A method for preparing carboxylated indole fused heterocycles from carbon dioxide

Abstract

The present invention relates to the fields of medicine, organic chemical industry and fine chemical industry, and in particular to a method for preparing a carboxylated indole fused heterocycle by carbon dioxide. Using unactivated olefins and carbon dioxide of an indole series as raw materials, in the presence of an inorganic base, a photocatalyst and a reducing agent, dimethyl sulfoxide or N,N-dimethylformamide or the like is used as a solvent, a 30W blue LED, room temperature reaction for 12 to 36 hours, then adding iodomethane and performing a synthesis reaction in a 55°C oil bath for 1 hour to obtain a product, and through simple post-processing, a series of carboxylated indole fused heterocycles can be obtained in a higher yield. Unactivated olefins of the indole series of various substituents can all participate in the reaction well to obtain the corresponding carboxylated indole fused heterocycle.

Description

Technical Field

[0001] The present invention relates to the fields of medicine, organic chemical industry and fine chemical industry, and in particular to a method for preparing carboxylated indole fused heterocycles from carbon dioxide. Background Art

[0002] Carboxylated indole fused heterocycles are an important class of structural units that are widely present in a variety of biologically active molecular structures, such as CRTH2 or S1P1 agonists, and U-87MG cell inhibitors (see: (a) Buzard, DJ; Lopez, L.; Moody, J. Kawasaki, A.; Schrader, TO; Kasem, M.; Johnson, B.; Zhu, X.; Thoresen, L.; Kim, SH; et.al. ACS Med. Chem. Lett. 2014, 5, 1334-1339. (b) Pan, Y.; Gong, X.; Hao, R.; Zeng, S.; Xu, J.; Shen, Z.; Huang, W. Asian J. Org. Chem. 2022, 11, e202100766. (c) Beaulieu, C.; Guay, D.;

[0003] Wang, Z. Leblanc, Y.; Roy, P.; Dufresne, C.; Zamboni, R.; Berthelette, C.; Day, S.; Tsou, N.; et.al. Med. Chem. Lett. 2008, 18, 2696-2700.). Many synthetic methods for this type of compound have been developed. For example, in the synthesis of S1P1 agonists, 2-ester indole is required as the starting material and is obtained through multiple synthetic steps (see: Schrader, TO; Johnson, BR; Lopez, L.; Kasem, M.; Gharbaoui, T.; Sengupta, D.; Buzard, D.; Basmadjian, C.; Jones, RM Org. Lett. 2012, 14, 6306-6309.). Secondly, Wu's group reported that under the action of visible light, using indole olefins as starting materials and ethyl oxalyl chloride as the ester source, a series of carboxylated indole fused heterocyclic compounds were obtained through olefin aromatic / esterification reactions (see: Chen, J.-Q.; Tu, X.; Qin, B.; Huang, S.; Zhang, J.; Wu, J. Org. Lett. 2022, 24, 642). Subsequently, Professor Wu Xiaofeng's research group further developed a series of amidated indole fused heterocycles through the arylation / carbonylation reaction of indole alkenes under transition metal catalysis, using molybdenum hexacarbonyl as a carbonyl source and nitro compounds as an amino source (see: Wang, S.; Li, S.; Liu, L.; Ying, J.; Wu, X.-F. Org. Lett. 2023, 25, 821-825.). The above work shows that the synthesis of carboxylated indole fused heterocycles has made great progress, but it inevitably requires the use of multi-step synthesis, expensive, and environmentally unfriendly carboxyl or carbonyl sources.

[0004] Therefore, further development of the construction of carboxylated indole fused heterocycles under mild conditions using cheap and readily available raw materials and green and environmentally friendly carboxyl sources has high research value. Summary of the Invention

[0005] In view of the shortcomings of the background technology, the present invention uses non-activated olefins of the indole series and carbon dioxide as raw materials, bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium bis(hexafluorophosphate) salt (Ir[dF(CF3)ppy]2(dtbbpy)·PF6), bis(2,2'-bipyridine)[2-(4-tert-butylphenyl)pyridine]iridium(III) hexafluorophosphate salt (Ir(ppy)2(dtbbpy)·PF6), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzI PN), or tris(2,2'-bipyridine)iridium (fac-Ir(ppy)3) as a catalyst, cesium carbonate, potassium carbonate, sodium carbonate, etc. as an inorganic base, N,N-dicyclohexylmethylamine, triethylamine, N,N-diisopropylethylamine, etc. as a reducing agent, dimethyl sulfoxide, or N,N-dimethylformamide, etc. as a solvent, 30W blue LED, react at room temperature for 12 to 36 hours, then add iodomethane and continue the synthesis reaction in a 55°C oil bath for another hour to obtain the product. After simple post-treatment, a series of carboxylated indole fused heterocycles can be obtained in high yields. The specific process is as follows:

[0006]

[0007] The structural formula of the non-activated olefins of the indole series is as follows:

[0008]

[0009] Among them, R 1 is substituted phenyl, methyl, ethyl or hydrogen; R 2 is methyl or hydrogen, Ar 1 is a phenyl group connected to a methyl group, a methoxy group, a halogen group, an oxytrifluoromethyl group, or a naphthyl group, Ar 2 It is a phenyl group connected with a methyl group, a methoxy group, a halogen group, or a tert-butyl group.

[0010] The pressure of carbon dioxide is 0.1 MPa.

[0011] The amount of the photocatalyst added is 2 mol% of the molar amount of the non-activated olefin; the amount of the reducing agent added is equal to the molar amount of the non-activated olefin, and the molar ratio of methyl iodide to the non-activated olefin is 4:1.

[0012] The post-reaction treatment of the present invention is simple and convenient, and only requires a simple column chromatography separation method, and a mixed solvent of petroleum ether and ethyl acetate is used as an eluent to obtain a series of pure carboxylated indole fused heterocycles with diverse structures.

[0013] Beneficial effects:

[0014] The present invention is the first to use non-activated olefins and carbon dioxide as raw materials, tris(2,2'-bipyridine)iridium as a photocatalyst, an inorganic base as an additive, N,N-diisopropylethylamine as a reducing agent, dimethyl sulfoxide as a solvent, a 30W blue LED, and react at room temperature for 12 to 36 hours. Then, iodomethane is added and the synthesis reaction is carried out in a 55°C oil bath for another hour. After simple post-treatment, a series of carboxylated indole fused heterocycles can be obtained in high yields, providing a simpler and more feasible route for the synthesis of such compounds, with important application value. In addition, the present invention is the first to realize the synthesis of structurally rich carboxylated indole fused heterocycle compounds by the carboxylation reaction of non-activated olefins using photocatalysts and CO2 under visible light catalysis conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 This is the UV-Vis diffuse reflectance image of the indole fused heterocycle synthesized in the present invention. (UV-Vis. a,b a In DCM(10 -5 M). b*＝ blank signal for DCM). DETAILED DESCRIPTION

[0016] The present invention will be described in detail below with reference to the embodiments. The reactions of the embodiments of the present invention are as follows.

[0017] Example 1

[0018] Methyl 2-(5,12-dimethyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0019]

[0020] To a dried Schlenk tube, 3-methyl-1-(2-methylallyl)-2-phenyl-1H-indole 1a (0.2 mmol, 52.2 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (for 30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). The organic layer was then separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, the product was separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 83%. The compound was a yellow oil.

[0021] NMR data: 1 H NMR (400MHz, Chloroform-d): δ7.85 (dd, J=7.7, 1.4Hz, 1H), 7.62 (dt, J=7.9, 1.0Hz, 1H), 7.43–7.21 (m, 5H), 7.12 (ddd, J=7.9 ,6.9,1.0Hz,1H),4.58(d,J=12.4Hz,1H),3.78(d,J=12.4Hz,1H),3.52(s,3H),2.63(s,3H),2.41–2.32(m,2H),1.58(s,3H). 13 CNMR(101MHz,CDCl3)δ171.4,139.9,135.6,129.7,129.2(2C),127.3,126.9,125 .8,124.8,122.0,119.0,118.7,108.7,107.3,51.4,48.9,42.0,38.0,22.2,10.8.

[0022] Example 2

[0023] Methyl 2-(3,5,12-trimethyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0024]

[0025] To a dried Schlenk tube, 3-methyl-1-(2-methylallyl)-2-(p-tolyl)-1H-indole 1b (0.2 mmol, 50.0 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 74%. The compound was a yellow oil.

