Visible light induced tandem radical addition-cyclization reaction for construction of arylheterocyclic linked indolinone compounds and preparation method thereof

Abstract

The present application relates to the field of photocatalytic organic synthesis, and particularly to a visible light induced tandem radical addition-cyclization reaction for constructing an aromatic heterocycle linked indole ketone compound and a preparation method thereof.By introducing an unsaturated group at the ortho position of a ketoxime ester, a new intramolecular cyclization pathway is generated to realize the construction of a new aromatic heterocycle radical, and a preparation method of the aromatic heterocycle linked indole ketone compound is further provided, and the specific molecular structure is shown in the following formula (I). The present application has the advantages of easy availability of raw materials, simple operation, mild conditions, simple synthesis route, high synthesis efficiency, strong functional group adaptability of the substrate, potential application value in the biological and medical fields due to the particularity and designability of the aromatic heterocycle linked indole ketone structure.

Description

Technical Field

[0001] This invention relates to the field of photocatalytic organic synthesis, specifically to an aromatic heterocyclic linked indole ketone compound constructed by visible light-induced tandem radical addition-cyclization reaction and its preparation method. Background Technology

[0002] Heterocyclic compounds have attracted widespread attention due to their numerous important medical and biological applications. Research interest in heterocyclic compounds is rapidly increasing due to their extensive synthetic studies and functional applications. They are present in over 90% of new drugs and bridge the gap between biology and chemistry, two fields with so many scientific discoveries and applications. Heterocyclic compounds also play roles in various fields, including medicinal chemistry and biochemistry. Among them, heterocyclic compounds containing N and O atoms are widely found in nature and are common active pharmaceutical molecules in medicinal chemistry, possessing important physiological and pharmacological activities such as anti-inflammatory, antibacterial, anti-HIV, antihypertensive, and antitumor effects. With the increasingly widespread application of heterocyclic compounds, the need for their synthesis has grown significantly in recent years. Developing efficient, economical, and selective synthetic methods for highly heterocyclic compounds remains a goal pursued by many researchers.

[0003] The 4-chromone framework is an important structural entity belonging to the oxygen-containing heterocyclic class. It is a major structural unit in a large class of pharmaceutical compounds, and the synthesized compounds possess various significant biological and pharmaceutical activities, such as anti-inflammatory and anti-allergic activities, anti-platelet aggregation activities, and anti-cancer activities. In recent years, various methods have been established to prepare these structures. The most common method is the Michael addition reaction of hydroxyacetophenone or its condensation reaction with aldehydes, which suffers from drawbacks such as multiple steps, harsh reaction conditions, limited substrate scope, and low yield. Currently, photocatalytic radical tandem cyclization has become a highly efficient method for constructing the 4-chromone framework, and many studies have been reported. The reported photocatalytic radical tandem cyclization reaction for constructing the 4-chromone framework is illustrated below. Figure 1 As shown.

[0004] However, some shortcomings still exist. For example, in addition to photocatalysts, these reactions often require additional oxidants, reducing agents, acids, bases or other auxiliaries, and the reaction conditions may also require heating. These reaction conditions are still quite harsh and bring trouble to the reaction processing. Therefore, it is of great significance to develop more efficient and atom-economical methods to construct these superior scaffolds under mild and environmentally friendly conditions.

[0005] Oxime esters are a class of widely used photoinitiators, the most typical being the commercially available oxime ester initiators OXE-01 and OXE-02, and the allyl ketoxime ester AMO. The molecular structures of these three are shown in formulas (III) to (V), respectively:

[0006]

[0007] Indolones, as an important class of organic synthetic intermediates, have common and advantageous skeletal structures. Their derivatives are widely found in the structures of many natural crops, nerve inhibitors, and other drug molecules due to their physiological activities such as anti-ulcer, antihypertensive, and antiviral properties, as shown in formulas (VI) to (VIII). 1,3,3-Trimethylindoline-2-one,

[0008]

[0009] R = OMe,horsfiline, or: R = H,coerulescine

[0010] Convolutamydine A.

[0011] Conventional synthetic methods for indoleketone derivatives involve the synthesis of N-arylacrylamides under transition metal (Ru, Pd, Ni) catalysis. These methods typically require the pre-introduction of reactive groups such as halogens onto the aromatic ring. This limitation significantly restricts the range of substrates usable and increases costs. Indoleketone derivatives can also be synthesized via photocatalysis, but this method again requires the pre-introduction of iodine atoms onto the aromatic ring. Since iodoaryl hydrocarbons are both expensive and reactive, this presents challenges in terms of cost and raw materials. Therefore, the simple and economical organic synthesis of molecules with their skeletal structures is of great significance. Summary of the Invention

[0012] To address the shortcomings of existing technologies, the first objective of this invention is to propose oxime ester derivatives that can generate 4-substituted aryl heterocyclic radicals. These oxime esters can serve as radical sources, and after being sensitized by a photocatalyst, they rapidly undergo bond breaking and decarboxylation to generate ketone radicals, which then rapidly undergo intramolecular ring closure to generate novel aryl heterocyclic radicals, providing new ideas for the design of compounds containing aryl heterocyclic fragments.

