Synthesis method and application of phosphinylated spirocyclic indoline derivatives

Abstract

The application provides a synthesis method of phosphonated spirocyclic indoline derivatives, catalyst, electrolyte, 3-substituted indole derivatives, diaryl phosphine oxide and triethylamine are added into an electrolytic solvent, an electrode is inserted, and after air replacement, electric stirring reaction is carried out under the condition of room temperature and inert gas protection to obtain phosphonated indoline derivatives; the application also discloses application of the phosphonated spirocyclic indoline derivatives in preparation of anticancer drugs. The application synthesizes the phosphonated spirocyclic indoline derivatives through electrochemistry, does not need to add an oxidant, is green and environment-friendly, has mild reaction conditions, simple operation, high atom economy, and the yield can reach 58%-88%, is suitable for large-scale industrial production, and is expected to be used in development of anticancer products.

Description

Technical Field

[0001] This invention belongs to the field of organic electrochemical synthesis technology, and in particular relates to a method and application of phosphonylation of spirocyclic indoline derivatives. Background Technology

[0002] Indoline molecular skeletons are widely found in the structures of biologically active drug molecules and natural products, thus the efficient construction of indoline molecular skeletons has attracted widespread attention. On the other hand, α-aminophosphate derivatives have proven to have significant application value in metabolic regulation and the development of potential drugs for various metabolic disorders. Given their enormous potential applications in biology, the concise and efficient preparation of α-aminophosphate derivatives has garnered considerable interest; however, the synthetic methods for phosphonyl spirocyclic indoline derivatives—an important component of cyclic aminophosphate derivative structures—remain relatively limited.

[0003] The current main research method utilizes a large amount of oxidant to initiate phosphorus radicals, followed by the addition of phosphorus radicals to indole double bonds and subsequent oxidation / cyclization reactions to synthesize phosphonylated spirocyclic indoline derivatives. For example, in 2019, Vincent's research group used three equivalents of Mn(OAc)3·2H2O as the oxidant, five equivalents of diethyl phosphite or diphenylphosphine oxide as the phosphorus reagent, and acetonitrile as the reaction solvent to prepare a series of phosphonylated indoline derivatives under reflux at 80°C for 20 hours (Org. Lett. 2019, 21, 4986-4990). Existing techniques require a large excess of oxidant as the phosphorus radical initiator and a large excess of diethyl phosphite or diphenylphosphine oxide as the phosphorus reagent. The reaction conditions require heating under reflux and a long reaction time. Furthermore, the yield of this synthetic method is generally low, even lower for some special groups, at only about 10%, and the substrate applicability is poor. In summary, existing methods have limitations such as low atom economy, cumbersome post-processing, and low yield, posing a significant challenge to the green and efficient synthesis and subsequent industrial production of this type of compound. Summary of the Invention

[0004] The technical problem to be solved by this invention is to provide a method for synthesizing and applying phosphonyl spirocyclic indoline derivatives. This method does not require the addition of an external oxidant, is environmentally friendly, has mild reaction conditions, is simple to operate, has high atom economy, and high yield. It is suitable for large-scale industrial production and is expected to be used in the development of anticancer products.

[0005] The technical solution adopted by the present invention to solve the above-mentioned technical problems is as follows:

[0006] A method for synthesizing a phosphonylated spirocyclic indoline derivative includes the following steps:

[0007] The catalyst, electrolyte, 3-substituted indole derivative as shown in formula (I), diarylphosphine as shown in formula (II), and triethylamine were added to the electrolytic solvent. After inserting the electrode and evacuating the gas, the reaction was carried out under the conditions of room temperature and inert gas protection by stirring with electricity to obtain the phosphonyl indoleline derivative as shown in formula (III).

[0008]

[0009] Where -R 1 Choose from -Boc, -Ac, -Ts, or -Bz;

[0010] -R 2 Selected from hydrogen, C1-C4 alkyl, halogen, C1-C4 alkoxy, cyano, C1-C4 benzyloxy, C1-C4 halobenzyloxy or C1-C4 haloalkoxy;

[0011] -R 3 Selected from -CH2OH, -COOH, or -CH2NHTs;

[0012] When -R 3 When X is -CH2OH, X is O and A is a -CH2- group; when -R 3 When X is -COOH, X is O, and A is a -C=O group; when -R 3 When X is -CH2NHTs, X is an NT and A is a -CH2- group;

[0013] -R 4 It is an aryl, C1-C4 alkylphenyl or halophenyl.

[0014] The catalyst is selected from ferrocene, TEMPO, or triarylamine.

[0015] The electrolyte is selected from one of tetra-n-butylammonium acetate, tetra-n-butylammonium tetrafluoroborate, or tetra-n-butylammonium perchlorate.

[0016] The electrolytic solvent is selected from any one or more of acetonitrile, tetrahydrofuran, DMF, DMSO, DCM, and methanol.

[0017] The molar ratio of the catalyst to the 3-substituted indole derivative is 0.1-0.4:1.

[0018] The molar ratio of the electrolyte to the 3-substituted indole derivative is 0.5-1.0:1.

[0019] The molar ratio of the diarylphosphoxy to the 3-substituted indole derivative is 1.0-3.0:1.

[0020] The molar ratio of the triethylamine to the 3-substituted indole derivative is 0.5-1.0:1.

[0021] The reaction time is 3-12 hours.

[0022] Application of a phosphonyl spirocyclic indoline derivative in the preparation of anticancer drugs.

[0023] Compared with the prior art, the advantages of the present invention are as follows:

[0024] (1) This invention provides a method for synthesizing phosphonyl spirocyclic indoline derivatives using electrons as a clean and residue-free oxidant, avoiding the use of external oxidants, reducing the generation of a large number of pollutants during the reaction process, and making it green and environmentally friendly.

[0025] (2) This invention utilizes electrochemical synthesis technology to greenly initiate phosphorus free radicals and utilizes phosphorus free radicals to add to / dearomatize the indole nucleus, which greatly improves the substrate applicability and atom economy of the reaction, and efficiently synthesizes phosphonyl spirocyclic indoleline derivatives with yields of 58%-88%.

[0026] (3) The method of the present invention has mild reaction conditions, low cost and simple operation. At the same time, the substrate of the present invention has wide applicability, good reaction selectivity and high efficiency, and can be applied to large-scale industrial production.

[0027] (4) The present invention also discloses the application of a phosphonyl spirocyclic indoline derivative in the preparation of anticancer drugs, which has good activity against Huh-7 liver cancer cells at a low concentration and is expected to be used in the development of anticancer products. Attached Figure Description

[0028] Figure 1 This is a synthetic route diagram of the present invention;

[0029] Figure 2 The product 3a of Example 1 in this invention 1 H nuclear magnetic resonance (H nuclear magnetic resonance) 1 H-NMR spectrum;

[0030] Figure 3 The product 3a of Example 1 in this invention 13 C nuclear magnetic resonance (C 13 C-NMR spectrum;

[0031] Figure 4 The product 3a of Example 1 in this invention 31 P nuclear magnetic resonance (P nuclear magnetic resonance) 31 P-NMR spectrum;

[0032] Figure 5This is a cell viability graph showing the results of the experiments with compounds 3j, 3i, 3p, 3d, 3h, 3e in this invention and the blank experiment. Detailed Implementation

[0033] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments.

[0034] The synthetic route of this invention is shown in the figure below:

[0035]

[0036] The objective of this invention is achieved through the following technical solutions.

[0037] The electrochemical synthesis method for phosphonylated spirocyclic indoline derivatives includes the following steps:

[0038] 1) Add the catalyst, electrolyte, 3-substituted indole derivative, diarylphosphine, and triethylamine to the electrolytic solvent, insert the electrode, evacuate the gas, and then stir the reaction under room temperature and inert gas protection for 3-12 hours to obtain the reaction solution.

[0039] 2) After the reaction is complete, the reaction solution is extracted, separated and purified, and evaporated to dryness under reduced pressure to obtain the phosphonyl indoline derivative.