[0026] NMR data: 1 H NMR (400MHz, Chloroform-d): δ7.78(d,J=7.9Hz,1H),7.62(d,J=7.8Hz,1H),7.34(d,J=8.2Hz,1H),7.26–7.19(m,3H),7.14–7.10(m,1H),4.60(d,J=12.4Hz 1H), 3.79 (d, J = 12.4Hz, 1H), 3.59 (s, 3H), 2.62 (s, 3H), 2.42 (s, 3H), 2.44–2.33 (m, 2H), 1.59 (s, 3H). 13 C NMR (CDCl3, 101MHz): δ171.5,140.0,136.7,135.5,130.0,129.3,128.0,126.4,125.8 ,125.4,121.8,119.0,118.6,108.7,106.6,51.4,48.9,42.1,38.0,22.3,21.6,10.7.

[0027] Example 3

[0028] Methyl2-(3-(tert-butyl)-5,12-dimethyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0029]

[0030] To a dried Schlenk tube, 2-(4-(tert-butyl)phenyl)-3-methyl-1-(2-methylallyl)-1H-indole 1c (0.2 mmol, 63.4 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 77%. The compound was a yellow oil.

[0031] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.80 (d, J = 8.2Hz, 1H), 7.62–7.60 (m, 1H), 7.45-7.40 (m, 2H), 7.35–7.30 (m, 1H), 7.23–7.19 (m, 1H), 7.13–7. 09(m,1H),4.59(d,J=12.4Hz,1H),3.80(d,J=12.4Hz,1H),3.53(s,3H),2.62(s,3H),2.45–2.35(m,2H),1.60(s,3H),1.37(s,9H). 13 C NMR (CDCl3, 101MHz): δ171.5,149.9,139.5,135.5,129.9,129.3,126.4,125.5,124.2,1 21.8,121.6,118.9,118.6,108.7,106.7,51.4,49.1,42.2,38.3,34.9,31.3,22.4,10.7.

[0032] Example 4

[0033] Methyl2-(3-methoxy-5,12-dimethyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0034]

[0035] To a dried Schlenk tube, 2-(4-methoxyphenyl)-3-methyl-1-(2-methylallyl)-1H-indole 1d (0.2 mmol, 58.2 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 72%. The compound was a yellow oil.

[0036] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.79(d,J=8.6Hz,1H),7.60–7.58(m,1H),7.33–7.30(m,1H),7.22–7.18(m,1H),7.12–7.08(m,1H),6.98(d,J=2.7Hz 1H),6.93–6.90(m,1H),4.58(d,J=2.7Hz 1H),3.85(s,3H),3.75(d,J=2.7Hz 1H),3.53(s,3H),2.59(s,3H),2.41–2.31(m,2H),1.56(s,3H). 13 C NMR (CDCl3, 101MHz): δ171.4,158.6,141.8,135.4,129.8,129.3,127.1,122.2,121.5 ,118.9,118.4,112.0,111.3,108.5,105.6,55.3,51.4,48.8,42.0,38.2,22.3,10.6.

[0037] Example 5

[0038] Methyl2-(5,12-dimethyl-3-phenyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0039]

[0040] To a dried Schlenk tube, 2-([1,1'-biphenyl]-4-yl)-3-methyl-1-(2-methylallyl)-1H-indole 1e (0.2 mmol, 67.4 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 60%. The compound was a yellow oil.

[0041] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.99 (d, J = 8.0Hz, 1H), 7.72–7.65 (m, 5H), 7.55–7.51 (m, 2H), 7.44–7.40 (m, 2H), 7.32–7.28 (m, 1H), 7 .21–7.17(m,1H),4.68(d,J=12.4Hz,1H),3.88(d,J=12.4Hz,1H),3.58(s,3H),2.72(s,3H),2.54–2.45(m,2H),1.70(s,3H). 13 C NMR (CDCl3, 101MHz): δ171.4,140.8,140.3,139.6,135.7,129.5,129.3,128.8,128.1,127.4,12 6.9,126.2,126.0,123.6,122.1,119.1,118.8,108.7,107.5,51.4,48.9,42.1,38.2,22.4,10.8.

[0042] Example 6

[0043] Methyl2-(3-fluoro-5,12-dimethyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0044]

[0045] To a dried Schlenk tube, 2-(4-fluorophenyl)-3-methyl-1-(2-methylallyl)-1H-indole 1f (0.2 mmol, 55.8 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 78%. The compound was a yellow oil.

[0046] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.82–7.79(m,1H),7.62–7.60(m,1H),7.34–7.31(m,1H),7.25–7.21(m,1H),7.16–7.05(m,3H),4.58(d,J=12.4Hz 1H), 3.76 (d, J = 12.4Hz 1H), 3.53 (s, 3H), 2.60 (s, 3H), 2.40–2.31 (m, 2H), 1.56 (s, 3H). 13C NMR (CDCl3, 101MHz): δ171.1, 162.6 (d, J = 247.7Hz), 142.4, 135.5, 129.2, 129.0, 127.4 (d, J = 8.1Hz), 125.4, 12 2.1,119.1,118.7,114.3(d,J=21.5Hz),112.3(d,J=22.8Hz),108.7,106.8,51.4,48.7,41.8,38.2,22.2,10.7.

