Method for constructing indolone compounds based on free radical mediated 1, 4-cyano migration, desulfurization and cyclization

Abstract

The invention discloses a method for constructing indolone compounds based on free radical mediated 1, 4-cyano migration, desulfurization and cyclization, and the method comprises the following steps: mixing 2-cyano-N, 2-dimethyl-N-(phenylsulfonyl) hex-5-enamide compounds, bromo-ester compounds, a photocatalyst and potassium phosphate in an organic solvent under a protective atmosphere, and carrying out a reaction under a protective atmosphere to obtain the indolone compounds. And carrying out 1, 4-cyano migration, desulfurization and cyclization reaction under an illumination condition to obtain the indolone compound. According to the present invention, based on the visible light catalysis non-activated olefin cyclization strategy, the carbon-sulfur bond breakage and the carbon-carbon bond formation are successfully achieved through the one-pot method, and the 1, 4-cyano group migration, desulfurization and cyclization are successfully synthesized to construct the indolone compound; the preparation method has the characteristics of mild conditions, stable and easily available raw materials, good compatibility with various functional groups and the like, and has practical application value.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for constructing indole ketone compounds based on radical-mediated 1,4-cyano migration, desulfurization and cyclization. Background Technology

[0002] Indolones and their derivatives are widely distributed in bioactive natural products and drug molecules. Due to their highly modifiable chemical properties and diverse therapeutic applications, these structures have become key research targets in drug discovery and optimization.

[0003] Synthetic methods for indolones and their derivatives mainly include Friedel-Crafts acylation / cyclization, transition metal-catalyzed C-H bond functionalization, and radical cyclization. However, these traditional methods generally face the following challenges: poor functional group compatibility, lengthy synthetic steps due to dependence on directing groups, high catalyst costs, and difficulty in controlling reaction selectivity.

[0004] Therefore, it is of great significance to research and develop a novel, practical and green synthetic route for indole ketones. Summary of the Invention

[0005] This invention addresses the shortcomings of existing technologies by providing a method for constructing indole ketones based on radical-mediated 1,4-cyano migration, desulfurization, and cyclization. Utilizing a visible-light-catalyzed, non-activated olefin cyclization strategy, a one-pot method successfully achieves carbon-sulfur bond breaking and carbon-carbon bond formation, resulting in the successful synthesis of indole ketones through 1,4-cyano migration, desulfurization, and cyclization. This strategy not only demonstrates broad substrate applicability and excellent functional group compatibility but also provides a novel, practical, and green synthetic route for the efficient construction of structurally diverse indole ketones.

[0006] To address the aforementioned technical problems, this invention provides a method for constructing indole ketone compounds based on radical-mediated 1,4-cyano migration, desulfurization, and cyclization, comprising the following steps:

[0007] Under a protective atmosphere, 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide compounds, brominated ester compounds, a photocatalyst, and potassium phosphate (K3PO4) are mixed in an organic solvent, and 1,4-cyano migration, desulfurization, and cyclization reactions are carried out under light irradiation to obtain the indole ketone compounds.

[0008] This invention utilizes a visible-light-catalyzed non-activated olefin cyclization strategy to successfully achieve carbon-sulfur bond breaking and carbon-carbon bond formation in a one-pot method, thereby successfully synthesizing 1,4-cyano groups through migration, desulfurization, and cyclization to construct indole ketone compounds. This strategy not only demonstrates broad substrate applicability and excellent functional group compatibility but also provides a novel, practical, and green synthetic route for the efficient construction of structurally diverse indole ketone compounds.

[0009] Furthermore, the general structural formula of the 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide compounds is as follows: R1 is hydrogen, fluorine, bromine, tert-butyl or phenyl.

[0010] Furthermore, the 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide compound is selected from one of 2-cyano-N,2-dimethyl-N-toluenesulfonylhex-5-enamide, 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide, 2-cyano-N-((4-fluorophenyl)sulfonyl)-N,2-dimethylhex-5-enamide, N-((3-bromophenyl)sulfonyl)-2-cyano-N,2-dimethylhex-5-enamide, N-((4-(tert-butyl)phenyl)sulfonyl)-2-cyano-N,2-dimethylhex-5-enamide, and N-([1,1'-biphenyl]-4-ylsulfonyl)-2-cyano-N,2-dimethylhex-5-enamide.

[0011] Furthermore, the general structural formula of the brominated ester compounds is as follows: In this , R is H, F or alkyl; R2 is methyl, ethyl, phenyl, 4-methoxyphenyl, 2,4,6-trimethylphenyl, 1-naphthyl, 4-fluorobenzyl, (perfluorophenyl)methyl, cyclohexylmethyl, 3,5-dimethoxybenzyl, dihydrofuran-2(3H)-keto, 2-(thiophen-2-yl)ethyl, furan-2-ylmethyl or 2-isopropyl-5-methylcyclohexyl.

[0012] Furthermore, the brominated ester compounds are selected from one of the following: methyl bromide difluoropropionate, ethyl 3-bromo-2,2-difluoropropionate, ethyl 3-bromo-2-fluoropropionate, ethyl bromide propionate, ethyl bromide butyrate, ethyl bromide valerate, ethyl bromide hexanoate, phenyl 2-bromoacetate, 4-methoxyphenyl 2-bromoacetate, m-tolyl 2-bromoacetate, 1-naphthyl 2-bromoacetate, 4-fluorobenzyl 2-bromoacetate, (perfluorophenyl)methyl 2-bromoacetate, cyclohexylmethyl 2-bromoacetate, 3,5-dimethoxybenzyl 2-bromoacetate, 3-bromodihydrofuran-2(3H)-one, 2-(thiophen-2-yl)ethyl 2-bromoacetate, furan-2-ylmethyl 2-bromoacetate, diethyl 2-bromo-2-methylmalonate, and 2-isopropyl-5-methylcyclohexyl 2-bromoacetate.

[0013] Furthermore, the indole ketone compound is a methyl 4-cyano-6-(1,3-dimethyl-2-oxoindophyllin-3-yl)-2,2-difluorohexanoate ester compound with the general structural formula [insert structural formula here]. In this molecule, R is H, F, or an alkyl group; R1 is hydrogen, fluorine, bromine, tert-butyl, or phenyl; and R2 is methyl, ethyl, phenyl, 4-methoxyphenyl, 2,4,6-trimethylphenyl, 1-naphthyl, 4-fluorobenzyl, (perfluorophenyl)methyl, cyclohexylmethyl, 3,5-dimethoxybenzyl, dihydrofuran-2(3H)-keto, 2-(thiophen-2-yl)ethyl, furan-2-ylmethyl, or 2-isopropyl-5-methylcyclohexyl.

