The invention relates to 2apos; -(trifluoromethyl)-4, 5-dihydro-spiro [furan-2, 3apos; synthesis method of-indoline] derivative

Abstract

The invention discloses a synthesis method of a 2 '-(trifluoromethyl)-4, 5-dihydro-spiro [furan-2, 3'-indoline] derivative, and belongs to the technical field of organic synthesis.The 2 '-(trifluoromethyl)-4, 5-dihydro-spiro [furan-2, 3'-indoline] derivative is obtained by synthesizing 2 '-(trifluoromethyl)-4, 5-dihydro-spiro [furan-2, 3'-indoline] in the presence of visible light, a photocatalyst and alkali. CF3Br and a 3-(3-hydroxypropyl) indole derivative are subjected to a free radical tandem cyclization reaction in an organic solvent to prepare the 3-(3-hydroxypropyl) indole derivative. According to the 2 '-(trifluoromethyl)-4, 5-dihydro-spiro [furan-2, 3'-indoline] derivative and the preparation method thereof, CF3Br is used as a trifluoromethyl source under photocatalysis for the first time, trifluoromethyl is directly introduced into an indoline ring of 4, 5-dihydro-spiro [furan-2, 3 '-indoline], the 2'-(trifluoromethyl)-4, 5-dihydro-spiro [furan-2, 3 '-indoline] derivative is obtained, and the compound has good activity and selectivity on cancer cells such as Huh-7, A549 and A549 / DDP.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing a 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative. Background Art

[0002] 3-Spiroindoline is an important class of heterocyclic compounds, and its structural units often exist in some natural products, drugs and bioactive molecules. Due to its good biological activity and potential therapeutic ability, it has attracted the attention of many organic chemists and biologists in recent years. For example, compounds with the following chemical structures A to F:

[0003]

[0004] Studies have shown that 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivative A has good activity and selectivity against Huh-7, A549 and A549 / DDP cancer cells (Org.Biomol.Chem.,2022,20,3475); Compound B, koumine, is an alkaloid obtained from koumine with high antitumor activity (J.Am.Chem.Soc.1981,103,4634); Compound C, pirimicaine, is extracted from coffee beans and has the effects of stimulating the nervous system, dilating blood vessels and diuresis (J.Chem.Soc,1960,1394); Compound D, baicalin, is a marine alkaloid isolated from the bryozoan papyrus fungus and has antibacterial activity (Tetrahedron Lett.2007,48,6364); Compound E, arborine, a new monoterpene indole alkaloid isolated from the genus of Malaysian scutellaria, whose chemical activity has not yet been demonstrated (J.Am.Chem.Soc.2019,141,7147); Compound F, type B Helicobacter, is a Clostridium lysine bacterium KMC003 isolated from acidic coal mine drainage, which has inhibitory activity against nitric oxide and reactive oxygen species (Org.Lett.2012,14,5002); Therefore, in order to further expand the new method of synthesizing this skeleton and its potential application value, it will be very necessary to explore new methods for synthesizing 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivatives.

[0005] At present, the methods for synthesizing 3-spiro indole derivatives include Fischer indoleation reaction, condensation reaction and dearomatization reaction of indole derivatives (Chem. Eur. J. 2015, 22, 2856). In recent years, various 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoleline] derivatives have been synthesized by using the free radical addition tandem cyclization strategy of 3-(3-hydroxypropyl) indole derivatives and free radical trifluoromethyl reagents. The trifluoromethyl reagents used are Umemoto's reagent and CF 3 SO 2 Na, the specific method is as follows:

[0006] (1) Radical addition tandem cyclization of 3-(3-hydroxypropyl)indole derivatives with Umemoto's reagent