[0047] Example 7

[0048] Methyl2-(1-fluoro-5,12-dimethyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0049]

[0050] To a dried Schlenk tube, 1 g (0.2 mmol, 55.8 mg) of 2-(2-fluorophenyl)-3-methyl-1-(2-methylallyl)-1H-indole, cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 52%. The compound was a yellow oil.

[0051] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.67–7.64(m,1H),7.34–7.20(m,4H),7.14–7.09(m,2H),4.55(d,J=12.5Hz ,1H),3.78(d,J=12.5Hz,1H),3.49(s,3H),2.49(d,J=7.4Hz,3H),2.23–2.14(m,2H),1.54(s,3H).13 C NMR (CDCl3, 101MHz): δ 171.2, 159.3 (d, J = 251.7Hz), 143.1 (d, J = 3.4Hz), 136.3, 129.2, 128.2 (d, J = 8.8Hz), 125.4, 122.4, 120.3 (d, J = 3.1 Hz) 119.2, 119.0, 117.6 (d, J = 15.7Hz), 115.2 (d, J = 23.1Hz) 110.4, 108.8, 51.4, 49.0, 40.9, 38.7 (d, J = 2.2Hz), 22.0, 11.0 (d, J = 16.1Hz).

[0052] Example 8

[0053] Methyl2-(5,9,10,12-tetramethyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0054]

[0055] To a dried Schlenk tube, 3,5,6-trimethyl-1-(2-methylallyl)-2-phenyl-1H-indole 1h (0.2 mmol, 57.8 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 75%. The compound was a yellow oil.

[0056] NMR data: 1H NMR (CDCl3, 400MHz): δ7.84–7.81(m,1H),7.46–7.44(m,1H),7.41–7.37(m,1H),7.32–7.28(m,1H),7.01(s,1H),6.69(s,1H),4.5 3(d,J=12.4Hz,1H),3.75(d,J=12.4Hz,1H),3.57(s,3H),2.84(s,3H),2.79(s,3H),2.48(s,3H),2.43–2.35(m,2H),1.60(s,3H). 13 C NMR (CDCl3, 101MHz): δ171.5,140.0,136.3,131.8,131.0,129.2(2C),127.1,126.5,12 5.9,125.4,124.7,123.0,108.4,106.7,51.3,48.9,41.7,38.0,22.1,21.7,20.8,13.3.

[0057] Example 9

[0058] Methyl2-(3-methoxy-5,12-dimethyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0059]

[0060] To a dried Schlenk tube, 5-methoxy-3-methyl-1-(2-methylallyl)-2-phenyl-1H-indole 1i (0.2 mmol, 58.2 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 76%. The compound was a yellow oil.

[0061] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.85–7.83(m,1H),7.43–7.35(m,2H),7.30-7.22(m,2H),7.05(d,J=2.4Hz 1H),6.91-6.88(m,1H),4.52(d,J=12.4Hz,1H),3.89(s,3H),3.76(d,J= 12.4Hz,1H),3.52(s,3H),2.60(s,3H),2.40–2.32(m,2H),1.57(s,3H). 13 CNMR(CDCl3,101MHz): δ171.4,153.8,139.7,131.0,130.4,129.3,129.2,127.3,126. 8,125.7,124.7,112.4,109.5,106.8,100.4,55.9,51.4,49.0,42.0,38.0,22.2,10.9.

[0062] Example 10

[0063] Methyl2-(10-fluoro-5,12-dimethyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0064]

[0065] To a dried Schlenk tube, 5-fluoro-3-methyl-1-(2-methylallyl)-2-phenyl-1H-indole 1j (0.2 mmol, 55.8 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 77%. The compound was a yellow oil.