[0040] Where -R 1 The options are -Boc, -Ac, -Ts, or -Bz;

[0041] -R 2 It can be selected from hydrogen; C1 to C4 alkyl groups, such as -Me; halogens, such as -F, -Cl, -Br; C1 to C4 alkoxy groups, such as -OMe; cyano; C1 to C4 benzyloxy groups, such as -OBn; C1 to C4 halobenzyloxy groups; C1 to C4 haloalkoxy groups, such as -OCF3;

[0042] -R 3 Selected from -CH2OH, -COOH, or -NHTs;

[0043] When -R 3 When X is -CH2OH, X is O and A is a -CH2- group; when -R 3 When X is -COOH, X is O, and A is a -C=O group; when -R 3 When X is -NHTs, X is NTs and A is -CH2- group;

[0044] -R 4 It can be selected from aryl-Ph; C1 to C4 alkylphenyl, such as -4-Me-Ph; halophenyl.

[0045] The distance between the cathode and anode in the electrode is 8mm. The anode can be a 30mm×7mm×2mm RVC mesh glassy carbon electrode or a graphite electrode. The cathode can be a 10mm×10mm×0.2mm platinum sheet electrode, or an iron, nickel, or copper electrode.

[0046] The current intensity for the reaction can be selected from 3 to 10 mA.

[0047] To further illustrate the present invention, a method for identifying amino acids provided by the present invention will be described in detail below with reference to the accompanying drawings and embodiments. However, it should be understood that the scope of protection of the present invention is not limited to the following embodiments.

[0048] Example 1

[0049] Add 55 mg (0.2 mmol) of tert-butyl 3-(3-hydroxypropyl)-1H-indole-1-carboxylic acid, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine and 65.8 mg (0.2 mmol) of tetra-n-butyltetrafluoroborate to a dried 10 mL three-necked flask. Insert two electrodes (graphite carbon anode and platinum cathode). Evacuate the system three times with argon gas. Then add 5 mL of acetonitrile and 1 mL of methanol under argon gas. Stir at room temperature and power with a 5 mA DC power supply. Detect the reaction by TLC. The reaction is complete in 6 h. The crude product was extracted with ethyl acetate (15 mL × 3), the organic phases were combined, washed with saturated brine (40 mL × 1), dried over anhydrous sodium sulfate, evaporated under reduced pressure, and the product 3a (2'-(diphenylphospho)-4,5-dihydro-3H-spiro[furan-2,3'-dihydroindole]-1'-carboxylic acid tert-butyl ester) was obtained in 74% yield.

[0050]

[0051] Example 2

[0052] To a dried 10 mL three-necked flask, add 43.4 mg (0.2 mmol) of 3-substituted indole substrate, 42.4 mg (0.21 mmol) of diphenylphosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 32.9 mg (0.1 mmol) of tetrabutylammonium tetrafluoroborate. Insert two electrodes (graphite carbon anode, platinum cathode). The system was purged three times with argon gas. Then, under argon conditions, add 5 mL of acetonitrile and 1 mL of methanol. Stir at room temperature, power supply 5 mA DC, and monitor the reaction by TLC. The reaction was complete in 7 h. Extract the crude product with ethyl acetate (15 mL × 3), combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate product 3b, with a yield of 77%.

[0053]

[0054] Example 3

[0055] Add 55.8 mg (0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 10.1 mg (0.1 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate to a dried 10 mL three-necked flask. Insert two electrodes (graphite carbon anode, platinum cathode). Evaporate the system three times with argon gas. Then add 5 mL of acetonitrile and 1 mL of methanol under argon atmosphere. Stir at room temperature, power 5 mA DC, and monitor the reaction by TLC. The reaction is complete after 7 h. Extract the crude product with ethyl acetate (15 mL × 3). Combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate product 3c, with a yield of 65%.

[0056]

[0057] Example 4

[0058] Add 57.8 mg (0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 15.2 mg (0.15 mmol) of triethylamine, and 45.2 mg (0.15 mmol) of tetrabutylammonium acetate to a dried 10 mL three-necked flask. Insert two electrodes (mesh glassy carbon anode and platinum cathode). Evaporate the system three times with argon gas. Then add 5 mL of acetonitrile and 1 mL of methanol under argon atmosphere. Stir at room temperature and monitor the reaction with a 5 mA DC power supply. The reaction was completed in 7 h. Extract the crude product with ethyl acetate (15 mL × 3). Combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate the product 3d, with a yield of 77%.

[0059]

[0060] Experimental Example 5

[0061] Add 76.2 mg (0.2 mmol) tert-butyl 5-(benzyloxy)-3-(3-hydroxypropyl)-1H-indole-1-carboxylic acid, 80.8 mg (0.4 mmol) diphenylphosphine, 11.1 mg (0.06 mmol) ferrocene, 20.2 mg (0.2 mmol) triethylamine and 68.4 mg (0.2 mmol) tetra-n-butylperchlorate to a dried 10 mL three-necked flask. Insert two electrodes (graphite carbon anode and platinum cathode). Evaporate the system three times with argon gas. Then add 5 mL acetonitrile and 1 mL methanol under argon gas conditions. Stir at room temperature and power with a 5 mA DC power supply. Monitor the reaction by TLC. The reaction is complete in 5 h. The crude product was extracted with ethyl acetate (15 mL × 3), the organic phases were combined, washed with saturated brine (40 mL × 1), dried over anhydrous sodium sulfate, evaporated under reduced pressure, and the product 3e (5'-(benzyloxy)-2'-(diphenylphospho)-4,5-dihydro-3H-spiro[furan-2,3'-dihydroindole]-1'-carboxylic acid tert-butyl ester) was obtained in 76% yield.

[0062]

[0063] Example 6

[0064] To a dried 10 mL three-necked flask, add 61.0 mg (0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 14.8 mg (0.08 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate. Insert two electrodes (mesh glassy carbon anode and platinum cathode). The system was purged three times with argon gas. Then, under argon conditions, add 5 mL of acetonitrile and 1 mL of methanol. Stir at room temperature, power supply 5 mA DC, and monitor the reaction by TLC. The reaction was complete in 7 h. Extract the crude product with ethyl acetate (15 mL × 3), combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate product 3f, with a yield of 72%.

[0065]

[0066] Example 7

[0067] 1 g of 71.8 mg (0.2 mmol) 3-substituted indole substrate, 80.8 mg (0.4 mmol) diphenylphosphine oxide, 7.4 mg (0.04 mmol) ferrocene, 20.2 mg (0.2 mmol) triethylamine, and 60.2 mg (0.2 mmol) tetrabutylammonium acetate were added to a dried 10 mL three-necked flask. Two electrodes (mesh glassy carbon anode and graphite cathode) were inserted, and the system was purged three times with argon gas. Then, 5 mL of acetonitrile and 1 mL of methanol were added under argon gas conditions. The mixture was stirred at room temperature and powered by a 5 mA DC power supply. The reaction was monitored by TLC, and the reaction was completed in 7 h. The crude product was extracted with ethyl acetate (15 mL × 3), the organic phases were combined, washed with saturated brine (40 mL × 1), dried over anhydrous sodium sulfate, evaporated under reduced pressure, and 3 g of product was obtained, with a yield of 82%.

[0068]

[0069] Example 8

[0070] To a dried 10 mL three-necked flask, add 70.8 mg (0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate. Insert two electrodes (mesh glassy carbon anode and platinum cathode). Evaporate the system three times with argon gas. Then, add 5 mL of acetonitrile and 1 mL of methanol under argon atmosphere. Stir at room temperature, power 5 mA DC, and monitor the reaction by TLC. The reaction is complete after 7 h. Extract the crude product with ethyl acetate (15 mL × 3), combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate the product for 3 h, with a yield of 70%.

[0071] Large-scale reaction: 1.150 g (3.258 mmol) of 3-substituted indole substrate, 1.316 g (6.516 mmol) of diphenylphosphine oxide, 121.0 mg (0.652 mmol) of ferrocene, 329.6 mg (3.258 mmol) of triethylamine and 980 mg (3.258 mmol) of tetrabutylammonium acetate were added to a dried 150 mL three-necked flask. Two electrodes (mesh glassy carbon anode and platinum cathode) were inserted, and the system was purged three times with argon gas. Then, 80 mL of acetonitrile and 16 mL of methanol were added under argon gas conditions. The mixture was stirred at room temperature, powered by a 5 mA DC power supply, and the reaction was monitored by TLC. The reaction was complete in 7 h. The crude product was extracted with ethyl acetate (240 mL × 3), the organic phases were combined, washed with saturated brine (400 mL × 1), dried over anhydrous sodium sulfate, evaporated under reduced pressure, and the product was separated after 3 h, with a yield of 82%.