[0013] The second objective of this invention is to provide a mild, universal, safe, simple, and economical synthetic method for such derivatives containing aryl heterocyclic fragments. Specifically, it involves the high-yield preparation of compounds with various aryl heterocyclic fragments via photocatalytic radical addition.

[0014] The third objective of this invention is to further react the obtained aryl heterocyclic radicals with the substrate N-phenyl-2-acrylamide and its derivatives to synthesize aryl heterocyclic linked indole ketones, whose unique skeletal structure endows them with potential for biopharmaceutical activity.

[0015] The schematic diagram of constructing the aryp-heterocyclic framework of the present invention is shown below. Figure 2 As shown, Figure 2 X can be O, N or S. When X is O, it is the construction method of 4-chromothion skeleton.

[0016] The present invention achieves its objective through the following technical solution:

[0017] A aryl heterocyclic linked indole ketone compound constructed by a visible light-induced tandem radical addition-cyclization reaction, characterized by the molecular structure shown in formula (I):

[0018]

[0019] The aryl heterocyclic linked indolone compound constructed by the visible light-induced tandem radical addition-cyclization reaction is characterized by: in formula (I):

[0020] R1, R2, R3, R4, R8, R9, R 10 and R 11 They are selected from any one of hydrogen, halogen atoms, -CN, -CF2CF3, -CF3, -NO2, OR, SR, SOR, SO2R, NRR', CH2OH, CH2OR, CH2OCOR, CH2SR, CH2SCOR, and CH2NRR' respectively;

[0021] R and R' are selected from either i or ii below:

[0022] i.C1~C 24 Straight-chain alkyl, C1-C 24 Branched alkyl, cycloalkyl, cyclohexylalkyl, and C6-C 24 Any one of alkylbenzenes,

[0023] ii. Any of the fluorocarbon chain structures formed by replacing hydrogen atoms with fluorine atoms in i above;

[0024] When R and R' are present at the same time, they form a 3- to 6-membered ring system or any one of benzo[a]aromatic ring, benzo[a]aromatic heterocycle and benzo[a]dioxane pentacyclic ring that forms a cyclic structure. One or more -CH2- in R and R' are independently replaced by any one of -O-, -N-, -S-, -CO-, -COO-, -OCO- and benzene ring.

[0025] R5 is selected from any one of alkyl, alkenyl and phenyl, wherein at least one -CH2- is replaced by any one of -O-, -N-, -S-, -CO-, -COO-, -OCO- and benzene ring, respectively;

[0026] R6 and R7 are selected from hydrogen atoms, alkyl groups and phenyl groups, respectively, wherein at least one -CH2- is independently replaced by any one of -O-, -N-, -S-, -CO-, -COO-, -OCO- and benzene rings;

[0027] X represents heteroatoms, including O, N, S, etc.

[0028] The method for preparing aryl heterocyclic linked indole ketone compounds constructed by visible light-induced tandem radical addition-cyclization reaction is characterized by: using a visible light-induced tandem radical addition-cyclization reaction, wherein reactant A and reactant B are mixed in solution and reacted for at least 12 hours under photocatalysis and irradiation with 460nm blue light emitted by an LED to generate product C, and the chemical equation for the reaction is shown in formula (II):

[0029]

[0030] In formula (II):

[0031] A is an N-arylacrylamide derivative, and the substrate for A can be any one of the following A1 to A11:

[0032]

[0033]

[0034] B is a ketoxime ester derivative with an allyl group at the ortho position, and the substrate for B can be any one of B1 to B12:

[0035]

[0036]

[0037]

[0038] Among A1~A11 and B1~B12:

[0039] R 12 and R 13 Select C1 to C 12The substituted alkyl, phenyl, benzyl, and R-substituted benzene ring are selected from any one of the following: alkyl, halogen, CN, NO2, CF3, R, OR, SR, SOR, SO2R, and NRR', wherein R and R' are selected to contain C1 to C2. 12 Straight-chain or branched alkyl groups or C6-C6 alkyl groups 12 Aryl, or containing C1 to C2 12 Straight-chain or branched alkyl groups or C6-C6 alkyl groups 12 The fluorocarbon chain structure formed by replacing hydrogen atoms with fluorine atoms in the aryl group, when R and R' are present at the same time, forms a 3- to 6-membered ring system. One or more -CH2- in R and R' are independently replaced by -O-, -N-, -S-, -CO-, -COO-, -OCO- or benzene rings.

[0040] The method for preparing aryl heterocyclic linked indole ketone compounds constructed by visible light-induced tandem radical addition-cyclization reaction is characterized by the following steps being carried out sequentially:

[0041] Take a stir bar, add 1 equivalent of a ketoxime ester derivative, 1-3 equivalents of a methacrylamide derivative, 0.05%mol-5%mol of photocatalyst, and an appropriate amount of solvent to the reactor, seal the reactor, and evacuate the reactor and refill it with nitrogen. React at a temperature of -10℃ to 50℃ for 12h to 36h.

[0042] After the reaction, the product was extracted with ethyl acetate or dichloromethane. The combined organic phases were washed with saturated brine, and the collected organic phase was further dried using anhydrous sodium sulfate. Then, the product was filtered and rotary evaporated to remove excess solvent, yielding a crude product. The crude product was then subjected to column chromatography using a mixture of petroleum ether and ethyl acetate as eluent. Finally, rotary evaporation yielded a product containing both aromatic heterocyclic rings and indoleone fragments. This product structure has significant application potential in the biological and pharmaceutical fields.

