A method for synthesizing a carbazole N-H functionalized product at room temperature and normal pressure based on Fe catalysis

Abstract

This invention relates to a method for synthesizing N-H functionalized carbazole products based on Fe catalysis at room temperature and pressure. The method involves mixing α-aryl-α-diazo ester with carbazole or a carbazole derivative in an organic solvent, adding an Fe catalyst and additives, and reacting at room temperature and pressure to obtain the N-H functionalized carbazole product. This invention uses metallic Fe as a catalyst to react α-aryl-α-diazo ester to generate α-(N-carbazole)-α-aryl ester compounds under nitrogen atmosphere at room temperature and pressure. It also offers a wider range of selectable substrates and, compared to traditional synthesis methods, has many advantages such as high yield, simple conditions, low waste emissions, simple reaction equipment, and ease of industrial production.

Description

Technical Field

[0001] This invention relates to a method for synthesizing carbazole NH functionalized products at room temperature and pressure based on Fe catalysis. Background Technology

[0002] The NH-functionalized form of carbazole is a core structure in many drug design molecules, such as 5-HT6 receptor antagonists, which can be used to treat central nervous system diseases. N-substituted carbazoles are generally synthesized via enantioselective reductive amination, and require Fischer indole alkylation to construct a heterocycle.

[0003] There are few reports on the direct synthesis of NH-functionalized carbazole products. Although the literature He, F.; Koenigs, RMBorane-Catalyzed Carbazolation Reactions of Aryldiazoacetates. Org. Lett. 2021, 23, 5831-5835, has reported a detailed synthetic method for these compounds, this method has the following limitations: 1. It requires heating conditions for the reaction; 2. It uses non-metallic boranes as catalysts. Existing reported methods for the direct synthesis of NH-functionalized carbazole products generally use noble metal and non-metallic catalysts, which are costly, complex, and not easy to scale up for industrial production.

[0004] Diazonium compounds, as carbene precursors, are highly versatile compounds in organic synthesis. They can generate highly reactive metal carbene species in the presence of transition metal catalysts, which then insert into the NH bond. The NH insertion reaction of diazonium compounds is a broad, mild, and selective method for amine acquisition. Therefore, the insertion reaction is considered one of the most efficient and atom-economical methods for establishing CN bonds. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a method for synthesizing carbazole NH-functionalized products at room temperature and pressure based on Fe catalysis.

[0006] The method of the present invention has high yield, simple conditions, low waste emission, simple reaction equipment, and is easy to industrialize.

[0007] This invention is achieved through the following technical solution:

[0008] A method for synthesizing carbazole NH-functionalized products at room temperature and pressure based on Fe catalysis includes the following steps:

[0009] In an organic solvent, α-aryl-α-diazo ester is mixed with carbazole or carbazole derivatives, and Fe catalyst and additives are added. The reaction is carried out at room temperature and pressure to obtain the NH-functionalized carbazole product.

[0010] The structure of α-aryl-α-diazo ester is shown in Formula I:

[0011]

[0012] R 1 Selected from alkyl, alkoxy, aromatic, halogen, or hydrogen; R 2 Selected from alkyl and benzyl groups.

[0013] According to a preferred embodiment of the present invention, the structure of the carbazole derivative is shown in Formula II:

[0014]

[0015] R 3 Selected from alkyl, alkoxy, aromatic, halogen, or hydrogen, R 4 It is selected from alkyl, alkoxy, aromatic, halogen or hydrogen.

[0016] According to a preferred embodiment of the present invention, the structure of the obtained carbazole NH-functionalized product is shown in Formula III:

[0017]

[0018] R 1 R 2 R 3 R 4 Same as above.

[0019] According to a preferred embodiment of the present invention, the organic solvent is toluene, xylene, dichloromethane, 1,2-dichloroethane, trichloromethane, or tetrachloromethane.

[0020] More preferably, the organic solvent is dichloromethane, 1,2-dichloroethane, trichloromethane, or tetrachloromethane.

[0021] According to a preferred embodiment of the present invention, the molar ratio of α-aryl-α-diazo ester to carbazole or carbazole derivative is 1:1 to 1:5.

[0022] More preferably, the molar ratio of α-aryl-α-diazo ester to carbazole or carbazole derivative is 1:2 to 1:4.

[0023] Most preferably, the molar ratio of α-aryl-α-diazo ester to carbazole or carbazole derivative is 1:3.

[0024] According to a preferred embodiment of the present invention, the Fe catalyst is 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III).

[0025] According to a preferred embodiment of the present invention, the synthetic route for 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III) is as follows:

[0026]

[0027] Specifically, 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III) is prepared by the following method:

[0028] In a round-bottom flask, 3-bromosalicylic acid (5.0 mmol, 1.0 eq), 2,4-difluorophenylboronic acid (5.5 mmol, 1.1 eq), K2CO3 (20.0 mmol, 4.0 eq), and Pd(PPh3)4 (0.1 mmol, 2 mol%) were added sequentially. Toluene (10 mL), ethanol (5 mL), and water (2.5 mL) were added as solvents. The reaction mixture was stirred in an oil bath at 90 °C under nitrogen protection. After the reaction was completed by TLC monitoring, the mixture was cooled to room temperature, diluted with dichloromethane (10 mL), washed with water (10 mL × 2), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The product S1 was obtained by silica gel column chromatography using ethyl acetate-petroleum ether as eluent.

