CN114160206B - Catalyst for catalytic synthesis of optically active indole compound, application and synthesis method thereof, and optically active indole compound - Google Patents

Abstract

The invention provides a catalyst for catalytically synthesizing an optically active indole compound, application, a synthesis method and the optically active indole compound. The catalyst provided by the invention can prepare the 3-alkenyl-3-substituted oxindole compound with optical activity through the high enantioselectivity and diastereoselectivity direct asymmetric olefination reaction of the 3-alkenyl indole compound on the isatin-like compound, and simultaneously obtain higher enantioselectivity and diastereoselectivity; the enantioselectivity is more than 91 percent ee, the diastereoselectivity dr is more than 20:1, and the product yield is more than 81 percent.

Description

Catalyst, application and synthesis method for catalytically synthesizing optically active indole compounds method and optically active indoles

technical field

The invention relates to the field of organic synthesis, in particular to a catalyst for catalyzing and synthesizing optically active indole compounds, an application, a synthesis method and optically active indole compounds.

Background technique

3-Alkenyl-2-oxindole is one of the most abundant and important structural motifs in organic synthesis. They are widely found in bioactive molecules and drugs. For example, spirotryprostatin B alkaloids exhibit cytotoxic activity. JP-8g has the potential to treat cancer and inflammation. In addition, chiral alcohols and chiral ammonia at the allyl position are widely present in many bioactive compounds, such as prostaglandin A1 and Fostriecin. Meanwhile, 3-substituted 3-aminooxindole unit analogs have great medicinal value, SSR-1494153 is a VIb receptor antagonist for the treatment of anxiety and depression, NITD609 is an excellent antimalarial Drug Candidates. Therefore, it is of great significance to develop new indoles at the C3 position. The construction of optically active allyl alcohols and allylamines at the C3 position of oxindole has attracted extensive attention in chemistry.

Isatin and its analogues have been widely used in synthetic chemistry due to their excellent medicinal value and easy availability of raw materials. However, the asymmetric alkenylation of isatin has rarely been reported before. In 2010, Zhou's research group reported the asymmetric synthesis of isatin and acrolein catalyzed by cinchona alkaloids, which achieved high yield and enantioselectivity. In 2016, Zhao's group reported the asymmetric alkenylation of isatin and arylboronic acid with chiral CoI2-bisphosphine complex at 70 °C, and obtained 93% ee. However, due to the poor reactivity of bare alkenyl groups, appropriate substituents are needed at the alkenyl reactive sites to enhance their reactivity. Therefore, how to achieve direct alkenylation of isatin and its analogues and obtain better synthetic results still needs further research.

Contents of the invention

In view of this, the object of the present invention is to provide a catalyst, application, synthesis method and optically active indole compound for catalyzing the synthesis of optically active indole compounds. The catalyst and synthesis method provided by the invention can catalyze and synthesize optically active C3-position indole compounds with high enantioselectivity and diastereoselectivity, and have high yield.

The catalyst provided by the invention can prepare optically active 3-alkenyl- 3-substituted oxindole compounds, and simultaneously obtain higher enantioselectivity and diastereoselectivity; enantioselectivity reaches more than 91% ee, diastereoselectivity dr>20:1, product yield It can reach more than 81%, and the purity can reach more than 99.9%. Compared with catalysts such as conventional Lewis acids, the catalyst provided by the invention has obvious improvements in selectivity and productivity.

The present invention provides the application of catalysts in the catalytic synthesis of optically active indole compounds. For the first time, the compound of formula (C ₁ ) and/or formula (C ₂ ) is used as a catalyst to catalyze the synthesis of optically active indole compounds, specifically through High Enantioselective and Diastereoselective Asymmetric Direct Alkenylation of 3-Alkenyl Indoles to Isatinoids to Prepare Optically Active 3-Alkenyl-3-Substituted Oxindoles , and obtain a good preparation effect.

The synthesis method of optically active indole compounds provided by the present invention can obtain optically active 3-alkenyl-3-substituted oxindole compounds with high enantioselectivity and diastereoselectivity, and the enantioselectivity reaches More than 91% ee, diastereoselectivity dr>20:1, product yield of more than 81%, and purity of more than 99.9%. The stereoselectivity of the product can still be maintained when the reaction is scaled up to the gram scale.

The optically active indole compound provided by the present invention is a new optically active indole compound not disclosed in the prior art. In the prior art, the oxidized indole compound has potential medicinal value and a natural product precursor, so for The research on this type of skeleton structure has practical value. The optically active indole compounds provided by the present invention are 3-alkenyl-3 substituted oxindole compounds, which enrich the types of indole compounds at the C3 position and provide more indole compounds. Indole skeleton precursor.

Description of drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings that need to be used in the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are only It is an embodiment of the present invention, and those skilled in the art can also obtain other drawings according to the provided drawings without creative work.

Fig. 1 is the proton nuclear magnetic resonance spectrogram of gained intermediate product _S1 in the raw material preparation example 1;

Fig. 2 is the carbon nuclear magnetic resonance spectrogram of gained intermediate product _S1 in the raw material preparation example 1;

Fig. 3 is the proton nuclear magnetic resonance spectrogram of gained product L _1b in the raw material preparation example 1;

Fig. 4 is the carbon nuclear magnetic resonance spectrogram of gained product L _1b in the raw material preparation example 1;

Fig. 5 is the single crystal structure diagram of chiral copper-based catalyst C _1b in Example 1 of the present invention;

Fig. 6 is the proton nuclear magnetic resonance spectrogram of the product formula III-1a obtained in Example 1 of the present invention;

Fig. 7 is the carbon nuclear magnetic resonance spectrogram of the product formula III-1a obtained in Example 1 of the present invention;

Fig. 8 is the HPLC spectrogram of the product formula III-1a obtained in Example 1 of the present invention;

Fig. 9 is the H NMR spectrum of the product formula III-1b obtained in Example 2 of the present invention;

Fig. 10 is the C-NMR spectrum of the product formula III-1b obtained in Example 2 of the present invention;

Figure 11 is the proton nuclear magnetic resonance spectrum of the product formula III-1c obtained in Example 3 of the present invention;

Figure 12 is the carbon nuclear magnetic resonance spectrum of the product formula III-1c obtained in Example 3 of the present invention;

Figure 13 is the proton nuclear magnetic resonance spectrum of the product formula III-1d obtained in Example 4 of the present invention;

Figure 14 is the carbon nuclear magnetic resonance spectrum of the product formula III-1d obtained in Example 4 of the present invention;

Figure 15 is the proton nuclear magnetic resonance spectrum of the product formula III-1e obtained in Example 5 of the present invention;

Figure 16 is the carbon nuclear magnetic resonance spectrum of the product formula III-1e obtained in Example 5 of the present invention;

Figure 17 is the proton nuclear magnetic resonance spectrum of the product formula III-2a obtained in Example 6 of the present invention;

Figure 18 is the carbon nuclear magnetic resonance spectrum of the product formula III-2a obtained in Example 6 of the present invention;

Fig. 19 is the HPLC spectrum of the product formula III-2a obtained in Example 6 of the present invention;

Figure 20 is the proton nuclear magnetic resonance spectrum of the product formula III-2b obtained in Example 7 of the present invention;

Figure 21 is the carbon nuclear magnetic resonance spectrum of the product formula III-2b obtained in Example 7 of the present invention;

Figure 22 is the proton nuclear magnetic resonance spectrum of the product formula III-2c obtained in Example 8 of the present invention;

Fig. 23 is the carbon nuclear magnetic resonance spectrum of the product formula III-2c obtained in Example 8 of the present invention.

