An ethyl-Tröger's base derivative, its preparation method and application

Abstract

This invention belongs to the field of organic chemical synthesis technology, specifically relating to an ethyl-base derivative, its preparation method, and its applications. The ethyl-base derivative provided by this invention is a compound with the structure shown in Formula I. The above-mentioned compound provided by this invention is an enantiomeric pure ethyl-base compound, possessing a nitrogen chiral center and a unique rigid structure, which can provide a structural basis for molecular recognition, supramolecular chemistry, asymmetric catalysis, and the discovery of novel drug molecules. In particular, the compound of this invention can serve as a chiral catalyst for the azahexacyclopropanation reaction of chalcones, with mild reaction conditions, moderate yield, and moderate enantioselectivity, making it suitable for application as a chiral catalyst.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis technology, specifically relating to an ethyl- Base derivatives, their preparation methods, and applications. Background Technology

[0002] In the field of central chirality research, the study of central chiral carbon is relatively mature. However, research on other chiral atoms, such as nitrogen chiral centers, remains scarce. This is because the lone pair electrons on nitrogen atoms are highly susceptible to flipping, leading to racemization. Therefore, the catalytic asymmetric synthesis of compounds containing nitrogen chiral centers is extremely challenging.

[0003] The base is a special structure with a nitrogen chiral center, classically... The methylene bridge within the base molecule is connected to the benzene ring in an almost perpendicular manner, preventing the lone pair of electrons on the chiral nitrogen atom from flipping. Therefore, The base is a nitrogen-chiral molecule with a C2 symmetry axis and a hydrophobic cavity. Given... The base contains two chiral nitrogen atoms and possesses a unique rigid structure, attracting increasing attention from researchers. Currently, Base derivatives have been successfully applied in cutting-edge fields such as DNA chiral recognition, supramolecular chemistry, materials chemistry, asymmetric catalysis, and drug development. However, currently reported... There are relatively few types of base derivatives, and there is also a lack of simple and quick ways to synthesize them. The preparation process of base derivatives is therefore limited. Further applications of base derivatives in numerous fields. Summary of the Invention

[0004] To solve the above-mentioned technical problems, the first objective of this invention is to provide an ethyl- Base derivatives are nitrogen-chiral molecules with unique three-dimensional structures and rigid structures, which can provide a structural basis for molecular recognition, supramolecular chemistry, asymmetric catalysis, and the discovery of novel drug molecules.

[0005] A second object of the present invention is to provide the above-mentioned ethyl- The preparation method of base derivatives is simple and easy to apply in industry.

[0006] A third object of the present invention is to provide the above-mentioned ethyl- Applications of base-type derivatives: This nitrogen-chiral compound can be used as a chiral catalyst to catalyze asymmetric nitrogen heterocyclic propanation.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] An ethyl- Base-type derivatives are compounds with the structure shown in Formula I:

[0009]

[0010] In formula I, Ar 1 Ar 2 It is an aryl group containing substituents;

[0011] Among them, Ar 1 The substituents are selected from one of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, benzyl, hydrogen, fluorine, chlorine, bromine, methoxy, and benzyloxy; Ar 2 The substituents are selected from one of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, benzyl, hydrogen, fluorine, chlorine, bromine, methoxy, benzyloxy, and trimethylsilyl.

[0012] Considering the synthesis yield and application effects of nitrogen-based chiral compounds, the ethyl- Base-type derivatives are compounds I-1 to I-20 with the following structures:

[0013]

[0014]

[0015] The above ethyl- The preparation method of base derivatives includes the following steps:

[0016]

[0017] Compound 1, compound 2, and an inorganic base were mixed in an organic solvent, and then subjected to a dienylation substitution reaction in the presence of palladium and a chiral ligand to obtain the ethyl group represented by formula I. Base-type derivatives.

[0018] As a preferred embodiment, the inorganic base is one of sodium carbonate, potassium carbonate, and cesium carbonate. More preferably, the inorganic base is sodium carbonate.

[0019] As a preferred embodiment, the organic solvent is one or more selected from chloroform, methane, dichloromethane, and tetrahydrofuran. More preferably, the organic solvent is chloroform.

[0020] As a preferred embodiment, in compound 2, R is one of methyl, ethyl, tert-butyl, and benzyl, and is more preferably methyl.

[0021] As a preferred embodiment, the palladium metal is Pd2(dba)3·CHCl3; the chiral ligand is N,N-bis((S)-1-phenylethyl)-4,5,6,7-tetrahydrodiindo[7,1-de:1',7'-fg][1,3,2]dioxaphosphata-octacyclo-12-amine.

[0022] As a preferred embodiment, the dielyl substitution reaction is carried out at a temperature of 50–70 °C for a time of 20–40 h. As a preferred embodiment, the molar ratio of compound 1, compound 2, inorganic base, palladium, and chiral ligand during the reaction is 1:(1.4–1.6):(1.8–2.2):(0.04–0.06):(0.14–0.16). As a further preferred embodiment, the molar ratio of compound 1, compound 2, inorganic base, palladium, and chiral ligand during the reaction is 1:1.5:2:0.05:0.15. The above ethyl- Applications of base derivatives as chiral catalysts in the catalytic propanation of nitrogen-containing heterocyclic compounds.

[0023] As a preferred embodiment, the aziridine propanation reaction is the aziridine propanation reaction of chalcone. The above-described technical solution of the present invention has the following advantages compared to the prior art:

[0024] The ethyl- provided by the present invention Base-type derivatives, which are enantiomeric pure ethyl- Base compounds, with their nitrogen chiral centers and unique rigid structures, can provide a material structural basis for molecular recognition, supramolecular chemistry, asymmetric catalysis, and the discovery of novel drug molecules.

