A process for the preparation of 4-(1-aryl-2-boryloxyethyl)-3,4-dihydroquinolin-2-ones

Abstract

The application provides a method for preparing 4-(1-aryl-2-boronic acid ester ethyl)-3,4-dihydroquinoline-2-ketone, and belongs to the field of synthesis of medical intermediates and fine chemical industry. The method uses olefin as an alkyl precursor, a complex formed by cuprous chloride and an organic phosphine ligand as a catalyst, and a copper boron active species is obtained by reaction with pinacol diboron, addition is carried out on the olefin, in-situ generation of an alkyl copper reagent containing a boronic acid ester group, then the reagent is subjected to 1,4-conjugate addition on quinoline-2-ketone, and a series of 4-(1-aryl-2-boronic acid ester ethyl)-3,4-dihydroquinoline-2-ketone compounds are prepared. The method has various structures of the used olefin, the catalyst and the ligand are both commercially available, the reaction condition is mild, and the applicable range of the substrate is wide. The method has important application value in the fields of drug research and development, synthesis of bioactive molecules and fine chemical industry.

Description

Technical Field

[0001] This invention relates to a method for preparing 4-(1-aryl-2-boronate ethyl)-3,4-dihydroquinoline-2-one, belonging to the fields of pharmaceutical intermediate synthesis and fine chemical industry. Background Technology

[0002] Nitrogen-containing heterocyclic skeletons, such as 3,4-dihydroquinoline-2-ones and their derivatives, are a prevalent and widely found in natural products, pharmaceuticals, and other bioactive compounds. For example, several drug molecules containing this structural unit, including cilostazol, aripiprazole, and carteolol, have been successfully marketed. Studies have shown that these compounds possess various biological activities, including antibacterial and antiviral activity. In particular, 3,4-dihydroquinoline-2-ones with a substituent at the C4 position not only form the core skeleton of many candidate drugs but are also important intermediates for the synthesis of more complex polycyclic alkaloids (Mini-Rev. Med. Chem. 2018, 18, 828; Catalysts 2023, 13, 1105). For example, the alkaloids Scandine and Meloscine (J.Nat.Prod.2014, 77, 327; Org.Lett.2019, 21, 7065), the HIV-1 non-nucleoside reverse transcriptase inhibitor 6-C1CPQ (Bioorg.Med.Chem.Lett.2006, 16, 4246), and the marine alkaloid Aniduquinolone A (Mar.Biotechnol.2015, 17, 408) with antifouling activity all contain a C4-substituted 3,4-dihydroquinoline-2-one structure, exhibiting potent and diverse biological activities.

[0003] The synthesis of 3,4-dihydroquinoline-2-one compounds has attracted much attention, especially the introduction of substituents at the C4 position. Traditional methods often employ cyclization strategies using N-arylacrylamides (Lewis acids, transition metals, or visible light catalysis), but these methods are limited to C4 aryl-substituted products; for more challenging C4 alkyl-substituted derivatives, the reactivity and selectivity are poor. In recent years, synthetic chemists have turned to developing direct, non-cyclized C4 alkylation strategies using readily available quinoline-2-ones as starting materials. The mainstream methods fall into two categories: one is the pre-synthesized 4-alkylquinoline-2-one catalytic hydrogenation, such as Glorius' Ru-NHC system, Xie's Ir-SpiroPAP system, and Zhou and Chen's manganese-catalyzed system (Angew. Chem., Int. Ed. 2021, 60, 23193; Org. Lett. 2021, 23, 3593; J. Am. Chem. Soc. 2026, 148, 10335); the other is the 1,4-nucleophilic alkyl addition of quinoline-2-one, such as Janekki's phosphonyl activation strategy and Harutyunyan's copper-catalyzed Grignard reagent conjugation (RSC Adv. 2015, 5, 78324; Angew. Chem., Int. Ed. 2019, 58, 12950). However, the above methods generally rely on pre-functionalized substrates or highly active organometallic reagents and are limited to the introduction of linear alkyl groups. Therefore, developing a general method for the efficient synthesis of 3,4-dihydroquinoline-2-ones with nonlinear alkyl groups (especially branched alkyl groups with functional group substitution) at the C4 position using stable, diverse, and structurally rich alkylating agents would not only provide an important foundation for the synthesis of pharmaceutical intermediates and the creation of active molecules, but also provide strong support for the synthesis of high-value-added fine chemicals.

[0004] This invention utilizes widely available and structurally diverse olefins as alkyl precursors and a complex formed from cuprous chloride and an organophosphorus ligand as a catalyst. Through reaction with pinacol diboronate, a copper-boron active species is generated in situ, which then undergoes addition to the olefin to obtain a branched alkyl copper reagent containing a borate ester group. This reagent then undergoes a 1,4-conjugated addition to quinoline-2-one, thereby preparing a series of 3,4-dihydroquinoline-2-one derivatives with a nonlinear, functionalized alkyl group at the C4 position, namely 4-(1-aryl-2-boronate ethyl)-3,4-dihydroquinoline-2-one compounds. The raw materials and catalysts used in this method (both olefins and catalysts are commercially available) are inexpensive and readily available. The reaction conditions are mild, the operation is simple, and the substrate range is wide. Summary of the Invention

[0005] The purpose of this invention is to provide a method for preparing 4-(1-aryl-2-boronate ethyl)-3,4-dihydroquinoline-2-one: using an olefin as a raw material, the olefin is reacted with pinacol bis(boronate) (B2pin2) under the catalysis of a complex formed by a phosphine ligand and cuprous chloride to construct a copper-boron active species; this species undergoes addition to the olefin to generate an alkyl copper intermediate with a borate ester group in situ; subsequently, this intermediate undergoes a 1,4-conjugated addition to the C4 position of quinoline-2-one to synthesize a series of 4-(1-aryl-2-boronate ethyl)-3,4-dihydroquinoline-2-one compounds.

[0006] To achieve the above-mentioned objectives, this invention proposes a method for preparing 4-(1-aryl-2-boronate ethyl)-3,4-dihydroquinoline-2-one, the synthetic route of which is shown below:

[0007]

[0008] This invention provides a method for preparing 4-(1-aryl-2-boronate ethyl)-3,4-dihydroquinoline-2-one, the steps of which are as follows:

[0009] Add pinacol diborate (as shown in general formula 3), cuprous chloride, phosphine ligand, and lithium tert-butoxide to a dry Schlenk reaction tube equipped with a stir bar. Vacuum the tube using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add the solvent and stir for 5 minutes. Then add the olefin (as shown in general formula 2) and continue stirring for 5 minutes. Finally, add quinoline-2-one (as shown in general formula 1). Seal the reaction system and control the temperature of the reaction system at 25–100 °C. Stir the reaction for 24–72 hours, cool to room temperature, quench with saturated ammonium fluoride solution, stir for 10 minutes, add saturated sodium chloride solution, and extract with ethyl acetate. Wash the organic phase with saturated sodium chloride solution, concentrate the organic phase, and separate the concentrate by silica gel column chromatography to obtain 4-(1-aryl-2-boronate ethyl)-3,4-dihydroquinoline-2-one (as shown in general formula 4).

[0010] In general formula 1, R 1 Selected from alkyl or halogen atoms, R 2 Selected from alkyl or aryl; R in general formula 2 3 Selected from alkyl or halogen atoms; the phosphine ligand is selected from one of tri-n-butylphosphine, tricyclohexylphosphine, dicyclohexylphenylphosphine, and 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthracene; the solvent is selected from one of N,N-dimethylacetamide and N,N-dimethylformamide.