Detailed ways

The invention provides a catalyst for catalyzing the synthesis of optically active indole compounds, and the catalyst is a chiral copper-based catalyst;

The chiral copper-based catalyst is a compound of formula (C ₁ ) and/or a compound of formula (C ₂ ):

in:

Ar ¹ and Ar ² are each independently selected from: substituted or unsubstituted aryl groups. The aryl group is preferably phenyl or naphthyl. In the substituted aryl group, the substituent is preferably an alkyl group, a haloalkyl group, or an alkoxy group. Wherein, the alkyl group is preferably a C1-C6 alkyl group; more preferably methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-pentyl or n-hexyl. The type of the alkyl group in the haloalkyl group is consistent with the above-mentioned types, and will not be repeated here; the halogen as the substituting element is preferably fluorine, chlorine, bromine or iodine. The alkoxy group is preferably a C1-C6 alkoxy group; more preferably a methoxy group, an ethoxy group or an isopropoxy group. Preferably, Ar ¹ and Ar ² are the same.

In the present invention, preferably, the chiral copper-based catalyst is selected from one or more of the following compounds:

The present invention also provides a method for preparing a catalyst for catalytically synthesizing optically active indole compounds described in the above technical scheme, comprising the following steps:

Divalent copper salt, nitrogen-containing organic base and ligand are mixed and reacted to form a catalyst;

The ligand is a compound of formula (L ₁ ) and/or a compound of formula (L ₂ ):

Wherein, the types of Ar ¹ and Ar ² are consistent with those described in the foregoing technical solution, and will not be repeated here.

In the present invention, the ligand is the compound of formula (L ₁ ) and/or compound of formula (L ₂ ). Compared with other ligands such as BOX ligands, etc., the catalyst obtained by using the above ligands in the present invention can catalyze subsequent synthesis reactions to obtain optically active indole compounds.

More preferably, the ligand is selected from one or more of the following compounds:

In the present invention, taking ligand _L1 as an example, it can be prepared by the following method:

a) L-phenylalanine, SOCl ₂ and ethanol mixed reaction, form compound A;

b) compound A reacts with bromide to form intermediate S1;

The bromide is Ar ¹ Br and Ar ² Br;

c) Reaction of the intermediate S1 with the salicylaldehyde derivative B to form the ligand L ₁ .

The synthetic route of above process is as follows:

The synthesis process of ligand L ₂ is similar to the synthesis process of ligand L ₁ above, only the L-phenylalanine raw material is adaptively replaced with the corresponding raw material.

In the present invention, the divalent copper salt is preferably one or more of copper bromide, copper fluoride, copper chloride, copper trifluoromethanesulfonate, copper nitrate, copper sulfate and copper acetate. In the present invention, the molar ratio of the divalent copper salt to the ligand is preferably (0.95-1.00):1.

In the present invention, the nitrogen-containing organic base is preferably N-ethylmorpholine, triethylamine, piperidine, 1,8-diazabicyclo[5.4.0]undec-7-ene, N, One or more of N-diisopropylethylamine and triethylenediamine. In the present invention, the molar ratio of the nitrogen-containing organic base to the ligand is preferably (2.00-2.05):1.

In the present invention, the reaction temperature is preferably 0-25°C, more preferably 10-20°C; the reaction time is preferably 2-4h. In the present invention, stirring is preferably accompanied during the reaction.

In the present invention, the above-mentioned steps for preparing the catalyst preferably specifically include:

A divalent copper salt, a nitrogen-containing organic base, a ligand and a solvent are mixed and reacted to obtain a chiral copper-based catalyst compound.

In the present invention, the type of the solvent is not particularly limited, and it can be a conventional solvent in the field. In the present invention, toluene, xylene, chloroform, dichloromethane, tetrahydrofuran, acetone, ethyl acetate, 1,4-bis One or more of oxyhexane, methyl tert-butyl ether, methanol, ethanol, isopropanol and water; more preferably ethanol. In the present invention, the concentration of the ligand in the solvent is preferably 0.10-0.11 mol/L.

In a solvent medium, after the above reaction, a chiral copper-based catalyst is generated in the system, and the complex containing the chiral copper-based catalyst is obtained, that is, the above-mentioned chiral copper-based catalyst complex (that is, in addition to the generated catalyst in the system, it also includes other components such as solvents).

In the present invention, the above-mentioned chiral copper-based catalyst and chiral copper-based catalyst complex can be used to catalyze the synthesis of optically active indole compounds, that is, the present invention can catalyze the synthesis of optically active indole compounds in two ways. synthesis. The first method is: directly put the above-mentioned chiral copper-based catalyst complex into the preparation system for subsequent synthesis of optically active indole compounds to catalyze the synthesis of optically active indole compounds. The second way is to separate and extract the above-mentioned chiral copper-based catalyst complex, separate the chiral copper-based catalyst, and then put the chiral copper-based catalyst as a catalyst into the preparation system for subsequent synthesis of optically active indole compounds , to catalyze the synthesis of optically active indoles. For the above-mentioned second method, the means of separation and extraction is preferably: use acetone as solvent, stir the catalyst system for 2-3 hours, then centrifugally settle, take the filtrate, spin dry, add methanol to wash and dry, and obtain a chiral copper-based catalyst.

About the application :

The present invention also provides an application of the catalyst described in the above technical solution in the catalytic synthesis of optically active indole compounds. Corresponding to the above, the above-mentioned applications include two methods: one is to use the chiral copper-based catalyst complex containing chiral copper-based catalysts to catalyze the synthesis of optically active indole compounds; the other is to use pure chiral copper-based catalysts for Catalytic synthesis of optically active indoles.