[0043] The method for preparing aryl heterocyclic linked indole ketone compounds constructed by visible light-induced tandem radical addition-cyclization reaction is characterized by:

[0044] The photocatalyst can be any one of Ir(ppy)3, fac-Ir(ppy)3 and Ru(bpy)3Cl2, with fac-Ir(ppy)3 being the preferred option;

[0045] The content of the photocatalyst is 1% mol;

[0046] The emission power of blue light is 0.2W / cm². 2 ~10W / cm 2 ;

[0047] The solvent can be any one of acetone, dichloroethane, acetonitrile, tetrahydrofuran, toluene, N,N-dimethylformamide and dioxane, with acetonitrile being the preferred option;

[0048] Stir at room temperature for 12 hours.

[0049] The method for preparing aryl heterocyclic linked indole ketone compounds constructed by visible light-induced tandem radical addition-cyclization reaction is characterized in that: the photocatalyst is fac-Ir(ppy)3; and the solvent is acetonitrile.

[0050] It is important to emphasize that the mechanism of this photocatalytic method involves the photocatalyst transferring an electron to the ketooxime ester via single-electron transfer under photoexcitation. During this single-electron transfer, the NO bond of the ketooxime ester dissociates to form an imine radical. This imine radical undergoes rapid C / C bond homolytic dissociation to generate an acyl radical, which preferentially undergoes intramolecular cyclization to form various novel carbon-centered radicals with aryl heterocyclic rings. These aryl heterocyclic radicals add to the unsaturated double bonds of the substrate and further cyclize to an aryl ring. Hydrogen migration then generates the final product, regenerating the photocatalyst.

[0051] The possible reaction mechanisms of selecting any one of substrates A1 to A11 and any one of substrates B1 to B12 are shown in equation (IX):

[0052]

[0053] The specific explanation is as follows: Under visible light irradiation, the excited fac-Ir(ppy)3 transfers one electron to the ketooxime ester (a) via single-electron transfer. During this single-electron transfer, the NO bond of the oxime ester dissociates to form an imine radical. The imine radical undergoes rapid homolytic dissociation of the C-C bonds to obtain an acyl radical (b), while simultaneously eliminating the CH3CN molecule. The acyl radical then rapidly undergoes intramolecular cyclization to obtain a 4-arphene-heterocyclic radical (c). Next, the 4-arphene-heterocyclic radical (c) adds to the substrate acrylamide derivative (d) and further cyclizes to the aryl ring (f). After hydrogen migration, the final product (g) is generated, and fac-Ir(ppy)3 is regenerated.

[0054] The raw materials of this invention are readily available, the operation is simple, the conditions are mild, the synthetic route is simple, the synthetic efficiency is high, and the substrate has strong functional group adaptability. Due to the special nature and designability of the aryl heterocyclic linked indole ketone structure, it has potential application value in the fields of biology and medicine. Attached Figure Description

[0055] Figure 1This is a schematic diagram of the reaction for constructing the 4-chromothion skeleton using photocatalytic radical tandem cyclization in existing technologies.

[0056] Figure 2 This is a schematic diagram of the construction of the aryl heterocyclic skeleton according to the present invention. Detailed Implementation

[0057] The following description elaborates on the above-mentioned technical solution of the present invention with reference to the specific reagents used and reaction conditions, and provides analytical data of the products prepared by the examples.

[0058] Example 1

[0059] According to the report in Prog.Org.Coat.2024, 189, 108290, taking the substrate with X=0 as an example, the preparation conditions are as follows:

[0060] Liao et al. reported that the prepared oximes were reacted with different acyl chlorides (1.5 equivalents) in triethylamine (1.5 equivalents) as an organic base in dichloromethane solvent to give a series of unsubstituted products B, as shown in formula (XII):

[0061]

[0062]

[0063] R1 and R2 are respectively taken from one of hydrogen, halogen atom, -CN, -CF2CF3, -CF3, -NO2, OR, SR, SOR, SO2R, NRR', CH2OH, CH2OR, CH2OCOR, CH2SR, CH2SCOR, and CH2NRR'.

[0064] For example, the preparation method of B1 involves R1=H reacting with 4-trifluoromethylbenzoyl chloride to obtain a white solid product. The analytical data are as follows:

[0065] 1 H NMR (400MHz, CDCl3) δ8.18(d,J=8.0Hz,2H),7.76(d,J=8.2Hz,2H),7.70(dd,J=7 .7,1.8Hz,1H),7.51(ddd,J=8.4,7.4,1.8Hz,1H),7.06(td,J=7.5,1.0Hz,1H),6 .98(d,J=8.4Hz,1H),5.95(ddt,J=17.3,10.7,5.4Hz,1H),5.32(dq,J=17.3,1.6 Hz, 1H), 5.20 (dq, J = 10.5, 1.3 Hz, 1H), 4.58 (dt, J = 5.5, 1.5 Hz, 2H), 2.38 (s, 3H).

[0066] 13 C NMR (101MHz, CDCl3) δ191.54,164.59,161.97,158.59,134.76,132.43,130. 79,130.06,126.71,125.73,125.70,121.22,118.21,113.30,69.71,13.18.

