Synthetic method of C3 axial chiral indole-p-benzoquinone derivative

Abstract

The invention discloses a synthesis method of a C3 axial chiral indole-p-benzoquinone derivative, and belongs to the technical field of organic asymmetric catalytic synthesis. According to the method, a chiral phosphoric acid bifunctional catalytic system is adopted, 3-indole-p-benzoquinone ester and an indole substrate are activated at the same time through a dynamic kinetic resolution strategy, remote functionalization reaction is achieved, and by means of the strategy, the yield of the 3-indole-p-benzoquinone ester is increased. A series of C3 axial chiral indole-p-benzoquinone derivatives are synthesized with good yield, medium regioselectivity and excellent enantioselectivity. The method disclosed by the invention is simple to operate, the reaction is carried out under relatively mild conditions, the yield is relatively high (72-85%), and the enantioselectivity is excellent (as high as gt; 99%, ee), the regioselectivity is good (9: 1rr), and the product is wide in application range and high in functional group compatibility. The invention provides an efficient method for constructing a C3 axial chiral indole skeleton, and the obtained chiral indole-p-benzoquinone derivative has important application value in drug synthesis and material science.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic asymmetric catalytic synthesis, and more particularly to a synthesis method of C3 axis chiral indole-p-benzoquinone derivatives. BACKGROUND

[0002] C3 axis chiral compounds of indole skeleton, as an important subclass of five-membered hetero-biaryl, are widely present in the core structures of various drug molecules with important biological activities. In glucocorticoid receptor antagonists, the structure plays a significant role in blood glucose regulation by regulating protein metabolism and gluconeogenesis; in HCV NS5B polymerase inhibitors, it exhibits excellent anti-hepatitis C virus activity. In addition, the unit of axis chiral indole compounds is also widely present in drug molecules with antioxidant, antibacterial and antitumor activities, and relevant research results have obtained many Chinese invention patents (CN117820316A, CN116768904A, etc.). In addition, C3 axis chiral indole derivatives also have important value in the field of asymmetric catalysis. They can be used as efficient chiral ligands (Tetrahedron: Asymmetry 1996, 7, 285-292) and organic catalysts (J. Org. Chem. 2018, 83, 10060-10069), and exhibit excellent stereocontrol ability in asymmetric Heck reaction, cross-coupling, C-H bond functionalization and hydrogenation reaction, etc. The multifunctionality of such compounds makes them important structural units in the fields of drug research and development and asymmetric synthesis.

[0003] In addition, the indole ring has unique reactivity, which can be used to change the electron density of the aromatic ring, adjust the steric hindrance, and enable them to participate in functionalization reactions as hydrogen bond donors.

[0004] Enantiomerically enriched axis chiral compounds are important backbones in natural substrates, biologically active compounds and material science, so catalytic asymmetric synthesis based on axis chiral compounds has attracted great interest in the chemical field. However, most of the constructed axis chiral backbones are six-membered (hetero) biaryl, which have relatively high rotational energy barrier and stable configuration. On the contrary, the catalytic asymmetric synthesis of axis chiral five-membered hetero-biaryl backbones is less studied, and the reason is that the distance between the ortho groups on both sides of the five-membered heteroaryl ring and the chiral axis is relatively far, the conformation is unstable, and the rotational energy barrier of the chiral axis is relatively low; if the steric hindrance of the ortho group is appropriately increased, the stability of the chiral axis can be improved, but it will also lead to the decrease of the activity of the reaction, so the asymmetric construction of axis chiral five-membered hetero-biaryl backbones has higher challenges. SUMMARY

[0005] The present application aims at overcoming the deficiencies of the prior art, and provides a synthesis method of C3 axis chiral indole-p-benzoquinone derivatives. The synthesis method of the present application is simple in operation, mild in reaction condition, high in reaction yield and excellent in enantioselectivity; the product of the present application has a wide range of applications, high yield and very good economic value. The C3 axis chiral indole derivative can be widely used as a chiral catalyst and a chiral ligand, and the strategy can be used to realize catalytic asymmetric synthesis of more axis chiral compounds.

[0006] In order to achieve the above-mentioned purpose, the present application adopts the following technical solutions:

[0007] The synthesis method of C3 axis chiral indole-p-benzoquinone derivatives comprises the following steps:

[0008] S1, weighing 3-indole-p-benzoquinone ester in a Schlenk reaction tube, adding a solvent to dissolve it to obtain a 3-indole-p-benzoquinone ester solution;

[0009] The 3-indole-p-benzoquinone ester is one of the following chemical structural formulas:

[0010] S2, adding a chiral phosphoric acid catalyst, an oxidizing agent and an indole substrate to the 3-indole-p-benzoquinone ester solution, stirring and reacting under an inert gas environment to obtain a reaction product;

[0011] The indole substrate is one of the following chemical structural formulas:

[0012] S3, after the reaction, the reaction system is concentrated under reduced pressure to remove the solvent to obtain a mixture, and the mixture is purified by column chromatography to obtain C3 axis chiral indole-p-benzoquinone derivatives in the form of two isomers as shown in formula (a) and formula (b);

[0013]

[0014] R 1 is one of hydrogen, methyl, fluorine, chlorine and bromine; R 2 is one of methyl, ethyl, isopropyl and benzyl; R 3 is one of methyl, ethyl, n-propyl, isopropyl, tert-butyl, isobutyl, n-butyl and benzyl; R 4 is one of hydrogen, fluorine, methyl, methoxy, chlorine and bromine; R 5 is one of tert-butyl, tert-pentyl and adamantyl.

[0015] Further, the chiral phosphoric acid catalyst is one of binaphthyl CPA or spiro chiral phosphoric acid CPA;

[0016] The binaphthyl CPA is one of the following chemical structural formulas: G1 is one of 2,4,6-(i-Pr)3C6H2, 4-ClC6H4, 9-anthryl, 2-naphthyl, SiPh3;

[0017] The spirochiral phosphoric acid CPA is one of the following chemical structural formulas: G2 is one of 4-ClC6H4, 4- t BuC6H4, SiPh3, 3,5-(t-Bu)2-4-OMeC6H2, 2,4,6-(Me)3C6H2.

[0018] Further, the oxidant is one of silver oxide, a combination of a compound as shown in formula Mn1 and tert-butyl hydroperoxide, (salen)Mn III Further, the oxidant is one of silver oxide, a combination of a compound as shown in formula Mn1 and tert-butyl hydroperoxide, (salen)Mn III Further, the oxidant is one of silver oxide, a combination of a compound as shown in formula Mn1 and tert-butyl hydroperoxide, (salen)Mn

[0019]

[0020] Further, the solvent is one of dichloromethane, toluene, acetonitrile, tetrahydrofuran and chloroform; the molar mass of 3-indoxyl-p-benzoquinone ester to the volume ratio of the solvent is 1:20.

[0021] Further, the reaction temperature is -20-25 DEG C. Further, the equivalent of the chiral phosphoric acid catalyst is 10-20 mol% based on the amount of substance of 3-indoxyl-p-benzoquinone ester. Further, the equivalent of the oxidant is 0.1-6 based on the amount of substance of 3-indoxyl-p-benzoquinone ester.

[0022] Further, the molar ratio of 3-indoxyl-p-benzoquinone ester to indole substrate is 1:1; the inert gas is N2; the reaction is monitored by thin layer chromatography, and when monitoring, the volume ratio of the developing agent petroleum ether to ethyl acetate is 3:1; when column chromatography is purified, the volume ratio of the eluent petroleum ether to ethyl acetate is 6:1.

[0023] In summary, the present application has the following beneficial effects:

[0024] The present application utilizes chiral phosphoric acid to simultaneously activate indoxyl-p-benzoquinone and nucleophilic reagent, realizes (dynamic) kinetic resolution of indoxyl-p-benzoquinone through remote functional group reaction, and directly catalyzes asymmetric synthesis of indoxyl-p-benzoquinone derivatives with C3 axis chirality. In the reaction, indoxyl-p-benzoquinone is not only an electrophile, but also an oxidant to oxidize the generated aromatic by-product phenol, and finally obtains stable quinone product, which has important application value in drug synthesis and material science. The present application has the following advantages:

[0025] (1) The synthesis method of the present application is simple in operation and mild in reaction condition.

[0026] (2) The product of the present application has a wide range of applications, high yield (72-85%), excellent enantioselectivity (up to >99%, ee), good regioselectivity (9:1 rr), strong functional group compatibility, and very good economic value.

