A method for synthesizing polycyclic indole compounds by photocatalytic cycloaddition reaction

Abstract

The present invention belongs to the field of chemical synthesis, and particularly relates to a method for synthesizing polycyclic indole compounds via a photocatalytic cycloaddition reaction. Specifically, under visible light irradiation and the addition of an iridium photosensitizer, an indole compound of Formula 1 and a bicyclo[1.1.0]butane compound of Formula 2 are subjected to a photocatalytic reaction to prepare a compound of Formula 3: wherein R1 is a halogen or hydrogen; R2 is COR4; R4 is an alkyl, alkoxy, or phenyl group; R3 is SO2PhX; X is hydrogen, halogen, alkyl, alkoxy, or trifluoromethyl; and the iridium photosensitizer has the structure:

Description

Technical Field

[0001] The invention belongs to the field of chemical synthesis, and in particular relates to a method for synthesizing polycyclic indole compounds through a photocatalytic cycloaddition reaction. Background Art

[0002] The function of a molecule is closely linked to its three-dimensional structure, a phenomenon particularly evident in medicinal chemistry. Consequently, over the past few decades, methods for constructing conformationally constrained three-dimensional molecular structures have garnered increasing attention and development. (Mann, N.; Gray, T. Molecules: The Elements and the Architecture of Everything; Running Press, 2018; pp. 1-240.) In particular, the recent discovery by F. Lovering's group of the "escape from flatland" concept of replacing planar benzene rings with three-dimensional saturated carbocyclic compounds has provided significant assistance. (J. Med. Chem. 2009, 52, 6752–6756; Med Chem Comm 2013, 4, 515–519.) In this context, carbon (sp3)-rich ring scaffolds, due to their inherent rigid conformation and metabolic stability, have the potential to improve the pharmacokinetics and physicochemical properties of compounds. Bicyclo[2.1.1]hexanes (BCHs), believed to be bioisomers of ortho- or meta-substituted benzene compounds, possess rigid and well-defined exit vectors and have garnered significant attention. Significant resources have been invested in developing methods for synthesizing compounds containing BCH building blocks. Typically, BCH compounds are synthesized via photocatalytic intramolecular [2+2] cycloadditions of 1,5-dienes. Cycloadditions of alkenes with bicyclo[1.1.0]butanes (BCBs) have become an increasingly popular synthetic approach in recent years and are increasingly considered the primary method for constructing these frameworks. However, the photoaffinity of the initial addition products, particularly in the case of ortho-cycloadditions, often leads to uncontrollable, continuous rearrangements, making the products of these ortho-cycloadditions difficult to identify, significantly hindering the development of these methods. In 2022, the Glorius and Brown groups, respectively, developed an ortho-selective intermolecular cycloaddition reaction between alkenes and BCBs via a photoinduced energy transfer step. (Nature 2022, 605, 477–482; J.Am.Chem.Soc.2022, 144, 7988–7994;) The former route is to excite electron-deficient conjugated olefins, while the latter is achieved by exciting naphthyl ketone-substituted BCBs. Subsequently, in 2023, Professor Deng Li's team developed a new method to directly obtain structurally complex polycyclic indoles from readily available indoles and bicyclo[1.1.0]butanes (BCBs) (Angew.Chem.Int.Ed.2023, e202308606). They used commercially available Lewis acids to promote the nucleophilic addition of indoles and the subsequent intramolecular Mannich reaction.

[0003]

[0004] On the basis of the existing technology, the present invention attempts to synthesize structural motifs that were previously difficult to obtain, filling the rare gaps in previous research. Summary of the Invention

[0005] The present invention first provides a compound of formula 3, the structural formula of which is:

[0006]

[0007] Wherein, R1 is halogen or hydrogen; R2 is COR4; R4 is alkyl, alkoxy, phenyl, R3 is SO2PhX; X is hydrogen, halogen, alkyl, alkoxy or trifluoromethyl.

[0008] On the other hand, the present invention provides a compound of formula 3 prepared by photocatalytic reaction of a compound of formula 1 and a compound of formula 2, wherein the photocatalytic reaction is initiated by visible light irradiation and the action of an iridium photosensitizer:

[0009]

[0010] Wherein, R1 is halogen or hydrogen; R2 is COR4; R4 is alkyl, alkoxy, phenyl, R3 is SO2PhX; X is hydrogen, halogen, alkyl, alkoxy or trifluoromethyl;

[0011] The structural formula of the iridium photosensitizer is:

[0012]

[0013] The molar ratio of the iridium photosensitizer to the compound of formula 1 is 0.02:1.