[0014] Furthermore, the photocatalyst is 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, with the following structural formula: .

[0015] Furthermore, the molar ratio of the photocatalyst, potassium phosphate, 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide compound, and brominated ester compound is (0.01-0.05):(2-3):1:(1.5-2).

[0016] Furthermore, the temperature for the 1,4-cyano migration, desulfurization, and cyclization reaction is 25-35°C, and the time is 24-30 hours.

[0017] Furthermore, the 1,4-cyano migration, desulfurization and cyclization reaction also includes filtration, concentration and purification steps.

[0018] Furthermore, the organic solvent is selected from one or more of acetonitrile, N,N-dimethylformamide (DMF), and dimethyl sulfoxide.

[0019] The beneficial effects of this invention are:

[0020] This invention is based on a visible light-catalyzed non-activated olefin cyclization strategy. Through a one-pot method, carbon-sulfur bond breaking and carbon-carbon bond formation were successfully achieved, and 1,4-cyano migration, desulfurization and cyclization were successfully synthesized to construct indole ketone compounds. The preparation method has the characteristics of mild conditions, stable and readily available raw materials, and good compatibility with various functional groups, and has practical application value. Detailed Implementation

[0021] The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] Example 1

[0023] This embodiment provides a method for synthesizing 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide compounds, as detailed below:

[0024] (1) Sodium hydride (20 mmol, 1.0 equivalent), ethyl cyanoacetate (40 mmol, 2.0 equivalent), and DMF (50 mL) were added to a dry round-bottom flask, and the temperature was controlled at 0 °C. Under nitrogen protection, the reaction mixture was stirred at 0 °C for 2 hours, and then 1-bromo-4-butene (20 mmol, 1.0 equivalent) was added dropwise. The reaction mixture was stirred overnight at room temperature. After the reaction was complete, the reaction was terminated with saturated ammonium chloride solution (40 mL). The reaction mixture was extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried over MgSO4, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography (ethyl acetate / petroleum ether) to obtain S1.

[0025] (2) Sodium hydride (12 mmol, 1.2 equivalents) and DMF (30 mL) were added sequentially to a dry round-bottom flask, followed by S1 (10 mmol, 1.0 equivalents) at 0 °C. The reaction mixture was stirred at room temperature under nitrogen for 1 hour, followed by the dropwise addition of iodomethane (CH3I, 12 mmol, 1.2 equivalents) at room temperature. The reaction mixture was stirred overnight at 60 °C and quenched with saturated ammonium chloride solution (40 mL). The reaction product was extracted with ethyl acetate, concentrated under vacuum, and purified by silica gel column chromatography (ethyl acetate / petroleum ether) to obtain S2.

[0026] (3) S2 (10 mmol, 1.0 equivalent) was dissolved in methanol (10 mL) and water (10 mL) and cooled to 0 °C. Lithium hydroxide (22 mmol, 2.2 equivalent) was added in one go, and the mixture was then slowly heated to room temperature. After the reaction was complete (confirmed by thin-layer chromatography, approximately 1 hour), the reaction was terminated with 1 M hydrochloric acid and extracted with ethyl acetate (3 times). The combined organic layers were washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to obtain S3.

[0027] (4a) S3 (4.4 mmol, 1.0 equivalent) was dissolved in dichloromethane (20 mL) with stirring, followed by the addition of oxaloyl chloride (8.8 mmol, 2 equivalent), and then seven drops of DMF were added at 0 °C. The reaction mixture was stirred at room temperature for 3 hours.

[0028] (4b) In another round-bottom flask, add NaH (4.8 mmol, 1.2 equivalents) to 10 mL of tetrahydrofuran. Cool the reaction mixture to 0 °C, then add an N-methylbenzenesulfonamide compound (4.4 mmol, 1 equivalent), and stir the reaction mixture at room temperature for 1 hour. After step (4a) is complete, remove the solvent by vacuum distillation, and add the product generated in this step to the 0 °C mixture from step 4b, then react at room temperature overnight. After the reaction is complete, wash with water (20 mL) and 1M hydrochloric acid (20 mL), concentrate under reduced pressure, and purify by silica gel column chromatography (ethyl acetate / petroleum ether) to give compound 1, namely a 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide compound.

[0029] The reaction formula is as follows:

[0030] .

[0031] Example 2

[0032] This embodiment provides a method for synthesizing brominated ester compounds, as detailed below:

[0033] Under a nitrogen atmosphere, 1.0 equivalent of phenol / benzyl alcohol or any cyclic or acyclic alcohol was dissolved in acetonitrile at 0°C, followed by the addition of 2 equivalents of pyridine. Subsequently, 1.5 equivalents of a bromoacetyl bromide compound was added dropwise over 10 minutes. The reaction was then carried out at 0°C for 15 minutes, quenched with water, and washed three times with dichloromethane. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The residue was purified by silica gel column chromatography, eluting with ethyl acetate / petroleum ether (1 / 40–1 / 20, v / v) to give a bromoester compound. The reaction formula is:

[0034] .

[0035] Example 3a

[0036] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and late cyclization reaction of 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide and methyl bromide difluoropropionate yielded methyl 4-cyano-2,2-difluoro-6-(1,3,6-trimethyl-2-oxoindoline-3-yl)hexanoate, as detailed below:

[0037] In a glove box, 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide 1a (0.17 mmol, 1.0 equivalent), methyl bromodifluoroacetate 2a (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stirrer), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a yellow oil in 76% yield. The reaction formula is as follows:

[0038] .

