A method for preparing 3-arylindole-2-one compounds

Abstract

This invention relates to the field of organic synthesis technology, and more particularly to a method for preparing 3-arylindole-2-one compounds. The invention utilizes compounds having the structure shown in Formula I as raw materials, and synthesizes 3-arylindole-2-one compounds through a carbonylation reaction under palladium(II) and Lewis acid co-catalysis. The preparation method provided by this invention produces only water as a byproduct, the reaction conditions are mild, meeting the requirements of green chemistry, and the synthesized indole-2-one compounds have a high yield.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for preparing 3-arylindole-2-one compounds. Background Technology

[0002] 3-Arylindolones are important heterocyclic structures, forming the core structure of many natural products and drugs. For example, 3-arylindolones can be used as neuroprotective agents, hormone receptors, and anticancer agents. Similarly, 3-arylindolones are also the cornerstone of the synthesis of multifunctional 3,3-disubstituted indolones. Therefore, the synthesis of 3-arylindolones has attracted widespread attention. Generally, synthetic methods can be divided into three categories: 1. Introducing an aryl group into the 3-position of an indole-2-one using arylation reactions; 2. Cycling a suitable precursor with a 3-aryl group to construct an indole unit; 3. Direct oxidation of 3-arylindoles.

[0003] Transition metal-catalyzed carbonylation, particularly palladium-catalyzed carbonylation, has proven to be an important tool for constructing carbonyl compounds. Palladium-catalyzed carbonylation is primarily based on the cross-coupling between nucleophiles and electrophiles. The electrophile must possess a strong leaving group; under basic conditions, the leaving group (i.e., halides, OTs, and OTf, etc.) leaves, producing an equimolar amount of byproducts. Alcohols are a relatively ideal choice as electrophiles because the only byproduct is water. However, carbonylation reactions using alcohols as electrophiles remain challenging due to the poor leaving ability of hydroxyl groups. Currently, no methods have been reported for preparing 3-arylindolones from alcohols via palladium-catalyzed carbonylation. Summary of the Invention

[0004] In view of this, the present invention provides a method for preparing 3-arylindole-2-one compounds. The present invention utilizes a carbonylation reaction co-catalyzed by a palladium catalyst precursor and a Lewis acid to synthesize 3-arylindole-2-one compounds, yielding high product yields and producing only water as a byproduct.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] A method for preparing a 3-arylindol-2-one compound includes the following steps:

[0007] A compound having the structure shown in Formula I, a polar organic solvent, a palladium catalyst precursor, and a Lewis acid are mixed and then subjected to a carbonylation reaction to obtain 3-arylindol-2-one compounds; the carbonylation reaction is carried out at a temperature of 90–110 °C and a reaction time of 10–14 h.

[0008]

[0009] The indole-2-one compounds have the structure shown in Formula II;

[0010]

[0011] In the structure shown in Formula I or Formula II, R 1 For Me, H, Et, Bn, Pr, Ph, Ac, or Boc; R 2 It is 5-Cl, 4-Cl, 4-Me, 5-MeO, 5-NH2, or H; R 3 It can be 4-F, 4-Cl, 4-Me, 4-Bu, 2-Me, 3-Me, 4-Ph, 4-MeO, 3-MeO or H.

[0012] Preferably, the polar organic solvent includes dimethylformamide, toluene, dioxane, or tetrahydrofuran.

[0013] Preferably, the Lewis acid is ZnCl2, Zn(OTf)3, Yb(OTf)3, Sc(OTf)3 or Y(OTf)3.

[0014] Preferably, the palladium catalyst precursor includes PdCl2, Pd(OAc)2, Pd(TFA)2 and Pd(PPh3)2Cl2.

[0015] Preferably, the molar ratio of the compound having the structure shown in Formula I to the palladium catalyst is 1:0.02 to 0.06.

[0016] Preferably, the molar ratio of the palladium catalyst precursor to the Lewis acid is 1-3:4-6.

[0017] Preferably, the carbonylation reaction is carried out in a CO atmosphere.

[0018] Preferably, the pressure of the CO atmosphere is 5 to 15 atm.

[0019] Preferably, the molar ratio of the compound having the structure shown in Formula I to the volume ratio of the polar organic solvent is 1 mmol: 5–15 mL.

