] Example 56 Synthesis of (S)-8-methyl-3-nitro-N-phenyl-4-vinyl-4H-chromene-2-amine

[0224]

[0225] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 90%, 99% ee. 1HNMR(400MHz, CDCl3)δ12.25(brs,1H),7.48–7.42(m,4H),7.33–7.30(m,1H),7.12–7.07(m,3H),5.92(ddd, J=16.7,9.5,6.6Hz,1H),5.09(d,J=7.2Hz,1H),5.04(d,J=16.0Hz,1H),5.00(d,J=4.2Hz,1H),2.17(s,3H). 13 C NMR (100MHz, CDCl3) δ157.2,146.9,137.4,135.0,130.1,129.4(2C),127.2,126.9 ,125.8,125.7,124.1(2C),123.1,115.6,108.2,39.7,16.3.HRMS(EI-TOF)m / z:[M] + calcd for C 18 H 16 N2O3:308.1155,found:308.1160;[α] D 25 =+15.2(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =8.088min(minor),23.630min(major).

[0226] Example 57 Synthesis of (S)-N,8-dimethyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0227]

[0228] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 90%, 62% ee. 1 HNMR(400MHz, CDCl3)δ10.43(brs,1H),7.16–7.05(m,3H),5.86(ddd,J=16.7,10.0,6.4Hz,1H),5.03 (d,J=10.0Hz,1H),4.98(d,J=16.8Hz,1H),4.92(d,J=6.4Hz,1H),3.24(d,J=5.2Hz,3H),2.37(s,3H). 13CNMR(100MHz, CDCl3)δ159.9,146.7,137.4,129.9,127.2,125.6,125.4,123.1,115.1,107.3,39.7,28.0,15.9.HRMS(EI-TOF)m / z:[M] + calcd forC 13 H 14 N2O3:246.0999,found:246.1002;[α] D 25 =+28.7(c 0.20, CH2Cl2); HPLC (Chiralpak IC-H, n-hexane / ethanol=80 / 20, flow rate=1.0mL / min, λ=220nm)t R =27.711min(major),36.674min(minor).

[0229] Example 58 Synthesis of (S)-N-isopropyl-8-methyl-3-nitro-4-vinyl-4H-chromene-2-amine

[0230]

[0231] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 90%, 55% ee. 1 HNMR (400MHz, CDCl3) δ10.43(brs,1H),7.15–7.06(m,3H),5.87(ddd,J=16.6,10.0,6.4Hz,1H),5.04(d,J=9.9Hz,1H),4. 99(d,J=16.9Hz,1H),4.93(d,J=6.3Hz,1H),4.36–4.23(m,1H),2.37(s,3H),1.43(d,J=6.5Hz,3H),1.40(d,J=6.5Hz,3H). 13 C NMR (100MHz, CDCl3) δ158.5,146.7,137.4,129.9,127.2,125.5,125.3,123.2,115.1,106.8,44.6,39.7,23.2,23.1,15.9.HRMS(EI-TOF)m / z:[M] + calcd for C 15 H 18 N2O3:274.1312,found:274.1320;[α] D 25=+5.8(c 0.20, CH2Cl2); HPLC (Chiralpak AS-H, n-hexane / ethanol=80 / 20, flowrate=1.0mL / min, λ=220nm)t R =5.749min(minor),68.704min(major).

[0232] Example 59 Determination of antibacterial activity of chiral 2-aminobenzopyran derivatives

[0233] The in vitro antibacterial activity was evaluated using the plate inhibition of mycelial growth rate method. Test strains, including *Rhizoctonia solani* (rice sheath blight), *Sclerotinia sclerotiorum* (rapeseed sclerotinia), *Fusarium graminearum* (wheat scab), and *Gyromitra esculenta* (cucumber rot), were activated on PDA plates. The compounds were prepared into 100 mg / L PDA plates. Mycelial discs of the test strains were placed in the center of the drug-containing petri dishes and incubated at 25°C until the test strains in the blank control dishes reached near the edge of the petri dishes. The colony diameter of each drug-containing plate was measured using the cross-sectional method, and the inhibition rate of the compounds on mycelial growth was calculated. The inhibition rates of each compound are shown in Table 2. The inhibition rate against diseases was calculated using the following formula:

[0234]

[0235] Table 2. Antibacterial activity of chiral 2-aminobenzopyran derivatives at 100 ppm

[0236]

[0237]

[0238] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention shall still fall within the scope of the technical solution of the present invention.