[0067] HRMS calcd.for C 20 H 16 NO4F3Na[M+Na] + :414.0929,found:414.0930.

[0068] Example 2

[0069] A1 and B1 react to produce C1, as shown in equation (XIII):

[0070]

[0071]

[0072] Take a 10 mL dry reaction tube, add a stir bar, 1-(2-(allyloxy)phenyl)-2-(((4-(trifluoromethyl)benzoyl)oxy)imino)prop-1-one (1a) (78.3 mg, 0.2 mmol, 1.0 equiv), 2-methyl-N-methyl-N-phenyl-2-acrylamide (1b) (52.6 mg, 0.3 mmol, 1.5 equiv), and fac-Ir(ppy)3 (1.3 mg, 0.002 mmol, 0.01 equiv), and add dry acetonitrile (2 mL). Evacuate the tube and refill with nitrogen. Repeat three times. Place the reaction tube under a 0.2 W blue LED lamp at room temperature and stir, using a fan for cooling. After stirring at room temperature for 12 h, detect the end of the reaction by thin-layer liquid chromatography. Extract with ethyl acetate (4 × 5 mL), combine the organic phases, and wash with saturated brine. The organic phase was collected, dried with anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation to obtain the crude product. The crude product was separated by column chromatography using a mixture of petroleum ether and ethyl acetate as eluent, and finally the product C1 was obtained by rotary evaporation with a yield of 81%, which was a white solid.

[0073] The data analysis is as follows:

[0074] 1H NMR(400MHz,CDCl3)δ7.81(ddd,J=10.2,7.9,1.6Hz,1H),7.42(dddt,J=8.8,7.2,3.6,1.8Hz,1H),7.27(d,J=8.0Hz,1H),7.25-7.22(m,1H),7.22-7.17(m,1H),7.09-7.02(m,1H),6.99-6.94(m,1H),6.92-6.87(m,1H),6.86-6z.80(m,1H),4.43(dt,J=11.5,4.3Hz,1H),4.13(ddd,J=21.3,11.4,9.5Hz,1H),3.20(d,J=2.4Hz,3H),2.59-2.49(m,1H),2.05-1.95(m,1.5H),1.86(td,J=12.8,4.4Hz,0.5H),1.64-1.54(m,0.5H),1.45-1.38(m,0.5H),1.36(d,J=3.6Hz,3H),1.23-1.15(m,0.5H),1.06(tdd,J=12.2,6.9,5.5Hz,0.5H)。

[0075] 13 C NMR(101MHz,CDCl3)δ194.08,193.75,180.31,180.25,161.43,161.39,161.37,143.25,143.23,143.20,143.17,143.15,135.95,135.56,133.44,133.30,128.13,128.10,127.69,127.66,127.47,127.45,127.37,127.35,127.22,127.12,122.83,122.35,121.60,121.10,120.57,120.43,117.90,117.48,108.32,107.92,70.58,70.33,70.10,69.93,48.36,48.14,45.91,45.72,45.69,45.49,35.91,35.10,26.30,26.15,24.24,24.07,23.80,23.62,21.31,21.24,20.94,20.91。

[0076] HRMS calcd.for C 21 H 21 NO3Na[M+Na] +:358.1419,found:358.1422.

[0077] Example 3

[0078] The reaction of A2 and B1 yields C2, as shown in equation (XIV):

[0079]

[0080] The preparation method for C2 is the same as that for product C1, except that the raw material A1 is replaced with A2. The yield is 84%, and it is a white solid. The analytical data are as follows:

[0081] 1 H NMR (400MHz, Chloroform-d) δ7.82 (td, J=8.0, 1.8Hz, 1H), 7.43 (dddd, J=8.6, 7.1, 3.2, 1.8Hz, 1H), 7.01-6.89 (m,4H),6.79-6.72(m,1H),4.47-4.42(m,1H),4.14(ddd,J=23.1,11.5,9.4Hz,1H),3.20(d,J=2.1Hz,3H),2.56 (ttd,J=9.4,7.0,6.5,4.6Hz,1H),2.11-1.91(m,1.5H),1.85(td,J=13.0,4.4Hz,0.5H),1.58(dddd,J=13.8,1 2.4, 5.8, 4.9Hz, 0.5H), 1.48-1.40 (m, 0.5H), 1.37 (d, J = 2.8Hz, 3H), 1.25-1.14 (m, 0.5H), 1.13-1.02 (m, 0.5H).

[0082] 13 C NMR (101MHz, CDCl3) δ193.89,193.60,179.94,179.87,161.44,161.37,160.70,160.6 6,158.30,158.27,135.76,127.35,127.27,121.41,121.36,117.67,117.66,114.21, 113.97,110.95,110.71,110.67,108.57,108.49,77.34,77.02,70.44,70.23,48.88,48.66,45.79,45.57,35.82,35.08,31.42,30.21,26.34,24.02,23.62,21.41,21.12.

[0083] HRMS: calcd.for C21 H 20 NO3FNa[M+Na] + :376.1325,found:376.1323.