[0025] The ethyl- provided by the present invention The method for preparing base-type derivatives starts with readily available tetrahydrodibenzodiazepine cyclic compounds and proceeds via palladium-catalyzed asymmetric dielyl alkyl substitution reactions to obtain nitrogen-chiral target compounds. The entire process is simple to operate, and the compound structures are easily modified, facilitating mass production and commercial applications. The ethyl- The application of base-type derivatives involves compounds with nitrogen chiral centers, which can serve as chiral catalysts for the azahexacyclic propanation of chalcones. The reaction conditions are mild, the yields are moderate, and the enantioselectivity is moderate, making them suitable for use as chiral catalysts and providing a structural basis for the development of novel catalysts. Attached Figure Description

[0026] Figure 1 The compound I-1 obtained in Example 1 of this invention 1 1H NMR results;

[0027] Figure 2 The compound I-1 obtained in Example 1 of this invention 13 1C NMR results;

[0028] Figure 3 The compound I-2 obtained in Example 2 of this invention 1 1H NMR results;

[0029] Figure 4 The compound I-2 obtained in Example 2 of this invention 13 1C NMR results;

[0030] Figure 5 Compound I-3 obtained in Example 3 of this invention 1 1H NMR results;

[0031] Figure 6 Compound I-3 obtained in Example 3 of this invention 13 1C NMR results;

[0032] Figure 7 Compound I-4 obtained in Example 4 of this invention 1 1H NMR results;

[0033] Figure 8 Compound I-4 obtained in Example 4 of this invention 13 1C NMR results;

[0034] Figure 9 Compound I-5 obtained in Example 5 of this invention 1 1H NMR results;

[0035] Figure 10 Compound I-5 obtained in Example 5 of this invention 13 1C NMR results. Detailed Implementation

[0036] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments are not intended to limit the present invention. Unless otherwise specified, the test methods used in the following embodiments are conventional methods; unless otherwise specified, the raw materials used are items commonly used in the art, publicly available, or commercially obtainable.

[0037] In this invention, the abbreviations of substituents have the meanings conventionally understood in the art, such as "Me" for methyl, "Et" for ethyl, and so on. n "Pr" stands for n-propyl. i "Pr" stands for isopropyl. n "Bu" represents n-butyl, t "Bu" refers to tert-butyl. n "Am" stands for n-pentyl, "Bn" for benzyl, "H" for hydrogen, "F" for fluorine, "Cl" for chlorine, "Br" for bromine, "MeO" for methoxy, "BnO" for benzyloxy, "TMS" for trimethylsilyl, and "Ph" for phenyl.

[0038] The ethyl- provided in the following embodiments of the present invention Base-type derivatives are compounds with the structure shown in Formula I:

[0039]

[0040] In formula I, Ar 1 Ar 2 It is an aryl group containing substituents;

[0041] Among them, Ar 1 The substituents in the group are selected from one of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, benzyl, hydrogen, fluorine, chlorine, bromine, methoxy, and benzyloxy; Ar 2 The substituents are selected from one of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, benzyl, hydrogen, fluorine, chlorine, bromine, methoxy, benzyloxy, and trimethylsilyl.

[0042] Specifically, in Examples 1 to 20 provided below, ethyl- The preparation method of base derivatives adopts the following technical route:

[0043]

[0044] Using the above technical route, ethyl- Base derivatives are designated as compounds I-1 to I-20. In the following examples, the palladium used is Pd2(dba)3·CHCl3; the chiral ligand is N,N-bis((S)-1-phenylethyl)-4,5,6,7-tetrahydrodiindo[7,1-de:1',7'-fg][1,3,2]dioxaphosphata-octacyclo-12-amine.

[0045] In the following examples, R in compound 2 is one of methyl, ethyl, tert-butyl, and benzyl, preferably methyl. In Examples 1-20 below, the starting material compound 1 used is a tetrahydrodibenzodiazepine compound, referred to sequentially as compound 1a to compound 1t, which can be conventionally prepared with reference to the following prior art:

[0046] [1]Functionalized analogues of base:scope and limitations of ageneral synthetic procedure and facility,predictable method for the separation of enantiomers.DOI:10.1016 / j.tet.2008.04.111;

[0047] [2]Synthesis of 5,6,11,12-tetrahydrodibenzo[b,f][1,5]diazocines and ademonstration of their reactivity to afford methano strap-modified base analogues.DOI:10.3998 / ark.5550190.0009.c17.

[0048] Example 1 This example provides an ethyl- Base derivative, denoted as compound I-1, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is as follows: Take a 10 mL Schlenk tube and add compound 1a (in compound 1a, Ar...) 1 =Ar 2=4-MePh, added in amounts of 23.8 mg, 0.1 mmol, 1.0 equiv; compound 2 (R = Me, 30 mg, 0.15 mmol, 1.2 equiv); sodium carbonate (20 mg, 0.2 mmol, 2.0 equiv); then 2 mL of anhydrous chloroform was added, followed by nitrogen purging. Under nitrogen protection, palladium (5 mg, 0.005 mmol, 0.05 equiv) and a chiral ligand (15 mg, 0.015 mmol, 0.15 equiv) were added to the reaction flask. The reaction was carried out at 60 °C for 24 hours. The reaction was then terminated by adding 3 mL of saturated ammonium chloride solution. The mixture was extracted three times with dichloromethane (3 × 6 mL), and the organic phases were combined. The mixture was dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified by column chromatography using ethyl acetate / petroleum ether = 30 / 1 to give compound I-1 (Ar 1 =Ar 2 =4-MePh)24.7mg, yield 85%, state is colorless oily liquid.

[0049] The analytical data of the product are as follows: optical rotation value: -344.01 (concentration: 0.45, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), peak time 1: 3.63 min, peak time 2: 4.79 min, enantioselectivity: 96%.

[0050] Nuclear magnetic resonance of compound I-1 obtained in Example 1 1 H NMR, 13 The C NMR spectra are as follows: Figure 1 , Figure 2 As shown. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ7.05(d,J=8.0Hz,1H),6.96(d,J=8.0Hz,1H),6.93-6.82(m,2H),6.71(s,1H),6.63(s,1H),6.07-5.90(m,1H),5.24-5.14(m, 1H),5.08-4.96(m,1H),4.67(d,J=17.3Hz,1H),4.50(d,J=17.5Hz,2H),4 .35(d,J=17.3Hz,1H),4.30-4.23(m,1H),3.89-3.74(m,2H),2.17(s,6H). 13C NMR (100MHz, CDCl3) δ 147.4, 143.9, 139.6, 137.0, 136.8, 134.7, 134.4, 129.7, 129.0, 128.5, 128.1, 127.9, 127.8, 114.9, 77.4, 77.0, 76.7, 67.2, 61.0, 60.6, 58.8, 20.8, 20.7. High-resolution characterization results are: HRMS (ESI) m / z calcd for C 20 H 22 N2[M+H] + =291.1856,found=291.1856.