[0072]

[0073] Example 9

[0074] To a dried 10 mL three-necked flask, add 58.6 mg (0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate. Insert two electrodes (mesh glassy carbon anode and platinum cathode). The system was purged three times with argon gas. Then, under argon conditions, add 5 mL of acetonitrile and 1 mL of methanol. Stir at room temperature, power 5 mA DC, and monitor the reaction by TLC. The reaction was complete in 7 h. Extract the crude product with ethyl acetate (15 mL × 3), combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate product 3i, with a yield of 69%.

[0075]

[0076] Example 10

[0077] To a dried 10 mL three-necked flask, add 1 J of 61.8 mg (0.2 mmol) 3-substituted indole substrate, 80.8 mg (0.4 mmol) diphenylphosphine oxide, 7.4 mg (0.04 mmol) ferrocene, 20.2 mg (0.2 mmol) triethylamine, and 60.2 mg (0.2 mmol) tetrabutylammonium acetate. Insert two electrodes (graphite carbon anode, platinum cathode). The system is purged three times with argon gas. Then, under argon conditions, add 5 mL of acetonitrile and 1 mL of methanol. Stir at room temperature, power supply 5 mA DC, and monitor the reaction by TLC. The reaction is complete after 7 h. Extract the crude product with ethyl acetate (15 mL × 3), combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate product 3J, with a yield of 66%.

[0078]

[0079] Example 11

[0080] To a dried 10 mL three-necked flask, add 57.8 mg (0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate. Insert two electrodes (mesh glassy carbon anode and stainless steel cathode). The system was purged three times with argon gas. Then, under argon conditions, add 5 mL of acetonitrile and 1 mL of methanol. Stir at room temperature, power 8 mA DC, and monitor the reaction by TLC. The reaction was complete in 2.5 h. Extract the crude product with ethyl acetate (15 mL × 3), combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate the product 3K, with a yield of 88%.

[0081]

[0082] Example 12

[0083] 1 L of 57.8 mg (0.2 mmol) 3-substituted indole substrate, 80.8 mg (0.4 mmol) diphenylphosphine oxide, 7.4 mg (0.04 mmol) ferrocene, 20.2 mg (0.2 mmol) triethylamine, and 60.2 mg (0.2 mmol) tetrabutylammonium tetrafluoroborate were added to a dried 10 mL three-necked flask. Two electrodes (mesh glassy carbon anode and platinum cathode) were inserted, and the system was purged three times with argon gas. Then, 5 mL of acetonitrile and 1 mL of methanol were added under argon gas. The mixture was stirred at room temperature and powered by a 10 mA DC power supply. The reaction was monitored by TLC and completed in 4 h. The crude product was extracted with ethyl acetate (15 mL × 3), and the organic phases were combined, washed with saturated brine (40 mL × 1), dried over anhydrous sodium sulfate, evaporated under reduced pressure, and 3 L of product was obtained, with a yield of 87%.

[0084]

[0085] Example 13

[0086] 1 mg (64.6 mg, 0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 14.8 mg (0.08 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate were added to a dried 10 mL three-necked flask. Two electrodes (mesh glassy carbon anode and platinum cathode) were inserted, and the system was purged three times with argon gas. Then, 5 mL of acetonitrile and 1 mL of methanol were added under argon gas. The mixture was stirred at room temperature and powered by a 7 mA DC power supply. The reaction was monitored by TLC and allowed to proceed for 7 hours until complete. The crude product was extracted with ethyl acetate (15 mL × 3), and the organic phases were combined, washed with saturated brine (40 mL × 1), dried over anhydrous sodium sulfate, and evaporated under reduced pressure to obtain product 3 mL, with a yield of 76%.

[0087]

[0088] Example 14

[0089] To a dried 10 mL three-necked flask, add 63.8 mg (0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 3.7 mg (0.02 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 68.2 mg (0.2 mmol) of tetrabutylammonium perchlorate. Insert two electrodes (graphite carbon anode, platinum cathode). The system was purged three times with argon gas. Then, under argon conditions, add 5 mL of acetonitrile and 1 mL of methanol. Stir at room temperature, power supply 3 mA, and monitor the reaction by TLC. The reaction was complete in 8 h. Extract the crude product with ethyl acetate (15 mL × 3), combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate product 3n, with a yield of 69%.

[0090]

[0091] Example 15

[0092] To a dried 10 mL three-necked flask, add 10 mg (61.4 mg, 0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate. Insert two electrodes (mesh glassy carbon anode and nickel cathode). Evaporate the system three times with argon gas. Then, add 5 mL of acetonitrile and 1 mL of methanol under argon atmosphere. Stir at room temperature, power a 10 mA DC power supply, and monitor the reaction by TLC. The reaction is complete in 4 h. Extract the crude product with ethyl acetate (15 mL × 3). Combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate product 30, yield 66%.

[0093]

[0094] Example 16

[0095] To a dried 10 mL three-necked flask, add 64.6 mg (0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate. Insert two electrodes (mesh glassy carbon anode and platinum cathode). Evaporate the system three times with argon gas. Then, add 5 mL of acetonitrile and 1 mL of methanol under argon atmosphere. Stir at room temperature, power supply 4 mA DC, and monitor the reaction by TLC. The reaction is complete after 7 h. Extract the crude product with ethyl acetate (15 mL × 3), combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate the product 3p, with a yield of 80%.

[0096]

[0097] Example 17

[0098] Add 1q of 73.4mg (0.2mmol) 3-(6-bromo-1-(tert-butyloxycarbonyl)-1H-indol-3-yl)propionic acid, 80.8mg (0.4mmol) diphenylphosphine oxide, 7.4mg (0.04mmol) ferrocene, 20.2mg (0.2mmol) triethylamine and 60.2mg (0.2mmol) tetra-n-butylammonium acetate to a dried 10mL three-necked flask. Insert two electrodes (mesh glassy carbon anode and platinum cathode). Evacuate the system three times with argon gas. Then add 5mL of acetonitrile and 1mL of methanol under argon gas. Stir at room temperature and power with a 5mA DC power supply. Monitor the reaction by TLC. The reaction is complete in 5h. The crude product was extracted with ethyl acetate (15 mL × 3), the organic phases were combined, washed with saturated brine (40 mL × 1), dried over anhydrous sodium sulfate, evaporated under reduced pressure, and the product 3q (6'-bromo-2'-(diphenylphospho)-5-oxo-4,5-dihydro-3H-pyran[furan-2,3'-indoline]-1'-carboxylic acid tert-butyl ester) was obtained in 68% yield.

[0099]

[0100] Example 18

[0101] To a dried 10 mL three-necked flask, add 64.6 mg (0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate. Insert two electrodes (mesh glassy carbon anode and platinum cathode). The system was purged three times with argon gas. Then, under argon conditions, add 5 mL of acetonitrile and 1 mL of methanol. Stir at room temperature, power supply 4 mA DC, and monitor the reaction by TLC. The reaction was complete in 7 h. Extract the crude product with ethyl acetate (15 mL × 3), combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate product 3r, with a yield of 68%.

[0102]

[0103] Example 19

[0104] Add 61.4 mg (0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate to a dried 10 mL three-necked flask. Insert two electrodes (graphite carbon anode, platinum cathode). Evaporate the system three times with argon gas. Then add 5 mL of acetonitrile and 1 mL of methanol under argon atmosphere. Stir at room temperature, power supply 2 mA DC, and monitor the reaction by TLC. The reaction is complete after 7 h. Extract the crude product with ethyl acetate (15 mL × 3). Combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate the product 3s, with a yield of 71%.

[0105]

[0106] Example 20

[0107] To a dried 10 mL three-necked flask, add 1 t of 60.6 mg (0.2 mmol) of 3-substituted indole substrate, 80.8 mg (0.4 mmol) of diphenylphosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate. Insert two electrodes (mesh glassy carbon anode and platinum cathode). The system was purged three times with argon gas. Then, under argon conditions, add 5 mL of THF and 1 mL of methanol. Stir at room temperature, power a 5 mA DC power supply, and monitor the reaction by TLC. The reaction was complete in 7 h. Extract the crude product with ethyl acetate (15 mL × 3), combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate to obtain 3 t of product, with a yield of 73%.