[0007] In 2021, Gianetti's group reported the use of Umemoto's reagent as a trifluoromethyl source, and under red light catalysis, the helical carbon cation N,N′-dipropyl-1,13-dimethoxyquinacridinium salt ( n Pr-DMQA + ) as a photocatalyst, undergoing intramolecular trifluoromethylation and dearomatization reactions with indole derivatives (J.Org.Chem.2021,86,10640), generating various substituted 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivatives. This method provides a simple and effective method to construct functionalized and potentially biologically important trifluoromethyl-containing 3,3-spiro indole compounds under mild conditions. The disadvantage is that the Umemoto's reagent used is expensive, cumbersome to prepare, and difficult to store. The reaction formula is:

[0008]

[0009] (2) 3-(3-Hydroxypropyl)indole derivatives and CF 3 SO 2 Na Radical Addition Tandem Cyclization

[0010] In 2017, Vincent's research group reported CF 3 SO 2Na is used as a trifluoromethyl source and cerium ammonium nitrate (CAN) as an oxidant. In acetonitrile solvent, it undergoes intramolecular trifluoromethylation and dearomatization reaction with indole derivatives (Org. Lett. 2017, 19, 6336) to generate various substituted 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivatives. This reaction has a wide range of substrate applications. The disadvantage is that an equivalent amount of CAN is used as an oxidant, which does not meet the standards of green chemistry. The reaction formula is:

[0011]

[0012] In 2022, Zhao Yufen's group (Org.Lett.2022,24,2788) and Zhu Tingshun's group (Org.Biomol.Chem.,2022,20,3475) reported the use of electrocatalytic redox strategy to 3 SO 2 Using Na as a trifluoromethyl source, a series of polysubstituted 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivatives were synthesized from 3-(3-hydroxypropyl) indole derivatives. It is worth noting that after Zhu Tingshun's research group synthesized 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivatives through electrocatalytic dearomatization, they focused on studying the anticancer activity of this class of compounds. The study showed that this class of compounds has good activity and selectivity against Huh-7, A549 and A549 / DDP cancer cells. The reaction formula is:

[0013]

[0014] In summary, people have synthesized various 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivatives from 3-(3-hydroxypropyl) indole derivatives through free radical tandem cyclization reaction strategies, but each method has its own defects and limitations. Trifluoromethyl is a common fluorinated group. The introduction of trifluoromethyl into organic compounds can significantly change the chemical, physical and biological properties of the parent compound, such as acidity and alkalinity, bioavailability, metabolic stability, lipid solubility and protein binding ability. The results of the literature survey show that 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivatives have good activity and selectivity against Huh-7, A549 and A549 / DDP cancer cells (Org. Biomol. Chem., 2022, 20, 3475.). In order to further explore the synthesis methods of compounds with anticancer activity and their analogs, and improve and enhance the biological activity of 3-spiroindoline compounds, it is very necessary to explore a new, efficient and simple synthesis method to prepare 3-spiroindoline compounds containing trifluoromethyl. Summary of the invention

[0015] The purpose of the present invention is to provide a method for synthesizing 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivatives to solve the problems existing in the above-mentioned prior art. In the present invention, the 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivatives are synthesized by CF under the induction of visible light and in the presence of a photocatalyst and a base. 3 The invention is the first to use CF under photocatalysis to prepare the iodine-containing ... 3 Br is used as a trifluoromethyl source to directly introduce the trifluoromethyl group into the indoline ring of 4,5-dihydro-spiro[furan-2,3′-indoline] to obtain a 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivative, which has good activity and selectivity against Huh-7, A549 and A549 / DDP cancer cells. The present invention provides a new method for the synthesis of 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivatives, which has the advantages of cheap and readily available raw materials, short reaction steps, high regioselectivity of the reaction, simple operation, mild reaction conditions, good reaction yield, etc.

[0016] A method for synthesizing a 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivative comprises the following steps: in the presence of visible light, a photocatalyst and a base, CF 3Br and 3-(3-hydroxypropyl)indole derivatives are reacted in an organic solvent through a free radical tandem cyclization reaction to prepare the 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivative.