[0051] Example 2 This example provides an ethyl- A base-type derivative, denoted as compound I-2, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1b (in compound 1b, Ar... 1 =Ar 2 =4-EtPh), the remaining steps are the same as in Example 1. The product obtained is compound I-2 (Ar 1 =Ar 2 =4-EtPh)28.9mg. Yield: 91%, state: colorless oily liquid.

[0052] The analytical data of the product are as follows: optical rotation value: -270.19 (concentration: 0.5, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), peak time 1: 3.51 min, peak time 2: 4.79 min, enantioselectivity: 94%.

[0053] Nuclear magnetic resonance of compound I-2 obtained in Example 2 1 H NMR, 13 The C NMR spectra are as follows: Figure 3 , Figure 4 As shown. NMR characterization results: 1H NMR (400MHz, CDCl3) δ7.08(d,J=8.0Hz,1H),7.00(d,J=8.0Hz,1H),6.91(t,J=8.5Hz,2H),6. 73(s,1H),6.65(s,1H),6.08-5.85(m,1H),5.18(d,J=17.5Hz,1H),5.00(d,J=10.8Hz,1H),4 .70(d,J=17.4Hz,1H),4.52(dd,J=17.4,4.9Hz,2H),4.38(d,J=17.2Hz,1H),4.28(t,J=5.4H z,1H),3.90-3.81(m,1H),3.77(d,J=15.3Hz,1H),2.49(q,J=7.5Hz,4H),1.19-1.02(m,6H). 13 C NMR (100MHz, CDCl3) δ 147.6, 144.0, 140.9, 140.7, 139.7, 137.0, 136.9, 129.8, 128.0, 127.7, 127.1, 126.7, 126.6, 114.8, 67.3, 61.1, 60.7, 58.9, 28.2, 28.1, 15.3, 15.0. High-resolution characterization results are: HRMS(ESI) m / z calcd for C 22 H 26 N2[M+H] + =319.2169,found=319.2169.

[0054] Example 3 This example provides an ethyl- A base-type derivative, denoted as compound I-3, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1c (in compound 1c, Ar...). 1 =Ar 2 =4- n The remaining steps were the same as in Example 1. The resulting product was compound I-3 (ArPh). 1 =Ar 2 =4- n PrPh) 30.4 mg. Yield 88%, state is colorless oily liquid.

[0055] The analytical data of the product are as follows: optical rotation value: -19.58 (concentration: 0.32, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), peak time 1: 3.42 min, peak time 2: 3.99 min, enantioselectivity: 97%.

[0056] Nuclear magnetic resonance of compound I-3 obtained in Example 3 1 H NMR, 13 The C NMR spectra are as follows: Figure 5 , Figure 6 As shown. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ7.06(d,J=8.0Hz,1H),6.98(d,J=8.0Hz,1H),6.87(dd,J=12.7,4.7Hz,2 H),6.71(s,1H),6.63(s,1H),6.04-5.87(m,1H),5.17(d,J=17.4Hz,1H),4.99(d,J=10.7Hz,1H ),4.69(d,J=17.3Hz,1H),4.57-4.45(m,2H),4.37(d,J=17.3Hz,1H),4.30-4.22(m,1H),3.92- 3.81(m,1H),3.76(d,J=14.9Hz,1H),2.47-2.36(m,4H),1.58-1.49(m,4H),0.90-0.83(m,6H). 13 C NMR (100MHz, CDCl3) δ 147.6, 144.0, 139.7, 139.5, 139.2, 137.0, 136.8, 129.7, 128.3, 127.8, 128.7, 127.3, 127.2, 114.8, 67.3, 61.1, 60.7, 59.0, 37.5, 37.4, 24.4, 24.2, 14.0. High-resolution characterization results are: HRMS(ESI) m / z calcd for C 24 H 30 N2[M+H] + =347.2482,found=347.2487.

[0057] Example 4 This example provides an ethyl- A base-type derivative, denoted as compound I-4, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1d (in compound 1d, Ar...). 1 =Ar 2 =4- i The remaining steps were the same as in Example 1. The resulting product was compound I-4 (ArPh). 1 =Ar 2 =4- i PrPh) 31.1 mg. Yield 90%, state is colorless oily liquid.

[0058] The analytical data of the product are as follows: optical rotation: -46.00 (concentration: 0.10, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), peak time 1: 3.42 min, peak time 2: 4.57 min, enantioselectivity: 97%.

[0059] Nuclear magnetic resonance of compound I-4 obtained in Example 4 1 H NMR, 13 The C NMR spectra are as follows: Figure 7 , Figure 8 As shown. The NMR characterization results of compound I-4 are as follows: 1 H NMR (400MHz, CDCl3) δ7.08(d,J=8.1Hz,1H),7.01(d,J=8.1Hz,1H),6.94(t,J=7.6Hz,2H),6 .75(s,1H),6.67(s,1H),6.03-5.85(m,1H),5.17(d,J=17.4Hz,1H),4.99(d,J=10.7Hz,1H), 4.70(d,J=17.4Hz,1H), 4.53(dd,J=17.4,7.6Hz,2H), 4.40(d,J=17.3Hz,1H), 4.27(t,J=5. 6Hz,1H),3.91-3.80(m,1H),3.75(d,J=14.8Hz,1H),2.82-2.69(m,2H),1.21-1.10(m,12H). 13C NMR (100MHz, CDCl3) δ 147.6, 145.5, 145.3, 139.8, 137.1, 137.0, 129.9, 128.0, 126.2, 125.7, 125.1, 125.0, 114.8, 67.3, 61.1, 60.8, 59.1, 33.4, 33.3, 24.0, 23.9, 23.8, 23.7. High-resolution characterization results are: HRMS (ESI) m / z calcd for C 24 H 30 N2[M+H] + =347.2482,found=347.2487.

[0060] Example 5 This example provides an ethyl- A base-type derivative, denoted as compound I-5, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1e (in compound 1e, Ar...). 1 =Ar 2 =4- n BuPh), the remaining steps are the same as in Example 1. The product obtained is compound I-5 (Ar). 1 =Ar 2 =4- n BuPh) 28.1 mg. Yield 75%, state is colorless oily liquid.

[0061] The analytical data of the product are as follows: optical rotation: -20.40 (concentration: 0.25, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), peak time 1: 3.42 min, peak time 2: 3.92 min, enantioselectivity: 94%.