[0020] This invention provides a method for preparing 3-arylindole-2-one compounds, comprising the following steps: mixing a compound having the structure shown in Formula I, a polar organic solvent, a palladium catalyst precursor, and a Lewis acid, followed by a carbonylation reaction to obtain 3-arylindole-2-one compounds; the carbonylation reaction is carried out at a temperature of 90–110 °C for a reaction time of 10–14 h. This invention uses palladium as a catalyst and a Lewis acid to co-catalyze the carbonylation reaction. With the coordination of the raw materials, polar organic solvent, palladium catalyst precursor, and Lewis acid, the prepared 3-arylindole-2-one compounds have a high reaction yield. Furthermore, the preparation method provided by this invention produces only water as a byproduct, and the reaction conditions are mild, meeting the requirements of green chemistry. Detailed Implementation

[0021] This invention provides a method for preparing 3-arylindol-2-one compounds, comprising the following steps:

[0022] A compound having the structure shown in Formula I, a polar organic solvent, a palladium catalyst precursor, and a Lewis acid are mixed and then subjected to a carbonylation reaction to obtain 3-arylindol-2-one compounds; the carbonylation reaction is carried out at a temperature of 90–110 °C and a reaction time of 10–14 h.

[0023]

[0024] The 3-arylindol-2-one compounds have the structure shown in Formula II;

[0025]

[0026] In the structure shown in Formula I or Formula II, R 1 For Me, H, Et, Bn, Pr, Ph, Ac, or Boc; R 2 It is 5-Cl, 4-Cl, 4-Me, 5-MeO, 5-NH2, or H; R 3 It can be 4-F, 4-Cl, 4-Me, 4-Bu, 2-Me, 3-Me, 4-Ph, 4-MeO, 3-MeO or H.

[0027] In this invention, the polar organic solvent preferably includes dimethylformamide, toluene, dioxane, or tetrahydrofuran, and more preferably tetrahydrofuran.

[0028] In this invention, the Lewis acid is preferably ZnCl2, Zn(OTf)3, Yb(OTf)3, Sc(OTf)3 or Y(OTf)3, and more preferably Y(OTf)3.

[0029] In this invention, the palladium catalyst precursor preferably includes PdCl2, Pd(OAc)2, Pd(TFA)2, and Pd(PPh3)2Cl2, and more preferably Pd(PPh3)2Cl2. In this invention, the molar ratio of the compound having the structure shown in Formula I to the palladium catalyst is preferably 1:0.02 to 0.06, and more preferably 1:0.04.

[0030] In this invention, the molar ratio of the palladium catalyst precursor to the Lewis acid is preferably 1-3:4-6, and more preferably 1:2.5.

[0031] In this invention, the carbonylation reaction is preferably carried out in a CO atmosphere, with a pressure of 5–15 atm, more preferably 10 atm. In a specific embodiment of this invention, the carbonylation reaction is carried out in a high-pressure reactor, and the carbonylation reaction specifically includes the following steps: adding a compound having the structure shown in Formula I, a polar organic solvent, a palladium catalyst precursor, and a Lewis acid sequentially into the high-pressure reactor; then replacing the air in the high-pressure reactor three times with CO gas to ensure that the CO pressure in the high-pressure reactor reaches 5–15 atm, and carrying out the carbonylation reaction to obtain 3-arylindol-2-one compounds.

[0032] In this invention, the molar ratio of the compound having the structure shown in Formula I to the volume ratio of the polar organic solvent is 1 mmol: 5 to 15 mL, more preferably 1 mmol: 10 mL.

[0033] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0034] Examples 1-12

[0035] A method for preparing a 3-arylindol-2-one compound includes the following steps:

[0036] A compound having the structure shown in Formula I, a polar organic solvent, a palladium catalyst precursor, and a Lewis acid were sequentially added to a high-pressure reactor. CO was then introduced into the reactor to carry out a carbonylation reaction, yielding 3-arylindol-2-one compounds. The carbonylation reaction was carried out at a temperature of 100°C for 12 hours.

[0037]

[0038] The 3-arylindol-2-one compounds have the structure shown in Formula II;

[0039]

[0040] In the compounds having the structures shown in Formula I and Formula II, R 1 For Me, R 2 H, R 3 The amount of H used is 1 mmol; the polar organic solvent is tetrahydrofuran, and the amount used is 10 mL; the palladium catalyst precursor is Pd(PPh3)2Cl2, and the amount used is 4 mol%; the carbonylation reaction is carried out under a CO atmosphere with a pressure of 10 atm; the types of Lewis acids are shown in Table 1, and the reaction yields of 3-arylindole-2-one compounds prepared using different Lewis acids are determined, and the reaction yields are the separation yields.