[0027] (3) C3 axial chiral indole derivatives are widely used as chiral catalysts and chiral ligands, and this strategy can be used to achieve more catalytic asymmetric synthesis of axial chiral compounds. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 Reaction scheme for synthesizing C3 axial chiral indole-p-benzoquinone derivatives;

[0029] Figure 2 Chemical structure of the product synthesized in Example 1;

[0030] Figure 3 Chemical structure of the product synthesized in Example 2;

[0031] Figure 4 Chemical structure of the product synthesized in Example 3;

[0032] Figure 5 Chemical structure of the product synthesized in Example 4;

[0033] Figure 6 Chemical structure of the product synthesized in Example 5;

[0034] Figure 7 Chemical structure of the product synthesized in Example 6;

[0035] Figure 8 Chemical structure of the product synthesized in Example 7;

[0036] Figure 9 Chemical structure of the product synthesized in Example 8;

[0037] Figure 10 Chemical structure of the product synthesized in Example 9;

[0038] Figure 11 Chemical structure of the product synthesized in Example 10;

[0039] Figure 12 Chemical structure of the product synthesized in Example 11;

[0040] Figure 13 Chemical structure of the product synthesized in Example 12;

[0041] Figure 14Chemical structure of the product synthesized for Example 13;

[0042] Figure 15 Chemical structure of the product synthesized for Example 14;

[0043] Figure 16 Chemical structure of the product synthesized for Example 15;

[0044] Figure 17 Chemical structure of the product synthesized for Example 16;

[0045] Figure 18 Chemical structure of the product synthesized for Example 17;

[0046] Figure 19 Chemical structure of the product synthesized for Example 18;

[0047] Figure 20 Chemical structure of the product synthesized for Example 19;

[0048] Figure 21 Chemical structure of the product synthesized for Example 20;

[0049] Figure 22 Chemical structure of the product synthesized for Example 21;

[0050] Figure 23 Chemical structure of the product synthesized for Example 22;

[0051] Figure 24 Chemical structure of the product synthesized for Example 23;

[0052] Figure 25 Chemical structure of the product synthesized for Example 24;

[0053] Figure 26 Chemical structure of the product synthesized for Example 25;

[0054] Figure 27 Chemical structure of the product synthesized for Example 26;

[0055] Figure 28 Chemical structure of the product synthesized for Example 27;

[0056] Figure 29 Chemical structure of the product synthesized for Example 28;

[0057] Figure 30 Chemical structure of the product synthesized for Example 29;

[0058] Figure 31The chemical structural formula of the product synthesized for example 30 is shown in the following figure:

[0059] Figure 32 The chemical structural formula of the product synthesized for example 31 is shown in the following figure. DETAILED DESCRIPTION

[0060] The technical solutions in the embodiments of the present application will be clearly and completely described in combination with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the present application.

[0061] The reaction formula for synthesizing the C3 axis chiral indole-p-benzoquinone derivative according to the present application is shown in the following figure: Figure 1 The specific synthesis method comprises the following steps:

[0062] S1, weigh 3-indole-p-benzoquinone ester in a Schlenk reaction tube, and dissolve it in one of dichloromethane, toluene, acetonitrile, tetrahydrofuran and chloroform (the solvent is preferably dichloromethane); the molar mass of 3-indole-p-benzoquinone ester to the volume of the solvent is 1:20.

[0063] The 3-indole-p-benzoquinone ester is one of the following chemical structural formulas: In the formula, R 3 is one of methyl, ethyl, n-propyl, isopropyl, tert-butyl, isobutyl, n-butyl and benzyl; R 4 is one of hydrogen, fluorine, methyl, methoxy, chlorine and bromine; R 5 is one of tert-butyl, tert-pentyl and adamantyl.

[0064] S2, add a chiral phosphoric acid catalyst, an oxidizing agent and an indole product (the indole product is added in three batches within 12 hours) to the 3-indole-p-benzoquinone ester solution prepared in step S1, and stir the reaction under an inert gas environment (N2) at -20-25℃ (the reaction temperature can be selected as -20℃, -10℃, -5℃, 0℃, 5℃, 10℃, 25℃, and preferably -5℃), and the reaction end point is monitored by thin layer chromatography (the volume ratio of the developing agent petroleum ether and ethyl acetate is 3:1), to obtain a reaction product. The molar ratio of 3-indole-p-benzoquinone ester to indole product is 1:1.

[0065] The indole product is one of the following structural formulas: In the formula, R 1 is one of hydrogen, methyl, fluorine, chlorine and bromine; R 2 is one of methyl, ethyl, isopropyl and benzyl.

[0066] The chiral phosphoric acid catalyst is one of binaphthyl CPA or spiro chiral phosphoric acid CPA; the equivalent of the chiral phosphoric acid catalyst is 10-20 mol% based on the amount of substance of 3-indole-p-benzoquinone ester;

[0067] The binaphthyl CPA is one of the following chemical structural formulae: In the formula, G1 is one of 2,4,6,-(i-Pr)3C6H2, 4-ClC6H4, 9-anthryl, 2-naphthyl, SiPh3;

[0068] The spiro chiral phosphoric acid CPA is one of the following chemical structural formulae: In the formula, G2 is one of 4-ClC6H4, 4- t BuC6H4, SiPh3, 3,5-(t-Bu)2-4-OMeC6H2, 2,4,6-(Me)3C6H2; the equivalent of the spiro chiral phosphoric acid CPA is preferably one of 10 mol%, 15 mol%, 20 mol% (more preferably 20 mol%);

[0069] The oxidizing agent is one of silver oxide, a combination of a compound as shown in formula Mn1 and tert-butyl hydroperoxide, (salen)Mn III complex; the (salen)Mn III complex (i.e. (Schiff base)Mn III complex) is one of the compounds as shown in formula Mn1 to formula Mn6.

[0070]

[0071] The equivalent of the oxidizing agent is 0.1-6 based on the amount of substance of 3-indole-p-benzoquinone ester; when the oxidizing agent is one of the compounds as shown in formula Mn1 to formula Mn6, the equivalent is preferably one of 10 mol%, 20 mol%, 40 mol%, 60 mol%, 80 mol%, 100 mol%, and more preferably 20 mol%; when the oxidizing agent is a combination of a compound as shown in formula Mn1 and tert-butyl hydroperoxide, the equivalent of the compound as shown in formula Mn1 is preferably 60 mol%, and the equivalent of tert-butyl hydroperoxide is preferably 4.

[0072] S3, after the reaction, the reaction system is concentrated under reduced pressure to remove the solvent, and the mixture is purified by column chromatography (petroleum ether: ethyl acetate = 6:1) to obtain C3 axis chiral indole-p-benzoquinone derivatives as shown in formula (a) and formula (b) in the form of two isomers;

[0073]

[0074] In the formula, R 1 is one of hydrogen, methyl, fluorine, chlorine and bromine; R 2It is one of methyl, ethyl, isopropyl, and benzyl; R 3 It is one of methyl, ethyl, n-propyl, isopropyl, tert-butyl, isobutyl, n-butyl, and benzyl; R 4 It is one of hydrogen, fluorine, methyl, methoxy, chlorine, or bromine; R 5 It is one of tert-butyl, tert-pentyl, and adamantyl.

[0075] Examples 1 to 31

[0076] C3-axis chiral indole-p-benzoquinone derivatives were synthesized using the following method and the raw materials shown in Tables 1 to 5:

[0077] Accurately weigh 0.1 mmol of 3-indole-p-benzoquinone ester into a 10 mL dry Schlenk reaction tube using an analytical balance, and dissolve it in 2 mL of dichloromethane. Based on the amount of 3-indole-p-benzoquinone ester, add 20 mol% equivalent of spirocyclic chiral phosphate CPA (chemical structural formula: [missing information]) sequentially to the reaction system. G2 = 2,4,6-(Me)3C6H2), and 20 mol% equivalent of compounds of formula Mn1. Four equivalents of peroxytert-butanol and 0.2 mmol of indole product (added in three batches over 12 hours) were stirred at -5°C under N2 atmosphere. The reaction endpoint was monitored by thin-layer chromatography (eluent: petroleum ether: ethyl acetate, volume ratio: 3:1). The disappearance of the purple spot of 3-indole-p-benzoquinone ester indicated the end of the reaction. After the reaction, the solvent was removed by vacuum concentration using a rotary evaporator. The mixture was then purified by column chromatography (eluent: petroleum ether: ethyl acetate, volume ratio: 6:1) to obtain two isomers of C3-axis chiral indole-p-benzoquinone derivatives.

[0078] Table 1

[0079]

[0080]

[0081] Table 2

[0082]

[0083] Table 3

[0084]

[0085] Table 4

[0086]

[0087] Table 5

[0088]

[0089]

[0090] Example 1

[0091] The resulting products are labeled 3-1a and 4-1a, and have the structural formula as Figure 2 shown.

[0092] Purple solid; 37.8 mg; yield = 81%; m.p. 150.1-150.5 °C; rr = 3:1; [a] 20.0 D = 420.02 (c 0.005 CH2Cl2); HPLC (IG column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 20.62 min (major), t2= 24.82 min (minor), ee = 94%; minor product: t1= 12.27 min (minor), t2= 23.02 min (major), ee = 96%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.41 (d, J = 17.4 Hz, 1H), 8.29 (d, J = 12.5 Hz, 1H), 7.62 - 7.46 (m, 1H), 7.40 - 7.29 (m, 1H), 7.25 - 7.04 (m, 6H), 7.02 (s, 1H), 3.48 (d, J = 4.1 Hz, 3H), 2.39 (s, 2H), 2.27 (s, 1H), 1.40 (d, J = 4.8 Hz, 9H). 13 C NMR (101 MHz, CDC13) δ 187.1, 186.4, 184.4, 184.1, 164.8, 164.4, 145.3, 144.8, 143.1, 142.1, 141.9, 141.7, 139.9, 139.5, 137.9, 137.7, 135.5, 135.4, 134.6, 134.5, 132.0, 131.4, 128.4, 128.2, 127.5, 122.4, 122.0, 121.1, 120.1, 119.2, 119.1, 118.7, 118.6, 110.8, 110.4, 106.9, 106.3, 101.6, 101.0, 52.4, 33.6, 33.5, 30.6, 14.1, 14.0; HRMS (ESI) m / z calcd for C 29 H 26 N2O4Na [M + Na] + = 489.1791, found = 489.1785.