[0029] S1 (3 mmol, 1.0 eq) was dissolved in EtOH (10 mL), and 1,2-diphenylethylenediamine (3 mmol, 1.0 eq) was added. The reaction mixture was stirred in an oil bath at 80 °C for 6 h under nitrogen protection. The reaction was cooled until a large amount of solid precipitated, and the mixture was filtered to obtain product S2.

[0030] S2 (2.0 mmol, 1.0 eq) was dissolved in 10 mL of a mixed solvent (MeOH / DCM = 1:1), the solution was cooled to 0 °C, sodium borohydride (4.0 mmol, 2.0 eq) was added, and the reaction was continued at 0 °C until the reaction was complete (S2 disappeared as monitored by TLC). The solvent was removed by evaporation, and silica gel column chromatography was performed with ethyl acetate-petroleum ether as the eluent to obtain ligand S3.

[0031] FeCl3 (1.05 mmol, 1.05 equivalent) was added to a mixed solution of S3 (1 mmol, 1.0 equivalent) and ethanol (10 mL), and the mixture was refluxed for 4 hours to obtain a purple solution. The reaction mixture was evaporated under vacuum, and the residue was analyzed by chromatography on silica gel (dichloromethane / MeOH = 19:1) to obtain catalyst S4.

[0032] According to a preferred embodiment of the present invention, the molar ratio of α-aryl-α-diazo ester to catalyst is 1:0.01 to 1:1.

[0033] More preferably, the molar ratio of α-aryl-α-diazo ester to catalyst is 1:0.01 to 1:0.1.

[0034] Most preferably, the molar ratio of α-aryl-α-diazo ester to Fe catalyst is 1:0.05.

[0035] According to a preferred embodiment of the present invention, the additive is NaBAR. F .

[0036] According to a preferred embodiment of the present invention, the molar ratio of α-aryl-α-diazo ester to additive is 1:0.05 to 1:1.

[0037] More preferably, the molar ratio of α-aryl-α-diazo ester to additive is 1:0.05 to 1:0.2.

[0038] Most preferably, the molar ratio of α-aryl-α-diazo ester to additive is 1:0.15.

[0039] According to a preferred embodiment of the present invention, the reaction time is 20-40 hours, and the reaction is carried out under a nitrogen atmosphere.

[0040] According to a preferred embodiment of the present invention, after the reaction is completed, ethyl acetate is added to quench the reaction, followed by washing with brine to separate the organic phase. The aqueous phase is then extracted with ethyl acetate, the organic phases are combined, and the product is obtained by column chromatography.

[0041] The reaction mechanism of this invention:

[0042] The general consensus regarding the NH insertion mechanism is that diazo compounds can generate highly active metal carbene species in the presence of transition metal iron catalysts, which insert into the NH bond through a stepwise ylide formation / proton shift process.

[0043]

[0044] Technical features and advantages of the present invention:

[0045] 1. This invention uses metallic Fe as a catalyst to react α-aryl-α-diazo esters to generate α-(N-carbazole)-α-aryl ester compounds under normal pressure and nitrogen atmosphere at room temperature, while also allowing for a wider range of substrates to be selected.

[0046] 2. Compared with traditional synthesis methods, the method of the present invention has many advantages such as high yield, simple conditions, low waste discharge, simple reaction equipment, and easy industrial production. Detailed Implementation

[0047] The above-mentioned and other technical features and advantages of the present invention will be described in more detail below with reference to the embodiments.

[0048] NaBAR F It is available from Shanghai Baika Chemical Technology Co., Ltd.

[0049] Example 1: Synthesis of tert-butyl-2-(9H-carbazole)-2-phenylacetic acid ester

[0050]

[0051] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo tert-butyl ester, 51 mg of carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25°C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 31 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 87%.

[0052] Pure α-(N-carbazole)-α-arylate: 1 H NMR (500MHz, CDCl3) δ8.24(d,J=7.7Hz,2H),7.49(m,2H),7.46–7.40(m,7H),7.37(t,J=7.4Hz,2H),6.65(s,1H),1.52(s,9H); 13 C NMR (126MHz, CDCl3) δ168.0,140.5,133.8,131.9,129.4,125.9,123.8,122.4,120.5,120.0,110.5,83.6,60.9,28.1; HRMS (ESI) m / z calculated for C 24 H 23 NO2[M+H] + 358.1802, found358.1805; HPLC: the ee value was determined by HPLC analysis (Chiralpak AD-H, i-PrOH / hexane=5 / 95, 1.0mL / min, 215nm), retention time: t minor =5.417min,t major =8.363min, ee=96%.

[0053] Example 2

[0054] The synthesis method is the same as that described in Example 1, except that:

[0055] The dosage of 1,2-diphenyl-3(2,4-difluorophenyl)salan-Fe(III) was 7.4 mg, and other procedures were carried out as in Example 1.