[0011] In the steps of the above method, the molar ratio of quinoline-2-one 1: olefin 2: pinacol diboronic acid ester 3: cuprous chloride: phosphine ligand: lithium tert-butoxide is 1.0:(2.0~2.5):(2.5~3.0):(0.1~0.2):(0.1~0.4):(0.1~0.2). Detailed Implementation

[0012] The following examples will help to understand the present invention, but are not intended to limit the scope of the invention.

[0013] Example 1: Synthesis of 1-methyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one

[0014]

[0015] Add 127 mg (0.5 mmol) pinacol diborate, 3 mg (0.03 mmol) cuprous chloride (CuCl), 12.2 mg (0.06 mmol) tri-n-butylphosphine (n-Bu3P), and 3.2 mg (0.04 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube, then purge with argon gas three times. While purging with argon, add 1 mL of N,N-dimethylacetamide (DMA) solvent. After stirring for 5 minutes, add 46 μL (0.4 mmol) styrene. Continue stirring for another 5 minutes, then add 32 mg (0.2 mmol) of styrene. 1-Methylquinoline-2-one was prepared by sealing the reaction system and controlling the reaction temperature at 45°C. After stirring for 48 hours, the mixture was cooled to room temperature, quenched with 3 mL of saturated ammonium fluoride solution, stirred for 10 minutes, and then 3 mL of saturated sodium chloride solution was added. The mixture was extracted with ethyl acetate, washed with 2 mL of saturated sodium chloride solution, concentrated, and separated by silica gel column chromatography to obtain 1-methyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one, with a yield of 71% (Cis-isomer:Trans-isomer = 27:73).

[0016] Cis-isomer: 1H NMR(500MHz,Chloroform-d)δ7.29-7.27(m,1H),7.26-7.24(d,J=7.0Hz,2H),7.23-7.20(dd,J=7.5,1.6Hz,1H),7.17-7.14(m,3H),7.05-7.01(td,J=7.4,1.1Hz,1H),6.97-6.94(dd,J=8.1,1.1Hz,1H),3.29-3.24(s,3H),2.94-2.87(m,2H),2.55-2.48(dd,J=16.1,5.3Hz,1H),2.48-2.42(dd,J=16.2,1.6Hz,1H),1.22-1.18(m,1H),1.05-1.01(dd,J=9.3,5.4Hz,1H),0.95-0.92(s,6H),0.91-0.88(s,7H). 13 C NMR(126MHz,Chloroform-d)δ169.49,143.54,140.26,130.05,128.39-128.33,127.82,126.68,122.39,114.94,83.08,44.63,43.85,34.90,29.36,24.79,24.44. 11 B NMR(160MHz,Chloroform-d)δ33.93.HRMS(ESI)m / z:calculated for[C 24 H 30 BNO3+H] + 392.2392,found392.2390;

[0017] Trans-isomer: 1 H NMR(500MHz,Chloroform-d)δ7.23-7.18(ddd,J=7.9,7.1,1.9Hz,1H),7.13-7.06(m,3H),6.91-6.82(m,5H),3.11-3.03(td,J=8.5,6.0Hz,1H),3.01-2.97(td,J=6.5,2.1Hz,1H),2.97-2.94(s,3H),2.89-2.84(dd,J=16.4,2.1Hz,1H),2.77-2.71(dd,J=16.4,6.9Hz,1H),1.31-1.24(m,2H),1.01-0.97(s,6H),0.93-0.91(s,6H). 13CNMR (126MHz, Chloroform-d) δ168.94, 142.88, 140.54, 129.42, 128.28, 127.55, 1 26.71, 126.43, 122.07, 114.59, 83.02, 45.67, 43.62, 35.84, 29.01, 24.58, 24.30. 11 B NMR (160MHz, Chloroform-d) δ34.84.HRMS (ESI) m / z: calculated for [C 24 H 30 BNO3+H] + 392.2392, found392.2390.

[0018] Example 2: Synthesis of 1-methyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one

[0019]

[0020] Add 127 mg (0.5 mmol) pinacol diborate, 12.6 mg (0.06 mmol) dicyclohexylphenylphosphine (PPhCy2), 3 mg (0.03 mmol) cuprous chloride (CuCl), and 3.2 mg (0.04 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stirrer. Evacuate the tube using a Schlenk double-row tube, then purge with argon gas three times. While purging with argon, add 1 mL of N,N-dimethylacetamide (DMA) solvent. After stirring for 5 minutes, add 46 μL (0.4 mmol) styrene. Continue stirring for another 5 minutes, then add 32 μL of styrene. 0.2 mmol of 1-methylquinoline-2-one was added to a sealed reaction system. The reaction system temperature was controlled at 45 °C. After stirring for 48 hours, the mixture was cooled to room temperature and quenched with 3 mL of saturated ammonium fluoride solution. After stirring for 10 minutes, 3 mL of saturated sodium chloride solution was added. The mixture was extracted with ethyl acetate, and the organic phase was washed with 2 mL of saturated sodium chloride solution. The organic phase was concentrated, and the concentrate was separated by silica gel column chromatography to obtain 1-methyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one, with a yield of 72% (Cis-:Trans- = 25:75).

[0021] Cis-isomer: 1H NMR(500MHz,Chloroform-d)δ7.29-7.27(m,1H),7.26-7.24(d,J=7.0Hz,2H),7.23-7.20(dd,J=7.5,1.6Hz,1H),7.17-7.14(m,3H),7.05-7.01(td,J=7.4,1.1Hz,1H),6.97-6.94(dd,J=8.1,1.1Hz,1H),3.29-3.24(s,3H),2.94-2.87(m,2H),2.55-2.48(dd,J=16.1,5.3Hz,1H),2.48-2.42(dd,J=16.2,1.6Hz,1H),1.22-1.18(m,1H),1.05-1.01(dd,J=9.3,5.4Hz,1H),0.95-0.92(s,6H),0.91-0.88(s,7H). 13 C NMR(126MHz,Chloroform-d)δ169.49,143.54,140.26,130.05,128.39-128.33,127.82,126.68,122.39,114.94,83.08,44.63,43.85,34.90,29.36,24.79,24.44. 11 B NMR(160MHz,Chloroform-d)δ33.93.HRMS(ESI)m / z:calculated for[C 24 H 30 BNO3+H] + 392.2392,found392.2390;

[0022] Trans-isomer: 1 H NMR(500MHz,Chloroform-d)δ7.23-7.18(ddd,J=7.9,7.1,1.9Hz,1H),7.13-7.06(m,3H),6.91-6.82(m,5H),3.11-3.03(td,J=8.5,6.0Hz,1H),3.01-2.97(td,J=6.5,2.1Hz,1H),2.97-2.94(s,3H),2.89-2.84(dd,J=16.4,2.1Hz,1H),2.77-2.71(dd,J=16.4,6.9Hz,1H),1.31-1.24(m,2H),1.01-0.97(s,6H),0.93-0.91(s,6H). 13CNMR (126MHz, Chloroform-d) δ168.94, 142.88, 140.54, 129.42, 128.28, 127.55, 1 26.71, 126.43, 122.07, 114.59, 83.02, 45.67, 43.62, 35.84, 29.01, 24.58, 24.30. 11 B NMR (160MHz, Chloroform-d) δ34.84.HRMS (ESI) m / z: calculated for [C 24 H 30 BNO3+H] + 392.2392, found392.2390.