[0084] Example 4

[0085] The reaction of A3 and B1 yields C3, as shown in equation (XV):

[0086]

[0087]

[0088] The preparation method of C3 is the same as that of product C1, except that the raw materials A1 and A3 are replaced with A3. The yield is 83%, and it is a white solid. The analytical data are as follows:

[0089] 1 H NMR (400MHz, CDCl3) δ7.85 (td, J=7.8, 1.8Hz, 1H), 7.46 (dddd, J=8.6, 7.2, 2.8, 1.8Hz, 1H), 7.31-7.26 (m, 1H), 7.26-7.23 (m, 1H), 7.19 (dd, J= 8.4,2.1Hz,1H),7.05-6.98(m,1H),6.97-6.91(m,1H),6.78(dd,J=8.3,6.5Hz,1H),4.47(ddd,J=11.5,4.6,1.5Hz,1H),4.17(ddd,J=20.6,11. 5,9.4Hz,1H),3.22(d,J=2.4Hz,3H),2.58(dtd,J=9.7,6.7,4.7Hz,1H),2.12-2.01(m,1H),2.01-1.93(m,1H),1.87(td,J=12.9,4.4Hz,0.5H), 1.60(td,J=7.3,3.8Hz,0.5H),1.51-1.43(m,0.5H),1.39(d,J=2.7Hz,3H),1.22(dddd,J=13.7,12.0,7.6,4.2Hz,0.5H),1.15-1.04(m,0.5H).

[0090] 13C NMR (101MHz, CDCl3) δ193.89,193.63,179.73,179.68,161.41,161.35,141.83,141. 78,135.80,135.24,135.07,128.18,128.08,127.89,127.37,127.29,123.16,123.1 2,121.44,121.40,120.52,120.41,117.69,117.67,109.03,109.02,70.39,70.25,48.65,48.44,45.77,45.58,35.75,35.12,26.35,26.32,24.03,23.63,21.34,21.13.

[0091] HRMS: calcd.for C 21 H 20 NO3NaCl[M+Na] + :392.1029,found:392.1034.

[0092] Example 5

[0093] The reaction of A4 and B1 yields C4, as shown in equation (XVI):

[0094]

[0095]

[0096] The preparation method for C4 is the same as that for product C1, except that the raw material A1 is replaced with A4, with a yield of 80%, and it is a white solid. The analytical data are as follows:

[0097] 1H NMR (400MHz, CDCl3) δ7.87-7.82(m,1H),7.50-7.43(m,1H),7.40(td,J=8.1,1.9Hz,1H),7.33-7.2 8(m,1H),7.01(t,J=7.5Hz,1H),6.93(t,J=7.3Hz,1H),6.73(dd,J=8.2,6.5Hz,1H),4.47(dd,J=11. 4,4.6Hz,1H),4.17(ddd,J=20.3,11.4,9.3Hz,1H),3.20(d,J=2.5Hz,3H),2.62-2.53(m,1H),2.01( dtd,J=26.2,12.9,8.4Hz,2H),1.86(td,J=12.9,4.3Hz,0H),1.66-1.41(m,1H),1.33-1.00(m,1H).

[0098] 13 C NMR (101MHz, CDCl3) δ193.84,193.60,179.58,179.54,161.39,161.33,14 2.32,142.27,135.80,135.63,135.46,130.79,127.35,127.28,125.84,12 1.42,120.50,120.40,117.67,115.47,115.36,109.57,70.35,70.24,48. 59,48.39,45.73,45.56,35.72,35.14,26.32,24.02,23.63,21.31,21.12.

[0099] HRMS calcd.for C 21 H 20 NO3NaBr[M+Na] + :436.0524,found:436.0523.

[0100] Example 6

[0101] C5 is obtained by reacting A5 and B1, as shown in formula (XVII):

[0102]

[0103] The preparation method of C5 is the same as that of product C1, except that the raw material A1 is replaced with A5. The yield is 82%, and it is a white solid. The analytical data are as follows:

[0104] 1H NMR (400MHz, CDCl3) δ7.82(t,J=8.5Hz,1H),7.42(t,J=7.9Hz,1H),6.97(td,J=7.6,3.7Hz,1H),6.90(dd,J=8.4,5.4Hz,1H),6.82(d ,J=9.6Hz,1H),6.80-6.60(m,2H),4.44(dd,J=11.6,4.6Hz,1H),4.15(dt,J=20.3,10.4Hz,1H),3.79(d,J=11.1Hz,3H),3.19(d,J=2 .5Hz,3H),2.54(dq,J=11.5,6.2Hz,1H),2.02(dtt,J=27.1,13.3,6.6Hz,1.5H),1.85(td,J=12.8,4.3Hz,0.5H),1.60(tt,J=12.0,5 .2Hz, 0.5H), 1.45 (dd, J=12.3, 6.4Hz, 0.5H), 1.37 (d, J=3.5Hz, 3H), 1.23 (d, J=21.9Hz, 0.5H), 1.07 (td, J=12.7, 12.2, 6.9Hz, 0.5H).

[0105] 13 C NMR (101MHz, CDCl3) δ194.02,193.72,179.99,179.93,161.43,161.38,156.23,156 .18,136.76,136.68,135.72,134.90,134.73,127.34,127.24,121.36,121.29,117. 68,111.99,111.88,110.32,110.20,108.39,108.37,70.44,70.28,55.83,55.78,48.84,48.62,45.84,45.60,35.88,35.12,26.31,26.29,24.20,23.79,21.42,21.15.