[0014] The molar ratio of the compound of the above-mentioned photocatalytic reaction formula 2 to the compound of formula 1 is 1.2:1.

[0015] The photocatalytic reaction solvent is an organic solvent, which is acetonitrile, tetrahydrofuran or toluene, preferably acetonitrile. The photocatalytic reaction is carried out under the irradiation of a 50W blue light source.

[0016] The photocatalytic reaction temperature is 18-30°C, preferably room temperature.

[0017] The photocatalytic reaction time is 16-24 hours, preferably 16 hours.

[0018] The specific structural formula of the product (compound of formula 3) prepared by the above-mentioned photocatalytic reaction can be:

[0019]

[0020] The present invention provides a method for synthesizing polycyclic indole compounds via a photocatalytic cycloaddition reaction, directly obtaining structurally complex polycyclic indoles from readily available indoles and bicyclo[1.1.0]butane compounds (BCBs). This is a simple, modular, and diastereoselective photocatalytic cycloaddition reaction. We selected a wider range of indoles as substrates for synthesis, constructing rigid polycyclic indole compounds containing up to four consecutive quaternary carbon centers in a single step. Furthermore, we explored a wider range of bicyclo[1.1.0]butane compounds (BCBs) and verified the feasibility and adaptability of this method. Therefore, applying this synthetic strategy can help us synthesize structural motifs that were previously difficult to obtain. DETAILED DESCRIPTION

[0021] To further understand the present invention, the following detailed description of a method for synthesizing polycyclic indole compounds via a photocatalytic cycloaddition reaction is provided by the present invention, with reference to the following examples. It should be understood that these examples are intended only to further illustrate the features of the present invention and are not intended to limit the scope of the present invention or the claims.

[0022] Example 1:

[0023]

[0024] Indole compound 1a (0.5 mmol, 1.0 eq.), bicyclo[1.1.0]butane compound 2a (0.6 mmol, 1.2 eq.), and iridium photosensitizer (11.2 mg, 0.01 mmol, 0.02 eq.) were added sequentially to a dry 25 mL photoreaction tube. The photoreaction tube was evacuated and replaced with nitrogen for five cycles. 5 mL of ultra-dry acetonitrile was added and stirred continuously for 16 h at room temperature under 50 W blue light source. A spot plate (n-Hexane:EA=4:1, R f =0.3-0.6) after testing the polarity of the product, the reaction solution was filtered to remove white precipitate impurities; the collected filtrate was spin-dried and mixed with silica gel, then loaded onto a column for column separation using n-hexane and ethyl acetate as eluents. The desired eluate was collected and spin-dried to obtain the target product; if the column separation still did not yield a completely pure target product, recrystallization was performed using MTBE in a 55°C water bath. After the product was completely dissolved in MTBE, n-hexane was added dropwise until a white solid appeared, followed by recrystallization at room temperature; after waiting for 24-48 hours for recrystallization to be complete, the recrystallization solution was aspirated, and the crystals were rinsed with n-hexane to obtain the pure target product 3a (80% yield, solid). 1HNMR (400MHz, CDCl3) δ7.91(d,J=8.0Hz,1H),7.84(d,J=7.2Hz,2H),7.60–7.50(m,4H),7.23(t,J=8.0Hz,1H),6.99(t,J= 7.6Hz,1H),4.11(s,1H),3.63(s,3H),3.14(s,1H),2.01–1.97(m,1H),1.93–1.89(m,2H),1.74–1.69(m,1H),1.42(s,9H). 13 C NMR (101MHz, CDCl3) δ171.2,150.5,145.8,137.4,134.0,129.2,128.6,127.6,124.7,12 2.5,114.1,81.9,76.8,69.3,53.4,52.3,43.3,42.8,34.4,28.1.HRMS(ESI)m / z:[M+Na] + Calculated for C 25 H 27 NNaO6S 492.1451; Found 492.1452.