[0093] Example 2

[0094] The resulting products are labeled 3-1b and 4-1b and have the structure as shown Figure 3

[0095] Purple solid; 36.0 mg; yield = 75%; m.p. 153.6-153.9 °C; rr = 3:1; [a] 20.0 D = 1980.08 (c 0.005 CH2Cl2); HPLC (IG column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 12.85 min (major), t2= 19.32 min (minor), ee = 90%; minor product: t1= 10.16 min (minor), t2= 21.42 min (major), ee = 95%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.44 - 8.21 (m, 2H), 7.44 - 7.25 (m, 3H), 7.21 - 6.93 (m, 5H), 3.48 (d, J = 4.6 Hz, 3H), 2.42 (s, 2H), 2.40 (s, 1H), 2.35 (d, 2H), 2.24 (d, J = 3.3 Hz, 1H), 1.40 (d, J = 4.9 Hz, 9H). 13 CNMR (101 MHz, CDC13) δ 187.2, 186.5, 184.5, 184.2, 164.8, 164.5, 145.2, 143.2, 142.3, 141.9, 141.6, 139.9, 139.4, 138.2, 137.9, 134.6, 134.5, 133.8, 133.7, 131.8, 131.2, 130.5, 128.4, 128.2, 127.7, 123.9, 122.0, 120.1, 120.0, 118.9, 118.8, 118.7, 118.6, 110.5, 110.4, 106.6, 106.0, 101.6, 101.0, 52.4, 33.6, 33.5, 30.6, 21.7, 21.6, 14.2, 14.1; HRMS (ESI) m / z calcd for C 30 H 28 N2O4Na [M + Na] + = 503.1947, found = 503.1945.

[0096] Example 3

[0097] The resulting products are labeled 3-1c and 4-1c and have the structure as shown​Figure 4 as shown.

[0098] Purple solid; 36.8 mg; yield = 76%; m.p. 162.3-162.8 °C; rr = 2:1 ; [a] 20.0 D = 2660.11 (c 0.005 CH2Cl2); HPLC (IE column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 15.23 min (major), t2= 27.80 min (minor), ee = 90%; minor product: t1= 19.42 min (minor), t2= 52.68 min (major), ee > 99%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.54 (d, J = 16.1 Hz, 1H), 8.35 (d, J = 8.7 Hz, 1H), 7.38 - 7.29 (m, 1H), 7.25 - 7.01 (m, 5H), 6.96 - 6.80 (m, 2H), 3.48 (d, J = 1.9 Hz, 3H), 2.35 (s, 2H), 2.24 (s, 1H), 1.39 (d, J = 2.1 Hz, 9H). 13 C NMR (101 MHz, CDC13) δ 187.1, 186.5, 184.3, 184.0, 164.7, 164.4, 158.7 (d, J = 235.8 Hz), 145.4, 145.0, 142.8, 142.0, 141.9, 141.8, 139.9, 139.6, 139.4, 139.3, 134.6, 132.0, 131.9, 131.4, 128.4, 128.1, 122.1, 120.1, 118.6, 118.5, 111.6, 111.5, 110.5 (d, J = 26.0 Hz), 110.4, 107.1, 106.5, 106.4, 104.8, 104.6, 104.4, 101.4, 100.9, 52.4, 33.6, 33.5, 30.5, 14.1, 14.0; 19 F NMR (376 MHz, CDC13) δ -122.61. HRMS (ESI) m / z Calcd for C 29 H 25 FN2O6[M + Na] + = 507.1696 Found = 507.1683.

[0099] Example 4

[0100] The obtained products are labeled 3-1d and 4-1d, and have the structural formula as shown in Figure 5

[0101] Purple solid; 40.0 mg; yield = 80%; m.p. 158.9-159.2 °C; rr = 6:1; [a] 20.0 D = 1200.05 (c 0.005 CH2Cl2); HPLC (ID column, isopropanol / n-hexane = 5 / 95, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 37.23 min (major), t2= 58.55 min (minor), ee = 92%; minor product: t1= 32.04 min (minor), t2= 66.23 min (major), ee = 96%; two regioisomers not separated: 1 H NMR (400 MHz, DMSO-d6) δ 11.89 (s, 1H), 11.19 (s, 1H), 7.52 - 7.46 (m, 1H), 7.40 - 7.26 (m, 3H), 7.15 - 7.04 (m, 2H), 7.01 - 6.89 (m, 2H), 3.44 (d, J = 4.0 Hz, 3H), 2.46 (s, 3H), 1.36 (d, J = 7.1 Hz, 9H). 13 C NMR (101 MHz, DMSO-d6) δ 187.3, 186.7, 184.5, 184.0, 164.8, 164.5, 146.0, 145.6, 142.5, 141.7, 141.7, 140.6, 140.5, 139.9, 135.4, 134.5, 134.4, 132.4, 128.9, 128.4, 128.3, 125.1, 121.8, 121.4, 119.3, 119.2, 119.1, 119.0, 118.8, 113.0, 111.0, 106.3, 105.6, 100.7, 100.2, 52.5, 33.9, 30.6, 13.8, 13.7; H RMS (ESI) m / z Calcd for C 29 H 25 ClN2O4Na [M+Na] + = 523.1401, found = 523.1406.

[0102] Example 5

[0103] The obtained products are labeled 3-1e and 4-1e, and have the structural formula as shown in Figure 6

[0104] ​​Purple solid; 43.8 mg; yield = 81%; m.p. 149.1 - 149.6 °C; rr = 4:1 ; [a] 20.0 D = 980.04 (c 0.005 CH2Cl2); HPLC (IE column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 11.24 min (major), t2= 18.84 min (minor), ee = 92%; minor product: t1= 13.72 min (minor), t2= 32.95 min (major), ee = 98%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.60 (d, J = 15.7 Hz, 1H), 8.36 (s, 1H), 7.68 - 7.56 (m, 1H), 7.38 - 7.31 (m, 1H), 7.23 - 6.93 (m, 6H), 3.48 (d, J = 3.0 Hz, 3H), 2.33 (s, 2H), 2.22 (s, 1H), 1.40 (s, 9H). 13 C NMR (101 MHz, CDC13) δ 187.1, 186.5, 184.3, 184.0, 164.7, 164.4, 145.4, 145.0, 142.6, 142.0, 141.9, 141.7, 139.9, 139.4, 139.1, 138.8, 134.6, 134.6, 134.2, 134.1, 132.4, 131.8, 129.8, 129.1, 128.3, 128.1, 125.2, 125.1, 122.1, 121.7, 121.5, 120.2, 120.1, 118.6, 118.5, 115.4, 114.3 112.3, 110.5, 106.4, 105.8, 101.4, 100.8, 52.4, 33.6, 33.6, 30.6, 14.0, 13.8; HRMS (ESI) m / z calcd for C 29 H 25 BrN2O4Na [M + Na] + = 567.0896, found = 567.0894.

[0105] Example 6

[0106] The resulting products are labeled 3-1f and 4-1f, and have the structural formulas shown below. Figure 7

[0107] Purple solid; 43.8 mg; yield = 81%; m.p. 149.1 - 149.6 °C; rr = 4:1 ; [a]​20.0 D = 600.02 (c 0.005 CH2Cl2); HPLC (ID column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 37.55 min (major), t2= 44.09 min (minor), ee = 94%; minor product: t1= 17.20 min (minor), t2= 33.85 min (major), ee > 99%; two regioisomers not separated: 1 H NMR (400 MHz, DMSO-d6) δ 11.59 (d, J = 8.0 Hz, 1H), 11.21 (s, 1H), 7.39 - 7.22 (m, 3H), 7.19 - 7.04 (m, 2H), 6.98 - 6.84 (m, 3H), 3.44 (d, J = 2.1 Hz, 3H), 2.40 (d, 4H), 2.36 (d, J = 10.3 Hz, 2H), 1.36 (d, J = 5.7 Hz, 9H). 13 C NMR 101 MHz, DMSO-d6) δ 187.1, 186.9, 184.5, 184.3, 164.9, 164.6, 146.0, 145.6, 143.5, 142.5, 142.0, 141.8, 139.8, 139.3, 138.9, 138.8, 136.5, 136.4, 135.4, 131.2, 131.0, 128.4, 128.3, 125.5, 122.3, 121.4, 119.3, 118.8, 111.5, 111.1, 106.4, 105.6, 100.8, 100.3, 52.6, 52.5, 33.9, 33.8, 30.6, 21.7, 14.0, 13.9; HRMS (ESI) m / z calcd for C 30 H 29 N2O4[M+H] + = 481.2127, found = 481.2125.

[0108] Example 7

[0109] The resulting products are labeled 3-1g and 4-1g, and have the structural formulae as Figure 8 shown.