[0066] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.84(dd,J=7.8,1.4Hz,1H),7.45–7.36(m,2H),7.32-7.29(m,1H),7.26–7.24(m,1H+overlapped with CDCl3),7.24–7.22(m,1H),6.99–6.94(m,1H),4.56(d,J=12.4Hz,1H),3.78( d,J=12.4Hz,1H),3.53(s,3H),2.58(s,3H),2.41–2.29(m,2H),1.58(s,3H). 13 C NMR (CDCl3, 101MHz): δ171.4,158.7(d,J=235.1Hz),139.8,132.2,131.2,129.4(d,J=9.4Hz),128.9,127.4,127.2,125.9,1 24.8, 110.3 (d, J = 26.5Hz), 109.3 (d, J = 9.7Hz), 107.1 (d, J = 5.1Hz), 103.4 (d, J = 23.3Hz), 51.4, 48.9, 42.0, 38.0, 22.2, 10.8.

[0067] Example 11

[0068] Methyl2-(5,12-dimethyl-10-(trifluoromethoxy)-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0069]

[0070] To a dried Schlenk tube, 3-methyl-1-(2-methylallyl)-2-phenyl-5-(trifluoromethoxy)-1H-indole 1k (0.2 mmol, 69.0 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 80%. The compound was a yellow oil.

[0071] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.86 (dd, J=7.8, 1.3Hz, 1H), 7.47–7.30 (m, 5H), 7.12–7.09 (m, 1H), 4.61 (d, J =12.4Hz,1H),3.80(d,J=12.4Hz,1H),3.55(s,3H),2.61(s,3H),2.37(d,J=2.7Hz,2H),1.60(s,3H). 13 C NMR (CDCl3, 101MHz): δ171.3, 142.6 (d, J = 2.0Hz), 134.0, 133.9, 131.5, 129.3, 128.7, 127.4 (d, J = 2.5Hz) ),126.0,124.8,120.9(d,J=256.0Hz),116.0,111.2,109.2,107.5,51.4,49.0,42.0,38.0,22.2,10.8.

[0072] Example 12

[0073] Methyl 2-(5,10,12-trimethyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0074]

[0075] To a dried Schlenk tube, 3,5-dimethyl-1-(2-methylallyl)-2-phenyl-1H-indole 1l (0.2 mmol, 55.0 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 79%. The compound was a yellow oil.

[0076] NMR data: 1 H NMRδ7.84(dd,J=7.8,1.3Hz,1H),7.44–7.34(m,3H),7.29–7.22(m,2H),7.06(dd,J=8.4,1.6Hz,1H),4.55(d,J =12.3Hz,1H),3.77(d,J=12.3Hz,1H),3.52(s,3H),2.60(s,3H),2.48(s,3H),2.41–2.31(m,2H),1.57(s,3H). 13 C NMR (101MHz, CDCl3) δ171.5,139.8,134.0,129.8,129.4,129.3,128.2,127.2,126.8 ,125.8,124.8,123.7,118.4,108.4,106.8,51.4,49.0,42.0,38.1,22.2,21.6,10.8.

[0077] Example 13

[0078] Methyl 2-(5,8,12-trimethyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0079]

[0080] In a dried Schlenk tube, 1 mL of 3,7-dimethyl-1-(2-methylallyl)-2-phenyl-1H-indole (0.2 mmol, 55.0 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). The organic layer was then separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, the product was separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 72%. The compound was a yellow oil.

[0081] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.82 (dd, J=7.8, 1.4Hz, 1H), 7.49–7.45 (m, 1H), 7.43–7.34 (m, 2H), 7.30–7.26 (m, 1H), 7.07–6.90 (m, 2H),5.18(d,J=12.5Hz,1H),4.02(d,J=12.5Hz,1H),3.55(s,3H),2.80(s,3H),2.60(s,3H),2.47–2.33(m,2H),1.56(s,3H). 13 C NMR (CDCl3,101MHz): δ171.6,140.0,134.5 130.2,129.6,129.3,127.2,126.8,126.0,125.2,124.3,120.6,119.0,116.8,107.8,51.4,51.1,41.5,38.1,21.9,20.5,10.9.

[0082] Example 14

[0083] Methyl2-(5,14-dimethyl-5,6-dihydrobenzo[5,6]indolo[2,1-a]isoquinolin-5-yl)acetate

[0084]

[0085] In a dried Schlenk tube, 3-methyl-1-(2-methylallyl)-2-phenyl-1H-benz[f]indole 1n (0.2 mmol, 62.2 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added in sequence. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 67%. The compound was a yellow oil.