[0106] HRMS calcd.for C 22 H 23 NO4Na[M+Na] + :388.1525,found:388.1529.

[0107] Example 7

[0108] C6 is obtained by reacting A6 and B1, as shown in formula (XVIII):

[0109]

[0110] The preparation method for C6 is the same as that for product C1, except that raw material A1 is replaced with A6, with a yield of 84%, and it is a white solid. Analytical data are as follows:

[0111] 1 H NMR(400MHz,Chloroform-d)δ7.81(ddd,J=11.5,7.9,1.8Hz,1H),7.41(dddd,J=8.6,7.1,3.9,1.8Hz,1H),7.22(dddd,J=16.1,10.1,8.8,1.9Hz,2H), 7.08-7.00(m,1H),7.00-6.93(m,1H),6.92-6.86(m,1H),6.84(t,J=7.5Hz ,1H),4.43(ddd,J=11.5,5.7,4.6Hz,1H),4.13(ddd,J=19.7,11.5,9.5Hz,1 H),3.76-3.60(m,2H),2.54(dddd,J=13.8,9.2,7.4,4.8Hz,1H),2.09-1.9 3(m,1.5H),1.87(td,J=12.7,4.4Hz,0.5H),1.70(hd,J=6.6,6.1,3.9Hz,2H ),1.64-1.54(m,0.5H),1.49-1.39(m,0.5H),1.36(d,J=4.1Hz,3H),1.20(d td,J=13.6,7.6,3.6Hz,0.5H),1.13-1.02(m,0.5H),0.94(q,J=7.4Hz,3H).

[0112] 13 C NMR (101MHz, CDCl3) δ193.93,193.59,179.85,179.81,161.47,161.40,142.34,142.28,13 5.64,133.75,133.63,127.83,127.80,127.33,127.24,122.77,122.48,122.40,121.33,12 1.26,120.65,120.51,117.63,108.22,108.19,77.33,77.02,76.70,70.46,70.29,48.18,47.99,45.85,45.61,35.94,35.10,34.58,34.57,24.05,23.66,21.33,21.03,12.71,12.69.

[0113] HRMS: calcd.for C 22 H 23 NO3Na[M+Na] + :372.1567,found:372.1576.

[0114] Example 8

[0115] C7 is obtained by reacting A7 and B1, as shown in equation (XIX):

[0116]

[0117] The preparation method for C7 is the same as that for product C1, except that raw material A1 is replaced with A7. The yield is 84%, and it is a white solid. The analytical data are as follows:

[0118] 1 H NMR(400MHz,Chloroform-d)δ7.81(ddd,J=11.5,7.9,1.8Hz,1H),7.41(dddd,J=8.6,7.1,3.9,1.8Hz,1H),7.22(dddd,J=16.1,10.1,8.8,1.9Hz,2H), 7.08-7.00(m,1H),7.00-6.93(m,1H),6.92-6.86(m,1H),6.84(t,J=7.5Hz ,1H),4.43(ddd,J=11.5,5.7,4.6Hz,1H),4.13(ddd,J=19.7,11.5,9.5Hz,1 H),3.76-3.60(m,2H),2.54(dddd,J=13.8,9.2,7.4,4.8Hz,1H),2.09-1.9 3(m,1.5H),1.87(td,J=12.7,4.4Hz,0.5H),1.70(hd,J=6.6,6.1,3.9Hz,2H ),1.64-1.54(m,0.5H),1.49-1.39(m,0.5H),1.36(d,J=4.1Hz,3H),1.20(d td,J=13.6,7.6,3.6Hz,0.5H),1.13-1.02(m,0.5H),0.94(q,J=7.4Hz,3H).

[0119] 13C NMR (101MHz, CDCl3) δ193.95,193.60,180.25,180.20,161.46,161.40,142.76,142.70,135.63 ,133.66,133.53,130.39,127.79,127.76,127.33,127.24,122.72,122.45,122.36,121.33,12 1.24,120.65,120.50,117.63,108.38,108.35,77.35,77.03,76.71,70.44,70.30,48.23,48.03,45.85,45.61,41.49,41.47,35.86,35.02,24.27,23.87,21.45,21.13,20.78,11.33,11.32.

[0120] HRMS: calcd.for C 23 H 25 NO3Na[M+Na] + :386.1732,found:386.1729.