[0017] The structural formula of the 3-(3-hydroxypropyl)indole derivative is The structural formula of the 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivative is Wherein, Ts is p-toluenesulfonyl, and R is H, -Me or -Br.

[0018] The reaction equation of the free radical tandem cyclization reaction is:

[0019]

[0020] In the formula, Ts is p-toluenesulfonyl, and R is H, -Me or -Br.

[0021] Preferably, the molar ratio of the 3-(3-hydroxypropyl)indole derivative to the base is 1:(1-2.5), and more preferably the molar ratio is 1:1.5.

[0022] Preferably, the base is K 2 CO 3 、Na 2 CO 3 , KHCO 3 、NaHCO 3 , DBU, DABCO or DIPAN, more preferably K 2 CO 3 .

[0023] Preferably, during the reaction, the CF 3 The pressure of Br is between 1.0 and 1.5 atm, and is more preferably maintained at 1.0 atm.

[0024] Preferably, the amount of the photocatalyst is 1 mol% to 2.5 mol% of the amount of the 3-(3-hydroxypropyl)indole derivative, and more preferably 2 mol%.

[0025] Preferably, the photocatalyst is a noble metal catalyst or an organic dye catalyst.

[0026] More preferably, the noble metal catalyst is [Ir(dtbpy)(ppy) 3 ]PF 6 or fac-Ir III (ppy) 3The organic dye catalyst is 4CzIPN (2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile) or 3DPA2FBN (2,4,6-tris(diphenylamino)-3,5-difluorobenzonitrile).

[0027] Preferably, the visible light is blue light with a wavelength of 390nm to 460nm and a power of 5W to 20W, more preferably 10W blue light.

[0028] Preferably, the organic solvent is DCM (dichloromethane), CH 3 CN, DMSO (dimethyl sulfoxide), THF (tetrahydrofuran), acetone or 1,4-dioxane, more preferably CH 3 CN.

[0029] Preferably, the reaction time is 12 to 48 hours, and the reaction temperature is room temperature.

[0030] Compared with the prior art, the present invention has the following advantages and technical effects:

[0031] (1) The present invention is the first to use trifluorobromomethane for a free radical tandem cyclization reaction involving 3-(3-hydroxypropyl)indole derivatives to construct 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivatives. 3 Br is a non-toxic, odorless, cheap and readily available industrial raw material. Compared with other fluorination agents, it has the advantages of low price, easy availability and high atom economy.

[0032] (2) The 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivatives synthesized in the present invention have good activity and selectivity against Huh-7, A549 and A549 / DDP cancer cells (Org. Biomol. Chem., 2022, 20, 3475).

[0033] (3) The synthesis method provided by the present invention has the characteristics of short reaction steps, high atomic utilization, simple operation, mild reaction conditions and high reaction yield, and uses visible light irradiation to generate free radicals, thereby achieving green synthesis.

[0034] (4) The 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivative synthesized by the present invention is 1 HNMR, 13 C NMR, 19 F NMR and high-resolution mass spectrometry detection, the product is a pure target compound with high purity. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0036] Figure 1 1H NMR chart of 1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 1;

[0037] Figure 2 13C NMR chart of 1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 1;

[0038] Figure 3 19F NMR chart of 1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 1;

[0039] Figure 4 This is a high-resolution mass spectrometry monitoring diagram of 1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 1;

[0040] Figure 5 1H NMR chart of 5′-methyl-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 2;

[0041] Figure 6 13C NMR chart of 5′-methyl-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 2;

[0042] Figure 7 19F NMR chart of 5′-methyl-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 2;

[0043] Figure 8 This is a high-resolution mass spectrometry monitoring diagram of 5′-methyl-1′-toluenesulfonyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 2;

[0044] Fig. 91H NMR chart of 5′-bromo-1′-toluenesulfonyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 3;

[0045] Fig.10 13C NMR chart of 5′-bromo-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 3;

[0046] Fig.11 19F NMR chart of 5′-bromo-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 3;

[0047] Fig.12 This is a high-resolution mass spectrum monitoring chart of 5′-bromo-1′-toluenesulfonyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 3. DETAILED DESCRIPTION

[0048] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0049] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0050] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0051] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present application description and examples are exemplary only.