[0023] Example 3: Synthesis of 1-methyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one

[0024]

[0025] Add 127 mg (0.5 mmol) pinacol diborate, 12 mg (0.02 mmol) 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene (XantPhos), 2 mg (0.02 mmol) cuprous chloride (CuCl), and 1.6 mg (0.02 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube, then purge with argon gas three times. While purging with argon, add 1 mL of N,N-dimethylacetamide (DMA) solvent. Stir for 5 minutes, then add 46 μL (0.4 mmol) styrene and continue stirring for another 5 minutes. After 1 minute, 32 mg (0.2 mmol) of 1-methylquinoline-2-one was added, the reaction system was sealed, the reaction temperature was controlled at 45 °C, and the reaction was stirred for 48 hours. After cooling to room temperature, 3 mL of saturated ammonium fluoride solution was added to quench the reaction, and after stirring for 10 minutes, 3 mL of saturated sodium chloride solution was added. The mixture was extracted with ethyl acetate, the organic phase was washed with 2 mL of saturated sodium chloride solution, the organic phase was concentrated, and the concentrate was separated by silica gel column chromatography to obtain 1-methyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one, with a yield of 70% (Cis-:Trans- = 28:72).

[0026] Cis-isomer: 1H NMR(500MHz,Chloroform-d)δ7.29-7.27(m,1H),7.26-7.24(d,J=7.0Hz,2H),7.23-7.20(dd,J=7.5,1.6Hz,1H),7.17-7.14(m,3H),7.05-7.01(td,J=7.4,1.1Hz,1H),6.97-6.94(dd,J=8.1,1.1Hz,1H),3.29-3.24(s,3H),2.94-2.87(m,2H),2.55-2.48(dd,J=16.1,5.3Hz,1H),2.48-2.42(dd,J=16.2,1.6Hz,1H),1.22-1.18(m,1H),1.05-1.01(dd,J=9.3,5.4Hz,1H),0.95-0.92(s,6H),0.91-0.88(s,7H). 13 C NMR(126MHz,Chloroform-d)δ169.49,143.54,140.26,130.05,128.39-128.33,127.82,126.68,122.39,114.94,83.08,44.63,43.85,34.90,29.36,24.79,24.44. 11 B NMR(160MHz,Chloroform-d)δ33.93.HRMS(ESI)m / z:calculated for[C 24 H 30 BNO3+H] + 392.2392,found392.2390;

[0027] Trans-isomer: 1 H NMR(500MHz,Chloroform-d)δ7.23-7.18(ddd,J=7.9,7.1,1.9Hz,1H),7.13-7.06(m,3H),6.91-6.82(m,5H),3.11-3.03(td,J=8.5,6.0Hz,1H),3.01-2.97(td,J=6.5,2.1Hz,1H),2.97-2.94(s,3H),2.89-2.84(dd,J=16.4,2.1Hz,1H),2.77-2.71(dd,J=16.4,6.9Hz,1H),1.31-1.24(m,2H),1.01-0.97(s,6H),0.93-0.91(s,6H). 13CNMR (126MHz, Chloroform-d) δ168.94, 142.88, 140.54, 129.42, 128.28, 127.55, 1 26.71, 126.43, 122.07, 114.59, 83.02, 45.67, 43.62, 35.84, 29.01, 24.58, 24.30. 11 B NMR (160MHz, Chloroform-d) δ34.84.HRMS (ESI) m / z: calculated for [C 24 H 30 BNO3+H] + 392.2392, found392.2390.

[0028] Example 4: Synthesis of 1-methyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one

[0029]

[0030] Add 153 mg (0.6 mmol) pinacol diborate, 22.5 mg (0.08 mmol) tricyclohexylphosphine (PCy3), 4 mg (0.04 mmol) cuprous chloride (CuCl), and 3.2 mg (0.04 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of N,N-dimethylacetamide (DMA) solvent. After stirring for 5 minutes, add 58 μL (0.5 mmol) styrene. Continue stirring for 5 minutes, then add 32 mg... (0.2 mmol) 1-methylquinoline-2-one was prepared by sealing the reaction system, controlling the reaction temperature at 25 °C, stirring for 72 hours, cooling to room temperature, quenching with 3 mL of saturated ammonium fluoride solution, stirring for 10 minutes, adding 3 mL of saturated sodium chloride solution, extracting with ethyl acetate, washing the organic phase with 2 mL of saturated sodium chloride solution, concentrating the organic phase, and separating the concentrate by silica gel column chromatography to obtain 1-methyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one, with a yield of 63% (Cis-:Trans- = 27:73).

[0031] Cis-isomer: 1H NMR(500MHz,Chloroform-d)δ7.29-7.27(m,1H),7.26-7.24(d,J=7.0Hz,2H),7.23-7.20(dd,J=7.5,1.6Hz,1H),7.17-7.14(m,3H),7.05-7.01(td,J=7.4,1.1Hz,1H),6.97-6.94(dd,J=8.1,1.1Hz,1H),3.29-3.24(s,3H),2.94-2.87(m,2H),2.55-2.48(dd,J=16.1,5.3Hz,1H),2.48-2.42(dd,J=16.2,1.6Hz,1H),1.22-1.18(m,1H),1.05-1.01(dd,J=9.3,5.4Hz,1H),0.95-0.92(s,6H),0.91-0.88(s,7H). 13 C NMR(126MHz,Chloroform-d)δ169.49,143.54,140.26,130.05,128.39-128.33,127.82,126.68,122.39,114.94,83.08,44.63,43.85,34.90,29.36,24.79,24.44. 11 B NMR(160MHz,Chloroform-d)δ33.93.HRMS(ESI)m / z:calculated for[C 24 H 30 BNO3+H] + 392.2392,found392.2390;

[0032] Ttans-isomer: 1 H NMR(500MHz,Chloroform-d)δ7.23-7.18(ddd,J=7.9,7.1,1.9Hz,1H),7.13-7.06(m,3H),6.91-6.82(m,5H),3.11-3.03(td,J=8.5,6.0Hz,1H),3.01-2.97(td,J=6.5,2.1Hz,1H),2.97-2.94(s,3H),2.89-2.84(dd,J=16.4,2.1Hz,1H),2.77-2.71(dd,J=16.4,6.9Hz,1H),1.31-1.24(m,2H),1.01-0.97(s,6H),0.93-0.91(s,6H). 13CNMR (126MHz, Chloroform-d) δ168.94, 142.88, 140.54, 129.42, 128.28, 127.55, 1 26.71, 126.43, 122.07, 114.59, 83.02, 45.67, 43.62, 35.84, 29.01, 24.58, 24.30. 11 B NMR (160MHz, Chloroform-d) δ34.84.HRMS (ESI) m / z: calculated for [C 24 H 30 BNO3+H] + 392.2392, found392.2390.

[0033] Example 5: Synthesis of 1-methyl-4-(2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)-1-(4-methylphenyl)ethyl)-3,4-dihydroquinoline-2-one

[0034]

[0035] Add 127 mg (0.5 mmol) pinacol diborate, 3 mg (0.03 mmol) cuprous chloride (CuCl), 17 mg (0.06 mmol) tricyclohexylphosphine (PCy3), and 3.2 mg (0.03 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube, then purge with argon gas three times. While purging with argon, add 1 mL of N,N-dimethylformamide (DMF) solvent. After stirring for 5 minutes, add 52 μL (0.4 mmol) 4-methylstyrene. Continue stirring for another 5 minutes, then add 32 mg (0.2 mmol) 1-Methylquinoline-2-one was prepared by sealing the reaction system, controlling the reaction temperature at 45℃, stirring for 48 hours, cooling to room temperature, quenching with 3 mL of saturated ammonium fluoride solution, stirring for 10 minutes, adding 3 mL of saturated sodium chloride solution, extracting with ethyl acetate, washing the organic phase with 2 mL of saturated sodium chloride solution, concentrating the organic phase, and separating the concentrate by silica gel column chromatography to obtain 1-methyl-4-(2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)-1-(4-methylphenyl)ethyl)-3,4-dihydroquinoline-2-one, with a yield of 67% (Cis-isomer:Ttans-isomer = 22:78).