[0056] Column chromatography yielded 31 mg of pure α-(N-carbazole)-α-arylate, with a yield of 87%.

[0057] Example 3

[0058] The synthesis method is the same as that described in Example 1, except that:

[0059] NaBAR F The dosage was 19 mg, and other procedures were carried out as in Example 1.

[0060] Column chromatography yielded 31 mg of pure α-(N-carbazole)-α-arylate, with a yield of 87%.

[0061] Example 4

[0062] The synthesis method is the same as that described in Example 1, except that:

[0063] The dosage of α-phenyl-α-diazo tert-butyl ester was 19 mg, and other procedures were carried out as in Example 1.

[0064] Column chromatography yielded 29 mg of pure α-(N-carbazole)-α-arylate, with a yield of 81%.

[0065] Example 5

[0066] The synthesis method is the same as that described in Example 1, except that:

[0067] 1,2-Dichloroethane was replaced with chloroform, and the rest was carried out as in Example 1.

[0068] Column chromatography yielded 29 mg of pure α-(N-carbazole)-α-arylate, with a yield of 81%.

[0069] Example 6

[0070] The synthesis method is the same as that described in Example 1, except that:

[0071] Tetrachloromethane was used instead of 1,2-dichloroethane, and the rest was carried out as in Example 1.

[0072] Column chromatography yielded 30 mg of pure α-(N-carbazole)-α-arylate, with a yield of 84%.

[0073] Example 7 Synthesis of tert-butyl-2-(9H-carbazole)-2-(4-fluorophenyl)acetic acid ester

[0074]

[0075] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 24 mg of tert-butyl-2-(4-fluorophenyl)-2-diazoacetic acid, 51 mg of carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 31 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 83%.

[0076] 1 H NMR (500MHz, CDCl3) δ8.16–8.11(m,2H),7.42–7.36(m,2H),7.28(m,6H),7.04(m,2H),6.46(s,1H),1.39(s,9H); 13 C NMR (126MHz, CDCl3) δ168.31, 162.62 (d, J = 247.4Hz), 140.51, 129.54, 129.48, 125.85, 123. 82,120.17(d,J=65.6Hz),115.75(d,J=21.7Hz).110.53,83.44,60.84,28.10; HRMS(ESI)m / z calculated for C 24 H 22 FNO2[M+H] + 376.1707, found

[0077] 376.1709; HPLC: the ee value was determined by HPLC analysis (ChiralpakAD-H, i-PrOH / hexane=2 / 98, 1.0mL / min, 337nm), retention time: t minor =7.607min,t major =13.040min, ee=96%.

[0078] Example 8: Synthesis of tert-butyl-2-(9H-carbazole)-2-(4-chlorophenyl)acetic acid ester

[0079]

[0080] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 25 mg of tert-butyl-2-(4-chlorophenyl)-2-diazoacetic acid, 51 mg of carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25°C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, followed by washing with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 33 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 84%.

[0081] 1 H NMR(500MHz, CDCl3)δ8.12(d,J=7.7Hz,2H),7.98–7.92(m,1H),7.51–7.46(m ,1H),7.40–7.35(m,2H),7.29(m,4H),7.23(m,3H),6.44(s,1H),1.37(s,9H); 13 C NMR (126MHz, CDCl3) δ185.6,168.0,163.3,141.4,140.5,134.2,133.3,131.4,131.2,129.4, 129.1,129.0,125.9,123.8,120.4,120.0,110.5,85.2,83.5,60.8,28.2,28.1; HRMS(ESI)m / z calculated for C 24 H 22 ClNO2[M+H] + 393.1412, found 393.1414; HPLC: the ee value was determined by HPLC analysis (Chiralpak AD-H, i-PrOH / hexane=10 / 90, 1.0mL / min, 338nm), retention time: t minor =5.197min,t major =6.993min, ee=96%.

[0082] Example 9: Synthesis of tert-butyl-2-(9H-carbazole)-2-(4-bromophenyl)acetic acid ester

[0083]

[0084] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 30 mg of tert-butyl-2-(4-bromophenyl)-2-diazoacetic acid, 51 mg of carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25°C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 36 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 83%.

[0085] 1 H NMR (500MHz, CDCl3) δ8.02(d,J=8.0Hz,2H),7.35(d,J=8.4Hz,2H),7.28(t,J=7.7Hz,2H),7.16(m,4H),7.06(d,J=8.2Hz,2H),6.31(s,1H),1.26(s,9H); 13 C NMR (126MHz, CDCl3) δ167.8,140.5,136.9,134.8,130.0,128.6,128.0,125.9,125.9,123.9,120.5,120.0,110.5,83.6,60.9,28.1; HRMS (ESI) m / z calculated for C 24 H 22 BrNO2[M+H] + 436.0907, found 436.0909; HPLC: the ee value was determined by HPLC analysis (Chiralpak AD-H, i-PrOH / hexane=10 / 90, 1.0mL / min, 291nm), retention time: t minor =5.387min,t major =7.390min, ee=92%.