[0052] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0053] The room temperature in the present invention refers to 25±2°C.

[0054] In addition, unless otherwise specified, % in Examples and Comparative Examples is based on mass.

[0055] The present invention provides a method for synthesizing a 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivative, using a 3-(3-hydroxypropyl) indole derivative as a raw material and a cheap and readily available trifluoromethane (CF 3 Br) is a fluorination agent, and under the induction of visible light and the action of photocatalyst and base, a free radical tandem cyclization reaction is performed to prepare 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivatives in one step. This invention uses CF for the first time 3 Br is used as a trifluoromethyl source to introduce a trifluoromethyl group into the C2 position of the indole ring of a 4,5-dihydro-spiro[furan-2,3′-indoline] derivative. The resulting 2′-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3′-indoline] derivative has good activity and selectivity against Huh-7, A549 and A549 / DDP cancer cells (Org. Biomol. Chem., 2022, 20, 3475). This method is green and safe, with cheap and readily available raw materials, high atom economy, good regioselectivity, mild reaction conditions and easy purification of products, and is a green synthesis.

[0056] The specific steps of the synthesis method of a 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative provided in an embodiment of the present invention are as follows: 3-(3-hydroxypropyl) indole derivative 1 (1 to 3 equiv.), photocatalyst (1 mol% to 2.5 mol%, representing the molar percentage of photocatalyst in 3-(3-hydroxypropyl) indole derivative), base (2 to 5 equiv.), and 1 to 5 mL of organic solvent are added into a 50 mL Schlenk flask. The Schlenk flask is evacuated and then filled with CF 3Br gas, repeat three to six times, and finally maintain the gas pressure in the Schlenk flask at 1.0atm~1.5atm (observed from the barometer). The reaction mixture is placed on a blue light source with a wavelength of 390nm~460nm and a power of 5W~20W, and stirred at room temperature for 12~48h. After the reaction is completed, the solvent is spin-dried, and column chromatography is performed with silica gel as the stationary phase and a mixed solvent of petroleum ether (PE) and ethyl acetate (EA) as the eluent (PE: EA = (1~10) : 1, volume ratio) to obtain the 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative 3.

[0057] All raw materials used in the examples of the present invention were purchased from commercial sources. Among them, the raw material 3-(3-hydroxypropyl) indole derivative was prepared according to the literature (Org. Lett. 2017, 19, 6336).

[0058] Example 1 A method for synthesizing 1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] (3a), the synthetic route is as follows:

[0059]

[0060] The specific synthesis process is as follows:

[0061] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), K 2 CO 3 (41.5mg,0.3mmol,1.5equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1, volume ratio, the same below) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 66.0 mg, yield 83%.

[0062] The 1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] (3a) synthesized above was 1 HNMR,13 CNMR, 19 FNMR high-resolution mass spectrometry detection shows that the product is a pure target compound, and the corresponding product characterization data are:

[0063] 1 H NMR (400 MHz, CDCl 3 )δ7.64(d,J=8.0,1H),7.59(d,J=8.0,2H),7.33(t,J=8.8,1H),7.16-7.08(m,4H),4.58(q ,J=8.8,1H),3.73-3.64(m,2H),2.47-2.38(m,1H),2.32-2.24(m,4H),2.21-2.08(m,2H).

[0064] 13 C{ 1 H}NMR (150MHz, CDCl 3 )144.4,141.8,134.0,133.6,130.4,129.2,128.0,125.4,123.7(q,J C-F =280.5Hz),123.1,117.3,87.8,70.4(q,J C-F =30.0Hz),66.8,29.5(q,J C-F =1.5Hz),26.1,21.6.

[0065] 19 F NMR (376 MHz, CDCl 3 )δ,-71.51,(d,J=7.90Hz);

[0066] HRMS(ESI):m / z calcd for C 19 H 17 O 3 NF 3 S[MH] + 396.0666, found 396.0876.