The present invention also provides a method for synthesizing optically active indole compounds, comprising the following steps:

Under the action of a catalyst, the 3-alkenyl indole compound shown in formula (I) reacts with the isatin-like compound to form an optically active 3-alkenyl-3 substituted oxindole compound;

The isatin-like compound is a compound of formula (II-1) and/or a compound of formula (II-2);

The optically active 3-alkenyl-3 substituted oxindole compound is a compound of formula (Ⅲ-1) and/or a compound of formula (Ⅲ-2);

Described catalyzer is the catalyzer described in above-mentioned technical scheme;

in:

^R is selected from: hydrogen, alkyl or halogen;

R ² and R ⁴ are each independently selected from: hydrogen, alkyl, halogen, nitro, trifluoromethyl;

R ³ is selected from: allyl, phenyl, substituted or unsubstituted benzyl.

In the present invention, under the action of a catalyst, it refers to the presence of a catalyst. Specifically, the above-mentioned chiral copper-based catalyst complex can be directly put into the system to catalyze the synthesis reaction, or the above-mentioned The above-mentioned chiral copper-based catalyst after separation and extraction is put into the system to catalyze the synthesis reaction, as long as the above-mentioned catalyst exists.

In order to simplify the operation, the present invention preferably adopts the first method, directly using the chiral copper-based catalyst complex to catalyze the synthesis reaction. That is, after the chiral copper-based catalyst complex is obtained according to the above preparation steps, the chiral copper-based catalyst complex is directly used for catalytic synthesis without separation and extraction.

In the present invention, the 3-alkenylindole compound is shown in the following formula (I):

Wherein, R ¹ is selected from: hydrogen, alkyl or halogen. The alkyl group is preferably a C1-C6 alkyl group; more preferably methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-pentyl or n-hexyl. The halogen is preferably fluorine, chlorine, bromine or iodine.

In the present invention, more preferably, the 3-alkenylindole compound represented by the formula (I) is selected from one or more of the following compounds:

In the present invention, the isatin-like compound is a compound of formula (II-1) and/or a compound of formula (II-2):

in:

R ² and R ⁴ are each independently selected from: hydrogen, alkyl, halogen, nitro, trifluoromethyl. The alkyl group is preferably a C1-C6 alkyl group; more preferably methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-pentyl or n-hexyl. The halogen is preferably fluorine, chlorine, bromine or iodine.

R ³ is selected from: allyl, phenyl, substituted or unsubstituted benzyl. In the substituted benzyl group, the substituent is preferably: F, Cl, Br, Me, OMe or CF ₃ .

In the formula (II-2), the group Boc- refers to tert-butoxycarbonyl; the group Bn- refers to benzyl.

In the present invention, more preferably, the isatin-like compound is selected from one or more of the following compounds:

In the present invention, the molar weight of the catalyst is 5%-30% of the molar weight of the isatin-like compound. In the present invention, the molar ratio of the isatin-like compound to the 3-alkenylindole compound represented by formula (I) is 1: (1-1.5).

In the present invention, as mentioned above, in order to simplify the operation, the present invention preferably adopts the first method, directly using the chiral copper-based catalyst complex to catalyze the synthesis reaction. That is, after the chiral copper-based catalyst complex is obtained according to the above preparation steps, the chiral copper-based catalyst complex is directly used for catalytic synthesis without separation and extraction. Specifically, after the chiral copper-based catalyst complex is obtained according to the previous preparation steps, the 3-alkenylindole compound and isatin-like compound shown in formula (I) are directly added to the chiral copper-based catalyst complex, react. In the present invention, the initial concentration of the 3-alkenylindole compounds represented by the formula (I) in the system is preferably 0.1-0.5 mol/L, more preferably 0.1-0.3 mol/L; the initial The concentration refers to the concentration when the 3-alkenylindole compound shown in formula (I) is added to the chiral copper-based catalyst complex.

In the present invention, the reaction temperature is preferably 0-25°C, more preferably 10-20°C; in some embodiments of the present invention, the reaction temperature is 15°C or 20°C. The reaction time is preferably 24-48 hours. After the above reaction, an optically active 3-alkenyl-3 substituted oxindole compound is formed in the system.

In the present invention, the obtained optically active 3-alkenyl-3 substituted oxindole compounds are compounds of formula (Ⅲ-1) and/or compounds of formula (Ⅲ-2):

Wherein, the types of R ¹ , R ² , R ² , and R ⁴ are consistent with those described in the previous technical solution, and will not be repeated here.

In the present invention, more preferably, the obtained optically active 3-alkenyl-3 substituted oxindole compounds are selected from one or more of the following compounds:

In the present invention, after the above-mentioned reaction, it is preferable to carry out separation and purification treatment. In the present invention, the separation and purification method is not particularly limited, and it can be a conventional method well known to those skilled in the art. In the present invention, column chromatography, liquid chromatography, distillation and other liquid-liquid separation methods or recrystallization are preferred. The solid-liquid separation method is more preferably column chromatography. In the column chromatography, the eluent used is preferably a mixed solvent of ethyl acetate and petroleum ether; the volume ratio of ethyl acetate to petroleum ether is preferably 1: (2-10). In the present invention, more preferably, the reaction solution obtained by the reaction is firstly extracted with ethyl acetate, then back-extracted with saturated brine, spin-dried, and then separated by column chromatography. After the above post-treatment, optically active 3-alkenyl-3 substituted oxindole compounds were obtained.

In the present invention, the raw material of formula (II-1) corresponds to the product of formula (III-1), and the raw material of formula (II-2) corresponds to the product of formula (III-2). When inputting formula (II-1) raw material separately, obtain formula (III-1) product; When inputting formula (II-2) raw material separately, obtain formula (III-2) product; When inputting formula (II-1) simultaneously ) raw material and formula (II-2) raw material, obtain formula (III-1) product and formula (III-2) product simultaneously.

The present invention also provides an optically active indole compound, the optically active indole compound has a structure of formula (Ⅲ-1) and/or a structure of formula (Ⅲ-2):

Wherein, the types of R ¹ , R ² , R ² , and R ⁴ are consistent with those described in the previous technical solution, and will not be repeated here.

In the present invention, more preferably, the optically active 3-alkenyl-3 substituted oxindole compound is selected from one or more of the following compounds:

The technical solution provided by the invention has the following beneficial effects:

1. The catalyst provided by the present invention can prepare optically active 3-alkenes through the high enantioselectivity and diastereoselective asymmetric direct alkenylation of 3-alkenyl indole compounds to isatin-like compounds Base-3-substituted oxindole compounds, and simultaneously obtain higher enantioselectivity and diastereoselectivity; enantioselectivity reaches above 91% ee, diastereoselectivity dr>20:1, product The yield reaches more than 81%, and the purity reaches more than 99.9%. Compared with catalysts such as conventional Lewis acids, the catalyst provided by the invention has obvious improvements in selectivity and productivity.