[0108]

[0109] Example 21

[0110] 1 unit of 85.6 mg (0.2 mmol) 3-substituted indole substrate, 80.8 mg (0.4 mmol) diphenylphosphine oxide, 7.4 mg (0.04 mmol) ferrocene, 20.2 mg (0.2 mmol) triethylamine, and 60.2 mg (0.2 mmol) tetrabutylammonium acetate were added to a dried 10 mL three-necked flask. Two electrodes (graphite carbon anode, platinum cathode) were inserted, and the system was purged three times with argon gas. Then, 5 mL of acetonitrile and 1 mL of methanol were added under argon gas conditions. The mixture was stirred at room temperature and powered by an 8 mA DC power supply. The reaction was monitored by TLC, and the reaction was completed in 4 h. The crude product was extracted with ethyl acetate (15 mL × 3), and the organic phases were combined, washed with saturated brine (40 mL × 1), dried over anhydrous sodium sulfate, evaporated under reduced pressure, and 3 units of product were obtained, with a yield of 58%.

[0111]

[0112] Example 22

[0113] Add 1v of 92.4 mg (0.2 mmol) 3-substituted indole substrate, 80.8 mg (0.4 mmol) diphenylphosphine oxide, 7.4 mg (0.04 mmol) ferrocene, 20.2 mg (0.2 mmol) triethylamine, and 60.2 mg (0.2 mmol) tetrabutylammonium acetate to a dried 10 mL three-necked flask. Insert two electrodes (mesh glassy carbon anode and platinum cathode). Evaporate the system three times with argon gas. Then add 5 mL of DCM and 1 mL of methanol under argon atmosphere. Stir at room temperature and monitor the reaction with a 7 mA DC power supply. The reaction was completed in 7 h. Extract the crude product with ethyl acetate (15 mL × 3). Combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate to obtain product 3v, with a yield of 65%.

[0114]

[0115] Example 23

[0116] To a dried 10 mL three-necked flask, add 1 L of 55.0 mg (0.2 mmol) 3-substituted indole substrate, 92.0 mg (0.4 mmol) bis(p-methylphenyl)phosphine oxide, 7.4 mg (0.04 mmol) ferrocene, 20.2 mg (0.2 mmol) triethylamine, and 60.2 mg (0.2 mmol) tetrabutylammonium acetate. Insert two electrodes (mesh glassy carbon anode, platinum cathode). Evaporate the system three times with argon gas. Then, add 5 mL of acetonitrile and 1 mL of methanol under argon atmosphere. Stir at room temperature, power 5 mA DC, and monitor the reaction by TLC. The reaction is complete after 7 h. Extract the crude product with ethyl acetate (15 mL × 3). Combine the organic phases, wash with saturated brine (40 mL × 1), dry to anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and separate the product (3 W), yield 63%.

[0117]

[0118] Example 24

[0119] To a dried 10 mL three-necked flask, 55.0 mg (0.2 mmol) of 3-substituted indole substrate, 92.0 mg (0.4 mmol) of bis(p-methylphenyl)phosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate were added sequentially. Two electrodes (mesh glassy carbon anode and platinum cathode) were inserted, and the system was purged three times with argon gas. Then, 5 mL of acetonitrile and 1 mL of methanol were added under argon gas conditions. The mixture was stirred at room temperature and powered by an 8 mA DC power supply. The reaction was monitored by TLC, and the reaction was completed in 7 h. The crude product was extracted with ethyl acetate (15 mL × 3), and the organic phases were combined, washed with saturated brine (40 mL × 1), dried over anhydrous sodium sulfate, and evaporated under reduced pressure to obtain product 3x, with a yield of 66%.

[0120]

[0121] Example 25

[0122] To a dried 10 mL three-necked flask, 70.6 mg (0.2 mmol) of 3-substituted indole substrate, 95.2 mg (0.4 mmol) of bis(4-fluorophenyl)phosphine oxide, 7.4 mg (0.04 mmol) of ferrocene, 20.2 mg (0.2 mmol) of triethylamine, and 60.2 mg (0.2 mmol) of tetrabutylammonium acetate were added sequentially over 1 hour. Two electrodes (graphite carbon anode and platinum cathode) were inserted, and the system was purged three times with argon gas. Then, 5 mL of acetonitrile and 1 mL of methanol were added under argon gas conditions. The mixture was stirred at room temperature and powered by an 8 mA DC power supply. The reaction was monitored by TLC, and the reaction was completed in 7 hours. The crude product was extracted with ethyl acetate (15 mL × 3), and the organic phases were combined, washed with saturated brine (40 mL × 1), dried over anhydrous sodium sulfate, and evaporated under reduced pressure to obtain product 3y, with a yield of 72%.

[0123]

[0124] Product 3a obtained in Example 1 1 H NMR spectrum, 13 C NMR and 31 The P NMR spectra are attached. Figure 2-4 As shown, the identification data is as follows:

[0125] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.94 (t, J = 8.7Hz, 2H), 7.71-7.65 (m, 3H), 7.55-7.41 (m, 4H), 7.38-7.34 (m, 3H), 7.22 (d, J = 7.3Hz, 1H), 7. 06(t,J=7.5Hz,1H),5.10(s,1H),3.74-3.66(m,2H),2.45-2.39(m,1H) ,2.27-2.21(m,1H),2.04-1.96(m,1H),1.67-1.59(m,1H),1.19(s,9H).

[0126] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 150.8, 142.1, 135.1, 131.9 (d, J = 2.4Hz), 1 31.4(d,J=94.4Hz), 131.3(d,J=2.2Hz), 131.1(d,J=97.6Hz), 131.0(d,J=9.2Hz) ,130.9(d,J=8.6Hz),129.0,128.8(d,J=11.1Hz),127.7(d,J=11.7Hz),123.1,12 2.4,116.3,88.3(d,J=7.6Hz),81.0,68.2(d,J=75.7Hz),65.4,28.8,27.2,25.6.

[0127] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 26.6

[0128] HRMS-ESI: Calcd for C 28 H 31 NO4P + [M+H] + 476.1985, found 476.1985.

[0129] The identification data of product 3b obtained in Example 2 are as follows:

[0130] 1 H NMR (600MHz, DMSO-d6, 333K): δ (ppm) 7.99 (t, J = 8.8Hz, 2H), 7.71-7.68 (m, 1H), 7.67-7. 64(m,2H),7.58-7.53(m,1H),7.50(t,J=7.3Hz,1H),7.44-7.41(m,2H),7.37(t,J=7.2H z,3H),7.26(d,J=7.2Hz,1H),7.11(t,J=7.6Hz,1H),5.36(s,1H),3.75-3.67(m,2H),2. 39-2.33(m,1H),2.28-2.23(m,1H),2.03-1.97(m,1H),1.81(s,3H),1.70-1.62(m,1H).

[0131] 13C NMR (200MHz, DMSO-d6, 333K): δ (ppm) 167.8, 142.3, 136.1, 132.2 (d, J = 2.2Hz), 13 1.8(d,J=7.8Hz),131.6,131.3(d,J=98.3Hz),131.0(d,J=9.3Hz),130.9(d,J=98 .2Hz),129.1,128.8(d,J=11.1Hz),127.9(overlapped),127.8(d,J=7.7Hz),124 .0,122.6,116.9,88.0(d,J=7.6Hz),68.5(d,J=72.6Hz),65.7,28.7,25.7,22.4.

[0132] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 26.6

[0133] HRMS-ESI: Calcd for C 25 H 25 NO3P + [M+H] + 418.1567, found 418.1566.

[0134] The identification data of product 3c obtained in Example 3 are as follows:

[0135] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.91 (s, 2H), 7.74-7.66 (m, 3H), 7.55 (t, J = 6. 6Hz,1H),7.47(t,J=7.6Hz,2H),7.44-7.40(m,3H),7.36(t,J=7.6Hz,2H),7.32(d,J =7.6Hz,1H),7.08(q,J=7.3Hz,2H),6.80(d,J=7.6Hz,2H),6.36(br,1H),5.57(s,1 H),3.78(t,J=7.0Hz,2H),2.44-2.35(m,2H),2.09-2.01(m,1H),1.72-1.64(m,1H).