[0110] purple solid; 38.7 mg; yield = 80%; m.p. 143.1-143.6 °C; rr = 3:1; [a] 20.0 D= 360.01 (c 0.005 CH2Cl2); HPLC (IG column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 14.76 min (major), t2= 20.75 min (minor), ee = 94%; minor product: t1= 10.23 min (minor), t2= 19.20 min (major), ee = 96%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.38 (d, J = 17.7 Hz, 1H), 8.23 (s, 1H), 7.46 (m, J = 88.2, 46.6 Hz, 2H), 7.23 - 6.74 (m, 6H), 3.41 (d, J = 65.5 Hz, 3H), 2.40 (s, 1H), 2.29 (s, 2H), 1.35 (d, J = 39.0 Hz, 9H). 13 C NMR (101 MHz, CDC13) δ 187.0, 186.3, 184.3, 183.9, 164.6, 164.3, 158.6, 144.8, 142.7, 141.9, 139.5, 137.7, 135.3, 134.5, 132.3, 131.7, 128.4, 128.2, 123.9, 122.1, 120.1, 118.7, 118.5, 110.4, 109.5 (d, J = 24.2 Hz), 107.0, 101.5, 97.5, 97.2, 52.3, 33.6, 33.5, 30.6, 30.5, 14.1, 14.0; HRMS (ESI) m / z calcd for C 29 H 25 FN2O4Na [M + Na] + = 507.1696, found = 507.1679.

[0111] Example 8

[0112] The resulting products are labeled 3-1h and 4-1h, and have the structural formulas shown below. Figure 9

[0113] Purple solid; 40.5 mg; yield = 81%; m.p. 157.9 - 158.6 °C; rr = 3:1; [a] 20.0 D ​= 580.02 (c 0.005 CH2Cl2); HPLC (IG column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 18.61 min (major), t2= 28.06 min (minor), ee = 92%; minor product: t1= 11.28 min (minor), t2= 22.30 min (major), ee = 96%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.59 - 8.42 (m, 1H), 8.43 - 8.25 (m, 1H), 7.46 - 7.28 (m, 2H), 7.24 - 6.98 (m, 5H), 6.98 - 6.92 (m, 1H), 3.48 (d, J = 2.6 Hz, 3H), 2.31 (d, J = 12.3 Hz, 2H), 2.22 (d, J = 6.3 Hz, 1H), 1.39 (d, J = 4.2 Hz, 9H). 13 C NMR (101 MHz, CDC13) δ 187.1, 186.5, 184.3, 184.1, 164.7, 145.4, 145.0, 142.7, 141.8, 141.8, 139.9, 139.5, 138.6, 135.9, 135.8, 134.6, 132.3, 131.8, 128.4, 128.1, 128.0, 126.0, 122.1, 121.5, 120.2, 120.1, 119.9, 118.6, 118.5, 110.8, 110.5, 106.9, 106.3, 101.4, 100.9, 52.4, 33.6, 30.6, 13.9; HRMS (ESI) m / z calcd for C 29 H 25 ClN2O4Na [M + Na] + = 523.1401, found = 523.1409.

[0114] Example 9

[0115] The resulting products are labeled 3-1i and 4-1i, and have the structural formulas shown below. Figure 10

[0116] Purple solid; 42.4 mg; yield = 78%; m.p. 143.9-144.3 °C; rr = 4:1; [a] 20.0 D ​= 560.04 (c 0.005 CH2Cl2); HPLC (IE column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 17.88 min (major), t2= 23.07 min (minor), ee = 92%; minor product: t1= 12.57 min (minor), t2= 19.77 min (major), ee = 97%; two regioisomers not separated: 1 H NMR (400 MHz, DMSO-d6) δ 11.85 (s, 1H), 11.20 (s, 1H), 7.63 - 7.51 (m, 1H), 7.41 - 7.17 (m, 4H), 7.10 - 7.03 (m, 1H), 7.00 - 6.90 (m, 2H), 3.42 (d, 3H), 2.44 (s, 2H), 2.36 (s, 1H), 1.34 (s, 9H). 13 C NMR (101 MHz, DMSO-d6) δ 187.2, 184.2, 164.8, 164.5, 146.1, 141.8, 141.7, 140.0, 139.8, 136.9, 135.4, 132.3, 128.3, 126.7, 123.3, 121.5, 119.3, 118.9, 114.3, 114.0, 111.1, 105.9, 100.2, 52.6, 33.9, 33.8, 30.6, 13.8; HRMS (ESI) m / z calcd for C 29 H 25 BrN2O4Na [M+Na] + = 567.0896, found = 567.0894.

[0117] Example 10

[0118] The resulting products are labeled 3-1j and 4-1j, and have the structural formulas Figure 11 as shown.

[0119] Purple solid; 43.9 mg; yield = 79%; m.p. 132.0 - 132.6 °C; rr = 4:1; [a] 20.0 D=180.01 (c0.005CH2Cl2); HPLC (IB column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1 = 35.78 min (major), t2 = 44.00 min (minor), ee = 93%; minor product: t1 = 25.20 min (major), t2 = 33.48 min (minor), ee = 97%; two unseparated regioisomers: 1 H NMR(400MHz, CDCl3)δ8.30(d,J=21.8Hz,1H),8.11(d,J=16.2Hz,1H),7.47–7.05(m,10H),7.00–6.92(m,1H), 6.80–6.71(m,2H),5.06–4.78(m,2H),2.45(d,J=13.9Hz,5H),2.36(d,J=19.6Hz,1H),1.29(d,J=5.9Hz,9H). 13 C NMR (101MHz, CDCl3) δ187.1,186.3,183.9,164.2,145.1,144.7,142.3,141.7, 141.5,139.5,137.5,134.9,134.7,134.6,132.1,131.6,128.4,128.3,128.2,1 28.0, 127.1, 123.1, 122.1, 121.3, 120.2, 119.9, 118.9, 116.9, 116.8, 110.4, 106.9, 101.1, 67.3, 33.5, 33.4, 30.5, 16.6, 16.5, 14.3, 14.2; HRMS(ESI) m / z theoretical value C 36 H 32 N₂O₄Na[M+Na] + =579.2260, measured value =579.2267.

[0120] Example 11

[0121] The obtained products were labeled as 3-1k and 4-1k, with the following structural formulas: Figure 12 As shown.

[0122] Purple solid; 37.9 mg; yield = 79%; mp 138.6–138.9 °C; rr = 2:1; [α] 20.0 D= 380.04 (c 0.005 CH2Cl2); HPLC (ID column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 22.63 min (major), t2= 29.90 min (minor), ee = 93%; minor product: t1= 12.60 min (minor), t2= 20.28 min (major), ee = 96%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.66 - 8.47 (m, 1H), 8.44 - 8.30 (m, 1H), 7.59 - 7.45 (m, 1H), 7.39 - 7.30 (m, 1H), 7.22 - 6.97 (m, 7H), 3.46 (d, J = 3.7 Hz, 3H), 2.82 - 2.66 (m, 1H), 2.65 - 2.59 (m, 1H), 1.38 (d, J = 6.7 Hz, 9H), 1.29 - 1.23 (m, 2H), 1.21 - 1.16 (m, 1H). 13 C NMR (101 MHz, CDC13) δ 187.2, 186.4, 184.5, 184.1, 164.9, 164.5, 145.3, 144.9, 143.4, 143.1, 142.4, 142.1, 141.7, 140.0, 139.4, 135.6, 135.5, 134.7, 134.6, 132.2, 131.7, 128.4, 128.2, 127.4, 122.4, 122.0, 121.0, 120.1, 120.0, 119.3, 119.1, 118.7, 118.6, 111.0, 110.5, 105.4, 101.0, 52.4, 33.6, 33.5, 30.6, 30.5, 21.1, 21.0, 13.9, 13.8; HRMS (ESI) m / z calcd for C 30 H 28 N2O4Na [M + Na] + = 503.1947, found = 503.1944.

[0123] Example 12

[0124] The resulting products are labeled 3-1l and 4-1l, and have the structural formulas shown below. Figure 13

[0125] Purple solid; 39.5 mg; yield = 80%; m.p. 152.4 - 152.8 °C; rr = 2:1; [a] 20.0 D ​= 340.01 (c 0.005 CH2Cl2); HPLC (ID column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 16.32 min (major), t2= 23.00 min (minor), ee = 94%; minor product: t1= 9.83 min (minor), t2= 14.23 min (major), ee = 95%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.44 (d, J = 19.6 Hz, 1H), 8.25 (d, J = 13.3 Hz, 1H), 7.56 - 7.47 (m, 1H), 7.38 - 7.29 (m, 2H), 7.25 - 7.02 (m, 6H), 3.49 (s, 1H), 3.48 (s, 2H), 3.27 - 3.05 (m, 1H), 1.40 (d, J = 9.7 Hz, 9H), 1.37 - 1.27 (m, 6H). 13 C NMR (101 MHz, CDC13) δ 187.2, 186.3, 184.5, 183.9, 164.8, 164.4, 147.0, 146.7, 145.2, 144.9, 143.4, 142.3, 142.1, 141.6, 140.0, 139.3, 135.5, 135.3, 134.6, 134.5, 132.8, 132.3, 128.4, 128.2, 127.4, 122.4, 122.0, 120.9, 120.1, 119.3, 119.2, 118.7, 110.9, 110.4, 110.4, 105.3, 104.6, 101.6, 101.0, 52.4, 52.3, 33.6, 33.5, 30.6, 30.5, 26.8, 26.7, 23.1, 22.8, 22.7; HRMS (ESI) m / z calcd for C 31 H 30 N2O4[M+H] + = 533.1843, found = 533.1845.