[0036] Cis-isomer: 1H NMR(500MHz,Chloroform-d)δ7.28-7.24(dd,J=15.5,1.6Hz,1H),7.23-7.20(dd,J=7.5,1.6Hz,1H),7.08-7.01(m,5H),6.96-6.93(dd,J=8.1,1.1Hz,1H),3.27-3.24(s,3H),2.88-2.84(m,2H),2.52-2.47(dd,J=16.2,4.8Hz,1H),2.47-2.42(dd,J=16.2,1.6Hz,1H),2.30-2.27(s,3H),1.08-1.05(m,1H),1.05-1.01(d,J=5.5Hz,1H),0.95-0.92(s,6H),0.92-0.90(s,6H). 13 C NMR(126MHz,Chloroform-d)δ169.37,143.68,137.88,131.80,130.76,128.37-128.29,128.19-128.11,126.62,114.81,83.05,44.65,43.77,35.00,29.34,24.77,24.43,20.78. 11 B NMR(160MHz,Chloroform-d)δ33.97.HRMS(ESI)m / z:calculated for[C 25 H 32 BNO3+H] + 406.2548,found 406.2544;

[0037] Ttans-isomer: 1H NMR (500MHz, Chloroform-d) δ7.23-7.17 (dt, J=8.1, 4.5Hz, 1H), 6.93-6.87 (m, 4H), 6.84-6.81 (d, J =8.1Hz, 1H), 6.75-6.70 (d, J = 8.1Hz, 2H), 3.07-3.01 (td, J = 8.4, 5.8Hz, 1H), 3.00-2.95 (td, J = 6.4, 2.2Hz, 1H), 2.95-2.92 (s, 3H), 2.87-2.81 (dd, J=16.5, 2.3Hz, 1H), 2.76-2.68 (dd, J=16.4, 6.9Hz, 1 H), 2.24-2.20(s, 3H), 1.26-1.24(s, 1H), 1.24-1.23(m, 1H), 1.02-0.98(s, 6H), 0.96-0.93(s, 6H). 13 C NMR (126MHz, Chloroform-d) δ169.1, 140.7, 139.8, 135.9, 129.6, 128.3, 128. 2, 127.6, 126.9, 122.2, 114.7, 83.1, 45.5, 43.6, 35.9, 29.1, 24.7, 24.5, 21.0. 11 B NMR (160MHz, Chloroform-d) δ34.74.HRMS (ESI) m / z: calculated for [C 25 H 32 BNO3+H] + 406.2548, found 406.2544.

[0038] Example 6: Synthesis of 4-(1-(4-chlorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-1-methyl-3,4-dihydroquinoline-2-one

[0039]

[0040] Add 127 mg (0.5 mmol) pinacol diborate, 3 mg (0.03 mmol) cuprous chloride (CuCl), 17 mg (0.06 mmol) tricyclohexylphosphine (PCy3), and 3.2 mg (0.04 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube, then purge with argon gas three times. While purging with argon, add 1 mL of N,N-dimethylacetamide (DMA) solvent. After stirring for 5 minutes, add 48 μL (0.4 mmol) 4-chlorostyrene. Continue stirring for another 5 minutes, then add 32 mg (0.2 mmol) 1-Methylquinoline-2-one was prepared by sealing the reaction system, controlling the reaction temperature at 45°C, stirring for 48 hours, cooling to room temperature, quenching with 3 mL of saturated ammonium fluoride solution, stirring for 10 minutes, adding 3 mL of saturated sodium chloride solution, extracting with ethyl acetate, washing the organic phase with 2 mL of saturated sodium chloride solution, concentrating the organic phase, and separating the concentrate by silica gel column chromatography to obtain 4-(1-(4-chlorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-1-methyl-3,4-dihydroquinoline-2-one, with a yield of 47% (Cis-isomer:Trans-isomer = 40:60).

[0041] Cis-isomer: 1 H NMR (500MHz, Chloroform-d) δ7.30-7.27 (dd, J=8.0, 1.6Hz, 1H), 7.25-7.22 (m, 2H), 7.22-7.18 (dd, J =7.4, 1.5Hz, 1H), 7.10-7.06 (m, 2H), 7.06-7.01 (td, J = 7.4, 1.1Hz, 1H), 6.98-6.94 (d, J = 8.1Hz, 1H), 3 .29-3.21 (s, 3H), 2.94-2.83 (m, 2H), 2.57-2.49 (dd, J=16.2, 5.8Hz, 1H), 2.46-2.39 (dd, J=16.1, 1.6H z, 1H), 1.21-1.14 (dd, J=15.3, 10.6Hz, 1H), 1.10-1.07 (m, 1H), 0.99-0.95 (s, 6H), 0.94-0.91 (s, 6H). 13C NMR(126MHz,Chloroform-d)δ169.22,142.00,140.18,132.34,129.95,129.72,128.37,127.97,122.51,115.03,83.21,44.40,43.45,34.75,29.33,24.83,24.43. 11 B NMR(160MHz,Chloroform-d)δ33.02.HRMS(ESI)m / z:calculated for[C 24 H 29 BClNO3+H] + 426.2002,found426.2001;

[0042] Trans-isomer: 1 H NMR(500MHz,Chloroform-d)δ7.30-7.27(dd,J=7.7,1.6Hz,1H),7.25-7.21(m,2H),7.21-7.18(dd,J=7.4,1.6Hz,1H),7.09-7.06(m,2H),7.05-7.01(td,J=7.4,1.1Hz,1H),6.97-6.93(dd,J=8.1,1.1Hz,1H),3.27-3.20(s,3H),2.94-2.83(m,2H),2.57-2.48(dd,J=16.2,5.8Hz,1H),2.47-2.39(dd,J=16.3,1.6Hz,1H),1.21-1.14(dd,J=15.3,10.6Hz,1H),1.10-1.04(dd,J=15.4,5.2Hz,1H),0.99-0.95(s,6H),0.93-0.90(s,6H). 11 B NMR(160MHz,Chloroform-d)δ33.21. 13 C NMR(126MHz,Chloroform-d)δ169.2,142.0,140.2,132.4,130.0,129.7,128.4,128.0,127.9,122.5,115.0,83.2,44.4,43.5,34.8,29.3,24.8,24.4.HRMS(ESI)m / z:calculated for[C 24 H 29 BClNO3+H] + 426.2002,found 426.2001。

[0043] Example 7: Synthesis of 4-(1-(3-bromophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronylpentan-2-yl)ethyl)-1-methyl-3,4-dihydroquinoline-2-one

[0044]

[0045] Add 127 mg (0.5 mmol) pinacol diborate, 3 mg (0.03 mmol) cuprous chloride (CuCl), 17 mg (0.06 mmol) tricyclohexylphosphine (PCy3), and 3.2 mg (0.04 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube, then purge with argon gas three times. While purging with argon gas, add 1 mL of N,N-dimethylacetamide (DMA) solvent. After stirring for 5 minutes, add 52 μL (0.4 mmol) 3-bromostyrene. Continue stirring for another 5 minutes, then add 32 mg (0.2 mmol) 1-Methylquinoline-2-one was prepared by sealing the reaction system, controlling the reaction temperature at 45°C, stirring for 48 hours, cooling to room temperature, quenching with 3 mL of saturated ammonium fluoride solution, stirring for 10 minutes, adding 3 mL of saturated sodium chloride solution, extracting with ethyl acetate, washing the organic phase with 2 mL of saturated sodium chloride solution, concentrating the organic phase, and separating the concentrate by silica gel column chromatography to obtain 4-(1-(3-bromophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronylpentan-2-yl)ethyl)-1-methyl-3,4-dihydroquinoline-2-one, with a yield of 51% (Cis-isomer:Trans-isomer = 29:71).