[0025] Example 2:

[0026]

[0027] Indole compound 1b (0.5 mmol, 1.0 eq.), bicyclo[1.1.0]butane compound 2b (0.6 mmol, 1.2 eq.), and iridium photosensitizer (11.2 mg, 0.01 mmol, 0.02 eq.) were added sequentially to a dry 25 mL photoreaction tube. The photoreaction tube was evacuated and replaced with nitrogen for five cycles. 5 mL of ultra-dry acetonitrile was added and stirred continuously for 16 h at room temperature under 50 W blue light source. A spot plate (n-Hexane:EA=4:1, R f =0.3-0.6) after testing the polarity of the product, the reaction solution was filtered to remove the white precipitate impurities; the collected filtrate was spin-dried and mixed with silica gel, then loaded onto a column for column separation using n-hexane and ethyl acetate as eluents. The desired eluate was collected and spin-dried to obtain the target product; if the column separation still did not yield a completely pure target product, recrystallization was performed using MTBE in a 55°C water bath. After the product was completely dissolved in MTBE, n-hexane was added dropwise until a white solid appeared, followed by recrystallization at room temperature; after waiting for 24-48 hours for recrystallization to be complete, the recrystallization solution was aspirated, and the crystals were rinsed with n-hexane to obtain the pure target product 3b (76% yield, solid). 1HNMR(400MHz, CDCl3) δ7.91(d,J=8.0Hz,1H),7.31(d,J=8.4Hz,2H),7.21(t,J =8.0Hz,1H),6.95–6.89(m,3H),6.84(t,J=7.6Hz,1H),5.18(d,J=12.0Hz,1H) ,5.06(d,J=12.0Hz,1H),4.08(s,1H),3.81(s,3H),3.71(s,3H),3.12(s,1H), 2.20–2.18(m,1H),2.10–2.03(m,1H),1.94–1.91(m,1H),1.57–1.43(m,10H). 13 C NMR (101MHz, CDCl3) δ171.6,170.3,159.8,151.0,145.9,130.4,128.9,127.9,127.4,125.2,122. 8,114.4,114.0,81.7,76.5,66.3,55.8,55.3,52.3,44.7,44.3,34.0,28.3.HRMS(ESI)m / z:[M+Na] + Calculated for C 28 H 31 NNaO7 516.1993; Found 516.1993.

[0028] Example 3:

[0029]

[0030] Indole compound 1c (0.5 mmol, 1.0 eq.), bicyclo[1.1.0]butane compound 2c (0.6 mmol, 1.2 eq.), and iridium photosensitizer (11.2 mg, 0.01 mmol, 0.02 eq.) were added sequentially to a dry 25 mL photoreaction tube. The photoreaction tube was evacuated and replaced with nitrogen for five cycles. 5 mL of ultra-dry acetonitrile was added, and the mixture was stirred continuously for 16 h at room temperature under 50 W blue light source. A spot plate (n-Hexane:EA=4:1, R f= 0.3-0.6) after testing the polarity of the product, the reaction solution was filtered to remove the white precipitate impurities; the collected filtrate was spin-dried and mixed with silica gel, then loaded onto a column for column separation using n-hexane and ethyl acetate as eluents. The desired eluate was collected and spin-dried to obtain the target product; if the column separation still did not yield a completely pure target product, recrystallization was performed using MTBE in a 55°C water bath. After the product was completely dissolved in MTBE, n-hexane was added dropwise until a white solid appeared, followed by recrystallization at room temperature; after waiting for 24-48 hours for recrystallization to be complete, the recrystallization solution was aspirated, and the crystals were rinsed with n-hexane to obtain the pure target product 3c (64% yield, oil). 1 H NMR(400MHz, CDCl3)δ7.87(d,J=8.0Hz,1H),7.45–6.78(m,8H),3.99(s,1H),3.63(s,3H),3.2 7(s,3H),2.77(s,1H),1.92–1.90(m,1H),1.78–1.64(m,1H),1.39(s,9H),1.06–0.79(m,2H). 13 C NMR (101MHz,CDCl3)δ171.6,

[0031] 170.1,151.1,145.9,142.9,129.3,129.0,128.2,127.8,124.8,122.7,114.6,8 1.6,75.9,57.5,57.2,52.2,45.8,43.6,38.9,35.6,28.2.HRMS(ESI)m / z:[M+Na] + Calculated for C 27 H 30 N2NaO5 485.2047;

[0032] Found 485.2047.