[0126] Example 13

[0127] The obtained products are labeled 3-1m and 4-1m, and the structural formulas are shown as Figure 14

[0128] Purple solid; 40.2 mg; yield = 79%; m.p. 155.6 - 155.9 °C; rr = 2:1; [a] 20.0 D ​= 320.08 (c 0.005 CH2Cl2); HPLC (IE column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 8.78 min (major), t2= 15.95 min (minor), ee = 94%; minor product: t1= 9.99 min (minor), t2= 12.07 min (major), ee = 99%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.66 - 8.47 (m, 1H), 8.44 - 8.30 (m, 1H), 7.59 - 7.45 (m, 1H), 7.39 - 7.30 (m, 1H), 7.22 - 6.97 (m, 7H), 3.46 (d, J = 3.7 Hz, 3H), 2.82 - 2.66 (m, 1H), 2.65 - 2.59 (m, 1H), 1.38 (d, J = 6.7 Hz, 9H), 1.29 - 1.23 (m, 2H), 1.21 - 1.16 (m, 1H). 13 C NMR (101 MHz, CDC13) δ 187.2, 186.3, 184.5, 183.9, 164.8, 164.4, 147.2, 146.8, 145.2, 144.8, 143.5, 142.5, 142.0, 141.5, 140.0, 139.3, 134.6, 134.5, 133.7, 133.6, 132.6, 132.1, 130.5, 130.4, 128.4, 128.2, 127.6, 123.9, 122.0, 121.9, 120.0, 118.9, 118.7, 110.6, 110.4, 110.3, 104.9, 104.2, 101.7, 101.1, 52.3, 33.6, 33.5, 30.6, 30.5, 26.8, 26.7, 23.1, 22.8, 22.7, 21.6; HRMS (ESI) m / z calcd for C 32 H 32 N2O4Na [M + Na] + = 531.2260, found = 531.2243.

[0129] Example 14

[0130] The resulting products are labeled 3-1n and 4-1n, and have the structural formulas shown below. Figure 15

[0131] Purple solid; 38.4 mg; yield = 75%; m.p. 146.7 - 147.2 °C; rr = 2:1; [a] 20.0 D ​= 240.01 (c 0.005 CH2Cl2); HPLC (IE column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 10.01 min (major), t2= 17.79 min (minor), ee = 93%; minor product: t1= 10.99 min (minor), t2= 16.65 min (major), ee > 99%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.70 - 8.50 (m, 1H), 8.32 (d, J = 11.6 Hz, 1H), 7.39 - 7.25 (m, 2H), 7.21 - 7.03 (m, 4H), 6.99 - 6.84 (m, 2H), 3.49 (d, J = 1.9 Hz, 3H), 3.26 - 3.01 (m, 1H), 1.40 (s, 6H), 1.38 (s, 3H), 1.35 - 1.31 (m, 3H), 1.28 - 1.25 (m, 3H). 13 C NMR (101 MHz, CDC13) δ 187.1, 186.3, 184.4, 183.8, 164.7, 164.4, 159.8, 157.5, 148.6, 148.3, 145.3, 144.9, 143.1, 142.1, 142.0, 141.7, 139.9, 139.3, 134.6, 134.5, 132.8, 132.3, 131.9, 131.8, 128.3, 128.2, 128.0, 127.9, 122.1, 120.1, 118.7, 118.6, 111.7, 111.6, 110.7, 110.4, 105.5, 104.8, 104.7, 104.5, 104.4, 101.5, 100.9, 52.4, 33.6, 33.5, 30.6, 30.5, 26.8, 26.7, 22.9, 22.7, 22.6. 19 F NMR (376 MHz, CDC13) δ -122.61, -122.67; HRMS (ESI) m / z Calcd for C 31 H 29 FN2O4Na [M + Na] + = 535.2009, Found = 535.2010.

[0132] Example 15

[0133] The resulting products are labeled 3-1o and 4-1o, and have the structural formulas as Figure 16 shown.

[0134] Purple solid; 40.1 mg; yield = 74%; m.p. 139.6-140.0 °C; rr = 3:1 ; [a] 20.0 D = 430.09 (c 0.005 CH2Cl2); HPLC (IG column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 23.52 min (major), t2= 25.61 min (minor), ee = 94%; minor product: t1= 12.38 min (minor), t2= 20.76 min (major), ee = 95%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.21 (d, J = 10.4 Hz, 2H), 7.68 - 7.51 (m, 1H), 7.42 - 7.27 (m, 6H), 7.26 - 7.01 (m, 7H), 4.21 (s, 1H), 4.09 (s, 1H), 3.50 (d, J = 3.4 Hz, 3H), 1.40 (d, J = 9.7 Hz, 9H). 13 C NMR (101 MHz, CDC13) δ 187.0, 183.8, 164.6, 145.3, 141.8, 141.5, 139.9, 139.5, 137.6, 135.5, 134.5, 132.6, 132.3, 129.3, 129.1, 129.0, 128.2, 127.5, 127.2, 122.7, 122.0, 121.2, 120.1, 120.0, 119.3, 118.8, 118.7, 111.0, 110.3, 106.5, 101.0, 77.4, 77.3, 77.1, 76.7, 52.3, 34.4, 34.1, 33.6, 33.5, 30.6, 30.5; HRMS (ESI) m / z calcd for C 35 H 30 N2O4Na [M + Na] + = 565.2104, found = 565.2100.

[0135] Example 16

[0136] The resulting products are labeled 3-1p and 4-1p, and have the structural formulas shown below. Figure 17

[0137] Purple solid; 40.1 mg; yield = 74%; m.p. 139.6-140.0 °C; rr = 3:1 ; [a] 20.0 D ​= 320.01 (c 0.005 CH2Cl2); HPLC (IE column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 10.78 min (major), t2= 21.75 min (minor), ee = 88%; minor product: t1= 8.96 min (minor), t2= 15.20 min (major), ee = 94%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.65 (d, J = 15.7 Hz, 1H), 8.36 (d, J = 5.4 Hz, 1H), 7.57 - 7.28 (m, 2H), 7.26 - 6.91 (m, 6H), 4.04 - 3.89 (m, 2H), 2.34 (s, 2H), 2.24 (s, 1H), 1.41 (d, J = 1.8 Hz, 9H), 0.82 - 0.69 (m, 3H). 13 C NMR (101 MHz, CDC13) δ 187.2, 186.6, 184.4, 184.1, 164.2, 163.9, 145.2, 144.9, 142.6, 141.7, 141.6, 139.9, 139.4, 139.3, 138.9, 134.6, 134.5, 133.9, 133.8, 132.3, 131.8, 128.6, 128.5, 128.3, 126.7, 122.5, 122.1, 120.1, 120.0, 118.9, 118.7, 118.5, 111.9, 110.4, 106.5, 105.9, 101.5, 100.9, 61.6, 35.6, 33.6, 33.5, 30.6, 25.5, 24.2, 13.9, 13.4; HRMS (ESI) m / z calcd for C 30 H 27 ClN2O4Na [M + Na] + = 537.1557, found = 537.1562.

[0138] Example 17

[0139] The resulting products are labeled 3-1q and 4-1q, and have the structural formulas shown below. Figure 18

[0140] Purple solid; 40.6 mg; yield = 79%; m.p. 139.8-140.3 °C; rr = 3:1; [a] 20.0 D ​= 380.15 (c 0.005 CH2Cl2); HPLC (IE column, isopropanol / n-hexane = 20 / 80, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 4.67 min (major), t2= 6.51 min (minor), ee = 94%; minor product: t1= 5.43 min (minor), t2= 9.22 min (major), ee > 99%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.60 (d, J = 16.7 Hz, 1H), 8.34 (d, J = 5.3 Hz, 1H), 7.55 - 7.43 (m, 1H), 7.39 - 7.32 (m, 1H), 7.26 - 7.00 (m, 5H), 6.97 (s, 1H), 3.95 - 3.82 (m, 2H), 2.35 (s, 2H), 2.24 (s, 1H), 1.40 (d, J = 9.2 Hz, 9H), 1.27 - 1.18 (m, 2H), 0.68 - 0.54 (m, 3H). 13 C NMR (101 MHz, CDC13) δ 187.2, 186.0, 184.4, 184.1, 164.4, 164.0, 145.3, 144.9, 142.6, 141.7, 141.6, 141.4, 139.9, 139.5, 139.3, 138.9, 134.6, 134.5, 133.9, 133.8, 132.3, 131.9, 128.5, 128.3, 126.7, 122.6, 122.1, 120.1, 118.9, 118.7, 118.5, 111.9, 110.5, 106.5, 105.9, 101.0, 67.3, 33.6, 33.5, 30.6, 21.5, 13.9, 13.8, 10.0; HRMS (ESI) m / z calcd for C 32 H 29 ClN2O4Na [M + Na] + = 551.1714, found = 551.1707.

[0141] Example 18

[0142] The resulting products are labeled 3-1r and 4-1r, and have the structural formulas shown below. Figure 19

[0143] Purple solid; 43.8 mg; yield = 83%; m.p. 141.1 - 141.7 °C; rr = 4:1; [a] 20.0 D ​= 460.02 (c 0.005 CH2Cl2); HPLC (IG column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 8.79 min (major), t2= 19.68 min (minor), ee = 92%; minor product: t1= 7.89 min (minor), t2= 12.