[0086] Example 10 Synthesis of tert-butyl-2-(9H-carbazole)-2-(3-chlorophenyl)acetic acid ester

[0087]

[0088] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 25 mg of tert-butyl-2-(3-chlorophenyl)-2-diazoacetic acid, 51 mg of carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of 1,2-dichloroethane were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 32 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 83%.

[0089] 1 H NMR (500MHz, CDCl3) δ8.12–8.06(m,2H),7.37–7.31(m,3H),7.29–7.18(m,7H),7.10(m,1H),6.40(s,1H),1.33(s,9H); 13 C NMR (126MHz, CDCl3) δ167.8,140.5,136.9,134.8,130.0,128.6,128.0,126.0,125.9,123.9,120.5,120.0,110.5,83.6,60.9,28.1; HRMS(ESI) m / z calculated for C 24 H 22 ClNO2[M+H] + 393.1412, found 393.1414; HPLC: theee value was determined by HPLC analysis (Chiralpak AD-H, i-PrOH / hexane=10 / 90, 1.0mL / min, 295nm), retention time: t minor =5.163min,t major =7.580min, ee=95%.

[0090] Example 11 Synthesis of tert-butyl-2-(9H-carbazole)-2-(4-methylphenyl)acetic acid ester

[0091]

[0092] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 23 mg of tert-butyl-2-(4-methylphenyl)-2-diazoacetic acid, 51 mg of carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 32 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 86%.

[0093] 1 H NMR (500MHz, CDCl3) δ8.08(d,J=7.7Hz,2H),7.33(m,2H),7.25–7.19(m,3H),7.13(dd,J=22.2,8.2Hz,4H),6.44(s,1H),2.32(s,3H),1.37(s,9H); 13 C NMR (126MHz, CDCl3) δ168.7,140.7,138.1,131.8,129.5,127.7,125.7,123.8,120.3,119.7,110.7,83.1,61.3,28.2,21.3; HRMS (ESI) m / z calculated for C 25 H 25 NO2[M+H] + 372.1958, found372.1962; HPLC: the ee value was determined by HPLC analysis (Chiralpak AD-H, i-PrOH / hexane=10 / 90, 1.0mL / min, 293nm), retention time: t minor =5.023min,t major =8.170min, ee=95%.

[0094] Example 12 Synthesis of tert-butyl-2-(9H-carbazole)-2-(3-methylphenyl)acetic acid ester

[0095]

[0096] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 23 mg of tert-butyl-2-(3-methylphenyl)-2-diazoacetic acid, 51 mg of carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 31 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 85%.

[0097] 1 H NMR(500MHz, CDCl3)δ8.21(d,J=7.7Hz,2H),7.50–7.44(m,2H),7.40(d,J=8.2H z,2H),7.33(m,3H),7.25–7.21(m,2H),6.59(s,1H),2.38(s,3H),1.50(s,9H); 13 C NMR (126MHz, CDCl3) δ168.6,140.7,138.4,134.7,129.1,128.6,128.4,125. 7,124.7,123.7,120.3,119.7,110.7,83.1,61.5,28.1,21.6; HRMS(ESI)m / z calculated for C 25 H 25 NO2[M+H] + 372.1958, found372.1962; HPLC: the ee value was determined by HPLC analysis (Chiralpak AD-H, i-PrOH / hexane=2 / 98, 1.0mL / min, 292nm), retention time: t minor =6.440min,t major =8.703min, ee=92%.

[0098] Example 13 Synthesis of tert-butyl-2-(9H-carbazole)-2-(3-methoxyphenyl)acetic acid ester

[0099]

[0100] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 25 mg of tert-butyl-2-(3-methoxyphenyl)-2-diazoacetic acid, 51 mg of carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of 1,2-dichloroethane were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 32 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 83%.

[0101] 1 H NMR(500MHz, CDCl3)δ8.18(d,J=7.7Hz,2H),7.47–7.41(m,2H),7.38(d,J=8.2H z,2H),7.31(m,3H),6.99–6.90(m,3H),6.57(s,1H),3.74(s,3H),1.48(s,9H); 13 C NMR (126MHz, CDCl3) δ168.3,159.9,140.6,136.3,129.8,125.7,123.7,120. 3,120.0,119.7,113.7,113.5,110.7,83.1,61.5,55.3,28.1; HRMS(ESI)m / z calculated for C 25 H 25 NO3[M+H] + 388.1907, found388.1910; HPLC: the ee value was determined by HPLC analysis (Chiralpak AD-H, i-PrOH / hexane=5 / 95, 1.0mL / min, 254nm), retention time: t minor =7.127min,t major =9.037min, ee=96%.

[0102] Example 14 Synthesis of tert-butyl-2-(1,1'-biphenyl)-2-(9H-carbazole)acetate

[0103]

[0104] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 29 mg of tert-butyl-2-(1,1'-biphenyl)-2-diazoacetic acid, 51 mg of carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 35 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 81%.