[0039] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.01 (d, J = 7.5 Hz, 1H), 6.84 (ddt, J = 7.5, 2.2, 1.1 Hz, 1H), 6.62 (s, 1H), 3.81 (d, J = 2.2 Hz, 3H), 3.13 (s, 3H), 2.72 – 2.56 (m, 1H), 2.33 (s, 3H), 2.20 – 2.00 (m, 2H), 1.98 –1.89 (m, 1H), 1.87 – 1.72 (m, 1H), 1.30 (s, 3H), 1.25 – 1.08 (m, 2H); 19F NMR (376 MHz, CDCl3) δ -103.83, -104.13, -104.54, -104.84, -105.71, -105.91, -106.42, -106.62; 13 C NMR (101 MHz, CDCl3) δ 180.12, 180.01, 163.27, 162.95,162.63, 143.17, 143.14, 138.44, 138.40, 132.30, 130.95, 129.95, 129.74,128.84, 123.48, 123.40, 123.33, 122.24, 119.89, 119.80, 116.64, 116.56,114.12, 114.05, 111.62, 111.55, 109.24, 108.03, 77.45, 77.13, 76.81, 63.50, 47.57, 47.54, 47.41, 47.39, 37.02, 36.78, 36.69, 36.55, 36.46, 36.22, 35.32, 34.68, 28.95, 27.93, 27.63, 26.17, 24.97, 24.93, 24.89, 24.55, 24.51, 24.47, 24.06, 23.79, 21.76.

[0040] Example 3b

[0041] The difference between this example and Example 3a is that the solvent is replaced with N,N-dimethylformamide, while the other steps and parameters remain unchanged, and the yield of the obtained product is 55%.

[0042] Example 3c

[0043] The difference between this example and Example 3a is that the solvent is replaced with dimethyl sulfoxide, while the other steps and parameters remain unchanged, and the yield of the obtained product is 72%.

[0044] Example 3d

[0045] The difference between this embodiment and embodiment 3a is that the light source is replaced with violet light, while the other steps and parameters remain unchanged, and the yield of the obtained product is 56%.

[0046] Example 4

[0047] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and late cyclization reaction of 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide and methyl bromide difluoropropionate yielded methyl 4-cyano-6-(1,3-dimethyl-2-oxoindenzoline-3-yl)-2,2-difluorohexanoate, as detailed below:

[0048] In a glove box, 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide (0.17 mmol, 1.0 equivalent), methyl bromodifluoroacetate 2a (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a yellow oil in 73% yield.

[0049] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.34 – 7.26 (m, 1H), 7.21 (dd, J = 7.4, 1.3 Hz, 1H), 7.11 (tdd, J = 7.5, 2.3, 1.0 Hz, 1H), 6.87 (dd, J= 7.7, 1.4 Hz, 1H), 3.88 (d, J = 2.0 Hz, 3H), 3.22 (s, 3H), 2.80 – 2.63 (m,1H), 2.50 – 2.29 (m, 1H), 2.25 – 1.97 (m, 3H), 1.88 (ddd, J = 13.4, 11.5, 4.9Hz, 1H), 1.39 (d, J = 1.3 Hz, 3H), 1.28 – 1.18 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 180.28, 180.23, 179.99, 179.89, 163.71, 163.39, 163.07, 143.01,142.98, 142.92, 142.88, 133.01, 132.94, 132.83, 132.74, 130.97, 128.85,128.33, 128.30, 127.19, 123.25, 123.20, 123.15, 123.07, 122.54, 122.51,120.12, 120.00, 119.81, 119.72, 116.66, 116.59, 114.15, 114.08, 111.65, 111.58, 108.48, 108.46, 108.40, 77.44, 77.32, 77.12, 76.80, 53.75, 47.99, 47.86, 47.71, 37.05, 36.87, 36.82, 36.73, 36.61, 36.58, 36.49, 36.41, 36.25, 36.17, 35.94, 35.24, 34.86, 34.60, 34.50, 31.90, 31.42, 30.55, 30.18, 29.68, 29.63, 29.30, 27.86, 27.55, 27.45, 26.32, 26.27, 24.97, 24.93, 24.89, 24.55, 24.51, 24.47, 23.96, 23.90, 23.68, 23.64.

[0050] Example 5

[0051] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and late cyclization reaction of 2-cyano-N-((4-fluorophenyl)sulfonyl)-N,2-dimethylhex-5-enamide and methyl bromide difluoropropionate yielded methyl 4-cyano-2,2-difluoro-6-(6-fluoro-1,3-dimethyl-2-oxoindoline-3-yl)hexanoate, as detailed below:

[0052] In a glove box, 2-cyano-N-((4-fluorophenyl)sulfonyl)-N,2-dimethylhexyl-5-enamide (0.17 mmol, 1.0 equivalent), methyl bromodifluoroacetate 2a (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a yellow oil in 70% yield.

[0053] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.14 (dd, J = 8.2, 5.2Hz, 1H), 6.78 (ddt, J = 9.5, 8.2, 2.4 Hz, 1H), 6.61 (ddd, J = 8.8, 2.4, 1.3Hz, 1H), 3.89 (d, J = 2.4 Hz, 3H), 3.20 (s, 3H), 2.81 – 2.64 (m, 1H), 2.55 –2.29 (m, 1H), 2.26 – 2.08 (m, 2H), 2.06 – 1.95 (m, 2H), 1.86 (ddd, J = 13.4,11.4, 5.1 Hz, 1H), 1.38 (d, J = 1.1 Hz, 4H), 1.32 – 1.20 (m, 1H); 19 F NMR (376MHz, CDCl3) δ -103.83, -104.06, -104.07, -104.54, -104.79, -105.66, -105.79, -106.36, -106.50, -111.94, -111.97; 13C NMR (101 MHz, CDCl3) δ 180.80, 180.76,180.29, 180.18, 164.29, 163.71, 163.39, 163.07, 161.84, 144.52, 144.41,144.19, 130.00, 129.92, 128.20, 128.17, 127.97, 127.94, 123.64, 123.58,123.54, 123.49, 120.01, 119.85, 119.74, 119.64, 116.64, 116.56, 116.48, 116.25, 114.13, 114.05, 111.54, 109.48, 109.28, 109.25, 109.19, 109.05, 108.97, 97.63, 97.44, 97.35, 97.17, 77.38, 77.26, 77.06, 76.74, 53.78, 47.77, 47.66, 47.55, 47.39, 37.06, 36.83, 36.72, 36.59, 36.49, 36.25, 36.08, 35.26, 35.21, 34.62, 34.38, 29.69, 29.27, 27.81, 27.48, 27.27, 26.52, 26.42, 25.00, 24.95, 24.91, 24.59, 24.55, 24.51, 24.46, 24.04, 23.98, 23.75.