[0062] Nuclear magnetic resonance of compound I-5 obtained in Example 5 1 H NMR, 13 The C NMR spectra are as follows: Figure 9 , Figure 10 As shown. NMR characterization results: 1H NMR(400MHz, CDCl3)δ6.98(d,J=8.0Hz,1H),6.90(d,J=8.0Hz,1H),6.83-6.77(m,2H),6.63(s,1H) ,6.55(s,1H),5.96-5.77(m,1H),5.09(d,J=17.4Hz,1H),4.92(d,J=10.7Hz,1H),4.61(d,J=17.3H z,1H),4.44(d,J=19.3Hz,2H),4.29(d,J=17.2Hz,1H),4.23-4.17(m,1H),3.83-3.73(m,1H),3.68 (d,J=14.8Hz,1H),2.38-2.32(m,4H),1.46-1.37(m,4H),1.23-1.17(m,4H),0.80(t,J=7.3Hz,6H). 13 C NMR (100MHz, CDCl3) δ 147.5, 144.0, 139.7, 139.7, 139.5, 137.0, 136.8, 129.7, 128.2, 127.9, 127.6, 127.2, 127.1, 114.8, 67.3, 61.1, 60.7, 59.0, 35.0, 33.5, 33.3, 22.5, 22.5, 14.0. High-resolution characterization results are: HRMS (ESI) m / z calcd for C 26 H 34 N2[M+H] + =375.2795,found=375.2800.

[0063] Example 6 This example provides an ethyl- A base-type derivative, denoted as compound I-6, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1f (in compound 1f, Ar...). 1 =Ar 2 =4- t BuPh), the remaining steps are the same as in Example 1. The product obtained is compound I-6 (ArPh). 1 =Ar 2 =4- t BuPh) 30.3 mg. Yield 81%, state is colorless oily liquid.

[0064] The analytical data of the product are as follows: optical rotation value: -79.64 (concentration: 0.3, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), peak time 1: 3.36 min, peak time 2: 4.41 min, enantioselectivity: 96%.

[0065] Numerous NMR spectra are involved for the following compounds in this invention, and will not be detailed here. Only the NMR characterization results are described below. NMR characterization results for compound I-6: 1 H NMR (400MHz, CDCl3) δ7.17-7.06(m,3H),7.02(d,J=8.3Hz,1H),6.89(d,J=2.0Hz,1 H),6.81(d,J=0.9Hz,1H),5.99-5.85(m,1H),5.16(d,J=17.4Hz,1H),5.04-4.94(m ,1H),4.72(d,J=17.4Hz,1H),4.54(dd,J=17.4,8.3Hz,2H),4.41(d,J=17.2Hz,1H) ,4.30-4.22(m,1H),3.88-3.79(m,1H),3.77-3.70(m,1H),1.22(d,J=3.0Hz,18H). 13 C NMR (100MHz, CDCl3) δ 147.9, 147.6, 147.3, 143.7, 139.8, 136.7, 136.6, 129.6, 127.8, 124.9, 124.4, 124.2, 124.1, 114.8, 67.35, 61.27, 60.9, 59.2, 34.2, 31.4. High-resolution characterization results are: HRMS (ESI) m / z calcd for C 26 H 34 N2[M+H] + =375.2795,found=375.2800.

[0066] Example 7 This example provides an ethyl- Base derivative, denoted as compound I-7, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1g (in compound 1g, Ar... 1 =Ar 2 =4- n The remaining steps were the same as in Example 1. The resulting product was compound I-7 (ArPh). 1=Ar 2 =4- n AmPh) 31.8 mg. Yield 79%, state is colorless oily liquid.

[0067] The analytical data of the product are as follows: optical rotation: -9.4 (concentration: 0.38, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 3.37 min, elution time 2: 3.79 min, enantioselectivity: 93%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ7.06 (d, J=8.0Hz, 1H), 6.98 (d, J=8.0Hz, 1H), 6.93-6.84 (m, 2H), 6.70 (d, J= 1.3Hz,1H),6.63(d,J=1.4Hz,1H),6.03-5.84(m,1H),5.24-5.12(m,1H),5.06-4.79(m,1H),4.69( d,J=17.3Hz,1H),4.57-4.42(m,2H),4.37(d,J=17.2Hz,1H),4.31-4.22(m,1H),3.91-3.79(m,1H ),3.79-3.66(m,1H),2.49-2.37(m,4H),1.58-1.45(m,4H),1.31-1.23(m,8H),0.88-0.81(m,6H). 13 C NMR (100MHz, CDCl3) δ 147.5, 144.0, 139.8, 139.7, 139.5, 137.0, 136.9, 129.7, 128.2, 127.9, 127.6, 127.2, 127.1, 114.8, 67.3, 61.1, 60.7, 59.0, 35.33, 31.71, 31.7, 31.0, 30.8, 22.5, 14.0. High-resolution characterization results are: HRMS(ESI) m / z calcd for C 28 H 38 N2[M+Na] + =425.2928, found=425.2930.

[0068] Example 8 This example provides an ethyl- A base-type derivative, denoted as compound I-8, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1h (in compound 1h, Ar...).1 =Ar 2 =4-BnPh), the remaining steps are the same as in Example 1. The product obtained is compound I-8 (Ar 1 =Ar 2 =4-BnPh)37.6mg. Yield 85%, state is colorless oily liquid.

[0069] The analytical data of the product are as follows: optical rotation: -749.03 (concentration: 0.2, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 4.88 min, elution time 2: 7.14 min, enantioselectivity: 96%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ7.27-7.21(m,4H),7.20-7.14(m,2H),7.14-7.08(m,4H),7.07-7.04(m,1H), 6.97(d,J=8.0Hz,1H),6.89-6.82(m,2H),6.71(s,1H),6.63(s,1H),5.99-5.82(m,1H),5.15(dd,J= 17.4,0.7Hz,1H),4.98(dd,J=10.8,0.9Hz,1H),4.64(d,J=17.4Hz,1H),4.48(d,J=17.4Hz,2H),4.3 3(d,J=17.3Hz,1H),4.28-4.20(m,1H),3.84(d,J=7.5Hz,1H),3.80(s,4H),3.73(d,J=14.9Hz,1H). 13 C NMR (100MHz, CDCl3) δ 148.0, 144.5, 141.1, 140.9, 139.6, 137.9, 137.7, 137.2, 137.1, 130.1, 129.1, 129.0, 128.8, 128.5, 128.4, 128.2, 127.8, 127.7, 126.1, 115.0, 67.3, 61.0, 60.6, 58.9, 41.4, 41.3. High-resolution characterization results are: HRMS (ESI) m / z calcd for C 32 H 30 N2[M+Na] + =465.2302,found=465.2307.