[0105] 1 H NMR (500MHz, CDCl3) δ8.06(d,J=7.7Hz,2H),7.50(m,5H),7.36(t,J=7.6Hz,3H),7.33–7.27(m,6H),7.19(m,3H),6.46(s,1H),1.33(s,9H); 13 C NMR (126MHz, CDCl3) δ168.5,141.2,140.7,140.6,133.8,129.0,128.2,127.7,1 27.5,127.3,125.8,123.8,120.4,119.8,110.7,83.4,61.3,28.2; HRMS(ESI)m / z calculated forC 30 H 27 NO2[M+H] + 434.2115, found 434.2118; HPLC: the ee value was determined by HPLC analysis (Chiralpak AD-H, i-PrOH / hexane=10 / 90, 1.0mL / min, 338nm), retention time: t minor =6.943min,t major =13.687min, ee=94%.

[0106] Example 15 Synthesis of methyl-2-(9H-carbazole)-2-phenylacetic acid ester

[0107]

[0108] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 18 mg of α-phenyl-α-diazomethyl ester, 51 mg of carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, followed by washing with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 27 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 85%.

[0109] 1 H NMR (500MHz, CDCl3) δ8.02(d,J=8.1Hz,2H),7.28(t,J=7.7Hz,2H),7.25–7.21(m,3H),7.19–7.12(m,6H),6.53(s,1H),3.68(s,3H); 13 C NMR(126MHz, CDCl3)δ170.0,140.4,134.2,128.9,128.6,127.6,126.0,123.8,120.5,120.0,110.4,60.5,53.0; HRMS(ESI)m / z calculated for C 21 H 17 NO2[M+H] + 316.1332, found 316.1335.

[0110] Example 16 Synthesis of ethyl-2-(9H-carbazole)-2-phenylacetic acid ester

[0111]

[0112] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazoethyl ester, 51 mg of carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, followed by washing with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 27 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 82%.

[0113] 1H NMR (500MHz, CDCl3) δ8.09(d,J=7.7Hz,2H),7.34(m,2H),7.30(m,3H),7.27–7.20(m,6H),6.58(s,1H),4.28–4.20(m,2H),1.16(t,J=7.1Hz,3H); 13 C NMR (126MHz, CDCl3) δ169.5,140.5,134.4,128.9,128.5,127.6,125.9,123.8,120.4,119.9,110.5,62.2,60.7,14.3; HRMS (ESI) m / z calculated for C 22 H 19 NO2[M+H] + 330.1489, found 330.1490.

[0114] Example 17 Synthesis of benzyl-2-(9H-carbazole)-2-phenylacetic acid ester

[0115]

[0116] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 25 mg of α-phenyl-α-diazobenzyl ester, 51 mg of carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 32 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 82%.

[0117] 1 H NMR (500MHz, CDCl3) δ8.11 (d, J = 7.7Hz, 2H), 7.35–7.20 (m, 15H), 7.15–7.09 (m, 2H), 6.65 (s, 1H), 5.22 (s, 2H); 13 C NMR (126MHz, CDCl3) δ169.4,140.5,135.1,134.2,128.9,128.7,128.6,128.5 ,128.4,127.7,126.0,123.8,120.4,120.0,110.5,67.7,60.7; HRMS(ESI)m / z calculated for C 27 H21 NO2[M+H] + 392.1645, found 392.1648.

[0118] Example 18 Synthesis of tert-butyl-2-(3,6-dichloro-9H-carbazole)-2-phenylacetic acid ester

[0119]

[0120] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo-tert-butyl ester, 72 mg of 3,6-dichloro-9H-carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 34 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 80%.

[0121] 1 H NMR(500MHz, CDCl3)δ8.00(d,J=2.0Hz,2H),7.37–7.34(m,3H),7.32(d,J=2.1Hz,1H),7. 30(d,J=2.1Hz,1H),7.26–7.21(m,2H),7.16(d,J=8.8Hz,2H),6.41(s,1H),1.40(s,9H); 13 C NMR (126MHz, CDCl3) δ168.0,139.5,134.1,129.0,128.7,127.6,126.6,125.8,124.0,120.3,112.0,83.8,61.8,28.2; HRMS (ESI) m / z calculated for C 24 H 21 Cl2NO2[M+H] +

[0122] 426.1022, found 426.1026.

[0123] Example 19 Synthesis of tert-butyl-2-(3,6-dibromo-9H-carbazole)-2-phenylacetic acid ester

[0124]

[0125] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo-tert-butyl ester, 165 mg of 3,6-dibromo-9H-carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 41 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 79%.

[0126] 1 H NMR (500MHz, CDCl3) δ8.15(m,2H),7.44(m,2H),7.35(m,3H),7.25–7.21(m,2H),7.12(d,J=8.8Hz,2H),6.41(s,1H),1.40(s,9H); 13 C NMR (126MHz, CDCl3) δ168.0,139.6,134.0,129.3,129.1,128.7,127.6,124.5,123.3,113.1,112.4,83.8,61.7,28.2; HRMS (ESI) m / z calculated for C 24 H 21 Br2NO2[M+H] + 515.9991, found 515.9995.

[0127] Example 20 Synthesis of tert-butyl-2-(3,6-dimethoxy-9H-carbazole)-2-phenylacetic acid ester

[0128]

[0129] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo tert-butyl ester, 69 mg of 3,6-dimethoxy-9H-carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 33 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 78%.