[0136] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 167.1, 141.9, 136.2, 135.0, 132.1 (d, J = 2.4Hz), 13 1.6(d,J=2.3Hz), 131.3(d,J=93.6Hz, overlapped), 131.2(d,J=9.4Hz), 130.7(d,J=100 .4Hz),130.8(d,J=8.5Hz),129.9,128.8(d,J=11.2Hz),128.5,128.2,127.7(d,J=11.7H z),126.2,124.2,122.8,116.0,88.0(d,J=7.0Hz),68.8(d,J=72.8Hz),65.8,28.7,25.7.

[0137] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.6

[0138] HRMS-ESI: Calcd for C 30 H 27 NO3P + [M+H] + 480.1723, found 480.1724.

[0139] The identification data of the product obtained in Example 4 at 3 days are as follows:

[0140] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.93 (t, J = 8.6Hz, 2H), 7.71-7.65 (m, 3H), 7.48 (t, J = 7.3Hz, 1H), 7.44-7.34 (m, 5H), 7.16 (d, J = 8.1Hz, 1H), 7. 03(s,1H),5.08(s,1H),3.72-3.65(m,2H),2.41-2.35(m,1H),2.30(s,3H ),2.27-2.21(m,1H),2.03-1.95(m,1H),1.64-1.56(m,1H),1.17(s,9H). 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 150.8, 139.8, 135.1, 132.3, 132.0 (d, J = 2.3H z),131.3(d,J=2.4Hz),131.5(d,J=93.8Hz),131.2(d,J=98.0Hz),131.1(d,J=9.2 Hz),130.9(d,J=8.5Hz),129.4,128.8(d,J=11.0Hz),127.7(d,J=11.5Hz),122.8, 116.0,88.3(d,J=6.4Hz),80.7,68.3(d,J=71.1Hz),65.4,28.8,27.3,25.7,20.3.

[0141] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.0

[0142] HRMS-ESI: Calcd for C 29 H 33 NO4P + [M+H] + 490.2142, found 490.2143.

[0143] The identification data of product 3e obtained in Example 5 are as follows:

[0144] 1 H NMR (500MHz, Acetone-d6, 300K): δ (ppm) 8.04 (br, 2H), 7.80-7.65 (m, 3H), 7.63 -7.49(m,3H),7.49-7.45(m,3H),7.40(t,J=7.3Hz,2H),7.36-7.31(m,3H),7.0 0(br,1H),6.88(s,1H),5.22(s,1H),5.11(s,2H),3.75-3.68(m,2H),2.60-2.5 2(m,1H),2.31-2.21(m,1H),2.02-1.99(m,1H),1.78-1.70(m,1H),1.25(s,9H).

[0145] 13C NMR (125MHz, Acetone-d6, 300K): δ (ppm) 156.4, 152.4, 138.5, 138.1, 133.3 (d, J = 99.7Hz), 132.9, 132.6 (d, J = 9.0Hz), 132.4 (d, J = 7. 5Hz),129.7(d,J=10.8Hz),129.3,128.6,128.4,118.5,116.2,110.5,89.6,81.9,71.0,69.8(d,J=74.3Hz),66.8,30.6,28.2,27.1.

[0146] 31 P NMR (162MHz, Acetone-d6, 300K): δ (ppm) 27.0, 25.0

[0147] HRMS-ESI: Calcd for C 35 H 37 NO5P + [M+H] + 582.2404, found 582.2406.

[0148] The identification data of product 3f obtained in Example 6 are as follows:

[0149] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.94 (t, J = 8.5Hz, 2H), 7.70-7.64 (m, 3H), 7 .49-7.42(m,4H),7.37(td,J=7.6Hz,J=2.7Hz,2H),6.93(dd,J=8.7Hz,J=2.6Hz,1 H),6.79(d,J=2.6Hz,1H),5.08(s,1H),3.76(s,3H),3.73-3.67(m,2H),2.43-2. 37(m,1H),2.27-2.21(m,1H),2.04-1.95(m,1H),1.65-1.57(m,1H),1.18(s,9H).

[0150] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 155.8, 150.9, 136.4, 135.6, 131.9 (d, J = 2.3Hz) ,131.5(d,J=92.6Hz, overlapped),131.3(d,J=2.2Hz),131.2(d,J=97.4Hz),131.0(d ,J=9.2Hz),130.9(d,J=8.4Hz),128.7(d,J=11.1Hz),127.7(d,J=11.5Hz),117.0,114 .4,108.4,88.4(d,J=7.4Hz),80.6,68.5(d,J=77.5Hz),65.5,55.5,28.7,27.3,25.6.

[0151] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 26.9

[0152] HRMS-ESI: Calcd for C 29 H 33 NO5P + [M+H] + 506.2091, found 506.2094.

[0153] The identification data for 3g of the product obtained in Example 7 are as follows:

[0154] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.97 (t, J = 9.8Hz, 2H), 7.74-7.64 (m, 3H), 7.59 (s, 1H), 7.51-7.45 (m, 3H), 7.39-7.34 (m, 3H), 7. 23(s,1H),5.15(s,1H),3.76-3.67(m,2H),2.46-2.40(m,1H),2.30-2.24(m,1H),2.01-1.96(m,1H),1.65-1.57(m,1H),1.19(s,9H).

[0155] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 150.6, 144.0, 141.0, 137.3, 132.1 (d, J = 2.5Hz ),131.5,131.14(d,J=9.2Hz),131.11(d,J=92.6Hz),130.9(d,J=8.4Hz),130.8(d, J=98.4Hz),128.8(d,J=11.1Hz),127.8(d,J=11.6Hz),121.9,119.9(d,J=256.1Hz) ,117.4,115.7,87.9(d,J=6.5Hz),81.5,68.4(d,J=75.8Hz),65.8,28.6,27.1,25.6.

[0156] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 26.5

[0157] 19 F NMR (470MHz, DMSO-d6, 333K): δ (ppm)-57.0

[0158] HRMS-ESI: Calcd for C 29 H 30 F3NO5P + [M+H] + 560.1808, found 560.1811.

[0159] The identification data of the product obtained in Example 8 after 3 hours are as follows:

[0160] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.95 (t, J = 8.9Hz, 2H), 7.71-7.66 (m, 3H), 7.54-7.50 (m, 2H), 7.49-7.39 ( m,6H),5.11(s,1H),3.74-3.66(m,2H),2.36-2.27(m,2H),2.04-1.95(m,1H),1.60-1.53(m,1H),1.18(s,9H).

[0161] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 150.5, 141.4, 137.8, 132.1 (d, J = 2.3Hz), 13 1.8,131.5(d,J=2.5Hz),131.12(d,J=9.3Hz),131.10(d,J=92.5Hz),130.9(d,J= 98.9Hz),130.8(d,J=8.4Hz),128.9(d,J=11.1Hz),127.8(d,J=11.4Hz),125.2,1 18.2,114.9,88.1(d,J=6.1Hz),81.4,68.1(d,J=74.1Hz),65.8,28.7,27.2,25.6.

[0162] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.0

[0163] HRMS-ESI: Calcd for C 28 H 30 BrNO4P + [M+H] + 554.1090, found 554.1094.

[0164] The identification data of product 3i obtained in Example 9 are as follows:

[0165] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.95 (t, J = 8.9Hz, 2H), 7.72-7.65 (m, 3H), 7 .51-7.43(m,4H),7.39(td,J=7.6Hz,J=2.6Hz,2H),7.17(td,J=9.0Hz,J=2.6Hz, 1H),7.12(dd,J=8.4Hz,J=2.6Hz,1H),5.11(s,1H),3.75-3.66(m,2H),2.41-2.3 5(m,1H),2.28-2.22(m,1H),2.05-1.97(m,1H),1.65-1.57(m,1H),1.18(s,9H).

[0166] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 158.5 (d, J = 240.0Hz), 150.7, 138.3, 137.3 (d, J = 7.8Hz), 132. 1(d,J=2.3Hz), 131.5(d,J=2.2Hz), 131.3(d,J=94.4Hz), 131.1(d,J=9.3Hz), 130.92(d,J=98.0Hz) ,130.86(d,J=8.6Hz),128.8(d,J=11.1Hz),127.8(d,J=11.5Hz),117.5(d,J=8.3Hz),118.2(d,J=2 3.4Hz), 109.6 (d, J = 24.2Hz), 88.0 (d, J = 6.4Hz), 81.1, 68.4 (d, J = 75.6Hz), 65.7, 28.7, 27.2, 25.6.