[0070] Example 9 This example provides an ethyl- A base-type derivative, denoted as compound I-9, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1i (in compound 1i, Ar...). 1 =Ar 2 =Ph), the remaining steps are the same as in Example 1. The product obtained is compound I-9 (Ar 1 =Ar 2 =Ph)21.7mg. Yield 83%, state is colorless oily liquid.

[0071] The analytical data of the product are as follows: optical rotation: -17.60 (concentration: 0.25, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 3.97 min, elution time 2: 4.77 min, enantioselectivity: 81%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ7.19-7.13(m,1H),7.12-7.02(m,3H),6.99-6.88(m,3H ),6.83(d,J=7.5Hz,1H),6.06-5.84(m,1H),5.27-5.12(m,1H),5.12-4.97(m, 1H),4.74(d,J=17.4Hz,1H),4.59(d,J=5.9Hz,1H),4.55(d,J=5.8Hz,1H),4.4 2(d,J=17.3Hz,1H),4.36-4.27(m,1H),3.97-3.85(m,1H),3.84-3.74(m,1H). 13 C NMR (100MHz, CDCl3) δ 150.0, 146.6, 139.4 137.2, 137.0, 130.0, 128.5, 128.1, 127.9, 127.3, 127.2, 125.3, 125.0, 115.0, 67.2, 61.0, 60.7, 58.7. High-resolution characterization results are: HRMS(ESI) m / z calcd for C 18 H 18 N2[M+H] + =263.1543,found=263.1547.

[0072] Example 10 This example provides an ethyl- Base-type derivative, denoted as compound I-10, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1j (in compound 1j, Ar...). 1 =Ar 2 =4-FPh), the remaining steps are the same as in Example 1. The product obtained is compound I-10 (Ar 1 =Ar 2 =4-FPh)25.3mg. Yield 85%, state is colorless oily liquid.

[0073] The analytical data of the product are as follows: optical rotation: -150.58 (concentration: 0.35, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 4.03 min, elution time 2: 5.24 min, enantioselectivity: 91%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ7.18-7.07(m,1H),7.07-6.98(m,1H),6.83-6.70(m,2H),6.61(dd,J=9.1,2.9Hz,1H),6.54(dd,J=9.0,2.9Hz,1H),6.0 1-5.83(m,1H),5.23-5.14(m,1H),5.09-4.93(m,1H),4.71-4.59(m,1H ),4.48(dd,J=17.4,3.4Hz,2H),4.36-4.24(m,2H),3.86-3.74(m,2H). 13 C NMR (100MHz, CDCl3) δ160.1 (J=243Hz), 159.4 (J=243Hz), 158.7, 145.7, 145.6, 142.2, 142.1, 139.2 (J=22Hz), 139.0 (J=24H z),131.6,131.5,129.7,129.6,115.2,114.6,114.4,114.3,114.3,114.1(J=5Hz),,114.0,113.9,67.0,60.8,60.5,58.6. 19 F NMR (376MHz, CDCl3) δ -117.52, -117.89. High-resolution characterization results are: HRMS (ESI) m / z calcd for C 18 H 16 F2N2[M+H] + =299.1355,found=299.1357.

[0074] Example 11 This example provides an ethyl- A base-type derivative, denoted as compound I-11, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1k (in compound 1k, Ar...). 1 =Ar 2 =4-ClPh), the remaining steps are the same as in Example 1. The product obtained is compound I-11 (Ar 1 =Ar 2 =4-ClPh)23.4mg. Yield 71%, state is colorless oily liquid.

[0075] The analytical data of the product are as follows: optical rotation: -56.06 (concentration: 0.3, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 4.03 min, elution time 2: 5.51 min, enantioselectivity: 84%. NMR characterization results: 1 H NMR (400MHz, DMSO) δ7.18-6.99(m,5H),6.95(s,1H),5.94-5.76(m,1H),5.19(d,J=17.5Hz,1H),5.06-4.92(m,1H ),4.74(d,J=17.6Hz,1H),4.46(d,J=17.7Hz,1H),4.40-4.24(m,3H),4.00-3.74(m,1H),3.69(d,J=14.8Hz,1H). 13 C NMR (100MHz, DMSO) δ 149.4, 146.3, 139.8, 139.7, 139.4, 131.9, 130.1, 129.3, 128.9, 128.5, 127.9, 127.5, 127.3, 115.8, 66.3, 59.9, 59.8, 57.8. High-resolution characterization results are: HRMS (ESI) m / z calcd for C 18 H 16 Cl2N2[M+H] + =331.0764, found=331.0760.

[0076] Example 12 This example provides an ethyl- Base derivative, denoted as compound I-12, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1l (in compound 1l, Ar...). 1 =Ar 2 =4-OMePh), the remaining steps are the same as in Example 1. The product obtained is compound I-12 (Ar 1 =Ar 2 =4-OMePh)29.0mg. Yield 90%, state is colorless oily liquid.

[0077] The analytical data of the product are as follows: optical rotation: -147.78 (concentration: 0.3, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 4.32 min, elution time 2: 8.36 min, enantioselectivity: 98%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ7.09(d,J=8.6Hz,1H),7.01(d,J=8.6Hz,1H),6.68-6.58(m,2H),6.47-6.31(m,2H),6.02-5.86(m,1H),5.17(d,J=17.5Hz,1H) ,5.00(d,J=10.8Hz,1H),4.66(d,J=17.3Hz,1H),4.48(d,J=14.8Hz,2H),4 .33(d,J=17.3Hz,1H),4.27-4.11(m,1H),3.89-3.73(m,2H),3.67(s,6H). 13 CNMR (100MHz, CDCl3) δ 157.0, 156.7, 142.9, 139.6, 139.3, 138.6, 138.4, 131.0, 129.1, 114.8, 112.9, 112.9, 112.8, 112.3, 67.3, 61.2, 60.9, 59.0, 55.3, 55.2. High-resolution characterization results are: HRMS (ESI) m / z calcd for C 20 H 22 N₂O₂[M+H] + =323.1755,found=323.1757.