[0041] In this invention, the separation is performed by column chromatography.

[0042] Table 1. Reaction yields of 3-arylindol-2-one compounds prepared from different Lewis acids.

[0043]

[0044]

[0045] As shown in Table 1, the reaction yield of 3-arylindol-2-one compounds was 33% when only palladium catalyst precursor was used. Using TsOH, F3CCOOH, or MsOH in conjunction with palladium catalyst for carbonylation did not significantly improve the reaction yield of 3-arylindol-2-one compounds. When FeCl3 was used in conjunction with palladium catalyst precursor for carbonylation, no 3-arylindol-2-one compounds were obtained because FeCl3, as an additive, damaged the starting material, thus failing to yield the target product. When 10 mol% Y(OTf)3 was used as a Lewis acid catalyst, the reaction yield of the target product was 86%. Increasing or decreasing the amount of Y(OTf)3 significantly reduced the reaction yield of the target product.

[0046] Examples 13-18

[0047] A method for preparing a 3-arylindol-2-one compound includes the following steps:

[0048] A compound having the structure shown in Formula I, a polar organic solvent, a palladium catalyst precursor, and a Lewis acid were mixed and subjected to a carbonylation reaction to obtain 3-arylindol-2-one compounds; the carbonylation reaction was carried out at a temperature of 100°C for a reaction time of 12 h.

[0049]

[0050] The 3-arylindol-2-one compounds have the structure shown in Formula II;

[0051]

[0052] In the compound having the structure shown in Formula I, R 1 For Me, R 2 H, R 3 The amount of H used is 1 mmol; the Lewis acid is Y(OTf)3, and the amount used is 10 mol%; the palladium catalyst precursor is Pd(PPh3)2Cl2, and the amount used is 4 mol%; the carbonylation reaction is carried out in a CO atmosphere with a pressure of 10 atm; the types of polar organic solvents are shown in Table 2. The reaction yields of 3-arylindole-2-one compounds prepared using different polar organic solvents were determined, and the reaction yields were the separation yields.

[0053] Table 2. Reaction yields for the preparation of 3-arylindol-2-one compounds using organic solvents of different polarities.

[0054]

[0055] As shown in Table 2, the reaction yield decreased significantly when acetonitrile (CH3CN) was used as the solvent. This may be due to the poisoning of Lewis acid Y(OTf)3 caused by the strong coordination ability of acetonitrile. The reaction yield also decreased significantly compared with Example 1 when DCM was used as the solvent. Moderate reaction yields were obtained when DMF, toluene, and dioxane were used as solvents. Among them, the reaction yield was the highest at 86% when THF was used as the reaction solvent.

[0056] Examples 19-22

[0057] A method for preparing a 3-arylindol-2-one compound includes the following steps:

[0058] A compound having the structure shown in Formula I, an organic solvent, a palladium catalyst precursor, and a Lewis acid were mixed and subjected to a carbonylation reaction to obtain 3-arylindol-2-one compounds; the carbonylation reaction was carried out at a temperature of 100°C for a reaction time of 12 h.

[0059]

[0060] The 3-arylindol-2-one compounds have the structure shown in Formula II;

[0061]

[0062] In the compound having the structure shown in Formula I, R 1 For Me, R 2H, R 3 The amount of H used is 1 mmol; the Lewis acid is Y(OTf)3, and the amount used is 10 mol%; the polar organic solvent is tetrahydrofuran, and the amount used is 10 mL; the atmosphere used for the carbonylation reaction is a CO atmosphere, and the pressure of the CO atmosphere is 10 atm; the types of palladium catalyst precursors are shown in Table 3, and the amount used is 4 mol%. The reaction yields of 3-arylindol-2-one compounds prepared using different palladium catalyst precursors were determined, and the reaction yields were the separation yields.

[0063] Table 3. Reaction yields of 3-arylindol-2-one compounds prepared from different palladium catalyst precursors.

[0064]

[0065] As shown in Table 3, the reaction yield was low when Pd(OAc)2 was used as the palladium catalyst precursor; moderate reaction yields were obtained when PdCl2 and Pd(TFA)2 were used as palladium catalyst precursors; and the highest reaction yield of 86% was obtained when Pd(PPh3)2Cl2 was used as the palladium catalyst precursor.