[0167] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 26.7

[0168] 19 F NMR (470MHz, DMSO-d6, 333K): δ (ppm)-119.5

[0169] HRMS-ESI: Calcd for C 28 H 30 FNO4P + [M+H] + 494.1891, found 494.1893.

[0170] The identification data of product 3j obtained in Example 10 are as follows:

[0171] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.95 (t, J = 8.8Hz, 2H), 7.72-7.66 (m, 3H), 7.52-7.48 (m, 2H), 7.47-7.43 (m, 2H), 7.42-7.38 (m ,3H),7.30(d,J=2.1Hz,1H),5.11(s,1H),3.75-3.67(m,2H),2.38-2.26(m,2H),2.05-1.96(m,1H),1.63-1.54(m,1H),1.18(s,9H).

[0172] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 150.5, 140.9, 137.4, 132.1 (d, J = 2.5Hz), 131.5 (d,J=2.3Hz),131.12(d,J=9.3Hz),131.11(d,J=93.4Hz, overlapped),130.9(d,J=10 0.6Hz), 130.8 (d, J = 8.6Hz), 128.89 (d, J = 11.2Hz), 128.86, 127.8 (d, J = 11.4Hz), 127. 1,122.4,117.7,88.1(d,J=6.6Hz),81.4,68.2(d,J=75.6Hz),65.8,28.7,27.2,25.6.

[0173] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 26.9

[0174] HRMS-ESI: Calcd for C 28 H 30 ClNO4P + [M+H] + 510.1595, found 510.1597.

[0175] The identification data of product 3k obtained in Example 11 are as follows:

[0176] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.98-7.94 (m, 2H), 7.70-7.64 (m, 3H) ,7.51-7.47(m,3H),7.39-7.35(m,2H),7.14-7.11(m,1H),7.05-7.01(m,2 H),5.13(d,J=2.0Hz,1H),3.76-3.73(m,2H),2.39-2.33(m,1H),2.21-2.1 5(m,1H),2.17(s,3H),2.05-1.97(m,1H),1.72-1.64(m,1H),1.25(s,9H). 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 152.6 (d, J = 4.7Hz), 142.1, 136.7, 131.9 (d, J =2.6Hz),131.8(d,J=93.1Hz),131.3(d,J=2.6Hz),130.96(d,J=7.5Hz),130.95(d, J=99.0Hz),130.9,130.8,128.7(d,J=11.0Hz),128.3,127.5(d,J=11.6Hz),124.8 ,119.5,89.1(d,J=8.3Hz),80.8,70.4(d,J=78.0Hz),65.7,28.6,27.2,25.5,18.8.

[0177] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 26.1

[0178] HRMS-ESI: Calcd for C 29 H 33 NO4P + [M+H] + 490.2142, found 490.2140.

[0179] The identification data of product 3l obtained in Example 12 are as follows:

[0180] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 8.02 (t, J = 8.9Hz, 2H), 7.74-7.67 (m, 3H), 7.55-7.44 (m, 6H), 7.4 1-7.38(m,2H),7.13(t,J=7.6Hz,1H),5.46(s,1H),2.79-2.71(m,3H),2.37-2.32(m,1H),1.21(s,9H).

[0181] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 174.2, 150.4, 142.4, 132.33 (d, J = 2.4Hz), 132. 26,131.7(d,J=2.4Hz), 131.2(d,J=9.4Hz), 131.1(d,J=8.7Hz), 130.6(d,J=93.9Hz), 130.5, 130.3 (d, J = 103.6Hz), 128.9 (d, J = 11.3Hz), 127.9 (d, J = 11.8Hz), 123.6, 122. 8,116.5,90.3(d,J=9.9Hz),81.6,67.8(d,J=72.8Hz),28.9,27.2,25.5(d,J=2.3Hz).

[0182] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.2

[0183] HRMS-ESI: Calcd for C 28 H 29 NO5P + [M+H] + 490.1778, found 490.1779.

[0184] The identification data of product 3m obtained in Example 13 are as follows:

[0185] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 8.07-8.03 (m, 3H), 7.91 (dd, J = 8.5Hz, J = 1.4Hz, 1H), 7.76-7.66 (m, 4H), 7.55 (t, J=7.1Hz,1H),7.49-7.42(m,4H),5.63(s,1H),2.85-2.78(m,2H),2.67-2.60(m,1H),2.38-2.29(m,1H),1.21(s,9H).

[0186] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 173.9, 149.7, 145.9, 135.3, 133.9, 132.6 (d, J = 2 .7Hz),131.9(d,J=2.7Hz),131.3(d,J=9.4Hz),131.0(d,J=9.0Hz),130.1(d,J=94.0Hz ),130.0(d,J=100.1Hz),129.0(d,J=11.4Hz),128.1(d,J=11.7Hz),127.1,118.3,116 .9,105.8,89.2(d,J=9.5Hz),82.7,67.6(d,J=72.9Hz),28.6,27.1,25.1(d,J=2.4Hz).

[0187] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.7

[0188] HRMS-ESI: Calcd for C 29 H 28 N2O5P + [M+H] + 515.1730, found 515.1729.

[0189] The identification data of product 3n obtained in Example 14 are as follows:

[0190] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 8.01 (t, J = 8.9 Hz, 2H), 7.73-7.66 (m, 3H), 7.51 (t, J = 7.2 Hz, 1H), 7.48-7.38 (m, 5H), 7.07 ( d,J=2.5Hz,1H),7.02(dd,J=8.8Hz,J=2.5Hz,1H),5.43(s,1H),3.78(s,3H),2.80-2.66(m,3H),2.35-2.28(m,1H),1.20(s,9H).

[0191] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 174.2, 156.1, 150.5, 135.9, 133.4, 132.3 (d, J = 2 .4Hz),131.7(d,J=2.3Hz),131.2(d,J=9.4Hz),131.0(d,J=9.0Hz),130.7(d,J=93.8H z),130.3(d,J=102.8Hz),128.9(d,J=11.3Hz),127.8(d,J=11.6Hz),117.3,116.2,10 8.6,90.4(d,J=9.6Hz),81.2,68.1(d,J=73.0Hz),55.6,28.9,27.2,25.4(d,J=2.4Hz).

[0192] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.4

[0193] HRMS-ESI: Calcd for C 29 H 31 NO6P + [M+H] + 520.1884, found 520.1883.

[0194] The identification data of product 3o obtained in Example 15 are as follows:

[0195] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 8.03 (t, J = 8.9Hz, 2H), 7.74-7.68 (m, 3H), 7.60-7.45 (m, 4H), 7.4 5-7.34(m,3H),7.27(t,J=8.2Hz,1H),5.52(s,1H),2.80-2.69(m,3H),2.37-2.32(m,1H),1.20(s,9H).

[0196] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 174.1, 158.6 (d, J = 240.9Hz), 150.3, 138.7, 134.3 (d, J = 8.1Hz), 132.4(d,J=2.4Hz), 131.8(d,J=2.5Hz), 131.2(d,J=9.2Hz), 131.0(d,J=8.7Hz), 130.5(d,J=94.8Hz), 130.2(d,J=99.8Hz), 128.9(d,J=11.3Hz), 127.9(d,J=11.6Hz), 117.7(d,J=7.9Hz), 117.0(d,J=23.4 Hz), 110.2 (d, J = 25.0Hz), 89.8 (d, J = 9.4Hz), 81.7, 68.0 (d, J = 74.8Hz), 28.7, 27.2, 25.3 (d, J = 2.0Hz).

[0197] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.4

[0198] 19 F NMR (470MHz, DMSO-d6, 333K): δ (ppm)-118.7

[0199] HRMS-ESI: Calcd for C 28 H 28 FNO5P + [M+H] + 508.1684, found 508.1687.