[0144] t1= 8.79 min (major), t2= 19.68 min (minor), ee = 92%; minor product: t1= 7.89 min (minor), t2= 12.

[0145] 63 min (major), ee > 99%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.51 (d, J = 15.6 Hz, 1H), 8.25 (d, J = 6.8 Hz, 1H), 7.55 - 7.44 (m, 1H), 7.40 - 7.26 (m, 2H), 7.16 - 6.91 (m, 5H), 4.93 - 4.76 (m, 1H), 2.40 (s, 2H), 2.30 (s, 1H), 1.42 (s, 9H), 0.91 - 0.64 (m, 6H). 13 C NMR (101 MHz, CDC13) δ 187.3, 183.9, 163.6, 144.9, 141.6, 141.1, 140.0, 139.0, 134.5, 133.8, 132.4, 128.6, 128.4, 126.8, 122.6, 122.1, 119.9, 119.2, 118.8, 110.3, 106.1, 101.1, 69.5, 33.5, 30.6, 21.1, 20.8, 14.1; HRMS (ESI) m / z calcd for C 32 H 29 ClN2O4Na [M + Na] + = 551.1714, found = 551.1713.

[0146] Example 19

[0147] The resulting products are labeled 3-1s and 4-1s, and have the structural formulas shown. Figure 20

[0148] Purple solid; 43.4 mg; yield = 80%; m.p. 159.3 - 159.6 °C; rr = 3:1; [a] 20.0 D = 440.02 (c 0.005 CH2Cl2); HPLC (IE column, isopropanol / n-hexane = 20 / 80, flow rate 1.0 mL / min, λ = 254 nm), major product:

[0149] ​t1 = 9.66 min (major), t2 = 16.46 min (minor), ee = 92%; minor product: t1 = 12.53 min (minor), t2 = 2

[0150] 7.95 min (major), ee > 99%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.58 (d, J = 17.5 Hz, 1H), 8.30 (d, J = 6.0 Hz, 1H), 7.65 - 7.27 (m, 3H), 7.17 - 7.02 (m, 4H), 6.97 - 6.93 (m, 1H), 4.02 - 3.82 (m, 2H), 2.34 (s, 2H), 2.24 (s, 1H), 1.41 (s, 9H), 1.22 - 1.09 (m, 2H), 1.00 - 0.90 (m, 2H), 0.73 - 0.63 (m, 3H). 13 C NMR (101 MHz, CDC13) δ 187.2, 186.5, 184.4, 184.1, 164.4, 163.9, 145.2, 144.8, 142.5, 141.7, 141.5, 141.3, 139.9, 139.5, 139.2, 138.8, 134.6, 134.5, 133.9, 133.8, 133.2, 132.3, 131.9, 128.9, 128.6, 128.3, 126.8, 126.7, 124.6, 124.3, 122.6, 122.5, 122.1, 121.4, 120.1, 118.9, 118.8, 118.6, 113.7, 111.8, 111.5, 110.4, 108.6, 106.6, 105.9, 101.7, 101.1, 65.7, 65.5, 33.6, 33.5, 30.6, 30.2, 19.2, 18.7, 18.6, 14.4, 14.0, 13.9, 13.8, 13.5; HRMS (ESI) m / z calcd for C 33 H 31 ClN2O4Na [M + Na] + = 565.1870, found = 565.1865.

[0151] Example 20

[0152] The resulting products are labeled 3-1t and 4-1t, and have the structural formulas shown. Figure 21

[0153] Purple solid; 43.4 mg; yield = 80%; m.p. 120.6 - 121.1 °C; rr = 4:1; [a]​20.0 D = 580.02 (c 0.005 CH2Cl2); HPLC (IG column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), main product: t1 = 8.38 min (major), t2 = 12.90 min (minor), ee = 91%; minor product: t1 = 11.29 min (minor), t2 = 1

[0154] t1 = 8.38 min (major), t2 = 12.90 min (minor), ee = 91%; minor product: t1 = 11.29 min (minor), t2 = 1

[0155] 7.20 min (major), ee > 99%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.54 (s, 1H), 8.25 (s, 1H), 7.43 - 7.33 (m, 1H), 7.26 - 7.12 (m, 2H), 7.05 - 6.85 (m, 5H), 3.73 - 3.56 (m, 2H), 2.25 (s, 2H), 2.15 (s, 1H), 1.57 - 1.42 (m, 1H), 1.33 (s, 9H), 0.63 - 0.47 (m, 6H). 13 C NMR (101 MHz, CDC13) δ 187.2, 186.6, 184.4, 184.2, 164.4, 145.3, 144.9, 142.5, 141.7, 141.5, 141.3, 139.9, 139.4, 139.2, 138.9, 134.6, 134.6, 133.9, 133.8, 132.2, 131.9, 128.5, 128.3, 126.8, 122.6, 122.5, 122.1, 120.1, 118.8, 118.7, 111.9, 110.5, 106.6, 105.9, 101.7, 101.1, 71.8, 67.9, 33.6, 33.5, 30.6, 27.5, 18.7, 13.9; HRMS (ESI) m / z calcd for C 33 H 32 ClN2O4[M+H] + = 543.2050, found = 543.2056.

[0156] Example 21

[0157] The resulting products are labeled 3-1u and 4-1u, and have the structural formulas as Figure 22 shown.

[0158] purple solid; 40.7 mg; yield = 75%; m.p. 131.1 - 131.7 °C; rr = 6:1; [a] 20.0D = 180.04 (c 0.005 CH2Cl2); HPLC (IE column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 12.28 min (major), t2= 23.83 min (minor), ee = 94%; minor product: t1= 16.98 min (minor), t2= 40.45 min (major), ee > 99%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.38 (s, 1H), 8.18 (s, 1H), 7.59 - 7.49 (m, 1H), 7.37 - 7.27 (m, 2H), 7.24 - 6.94 (m, 5H), 2.47 (s, 3H), 1.42 (d, J = 3.7 Hz, 9H), 1.01 (s, 9H). 13 C NMR (101 MHz, CDC13) δ 187.6, 183.9, 163.1, 144.8, 140.6, 138.7, 134.5, 132.6, 128.7, 122.7, 122.0, 119.9, 119.5, 118.9, 111.7, 110.2, 101.3, 83.2, 77.4, 77.0, 76.7, 33.5, 30.6, 27.4, 14.2; HRMS (ESI) m / z calcd for C 33 H 32 ClN2O4[M+H] + = 543.2050, found = 543.2060.

[0159] Example 22

[0160] The resulting products are labeled 3-1v and 4-1v, and have the structural formulas shown below. Figure 23

[0161] Purple solid; 43.2 mg; yield = 75%; m.p. 156.3-156.6 °C; rr = 5:1; [a] 20.0 D = 980.07 (c 0.005 CH2Cl2); HPLC (IE column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 9.66 min (major), t2= 16.46 min (minor), ee = 91%; minor product: t1= 12.53 min (minor), t2= 27.95 min (major), ee > 99%; two regioisomers not separated: 1 ​H NMR (400 MHz, CDC13) δ 8.53 (d, J = 21.3 Hz, 1H), 8.19 (d, J = 9.5 Hz, 1H), 7.54 - 7.42 (m, 1H), 7.37 - 7.30 (m, 1H), 7.25 - 6.88 (m, 9H), 6.79 - 6.73 (m, 2H), 5.05 - 4.79 (m, 2H), 2.35 (s, 2H), 2.24 (s, 1H), 1.29 (d, J = 2.6 Hz, 9H). 13 C NMR (101 MHz, CDC13) δ 187.0, 184.3, 183.9, 164.1, 163.7, 145.3, 141.7, 139.5, 139.2, 138.8, 134.6, 134.5, 133.9, 133.8, 132.3, 131.9, 128.6, 128.3, 128.3, 128.1, 126.8, 122.6, 122.1, 120.2, 118.8, 118.8, 118.6, 110.5, 106.6, 105.9, 100.9, 67.4, 33.5, 33.4, 30.5, 14.1, 13.9; HRMS (ESI) m / z calcd for C 35 H 29 ClN2O4Na [M + Na] + = 599.1714, found = 599.1710.

[0162] Example 23

[0163] The obtained products are labeled 3-1w and 4-1w, and the structural formulas are shown as Figure 24

[0164] Purple solid; 43.7 mg; yield = 85%; m.p. 161.5 - 161.8 °C; rr = 6:1; [a] 20.0 D = 320.01 (c 0.005 CH2Cl2); HPLC (AD column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 17.67 min (major), t2= 30.78 min (minor), ee = 90%; minor product: t1= 12.52 min (minor), t2= 16.08 min (major), ee = 90%; two regioisomers not separated: 1 ​H NMR (400 MHz, CDC13) δ 8.38 (s, 1H), 8.11 (s, 1H), 7.54 (s, 1H), 7.25 - 7.09 (m, 4H), 7.02 - 6.92 (m, 2H), 3.52 (d, J = 3.1 Hz, 3H), 2.44 (d, J = 33.5 Hz, 5H), 2.37 (d, J = 5.2 Hz, 1H), 1.41 (s, 9H). 13 C NMR (101 MHz, CDC13) δ 187.0, 183.8, 164.6, 145.3, 141.9, 141.5, 139.8, 138.9, 133.8, 132.8, 132.6, 129.4, 128.6, 128.5, 126.9, 123.6, 122.7, 118.8, 118.3, 111.7, 110.0, 106.1, 100.5, 52.3, 33.6, 30.6, 21.5, 14.2; HRMS (ESI) m / z calcd for C 30 H 27 ClN2O4Na [M + Na] + = 537.1557, found = 537.1553.