[0086] NMR data: 1 H NMR (CDCl3, 400MHz): δ8.62 (dd, J=8.3, 1.1Hz, 1H), 7.95–7.88 (m, 2H), 7.65–7.54 (m, 3H), 7.47–7.40 (m, 3H), 7.34 –7.30(m,1H),4.74(d,J=12.5Hz,1H),3.87(d,J=12.5Hz,1H),3.54(s,3H),3.05(s,3H),2.33(s,2H),1.61(s,3H). 13 C NMR (CDCl3, 101MHz): δ171.5,140.1,132.5,129.8,129.6,129.1,129.0,128.9,127.3,126.7,12 6.0,125.6,124.7,123.4,123.2,122.7,121.7,110.7,110.4,51.4,49.0,41.5,38.2,21.9,14.3.

[0087] Example 15

[0088] Methyl 2-(5-methyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0089]

[0090] In a dried Schlenk tube, 1-(2-methylallyl)-2-phenyl-1H-indole 1o (0.2 mmol, 49.9 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added in sequence. The reaction vessel was evacuated to approximately -0.1 MPa (for 30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). The organic layer was then separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, the product was separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 83%. The compound was a yellow oil.

[0091] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.80–7.77(m,1H),7.64(dt,J=7.9,1.0Hz,1H),7.41–7.36(m,2H),7.35–7.26(m,2H+overlapped with CDCl3),7.24–7.20(m,1H),7.11(ddd,J=7.9,7.0,1.1Hz,1H),6.88(s,1H),4.62(d,J=12.4Hz,1H) ,3.84(d,J=12.4Hz,1H),3.52(s,3H),2.51(d,J=14.5Hz,1H),2.43(d,J=14.5Hz,1H),1.61(s,3H). 13 CNMR(CDCl3,101MHz): δ171.3,138.8,136.9,134.8,128.6,127.9,127.8,127.5 ,124.8,124.7,121.8,120.7,119.9,109.1,96.7,51.4,49.1,42.7,37.7,22.7.

[0092] Example 16

[0093] Methyl 2-(12-ethyl-5-methyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0094]

[0095] In a dried Schlenk tube, 3-ethyl-1-(2-methylallyl)-2-phenyl-1H-indole 1p (0.2 mmol, 55.0 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added in sequence. The reaction vessel was evacuated to approximately -0.1 MPa (for 30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). The organic layer was then separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, the product was separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 78%. The compound was a yellow oil.

[0096] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.82–7.79(m,1H),7.82–7.64(m,1H),7.44–7.21(m,5H),7.13–7.09(m,1H+overlapped with CDCl3),4.60(d,J=12.4Hz,1H),3.80(d,J=12.3Hz,1H),3.52(s,3H),3.18–3.00(m,2H),2.40–2.31(m,2H),1.58(s,3H),1.40(t,J=7.5Hz,3H). 13 C NMR (101MHz, CDCl3)171.5,140.1,135.8,129.2,129.1,128.5,127.5,127.1,125.7, 124.9,122.1,119.1,118.8,114.5,108.9,51.4,49.0,42.0,38.0,22.3,18.4,15.3.

[0097] Example 17

[0098] Methyl2-(5-methyl-12-propyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0099]

[0100] In a dried Schlenk tube, 1-(2-methylallyl)-2-phenyl-3-propyl-1H-indole 1q (0.2 mmol, 57.8 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added in sequence. The reaction vessel was evacuated to approximately -0.1 MPa (for 30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). The organic layer was then separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, the product was separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 75%. The compound was a yellow oil.

[0101] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.80 (dd, J=7.7, 1.4Hz, 1H), 7.64 (dt, J=7.9, 1.0Hz, 1 H),7.42–7.32(m,3H),7.29–7.20(m,2H),7.10(ddd,J=7.9,7.0,1.0Hz,1H), 4.58(d,J=12.4Hz,1H),3.78(d,J=12.4Hz,1H),3.50(s,3H),3.11–2.98(m,2 H),2.37–2.29(m,2H),1.88–1.72(m,2H),1.56(s,3H),1.08(t,J=7.3Hz,3H). 13 C NMR(CDCl3,101MHz): δ171.4,140.0,135.6,129.4,129.1,128.9,127.4,127.0,125.6,1 24.8,122.0,119.0,119.0,113.0,108.8,51.3,48.9,41.9,37.9,27.2,24.0,22.2,14.4.

[0102] Example 18

[0103] Methyl2-(5-methyl-12-phenyl-5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0104]

[0105] To a dried Schlenk tube, 1-(2-methylallyl)-2,3-diphenyl-1H-indole 1r (0.2 mmol, 64.6 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added in sequence. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 69%. The compound was a yellow oil.