[0046] Cis-isomer: 1H NMR(500MHz,Chloroform-d)δ7.33-7.29(m,1H),7.29-7.26(td,J=3.7,3.1,1.8Hz,2H),7.22-7.19(dd,J=7.5,1.6Hz,1H),7.17-7.13(t,J=7.6Hz,1H),7.12-7.09(dt,J=7.8,1.5Hz,1H),7.06-7.02(td,J=7.4,1.1Hz,1H),6.99-6.95(dd,J=8.2,1.0Hz,1H),3.29-3.24(s,3H),2.93-2.87(m,2H),2.59-2.51(dd,J=16.3,5.6Hz,1H),2.49-2.42(dd,J=16.3,1.5Hz,1H),1.16-1.11(dd,J=11.6,4.7Hz,1H),1.08-1.04(dd,J=10.4,4.9Hz,1H),1.00-0.96(s,6H),0.96-0.92(s,6H). 13 C NMR(126MHz,Chloroform-d)δ169.19,146.17,140.26,131.19,130.00,129.90,129.81,128.04,127.77,127.36,122.54,115.04,83.24,44.09,43.79,34.88,29.36,24.85,24.52. 11 B NMR(160MHz,Chloroform-d)δ33.21.HRMS(ESI)m / z:calculated for[C 24 H 29 BBrNO3+H] + 470.1497,found 470.1495;

[0047] Trans-isomer: 1H NMR (500MHz, Chloroform-d) δ7.25-7.21 (m, 2H), 7.03-6.98 (t, J=7.8Hz, 1H), 6.93-6.87 (m, 3H) , 6.87-6.82 (td, J=7.8, 1.4Hz, 2H), 3.06-3.02 (m, 1H), 3.02-3.00 (s, 3H), 3.00-2.95 (td, J=6.4, 2.2Hz, 1H), 2.87-2.81 (dd, J=16.4, 2.2Hz, 1H), 2.79-2.71 (dd, J=16.4, 6.6Hz, 1H), 1.32-1.26 (d d, J=15.5, 6.0Hz, 1H), 1.26-1.21 (dd, J=10.9, 4.4Hz, 1H), 1.04-1.01 (s, 6H), 0.97-0.94 (s, 6H). 13 C NMR (126MHz, Chloroform-d) δ168.8, 145.7, 140.6, 131.1, 129.6, 129.5, 130, 128 .0, 127.5, 126.3, 122.4, 121.8, 114.9, 83.3, 45.6, 43.6, 36.0, 29.2, 24.8, 24.5. 11 B NMR (160MHz, Chloroform-d) δ33.33.HRMS (ESI) m / z: calculated for [C 24 H 29 BBrNO3+H] + 470.1497, found 470.1496.

[0048] Example 8: Synthesis of 4-(1-(2-chlorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-1-methyl-3,4-dihydroquinoline-2-one

[0049]

[0050] Add 127 mg (0.5 mmol) pinacol diborate, 3 mg (0.03 mmol) cuprous chloride (CuCl), 17 mg (0.06 mmol) tricyclohexylphosphine (PCy3), and 3.2 mg (0.04 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube, then purge with argon gas three times. While purging with argon, add 1 mL of N,N-dimethylacetamide (DMA) solvent. After stirring for 5 minutes, add 51 μL (0.4 mmol) 2-chlorostyrene. Continue stirring for another 5 minutes, then add 32 mg (0.2 mmol) 1-Methylquinoline-2-one was prepared by sealing the reaction system, controlling the reaction temperature at 45℃, stirring for 48 hours, cooling to room temperature, quenching with 3 mL of saturated ammonium fluoride solution, stirring for 10 minutes, adding 3 mL of saturated sodium chloride solution, extracting with ethyl acetate, washing the organic phase with 2 mL of saturated sodium chloride solution, concentrating the organic phase, and separating the concentrate by silica gel column chromatography to obtain 4-(1-(2-chlorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-1-methyl-3,4-dihydroquinoline-2-one, with a yield of 46% (Cis-isomer:Trans-isomer = 39:61).

[0051] Cis-isomer: 1 H NMR (500MHz, Chloroform-d) δ7.37-7.31 (m, 1H), 7.30-7.24 (dd, J=15.4, 1.7Hz, 3H), 7.23-7.17 ( dd, J=6.4, 1.7Hz, 2H), 7.15-7.09 (ddd, J=8.6, 6.3, 2.6Hz, 1H), 7.01-6.95 (dd, J=7, 7, 3, 4Hz, 2H), 3.78-3.59 (s, 1H), 3.38-3.27 (s, 3H), 3.08-2.92 (m, 1H), 2.64-2.56 (dd, J=16.5, 6.5Hz, 1H), 2.49 -2.38 (d, J=16.8Hz, 1H), 1.29-1.23 (dt, J=8.5, 5.6Hz, 2H), 0.98-0.92 (s, 6H), 0.92-0.88 (s, 6H). 13 C NMR (126MHz, Chloroform-d) δ169.62, 140.45, 130.28, 127.98, 126.90, 122.27, 114.93, 83.15, 35.42, 29.84, 29.50, 24.72, 24.39. 11B NMR (160MHz, Chloroform-d) δ33.20.HRMS (ESI) m / z: calculated for [C 24 H 29 BClNO3+H] + 426.2002, found 426.1998;

[0052] Trans-isomer: 1 H NMR (500MHz, Chloroform-d) δ7.23-7.17 (m, 2H), 7.16-7.10 (td, J=7.5, 1.4Hz, 1H), 7.09-7.01 (m, 2H) , 6.92-6.88 (m, 1H), 6.86-6.82 (td, J=7.4, 1.1Hz, 1H), 6.81-6.76 (dd, J=7.5, 1.7Hz, 1H), 3.87-3.73 (d t, J=10.4, 6.9Hz, 1H), 3.25-3.16 (s, 3H), 3.06-2.97 (td, J=6.9, 2.4Hz, 1H), 2.94-2.86 (dd, J=16.3, 2. 5Hz, 1H), 2.71-2.61 (dd, J=16.4, 6.7Hz, 1H), 1.28-1.22 (m, 2H), 1.01-0.91 (s, 6H), 0.90-0.81 (s, 6H). 13 CNMR (126MHz, Chloroform-d) δ169.28, 141.37, 140.88, 135.06, 129.29, 128.94, 128.73, 127. 71, 127.51, 127.24, 126.43, 122.36, 114.75, 83.15, 42.98, 39.91, 34.34, 29.39, 24.70, 24.23. 11 B NMR (160MHz, Chloroform-d) δ32.84.HRMS (ESI) m / z: calculated for [C 24 H 29 BClNO3+H] + 426.2002, found 426.1997.

[0053] Example 9: Synthesis of 6-chloro-1-methyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one

[0054]

[0055] Add 127 mg (0.5 mmol) pinacol diboronate, 3 mg (0.03 mmol) cuprous chloride (CuCl), 17 mg (0.06 mmol) tricyclohexylphosphine (PCy3), and 3.2 mg (0.04 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube, then purge with argon gas three times. While purging with argon, add 1 mL of N,N-dimethylacetamide (DMA) solvent. After stirring for 5 minutes, add 46 μL (0.4 mmol) styrene. Continue stirring for 5 minutes, then add 39 mg (0.2 mmol) 6- Chloro-1-methylquinoline-2-one was prepared by sealing the reaction system, controlling the reaction temperature at 45°C, stirring for 48 hours, cooling to room temperature, quenching with 3 mL of saturated ammonium fluoride solution, stirring for 10 minutes, adding 3 mL of saturated sodium chloride solution, extracting with ethyl acetate, washing the organic phase with 2 mL of saturated sodium chloride solution, concentrating the organic phase, and separating the concentrate by silica gel column chromatography to obtain 6-chloro-1-methyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one, with a yield of 77% (Cis-isomer:Trans-isomer = 34:66).