[0033] Example 4:

[0034]

[0035] Indole compound 1d (0.5 mmol, 1.0 eq.), bicyclo[1.1.0]butane compound 2d (0.6 mmol, 1.2 eq.), and iridium photosensitizer (11.2 mg, 0.01 mmol, 0.02 eq.) were added sequentially to a dry 25 mL photoreaction tube. The photoreaction tube was evacuated and replaced with nitrogen for five cycles. 5 mL of ultra-dry acetonitrile was added, and the mixture was stirred continuously for 16 h at room temperature under irradiation with a 50 W blue light source. A spot plate (n-Hexane:EA=4:1, Rf =0.3-0.6) after testing the polarity of the product, the reaction solution was filtered to remove white precipitate impurities; the collected filtrate was spin-dried and mixed with silica gel, then loaded onto a column for column separation using n-hexane and ethyl acetate as eluents. The desired eluate was collected and spin-dried to obtain the target product; if the column separation still did not yield a completely pure target product, recrystallization was performed using MTBE in a 55°C water bath. After the product was completely dissolved in MTBE, n-hexane was added dropwise until a white solid appeared, followed by recrystallization at room temperature; after waiting for 24-48 hours for recrystallization to be complete, the recrystallization solution was aspirated, and the crystals were rinsed with n-hexane to obtain the pure target product 3d (75% yield, solid). 1 HNMR (400MHz, CDCl3) δ7.95(d,J=8.0Hz,1H),7.72(d,J=7.6Hz,2H),7.55(t,J=7.6Hz,1H),7.40(t,J=7.6Hz,2H),7.21(t,J=7.6Hz,1H),6.81(t,J =7.6Hz,1H),6.62(d,J=7.6Hz,1H),4.23(s,1H),3.76(s,3H),3.19(s,1H ),2.49–2.34(m,2H),1.99–1.93(m,1H),1.74–1.69(m,1H),1.51(s,9H). 13 C NMR (101MHz, CDCl3) δ199.6,171.8,151.1,145.9,136.9,133.6,129.1,128.8,128.6,127.0,124.9,122.7,114.7,81.9,62.5,

[0036] 58.0,52.4,45.9,44.2,35.4,28.4.HRMS(ESI)m / z:[M+Na] + Calculated for C 26 H 27 NNaO5 456.1781; Found 456.1780.

[0037] Example 5:

[0038]

[0039] Indole compound 1e (0.5 mmol, 1.0 eq.), bicyclo[1.1.0]butane compound 2e (0.6 mmol, 1.2 eq.), and iridium photosensitizer (11.2 mg, 0.01 mmol, 0.02 eq.) were added sequentially to a dry 25 mL photoreaction tube. The photoreaction tube was evacuated and replaced with nitrogen for five cycles. 5 mL of ultra-dry acetonitrile was added and stirred continuously for 16 h at room temperature under 50 W blue light source. A spot plate (n-Hexane:EA=4:1, R f =0.3-0.6) after testing the polarity of the product, the reaction solution was filtered to remove white precipitate impurities; the collected filtrate was spin-dried and mixed with silica gel, then loaded onto a column for column separation using n-hexane and ethyl acetate as eluents. The desired eluate was collected and spin-dried to obtain the target product; if the column separation still did not yield a completely pure target product, recrystallization was performed using MTBE in a 55°C water bath. After the product was completely dissolved in MTBE, n-hexane was added dropwise until a white solid appeared, followed by recrystallization at room temperature; after waiting for 24-48 hours for recrystallization to be complete, the recrystallization solution was aspirated, and the crystals were rinsed with n-hexane to obtain the pure target product 3e (50% yield, solid). 1 HNMR(400MHz, CDCl3)δ8.07–7.89(m,3H),7.59(d,J=7.6Hz,1H),7.31–7.24(m,3H),7.04(t,J=7.6Hz,1H),4 .17(s,1H),3.70(s,3H),3.21(s,1H),2.09–2.04(m,1H),1.98–1.93(m,2H),1.79–1.74(m,1H),1.48(s,9H).

[0040] 13 C NMR (101MHz, CDCl3) δ170.6,165.9(d,J=255Hz),150.5,145.9,133.6(d,J=3Hz),131.6(d,J =10Hz),129.4,127.6,124.6,122.6,116.6(d,J=22Hz),114.2,82.0,76.8,69.5,53.5,52.4,

[0041] 43.4,42.8,34.5,28.1. 19 F NMR(376MHz,CDCl3)δ-102.8.HRMS(ESI)m / z:[M+Na] +

[0042] Calculated for C 25 H26 FNNaO6S 510.1357; Found 510.1358.