[0106] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.57–7.35(m,9H),7.28–7.19(m,2H),7.12–7.08(m,1H),7.04(td,J=7.6,1.2Hz,1H),4.67( d,J=12.4Hz,1H),3.85(d,J=12.4Hz,1H),3.54(s,3H),2.58(d,J=14.5Hz,1H),2.50(d,J=14.5Hz,1H),1.64(s,3H). 13 C NMR (CDCl3, 101MHz): δ171.4,134.0,135.8,135.6,130.5,129.7,128.7,128.6,128.0,127.5, 126.9,126.6,126.5,124.6,122.5,120.0,119.5,114.0,108.9,51.4,49.1,42.2,37.9,22.4.

[0107] Example 19

[0108] Methyl 2-(5,6-dihydroindolo[2,1-a]isoquinolin-5-yl)acetate

[0109]

[0110] To a dried Schlenk tube, 1-allyl-2-phenyl-1H-indole 1s (0.2 mmol, 46.6 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added in sequence. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 42%. The compound was a yellow oil.

[0111] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.77(d,J=7.7Hz,1H),7.65(d,J=7.9Hz,1H),7.36–7.27(m,4H),7.24–7.20(m,1H),7.12(t,J=7.5Hz,1H ),6.89(s,1H),4.47(dd,J=12.4,2.3Hz,1H),4.14(dd,J=12.5,4.1Hz,1H),3.72–3.70(m,1H),3.65(s,3H),2.60–3.45(m,2H). 13 C NMR(CDCl3,101MHz): δ172.3,137.1,134.8,134.7,128.8,128.2,127.9,127 .8,127.7,124.6,121.8,120.8,112.0,109.0,96.8,51.7,43.8,38.0,35.8.

[0112] Example 20

[0113] Methyl 4-(6-cyano-1-methoxy-1-oxohexan-2-yl)benzoate

[0114]

[0115] To a dried Schlenk tube, methyl 4-vinylbenzoate 1t (0.2 mmol, 29.2 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added in sequence. The reaction vessel was evacuated to approximately -0.1 MPa (for 30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). The organic layer was then extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, the product was separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 45%. The compound was a yellow oil.

[0116] NMR data: 1 H NMR (CDCl3, 400MHz): δ7.70–7.67(m,1H),7.59–7.56(m,1H),7.36–7.34(m,3H),7.30–7.28(m,1H),7.25–7.21(m,1H),7.15–7.11(m,1H),6 .66(s,1H),4.29–4.23(m,1H),3.94–3.87(m,1H),3.56(s,3H),3.42– 3.36(m,1H),2.71–2.66(m,1H),2.59–2.49(m,2H),2.00–1.92(m,1H). 13 C NMR(CDCl3,101MHz): δ172.5,140.9,139.1,136.5,133.1,129.4,128.4,128.1 ,127.2,126.2,121.5,120.8,119.4,108.7,99.9,51.7,40.5,38.4,37.0,36.8.

[0117] Example 21

[0118] To a dried Schlenk tube, 3-methyl-1-(2-methylallyl)-2-phenyl-1H-indole 1a (0.2 mmol, 52.2 mg), cesium carbonate (0.6 mmol, 196 mg), Ir[dF(CF3)ppy]2(dtbbpy)·PF6 (2 mol%, 4.4 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 51%. The compound was a yellow oil.

[0119] Example 22

[0120] To a dried Schlenk tube, 3-methyl-1-(2-methylallyl)-2-phenyl-1H-indole 1a (0.2 mmol, 52.2 mg), cesium carbonate (0.6 mmol, 196 mg), Ir(ppy)2(dtbbpy)·PF6 (2 mol%, 3.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 32%. The compound was a yellow oil.

[0121] Example 23

[0122] To a dried Schlenk tube, 3-methyl-1-(2-methylallyl)-2-phenyl-1H-indole 1a (0.2 mmol, 52.2 mg), cesium carbonate (0.6 mmol, 196 mg), 4CzIPN (2 mol%, 3.2 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). The organic layer was then extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, the product was separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 13%. The compound was a yellow oil.

[0123] Example 24

[0124] To a dried Schlenk tube, 3-methyl-1-(2-methylallyl)-2-phenyl-1H-indole 1a (0.2 mmol, 52.2 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-dicyclohexylmethylamine (0.2 mmol, 42.8 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 75%. The compound was a yellow oil.