[0066] Examples 23-26

[0067] A method for preparing a 3-arylindol-2-one compound includes the following steps:

[0068] A compound having the structure shown in Formula I, a polar organic solvent, a palladium catalyst precursor, and a Lewis acid were mixed and subjected to a carbonylation reaction to obtain 3-arylindol-2-one compounds; the carbonylation reaction was carried out at a temperature of 100°C for a reaction time of 12 h.

[0069]

[0070] The 3-arylindol-2-one compounds have the structure shown in Formula II;

[0071]

[0072] In the compound having the structure shown in Formula I, R 1 For Me, R 2 H, R 3The H content was 1 mmol; the Lewis acid was Y(OTf)3, with a dosage of 10 mol%; the polar organic solvent was tetrahydrofuran, with a dosage of 10 mL; the palladium catalyst precursor was Pd(PPh3)2Cl2, with a dosage of 4 mol%; the carbonylation reaction was carried out under a CO atmosphere, and the pressure of the CO atmosphere is shown in Table 4. The reaction yields of 3-arylindole-2-one compounds prepared under different CO atmosphere pressures were determined, and the reaction yields were the separation yields.

[0073] Table 4. Reaction yields of 3-arylindol-2-one compounds prepared under different CO atmosphere pressures.

[0074]

[0075]

[0076] As shown in Table 4, the CO atmosphere, as a necessary condition for the carbonylation reaction, has a significant impact on the reaction activity. Increasing the CO atmosphere pressure slightly reduces the reaction activity; decreasing the CO pressure also reduces the reaction yield, and the lower the pressure, the lower the conversion rate. The highest reaction yield, 86%, is achieved at a CO pressure of 10 atm.

[0077] Examples 27-35

[0078] A method for preparing a 3-arylindol-2-one compound includes the following steps:

[0079] A compound having the structure shown in Formula I, a polar organic solvent, a palladium catalyst precursor, and a Lewis acid were mixed and subjected to a carbonylation reaction to obtain 3-arylindol-2-one compounds; the carbonylation reaction was carried out at a temperature of 100°C for a reaction time of 12 h.

[0080]

[0081] The 3-arylindol-2-one compounds have the structure shown in Formula II;

[0082]

[0083] In the compound having the structure shown in Formula I, R 1 The substituents are shown in Table 5, R 2 H, R 3The H content is 1 mmol; the Lewis acid is Y(OTf)3, 10 mol%; the polar organic solvent is tetrahydrofuran, 10 mL; the palladium catalyst precursor is Pd(PPh3)2Cl2, 4 mol%; the carbonylation reaction is carried out under a CO atmosphere at a pressure of 10 atm, and the measurements are performed using different R... 1 The reaction yield of 3-arylindol-2-one compounds prepared under the substituents is the separation yield.

[0084] Table 5 Different R 1 The reaction yield of the preparation of 3-arylindol-2-one compounds by substituents

[0085]

[0086] As shown in Table 5, when the raw material used is a free amino group (1b), it exhibits good reactivity. Raw material 1b provides the expected product 2b with a separation yield of 90%. Raw materials 1c-1e with Et, Bn, and iPr substituents on the N atom are also successfully converted into the corresponding target products 2c-2e with good yields.

[0087] Furthermore, the electron-withdrawing groups on the nitrogen atom significantly hindered the reaction efficiency. Starting material 1f, with a phenyl group on the nitrogen atom, yielded the target product 2f in 35% yield. Starting material 1g, with a strong electron-withdrawing group Ts on the nitrogen atom, failed to yield 2g of product, resulting in an 80% recovery rate for the starting material 1g. This is likely because the Ts group significantly reduced the nucleophilicity of the nitrogen atom, preventing the cyclization reaction from completing. Starting materials 1h and 1i, with electron-withdrawing substituents Ac and Boc on the nitrogen atom, did participate in the reaction, but yielded product 2b without the corresponding protecting group.

[0088] Examples 36-50

[0089] A method for preparing a 3-arylindol-2-one compound includes the following steps:

[0090] A compound having the structure shown in Formula I, a polar organic solvent, a palladium catalyst precursor, and a Lewis acid were mixed and subjected to a carbonylation reaction to obtain 3-arylindol-2-one compounds; the carbonylation reaction was carried out at a temperature of 100°C for a reaction time of 12 h.