[0054] Example 6

[0055] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile is used as a photocatalyst, potassium phosphate is used as a base, and the 1,4-cyano migration, desulfurization and late cyclization reaction of N-((4-(tert-butyl)phenyl)sulfonyl)-2-cyano-N,2-dimethylhexyl-5-enamide and methyl bromide difluoropropionate produces methyl 6-(6-(tert-butyl)-1-ethyl-3-methyl-2-oxoindoline-3-yl)-4-cyano-2,2-difluorohexanoate, as detailed below:

[0056] In a glove box, N-((4-(tert-butyl)phenyl)sulfonyl)-2-cyano-N,2-dimethylhex-5-enamide (0.17 mmol, 1.0 equivalent), methyl bromodifluoroacetate 2a (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a yellow oil in 74% yield.

[0057] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.11 (t, J = 1.6 Hz, 2H), 6.87 (t, J = 1.1 Hz, 1H), 3.88 (d, J = 1.6 Hz, 3H), 3.84 – 3.71 (m, 2H), 2.80– 2.62 (m, 1H), 2.42 (ddq, J = 28.8, 14.5, 4.8 Hz, 1H), 2.14 (dddd, J =24.6, 11.4, 8.9, 7.1, 4.2 Hz, 2H), 2.06 – 1.97 (m, 1H), 1.87 (dddd, J = 13.3,11.4, 5.3 Hz, 1H), 1.47 – 1.38 (m, 1H), 1.36 (dd, J = 4.3, 2.0 Hz, 12H), 1.26 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 179.75, 179.67, 163.76, 163.44,163.12, 151.95, 151.84, 141.94, 130.17, 129.96, 122.19, 122.16, 119.88,119.79, 119.64, 119.55, 116.64, 114.11, 111.62, 105.74, 105.71, 77.37, 77.05,76.73, 53.74, 47.38, 47.24, 37.13, 36.89, 36.82, 36.65, 36.58, 36.35, 35.38, 35.02, 34.64, 34.51, 31.56, 31.47, 29.70, 27.84, 27.66, 27.59, 25.04, 25.00, 24.95, 24.54, 24.49, 24.45, 24.01, 23.87, 23.71, 12.86.

[0058] Example 7

[0059] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and subsequent cyclization reactions of N-([1,1'-biphenyl]-4-ylsulfonyl)-2-cyano-N,2-dimethylhexyl-5-enamide and methyl bromide difluoropropionate were carried out to generate methyl 4-cyano-6-(1-ethyl-3-methyl-2-oxo-6-phenylindoline-3-yl)-2,2-difluorohexanoate, as detailed below:

[0060] In a glove box, N-([1,1'-biphenyl]-4-ylsulfonyl)-2-cyano-N,2-dimethylhex-5-enamide (0.17 mmol, 1.0 equivalent), methyl bromodifluoroacetate 2a (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a yellow oil in 68% yield.

[0061] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.63 – 7.55 (m, 2H), 7.52– 7.44 (m, 2H), 7.44 – 7.33 (m, 2H), 7.32 – 7.25 (m, 2H), 3.87 (dd, J = 3.9,2.0 Hz, 3H), 3.85 – 3.73 (m, 2H), 2.74 (ddq, J = 26.5, 9.3, 4.7 Hz, 1H), 2.44 (ddtd, J = 23.6, 18.7, 14.5, 9.6 Hz, 1H), 2.25 – 2.04 (m, 3H), 1.92 (ddt, J =13.3, 11.1, 5.1 Hz, 1H), 1.55 – 1.45 (m, 1H), 1.43 (dd, J = 4.7, 1.2 Hz, 3H), 1.29 (td, J = 7.3, 1.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 179.55, 179.44,179.26, 163.73, 163.41, 163.09, 142.74, 141.98, 141.92, 141.55, 140.97,140.77, 138.59, 136.39, 136.31, 133.61, 132.15, 131.94, 129.87, 128.90,128.36, 127.93, 127.69, 127.25, 127.16, 127.12, 126.91, 122.95, 121.85, 121.77, 121.64, 121.60, 119.81, 119.71, 116.58, 114.14, 111.17, 108.68, 107.37, 77.38, 77.06, 76.74, 53.80, 53.76, 53.18, 47.85, 47.70, 47.61, 47.57, 47.49, 47.41, 37.15, 36.92, 36.80, 36.68, 36.56, 36.33, 35.42, 34.91, 34.80, 34.71, 34.65, 27.87, 27.81, 27.56, 25.10, 25.06, 25.02, 24.62, 24.57, 24.53, 24.09, 23.87, 23.82, 23.46, 12.85, 12.78.

[0062] Example 8

[0063] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and late cyclization reactions of N-((3-bromophenyl)sulfonyl)-2-cyano-N,2-dimethylhexyl-5-enamide and methyl bromide difluoropropionate yielded methyl 6-(7-bromo-1-ethyl-3-methyl-2-oxoindoline-3-yl)-4-cyano-2,2-difluorohexanoate, as detailed below:

[0064] In a glove box, N-((3-bromophenyl)sulfonyl)-2-cyano-N,2-dimethylhex-5-enamide (0.17 mmol, 1.0 equivalent), methyl bromodifluoroacetate 2a (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a yellow oil in 66% yield.

[0065] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.41 (dt, J = 8.2, 1.1Hz, 1H), 7.13 (dt, J = 7.3, 1.2 Hz, 1H), 6.95 (ddd, J = 8.2, 7.3, 2.8 Hz,1H), 4.19 (q, J = 7.0 Hz, 2H), 3.89 (d, J = 3.1 Hz, 3H), 2.74 (dtd, J = 21.1,9.5, 4.9 Hz, 1H), 2.43 (dddd, J = 35.6, 18.8, 14.5, 9.5 Hz, 1H), 2.24 – 1.95(m, 3H), 1.84 (ddd, J = 13.4, 11.7, 4.7 Hz, 1H), 1.47 – 1.40 (m, 1H), 1.37(d, J = 1.6 Hz, 3H), 1.34 (t, J = 6.1 Hz, 1H), 1.29 (dd, J = 7.0, 1.5 Hz, 3H); 19 F NMR (376 MHz, CDCl3) δ -103.71, -104.14, -104.42, -104.85, -105.72, -105.85, -106.43, -106.56; 13C NMR (101 MHz, CDCl3) δ 179.98, 178.58, 163.38,141.23, 139.87, 136.53, 136.31, 135.37, 134.10, 131.16, 126.04, 124.05,123.96, 121.62, 119.68, 119.52, 115.51, 115.40, 109.87, 102.38, 77.34, 77.03,76.71, 53.77, 47.85, 47.67, 47.27, 47.09, 36.83, 36.59, 36.52, 36.23, 35.63, 35.28, 34.83, 34.78, 34.70, 29.78, 29.70, 29.32, 27.76, 27.65, 27.35, 27.22, 25.05, 24.48, 24.18, 23.90, 23.60, 15.03, 12.64.