[0043] Example 6:

[0044]

[0045] Indole compound 1f (0.5 mmol, 1.0 eq.), bicyclo[1.1.0]butane compound 2f (0.6 mmol, 1.2 eq.), and iridium photosensitizer (11.2 mg, 0.01 mmol, 0.02 eq.) were added sequentially to a dry 25 mL photoreaction tube. The photoreaction tube was evacuated and replaced with nitrogen, and the cycle was repeated five times. 5 mL of ultra-dry acetonitrile was added, and the tube was stirred continuously for 16 h at room temperature under 50 W blue light source. A spot plate (n-Hexane:EA=4:1, R f =0.3-0.6) after testing the polarity of the product, the reaction solution was filtered to remove the white precipitate impurities; the collected filtrate was spin-dried and mixed with silica gel, then loaded onto a column for column separation using n-hexane and ethyl acetate as eluents. The desired eluate was collected and spin-dried to obtain the target product; if the column separation still did not yield a completely pure target product, recrystallization was performed using MTBE in a 55°C water bath. After the product was completely dissolved in MTBE, n-hexane was added dropwise until a white solid appeared, followed by recrystallization at room temperature; after waiting for 24-48 hours for recrystallization to be complete, the recrystallization solution was aspirated, and the crystals were rinsed with n-hexane to obtain the pure target product 3f (48% yield, solid). 1 HNMR (400MHz, CDCl3) δ7.91(d,J=8.4Hz,1H),7.74(d,J=8.0Hz,2H),7.59(d,J=7.6Hz,1H),7.34(d,J=8.0Hz,2H),7.25(t,J=8.0Hz,

[0046] 1H),7.02(t,J=7.6Hz,1H),4.09(s,1H),3.66(s,3H),3.15(s,1H),2.43(s,3H),2.01–1.90(m,3H),1.78–1.70(m,1H),1.44(s,9H). 13 C NMR (101MHz, CDCl3) δ170.8,150.7,145.9,145.1,

[0047] 134.6,129.9,129.3,128.8,127.7,124.8,122.7,114.2,82.0,77.0,69.5,53.6,52.4,43.4,42.8,34.5,

[0048] 28.2,21.7.HRMS(ESI)m / z:[M+Na] + Calculated for C 26 H 29 NNaO6S 506.1608; Found 506.1605.

[0049] Example 7:

[0050]

[0051] To a dry 25 mL photoreaction tube, 1 g (0.5 mmol, 1.0 eq.) of indole compound, 2 g (0.6 mmol, 1.2 eq.) of bicyclo[1.1.0]butane compound, and iridium photosensitizer (11.2 mg, 0.01 mmol, 0.02 eq.) were added in sequence; the photoreaction tube was evacuated and replaced with nitrogen, and the cycle was repeated five times; 5 mL of ultra-dry acetonitrile was added, and the tube was stirred continuously for 16 h at room temperature under irradiation with a 50 W blue light source; a spot plate (n-Hexane:EA=4:1, R f = 0.3-0.6) after testing the polarity of the product, the reaction solution was filtered to remove white precipitate impurities; the collected filtrate was spin-dried and mixed with silica gel, then loaded onto a column for column separation using n-hexane and ethyl acetate as eluents. The desired eluate was collected and spin-dried to obtain the target product; if the column separation still did not yield a completely pure target product, recrystallization was performed using MTBE in a 55°C water bath. After the product was completely dissolved in MTBE, n-hexane was added dropwise until a white solid appeared, followed by recrystallization at room temperature; after waiting for 24-48 hours for recrystallization to be complete, the recrystallization solution was aspirated, and the crystals were rinsed with n-hexane to obtain 3 g (46% yield, solid) of the pure target product. 1 HNMR (400MHz, CDCl3) δ7.93(d,J=8.0Hz,1H),7.81(d,J=8.0Hz,2H),7.58–7.51(m,3H),7.28(t,J=7.2Hz,1H),7.03(t,J=7.6

[0052] Hz,1H),4.14(s,1H),3.69(s,3H),3.19(s,1H),2.06–2.01(m,1H),1.96–1.91(m,2H),1.78–1.73(m,1H),1.46(s,9H). 13C NMR (101MHz, CDCl3) δ170.7,150.6,146.0,140.8,136.1,130.1,129.7,129.5,127.6,124.5 ,122.7,114.3,82.2,76.8,69.5,53.6,52.5,43.4,42.9,35.0,28.2.HRMS(ESI)m / z:[M+Na] + Calculated for C 25 H 26 ClNNaO6S 526.1062; Found 526.1063.