2. The invention provides a preparation method of the catalyst, which can effectively synthesize the chiral copper-based catalyst and obtain high yield and high purity.

3. The present invention provides the application of catalysts in the catalytic synthesis of optically active indole compounds. For the first time, the compound of formula (C ₁ ) and/or formula (C ₂ ) is used as a catalyst for the catalytic synthesis of optically active indole compounds. Specific preparation of optically active 3-alkenyl-3-substituted oxindole by highly enantioselective and diastereoselective asymmetric direct alkenylation of 3-alkenylindole to isatinoid Compounds, and obtain good preparation effect.

4. The synthesis method of optically active indole compounds provided by the present invention can obtain optically active 3-alkenyl-3-substituted oxindole compounds with high enantioselectivity and diastereoselectivity, enantioselective The specificity reaches more than 91% ee, the diastereoselectivity dr>20:1, the product yield reaches more than 81%, and the purity reaches more than 99.9%. The obtained product is monochiral, and the chirality reaches more than 91%. The stereoselectivity of the product can still be maintained when the reaction is scaled up to the gram scale.

5. The optically active indole compound provided by the present invention is a new optically active indole compound not disclosed in the prior art. In the prior art, the oxindole compound has potential medicinal value and a natural product precursor, Therefore, the research on this kind of skeleton structure has practical value. The optically active indole compounds provided by the present invention are 3-alkenyl-3 substituted oxindole compounds, which enrich the types of indole compounds at the C3 position. Moreover, natural products and drug molecules generally have monochirality, but the chirality of the optically active indole compounds synthesized by the present invention reaches more than 91%, which is of great significance.

In order to further understand the present invention, the preferred embodiments of the present invention are described below in conjunction with examples, but it should be understood that these descriptions are only to further illustrate the features and advantages of the present invention, rather than limiting the claims of the present invention.

In the following examples, solvents were purchased from Sinopharm Group, and drug raw materials were purchased from Shanghai Beide Pharmaceutical Technology Co., Ltd. In the HPLC analysis, the silica gel plate used was purchased from Yantai Xinnuo Chemical Co., Ltd., and the pure n-hexane and isopropanol used in the chromatography were purchased from TEDIA Company. Room temperature means 25°C.

Raw Material Preparation Example 1: Preparation of Ligand L _1b

S1. Preparation of intermediate S1:

To a suspension of L-phenylalanine (3.0 g) (the solvent in the suspension is ethanol) was added dropwise SOCl ₂ at 0°C. After reacting for a while, the solvent was evaporated to give a white solid, which was further treated with saturated aqueous _Na2CO3 until the _pH reached 8-9. The mixture was extracted twice with ethyl acetate. The combined organic phases were dried over _{anhydrous Na2SO4} and the solvent was removed under reduced pressure to give pure (S)-ethyl-2-amino-3-phenylpropionate (3.395 g, 96%). A thoroughly dry two-neck round bottom flask was equipped with a reflux condenser, additional funnel and nitrogen inlet. Magnesium powder (1.5 g, 62 mmol) and 15 mL of tetrahydrofuran were then placed in the apparatus. A solution of p-bromotoluene (4.34 mL, 42 mmol) in tetrahydrofuran (25 mL) was added slowly. After the addition was complete, the mixture was refluxed for an additional 1 hour. After cooling to 0° C., a solution of ethyl (S)-2-amino-3-phenylpropanoate (2 g, 10.4 mmol) in tetrahydrofuran (10 mL) was added slowly, and the reaction mixture was further refluxed for 2 hours. The reaction was quenched with saturated aqueous NH4Cl at 0 °C. The solution was filtered and extracted with dichloromethane (25 mL x 3). The combined organic phases were dried over anhydrous _Na2SO4 and evaporated _under reduced pressure to give a yellow solid. The crude product was purified by crystallization from methanol to afford intermediate S ₁ (2.65 g, 81% yield) as a white solid.

S2. Preparation of ligand L _1b :

To a solution of intermediate S ₁ (0.5 mmol) in methanol (5 mL) was added salicylaldehyde derivative (0.5 mmol). The solution was stirred at room temperature for 2 hours, then the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (petroleum/ethyl acetate=10/1 as eluent) to obtain the corresponding Schiff base ligand (L _1b ) quantitatively.

The synthetic route of above steps S1～S2 is as follows:

Sample Characterization:

(1) Characterization of intermediate S1:

The intermediate product _S1 obtained in the raw material preparation example 1 is analyzed by nuclear magnetic resonance, and its hydrogen nuclear magnetic resonance spectrum is obtained, as shown in Figure 1. ¹ H NMR (400MHz, CDCl ₃ ): δ7.51-7.45(m, 4H), 7.30-7.26(m, 2H), 7.22-7.16(m, 3H), 7.13-7.10(m, 4H), 4.13- 4.10(m,1H),2.66(d,J=13.7Hz,1H),2.46-2.39(m,1H),2.29(s,3H),2.28(s,3H),1.21(br,2H);

Utilize nuclear magnetic resonance to analyze the intermediate product _S1 obtained in the raw material preparation example 1, obtain its carbon nuclear magnetic resonance spectrogram, as shown in Figure 2. ¹³ C NMR (100MHz, CDCl ₃ ): δ144.3, 141.8, 140.0, 136.4, 136.1, 129.3, 129.2, 129.1, 128.8, 126.5, 125.8, 125.4, 78.5, 58.3, 37.0, 21.1, 21.0; IR (film): 343 ,3391,3025,2923,2869,1602,1510,1453,1377,1174,813,782,734;

Using a mass spectrometer (Waters ^TM Q-TOF Premier) to analyze the intermediate product _S1 obtained in the raw material preparation example 1, the result obtained is HRMS (ESI) m/z, calcd for C ₂₃ H ₂₅ NO 331.1936, found 331.1933

(2) Characterization of Ligand L _1b :

The product L _1b obtained in the raw material preparation example 1 was analyzed by nuclear magnetic resonance, and its hydrogen nuclear magnetic resonance spectrum was obtained, as shown in FIG. 3 . ¹ H NMR (400MHz, CDCl ₃ ): δ13.97(br,1H),7.55-7.48(m,4H),7.32(d,J=8.3Hz,2H),7.20-7.10(m,5H),7.05 -6.97(m,5H),6.76(t,J=7.6Hz,1H),4.32(dd,J=10.3Hz,1.8Hz,1H),3.04(dd,J=13.8Hz,1.6Hz,1H), 2.84(dd,J=13.8Hz,10.3Hz,1H),2.80(s,1H),2.33(s,3H),2.22(s,3H);