[0066] Example 9

[0067] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and subsequent cyclization reaction of 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide and ethyl 3-bromo-2,2-difluoropropionate were carried out to generate ethyl 4-cyano-2,2-difluoro-6-(1,3,6-trimethyl-2-oxoindoline-3-yl)hexanoate, as detailed below:

[0068] In a glove box, 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide (0.17 mmol, 1.0 equivalent), ethyl 3-bromo-2,2-difluoropropionate (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a yellow oil in 75% yield.

[0069] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.08 (d, J = 7.5 Hz, 1H), 6.93 – 6.89 (m, 1H), 6.70 (s, 1H), 4.32 (qd, J = 7.2, 2.0 Hz, 2H), 3.20 (s,3H), 2.80 – 2.63 (m, 1H), 2.23 – 1.97 (m, 3H), 1.92 – 1.74 (m, 1H), 1.48 –1.38 (m, 1H), 1.38 – 1.33 (m, 6H), 1.32 – 1.18 (m, 1H); 19 F NMR (376 MHz, CDCl3) δ -104.17, -104.43, -104.88, -105.13, -105.80, -105.98, -106.51, -106.69; 13 C NMR (101 MHz, CDCl3) δ 180.12, 180.01, 163.27, 162.95, 162.63,143.17, 143.14, 138.44, 138.40, 132.30, 130.95, 129.95, 129.74, 128.84,123.48, 123.40, 123.33, 122.24, 119.89, 119.80, 116.64, 116.56, 114.12,114.05, 111.62, 111.55, 109.24, 108.03, 77.45, 77.13, 76.81, 63.50, 47.57, 47.54, 47.41, 47.39, 37.02, 36.78, 36.69, 36.55, 36.46, 36.22, 35.32, 34.68, 28.95, 27.93, 27.63, 26.17, 24.97, 24.93, 24.89, 24.55, 24.51, 24.47, 24.06, 23.79, 21.76, 13.82.

[0070] Example 10

[0071] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and subsequent cyclization reaction of 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide and ethyl bromide propionate yielded ethyl 4-cyano-6-(1,3,6-trimethyl-2-oxoindoline-3-yl)hexanoate, as detailed below:

[0072] In a glove box, 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide (0.17 mmol, 1.0 equivalent), ethyl bromide propionate (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a yellow oil in 65% yield.

[0073] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.07 (dd, J = 7.5, 5.4Hz, 1H), 6.93 – 6.88 (m, 1H), 6.69 (d, J = 1.5 Hz, 1H), 4.11 (qd, J = 7.2,2.9 Hz, 2H), 3.20 (s, 3H), 2.58 – 2.41 (m, 2H), 2.40 (d, J = 1.6 Hz, 3H), 2.38 – 2.33 (m, 1H), 2.16 – 1.90 (m, 2H), 1.87 – 1.65 (m, 3H), 1.38 – 1.34(m, 3H), 1.27 – 1.22 (m, 3H), 1.21 – 1.06 (m, 1H); 13C NMR (101 MHz, CDCl3) δ180.26, 180.17, 172.11, 172.05, 145.11, 143.22, 138.28, 130.21, 129.96,123.42, 123.30, 122.25, 122.22, 121.01, 109.17, 77.42, 77.10, 76.78, 60.75,47.69, 47.51, 35.72, 35.12, 31.37, 31.11, 30.69, 27.38, 27.23, 26.89, 26.80,26.18, 24.13, 23.76, 21.79, 14.16.

[0074] Example 11

[0075] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and subsequent cyclization reaction of 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide and ethyl bromide ester yielded ethyl 4-cyano-2-propyl-6-(1,3,6-trimethyl-2-oxoindoline-3-yl)hexanoate, as detailed below:

[0076] In a glove box, 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide (0.17 mmol, 1.0 equivalent), ethyl bromoxyvalerate (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a colorless oil in 65% yield.

[0077] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 11H NMR (400 MHz, CDCl3) δ 7.10 – 7.03 (m, 1H), 6.92– 6.87 (m, 1H), 6.68 (d, J = 1.9 Hz, 1H), 4.18 – 4.06 (m, 2H), 3.20 (d, J =1.1 Hz, 3H), 2.57 (ddp, J = 11.1, 8.7, 3.1 Hz, 1H), 2.49 – 2.41 (m, 1H), 2.39(s, 3H), 2.12 – 1.71 (m, 3H), 1.64 – 1.39 (m, 4H), 1.37 – 1.34 (m, 3H), 1.33– 1.29 (m, 1H), 1.27 – 1.24 (m, 3H), 1.23 – 1.04 (m, 2H), 0.88 (td, J = 7.3,5.9 Hz, 3H); 13 13C NMR (101 MHz, CDCl3) δ 180.21 (d, J = 7.2 Hz), 175.06, 174.98,174.81, 143.24 (d, J = 3.6 Hz), 138.26 (d, J = 3.5 Hz), 130.25, 130.03,123.33 (d, J = 9.4 Hz), 122.27 (d, J = 5.6 Hz), 121.34, 121.20, 121.01,109.12, 60.62 (d, J = 3.9 Hz), 60.41, 47.68, 47.53, 43.09, 42.90 (d, J = 5.2Hz), 35.70, 35.13, 35.07 – 34.81 (m), 34.55, 34.16 (d, J = 8.1 Hz), 33.85,33.52, 30.41, 30.01, 29.90, 29.23, 27.96, 27.52 (d, J = 11.1 Hz), 26.85,26.16, 24.08, 23.76, 21.78, 20.13, 14.22 (d, J = 6.4 Hz), 13.86 (d, J = 6.3Hz).

[0078] Example 12

[0079] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and subsequent cyclization reactions of 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide and m-tolyl 2-bromoacetate yielded m-phenyl 4-cyano-6-(1,3,6-trimethyl-2-oxoindoline-3-yl)hexanoate, as detailed below:

[0080] In a glove box, 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide (0.17 mmol, 1.0 equivalent), m-tolyl-2-bromoacetate (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a colorless oil in 70% yield.