[0078] Example 13 This example provides an ethyl- A base-type derivative, denoted as compound I-13, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1m (in compound 1m, Ar...). 1 =Ar 2 =4-OBnPh), the remaining steps are the same as in Example 1. The product obtained is compound I-13 (Ar 1 =Ar 2 =4-OBnPh)43.1mg. Yield 91%, state is colorless oily liquid.

[0079] The analytical data of the product are as follows: optical rotation: -144.67 (concentration: 0.3, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 5.37 min, elution time 2: 8.93 min, enantioselectivity: 98%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ7.41-7.27(m,10H),7.10(d,J=8.6Hz,1H),7.01(d,J=8.6H z,1H),6.76-6.64(m,2H),6.50(dd,J=26.6,2.8Hz,2H),6.05-5.88(m,1H),5.18 (d,J=17.4Hz,1H),5.04-4.98(m,1H),4.91(d,J=5.0Hz,4H),4.66(d,J=17.4Hz, 1H),4.55-4.41(m,2H),4.33(d,J=17.3Hz,1H),4.26(s,1H),3.88-3.70(m,2H). 13 C NMR (100MHz, CDCl3) δ 156.3, 156.1, 143.2, 139.6, 138.7, 138.5, 137.1, 137.1, 131.2, 129.1, 128.6, 128.0, 127.9, 127.6, 127.5, 114.9, 113.8, 113.7, 113.6, 113.3, 70.1, 70.0, 67.3, 61.2, 60.9, 59.0. High-resolution characterization results are: HRMS(ESI) m / z calcd for C 32 H 30 N₂O₂[M+H] + =475.2381,found=475.2386.

[0080] Example 14 This example provides an ethyl- A base derivative, denoted as compound I-14, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1n (in compound 1n, Ar...). 1 =Ar 2 =3-MePh), the remaining steps are the same as in Example 1. The product obtained is compound I-14 (Ar 1 =Ar 2 =3-MePh)25.2mg. Yield 87%, state is colorless oily liquid.

[0081] The analytical data of the product are as follows: optical rotation: -61.24 (concentration: 0.58, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 1 / 99, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 4.34 min, elution time 2: 5.28 min, enantioselectivity: 91%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ6.97(s,1H),6.88(s,1H),6.82-6.64(m,4H),6.10-5.86(m,1H),5.18(d,J=17.5Hz,1H),5.00(d,J=10.8Hz,1H),4.68(d,J=17 .2Hz,1H),4.52(dd,J=17.2,7.0Hz,2H),4.38(d,J=17.1Hz,1H),4.28(t,J =5.4Hz,1H),3.93-3.82(m,1H),3.81-3.71(m,1H),2.21(d,J=5.4Hz,6H). 13 CNMR (100MHz, CDCl3) δ 149.9, 146.4, 139.5, 136.8, 136.8, 134.0, 133.7, 130.5, 128.6, 128.3, 127.7, 126.2, 125.8, 114.9, 67.3, 60.8, 60.4, 58.8, 20.9, 20.8. High-resolution characterization results are: HRMS (ESI) m / z calcd for C 20 H 22 N2[M+H] + =291.1856,found=291.1861.

[0082] Example 15 This example provides an ethyl- Base derivative, denoted as compound I-15, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1o (in compound 1o, Ar...). 1 =Ar 2 =3-EtPh), the remaining steps are the same as in Example 1. The product obtained is compound I-15 (Ar 1 =Ar 2 =3-EtPh)25.6mg. Yield 81%, state is colorless oil.

[0083] The analytical data of the product are as follows: optical rotation: -32.33 (concentration: 0.3, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 3.73 min, elution time 2: 4.19 min, enantioselectivity: 90%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ6.92 (s, 1H), 6.84 (s, 1H), 6.78-6.70 (m, 3H), 6.68 (d, J = 7.8Hz, 1 H),6.00-5.79(m,1H),5.11(d,J=17.5Hz,1H),5.01-4.85(m,1H),4.62(d,J=17.3Hz,1 H),4.46(dd,J=17.2,10.7Hz,2H),4.33(d,J=17.2Hz,1H),4.22(t,J=5.6Hz,1H),3.85 -3.75(m,1H),3.70(dd,J=14.9,0.9Hz,1H),2.46(p,J=7.6Hz,4H),1.14-1.06(m,6H). 13 C NMR (100MHz, CDCl3) δ 149.9, 146.5, 143.2, 139.6, 134.3, 134.1, 129.2, 128.3, 127.7, 127.3, 124.9, 124.6, 114.87, 67.3, 60.8, 60.4, 58.9, 28.2, 28.1, 15.3, 15.1. High-resolution characterization results are: HRMS (ESI) m / z calcd for C 22 H 26 N2[M+H] + =319.2169,found=319.2175.

[0084] Example 16 This example provides an ethyl- Base derivative, denoted as compound I-16, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1p (in compound 1p, Ar...). 1 =Ar 2 =3,4-diMePh), the remaining steps are the same as in Example 1. The product obtained is compound I-16 (Ar 1 =Ar 2 =3,4-diMePh) 26.7 mg. Yield 84%, state is colorless oily liquid.

[0085] The analytical data of the product are as follows: optical rotation: -15.01 (concentration: 0.43, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 3.71 min, elution time 2: 4.06 min, enantioselectivity: 95%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ6.93(s,1H),6.85(s,1H),6.66(s,1H),6.58(s,1H),6.13-5. 75(m,1H),5.18(d,J=17.5Hz,1H),5.05-4.93(m,1H),4.64(d,J=17.2Hz,1H),4.50( d,J=5.7Hz,1H),4.46(d,J=5.5Hz,1H),4.34(d,J=17.1Hz,1H),4.29-4.18(m,1H), 3.88-3.79(m,1H),3.79-3.72(m,1H),2.12(d,J=3.3Hz,6H),2.07(d,J=1.1Hz,6H). 13 C NMR (100MHz, CDCl3) δ 147.6, 144.0, 139.7, 135.3, 135.2, 134.3, 134.1, 133.4, 133.1, 130.9, 129.5, 129.0, 128.9, 114.75, 67.39, 60.7, 60.3, 59.0, 19.3, 19.3, 19.1, 19.0. High-resolution characterization results are: HRMS(ESI) m / z calcd for C 22 H 26 N2[M+H] + =319.2169,found=319.2173.

[0086] Example 17 This example provides an ethyl- A base-type derivative, denoted as compound I-17, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1q (in compound 1q, Ar...). 1 =Ar 2 =3,4-diOMePh), the remaining steps are the same as in Example 1. The product obtained is compound I-17 (Ar 1 =Ar 2 =3,4-diOMePh) 34.0 mg. Yield 89%, state is colorless oily liquid.