[0053] Example 8:

[0054]

[0055] Indole compound 1h (0.5 mmol, 1.0 eq.), bicyclo[1.1.0]butane compound 2h (0.6 mmol, 1.2 eq.), and iridium photosensitizer (11.2 mg, 0.01 mmol, 0.02 eq.) were added to a dry 25 mL photoreaction tube in sequence; the photoreaction tube was evacuated and replaced with nitrogen, and the cycle was repeated five times; 5 mL of ultra-dry acetonitrile was added, and the tube was stirred continuously for 16 h at room temperature under 50 W blue light source; a spot plate (n-Hexane:EA=4:1, R f = 0.3-0.6) after testing the polarity of the product, filter the reaction solution to remove white precipitate impurities; the collected filtrate is spin-dried and mixed with silica gel, then loaded onto a column for column separation using n-hexane and ethyl acetate as eluents. The desired eluate is collected and spin-dried to obtain the target product; if the column separation still does not yield a completely pure target product, recrystallize it using MTBE in a 55°C water bath. After the product is completely dissolved in MTBE, add n-hexane dropwise until a white solid appears, followed by recrystallization at room temperature; wait 24-48 hours for recrystallization to be complete, remove the recrystallization solution by aspiration, and rinse the crystals with n-hexane to obtain the pure target product (43% yield, solid). 1 HNMR(400MHz, CDCl3)δ7.86–7.84(m,3H),7.66(t,J=7.6Hz,1H),7.56(t,J=7.6Hz,2H),7.50(s,1H),7.21–7.18(m,1H), 4.18–4.12(m,2H),4.08(s,1H),3.15(s,1H),2.04–1.93(m,3H),1.73–1.68(m,1H),1.43(s,9H),1.19(t,J=7.2Hz,3H). 13C NMR (101MHz, CDCl3) δ169.9,150.6,144.8,137.5,134.2,129.4,128.8,127.8,127.6,126. 6,115.2,82.5,77.4,69.6,61.8,53.3,43.4,42.9,34.9,28.3,14.2.HRMS(ESI)m / z:[M+Na] + Calculated for C 26 H 28 ClNNaO6S 540.1218; Found 540.1227.

[0056] Example 9:

[0057]

[0058] Indole compound 1i (0.5 mmol, 1.0 eq.), bicyclo[1.1.0]butane compound 2i (0.6 mmol, 1.2 eq.), and iridium photosensitizer (11.2 mg, 0.01 mmol, 0.02 eq.) were added sequentially to a dry 25 mL photoreaction tube. The photoreaction tube was evacuated and replaced with nitrogen, and the cycle was repeated five times. 5 mL of ultra-dry acetonitrile was added, and the tube was stirred continuously for 16 h at room temperature under 50 W blue light source. A spot plate (n-Hexane:EA=4:1, R f =0.3-0.6) after testing the polarity of the product, the reaction solution was filtered to remove white precipitate impurities; the collected filtrate was spin-dried and mixed with silica gel, then loaded onto a column for column separation using n-hexane and ethyl acetate as eluents. The desired eluate was collected and spin-dried to obtain the target product; if the column separation still did not yield a completely pure target product, recrystallization was performed using MTBE in a 55°C water bath. After the product was completely dissolved in MTBE, n-hexane was added dropwise until a white solid appeared, followed by recrystallization at room temperature; after waiting for 24-48 hours for recrystallization to be complete, the recrystallization solution was aspirated, and the crystals were rinsed with n-hexane to obtain the pure target product 3i (51% yield, solid). 1 HNMR(400MHz, CDCl3)δ7.90(d,J=8.4Hz,1H),7.77–7.75(m,2H),7.58(d,J=7.6Hz,1H),7.24(t,J=7.6Hz,1H),7.02– 6.98(m,3H),4.07(s,1H),3.83(s,3H),3.65(s,1H),3.14(s,1H),1.99–1.88(m,3H),1.72–1.68(m,1H),1.42(s,9H). 13C NMR (101MHz, CDCl3) δ170.8,163.9,150.6,145.9,130.9,129.2,128.9,127.7,124.8,122.6,

[0059] 114.5,114.1,82.0,76.9,69.6,55.7,53.5,52.4,43.3,42.7,34.3,28.1.HRMS(ESI)m / z:[M+Na] +

[0060] Calculated for C 26 H 29 NNaO7S 522.1557; Found 522.1552.