[0130] 1 H NMR(500MHz, CDCl3)δ7.52(d,J=2.5Hz,2H),7.35–7.30(m,3H),7.29–7.24(m,2H),7.1 3(d,J=8.9Hz,2H),6.97(dd,J=8.9,2.5Hz,2H),6.38(s,1H),3.92(s,6H),1.38(s,9H); 13 C NMR(126MHz, CDCl3)δ168.5,153.7,136.1,134.8,128.6,128.1,127.5,123.8,114.7,111.4,102.9,82.9,61.6,56.0,28.0; HRMS(ESI)m / z calculated for C 26 H 27 NO4[M+H] + 418.2013, found418.2016.

[0131] Example 21 Synthesis of tert-butyl-2-(3,6-dimethyl-9H-carbazole)-2-phenylacetic acid ester

[0132]

[0133] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo-tert-butyl ester, 60 mg of 3,6-dimethyl-9H-carbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 30 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 79%.

[0134] 1 H NMR (500MHz, CDCl3) δ7.86(s,2H),7.32(m,3H),7.29–7.24(m,2H),7.18–7.10(m,4H),6.42(s,1H),2.51(s,6H),1.40(s,9H); 13C NMR (126MHz, CDCl3) δ168.7,139.1,135.0,128.8,128.7,128.2,127.7,126.9,123.7,120.3,110.3,83.1,61.5,28.2,21.5; HRMS (ESI) m / z calculated for C 26 H 27 NO2[M+H] + 386.2115, found386.2116.

[0135] Example 22 Synthesis of tert-butyl-2-(2-chloro-9H-carbazole)-2-phenylacetic acid ester

[0136]

[0137] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo-tert-butyl ester, 60 mg of 2-chlorocarbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at 25°C for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 30 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 76%.

[0138] 1 H NMR(500MHz, CDCl3)δ8.05(m,1H),7.99(d,J=8.2Hz,1H),7.39–7.32(m,4H),7 .27(m,2H),7.25(m,2H),7.23(m,1H),7.20(m,1H),6.41(s,1H),1.41(s,9H); 13 C NMR (126MHz, CDCl3) δ168.2,134.3,133.3,133.1,131.5,129.0,128.6,127.7,1 26.1,123.1,122.5,121.1,120.3,111.0,110.8,83.6,61.7,28.2; HRMS(ESI)m / z calculated forC 24 H 22 ClNO2[M+H] +

[0139] 393.1412, found 392.1415.

[0140] Example 23 Synthesis of tert-butyl-2-(2-bromo-9H-carbazole)-2-phenylacetic acid ester

[0141]

[0142] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo tert-butyl ester, 75 mg of 2-bromocarbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 32 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 73%.

[0143] 1 H NMR (500MHz, CDCl3) δ7.98(d,J=7.7Hz,1H),7.86(d,J=8.3Hz,1H),7.35–7.25(m,6H),7.22–7.14(m,4H),6.35(s,1H),1.34(s,9H); 13 C NMR (126MHz, CDCl3) δ168.1,141.4,140.8,134.3,128.9,128.6,127.7,126.3,123.2,1 23.0,122.8,121.5,120.4,120.3,119.3,113.8,110.9,83.6,61.7,28.1; HRMS(ESI)m / z calculated for C 24 H 22 BrNO2[M+H] + 436.0907, found 436.0909.

[0144] Example 24 Synthesis of tert-butyl-2-(2-methoxy-9H-carbazole)-2-phenylacetic acid ester

[0145]

[0146] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo tert-butyl ester, 60 mg of 2-methoxycarbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 27 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 70%.

[0147] 1 H NMR(500MHz, CDCl3)δ7.93(d,J=7.6Hz,1H),7.89(d,J=8.5Hz,1H),7.29–7.25(m,3H),7.24–7.19(m,3H) ,7.15(m,2H),6.78(dd,J=8.5,2.2Hz,1H),6.63(d,J=2.1Hz,1H),6.36(s,1H),3.70(s,3H),1.33(s,9H); 13 C NMR (126MHz, CDCl3) δ168.5,158.9,142.0,140.8,134.7,128.8,128.4,127.8,124.5,123 .9,121.0,120.0,119.5,117.6,110.3,108.3,95.3,83.2,61.6,55.7,28.2; HRMS(ESI)m / z calculated for C 25 H 25 NO3[M+H] + 388.1905, found 388.1906.

[0148] Example 25 Synthesis of tert-butyl-2-(2-methyl-9H-carbazole)-2-phenylacetic acid ester

[0149]

[0150] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo tert-butyl ester, 54 mg of 2-methylcarbazole, and NaBAR. F14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 27 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 73%.

[0151] 1 H NMR (500MHz, CDCl3) δ8.08–8.05(m,1H),7.99(d,J=7.8Hz,1H),7.36–7.27(m,6H ),7.23–7.19(m,2H),7.12–7.06(m,2H),6.46(s,1H),2.48(s,3H),1.39(s,9H); 13 C NMR (126MHz, CDCl3) δ168.6,141.2,140.6,136.0,134.9,128.8,128.3,127.7,125.2,123.9,121 .5,121.3,120.0,119.9,119.6,110.8,110.6,83.2,61.5,28.1,22.5; HRMS(ESI)m / zcalculated for C 25 H 25 NO2[M+H] + 372.1958, found 372.1960.