[0067] Figure 1 1H NMR chart of 1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 1;

[0068] Figure 2 13C NMR chart of 1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 1;

[0069] Figure 3 19F NMR chart of 1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 1;

[0070] Figure 4 This is a high-resolution mass spectrum monitoring chart of 1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 1.

[0071] Example 2 Synthesis of 5′-methyl-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] (3b), the synthesis route is as follows:

[0072]

[0073] The specific synthesis process is as follows:

[0074] 3-(5-methyl-1-tosyl-1H-indol-3-yl)propan-1-ol 1b (69 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), K 2 CO 3 (41.5mg,0.3mmol,1.5equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 2: 1, volume ratio, the same below) to obtain 5'-methyl-1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3b): white solid, 64.2 mg, yield 78%.

[0075] The 5′-methyl-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] (3b) synthesized above was 1 H NMR, 13 C NMR, 19 F NMR high-resolution mass spectrometry detection results show that the product is a pure target compound, and the corresponding product characterization data are:

[0076] 1 H NMR (400 MHz, CDCl 3 )δ7.58(d,J=8.4,2H),7.53(d,J=8.0,1H),7.15-7.13(m,3H),6.95(s,1H),4.53(q,J=8.0,1H),3.7 2-3.62(m,2H),2.48-2.38(m,1H),2,32(s,3H),2,29(s,3H),2.72-2.22(m,1H),2.18-2.07(m,2H).

[0077] 13 C{ 1 H}NMR (150MHz, CDCl 3 )144.3,139.5,135.3,134.0,133.5.131.2,129.2,128.0,123.7(q,J C-F =280.5Hz),123.5,117.2,88.0,70.6(q,J C-F =30.0Hz),66.9,29.5(q,J C-F =3.0Hz),26.1,21.6,21.1.

[0078] 19 F NMR (376 MHz, CDCl 3 )δ,-71.13,(d,J=7.52Hz);

[0079] HRMS(ESI):m / z calcd for C 20 H 21 O 3 NF 3 S[M+H] + 412.1189, found 412.1188.

[0080] Figure 5 1H NMR chart of 5′-methyl-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 2;

[0081] Figure 6 13C NMR chart of 5′-methyl-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 2;

[0082] Figure 719F NMR chart of 5′-methyl-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 2;

[0083] Figure 8 This is a high-resolution mass spectrum monitoring chart of 5′-methyl-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 2.

[0084] Example 3 Synthesis of 5′-bromo-1′-toluenesulfonyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] (3c), the synthesis route is as follows:

[0085]

[0086] The specific synthesis process is as follows:

[0087] 3-(5-Bromo-1-tosyl-1H-indol-3-yl)propan-1-ol 1c (82 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), K 2 CO 3 (41.5mg,0.3mmol,1.5equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 2: 1, volume ratio, the same below) to obtain 5'-bromo-1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3c): white solid, 65.7 mg, yield 69%.

[0088] The 5′-bromo-1′-toluenesulfonyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] (3c) synthesized above was 1 H NMR, 13 C NMR, 19 F NMR high-resolution mass spectrometry detection results show that the product is a pure target compound, and the corresponding product characterization data are:

[0089] 1H NMR (400 MHz, CDCl 3 )δ7.58(d,J=8.0,2H),7.52(d,J=8.4,1H),7.44(dd,J=8.8,2.0,1H),7.24(d,J=2.0,1H),7.16(d,J= 8.0,2H),4.56(q,J=8.0,1H),3.70-3.66(m,1H),2.48-2.41(m,1H),2,34(s,3H),2.26-2.08(m,4H).

[0090] 13 C{ 1 H}NMR (150MHz, CDCl 3 )144.7,140.9,135.9,135.7,133.3,129.3,128.0,126.4,123.5(q,J C-F =282.0Hz),118.8,118.1,87.5,70.7(q,J C-F =30.0Hz),67.1,29.5(q,J C-F =3.0Hz),26.1,21.6.