[0056] Cis-isomer: 1 H NMR (500MHz, Chloroform-d) δ7.28-7.25 (d, J=7.5Hz, 1H), 7.25-7.20 (d, J=10.5Hz, 3 H), 7.19-7.15 (m, 1H), 7.15-7.11 (dd, J=6.9, 1.8Hz, 2H), 6.88-6.84 (d, J=8.3Hz, 1H) , 3.24-3.19 (s, 3H), 2.94-2.86 (m, 2H), 2.53-2.43 (m, 2H), 1.24-1.18 (dd, J=15.2, 10 .5Hz, 1H), 1.12-1.07 (dd, J=10.4, 3.3Hz, 1H), 0.99-0.94 (s, 6H), 0.94-0.90 (s, 6H). 13 C NMR (126MHz, Chloroform-d) δ169.01, 143.01, 138.96, 130.07, 129.72, 128.3 7, 127.63, 126.84, 116.09, 83.18, 44.28, 43.85, 34.51, 29.42, 24.78, 24.47. 11B NMR (160MHz, Chloroform-d) δ33.33.HRMS (ESI) m / z: calculated for [C 24 H 29 BClNO3+H] + 426.2002, found 426.1998;

[0057] Trans-isomer: 1 H NMR (500MHz, Chloroform-d) δ7.19-7.13 (dd, J=8.6, 2.4Hz, 1H), 7.16-7.07 (m, 3H), 6.87-6.82 (m, 3H ), 6.77-6.72 (d, J=8.6Hz, 1H), 3.10-3.01 (dt, J=11.5, 5.9Hz, 1H), 2.98-2.92 (td, J=6.5, 2, 0Hz, 1H), 2.93-2.89 (s, 3H), 2.89-2.82 (dd, J=16.5, 2.0Hz, 1H), 2.75-2.67 (dd, J=16.5, 6.9Hz, 1H), 1.35-1.2 8 (dd, J=15.1, 11.3Hz, 1H), 1.27-1.22 (dd, J=13.6, 7.3Hz, 1H), 1.00-0.95 (s, 6H), 0.93-0.90 (s, 6H). 13 C NMR (126MHz, Chloroform-d) 6168.61, 142.45, 139.39, 129.40, 128.59, 128.34, 127.8 2, 127.55, 127.43, 126.84, 115.87, 83.24, 45.87, 43.69, 35.69, 29.21, 24.72, 24.40. 11 B NMR (160MHz, Chloroform-d) δ33.26.HRMS (ESI) m / z: calculated for [C 24 H 29 BClNO3+H] + 426.2002, found 426.1997.

[0058] Example 10: Synthesis of 1,7-dimethyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one

[0059]

[0060] Add 127 mg (0.5 mmol) pinacol diboronate, 3 mg (0.03 mmol) cuprous chloride (CuCl), 17 mg (0.06 mmol) tricyclohexylphosphine (PCy3), and 3.2 mg (0.04 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube, then purge with argon gas three times. While purging with argon, add 1 mL of N,N-dimethylacetamide (DMA) solvent. After stirring for 5 minutes, add 46 μL (0.4 mmol) styrene. Continue stirring for 5 minutes, then add 37 mg (0.2 mmol) 1 1,7-Dimethylquinoline-2-one was prepared by sealing the reaction system, controlling the reaction temperature at 45°C, stirring for 48 hours, cooling to room temperature, quenching with 3 mL of saturated ammonium fluoride solution, stirring for 10 minutes, adding 3 mL of saturated sodium chloride solution, extracting with ethyl acetate, washing the organic phase with 2 mL of saturated sodium chloride solution, concentrating the organic phase, and separating the concentrate by silica gel column chromatography to obtain 1,7-dimethyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one, with a yield of 61% (Cis-isomer:Trans-isomer = 26:74).

[0061] Cis-isomer: 1 H NMR (500MHz, Chloroform-d) δ7.30-7.26 (m, 2H), 7.21-7.15 (m, 3H), 7.14-7.10 (d, J=7.5Hz, 1H), 6.90-6 .83 (dd, J=7.5, 1.6Hz, 1H), 6.83-6.77 (d, J=1.5Hz, 1H), 3.32-3.27 (s, 3H), 2.93-2.83 (pd, J=9.8, 4.9Hz , 2H), 2.55-2.48 (dd, J=16.1, 5.4Hz, 1H), 2.48-2.43 (dd, J=16.1, 1.8Hz, 1H), 2.41-2.38 (s, 3H), 1.25-1 .17 (dd, J=15.1, 10.4Hz, 1H), 1.11-1.05 (dd, J=15.2, 4.5Hz, 1H), 0.98-0.93 (s, 6H), 0.93-0.89 (s, 6H). 13C NMR(126MHz,Chloroform-d)δ169.64,143.75,140.10,137.59,129.90,128.36,128.32,126.60,125.24,123.00,115.75,83.03,44.28,43.83,35.14,29.36,24.77,24.42,21.63. 11 B NMR(160MHz,Chloroform-d)δ33.39.HRMS(ESI)m / z:calculated for[C 25 H 32 BNO3+H] + 406.2548,found 406.2545;

[0062] Trans-isomer: 1 H NMR(500MHz,Chloroform-d)δ7.16-7.13(d,J=7.6Hz,1H),7.03-6.98(dd,J=6.9,1.9Hz,1H),6.88-6.83(m,2H),6.78-6.73(m,2H),6.72-6.68(dd,J=7.6,1.5Hz,1H),6.66-6.63(d,J=1.6Hz,1H),3.14-3.09(m,1H),3.07-3.02(m,1H),2.94-2.92(s,3H),2.73-2.66(dd,J=16.4,6.9Hz,1H),2.55-2.48(dd,J=16.3,6.2Hz,1H),2.34-2.28(s,3H),1.28-1.24(d,J=8.7Hz,2H),0.99-0.97(s,6H),0.93-0.89(s,6H). 13 C NMR(126MHz,Chloroform-d)δ169.23,143.12,140.57,137.43,129.36,128.50,128.44,127.92,127.65,122.88,115.56,83.11,45.83,43.28,36.05,29.13,24.70,24.43,19.24. 11 B NMR(160MHz,Chloroform-d)δ34.02.HRMS(ESI)m / z:calculated for[C 25 H 32 BNO3+H] +406.2548, found 406.2549.

[0063] Example 11: Synthesis of 8-chloro-1-methyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one

[0064]

[0065] Add 127 mg (0.5 mmol) pinacol diboronate, 3 mg (0.03 mmol) cuprous chloride (CuCl), 17 mg (0.06 mmol) tricyclohexylphosphine (PCy3), and 3.2 mg (0.04 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube, then purge with argon gas three times. While purging with argon, add 1 mL of N,N-dimethylacetamide (DMA) solvent. After stirring for 5 minutes, add 46 μL (0.4 mmol) styrene. Continue stirring for another 5 minutes, then add 39 mg (0.2 mmol) 8- 8-Chloro-1-methylquinoline-2-one was prepared by sealing the reaction system, controlling the reaction temperature at 65°C, stirring for 48 hours, cooling to room temperature, quenching with 3 mL of saturated ammonium fluoride solution, stirring for 10 minutes, adding 3 mL of saturated sodium chloride solution, extracting with ethyl acetate, washing the organic phase with 2 mL of saturated sodium chloride solution, concentrating the organic phase, and separating the concentrate by silica gel column chromatography to obtain 8-chloro-1-methyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one, with a yield of 31% (Cis-isomer:Trans-isomer = 39:61).