[0152] Example 26 Synthesis of tert-butyl-2-(3-chloro-9H-carbazole)-2-phenylacetic acid ester

[0153]

[0154] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo tert-butyl ester, 60 mg of 3-chlorocarbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 30 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 77%.

[0155] 1H NMR(500MHz, CDCl3)δ8.05(m,2H),7.42–7.38(m,1H),7.37–7.33(m,3H),7.2 8(m,2H),7.26–7.24(m,3H),7.12(d,J=8.8Hz,1H),6.45(s,1H),1.39(s,9H); 13 C NMR (126MHz, CDCl3) δ168.3,141.3,138.8,134.4,128.9,128.5,127.7,126.6,125.8,125.4, 125.1,122.8,120.6,120.2,120.1,112.1,110.6,83.5,61.6,28.2; HRMS(ESI)m / zcalculated for C 24 H 22 ClNO2[M+H] + 393.1412, found 393.1415.

[0156] Example 27 Synthesis of tert-butyl-2-(3-methyl-9H-carbazole)-2-phenylacetic acid ester

[0157]

[0158] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo tert-butyl ester, 54 mg of 3-methylcarbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25°C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 30 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 81%.

[0159] 1 H NMR(500MHz, CDCl3)δ8.06(d,J=7.6Hz,1H),7.89(s,1H),7.35–7.30(m,4H),7.2 7(m,2H),7.25–7.19(m,2H),7.15(m,2H),6.45(s,1H),2.51(s,3H),1.39(s,9H); 13C NMR (126MHz, CDCl3) δ168.6,140.9,138.9,134.9,129.1,128.8,128.3,127.7,127.1,125.6,123 .9,123.6,120.3,120.3,119.5,110.6,110.5,83.2,61.5,28.2,21.5; HRMS(ESI)m / zcalculated for C 25 H 25 NO2[M+H] + 372.1958, found 372.1960.

[0160] Example 28 Synthesis of tert-butyl-2-(4-bromo-9H-carbazole)-2-phenylacetic acid ester

[0161]

[0162] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo tert-butyl ester, 75 mg of 4-bromocarbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of 1,2-dichloroethane were added to a 200 mL nitrogen balloon and stirred at room temperature (25°C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 33 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 76%.

[0163] 1 H NMR (500MHz, CDCl3) δ8.87–8.82(m,1H),7.45–7.38(m,2H),7.35–7.31(m,4H),7.27–7.23(m,3H),7.19(m,2H),6.50(s,1H),1.39(s,9H); 13 C NMR (126MHz, CDCl3) δ168.2,141.7,140.9,134.4,128.9,128.5,127.6,126.5,126.1,1 24.1,123.3,122.9,122.4,119.9,116.9,110.3,109.8,83.6,61.5,28.2; HRMS(ESI)m / z calculated for C 24 H 22 BrNO2[M+H] +436.0907, found 436.0909.

[0164] Example 29 Synthesis of tert-butyl-2-(4-methoxy-9H-carbazole)-2-phenylacetic acid ester

[0165]

[0166] Take a 10 mL Schlenk reaction tube and add 3.7 mg of 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III), 22 mg of α-phenyl-α-diazo tert-butyl ester, 60 mg of 4-methoxycarbazole, and NaBAR. F 14 mg of 1,2-dichloroethane and 1 mL of nitrogen were added to a 200 mL nitrogen balloon and stirred at room temperature (25 °C) for 24 hours. After the reaction was complete, 15 mL of ethyl acetate was added to quench the reaction, and the mixture was washed with 5 mL of brine. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 30 mg of pure α-(N-carbazole)-α-aryl ester, with a yield of 78%.

[0167] 1 H NMR(500MHz, CDCl3)δ8.06(d,J=7.7Hz,1H),7.57(m,1H),7.37–7.31(m,4H),7.27(m ,3H),7.21(m,1H),7.12(m,1H),6.97(m,1H),6.44(s,1H),3.92(s,3H),1.39(s,9H); 13 C NMR (126MHz, CDCl3) δ168.6,154.1,141.3,135.5,134.9,128.8,128.3,127.7,125.8,124. 3,123.6,120.3,119.4,114.7,111.8,110.5,103.3,83.2,61.6,56.2,28.2; HRMS(ESI)m / z calculated for C 25 H 25 NO3[M+H] + 388.1905, found 388.1906.

[0168] Comparative Example 1

[0169] The synthesis method is the same as that described in Example 1, except that:

[0170] The reaction time was 48 hours, and other procedures were carried out as in Example 1. After the reaction was completed, 15 mL of ethyl acetate was added to quench the reaction, and 5 mL of brine was added to wash the mixture. The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and separated by column chromatography to obtain 26 mg of pure α-(N-carbazole)-α-arylate, with a yield of 73%.

[0171] Compared with Example 1, it can be seen that extending the reaction time reduces the yield.