[0087] The analytical data of the product are as follows: optical rotation: -64.31 (concentration: 0.37, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 10.54 min, elution time 2: 11.80 min, enantioselectivity: 95%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ6.71(s,1H),6.63(s,1H),6.39(s,1H),6.32(s,1H),6.03-5.90(m,1H),5.18(d,J=17.5Hz,1H),5.02(d,J=10.6Hz,1H),4.67 (d,J=17.1Hz,1H),4.48(d,J=17.1Hz,2H),4.34(d,J=17.0Hz,1H),4.29- 4.19(m,1H),3.90-3.84(m,1H),3.82(d,J=5.0Hz,6H),3.78-3.70(m,7H). 13 C NMR (100MHz, CDCl3) δ 147.8, 147.7, 146.6, 146.4, 142.5, 139.5, 138.9, 128.6, 128.3, 114.9, 112.9, 111.2, 110.4, 109.8, 67.7, 60.6, 60.3, 59.5, 55.9, 55.8, 55.7. High-resolution characterization results are: HRMS (ESI) m / z calcd for C 22 H 26 N₂O₄[M+H] + =383.1966,found=383.1965.

[0088] Example 18 This example provides an ethyl- A base-type derivative, denoted as compound I-18, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1r (in compound 1r, Ar...). 1 =Ar 2 =3,5-diOMePh), the remaining steps are the same as in Example 1. The product obtained is compound I-18 (Ar 1 =Ar 2 =3,5-diOMePh)28.3mg. Yield 89%, state is colorless oily liquid.

[0089] The analytical data of the product are as follows: optical rotation: -23.00 (concentration: 0.2, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 1 / 99, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 3.81 min, elution time 2: 4.60 min, enantioselectivity: 93%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ6.74 (d, J = 27.4Hz, 2H), 6.62-6.49 (m, 2H), 5.93-5.69 ( m,1H),5.08(d,J=17.5Hz,1H),4.91(d,J=10.7Hz,1H),4.60(d,J=17.6Hz,1H ),4.48(d,J=17.5Hz,1H),4.37(d,J=17.6Hz,1H),4.24-4.11(m,2H),3.87-3 .71(m,1H),3.69-3.58(m,1H),2.11(d,J=3.9Hz,6H),2.00(d,J=16.3Hz,6H). 13 C NMR (100MHz, CDCl3) δ 149.4, 145.7, 138.7, 135.1, 135.04, 134.9, 134.4, 131.2, 131.0, 127.6, 127.3, 126.9, 125.7, 113.5, 65.6, 57.5, 57.43, 56.77, 19.7, 19.6, 18.5, 18.4. High-resolution characterization results are: HRMS (ESI) m / z calcd for C 22 H 26 N2[M+H] + =319.2169,found=319.2174.

[0090] Example 19 This example provides an ethyl- A base-type derivative, denoted as compound I-19, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1s (in compound 1s, Ar...). 1 =Ar 2 =3,4,5-triMePh), the remaining steps are the same as in Example 1. The product obtained is compound I-19 (Ar 1 =Ar 2 =3,4,5-triMePh) 28.7 mg. Yield 83%, state is colorless oily liquid.

[0091] The analytical data of the product are as follows: optical rotation: -21.42 (concentration: 0.12, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 30 / 70, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 3.51 min, elution time 2: 3.79 min, enantioselectivity: 95%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ6.78 (s, 1H), 6.72 (s, 1H), 6.13-5.51 (m, 1H), 5.08 (d, J = 1 7.4Hz,1H),4.89(d,J=10.7Hz,1H),4.67(d,J=17.5Hz,1H),4.56(d,J=17.4Hz, 1H),4.43(d,J=17.5Hz,1H),4.23(d,J=17.4Hz,1H),4.20-4.11(m,1H),3.78-3 .68(m,1H),3.68-3.58(m,1H),2.08(s,6H),1.95(d,J=2.7Hz,9H),1.91(s,3H). 13 C NMR (100MHz, CDCl3) δ 147.8, 143.8, 140.0, 134.9, 134.8, 134.4, 132.7, 132.6, 132.2, 131.9, 129.1, 127.2, 114.4, 66.7, 59.8, 59.1, 58.8, 20.7, 20.63, 15.5, 15.4, 15.4, 15.3. High-resolution characterization results are: HRMS(ESI) m / z calcd for C 24 H 30 N2[M+H] + =347.2482,found=347.2482.

[0092] Example 20 This example provides an ethyl- A base-type derivative, denoted as compound I-20, is an enantiomeric chiral compound with the following structural formula: The preparation method of this compound is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1t (in compound 1t, Ar...). 1 =4-BrPh,Ar 2 =4-TMSMePh), the remaining steps are the same as in Example 1. The product obtained is compound I-20 (Ar 1 =4-BrPh,Ar 2 =4-TMSMePh) 49.2 mg. Yield 95%, state is colorless oily liquid. Among them, the product compound I-20 contains diastereomers, so the connecting bond at H in the structural formula is temporarily represented by a wavy line.

[0093] The analytical data of the product are as follows: Optical rotation: -304.01 (concentration: 0.15, solvent: dichloromethane); HPLC (IB chiral column, isopropanol / n-hexane = 2 / 98, flow rate: 1.0 mL / min, wavelength: 254 nm), peak time 1: 3.73 min, peak time 2: 9.79 min, enantioselectivity: 97%; peak time 3: 4.03 min, peak time 4: 6.18 min, enantioselectivity: 97%; diastereoselectivity: 1:2. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ7.10-6.89(m,3H),6.90-6.80(m,2H),6.78(d,J=8.3Hz,1H),5.85-5.65(m,1H),5.08-4.91(m,1H),4.91-4. 76(m,1H),4.62-4.44(m,1H),4.40-4.28(m,2H),4.27-4.15(m,1H),4.15-4.04(m,1H),3.74-3.55(m,2H),0.00(d,J=2.6Hz,9H). 13C NMR (100MHz, CDCl3) δ 151.4, 150.4, 147.9, 147.0, 140.7, 140.5, 140.2, 140.0, 138.3, 138.0, 136.8, 136.7, 134.7, 134.1, 133.6, 133.5, 133.0, 132.2, 131.7, 131.4, 131.2, 131.1, 130.2, 128.4, 119.2, 118.8, 116.3, 116.2, 68.2, 68.0, 61.9, 61.6, 61.5, 61.1, 59.8, 59.4, 0.0, -0.0. High-resolution characterization results are: HRMS (ESI) m / z calcd forC 21 H 25 BrN2Si[M+H] + =413.1044,found=413.1040.