[0165] Example 24

[0166] The obtained products are labeled 3-1x and 4-1x, and have the structural formulas as Figure 25 shown.

[0167] Purple solid; 39.8 mg; yield = 75%; m.p. 176.9 - 177.4 °C; rr = 5:1; [a] 20.0 D = 280.01 (c 0.005 CH2Cl2); HPLC (ID column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 21.58 min (major), t2= 25.36 min (minor), ee = 80%; minor product: t1= 19.69 min (minor), t2= 62.98 min (major), ee > 99%; two regioisomers not separated: 1H NMR (400MHz, CDCl3) δ8.52(d,J=12.1Hz,1H),8.21(d,J=7.7Hz,1H),7.53(s,1H),7.17–7.07(m,3H),6.98(d,J=2.2 Hz,1H),6.84–6.72(m,2H),3.81(s,2H),3.79(s,1H),3.52(d,J=3.3Hz,3H),2.40(s,2H),2.30(s,1H),1.39(s,9H). 13 C NMR (101MHz, CDCl3) δ 187.1, 183.9, 164.6, 154.4, 146.2, 141.8, 141.6, 139.7, 139.1, 133.8, 132.5, 129.6, 128.6, 126.8, 122.7, 118.8, 112.4, 112.2, 111.8, 111.2, 106.0, 100.8, 56.1, 56.0, 52.4, 33.6, 30.6, 14.1, 14.0; HRMS (ESI) m / z theoretical value C 30 H 27 ClN₂O₅N a[M+Na] + =553.1506, measured value =553.1509.

[0168] Example 25

[0169] The obtained products were labeled as 3-1y and 4-1y, with the following structural formulas: Figure 26 As shown.

[0170] Purple solid; 42.5 mg; yield = 82%; mp 173.2–173.9 °C; rr = 9:1; [α] 20.0 D =480.02 (c0.005CH2Cl2); HPLC (IE column, isopropanol / n-hexane = 20 / 80, flow rate 1.0 mL / min, λ = 254 nm), major product: t1 = 9.65 min (major), t2 = 12.92 min (minor), ee = 90%; minor product: t1 = 13.50 min (minor), t2 = 29.58 min (major), ee > 99%; two unseparated regioisomers: 1 H NMR (400MHz, CDCl3) δ8.46(s,1H),8.26(s,1H),7.58–7.44(m,1H),7.23–7.10(m,3H),7.06–6.83(m,3H),3.54(s,3H),2.45(s,3H),1.41(s,9H).13 C NMR (101 MHz, CDC13) δ 186.9, 183.7, 164.5, 158.2 (d, J = 235.0 Hz), 147.2, 141.6, 141.1, 140.1, 139.1, 133.8, 132.4, 130.9, 128.6, 126.9, 122.8, 118.8, 111.7, 111.2, 110.4 (d, J = 26.2 Hz), 106.0, 103.9, 103.7, 52.4, 33.7, 30.5, 14.2. 19 FNMR (376 MHz, CDC13) δ -123.79; HRMS (ESI) m / z Calcd for C 29 H 24 ClFN2O4Na [M + Na] + = 541.1307, found = 541.1301.

[0171] Example 26

[0172] The obtained products are labeled 3-1z and 4-1z, and the structural formulas are shown as Figure 27

[0173] Purple solid; 37.4 mg; yield = 75%; m.p. 170.1-170.5 °C; rr = 2:1; [a] 20.0 D = 350.05 (c 0.005 CH2Cl2); HPLC (IB column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 29.51 min (minor), t2= 32.38 min (major), ee = 90%; minor product: t1= 22.36 min (major), t2= 24.50 min (minor), ee = 83%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.52 (d, J = 19.0 Hz, 1H), 8.07 (d, J = 8.2 Hz, 1H), 7.22-7.18 (m, 1H), 7.18-6.90 (m, 5H), 6.90-6.81 (m, 1H), 3.51 (s, 3H), 2.46 (s, 3H), 2.36 (s, 2H), 2.25 (s, 1H), 1.42 (d, J = 1.8 Hz, 9H). 13 ​CNMR (101 MHz, CDC13) δ 187.1, 186.4, 184.4, 184.0, 164.7, 164.4, 158.7 (d, J = 235.9 Hz), 144.9, 144.5, 142.7, 142.1, 141.9, 141.8, 139.8, 139.5, 139.3, 134.1, 133.9, 132.0, 131.9, 131.8, 131.4, 128.1, 128.0, 127.9, 127.7, 122.8, 120.4, 119.6, 116.4, 116.3, 111.5, 111.4, 110.5 (d, J = 26.1 Hz), 106.5, 104.8, 104.7, 104.6, 104.4, 102.0, 101.5, 52.4, 33.6, 33.6, 30.6, 16.6, 14.1, 14.0. 19 F NMR (376 MHz, CDC13) δ -122.60, -122.63; HRMS (ESI) m / z calcd for C 30 H 27 F N2O4Na [M + Na] + = 521.1853, found = 521.1845.

[0174] Example 27

[0175] The obtained products are labeled 3-1aa and 4-1aa, and have the structural formula as Figure 28 shown.

[0176] Purple solid; 40.9 mg; yield = 79%; m.p. 168.4-168.8 °C; rr = 5:1; [a] 20.0 D = 480.01 (c 0.005 CH2CI2); HPLC (IB column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 33.98 min (minor), t2= 49.78 min (major), ee = 94%; minor product: t1= 20.64 min (major), t2= 23.67 min (minor), ee > 99%; two regioisomers not separated: 1H NMR (400 MHz, CDC13) δ 8.53 (d, J = 17.9 Hz, 1H), 8.42 (d, J = 7.1 Hz, 1H), 7.55 - 7.43 (m, 1H), 7.18 - 7.06 (m, 3H), 6.99 - 6.81 (m, 3H), 3.52 (d, J = 2.0 Hz, 3H), 2.41 (s, 2H), 2.31 (s, 1H), 1.43 (s, 9H). 13 CNMR (101 MHz, CDC13) δ 186.8, 183.7, 164.4, 146.1, 141.6, 141.1, 140.1, 139.1, 133.8, 132.3, 131.5 (d, J = 5.1 Hz), 128.6, 126.9, 124.6, 122.9, 122.7, 120.4, 118.8, 118.6, 114.5, 113.7, 111.8, 111.4, 107.1, 106.9, 105.9, 101.7, 52.5, 33.7, 33.6, 30.5, 14.5, 14.1. 19 F NMR (376 MHz, CDC13) δ -135.96, -136.01; HRMS (ESI) m / z Calcd for C 29 H 24 ClFN2O4Na [M + Na] + = 541.1307, found = 541.1300.

[0177] Example 28

[0178] The obtained products are labeled 3-1ab and 4-1ab, and the structural formulas are shown as Figure 29

[0179] Purple solid; 42.7 mg; yield = 80%; m.p. 175.4 - 175.9 °C; rr = 3:1; [a] 20.0 D = 430.01 (c 0.005 CH2Cl2); HPLC (IB column, isopropyl alcohol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1 = 40.33 min (minor), t2 = 61.55 min (major), ee = 87%; minor product: t1 = 19.87 min (major), t2 = 20.03 min (minor), ee = 90%; two regioisomers not separated: 1 ​H NMR (400 MHz, CDC13) δ 8.56 (d, J = 17.0 Hz, 1H), 8.33 (d, J = 7.5 Hz, 1H), 7.65 - 7.26 (m, 2H), 7.17 - 7.07 (m, 3H), 7.03 - 6.96 (m, 2H), 3.52 (d, J = 1.9 Hz, 3H), 2.38 (s, 2H), 2.28 (s, 1H), 1.44 (s, 9H). 13 CNMR (101 MHz, CDC13) δ 203.3, 186.8, 186.1, 184.1, 183.8, 164.5, 164.1, 157.8, 146.1, 145.8, 142.5, 141.7, 141.1, 140.9, 140.1, 139.6, 139.2, 138.9, 137.8, 134.5, 133.8, 133.8, 133.2, 132.3, 131.8, 129.6, 129.4, 128.5, 126.9, 125.4, 124.6, 124.4, 122.7, 122.6, 121.6, 121.5, 121.1, 121.0, 118.9, 118.8, 117.4, 117.3, 115.9, 113.7, 111.8, 111.5, 106.5, 105.9, 102.5, 101.9, 77.4, 77.3, 77.1, 76.8, 52.5, 33.7, 30.5, 25.1, 14.4, 14.1, 14.0; HRMS (ESI) m / z calcd for C 29 H 24 Cl2N2O4Na[M+Na] + = 557.1011, found = 557.1015.