[0172] Comparative Example 2

[0173] The synthesis method is the same as that described in Example 1, except that:

[0174] Connect a 200mL oxygen bulb, and proceed as in Example 1.

[0175] Column chromatography yielded 12 mg of pure α-(N-carbazole)-α-arylate, with a yield of 34%.

[0176] Compared with Example 1, it can be seen that the yield is severely affected in an oxygen atmosphere.

[0177] Comparative Example 3

[0178] The synthesis method is the same as that described in Example 1, except that:

[0179] Stir at 0°C for 24 hours. Other procedures are the same as in Example 1.

[0180] Column chromatography yielded 15 mg of pure α-(N-carbazole)-α-arylate, with a yield of 42%.

[0181] Compared with Example 1, it can be seen that carrying out the experiment at low temperature will seriously affect the yield.

[0182] Comparative Example 4

[0183] The synthesis method is the same as that described in Example 1, except that:

[0184] Stir at 60°C for 24 hours, and proceed as in Example 1.

[0185] Column chromatography yielded 24 mg of pure α-(N-carbazole)-α-arylate, with a yield of 67%.

[0186] Compared with Example 1, it can be seen that excessively high reaction temperature can also affect the yield.

[0187] Comparative Example 5

[0188] The synthesis method is the same as that described in Example 1, except that:

[0189] This reaction does not require the addition of NaBAR. FThe rest is carried out according to Example 1.

[0190] Column chromatography yielded 15 mg of pure α-(N-carbazole)-α-arylate, with a yield of 42%.

[0191] No NaBAR added F The product yield is low.

[0192] Comparative Example 6

[0193] The synthesis method is the same as that described in Example 1, except that:

[0194] The dosage of carbazole was 85 mg, and other procedures were carried out as in Example 1.

[0195] Column chromatography yielded 21 mg of pure α-(N-carbazole)-α-arylate, with a yield of 59%.

[0196] High carbazole dosage leads to reduced yield.

[0197] Comparative Example 7

[0198] The synthesis method is the same as that described in Example 1, except that:

[0199] The amount of 1,2-diphenyl-3(2,4-difluorophenyl)salan-Fe(III) was 1 mg, and the rest was carried out as in Example 1. Column chromatography was used to separate 22 mg of pure α-(N-carbazole)-α-arylate, with a yield of 62%.

[0200] Low catalyst dosage leads to reduced yield.

[0201] Comparative Example 8

[0202] The synthesis method is the same as that described in Example 1, except that:

[0203] NaBAR F The dosage was 1 mg, and other procedures were performed as in Example 1.

[0204] Column chromatography yielded 20 mg of pure α-(N-carbazole)-α-arylate, with a yield of 56%.

[0205] NaBAR F Low dosage leads to reduced yield.

Claims

1. A method for synthesizing carbazole NH-functionalized products at room temperature and pressure based on Fe catalysis, comprising the following steps: In an organic solvent, α-aryl-α-diazo ester is mixed with carbazole or carbazole derivatives, and Fe catalyst and additives are added. The reaction is carried out at room temperature and pressure to obtain the NH-functionalized carbazole product. The Fe catalyst is 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III); The additive mentioned is NaBAR F The molar ratio of α-aryl-α-diazo ester to additive is 1:0.05 to 1:1; The structure of α-aryl-α-diazo ester is shown in Formula I: Formula I, R 1 Selected from alkyl, alkoxy, aromatic, halogen, or hydrogen; R 2 Selected from alkyl and benzyl groups; The structure of the carbazole derivative is shown in Formula II: Formula II, R 3 Selected from alkyl, alkoxy, aromatic, halogen, or hydrogen, R 4 Selected from alkyl, alkoxy, aromatic, halogen, or hydrogen; The structure of the obtained carbazole NH functionalized product is shown in Formula III: Formula III; R 1 R 2 R 3 R 4 Same as above.

2. The method according to claim 1, characterized in that, The organic solvent is toluene, xylene, dichloromethane, 1,2-dichloroethane, trichloromethane, or tetrachloromethane.

3. The method according to claim 1, characterized in that, The organic solvent is dichloromethane, 1,2-dichloroethane, trichloromethane, or tetrachloromethane.

4. The method according to claim 1, characterized in that, The molar ratio of α-aryl-α-diazo ester to carbazole or carbazole derivative is 1:1 to 1:

5.

5. The method according to claim 1, characterized in that, The synthetic route for 1,2-diphenyl-3-(2,4-difluorophenyl)salan-Fe(III) is shown in Formula IV: Formula IV.

6. The method according to claim 1, characterized in that, The molar ratio of α-aryl-α-diazo ester to catalyst is 1:0.01 to 1:

1.

7. The method according to claim 1, characterized in that, The molar ratio of α-aryl-α-diazo ester to additive is 1:0.05 to 1:0.

2.

8. The method according to claim 1, characterized in that, The reaction time is 20-40 h, and the reaction is carried out under a nitrogen atmosphere. After the reaction is completed, ethyl acetate is added to quench the reaction, and the mixture is washed with brine to separate the organic phase. The aqueous phase is extracted with ethyl acetate, the organic phases are combined, and the product is obtained by column chromatography.

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