The product L _1b obtained in the raw material preparation example 1 was analyzed by nuclear magnetic resonance, and its hydrogen nuclear magnetic resonance spectrum was obtained, as shown in FIG. 4 . ¹³ C NMR (100MHz, CDCl ₃ ): δ165.8, 160.4, 142.4, 141.3, 138.9, 136.9, 136.8, 135.3, 130.1, 129.8, 129.4, 129.2, 128.5, 126.6, 126.1, 125.9, 119.0, 119.6, 3 37.5, 21.1, 21.0; IR (film): 3584, 3430, 3027, 2925, 1634, 1508, 1455, 1332, 1154, 1120, 1078, 817, 753, 733;

The product L _1b obtained in the raw material preparation example 1 was analyzed by a mass spectrometer (Waters ^TM Q-TOF Premier), and the result was HRMS (ESI) m/z, calcd for C ₃₁ H ₂₈ F ₃ NO ₂ 503.2072, found 503.2069.

Example 1

Add copper bromide (2.2mg, 0.01mmol), ligand (L _1b , 5.0mg, 0.01mmol), ethanol (1.0ml), N-ethylmorpholine (2.5μl, 0.02 mmol), stirred and reacted at room temperature for 2 h to obtain a chiral copper-based catalyst complex (wherein the yield of the chiral copper-based catalyst C _1b was 100%, and the purity was 100%). Then, at 20°C, 3-alkenylindole (formula I-1, 33.0 mg, 0.15 mmol), N-benzyl isatin (formula II-1a, 23.7 mg, 0.1 mmol), after the reaction was completed (TLC tracking detection), the reaction solution containing optically active indole compounds was obtained. Sequentially extracted with ethyl acetate, back-extracted with saturated brine, dried over anhydrous sodium sulfate, and spin-dried the obtained residue with petroleum ether/ethyl acetate system (volume ratio of ethyl acetate to petroleum ether: 1:5) as washing The solvent was removed and passed through the column to obtain light yellow solid formula III-1a (40.6 mg, 91% ee, dr>20:1; yield 89%, purity 100%).

In the above preparation process, the synthetic route of catalyst is as follows:

In the resulting chiral copper-based catalyst complex, the single crystal structure of the chiral copper-based catalyst C _1b is shown in Figure 5, and the structural parameter information corresponding to the single crystal structure in Figure 5 can be found in Table 1 below.

The single crystal structure information of the chiral copper-based catalyst C _1b obtained in Table 1 Example 1

molecular formula C₆₂H₅₂Cu₂F₆N₂O₄ molecular weight 1130.14 Space group P.1 Z 4 a,A° 23.8750(9) b,A° 15.9632(4) c,A° 16.7720(5) a,° 90.00 β,° 111.60 γ,° 90.00 V,A^°3 5943.1(3) T, K 293 p,g/cm³ 1.328

In the above preparation process, the synthetic route of optically active indole compounds is as follows:

The product formula III-1a obtained in Example 1 was analyzed by nuclear magnetic resonance (Bruker AC-300FT), and its hydrogen nuclear magnetic resonance spectrum was obtained, as shown in FIG. 6 . ¹ H NMR (500MHz, CD ₃ OD) δ7.88 (d, J = 7.9Hz, 1H), 7.35 (dd, J = 7.3, 3.1Hz, 2H), 7.29–7.23 (m, 4H), 7.21 (ddd ,J=8.4,5.6,2.4Hz,1H),7.14(ddd,J=7.9,3.2,2.1Hz,2H),7.11–7.05(m,2H),7.05–7.00(m,2H),6.97(t ,J=7.4Hz,1H),6.78(s,1H),6.65(d,J=7.1Hz,2H),6.50(s,1H),6.40(d,J=7.8Hz,1H),4.75(d , J=15.8Hz, 1H), 3.84(d, J=15.8Hz, 1H).

The product formula III-1a obtained in Example 1 was analyzed by nuclear magnetic resonance, and its carbon nuclear magnetic resonance spectrum was obtained, as shown in FIG. 7 . ¹³ C NMR (125MHz, CD ₃ OD) δ178.2, 142.1, 139.5, 138.7, 137.5, 135.7, 133.6, 129.2, 128.7, 128.3, 127.2, 127.0, 127.0, 126.7, 125.8, 124.8, 124.4, 124.8, 124.8, 3, 120.0, 119.5, 118.0, 111.3, 109.3, 75.9, 43.0.

Using a mass spectrometer (Waters ^TM Q-TOF Premier) to analyze the product formula III-1a obtained in Example 1, and obtain the result HRMS (ESI) m/z, for C ₃₁ H ₂₄ N ₂ O ₂ [M+Na] ⁺ Calculated 479.1735, found 479.1728.

Among them, the chirality of the obtained product formula III-1a was characterized by high performance liquid chromatography (TLC method), and the result is shown in FIG. 8 , and its chirality reached 91%.

Example 2

According to Example 1, a chiral copper-based catalyst composite was prepared. Then, at 20°C, 3-alkenylindole (formula I-1, 33.0 mg, 0.15 mmol), N-allyl isatin (formula II-1b, 18.7 mg, 0.1 mmol), after the reaction was completed (TLC follow-up detection), a reaction solution containing optically active indole compounds was obtained. Sequentially extracted with ethyl acetate, back-extracted with saturated brine, dried over anhydrous sodium sulfate, and spin-dried the obtained residue with petroleum ether/ethyl acetate system (volume ratio of ethyl acetate to petroleum ether: 1:5) as washing The solvent was removed and passed through the column to obtain light yellow solid formula III-1b (37.7 mg, 91% ee, dr>20:1; yield 93%, purity 100%).

In the above preparation process, the synthetic route of optically active indole compounds is as follows:

The product formula III-1b obtained in Example 2 was analyzed by nuclear magnetic resonance (Bruker AC-300FT), and its hydrogen nuclear magnetic resonance spectrum was obtained, as shown in FIG. 9 . ¹ H NMR (500MHz, CD3OD) δ7.85 (d, J = 8.0Hz, 1H), 7.35 (dd, J = 10.9, 7.7Hz, 2H), 7.22–7.05 (m, 4H), 7.01 (dd, J =13.4,7.2Hz,3H),6.74(s,1H),6.63(d,J=7.1Hz,2H),6.51(d,J=7.8Hz,1H),6.49(s,1H),5.76–5.50 (m, 1H), 5.13 (ddd, J = 13.8, 11.6, 1.2Hz, 2H), 4.13–3.94 (m, 1H), 3.41 (dd, J = 16.4, 5.9Hz, 1H).