[0081] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.07 (t, J = 7.7 Hz, 1H),6.93 – 6.82 (m, 3H), 6.70 – 6.67 (m, 1H), 3.19 (s, 3H), 2.82 – 2.67 (m, 2H),2.67 – 2.56 (m, 1H), 2.39 (d, J = 4.2 Hz, 3H), 2.24 (s, 3H), 2.13 (td, J =12.8, 4.9 Hz, 1H), 2.06 (s, 6H), 2.03 – 1.78 (m, 4H), 1.36 (s, 3H), 1.27 (dh,J = 13.0, 3.5, 2.9 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 180.25, 180.17, 170.18,170.11, 145.73, 143.24, 138.33, 135.49, 130.21, 129.97, 129.70, 129.49,129.30, 127.28, 123.46, 123.35, 122.25, 122.21, 120.97, 120.88, 109.24,77.52, 77.20, 76.88, 47.70, 47.54, 35.72, 35.18, 31.15, 31.06, 30.97, 30.73, 27.46, 27.26, 26.95, 26.85, 26.20, 24.16, 23.81, 21.81, 20.77, 16.28.

[0082] Example 13

[0083] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and subsequent cyclization reaction of 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide and 4-fluorobenzyl 2-bromoacetate yielded 4-fluorobenzyl 4-cyano-6-(1,3,6-trimethyl-2-oxoindoline-3-yl)hexanoate, as detailed below:

[0084] In a glove box, 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide (0.17 mmol, 1.0 equivalent), 4-fluorobenzyl 2-bromoacetate (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a colorless oil in 65% yield.

[0085] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1H NMR (400 MHz, CDCl3) δ 7.31 (ddd, J = 8.7, 5.2,1.6 Hz, 2H), 7.09 – 7.00 (m, 3H), 6.90 (ddt, J = 7.5, 5.1, 1.0 Hz, 1H), 6.68(s, 1H), 5.09 – 5.01 (m, 2H), 3.19 (s, 3H), 2.57 – 2.41 (m, 3H), 2.39 (s,3H), 2.12 – 1.95 (m, 1H), 1.87 – 1.73 (m, 3H), 1.35 (s, 3H), 1.29 – 1.02 (m,2H); 19 F NMR (376 MHz, CDCl3) δ -113.34; 13 C NMR (101 MHz, CDCl3) δ 180.25,180.15, 171.88, 171.80, 163.95, 161.49, 143.21, 138.31, 131.48, 131.45,130.95, 130.41, 130.38, 130.33, 130.30, 130.21, 129.95, 129.73, 128.86,127.28, 123.43, 123.31, 122.24, 122.20, 121.01, 120.91, 115.68, 115.46,109.18, 77.40, 77.08, 76.76, 65.87, 65.59, 47.69, 47.49, 35.70, 35.10, 31.36, 31.08, 30.67, 27.38, 27.18, 26.87, 26.75, 26.18, 24.14, 23.74, 21.79.

[0086] Example 14

[0087] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile is used as a photocatalyst, potassium phosphate is used as a base, and the 1,4-cyano migration, desulfurization and late cyclization reaction of 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide and (perfluorophenyl)methyl 2-bromoacetate produces (perfluorophenyl)methyl 4-cyano-6-(1,3,6-trimethyl-2-oxoindoline-3-yl)hexanoate, as detailed below:

[0088] In a glove box, 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide (0.17 mmol, 1.0 equivalent), (perfluorophenyl)methyl 2-bromoacetate (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a colorless oil in 72% yield.

[0089] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.07 (dd, J = 7.5, 5.2Hz, 1H), 6.94 – 6.87 (m, 1H), 6.69 (s, 1H), 5.19 (q, J = 1.8 Hz, 2H), 3.20(s, 3H), 2.64 (d, J = 5.4 Hz, 1H), 2.55 – 2.45 (m, 2H), 2.40 (s, 3H), 2.14 –1.94 (m, 2H), 1.89 – 1.67 (m, 4H), 1.36 (s, 4H), 1.29 – 1.23 (m, 1H); 19 F NMR (376 MHz, CDCl3) δ -141.77, -141.79, -141.81, -141.82, -141.85, -141.87, -152.18, -152.21, -152.24, -152.26, -152.29, -152.32, -161.32, -161.34, -161.36, -161.38, -161.39, -161.41, -161.43, -161.45, -161.46, -161.48; 13C NMR(101 MHz, CDCl3) δ 180.26, 180.16, 171.37, 171.31, 146.90, 144.45, 143.47,143.20, 138.80, 138.32, 136.27, 136.09, 135.88, 130.18, 129.92, 129.71,128.84, 127.26, 123.43, 123.32, 122.23, 122.19, 120.89, 120.80, 109.19,77.40, 77.28, 77.08, 76.76, 53.51, 47.68, 47.49, 35.66, 35.06, 31.04, 31.00, 30.63, 29.69, 29.30, 27.37, 27.03, 26.86, 26.61, 26.17, 24.12, 23.73, 21.75, 21.50.

[0090] Example 15

[0091] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and subsequent cyclization reactions of 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide and cyclohexylmethyl 2-bromoacetate yielded cyclohexylmethyl 4-cyano-6-(1,3,6-trimethyl-2-oxoindolin-3-yl)hexanoate, as detailed below:

[0092] In a glove box, 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide (0.17 mmol, 1.0 equivalent), cyclohexylmethyl 2-bromoacetate (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred at room temperature under blue LED light for 24 hours. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a colorless oil in 70% yield.

[0093] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1H NMR (400 MHz, CDCl3) δ 7.07 (dd, J = 7.5, 5.7Hz, 1H), 6.92 – 6.87 (m, 1H), 6.69 (d, J = 1.7 Hz, 1H), 3.87 (dd, J = 6.6,2.6 Hz, 2H), 3.20 (s, 3H), 2.59 – 2.41 (m, 3H), 2.40 (d, J = 1.7 Hz, 4H), 2.15 – 1.94 (m, 2H), 1.89 – 1.77 (m, 2H), 1.76 – 1.68 (m, 5H), 1.36 (s, 4H),1.29 – 1.09 (m, 5H), 1.01 – 0.87 (m, 2H); 13 C NMR (101 MHz, CDCl3) δ 180.25,180.17, 172.21, 172.15, 143.21, 138.27, 130.22, 129.98, 129.70, 127.27,123.42, 123.30, 122.23, 122.20, 121.09, 121.01, 109.17, 77.44, 77.33, 77.12,76.80, 69.93, 47.69, 47.51, 37.00, 35.71, 35.13, 31.37, 31.33, 31.13, 30.71, 29.61, 27.37, 27.27, 26.87, 26.83, 26.30, 26.18, 25.61, 24.12, 23.75, 21.78.