[0121] Example 9

[0122] C8 is obtained by reacting A8 and B1, as shown in formula (XX):

[0123]

[0124] The preparation method for C8 is the same as that for product C1, except that raw material B1 is replaced with B7. The yield is 80%, and it is a white solid. The analytical data are as follows:

[0125] 1 H NMR (400MHz, Chloroform-d) 1H NMR(400MHz,Chloroform-d)δ7.81(ddd,J=9.9,7.8,1.8Hz,1H),7.41(dddd,J=8.6,7.1,3.6,1.8Hz,1H),7.23-7.16(m,2H),7.06(ddd,J=7.7,4.7,2.9Hz,1H),7.04-6.99(m,1H),6.98-6.93(m,1H),6.90(dd,J=8.4,5.9Hz,1H),4.63(dtd,J=14.1,7.0,3.0Hz,1H),4.43(ddd,J=11.2,6.1,4.6Hz,1H),4.12(ddd,J=18.8,11.5,9.6Hz,1H),2.53(ddtd,J=11.4,9.5,7.2,6.7,4.9Hz,1H),2.09-1.92(m,2H),1.84(td,J=12.7,4.5Hz,0.5H),1.59(ddt,J=13.8,12.1,5.2Hz,0.5H),1.47(td,J=4.0,1.9Hz,6H),1.34(d,J=3.4Hz,3H),1.24-1.14(m,0.5H),1.03(dddd,J=13.6,12.0,7.1,5.2Hz,0.5H)。

[0126] 13 C NMR(101MHz,CDCl3)δ193.92,193.57,179.93,179.89,161.47,161.40,141.94,141.89,141.64,135.62,133.97,133.87,130.30,128.62,127.66,127.58,127.56,127.33,127.24,122.83,122.12,122.04,121.32,121.25,120.66,120.52,117.62,109.78,109.74,77.32,77.00,76.69,70.46,70.29,47.92,47.74,45.83,45.57,43.69,36.13,35.26,24.17,23.80,21.26,20.98,20.94,20.61,19.56,19.53,19.38。

[0127] HRMS:calcd.for C 23 H 25 NO3Na[M+Na] +:386.1732,found:386.1729.

[0128] Example 10

[0129] C9 is obtained by reacting A9 and B1, as shown in formula (XXI):

[0130]

[0131] The preparation method for C9 is the same as that for product C1, except that raw material A1 is replaced with A9. The yield is 75%, and the product is a pale yellow solid. Analytical data are as follows:

[0132] 1 H NMR(400MHz,Chloroform-d)δ7.82(dt,J=9.8,4.9Hz,1H),7.49(t,J=7.8Hz,2H),7.39(t,J=5.5Hz,4H),7.26(t,J=7.7H z,1H),7.16(t,J=8.0Hz,1H),7.09(ddd,J=13.2,7.5,3.1Hz,1H),6.96(tt,J=6.8,2.7Hz,1H),6.93-6.85(m,1H),6.84- 6.77(m,1H),4.48-4.39(m,1H),4.22-4.07(m,1H),2.66-2.50(m,1H),2.11(td,J=13.0,5.0Hz,1.5H),2.00-1.91(m,0. 5H),1.81-1.68(m,0.5H),1.66-1.53(m,0,5H),1.48(dd,J=4.4,2.2Hz,3H),1.43-1.28(m,0.5H),1.28-1.16(m,0.5H).

[0133] 13C NMR (101MHz, CDCl3) δ193.88,193.58,179.71,179.68,161.49,161.44,143.24,143.17,135.70,13 4.62,133.30,133.17,129.56,129.55,129.08,127.95,127.85,127.82,127.36,127.28,127.17,1 26.61,126.55,123.21,123.14,122.92,121.39,121.32,120.67,120.54,117.69,109.42,77.41,77.09,76.77,70.48,70.30,48.44,48.23,45.87,45.62,36.36,35.51,24.41,24.00,21.47,21.19.

[0134] HRMS: calcd.for C 26 H 24 NO3[M+H] + :398.1756,found:398.1758.

[0135] Example 11

[0136] C10 is obtained by reacting A10 and B1, as shown in formula (XXII):

[0137]

[0138] The preparation method for C10 is the same as that for product C1, except that the raw material A1 is replaced with A10. The yield is 72%, and the solid is pale yellow. Analytical data are as follows:

[0139] 1H NMR(400MHz,Chloroform-d)δ7.84(ddt,J=9.8,7.8,1.9Hz,1H),7.50(ddd,J=8.8,7.3,2.1Hz,1H),7.45-7.37(m,2H),7.35-7.27(m,2H),7.23-7.14(m,1H),7.13-7.04(m,1H),7.03-6.95(m,2H),6.91(ddd,J=8.2,6.5,1.3Hz,1H),6.84-6.77(m,0.5H),6.73(dd,J=8.0,6.2Hz,0.5H),4.50-4.42(m,1H),4.24-4.09(m,1H),2.59(dtdd,J=18.4,9.2,5.9,1.7Hz,1H),2.44-2.32(m,3H),2.17-2.01(m,1.5H),1.96(tt,J=12.9,4.1Hz,0.5H),1.76(dddd,J=17.1,11.0,5.3,2.6Hz,0.5H),1.62(ttd,J=13.5,6.8,3.1Hz,0.5H),1.49(dd,J=4.3,2.8Hz,3H),1.41-1.34(m,0.5H),1.24-1.17(m,0.5H)。

[0140] 13C NMR (101MHz, CDCl3) δ193.95,193.90,193.64,193.59,179.78,179.76,179.66,179.6 5,161.49,161.44,143.47,143.41,140.84,140.79,137.91,137.90,135.69,134.81, 133.39,133.29,133.21,133.16,132.75,132.67,131.93,130.19,130.17,129.75,129.50,129.48,129.00,128.13,127.82,127.78,127.76,127.35,127.27,127.26,127.0 8,126.99,126.47,126.46,126.41,123.65,123.63,123.08,123.00,122.86,121.37,121.30,121.29,120.67,120.54,117.68,109.41,109.19,77.40,77.08,76.77,70.49 ,70.46,70.34,70.30,48.47,48.40,48.25,48.19,45.92,45.88,45.65,45.62,36.35,36.34,35.54,35.47,24.48,24.39,24.02,23.98,21.47,21.25,21.18,21.13,21.11.