[0061] Example 10:

[0062]

[0063] Indole compound 1j (0.5 mmol, 1.0 eq.), bicyclo[1.1.0]butane compound 2j (0.6 mmol, 1.2 eq.), and iridium photosensitizer (11.2 mg, 0.01 mmol, 0.02 eq.) were added sequentially to a dry 25 mL photoreaction tube. The photoreaction tube was evacuated and replaced with nitrogen for five cycles. 5 mL of ultra-dry acetonitrile was added, and the tube was stirred continuously for 16 h at room temperature under 50 W blue light source. A spot plate (n-Hexane:EA=4:1, R f =0.3-0.6) after testing the polarity of the product, the reaction solution was filtered to remove white precipitate impurities; the collected filtrate was spin-dried and mixed with silica gel, then loaded onto a column for column separation using n-hexane and ethyl acetate as eluents. The desired eluate was collected and spin-dried to obtain the target product; if the column separation still did not yield a completely pure target product, recrystallization was performed using MTBE in a 55°C water bath. After the product was completely dissolved in MTBE, n-hexane was added dropwise until a white solid appeared, followed by recrystallization at room temperature; after waiting for 24-48 hours for recrystallization to be complete, the recrystallization solution was aspirated, and the crystals were rinsed with n-hexane to obtain the pure target product 3j (42% yield, solid). 1HNMR(400MHz, CDCl3) δ7.86(d,J=7.2Hz,2H),7.80–7.78(m,1H),7.69–7.63(m,2H),7.58(d,J=7.6Hz,2H),7.35(d,J=8.4Hz, 1H),4.23–4.15(m,2H),4.10(s,1H),3.16(s,1H),2.06–1.94(m,3H),1.73–1.69(m,1H),1.44(s,9H),1.20(t,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ169.9,150.6,145.3,137.5,134.2,132.3,130.6,

[0064] 129.4,128.8,127.0,115.7,115.0,82.6,77.4,69.6,61.8,53.2,43.3,42.9,34.9,28.3,14.2.HRMS(ESI)m / z:[M+Na] + Calculated for C 26 H 28 BrKNO6S 600.0452; Found600.0456.

[0065] Example 11:

[0066]

[0067] Indole compound 1k (0.5 mmol, 1.0 eq.), bicyclo[1.1.0]butane compound 2k (0.6 mmol, 1.2 eq.), and iridium photosensitizer (11.2 mg, 0.01 mmol, 0.02 eq.) were added sequentially to a dry 25 mL photoreaction tube. The photoreaction tube was evacuated and replaced with nitrogen for five cycles. 5 mL of ultra-dry acetonitrile was added, and the tube was stirred continuously for 16 h at room temperature under 50 W blue light source. A spot plate (n-Hexane:EA=4:1, R f=0.3-0.6) after testing the polarity of the product, the reaction solution was filtered to remove white precipitate impurities; the collected filtrate was spin-dried and mixed with silica gel, then loaded onto a column for column separation using n-hexane and ethyl acetate as eluents. The desired eluate was collected and spin-dried to obtain the target product; if the column separation still did not yield a completely pure target product, recrystallization was performed using MTBE in a 55°C water bath. After the product was completely dissolved in MTBE, n-hexane was added dropwise until a white solid appeared, followed by recrystallization at room temperature; after waiting for 24-48 hours for recrystallization to be complete, the recrystallization solution was aspirated, and the crystals were rinsed with n-hexane to obtain the pure target product 3k (44% yield, solid). 1 HNMR(400MHz, CDCl3)δ8.00(d,J=8.4Hz,2H),7.94–7.91(m,1H),7.83(d,J=8.0Hz,2H),7.53(d,J=7.2 Hz,1H),7.29–7.25(m,1H),7.01(t,J=7.2Hz,1H),4.17(s,1H),3.69(s,3H),3.20(s,1H),2.09–2.14(m ,1H),1.96–1.91(m,2H),1.79–1.73(m,1H),1.44(s,9H).13CNMR(101MHz,CDCl3)δ170.7,150.4,146. 1,141.3,135.7(q,J=33Hz),129.6,129.5,127.6,126.4(q,J=3Hz),124.4,123.1(q,J=273Hz),122.8,