[0091] 19 F NMR (376 MHz, CDCl 3 )δ,-71.11,(d,J=7.52Hz);

[0092] HRMS(ESI):m / z calcd for C 19 H 17 O 3 NBrF 3 S[M+H] + 476.0139, found 476.0137.

[0093] Fig. 9 1H NMR chart of 5′-bromo-1′-toluenesulfonyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 3;

[0094] Fig.10 13C NMR chart of 5′-bromo-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 3;

[0095] Fig.1119F NMR chart of 5′-bromo-1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 3;

[0096] Fig.12 This is a high-resolution mass spectrum monitoring chart of 5′-bromo-1′-toluenesulfonyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] synthesized in Example 3.

[0097] Example 4

[0098] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), Na 2 CO 3 (31.8mg,0.3mmol,1.5equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using petroleum ether and ethyl acetate as eluents (PE: EA = 3: 1, volume ratio, the same below) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 50.9 mg, yield 64%.

[0099] Example 5

[0100] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), KHCO 3 (30.0mg,0.3mmol,1.5equiv), 3mLCH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 50.1 mg, yield 63%.

[0101] Example 6

[0102] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), NaHCO 3 (25.2mg,0.3mmol,1.5equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 48.5 mg, yield 61%.

[0103] Example 7

[0104] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), DBU (45.7 mg, 0.3 mmol, 1.5 equiv), 3 mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE:EA=3:1) to obtain 1′-tosyl-2′-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3′-indoline] (3a): white solid, 35.0 mg, yield 44%.

[0105] Example 8

[0106] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), DABCO (33.7 mg, 0.3 mmol, 1.5 equiv), 3 mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 43.7 mg, yield 55%.

[0107] Example 9

[0108] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), DIPAN (38.8 mg, 0.3 mmol, 1.5 equiv), 3 mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 19.5 mg, yield 20%.

[0109] Example 10

[0110] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), K 2 CO 3 (27.6mg,0.2mmol,1.0equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36h. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a):

[0111] White solid, 51.7 mg, yield 65%.

[0112] Embodiment 11

[0113] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), K 2 CO 3 (55.2mg,0.4mmol,2.0equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 59.6 mg, yield 75%.

[0114] Example 12

[0115] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), K 2 CO 3 (69.0mg,0.5mmol,2.5equiv), 3mLCH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 65.2 mg, yield 82%.

[0116] Embodiment 13

[0117] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), [Ir(dtbpy)(ppy) 3 ]PF 6 (3.94 mg, 2 mol%), K 2 CO 3 (41.5mg,0.3mmol,1.5equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 38.2 mg, yield 48%.

[0118] Embodiment 14

[0119] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), fac-Ir III (ppy) 3 (2.62 mg, 2 mol%), K 2 CO 3 (41.5mg,0.3mmol,1.5equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 48.5 mg, yield 61%.

[0120] Embodiment 15

[0121] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 3DPA2FBN (2.56 mg, 2 mol%), K 2 CO 3 (41.5mg,0.3mmol,1.5equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 28.6 mg, yield 36%.

[0122] Example 16

[0123] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (1.58 mg, 1 mol%), K 2 CO 3 (41.5mg,0.3mmol,1.5equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36h. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a):

[0124] White solid, 42.9 mg, yield 54%.

[0125] Embodiment 17

[0126] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (2.37 mg, 1.5 mol%), K 2 CO 3 (41.5mg,0.3mmol,1.5equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 49.3 mg, yield 62%.

[0127] Embodiment 18

[0128] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.94 mg, 2.5 mol%), K 2 CO 3 (41.5mg,0.3mmol,1.5equiv), 3mL CH 3 CN was added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 63.6 mg, yield 80%.

[0129] Embodiment 19

[0130] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), K 2 CO 3 (41.5 mg, 0.3 mmol, 1.5 equiv) and 3 mL of DCM were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 25.4 mg, yield 32%.