[0091]

[0092] The 3-arylindol-2-one compounds have the structure shown in Formula II;

[0093]

[0094] In the compound having the structure shown in Formula I, R 1 H, R 2 and R 3 The substituents are shown in Table 6, with a dosage of 1 mmol; the Lewis acid is Y(OTf)3, with a dosage of 10 mol%; the polar organic solvent is tetrahydrofuran, with a dosage of 10 mL; the palladium catalyst precursor is Pd(PPh3)2Cl2, with a dosage of 4 mol%; the carbonylation reaction is carried out under a CO atmosphere with a pressure of 10 atm, and the measurements are performed using different R... 1 The reaction yield of 3-arylindol-2-one compounds prepared under the substituents is the separation yield.

[0095] Table 6 Different R 2 and R 3 The reaction yield of the preparation of 3-arylindol-2-one compounds by substituents

[0096]

[0097]

[0098] As shown in Table 6, both electron-donating and electron-withdrawing substituents (e.g., Me, MeO, Cl) on the aniline moiety can undergo carbonylation reactions, and the starting material with electron-withdrawing substituents on the aniline exhibits a higher yield than that with electron-donating substituents. Furthermore, in Example 40, when the aniline moiety was attached to a free amino group, the starting material also successfully underwent carbonylation, albeit with a slightly lower yield of 21%; while in Example 41, when the amino moiety was attached to a strong electron-withdrawing group NO2, no corresponding product was obtained.

[0099] Table 6 also shows that in Examples 42 and 43, when R 3 Electron-withdrawing substituents (e.g., 4-F, 4-Cl) can yield the corresponding products 2p and 2q in superior yields; in Examples 44-47, when R 3 The weak electron-donating substituents (i.e., 4-Me, 4-tBu, 2-Me, and 3-Me) of the starting material 1r-1u were successfully converted to the desired product 2r-2u in good yield; in Examples 49 and 50, when R 3 Strong electron-donating substituents (e.g., 4-MeO and 3-MeO) yielded products 1w and 1x in moderate yields, indicating that the reaction efficiency was slightly hindered by the strong electron-donating substituents on the phenyl group.

[0100] In addition, during the preparation of the 3-arylindol-2-one compounds provided in Examples 1 to 50, the only byproduct generated was water.

[0101] Characterization data of raw material 1d used in Example 30: 2-[(1-methylethyl)amino]-α-phenyl-benzyl alcohol:

[0102]

[0103] White powder, 88% reaction yield. 1 H NMR (400MHz, CDCl3) δ7.36(d,J=7.8Hz,2H),7.31(t,J=7.5Hz,2H),7.22(t,J=7.1Hz,1H),7.07(t,J=7.7Hz,1H),7.01(d,J=7.5Hz,1H),6.67–6. 37(m,2H),6.08(q,J=8.0Hz,1H),5.72(d,J=3.9Hz,1H),4.97(d,J=7.8Hz,1H),3.59-3.44(m,1H),1.09(d,J=6.2Hz,3H),0.96(d,J=6.2Hz,3H). 13 C NMR (101MHz, DMSO-d6) δ 145.7, 143.8, 128.3, 128.1, 127.7, 126.6, 126.3, 115.0, 111.1, 73.3, 43.0, 22.7, 22.4. HRMS (ESI) m / z calculated as C 16 H 19 NO(M+H) + 242.1539, baseline 242.1537.

[0104] Characterization data of raw material 1o: (2-aminophenyl)(4-tert-butylphenyl)methanol used in Example 41:

[0105]

[0106] White powder, 81% reaction yield. 1 H NMR (400MHz, DMSO-d6) δ7.35-7.30(m,4H),7.08(d,J=7.6Hz,1H),6.96(t,J=7.5Hz,1H),6.62(d,J=7.9 Hz,1H),6.55(t,J=7.4Hz,1H),5.81(d,J=3.9Hz,1H),5.71(d,J=3.8Hz,1H),4.95(s,2H),1.29(s,9H). 13C NMR (101MHz, DMSO-d6) δ 148.8, 145.7, 141.2, 128.0, 127.4, 126.2, 124.5, 115.7, 115.2, 71.9, 34.1, 31.2. HRMS (ESI) m / z calculated as C 17 H 21 NO(M+H) + 256.1695, baseline 256.1667.