[0068] 114.4,82.3,76.8,69.5,53.6,52.6,43.5,43.1,34.9,28.3. 19 F NMR (376 MHz, CDCl3) δ

[0069] -63.2.HRMS(ESI)m / z:[M+Na] + Calculated for C 26 H 26 F3KNO6S 576.1065; Found576.1063.

[0070] Example 12:

[0071]

[0072] Indole compound 1l (0.5 mmol, 1.0 eq.), bicyclo[1.1.0]butane compound 2l (0.6 mmol, 1.2 eq.), and iridium photosensitizer (11.2 mg, 0.01 mmol, 0.02 eq.) were added sequentially to a dry 25 mL photoreaction tube. The photoreaction tube was evacuated and replaced with nitrogen, and the cycle was repeated five times. 5 mL of ultra-dry acetonitrile was added, and the tube was stirred continuously for 16 h at room temperature under irradiation with a 50 W blue light source. A spot plate (n-Hexane:EA=4:1, R f =0.3-0.6) after testing the polarity of the product, filter the reaction solution to remove white precipitate impurities; the collected filtrate is spin-dried and mixed with silica gel, then loaded onto a column for column separation using n-hexane and ethyl acetate as eluents. The desired eluate is collected and spin-dried to obtain the target product; if the column separation still does not yield a completely pure target product, recrystallize it using MTBE in a 55°C water bath. After the product is completely dissolved in MTBE, add n-hexane dropwise until a white solid appears, followed by recrystallization at room temperature; wait 24-48 hours for recrystallization to be complete, remove the recrystallization solution by aspiration, and rinse the crystals with n-hexane to obtain the pure target product 31 (45% yield, solid). 1 HNMR (400MHz, CDCl3) δ7.94(br,1H),7.87(d,J=7.2Hz,2H),7.67(t,J=7.2Hz,1H),7.57(t,J=7.6Hz,2H),7.07(d,J=1. 6Hz,1H),4.40(s,1H),3.73(s,3H),3.12(s,1H),2.18–2.14(m,1H),1.85–1.77(m,2H),1.71–1.69(m,2H),1.43(s,9H). 13 C NMR (101MHz, CDCl3) δ169.9,150.3,147.9,138.0,136.4,134.1,133.7,129.4,129.2,124.0 ,122.6,113.3,83.2,78.1,69.7,52.8,52.4,43.3,42.9,35.3,28.2.HRMS(ESI)m / z:[M+Na] + Calculated for C 25 H 25 Cl2NNaO6S 560.0672,Found 560.0677.

Claims

1. A method for preparing a compound of formula 3, characterized in that: The compound of formula 1 and the compound of formula 2 are subjected to a photocatalytic reaction to prepare a compound of formula 3, wherein the photocatalytic reaction is initiated by visible light irradiation and the action of an iridium photosensitizer: Wherein, R1 is halogen or hydrogen; R2 is COR4; R4 is alkyl, alkoxy, or phenyl; R3 is SO2PhX; X is hydrogen, halogen, alkyl, alkoxy, or trifluoromethyl; The structural formula of the iridium photosensitizer is:

2. The preparation method according to claim 1, characterized in that The molar ratio of the iridium photosensitizer to the compound of formula 1 is 0.02:

1.

3. The preparation method according to claim 1, characterized in that The molar ratio of the compound of formula 2 to the compound of formula 1 is 1.2:

1.

4. The preparation method according to claim 1, characterized in that The photocatalytic reaction is carried out in the presence of an organic solvent, which is acetonitrile, toluene or tetrahydrofuran.

5. The preparation method according to claim 1, characterized in that The photocatalytic reaction is carried out under the irradiation of a 50W blue light source.

6. The preparation method according to claim 1, characterized in that The photocatalytic reaction temperature is 18-30°C.

7. The preparation method according to claim 1, characterized in that The photocatalytic reaction time is 16-24 hours.

8. The preparation method according to claim 1, characterized in that The post-treatment process includes column separation and recrystallization operations.

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