The product formula III-1b obtained in Example 2 was analyzed by nuclear magnetic resonance, and its carbon nuclear magnetic resonance spectrum was obtained, as shown in FIG. 10 . ¹³ C NMR (125MHz, CD3OD) δ177.7, 142.2, 139.4, 138.8, 137.5, 133.7, 131.3, 129.2, 128.8, 127.0, 126.7, 125.7, 124.8, 124.5, 124.2, 122.8, 121.5, 190.5, 118.0, 18 111.3, 109.2, 75.9, 41.7.

Using a mass spectrometer (Waters ^TM Q-TOF Premier) to analyze the product formula III-1b obtained in Example 2, and obtain the result HRMS (ESI) m/z, for C ₂₇ H ₂₂ N ₂ O ₂ [M+Na] ⁺ The calculated value of 425.1579, the found value of 429.1576.

Example 3

According to Example 1, a chiral copper-based catalyst composite was prepared. Then, at 20°C, 3-(4-methoxyphenyl)vinylindole (formula I-3, 38.0mg, 0.15mmol), N-allyl isatin were sequentially added to the above complex system (Formula II-1b, 18.7 mg, 0.1 mmol), after the reaction was completed (TLC tracking detection), a reaction solution containing optically active indole compounds was obtained. Sequentially extracted with ethyl acetate, back-extracted with saturated brine, dried over anhydrous sodium sulfate, and spin-dried the obtained residue with petroleum ether/ethyl acetate system (volume ratio of ethyl acetate to petroleum ether: 1:5) as washing The solvent was removed and passed through the column to obtain light yellow solid formula III-1c (40.5 mg, 91% ee, dr>20:1; yield 93%, purity 100%).

In the above preparation process, the synthetic route of optically active indole compounds is as follows:

The product formula III-1c obtained in Example 3 was analyzed by nuclear magnetic resonance (Bruker AC-300FT), and its hydrogen nuclear magnetic resonance spectrum was obtained, as shown in FIG. 11 . ¹ H NMR (500MHz, MeOD) δ7.82(d, J=8.0Hz, 1H), 7.35(t, J=7.2Hz, 2H), 7.17(t, J=7.6Hz, 1H), 7.12(t, J＝7.4Hz, 1H), 7.07(t, J＝7.4Hz, 1H), 7.02(t, J＝7.4Hz, 1H), 6.70(s, 1H), 6.66–6.31(m, 6H), 5.65( ddd,J=22.0,10.4,5.2Hz,1H), 5.19(d,J=17.3Hz,1H),5.12(d,J=10.3Hz,1H),4.08(dd,J=16.3,4.4Hz,1H ),3.74(s,3H),3.54(dd,J=16.3,5.5Hz,1H).

The product formula III-1c obtained in Example 3 was analyzed by nuclear magnetic resonance, and its carbon nuclear magnetic resonance spectrum was obtained, as shown in FIG. 12 . ¹³ C NMR (125MHz, MeOD) δ177.7, 158.6, 142.3, 139.1, 137.5, 133.8, 131.4, 131.2, 130.4, 128.8, 125.7, 124.9, 124.6, 124.2, 122.8, 121.4, 120.1, 114.3, 12.6, 118 111.3, 109.1, 75.9, 54.3, 41.8.

Using a mass spectrometer (Waters ^TM Q-TOF Premier) to analyze the product formula III-1c obtained in Example 3, and obtain the result HRMS (ESI) m/z, for C ₂₈ H ₂₄ N ₂ O ₃ [M+Na] ⁺ The calculated value of 459.1685, the found value of 459.1688.

Example 4

According to Example 1, a chiral copper-based catalyst composite was prepared. Then, at 20°C, 3-vinylindole (formula I-1, 33.0 mg, 0.15 mmol), 5-methyl-N-benzyl isatin (formula II-1c , 20.1 mg, 0.1 mmol), after the reaction was completed (TLC tracking detection), a reaction solution containing optically active indole compounds was obtained. Sequentially extracted with ethyl acetate, back-extracted with saturated brine, dried over anhydrous sodium sulfate, and spin-dried the obtained residue with petroleum ether/ethyl acetate system (volume ratio of ethyl acetate to petroleum ether: 1:5) as washing The solvent was removed and passed through the column to obtain light yellow solid formula III-1d (38.0 mg, 92% ee, dr>20:1; yield 81%, purity 100%).

In the above preparation process, the synthetic route of optically active indole compounds is as follows:

The product formula III-1d obtained in Example 4 was analyzed by nuclear magnetic resonance (Bruker AC-300FT), and its hydrogen nuclear magnetic resonance spectrum was obtained, as shown in FIG. 13 . ¹ H NMR (500MHz, MeOD) δ7.85(d, J=7.9Hz, 1H), 7.35(d, J=8.0Hz, 1H), 7.29-7.24(m, 4H), 7.23-7.20(m, 1H ),7.16–7.11(m,3H),7.09(t,J=7.5Hz,1H),7.02(t,J=7.4Hz,2H),6.87(d,J=7.9Hz,1H),6.75(s ,1H),6.67(d,J=7.3Hz,2H),6.53(s,1H),6.32(d,J=8.0Hz,1H),4.72(d,J=15.7Hz,1H),3.91(d ,J＝15.7Hz,1H),2.23(s,3H).

The product formula III-1d obtained in Example 4 was analyzed by nuclear magnetic resonance, and its carbon nuclear magnetic resonance spectrum was obtained, as shown in FIG. 14 . ¹³ C NMR (125MHz, MeOD) δ178.1, 139.7, 139.4, 138.9, 137.5, 135.9, 133.2, 132.5, 129.2, 128.9, 128.3, 127.1, 127.1, 127.0, 126.9, 125.7, 125.1, 124.4.9, 12 119.5, 118.1, 111.3, 109.0, 76.1, 43.0, 19.7.

Using a mass spectrometer (Waters ^TM Q-TOF Premier) to analyze the product formula III-1d obtained in Example 4, and obtain the result HRMS (ESI) m/z, for C ₃₂ H ₂₆ N ₂ O ₂ [M+Na] ⁺ The calculated value of 493.1892, the found value of 493.1885.

Example 5

According to Example 1, a chiral copper-based catalyst composite was prepared. Then, at 20°C, 3-vinylindole (formula I-1, 33.0 mg, 0.15 mmol), 5-methoxy-N-benzyl isatin (formula II- 1d, 20.1 mg, 0.1 mmol), after the completion of the reaction (TLC tracking detection), a reaction solution containing optically active indole compounds was obtained. Sequentially extracted with ethyl acetate, back-extracted with saturated brine, dried over anhydrous sodium sulfate, and spin-dried the obtained residue with petroleum ether/ethyl acetate system (volume ratio of ethyl acetate to petroleum ether: 1:5) as washing The solvent was removed and passed through the column to obtain light yellow solid formula III-1e (40.8 mg, 96% ee, dr>20:1; 84% yield, purity 100%).