[0200] The identification data of product 3p obtained in Example 16 are as follows:

[0201] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 8.04 (t, J = 9.0Hz, 2H), 7.78-7.68 (m, 3H), 7.63 (s, 1H), 7.55 -7.41(m,7H),5.54(s,1H),2.81-2.73(m,2H),2.66-2.62(m,1H),2.35-2.26(m,1H),1.20(s,9H). 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 174.0, 150.1, 141.3, 134.5, 132.4 (d, J = 2.2Hz) ,131.8(d,J=2.3Hz),131.2(d,J=9.5Hz),131.0(d,J=9.0Hz),130.34(d,J=93.3Hz),1 30.32, 130.2 (d, J = 100.4Hz), 128.9 (d, J = 11.5Hz), 128.0 (d, J = 11.7Hz), 127.6, 123. 0,117.8,89.8(d,J=9.3Hz),81.9,67.8(d,J=73.2Hz),28.7,27.1,25.2(d,J=2.3Hz).

[0202] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.6

[0203] HRMS-ESI: Calcd for C 28 H 28 ClNO5P + [M+H] + 524.1388, found 524.1390.

[0204] The identification data of product 3q obtained in Example 17 are as follows:

[0205] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 8.05 (t, J = 8.7Hz, 2H), 7.73-7.69 (m, 4H), 7.54-7.44 (m ,6H),7.32(d,J=7.9Hz,1H),5.53(s,1H),2.73-2.65(m,3H),2.35-2.29(m,1H),1.20(s,9H).

[0206] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 174.0, 150.0, 143.8, 132.5 (d, J = 2.6Hz), 131.9 1,131.85(d,J=2.4Hz), 131.3(d,J=9.4Hz), 131.1(d,J=9.0Hz), 130.3(d,J=95.0Hz), 130.1(d,J=100.2Hz),129.0(d,J=11.5Hz),128.0(d,J=11.5Hz),126.3,124.6,123.3 ,119.3,89.7(d,J=10.0Hz),82.2,67.7(d,J=74.4Hz),28.8,27.1,25.2(d,J=2.1Hz).

[0207] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.2

[0208] HRMS-ESI: Calcd for C 28 H 28 BrNO5P + [M+H] + 568.0883, found 568.0884.

[0209] The identification data of product 3r obtained in Example 18 are as follows:

[0210] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 8.04 (t, J = 8.9Hz, 2H), 7.75-7.67 (m, 3H), 7.55-7.42 (m, 7H), 7.19(dd,J=8.2Hz,J=1.8Hz,1H),5.53(s,1H),2.76-2.62(m,3H),2.36-2.27(m,1H),1.20(s,9H).

[0211] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 174.1, 150.0, 143.7, 135.0, 132.5 (d, J = 2.7Hz) ,131.9(d,J=2.2Hz),131.5,131.3(d,J=9.3Hz),131.1(d,J=8.9Hz),130.3(d,J=93. 5Hz),130.1(d,J=100.4Hz),129.0(d,J=11.5Hz),128.0(d,J=11.6Hz),124.3,123.5 ,116.4,89.7(d,J=10.0Hz),82.3,67.9(d,J=72.8Hz),28.8,27.1,25.3(d,J=2.2Hz).

[0212] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.2

[0213] HRMS-ESI: Calcd for C 28 H 28 ClNO5P + [M+H] + 524.1388, found 524.1390.

[0214] The identification data of product 3s obtained in Example 19 are as follows:

[0215] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 8.03 (t, J = 8.6Hz, 2H), 7.74-7.68 (m, 3H), 7.53-7.47 (m, 4H), 7.44-7.42 (m, 2H), 7 .27(d,J=8.4Hz,1H),6.94(td,J=8.7Hz,J=2.1Hz,1H),5.52(s,1H),2.74-2.68(m,3H),2.37-2.30(m,1H),1.20(s,9H).

[0216] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 174.1, 163.4 (d, J = 244.8Hz), 150.0, 144.0 (d, J = 14.0Hz), 132.4 (d, J=2.5Hz),131.8(d,J=2.6Hz),131.2(d,J=9.4Hz),131.1(d,J=8.9Hz),130.4(d,J=94.0Hz),130.1(d,J=9 9.6Hz), 128.9 (d, J = 11.6Hz), 128.5 (d, J = 2.6Hz), 128.0 (d, J = 11.7Hz), 124.5 (d, J = 10.4Hz), 110.2 (d, J = 2 3.0Hz), 104.2 (d, J = 28.6Hz), 89.8 (d, J = 9.5Hz), 82.2, 68.3 (d, J = 72.7Hz), 28.9, 27.1, 25.4 (d, J = 2.0Hz).

[0217] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.1

[0218] 19 F NMR (470MHz, DMSO-d6, 333K): δ (ppm)-109.7

[0219] HRMS-ESI: Calcd for C 28 H 28 FNO5P + [M+H] + 508.1684, found 508.1687.

[0220] The identification data of product 3t obtained in Example 20 are as follows:

[0221] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 8.01 (t, J = 8.6Hz, 2H), 7.73-7.68 (m, 3H), 7.53-7.45 (m, 3H), 7.44-7.36 (m, 3H), 7. 34(d,J=7.7Hz,1H),6.95(d,J=7.6Hz,1H),5.43(s,1H),2.76-2.67(m,3H),2.39(s,3H),2.33-2.27(m,1H),1.20(s,9H).

[0222] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 174.2, 150.4, 142.7, 140.5, 132.3 (d, J = 2.4Hz), 131.7(d,J=2.3Hz),131.2(d,J=9.4Hz),131.1(d,J=8.8Hz),130.6(d,J=93.3Hz),130 .4(d,J=99.7Hz),129.6,128.9(d,J=11.4Hz),127.9(d,J=11.6Hz),124.3,122.5,117 .1,90.4(d,J=10.0Hz),81.5,68.1(d,J=75.4Hz),29.0,27.2,25.6(d,J=2.3Hz),21.2.

[0223] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.0

[0224] HRMS-ESI: Calcd for C 29 H 31 NO5P + [M+H] + 504.1934, found 504.1937.

[0225] The identification data of product 3u obtained in Example 21 are as follows:

[0226] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.91 (t, J = 8.1Hz, 2H), 7.71-7.63 (m, 3H), 7.63-7.56 (m, 1H), 7.52- 7.46(m,3H),7.37(td,J=7.6Hz,J=2.8Hz,2H),7.32(t,J=7.6Hz,1H),7.09(d,J=8.0Hz,2H),6.95(d,J=7. 9Hz,2H),6.70(t,J=7.4Hz,1H),6.67(t,J=7.3Hz,1H),5.50(s,1H),3.51-3.47(m,1H),3.38-3.33(m,1H ),2.97-2.92(m,1H),2.32(s,3H),2.23-2.17(m,1H),1.81-1.75(m,1H),1.45-1.40(m,1H),1.17(s,9H).

[0227] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 151.4, 144.0, 142.0, 136.7, 131.92, 131. 87(d,J=92.3Hz),131.3(d,J=2.1Hz),131.2(d,J=9.0Hz),130.9(d,J=8.4Hz),1 29.0,128.8(d,J=11.2Hz),128.7,127.8(d,J=11.1Hz),126.0,123.5,122.8,11 7.1,80.4,72.7,69.7(d,J=78.3Hz),49.4,36.1(d,J=5.5Hz),27.2,22.9,20.6.

[0228] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 26.8

[0229] HRMS-ESI: Calcd for C 35 H 38 N2O5PS + [M+H] + 629.2234, found 629.2234.

[0230] The identification data of product 3v obtained in Example 22 are as follows:

[0231] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.93 (t, J = 8.7Hz, 2H), 7.72-7.66 (m, 3H), 7.54-7.49 (m, 4H) ,7.40(td,J=8.2Hz,J=2.5Hz,2H),7.30(dd,J=8.6Hz,J=2.1Hz,1H),7.11(d,J=8.1Hz,2H),6.95( d,J=7.9Hz,2H),6.56(d,J=2.0Hz,1H),5.48(s,1H),3.59-3.55(m,1H),3.47-3.42(m,1H),2.97- 2.92(m,1H),2.34(s,3H),2.28-2.22(m,1H),1.73-1.66(m,1H),1.32-1.27(m,1H),1.17(s,9H). 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 151.2, 142.9, 142.2, 136.8, 133.5, 132.1 (d, J =2.2Hz),131.49(d,J=91.5Hz),131.5(d,J=2.2Hz),131.3(d,J=9.0Hz),130.9(d,J= 8.5Hz), 129.0, 128.9 (d, J = 11.5Hz), 128.8, 127.9 (d, J = 10.7Hz), 127.2, 125.7, 123. 8,118.3,80.8,72.1,69.9(d,J=79.8Hz),50.0,36.1(d,J=5.5Hz),27.1,22.8,20.6.