[0066] Cis-isomer: 1 H NMR (500MHz, Chloroform-d) δ7.33-7.29 (m, 3H), 7.23-7.20 (m, 3H), 7.20-7.17 (dd, J=7.5, 1.5Hz, 1H), 7.05-7.01 (m, 1H), 3.46-3.42 (s, 3H), 2.8 8-2.84(m, 2H), 2.49-2.44(dd, J=15.5, 4.6Hz, 1H), 2.40-2.35(dd, J=15 .6, 1.4Hz, 1H), 1.25-1.20(m, 2H), 0.97-0.95(s, 6H), 0.94-0.92(s, 6H). 13C NMR(126MHz,Chloroform-d)δ171.62,143.67,139.37,134.75,130.46,128.46,128.27,128.08,126.79,124.61,124.48,83.09,45.73,42.97,35.90,35.57,24.89,24.45. 11 B NMR(160MHz,Chloroform-d)δ33.49.HRMS(ESI)m / z:calculated for[C 24 H 29 BClNO3+H] + 426.2002,found 426.1996;

[0067] Trans-isomer: 1 H NMR(500MHz,Chloroform-d)δ7.21-7.17(dd,J=8.1,1.5Hz,1H),7.16-7.11(dd,J=8.2,6.6Hz,2H),7.10-7.05(m,1H),6.94-6.89(dd,J=7.0,1.8Hz,2H),6.83-6.77(t,J=7.7Hz,1H),6.68-6.62(dd,J=7.5,1.5Hz,1H),3.07-3.03(s,3H),2.99-2.90(m,2H),2.88-2.81(dd,J=15.8,2.2Hz,1H),2.71-2.64(dd,J=15.8,5.8Hz,1H),1.39-1.32(dd,J=15.2,5.6Hz,1H),1.32-1.26(dd,J=15.2,10.7Hz,1H),1.00-0.96(s,6H),0.92-0.89(s,6H). 13 C NMR(126MHz,Chloroform-d)δ171.23,143.21,139.47,133.62,130.31,128.42,128.00,127.68,126.67,124.26,124.04,83.16,44.96,44.76,36.35,35.77,24.72,24.42. 11 B NMR(160MHz,Chloroform-d)δ33.39.HRMS(ESI)m / z:calculated for[C 24 H 29 BClNO3+H] +426.2002, found426.1996.

[0068] Example 12: Synthesis of 1,5,7-trimethyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one

[0069]

[0070] Add 127 mg (0.5 mmol) pinacol diboronate, 3 mg (0.03 mmol) cuprous chloride (CuCl), 17 mg (0.06 mmol) tricyclohexylphosphine (PCy3), and 3.2 mg (0.04 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add 1 mL of N,N-dimethylacetamide (DMA) solvent. After stirring for 5 minutes, add 46 μL (0.4 mmol) styrene. Continue stirring for 5 minutes, then add 38 mg (0.2 mmol) 1,5-dimethylacetamide. 1,5,7-trimethylquinoline-2-one was prepared by sealing the reaction system, controlling the reaction temperature at 100℃, stirring for 24 hours, cooling to room temperature, quenching with 3 mL of saturated ammonium fluoride solution, stirring for 10 minutes, adding 3 mL of saturated sodium chloride solution, extracting with ethyl acetate, washing the organic phase with 2 mL of saturated sodium chloride solution, concentrating the organic phase, and separating the concentrate by silica gel column chromatography to obtain 1,5,7-trimethyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one, with a yield of 33% (Cis-isomer:Trans-isomer = 25:75).

[0071] 1H NMR(500MHz,Chloroform-d)δ7.25-7.08(m,5H minor+3H major),7.06-7.01(dd,J=6.9,1.6Hz,2H,major),6.77-6.74(d,J=7.2Hz,1H,minor),6.67-6.60(dd,J=21.4,1.6Hz,2H,major),6.60-6.59(d,J=1.6Hz,1H,minor),3.29-3.25(s,3H,major),3.19-3.13(ddd,J=8.2,6.1,1.8Hz,1H,minor),3.12-3.10(s,3H,minor),3.10-3.05(m,2H,major),3.02-2.95(ddd,J=11.2,8.6,5.7Hz,1H,minor),2.88-2.81(dd,J=16.5,1.4Hz,1H,major),2.52-2.45(m,1Hmajor+1H minor),2.44-2.41(s,3H,minor),2.41-2.36(dd,J=16.3,6.1Hz,1H,minor),2.33-2.31(s,3H,minor),2.30-2.28(s,3H,major),1.93-1.91(s,3H,major),1.35-1.27(m,2H,minor),1.18-1.11(m,2H,major),0.97-0.96(s,6H,minor),0.96-0.94(s,6H,major),0.93-0.91(s,6H,minor),0.84-0.81(s,6H,major). 13CNMR (126MHz, Chloroform-d) δ169.9(major), 169.7(minor), 144.4(major), 143.6(minor), 140.8(major), 140.5(minor), 136.9(minor), 136.8(major), 13 6.5(major), 136.3(minor), 128.5(major), 128.4(minor), 128.1(minor), 127.9(major), 126.6(minor), 126.3(major), 126.2(minor), 126.1(major), 124. 4(minor), 124.1(major), 114.0(minor), 113.9(major), 83.1(minor), 83.0(major), 44.3(major), 43.8(minor), 39.8(major), 39.3(minor), 34.6(minor), 34.4(major), 29.8(major), 29.6(minor), 24.8(minor), 24.7(major), 24.4(minor), 24.3(major), 21.5(minor), 21.5(major), 20.1(minor), 19.2(major). 11 B NMR (160MHz, Chloroform-d) δ33.73, 22.63.HRMS (ESI) m / z: calculated for [C 26 H 34 BNO3+H] + 420.2705, found 420.2704.

[0072] Example 13: Synthesis of 1-allyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one

[0073]

[0074] Add 127 mg (0.5 mmol) pinacol diborate, 3 mg (0.03 mmol) cuprous chloride (CuCl), 17 mg (0.06 mmol) tricyclohexylphosphine (PCy3), and 3.2 mg (0.04 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube, then purge with argon gas three times. While purging with argon, add 1 mL of N,N-dimethylacetamide (DMA) solvent. After stirring for 5 minutes, add 46 μL (0.4 mmol) styrene. Continue stirring for another 5 minutes, then add 37 mg (0.2 mmol) styrene. 1-Allylquinoline-2-one was prepared by sealing the reaction system, controlling the reaction temperature at 45°C, stirring for 48 hours, cooling to room temperature, quenching with 3 mL of saturated ammonium fluoride solution, stirring for 10 minutes, adding 3 mL of saturated sodium chloride solution, extracting with ethyl acetate, washing the organic phase with 2 mL of saturated sodium chloride solution, concentrating the organic phase, and separating the concentrate by silica gel column chromatography to obtain 1-allyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one, with a yield of 76% (Cis-isomer:Ttans-isomer = 37:63).

[0075] Cis-isomer: 1 H NMR (500MHz, Chloroform-d) δ7.18-7.11 (ddd, J=9.1, 7.2, 2.1Hz, 1H), 7.14-7.04 (m, 3H), 6.89-6.80 (dd, J=7.8, 2.4Hz, 5H), 5.82- 5.70 (ddt, J=17.3, 10.1, 4.9Hz, 1H), 5.16-5.09 (dq, J=10.4, 1.6Hz, 1H), 5.12-5.04 (dq, J=17.1, 1.7Hz, 1H), 4.47-4.38 (ddt, J=16 .9, 4.4, 2.0Hz, 1H), 3.76-3.67 (ddt, J=16.8, 5.3, 1.7Hz, 1H), 3.12-3.04 (dt, J=9.8, 6.8Hz, 1H), 3.03-2.96 (td, J=6.5, 2.3Hz, 1H) , 2.92-2.85 (dd, J=16.3, 2.3Hz, 1H), 2.84-2.76 (dd, J=16.3, 6.7Hz, 1H), 1.34-1.27 (m, 2H), 1.02-0.97 (s, 6H), 0.94-0.91 (s, 6H). 13C NMR(126MHz,Chloroform-d)δ168.61,142.45,139.39,129.40,128.59,128.34,127.82,127.55,127.43,126.84,115.87,83.24,45.87,43.69,35.69,29.21,24.72,24.40. 11 B NMR(160MHz,Chloroform-d)δ33.32.HRMS(ESI)m / z:calculated for[C 26 H 32 BNO3+H] + 418.2548,found 418.2542;