In the above preparation process, the synthetic route of optically active indole compounds is as follows:

The product formula III-1e obtained in Example 5 was analyzed by nuclear magnetic resonance (Bruker AC-300FT), and its hydrogen nuclear magnetic resonance spectrum was obtained, as shown in FIG. 15 . ¹ H NMR (500MHz, MeOD) δ7.86 (d, J = 7.9Hz, 1H), 7.35 (d, J = 8.0Hz, 1H), 7.29–7.23 (m, 4H), 7.23–7.18 (m, 1H ),7.16–7.06(m,3H),7.01(t,J=7.6Hz,2H),6.95(d,J=2.5Hz,1H),6.76(s,1H),6.69(d,J=7.2Hz ,2H),6.59(dd,J=8.6,2.5Hz,1H),6.53(s,1H),6.31(d,J=8.6Hz,1H),4.73(d,J=15.7Hz,1H),3.88 (d,J=15.7Hz,1H),3.67(s,3H).

The product formula III-1e obtained in Example 5 was analyzed by nuclear magnetic resonance, and its carbon nuclear magnetic resonance spectrum was obtained, as shown in Figure 16 ¹³ C NMR (125MHz, MeOD) δ178.0, 156.6, 139.6, 138.8, 137.5, 135.8, 135.4, 134.4, 129.2, 128.3, 127.1, 127.1, 127.0, 126.7, 125.8, 124.9, 124.3, 121.5, 120.1, 119.6, 118.1, 113.6, 111.3, 111.2, 109.8, 76.3, 51.9, 4

Using a mass spectrometer (Waters ^TM Q-TOF Premier) to analyze the product formula III-1e obtained in Example 5, and obtain the result HRMS (ESI) m/z, for C ₃₂ H ₂₆ N ₂ O ₃ [M+Na] ⁺ The calculated value of 509.1841, the found value of 509.1838.

Example 6

According to Example 1, a chiral copper-based catalyst composite was prepared. Then, at 15°C, 3-(4-methylphenyl)vinylindole (formula I-2, 35.0mg, 0.15mmol), N-benzylisatinimine, and (Formula II-2a, 33.6 mg, 0.1 mmol), after the completion of the reaction (TLC tracking detection), a reaction solution containing optically active indole compounds was obtained. Sequentially extracted with ethyl acetate, back-extracted with saturated brine, dried over anhydrous sodium sulfate, and spin-dried the obtained residue with petroleum ether/ethyl acetate system (volume ratio of ethyl acetate to petroleum ether: 1:5) as washing The solvent was removed and passed through the column to obtain light yellow solid formula III-2a (55.7 mg, 97% ee, dr>20:1; yield 98%, purity 100%).

In the above preparation process, the synthetic route of optically active indole compounds is as follows:

The product formula III-2a obtained in Example 6 was analyzed by nuclear magnetic resonance (Bruker AC-300FT), and its hydrogen nuclear magnetic resonance spectrum was obtained, as shown in FIG. 17 . ¹ H NMR (500MHz, CDCl ₃ ) δ8.44(s, 1H), 7.57(d, J=7.9Hz, 1H), 7.34(d, J=7.3Hz, 2H), 7.29(d, J=8.0Hz ,2H),7.27(d,J=7.3Hz,2H),7.22–7.18(m,1H),7.14(t,J=7.4Hz,1H),7.09–7.01(m,2H),6.98(q, J＝8.0Hz, 4H), 6.90(t, J＝7.4Hz, 1H), 6.55(d, J＝2.6Hz, 1H), 6.44(d, J＝5.6Hz, 1H), 6.17(s, 1H) ,5.44(s,1H),4.73(s,1H),4.34(s,1H),2.34(s,3H),1.25(s,9H).

The product formula III-2a obtained in Example 6 was analyzed by nuclear magnetic resonance, and its carbon nuclear magnetic resonance spectrum was obtained, as shown in FIG. 18 . ¹³ C NMR (125MHz, CDCl ₃ ) δ176.1, 153.8, 142.3, 139.4, 137.1, 136.9, 135.8, 135.3, 132.4, 129.6, 128.8, 128.7, 128.4, 128.3, 127.4, 125.6, 125.0, 1224.8, 1224.8, ,120.5,120.4,119.7,111.6,109.0,80.1,63.6,44.1,28.1,21.3.

Using a mass spectrometer (Waters ^TM Q-TOF Premier) to analyze the product formula III-2a obtained in Example 6, and obtain the result HRMS (ESI) m/z, for C ₃₇ H ₃₅ N ₃ O ₃ [M+Na] ⁺ The calculated value of 592.2576, the found value of 592.2579.

Among them, the chirality of the obtained product formula III-2a was characterized by high performance liquid chromatography (TLC method), and the result is shown in FIG. 19 , and its chirality reached 91%.

Example 7

According to Example 1, a chiral copper-based catalyst composite was prepared. Then, at 15°C, 3-(4-methoxyphenyl)vinylindole (formula I-3, 38.0mg, 0.15mmol), N-benzylisatinidine, Amine (Formula II-2a, 33.6mg, 0.1mmol), after the completion of the reaction (TLC tracking detection), a reaction solution containing optically active indole compounds was obtained. Sequentially extracted with ethyl acetate, back-extracted with saturated brine, dried over anhydrous sodium sulfate, and spin-dried the obtained residue with petroleum ether/ethyl acetate system (volume ratio of ethyl acetate to petroleum ether: 1:5) as washing The solvent was removed and passed through the column to obtain light yellow solid formula III-2b (57.9 mg, 97% ee, dr>20:1; yield 99%, purity 100%).

In the above preparation process, the synthetic route of optically active indole compounds is as follows:

The product formula III-2b obtained in Example 7 was analyzed by nuclear magnetic resonance (Bruker AC-300FT), and its hydrogen nuclear magnetic resonance spectrum was obtained, as shown in FIG. 20 . ¹ H NMR (500MHz, CDCl ₃ ) δ8.51(s, 1H), 7.55(d, J=7.8Hz, 1H), 7.37(d, J=7.4Hz, 2H), 7.31(d, J=8.1Hz ,2H),7.28(d,J=7.2Hz,2H),7.22(t,J=7.2Hz,1H),7.15(t,J=7.2Hz,1H),7.11–7.03(m,2H),7.01 (d, J=8.5Hz, 2H), 6.93(t, J=7.4Hz, 1H), 6.71(d, J=8.7Hz, 2H), 6.59(d, J=2.6Hz, 1H), 6.49(d ,J＝6.2Hz,1H),6.17(s,1H),5.48(s,1H),4.77(s,1H),4.44(s,1H),3.81(s,3H),1.27(s,9H) .