[0232] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.0

[0233] HRMS-ESI: Calcd for C 35 H 37 ClN2O5PS + [M+H] + 663.1844, found 663.1845.

[0234] The identification data of product 3w obtained in Example 23 are as follows:

[0235] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.88 (t, J = 9.1Hz, 2H), 7.49-7.44 (m, 4H), 7.37-7.28 (m, 3H), 7.20 (d, J = 6.1Hz, 2 H),7.13(t,J=7.4Hz,1H),5.37(s,1H),2.80-2.73(m,3H),2.43(s,3H),2.37-2.32(m,1H),2.29(s,3H),1.20(s,9H).

[0236] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 174.2, 150.3, 142.5 (d, J = 2.6Hz), 141.8 (d, J = 2.7Hz) ,132.3,131.2(d,J=9.7Hz),131.0(d,J=9.1Hz),130.5,129.5(d,J=11.8Hz),128.9(d,J=12 .1Hz),128.4(d,J=12.0Hz),127.4(d,J=95.9Hz),127.3(d,J=103.6Hz),123.5,122.8,116 .3,90.4(d,J=9.5Hz),81.5,67.9(d,J=75.4Hz),28.9,27.1,25.5(d,J=2.3Hz),20.8,20.6.

[0237] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.7

[0238] HRMS-ESI: Calcd for C 30 H 32 NNaO5P + [M+Na] + 540.1910, found 540.1909.

[0239] The identification data of product 3x obtained in Example 24 are as follows:

[0240] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 7.79 (t, J = 9.2Hz, 2H), 7.61-7.40 (m, 3H), 7.35 (t, J=7.6Hz,1H),7.28(t,J=9.3Hz,2H),7.22(d,J=7.4Hz,1H),7.17(dd,J=8.0Hz,J=2.0Hz, 2H),7.06(t,J=7.4Hz,1H),5.02(s,1H),3.72-3.65(m,2H),2.42(s,3H),2.41-2.38(m, 1H),2.28(s,3H),2.26-2.21(m,1H),2.04-1.96(m,1H),1.70-1.59(m,1H),1.18(s,9H).

[0241] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 150.7, 142.1 (d, J = 2.5Hz), 141.4 (d, J = 2.4Hz), 135 .2,131.1(d,J=9.5Hz),130.9(d,J=8.6Hz),129.3(d,J=11.4Hz),129.0,128.5(overlap ped),128.28(d,J=11.9Hz),128.27(d,J=94.7Hz),128.1(d,J=100.8Hz),123.0,122.4, 116.2,88.2(d,J=7.2Hz),80.9,68.2(d,J=71.3Hz),65.4,28.8,27.2,25.7,20.8,20.6.

[0242] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 27.2

[0243] HRMS-ESI: Calcd for C 30 H 35 NO4P + [M+H] + 504.2298, found 504.2299.

[0244] The identification data of product 3y obtained in Example 25 are as follows:

[0245] 1 H NMR (500MHz, DMSO-d6, 333K): δ (ppm) 8.03 (t, J = 11.7Hz, 2H), 7.53-7.48 (m, 5H), 7.43 (s, 1H), 7.40 (br, 1H), 7.25 (t, J=8.6Hz,2H),5.11(s,1H),3.77-3.68(m,2H),2.32-2.29(m,2H),2.06-1.98(m,1H),1.66-1.58(m,1H),1.22(s,9H).

[0246] 13C NMR (125MHz, DMSO-d6, 333K): δ (ppm) 164.4 (d, J = 252.0Hz), 164.2 (d, J = 253.8Hz), 150.4 ,141.1,137.7,134.0(t,J=10.3Hz),133.8(t,J=9.6Hz),131.8,127.1(d,J=96.5Hz),126 .8(d,J=102.0Hz),125.3,118.2,116.3(dd,J=22.0Hz,J=12.4Hz),115.1(dd,J=21.2Hz, J=12.4Hz),114.98,87.9(d,J=7.2Hz),81.6,67.9(d,J=73.6Hz),65.9,28.7,27.2,25.6.

[0247] 31 P NMR (162MHz, DMSO-d6, 333K): δ (ppm) 26.1

[0248] 19 F NMR (470MHz, DMSO-d6, 333K): δ (ppm)-106.6,-107.7

[0249] HRMS-ESI: Calcd for C 28 H 28 BrF2NO4P + [M+H] + 590.0902, found 590.0902.

[0250] Table 1. Summary of product structural formulas and yields from Examples 1-25

[0251]

[0252]

[0253]

[0254] Results analysis: Even for the series of special products such as the phosphonyl spirocyclic indoline containing N-heterocyclic rings attached to the indole group in Examples 21 and 22, the yield is as high as 58% or more, which is much higher than the yield reported in the prior art (around 10%).

[0255] Example 26: Determination of the anticancer activity of compound 3e (Huh-7 liver cancer cells)

[0256] 100 μL of cell suspension (5 × 10⁴ cells / mL) was seeded into 96-well plates and incubated for 48 h. Compounds 3j, 3i, 3p, 3d, 3h, and 3e were dissolved in complete medium (DMEM + 10% FBS) containing 0.1% DMSO, and incubated for another 48 h at 37°C in a 5% CO₂ incubator. Then, 10 μL of CCK-8 solution was added to each well, and incubation continued for 2–4 h. Absorbance was measured at 450 nm using a microplate reader. Cell viability was calculated by comparing the percentage of viable cells with the blank control. All tests were repeated in at least three independent experiments, and the results are attached. Figure 5 As shown in the figure. The data indicate that compound 3e exhibits good anticancer activity against Huh-7 liver cancer cells at a concentration of 20 μM, and it holds promise for use in the development of anticancer products.

[0257] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several improvements and modifications without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for synthesizing a phosphonylated spirocyclic indoline derivative, characterized in that... Includes the following steps: The catalyst, electrolyte, 3-substituted indole derivative as shown in formula (I), diarylphosphine as shown in formula (II), and triethylamine were added to the electrolytic solvent. After inserting the electrode and evacuating the gas, the reaction was carried out under the conditions of room temperature and inert gas protection by stirring with electricity to obtain the phosphonyl indoleline derivative as shown in formula (III). ； -R¹ is selected from -Boc, -Ac, -Ts, or -Bz; -R² is selected from hydrogen, C1~C4 alkyl, halogen, C1~C4 alkoxy, cyano, C1~C4 benzyloxy, C1~C4 halobenzyloxy or C1~C4 haloalkoxy; -R³ is selected from -CH2OH, -COOH, or -CH2NHTs; When -R³ is -CH₂OH, X is O and A is -CH₂-; when -R³ is -COOH, X is O and A is -C=O; when -R³ is -CH₂NHTs, X is NTs and A is -CH₂-. -R 4 It is an aryl, C1-C4 alkylphenyl, or halophenyl; The catalyst is ferrocene; the electrolyte is tetrabutylammonium acetate; and the electrolytic solvent is a mixture of acetonitrile and methanol in a volume ratio of acetonitrile:methanol = 5:

1.

2. The method for synthesizing a phosphonylated spirocyclic indoline derivative according to claim 1, characterized in that... The molar ratio of the catalyst to the 3-substituted indole derivative is 0.1-0.4:

1.

3. The method for synthesizing a phosphonylated spirocyclic indoline derivative according to claim 1, characterized in that... The molar ratio of the electrolyte to the 3-substituted indole derivative is 0.5-1.0:

1.

4. The method for synthesizing a phosphonylated spirocyclic indoline derivative according to claim 1, characterized in that... The molar ratio of the diarylphosphoxy to the 3-substituted indole derivative is 1.0-3.0:

1.

5. The method for synthesizing a phosphonylated spirocyclic indoline derivative according to claim 1, characterized in that... The molar ratio of the triethylamine to the 3-substituted indole derivative is 0.5-1.0:

1.

6. The method for synthesizing a phosphonylated spirocyclic indoline derivative according to claim 1, characterized in that... The reaction time is 3h-12h.

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