[0180] Example 29

[0181] The resulting products are labeled 3-1 ac and 4-1 ac, and have the structural formulas shown below. Figure 30

[0182] Purple solid; 47.4 mg; yield = 82%; m.p. 170.9 - 171.6 °C; rr = 4:1; [a] 20.0 D ​= 220.01 (c 0.005 CH2Cl2); HPLC (IE column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 41.02 min (minor), t2= 65.30 min (major), ee = 90%; minor product: t1= 19.71 min (major), t2= 23.13 min (minor), ee = 98%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.65 (d, J = 16.6 Hz, 1H), 8.26 (d, 1H), 7.51 - 7.42 (m, 1H), 7.32 - 7.27 (m, 2H), 7.11 - 7.04 (m, 2H), 6.98 - 6.93 (m, 2H), 3.52 (s, 3H), 2.36 (s, 2H), 2.26 (s, 1H), 1.43 (s, 9H). 13 C NMR (101 MHz, CDC13) δ 203.3, 186.7, 183.8, 164.4, 157.7, 146.1, 145.7, 141.7, 140.9, 140.1, 139.2, 138.9, 137.8, 134.5, 133.8, 133.2, 132.3, 131.8, 129.1, 128.5, 128.3, 126.9, 125.4, 124.6, 124.5, 124.4, 122.7, 121.5, 121.4, 120.1, 118.9, 118.8, 118.6, 117.9, 113.7, 111.8, 111.5, 108.6, 105.9, 104.0, 102.1, 52.5, 33.7, 30.5, 25.1, 14.4, 14.1; HRMS (ESI) m / z calcd for C 29 H 25 ClBrN2O4[M+H] + = 579.0739, found = 579.0746.

[0183] Example 30

[0184] The resulting products were labeled 3-1ad and 4-1ad, and the structural formulas are shown below. Figure 31

[0185] Purple solid; 40.6 mg; yield = 79%; m.p. 135.4-135.7 °C; rr = 2:1; [a] 20.0 D ​= 920.04 (c 0.005 CH2Cl2); HPLC (IG column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1= 11.34 min (major), t2= 20.03 min (minor), ee = 88%; minor product: t1= 14.20 min (minor), t2= 38.35 min (major), ee > 99%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.44 (d, J = 18.4 Hz, 1H), 8.20 (d, J = 10.1 Hz, 1H), 7.55 - 7.44 (m, 1H), 7.39 - 7.27 (m, 2H), 7.20 - 7.04 (m, 4H), 7.00 - 6.95 (m, 1H), 3.49 (d, J = 2.8 Hz, 3H), 2.42 (s, 2H), 2.31 (s, 1H), 1.80 - 1.68 (m, 2H), 1.43 - 1.31 (m, 6H), 0.81 (dd, J = 9.8, 4.9 Hz, 3H). 13 C NMR (101 MHz, CDC13) δ 186.9, 183.8, 164.5, 144.2, 141.7 141.5, 139.7, 138.9, 137.7, 134.6, 133.8, 132.5, 128.6, 128.1, 126.9, 122.7, 122.4, 122.1, 121.5, 120.0, 119.0, 118.8, 118.7, 113.7, 111.7, 111.4, 110.3, 106.7, 106.1, 102.3, 52.4, 37.2, 36.8, 36.7, 28.1, 27.9, 27.7, 27.5, 14.1, 14.0, 9.2; HRMS (ESI) m / z calcd for C 30 H 27 ClN2O4Na [M + Na] + = 537.1557, found = 537.1551.

[0186] Example 31

[0187] The resulting products are labeled 3-1ae and 4-1ae, and have the structural formulas shown below. Figure 32

[0188] Purple solid; 46.3 mg; yield = 80%; m.p. 179.0 - 179.5 °C; rr = 6:1; [a] 20.0 D ​= 580.02 (c 0.005 CH2Cl2); HPLC (IB column, isopropanol / n-hexane = 10 / 90, flow rate 1.0 mL / min, λ = 254 nm), major product: t1 = 36.00 min (minor), t2 = 47.07 min (major), ee = 95%; minor product: t1 = 21.14 min (minor), t2 = 25.68 min (major), ee = 90%; two regioisomers not separated: 1 H NMR (400 MHz, CDC13) δ 8.41 (d, J = 14.3 Hz, 1H), 8.29 (s, 1H), 7.64 - 7.54 (m, 1H), 7.47 - 7.40 (m, 1H), 7.36 - 7.27 (m, 2H), 7.13 - 6.99 (m, 4H), 3.50 (s, 3H), 2.45 (s, 3H), 2.17 - 2.07 (m, 6H), 1.97 (d, J = 11.6 Hz, 3H), 1.77 (s, 6H). 13 C NMR (101 MHz, CDC13) δ 202.8, 187.1, 183.8, 164.6, 157.6, 145.4, 141.9, 141.5, 139.8, 138.9, 137.7, 134.3, 133.8, 133.2, 132.5, 128.6, 128.4, 128.2, 126.9, 125.5, 124.7, 124.4, 122.7, 121.9, 121.6, 120.4, 120.0, 119.1, 118.9, 118.6, 113.7, 111.7, 111.4, 109.0, 106.2, 100.6, 52.4, 42.4, 42.2, 36.5, 35.8, 29.7, 28.5, 25.1, 14.6, 14.2; HRMS (ESI) m / z calcd for C 35 H 32 ClN2O6[M+H] + = 579.2050, found = 579.2045.

[0189] The above only describes the preferred embodiments of the present application, the protection scope of the present application is not limited to the above-mentioned embodiments, any technical solutions falling within the concept of the present application shall fall within the protection scope of the present application. It should be noted that for ordinary skilled persons in the art, some improvements and refinements without departing from the principles of the present application shall also be considered as the protection scope of the present application.

Claims

1. A method for the synthesis of C3 axially chiral indole-p-benzoquinone derivatives, characterized in that, The method comprises the following steps: S1, weighing 3-indole-p-benzoquinone ester in a Schlenk reaction tube, adding a solvent to dissolve the 3-indole-p-benzoquinone ester to obtain a 3-indole-p-benzoquinone ester solution; 3-indole-p-benzoquinone ester is one of the following chemical structures: S2, adding a chiral phosphoric acid catalyst, an oxidant and an indole substrate to the 3-indole-p-benzoquinone ester solution, and stirring the reaction under an inert gas environment; The indole substrate is one of the following chemical structures: S3, after the reaction, the reaction system is concentrated under reduced pressure to remove the solvent to obtain a mixture, and the mixture is purified by column chromatography to obtain C3 axis chiral indole-p-benzoquinone derivatives in the form of two isomers as shown in formula (a) and formula (b); in the structural formula: R 1 is one of hydrogen, methyl, fluorine, chlorine and bromine; R 2 is one of methyl, ethyl, isopropyl and benzyl; R 3 is one of methyl, ethyl, n-propyl, isopropyl, tert-butyl, isobutyl, n-butyl and benzyl; R 4 is one of hydrogen, fluorine, methyl, methoxy, chlorine, bromine; R 5 is one of tert-butyl, tert-amyl, adamantyl.

2. The method of claim 1, wherein the C3 axial chiral indole-p-benzoquinone derivative is represented by the following formula: ###0002### 2 The solvent is one of dichloromethane, toluene, acetonitrile, tetrahydrofuran and chloroform; the molar mass of 3-indole-p-benzoquinone ester and the volume of the solvent are in a ratio of 1:

20.

3. The method of synthesis of C3 axis chiral indole-p-benzoquinone derivatives as claimed in claim 1 wherein, The chiral phosphoric acid catalyst is one of binaphthyl CPA or spiro chiral phosphoric acid CPA; The CPA of the linked naphthalene type is one of the following chemical structural formulas: G1is one of 2,4,6,-(i-Pr)3C6H2, 4-ClC6H4, 9-anthryl, 2-naphthyl, SiPh3. Spirochiral phosphoric acid CPA is one of the following chemical structural formula: G2 is 4-ClC6H4, 4- t BuC6H4, SiPh3, 3,5-(t-Bu)2-4-OMeC6H2, 2,4,6-(Me)3C6H2.

4. The method of synthesis of C3 axis chiral indole-p-benzoquinone derivatives as claimed in claim 1 wherein, The oxidizing agent is a combination of silver oxide, a compound of formula Mn1 and t-butyl hydroperoxide, (salen)Mn III One of the compounds of formulae Mn1 to Mn6; (salen)Mn III The complex is one of the compounds of formulae Mn1 to Mn6; (salen)Mn 5. The method for synthesizing a C3-axis chiral indole-p-benzoquinone derivative according to claim 1, characterized in that, The reaction temperature is -20-25℃.

6. The method of synthesis of C3 axial chiral indole-p-benzoquinone derivatives as claimed in claim 1 wherein, The molar ratio of 3-indole-p-benzoquinone ester and the indole substrate is 1:1; the inert gas is N2; the reaction is monitored by thin layer chromatography, and when monitoring, the volume ratio of the developing agent petroleum ether and ethyl acetate is 3:1; when purifying by column chromatography, the volume ratio of the eluent petroleum ether and ethyl acetate is 6:

1.

7. The method of synthesis of C3 axis chiral indole-p-benzoquinone derivatives as claimed in claim 3, wherein, The equivalent of the chiral phosphoric acid catalyst is 10-20 mol% based on the amount of substance of 3-indole-p-benzoquinone ester.

8. The method of synthesis of C3 axis chiral indole-p-benzoquinone derivatives as claimed in claim 4, wherein, The equivalent of the oxidant is 0.1-6 based on the amount of substance of 3-indole-p-benzoquinone ester.

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