[0076] Trans-isomer: 1 H NMR(500MHz,Chloroform-d)δ7.28-7.19(m,4H),7.19-7.12(m,3H),7.04-6.99(td,J=7.4,1.1Hz,1H),6.98-6.94(dd,J=8.5,1.1Hz,1H),5.90-5.80(ddt,J=17.3,10.2,4.9Hz,1H),5.20-5.11(m,2H),4.79-4.70(ddt,J=16.8,4.4,2.0Hz,1H),4.13-4.05(ddt,J=16.8,5.1,1.8Hz,1H),2.98-2.89(pt,J=6.0,3.3Hz,2H),2.61-2.54(dd,J=16.1,5.6Hz,1H),2.52-2.45(dd,J=16.1,1.5Hz,1H),1.25-1.18(dd,J=14.1,9.5Hz,1H),1.10-1.04(m,1H),0.96-0.93(s,6H),0.92-0.89(s,6H). 13 C NMR(126MHz,Chloroform-d)δ168.65,143.10,140.17,133.17,129.53,128.46,127.70,126.98,126.56,122.24,116.18,115.40,83.14,45.69,45.42,43.90,35.98,24.73,24.43. 11 B NMR(160MHz,Chloroform-d)δ33.62.HRMS(ESI)m / z:calculated for[C26 H 32 BNO3+H] + 418.2548, found418.2546.

[0077] Example 14: Synthesis of 1-phenyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one

[0078]

[0079] Add 127 mg (0.5 mmol) pinacol diborate, 3 mg (0.03 mmol) cuprous chloride (CuCl), 17 mg (0.06 mmol) tricyclohexylphosphine (PCy3), and 3.2 mg (0.04 mmol) lithium tert-butoxide (LiOt-Bu) to a dry Schlenk reaction tube equipped with a stir bar. Evacuate the tube using a Schlenk double-row tube, then purge with argon gas three times. While purging with argon, add 1 mL of N,N-dimethylacetamide (DMA) solvent. After stirring for 5 minutes, add 46 μL (0.4 mmol) styrene. Continue stirring for another 5 minutes, then add 44 mg (0.2 mmol) styrene. l) 1-Phenylenol-2-one, the reaction system was sealed, the reaction temperature was controlled at 45℃, and the reaction was stirred for 48 hours. After cooling to room temperature, 3 mL of saturated ammonium fluoride solution was added to quench the reaction. After stirring for 10 minutes, 3 mL of saturated sodium chloride solution was added. The mixture was extracted with ethyl acetate, the organic phase was washed with 2 mL of saturated sodium chloride solution, the organic phase was concentrated, and the concentrate was separated by silica gel column chromatography to obtain 1-phenyl-4-(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxoboronyl-2-yl)ethyl)-3,4-dihydroquinoline-2-one, with a yield of 52% (Cis-isomer:Ttans-isomer = 27:73);

[0080] Cis-isomer: 1H NMR(500MHz,Chloroform-d)δ7.51-7.45(td,J=7.4,1.3Hz,2H),7.43-7.37(m,1H),7.29-7.23(m,3H),7.23-7.12(m,5H),7.08-7.03(td,J=7.7,1.7Hz,1H),7.03-6.98(td,J=7.3,1.3Hz,1H),6.39-6.33(dd,J=8.0,1.3Hz,1H),3.21-3.11(td,J=9.7,5.9Hz,1H),3.08-3.01(ddd,J=9.1,6.3,1.8Hz,1H),2.79-2.72(dd,J=15.9,6.3Hz,1H),2.65-2.57(dd,J=16.0,1.8Hz,1H),1.33-1.27(dd,J=15.3,10.0Hz,1H),1.27-1.23(m,1H),0.98-0.95(s,6H),0.95-0.92(s,6H). 13 C NMR(126MHz,Chloroform-d)δ169.20,143.76,141.32,138.59,129.91,129.78,128.56,128.41,128.14,128.09,127.48,126.69,122.70,117.56,83.10,44.80,44.44,35.43,24.92,24.51. 11 B NMR(128MHz,Chloroform-d)δ33.13.HRMS(ESI)m / z:calculated for[C 29 H 32 BNO3+H] + 454.2548,found454.2543;

[0081] Trans-isomer: 1H NMR(500MHz,Chloroform-d)δ7.48-7.41(t,J=7.6Hz,2H),7.40-7.34(t,J=7.4Hz,1H),7.20-7.12(d,J=6.5Hz,3H),7.03-6.88(ddd,J=10.3,6.3,2.2Hz,5H),6.87-6.84(dd,J=7.6,1.8Hz,1H),6.84-6.79(t,J=7.3Hz,1H),6.30-6.20(d,J=8.1Hz,1H),3.28-3.20(dt,J=10.0,6.9Hz,1H),3.18-3.11(td,J=6.6,2.5Hz,1H),3.07-3.01(m,1H),3.00-2.93(dd,J=16.1,6.7Hz,1H),1.44-1.37(m,2H),1.01-0.97(s,6H),0.94-0.91(s,6H). 13 C NMR(126MHz,Chloroform-d)δ168.98,143.53,141.42,138.37,129.76,129.51,128.73,128.12,128.06,127.27,126.59,122.35,116.95,83.16,46.04,44.34,36.16,29.85,24.77,24.44. 11 B NMR(160MHz,Chloroform-d)δ33.39.HRMS(ESI)m / z:calculated for[C 29 H 32 BNO3+H]+ 454.2548,found 454.2545。

Claims

1. A method for preparing 4-(1-aryl-2-boronate ethyl)-3,4-dihydroquinoline-2-one, comprising the following steps: Add pinacol diborate (as shown in general formula 3), cuprous chloride, phosphine ligand, and lithium tert-butoxide to a dry Schlenk reaction tube equipped with a stir bar. Vacuum the tube using a Schlenk double-row tube and purge with argon gas three times. While purging with argon gas, add the solvent and stir for 5 minutes. Then add the olefin (as shown in general formula 2) and continue stirring for 5 minutes. Finally, add quinoline-2-one (as shown in general formula 1). Seal the reaction system and control the temperature of the reaction system at 25–100 °C. Stir the reaction for 24–72 hours, cool to room temperature, quench with saturated ammonium fluoride solution, stir for 10 minutes, add saturated sodium chloride solution, and extract with ethyl acetate. Wash the organic phase with saturated sodium chloride solution, concentrate the organic phase, and separate the concentrate by silica gel column chromatography to obtain 4-(1-aryl-2-boronate ethyl)-3,4-dihydroquinoline-2-one (as shown in general formula 4). In general formula 1, R 1 Selected from alkyl or halogen atoms, R 2 Selected from alkyl or aryl; R in general formula 2 3 Selected from alkyl or halogen atoms; the phosphine ligand is selected from one of tri-n-butylphosphine, tricyclohexylphosphine, dicyclohexylphenylphosphine, and 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthracene; the solvent is selected from one of N,N-dimethylacetamide and N,N-dimethylformamide.

2. The method for preparing 4-(1-aryl-2-boronate ethyl)-3,4-dihydroquinoline-2-one according to claim 1, characterized in that... The molar ratio of quinoline-2-one 1: olefin 2: pinacol diboronic acid ester 3: cuprous chloride: phosphine ligand: lithium tert-butoxide is 1.0:(2.0~2.5):(2.5~3.0):(0.1~0.2):(0.1~0.4):(0.1~0.2).

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