[0141] HRMS: calcd.for C 27 H 25 NO3Na[M+Na] + :434.1732,found:434.1730.

[0142] Example 12

[0143] C11 is obtained by reacting A11 and B1, as shown in formula (XXIII):

[0144]

[0145] The preparation method of C11 is the same as that of product C1, except that the raw material A1 is replaced with A11, with a yield of 68%, and it is a pale yellow solid. The analytical data are as follows:

[0146] 1H NMR(400MHz,Chloroform-d)δ7.88-7.80(m,1H),7.67-7.60(m,1H),7.51(td,J=7.6,1.6 Hz,2H),7.47-7.43(m,1H),7.42(dd,J=5.6,3.8 Hz,1H),7.36(tdd,J=6.6,3.6,1.4 Hz,2H),7.30(dt,J=8.1,1.6 Hz,1H),6.99(t,J=7.4 Hz,1H),6.95-6.88(m,1H),6.70(dd,J=8.4,5.5 Hz,1H),4.52-4.41(m,1H),4.24-4.09(m,1H),2.66-2.53(m,1H),2.20-2.03(m,1.5H),2.02-1.88(m,0.5H),1.73(dddd,J=17.6,8.9,7.3,4.6 Hz,0.5H),1.63-1.53(m,0.5H),1.49(d,J=3.3 Hz,3H),1.41-1.28(m,0.5H),1.25-1.14(m,0.5H)。

[0147] 13 C NMR(101 MHz,CDCl3)δ193.78,193.53,179.01,178.98,161.44,161.38,142.29,142.23,135.80,135.78,135.45,135.28,134.17,132.77,132.75,130.78,129.70,129.68,128.24,128.22,128.15,128.08,127.38,127.33,126.48,126.41,126.14,126.12,121.45,121.42,117.69,117.68,115.92,115.81,110.92,109.29,77.33,77.01,76.70,70.39,70.27,48.64,48.44,45.79,45.58,36.17,35.51,24.29,23.91,21.37,21.19。

[0148] HRMS:calcd.for C 26 H 22 NO3NaBr[M+Na] + :498.0681,found:498.0683。

Claims

1. A method for preparing aryl heterocyclic linked indole ketone compounds constructed by visible light-induced tandem radical addition-cyclization reaction, characterized by: A visible light-induced tandem radical addition-cyclization reaction was selected. The reaction involved mixing reactants A and B in solution and reacting them for 12 hours under photocatalysis and irradiation with 460 nm blue light emitted by an LED to generate product C. The chemical equation for the reaction is shown in equation (II). + ——(II), In formula (II): A is an N-arylacrylamide derivative, and the substrate for A can be any one of the following A1 to A11: A1: A2: , A3: A4: , A5: A6: , A7: A8: , A9: A10: , A11： ； B is a ketoxime ester derivative with an allyl group at the ortho position, and the substrate for B can be any one of B1 to B12: B1: B2: , B3: ,B4: , B5: B6: , B7: ,B8: , B9： ， B10： ， B11： ， B12： ； The photocatalyst is selected from any one of Ir(ppy)3, fac-Ir(ppy)3, and Ru(bpy)3Cl2.

2. The method for preparing aryl heterocyclic linked indole ketone compounds constructed by visible light-induced tandem radical addition-cyclization reaction as described in claim 1, characterized in that: Follow these steps in sequence: Take a stir bar, add 1 equivalent of a ketoxime ester derivative, 1-3 equivalents of an N-arylacrylamide derivative, 0.05%mol-5%mol of photocatalyst, and an appropriate amount of solvent to the reactor, seal the reactor, and evacuate the reactor and refill it with nitrogen. React for 12 hours at a temperature of -10℃ to 50℃. After the reaction, the product was extracted with ethyl acetate or dichloromethane. The combined organic phases were washed with saturated brine, and the collected organic phases were further dried with anhydrous sodium sulfate. Then, the product was filtered and rotary evaporated to remove excess solvent to obtain a crude product. The crude product after the above steps was separated by column chromatography using a mixture of petroleum ether and ethyl acetate as eluent. Finally, the product containing both aromatic heterocyclic rings and indoleone fragments was obtained by rotary evaporation.

3. The method for preparing aryl heterocyclic linked indole ketone compounds constructed by visible light-induced tandem radical addition-cyclization reaction as described in claim 2, characterized in that: The content of the photocatalyst is 1%mol; The emission power of blue light is 0.2W / cm². 2 ~10W / cm 2 ; The solvent may be any one of acetone, dichloroethane, acetonitrile, tetrahydrofuran, toluene, N,N-dimethylformamide, and dioxane.

4. The method for preparing aryl heterocyclic linked indole ketone compounds constructed by visible light-induced tandem radical addition-cyclization reaction as described in claim 3, characterized in that: The photocatalyst used was fac-Ir(ppy)3; the solvent used was acetonitrile.

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