[0094] Experimental Example 1: Application Performance Test This experimental example uses the ethyl- prepared in Example 1 of this invention. Taking the base derivative (compound I-1) as an example, the application directions and performance of the compounds of the present invention are explained. Other compounds prepared using the present invention can also achieve comparable chiral catalytic effects. Specifically, the ethyl- A base derivative (compound I-1) was used to catalyze the azacyclic propanation of chalcone, and its catalytic performance as a chiral catalyst was investigated. The specific steps are as follows:

[0095]

[0096] Take a 50 mL round-bottom flask, and add 1 mL acetonitrile, 0.5 mL dichloromethane, compound 3 (i.e., chalcone, 20.8 mg, 0.1 mmol), and the ethyl- acetonitrile prepared in Example 1 of this invention at -30 °C. The base derivative (compound I-1, 0.04 mmol, 0.4 equiv) was followed by the addition of 2,4,6-trimethylbenzenesulfonylhydroxylamine (MSH, 0.022 g, 0.1 mmol) and cesium hydroxide monohydrate (CsOH·H2O, 0.025 g, 0.15 mmol). After stirring for 1 hour, MSH (0.011 g, 0.05 mmol) and CsOH·H2O (0.0125 g, 0.075 mmol) were added. After stirring for another hour, MSH (0.011 g, 0.05 mmol) and CsOH·H2O (0.0125 g, 0.075 mmol) were added, and the mixture was then reacted at -30 °C for 24 hours. The reaction was terminated by adding 5 mL of water, and the mixture was extracted with ethyl acetate (3 × 10 mL). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified by column chromatography with an eluent ratio of ethyl acetate / petroleum ether = 1 / 10 to obtain the target product compound 4, totaling 10 mg, with a yield of 45%, in the form of a white solid.

[0097] The analytical data of the product are as follows: optical rotation: +29.78 (concentration: 0.20, solvent: dichloromethane); HPLC (OD chiral column, isopropanol / n-hexane = 20 / 80, flow rate: 1.0 mL / min, wavelength: 254 nm), elution time 1: 6.12 min, elution time 2: 7.44 min, enantioselectivity: 60%. NMR characterization results: 1 H NMR (400MHz, CDCl3) δ8.08-7.92(m,2H),7.68-7.57(m,1H),7.49(t,J=7.7Hz,2H) ,7.44-7.28(m,5H),3.52(d,J=5.7Hz,1H),3.26-3.05(m,1H),2.76-2.55(m,1H). 13 C10 NMR (100MHz, CDCl3) δ 195.8, 138.4, 135.9, 133.9, 128.9, 128.6 128.4, 127.9, 126.2, 44.1, 43.6. High-resolution characterization results are: HRMS (ESI) m / z calcd for C10 NMR. 15 H 13 NO[M+Na] + =246.0890,found=246.0891.

[0098] The experimental results above show that the ethyl- provided by this invention... Base-type derivatives, due to their nitrogen-based chiral centers, can effectively catalyze the azahexacyclopropanation reaction of chalcones, and the reaction conditions are mild, resulting in moderate yields and enantioselectivity of the products. Therefore, the compounds of this invention are highly suitable for use as chiral catalysts and can also provide a structural basis for the development of novel catalysts.

[0099] In summary, the ethyl- provided by the present invention Base-type derivatives, possessing a nitrogen chiral center and a unique rigid structure, can provide a structural basis for molecular recognition, supramolecular chemistry, asymmetric catalysis, and the discovery of novel drug molecules. They are particularly suitable for use as chiral catalysts, providing a structural basis for the development of novel catalysts. The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention are within the scope of protection claimed by the present invention.

Claims

1. An ethyl- Base-type derivatives, characterized in that... Compounds with the structure shown in Formula I: In formula I, Ar 1 Ar 2 It is a phenyl group containing substituents; Among them, Ar 1 The substituents in the group are selected from one of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, benzyl, hydrogen, fluorine, chlorine, bromine, methoxy, and benzyloxy; Ar 2 The substituents are selected from one of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, benzyl, hydrogen, fluorine, chlorine, bromine, methoxy, benzyloxy, and trimethylsilyl.

2. The ethyl- according to claim 1 Base-type derivatives, characterized in that... Compounds I-1 to I-19 have the following structures:

3. An ethyl- Base-type derivatives, characterized in that... Compound I-20 has the following structure:

4. An ethyl- as described in claim 1 or 2 The method for preparing base-type derivatives is characterized by, Includes the following steps: Compound 1, compound 2, and an inorganic base were mixed in an organic solvent, and then subjected to a dienylation substitution reaction in the presence of palladium and a chiral ligand to obtain the ethyl group represented by formula I. Base-type derivatives; wherein, in compound 2, R is one of methyl, ethyl, tert-butyl, and benzyl; the palladium metal is Pd2(dba)3·CHCl3; and the chiral ligand is N,N-bis((S)-1-phenylethyl)-4,5,6,7-tetrahydrodiindeno[7,1-de:1',7'-fg][1,3,2]dioxaphosphata-octacyclo-12-amine.

5. The ethyl- according to claim 4 The method for preparing base-type derivatives is characterized by, The inorganic base is one of sodium carbonate, potassium carbonate, and cesium carbonate; the organic solvent is one or more of chloroform, methane, dichloromethane, and tetrahydrofuran.

6. The ethyl- according to claim 4 The method for preparing base-type derivatives is characterized by, The dienylation substitution reaction is carried out at a temperature of 50–70 °C for a time of 20–40 h.

7. The ethyl- according to any one of claims 4 to 6 The method for preparing base-type derivatives is characterized by, The molar ratio of compound 1, compound 2, inorganic base, palladium, and chiral ligand during the reaction is 1:(1.4-1.6):(1.8-2.2):(0.04-0.06):(0.14-0.16).

8. An ethyl- as described in any one of claims 1 to 3 The application of base-type derivatives is characterized by... Application of chiral catalysts in catalytic azahexacyclopropanation reactions; the azahexacyclopropanation reaction is the azahexacyclopropanation reaction of chalcone.

Images