[0094] Example 16

[0095] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and late cyclization reactions of 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide and 3-bromodihydrofuran-2(3H)-one yielded 2-((2-oxotetrahydrofuran-3-yl)methyl)-4-(1,3,6-trimethyl-2-oxoindoline-3-yl)butyronitrile, as detailed below:

[0096] In a glove box, 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide (0.17 mmol, 1.0 equivalent), 3-bromodihydrofuran-2(3H)-one (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a colorless oil in 65% yield.

[0097] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.08 (ddd, J = 6.9, 4.5,2.2 Hz, 1H), 6.95 – 6.87 (m, 1H), 6.72 – 6.67 (m, 1H), 4.40 – 4.12 (m, 2H), 3.20 (d, J = 1.5 Hz, 3H), 3.01 – 2.89 (m, 1H), 2.70 – 2.45 (m, 2H), 2.40 (d,J = 1.9 Hz, 3H), 2.17 – 1.81 (m, 4H), 1.75 – 1.55 (m, 1H), 1.51 – 1.41 (m,1H), 1.36 (d, J = 1.8 Hz, 3H), 1.33 – 1.06 (m, 2H); 13C NMR (101 MHz, CDCl3) δ180.14, 177.80, 143.20, 138.41, 130.96, 130.07, 129.81, 128.86, 123.50,123.42, 123.37, 123.34, 122.23, 120.63, 120.52, 109.26, 109.19, 77.41, 77.09,76.77, 66.53, 66.47, 65.58, 47.70, 47.66, 47.51, 42.67, 37.43, 37.28, 37.01,35.70, 35.54, 35.04, 34.92, 33.33, 33.14, 32.88, 32.13, 30.57, 30.02, 29.95, 29.74, 29.50, 29.20, 28.61, 28.54, 27.76, 27.50, 27.39, 26.75, 26.21, 24.11, 23.84, 23.81, 21.79, 19.19, 13.74.

[0098] Example 17

[0099] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and late cyclization reactions of 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide and 2-(thien-2-yl)ethyl 2-bromoacetate were used to generate 2-(thien-2-yl)ethyl 4-cyano-6-(1,3,6-trimethyl-2-oxoindolin-3-yl)hexanoate, as detailed below:

[0100] In a glove box, 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide (0.17 mmol, 1.0 equivalent), 2-(thiophen-2-yl)ethyl-2-bromoacetate (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred at room temperature under blue LED light for 24 hours. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a colorless oil in 71% yield.

[0101] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.19 – 7.13 (m, 1H), 7.06 (dd, J = 7.5, 6.0 Hz, 1H), 6.96 – 6.88 (m, 2H), 6.84 (d, J = 3.5 Hz, 1H), 6.68 (s, 1H), 4.33 – 4.23 (m, 2H), 3.20 (s, 3H), 3.14 (td, J = 6.7, 2.2 Hz,2H), 2.52 – 2.41 (m, 3H), 2.39 (s, 3H), 2.13 – 2.03 (m, 1H), 2.02 – 1.93 (m,1H), 1.85 – 1.64 (m, 3H), 1.36 (s, 3H), 1.24 – 1.10 (m, 1H); 13 C NMR (101 MHz, CDCl3) δ 180.16, 171.91, 143.23, 139.70, 138.30, 130.23, 129.98, 129.57,128.80, 126.94, 125.63, 124.14, 123.42, 123.31, 122.25, 122.22, 121.06,109.17, 77.39, 77.08, 76.76, 64.89, 47.69, 47.51, 35.70, 35.09, 31.37, 31.33,31.08, 30.64, 29.22, 27.39, 27.19, 26.87, 26.75, 26.19, 25.74, 24.14, 23.75, 21.79.

[0102] Example 18

[0103] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and late cyclization reactions of 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide and furan-2-ylmethyl 2-bromoacetate were used to generate furan-2-ylmethyl 4-cyano-6-(1,3,6-trimethyl-2-oxoindoline-3-yl)hexanoate, as detailed below:

[0104] In a glove box, 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide (0.17 mmol, 1.0 equivalent), furan-2-ylmethyl-2-bromoacetate (0.26 mmol, 1.5 equivalent), 4CzIPN (0.0017 mmol, 2 mol%), and K3PO4 (0.4 mmol, 2.0 equivalent) were added to a dried, screw-capped 4 mL vial (equipped with a magnetic stir bar), along with acetonitrile (1.5 mL). The reaction mixture was stirred for 24 hours at room temperature under blue LED light. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography to give a colorless oil in 70% yield.

[0105] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.42 (dd, J = 2.0, 0.8Hz, 1H), 7.06 (dd, J = 7.5, 5.8 Hz, 1H), 6.93 – 6.87 (m, 1H), 6.68 (s, 1H),6.42 – 6.33 (m, 2H), 5.07 – 5.03 (m, 2H), 3.20 (s, 3H), 2.57 – 2.41 (m, 3H), 2.40 – 2.38 (m, 3H), 2.13 – 1.93 (m, 2H), 1.86 – 1.69 (m, 3H), 1.35 (s, 3H),1.27 – 1.24 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 180.25, 180.16, 171.71, 171.64,149.15, 143.39, 143.23, 138.30, 130.24, 129.97, 129.56, 128.81, 123.43,123.30, 122.25, 122.21, 120.98, 120.90, 116.37, 110.84, 110.61, 109.16,77.34, 77.23, 77.02, 76.71, 58.29, 47.69, 47.51, 35.72, 35.10, 34.61, 31.23, 31.07, 30.65, 29.70, 28.93, 27.37, 27.19, 26.86, 26.74, 26.18, 24.13, 23.74, 23.47, 21.78.

[0106] Example 19

[0107] In this embodiment, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile was used as a photocatalyst, potassium phosphate as a base, and the 1,4-cyano migration, desulfurization, and late cyclization reaction of 2-cyano-N,2-dimethyl-N-p-toluenesulfonylhexyl-5-enamide and 4-methoxyphenyl 2-bromoacetate produced 4-methoxyphenyl 4-cyano-6-(1,3,6-trimethyl-2-oxoindoline-3-yl)hexanoate. .