Claims

1. A chiral 2-aminobenzopyran derivative or its optical isomer, and a pesticide-acceptable salt, characterized in that, It has the structure shown in Formula I. Formula I R 1 Selected from hydrogen, C 1-8 Alkyl, fluorine, chlorine, bromine, substituted or unsubstituted C 1-8 Alkoxy, C 1-8 One or more of the haloalkyl groups, substituted with C 1-8 The substituents of the alkoxy group are selected from halogens; R 2 Selected from nitro; R 3 Selected from C 1-8 Alkyl, C6 aryl, pyridine.

2. A chiral 2-aminobenzopyran derivative or its optical isomer, and a pesticide-acceptable salt, characterized in that, Selected from the following compounds 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 3. An agricultural composition comprising: (a) the derivative of any one of claims 1 to 2, or an optical isomer thereof, or a pesticide-acceptable salt thereof; and (b) Pesticide-acceptable carriers and / or excipients.

4. The use of the derivative of any one of claims 1 to 2 or the agricultural composition of claim 3 in the preparation of an agricultural fungicide, wherein the agricultural fungicide is used to control plant pathogens, and the plant pathogens are selected from Fusarium graminearum of wheat, Rhizoctonia solani of rice, Gray mold of cucumber, Sclerotinia sclerotium of rapeseed, Take-all of wheat, Gray mold of tomato, Late blight of potato, Phytophthora in pepper, Early blight of tomato, Bakanae disease of rice, Dry rot of potato, Anthracnose of cucumber, and Blast of rice.

5. A method for preparing a derivative according to any one of claims 1 to 2, characterized in that, The method includes the steps of reacting the compound shown in formula a and the compound shown in formula b under conditions of solvent, acid catalyst, metal catalyst, and ligand, to obtain a chiral compound having the structure shown in general formula I. 。 6. The preparation method according to claim 5, characterized in that, The reaction solvent is selected from one or more of the following: acetonitrile, tetrahydrofuran, toluene, trifluorotoluene, 1,2-dichloroethane, dichloromethane, 1,4-dioxane, methyl tert-butyl ether, cyclopentyl methyl ether, N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide, and N,N-dimethylacetamide, with a water content of less than 10 ppm. The metal catalyst used in the reaction is a complex of iridium, palladium, rhodium, ruthenium, or cobalt; The ligand is selected from one of the phosphoramidite ligands L1 to L12: Metal catalysts: The molar ratio of ligands is 1%:4%, 2%:8%, or 4%:16%; The acid catalyst is selected from one or more of the following: o-nitrobenzoic acid, m-nitrobenzoic acid, diphenyl phosphate, diphenylsulfonamide, trifluoroacetic acid, trichloroacetic acid, acetic acid, phosphoric acid, boron trifluoride diethyl ether complex, iron trifluoromethanesulfonate, scandium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, ytterbium trifluoromethanesulfonate, lanthanum trifluoromethanesulfonate, cerium trifluoromethanesulfonate, neodymium trifluoromethanesulfonate, europium trifluoromethanesulfonate, dysprosium trifluoromethanesulfonate, lutetium trifluoromethanesulfonate, erbium trifluoromethanesulfonate, and gadolinium trifluoromethanesulfonate. The reaction temperature is -20 to 35℃; The reaction time is 1 to 48 hours.

7. The preparation method according to claim 6, characterized in that, The metal catalyst used in the reaction was 1,5-cyclooctadiene iridium chloride dimer.

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