[0125] Example 25

[0126] To a dried Schlenk tube, 3-methyl-1-(2-methylallyl)-2-phenyl-1H-indole 1a (0.2 mmol, 52.2 mg), cesium carbonate (0.6 mmol, 196 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), triethylamine (0.2 mmol, 28.0 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). The organic layer was then extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, the product was separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 56%. The compound was a yellow oil.

[0127] Example 26

[0128] To a dried Schlenk tube, 3-methyl-1-(2-methylallyl)-2-phenyl-1H-indole 1a (0.2 mmol, 52.2 mg), potassium carbonate (0.6 mmol, 82.8 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (for 30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). The organic layer was then extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, the product was separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 37%. The compound was a yellow oil.

[0129] Example 27

[0130] To a dried Schlenk tube, 3-methyl-1-(2-methylallyl)-2-phenyl-1H-indole 1a (0.2 mmol, 52.2 mg), sodium carbonate (0.6 mmol, 63.6 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of dimethyl sulfoxide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). The organic layer was then extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, the product was separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 37%. The compound was a yellow oil.

[0131] Example 28

[0132] To a dried Schlenk tube, 3-methyl-1-(2-methylallyl)-2-phenyl-1H-indole 1a (0.2 mmol, 52.2 mg), sodium carbonate (0.6 mmol, 63.6 mg), fac-Ir(ppy)3 (2 mol%, 2.6 mg), N,N-diisopropylethylamine (0.2 mmol, 40 μL), and 2 mL of N,N-dimethylformamide were added sequentially. The reaction vessel was evacuated to approximately -0.1 MPa (30 s each time) and backfilled with CO2 (1 atm) three times. The Schlenk tube was then stirred at room temperature and irradiated with a 30 W blue LED lamp for 12 hours. After the reaction, MeI (0.8 mmol, 114 mg) was added to the reaction mixture, and the reaction mixture was stirred at 55°C for approximately 1 hour. The reaction mixture was extracted six times with saturated brine and ethyl acetate (2 mL x 6). Subsequently, the organic layer was extracted, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Finally, it was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1) with a yield of 45%. The compound was a yellow oil.

[0133] Table 1Absorption and emission dates

[0134] Compounds 2ba 2ca 2da <![CDATA[λ abs (nm)]]> 272 274 272

[0135] a In DCM(10 -5 M)

[0136] Highly fused heteroarenes have unique optoelectronic properties, such as Figure 1 As shown, the optoelectronic properties of these highly fused heteroaromatics were tested by UV-Vis diffuse reflectance and photoluminescence (PL) spectroscopy. The products with different substituents have higher absorption peaks in the ultraviolet range and higher emission peaks in the visible light range.

Claims

1. A method for preparing a carboxylated indole fused heterocycle from carbon dioxide, characterized in that: The method comprises the following steps: adding an indole series non-activated olefin, a photocatalyst, an inorganic base, a reducing agent, and a solvent into a dry Schlenk tube; and after all the raw materials involved in the reaction are added, injecting carbon dioxide gas to react to obtain a series of carboxylated indole fused heterocycles. The structural formula of the non-activated olefins of the indole series is as follows: , where n = 1 or 2; R 1 is methyl, ethyl or hydrogen; R 2 is methyl or hydrogen, Ar 1 is a phenyl group connected to a methyl group, a methoxy group, a halogen group, an oxytrifluoromethyl group, or a naphthyl group, Ar 2 It is a phenyl group connected to a methyl group, a methoxy group, a halogen group, or a tert-butyl group; The photocatalyst is 2,4,5,6-tetrakis (9-carbazolyl)-isophthalonitrile 4CzIPN or tris (2,2'-bipyridine) iridium fac -Ir(ppy)3, the amount of catalyst used is 2 mol% of the moles of non-activated olefins of the indole series; The reducing agent is one of N,N-dimethylcyclohexylamine, triethylamine, and N,N-diisopropylethylamine, and the molar amount of the reducing agent and the non-activated olefin is equal; The reaction conditions are as follows: 30 W blue LED is reacted at room temperature for 12 to 36 hours, then iodomethane is added and reacted in a 55°C oil bath for another hour; The pressure of the carbon dioxide is 0.1 MPa; The inorganic base is cesium carbonate, potassium carbonate, or sodium carbonate; and the solvent is dimethyl sulfoxide or N,N-dimethylformamide.

2. The method for preparing a carboxylated indole fused heterocycle from carbon dioxide as claimed in claim 1, wherein: The molar ratio of the methyl iodide to the non-activated olefin is 4:1.

Images