The product formula III-2b obtained in Example 7 was analyzed by nuclear magnetic resonance, and its carbon nuclear magnetic resonance spectrum was obtained, as shown in FIG. 21 . ¹³ C NMR (126MHz, CDCl ₃ ) δ176.1, 159.0, 153.8, 142.3, 139.2, 136.9, 135.8, 132.4, 131.0, 130.6, 128.7, 128.4, 127.5, 127.5, 125.5, 125.1, 124.0, 1202.4, 1202.4, ,119.9,113.4,113.1,111.7,109.0,80.2,63.5,55.3,44.1,28.2.

Using a mass spectrometer (Waters ^TM Q-TOF Premier) to analyze the product formula III-2b obtained in Example 7, and obtain the result HRMS (ESI) m/z, for C ₃₇ H ₃₅ N ₃ O ₄ [M+Na] ⁺ The calculated value of 608.2525 and the found value of 608.2520.

Example 8

According to Example 1, a chiral copper-based catalyst composite was prepared. Then, at 15°C, 3-vinylindole (formula I-1, 33.0 mg, 0.15 mmol), 5-methyl N-benzyl isatinimine (formula II- 2b, 35.0 mg, 0.1 mmol), after the completion of the reaction (TLC tracking detection), a reaction solution containing optically active indole compounds was obtained. Sequentially extracted with ethyl acetate, back-extracted with saturated brine, dried over anhydrous sodium sulfate, and spin-dried the obtained residue with petroleum ether/ethyl acetate system (volume ratio of ethyl acetate to petroleum ether: 1:5) as washing The solvent was removed and passed through the column to obtain light yellow solid formula III-2c (54.0 mg, 99% ee, dr>20:1; yield 95%, purity 100%).

In the above preparation process, the synthetic route of optically active indole compounds is as follows:

The product formula III-2c obtained in Example 8 was analyzed by nuclear magnetic resonance (Bruker AC-300FT), and its hydrogen nuclear magnetic resonance spectrum was obtained, as shown in FIG. 22 . ¹ H NMR (500MHz, CDCl ₃ ) δ8.42(s, 1H), 7.62(d, J=7.9Hz, 1H), 7.40–7.30(m, 4H), 7.25–7.20(m, 3H), 7.17( t,J=7.4Hz,3H),7.13–7.06(m,2H),7.00(d,J=7.1Hz,2H),6.81(d,J=7.8Hz,1H),6.54(d,J=2.6 Hz,1H),6.32(d,J=7.0Hz,1H),6.29(s,1H),5.45(s,1H),4.72(s,1H),4.29(s,1H),2.19(s,3H ),1.30(s,9H).

The product formula III-2c obtained in Example 8 was analyzed by nuclear magnetic resonance, and its carbon nuclear magnetic resonance spectrum was obtained, as shown in FIG. 23 . ¹³ C NMR (125MHz, CDCl ₃ ) δ175.6, 153.6, 139.5, 139.2, 138.0, 136.6, 135.6, 131.8, 131.5, 129.2, 128.4, 128.3, 127.8, 127.3, 127.1, 127.1, 127.0, 1245.8, 124.8, ,120.1,119.7,119.3,111.3,108.5,79.9,63.2,43.7,27.9,20.7.

Using a mass spectrometer (Waters ^TM Q-TOF Premier) to analyze the product formula III-2c obtained in Example 8, and obtain the result HRMS (ESI) m/z, for C ₃₇ H ₃₅ N ₃ O ₃ [M+Na] ⁺ The calculated value of 592.2576, the found value of 592.2572.

In this paper, specific examples are used to illustrate the principles and implementation methods of the present invention. The descriptions of the above embodiments are only used to help understand the method of the present invention and its core idea, including the best mode, and also make any technology in the art Any person is capable of practicing the invention, including making and using any devices or systems, and performing any incorporated methods. It should be pointed out that for those skilled in the art, without departing from the principle of the present invention, some improvements and modifications can be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements close to the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal expressions of the claims.

Claims (8)

1. a synthetic method of optically active indole compound, is characterized in that, comprises the following steps: Under the action of a catalyst, the 3-alkenyl indole compound represented by the formula (I) reacts with the isatin-like compound to form an optically active 3-alkenyl-3 substituted oxindole compound; The isatin-like compound is a compound of formula (II-1) and/or a compound of formula (II-2); The optically active 3-alkenyl-3 substituted oxindole compound is a compound of formula (Ⅲ-1) and/or a compound of formula (Ⅲ-2);

in: ^R is selected from: hydrogen, alkyl or halogen; R ² and R ⁴ are each independently selected from: hydrogen, alkyl, halogen, nitro, trifluoromethyl; R ³ is selected from: allyl, phenyl, substituted or unsubstituted benzyl; The catalyst is a chiral copper-based catalyst; The chiral copper-based catalyst is a compound of formula (C ₁ ) and/or a compound of formula (C ₂ ):

in: Ar ¹ and Ar ² are each independently selected from: substituted or unsubstituted aryl groups. 2. The synthetic method according to claim 1, characterized in that, the 3-alkenylindole compounds shown in the formula (I) are selected from one or more of the following compounds:

3. The synthesis method according to claim 1, characterized in that the temperature of the reaction is 0-25°C. 4. The synthesis method according to claim 1, characterized in that the molar weight of the catalyst is 5% to 30% of the molar weight of the isatin-like compound. 5. The synthesis method according to claim 1, characterized in that the molar ratio of the isatin-like compound to the 3-alkenylindole compound represented by formula (I) is 1: (1-1.5). 6. The synthetic method according to claim 1, wherein, in Ar ¹ and Ar ² , the aryl is phenyl or naphthyl; in the substituted aryl, the substituent is selected from alkyl, alkane Oxygen or haloalkyl. 7. The synthetic method according to claim 1, wherein the chiral copper-based catalyst is selected from one or more of the following compounds:

8. An optically active indole compound prepared by the synthetic method described in any one of claims 1 to 7, characterized in that, the optically active indole compound has a structure of formula (III-1) and/or Or formula (Ⅲ-2) structure;

in: ^R is selected from: hydrogen, alkyl or halogen; R ² and R ⁴ are each independently selected from: hydrogen, alkyl, halogen, nitro, trifluoromethyl; R ³ is selected from: allyl, phenyl, substituted or unsubstituted benzyl.

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