[0131] Embodiment 20

[0132] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), K 2 CO 3 (41.5 mg, 0.3 mmol, 1.5 equiv) and 3 mL DMSO were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 60.2 mg, yield 76%.

[0133] Embodiment 21

[0134] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), K 2 CO 3 (41.5 mg, 0.3 mmol, 1.5 equiv) and 3 mL of THF were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and then filled with CF 3Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 34.2 mg, yield 43%.

[0135] Embodiment 22

[0136] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), K 2 CO 3 (41.5 mg, 0.3 mmol, 1.5 equiv) and 3 mL of acetone were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and filled with CF 3 Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 53.3 mg, yield 67%.

[0137] Embodiment 23

[0138] 3-(1-Tosyl-1H-indol-3-yl)propan-1-ol 1a (66 mg, 0.2 mmol, 1.0 equiv), 4CzIPN (3.15 mg, 2 mol%), K 2 CO 3 (41.5 mg, 0.3 mmol, 1.5 equiv) and 3 mL of 1,4-dioxane were added to a 50 mL Schlenk flask. The Schlenk flask was evacuated and filled with CF 3Br gas, repeated three times, and finally the pressure in the Schlenk flask was maintained at 1.0 atm (observed from the barometer). The reaction mixture was placed under 10W blue light and stirred at room temperature for 36 hours. After the reaction was completed, the reaction mixture was concentrated and purified by column chromatography using a mixed solvent of petroleum ether and ethyl acetate as the eluent (PE: EA = 3: 1) to obtain 1'-tosyl-2'-(trifluoromethyl)-4,5-dihydro-3H-spiro[furan-2,3'-indoline] (3a): white solid, 26.2 mg, yield 33%.

[0139] The above are only preferred specific implementations of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed in the present application should be included in the protection scope of the present application. Therefore, the protection scope of the present application should be based on the protection scope of the claims.

Claims

1. A method for synthesizing a 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative, characterized in that: The following steps are included: In the presence of visible light, a photocatalyst and a base, CF3Br and a 3-(3-hydroxypropyl)indole derivative undergo a free radical tandem cyclization reaction in an organic solvent to prepare the 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative.

2. The method for synthesizing the 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative according to claim 1, characterized in that: The molar ratio of the 3-(3-hydroxypropyl)indole derivative to the base is 1:(1-2.5).

3. The method for synthesizing the 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative according to claim 1, characterized in that: The base is K2CO3, Na2CO3, KHCO3, NaHCO3, DBU, DABCO or DIPAN.

4. The method for synthesizing the 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative according to claim 1, characterized in that: During the reaction, the pressure of the CF3Br was maintained at 1.0-1.5 atm.

5. The method for synthesizing the 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative according to claim 1, characterized in that: The amount of the photocatalyst used is 1 mol% to 2.5 mol% of the amount of the 3-(3-hydroxypropyl)indole derivative used.

6. The method for synthesizing the 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative according to claim 5, characterized in that: The photocatalyst is a noble metal catalyst or an organic dye catalyst.

7. The method for synthesizing the 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative according to claim 6, characterized in that: The noble metal catalyst is [Ir(dtbpy)(ppy)3]PF6 or fac-Ir III (ppy)3, the organic dye catalyst is 4CzIPN or 3DPA2FBN.

8. The method for synthesizing the 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative according to claim 1, characterized in that: The visible light is blue light with a wavelength of 390nm to 460nm and a power of 5W to 20W.

9. The method for synthesizing the 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative according to claim 1, characterized in that: The organic solvent is DCM, CH3CN, DMSO, THF, acetone or 1,4-dioxane.

10. The method for synthesizing the 2'-(trifluoromethyl)-4,5-dihydro-spiro[furan-2,3'-indoline] derivative according to claim 1, characterized in that: The reaction time is 12 to 48 hours, and the reaction temperature is room temperature.

Images