[0108] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and characterized at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. 1 H NMR (400 MHz, CDCl3) δ 7.10 – 7.05 (m, 1H), 7.00– 6.94 (m, 2H), 6.93 – 6.85 (m, 3H), 6.69 (t, J = 2.2 Hz, 1H), 3.78 (s, 3H), 3.19 (s, 3H), 2.76 – 2.53 (m, 3H), 2.39 (d, J = 3.4 Hz, 3H), 2.17 – 2.03 (m,1H), 2.02 – 1.77 (m, 4H), 1.38 – 1.34 (m, 3H), 1.27 (dddd, J = 11.2, 8.5,6.3, 4.9 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 180.24, 180.15, 171.07, 171.01,157.35, 143.92, 143.22, 138.31, 130.19, 129.95, 123.45, 123.33, 122.25,122.20, 121.04, 120.95, 114.48, 109.21, 77.49, 77.17, 76.86, 55.59, 47.70,47.52, 35.70, 35.14, 31.41, 31.38, 31.09, 30.69, 27.40, 27.10, 26.94, 26.73,26.19, 24.15, 23.80, 21.80; HRMS ESI + , MeCN) m / z calcd for C25H28N2O4Na + (M+Na) + :443.1943, found at 443.1940.

[0109] The present invention has been described in detail above with reference to specific embodiments and exemplary examples; however, these descriptions should not be construed as limiting the present invention. Those skilled in the art will understand that various equivalent substitutions, modifications, or improvements can be made to the technical solutions and embodiments of the present invention without departing from the spirit and scope of the invention, and all such modifications and improvements fall within the scope of the present invention. The scope of protection of the present invention is defined by the appended claims.

Claims

1. A method for constructing indolones based on radical-mediated 1,4-cyano migration, desulfurization and cyclization, characterized in that, Includes the following steps: Under a protective atmosphere, 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide compounds, brominated ester compounds, a photocatalyst, and potassium phosphate are mixed in an organic solvent, and 1,4-cyano migration, desulfurization, and cyclization reactions are carried out under light irradiation to obtain the indole ketone compounds.

2. The method for constructing indolones based on radical-mediated 1,4-cyano migration, desulfurization and cyclization according to claim 1, characterized in that, The structural general formula of the 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide compound is wherein R1 is hydrogen, fluorine, bromine, tert-butyl or phenyl.

3. The method for constructing indolones based on radical-mediated 1,4-cyano migration, desulfurization and cyclization according to claim 2, characterized in that, The 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide compounds are selected from one of the following: 2-cyano-N,2-dimethyl-N-toluenesulfonylhex-5-enamide, 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide, 2-cyano-N-((4-fluorophenyl)sulfonyl)-N,2-dimethylhex-5-enamide, N-((3-bromophenyl)sulfonyl)-2-cyano-N,2-dimethylhex-5-enamide, N-((4-(tert-butyl)phenyl)sulfonyl)-2-cyano-N,2-dimethylhex-5-enamide, and N-([1,1'-biphenyl]-4-ylsulfonyl)-2-cyano-N,2-dimethylhex-5-enamide.

4. The method for constructing indolones based on radical-mediated 1,4-cyano migration, desulfurization and cyclization according to claim 1, wherein, The structural formula of the bromoester compound is wherein R is H, F or alkyl; R2 is methyl, ethyl, phenyl, 4-methoxyphenyl, 2,4,6-trimethylphenyl, 1-naphthyl, 4-fluorobenzyl, (perfluorophenyl)methyl, cyclohexylmethyl, 3,5-dimethoxybenzyl, dihydrofuran-2(3H)-onyl, 2-(thiophen-2-yl)ethyl, furan-2-ylmethyl or 2-isopropyl-5-methylcyclohexyl.

5. The method for constructing indolones based on radical-mediated 1,4-cyano migration, desulfurization and cyclization according to claim 4, characterized in that, The brominated ester compounds are selected from one of the following: methyl bromide difluoropropionate, ethyl 3-bromo-2,2-difluoropropionate, ethyl 3-bromo-2-fluoropropionate, ethyl bromide propionate, ethyl bromide butyrate, ethyl bromide valerate, ethyl bromide hexanoate, phenyl 2-bromoacetate, 4-methoxyphenyl 2-bromoacetate, m-tolyl 2-bromoacetate, 1-naphthyl 2-bromoacetate, 4-fluorobenzyl 2-bromoacetate, (perfluorophenyl)methyl 2-bromoacetate, cyclohexylmethyl 2-bromoacetate, 3,5-dimethoxybenzyl 2-bromoacetate, 3-bromodihydrofuran-2(3H)-one, 2-(thiophen-2-yl)ethyl 2-bromoacetate, furan-2-ylmethyl 2-bromoacetate, diethyl 2-bromo-2-methylmalonate, and 2-isopropyl-5-methylcyclohexyl 2-bromoacetate.

6. The method for constructing indole ketone compounds based on radical-mediated 1,4-cyano migration, desulfurization, and cyclization as described in claim 1, characterized in that... The photocatalyst is 2,4,5,6-tetra(9-carbazolyl)-1,3-dicyanobenzene, and its structural formula is .

7. The method for constructing indolones based on radical-mediated 1,4-cyano migration, desulfurization and cyclization according to claim 1, wherein, The molar ratio of the photocatalyst, potassium phosphate, 2-cyano-N,2-dimethyl-N-(phenylsulfonyl)hex-5-enamide compound, and brominated ester compound is (0.01-0.05):(2-3):1:(1.5-2). ​ 8. The method for constructing indolones based on radical-mediated 1,4-cyano migration, desulfurization and cyclization according to claim 1, wherein, The temperature for the 1,4-cyano migration, desulfurization, and cyclization reactions is 25-35℃.

9. The method for constructing indolones based on radical-mediated 1,4-cyano migration, desulfurization and cyclization according to claim 1, wherein, The 1,4-cyano migration, desulfurization and cyclization reaction also includes filtration, concentration and purification steps.

10. The method for constructing indolones based on radical-mediated 1,4-cyano migration, desulfurization and cyclization according to claim 1, characterized in that, The organic solvent is selected from one or more of acetonitrile, N,N-dimethylformamide and dimethyl sulfoxide.

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