[0107] Characterization data of the raw material 1p used in Example 42: α-(2-aminophenyl)[1,1'-biphenyl]-4-methanol:

[0108]

[0109] White powder 1 H NMR (400MHz, CDCl3) δ7.44-7.28(m,6H),7.25-7.19(m,3H),7.11(dd,J=7.7,1.4Hz ,1H),6.99-6.84(m,4H),6.43(s,1H),5.94(d,J=4.4Hz,1H),2.68(d,J=4.5Hz,1H). 13 C NMR (101MHz, CDCl3) δ 145.8, 143.5, 140.1, 138.5, 128.9, 127.8, 127.6, 127.2, 127.0, 126.6, 126.1, 115.8, 115.3, 71.7. HRMS (ESI) m / z calculated as C 19 H 17 NO(M+H) + 276.1382, baseline 276.1377.

[0110] Characterization data of the raw material 1v used in Example 48: 2-amino-4-methyl-α-phenyl-benzyl alcohol:

[0111]

[0112] White powder, 45% reaction yield. 1 H NMR (400MHz, CDCl3) δ7.37(q,J=8.2,7.7Hz,4H),7.30(t,J=6.7Hz,1H),6.89(d,J=7.7Hz,1 H), 6.56 (d, J = 7.7Hz, 1H), 6.50 (s, 1H), 5.82 (s, 1H), 3.91 (s, 2H), 2.70 (s, 1H), 2.26 (s, 3H). 13CNMR (101MHz, CDCl3) δ 144.7, 142.2, 138.8, 128.7, 128.4, 127.5, 126.5, 125.0, 119.2, 117.7, 74.6, 21.2. HRMS (ESI) m / z calculated as C 14 H 15 NO(M+Na) + 236.1045, baseline 236.1032.

[0113] Characterization data of product 2v: 1,3-dihydro-6-methyl-3-phenyl-2H-indole-2-one prepared in Example 48:

[0114]

[0115] White powder, 59% reaction yield. 1 H NMR (400MHz, DMSO-d6) δ10.48(s,1H),7.312(t,J=7.6Hz,2H),7.26(t,J=6.8Hz,1H),7.13 (d,J=7.6Hz,2H),6.90(d,J=7.5Hz,1H),6.74(t,J=7.6Hz,2H),4.68(s,1H),2.29(s,3H). 13 C NMR (101MHz, DMSO-d6) δ 177.4, 142.8, 137.9, 137.6, 128.6, 128.3, 127.5, 127.0, 124.5, 122.2, 110.1, 51.5, 21.2. HRMS (ESI) m / z calculated as C 15 H 13 NO(M+Na) + 246.0889, baseline 246.0877.

[0116] Characterization data of the product 2x: 1,3-dihydro-5-amino-3-phenyl-2H-indole-2-one prepared in Example 50:

[0117]

[0118] Purple powder, 21% reaction yield. 1H NMR (400MHz, DMSO-d6) δ10.10(s,1H),7.33(t,J=7.3Hz,2H),7.27(t,J=7.2Hz,1H),7.13(d,J=7 .1Hz,2H),6.60(d,J=8.2Hz,1H),6.43(d,J=8.2Hz,1H),6.33(s,1H),4.69(s,2H),4.59(s,1H). 13 C NMR (101MHz, DMSO-d6) δ 176.7, 143.8, 138.3, 132.3, 131.0, 128.8, 128.1, 126.9, 112.9, 111.7, 109.7, 52.3. HRMS (ESI) m / z calculated as C 14 H 12 N₂O(M+H) + 225.1022, baseline 225.1020.

[0119] Therefore, this invention provides an efficient, simple, and green method for synthesizing 3-arylindole-2-one compounds by using compounds having the structure shown in Formula I as raw materials, under co-catalysis of palladium(II) and a Lewis acid in a CO atmosphere, through a carbonylation reaction. Furthermore, this preparation method produces only water as a byproduct, has mild reaction conditions, and yields high amounts of the synthesized 3-arylindole-2-one compounds.

[0120] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing a 3-arylindol-2-one compound, characterized in that, Includes the following steps: A compound having the structure shown in Formula I, a polar organic solvent, a palladium catalyst precursor, and a Lewis acid are mixed and then subjected to a carbonylation reaction to obtain 3-arylindol-2-one compounds; the carbonylation reaction is carried out at a temperature of 90~110 °C and a reaction time of 10~14 h. The polar organic solvent is dimethylformamide, toluene, or tetrahydrofuran; The Lewis acid is ZnCl2, Zn(OTf)3, Yb(OTf)3, Sc(OTf)3 or Y(OTf)3; The palladium catalyst precursor is PdCl2 or Pd(PPh3)2Cl2; The carbonylation reaction is carried out in a CO atmosphere; the pressure of the CO atmosphere is 5~15 atm; Formula I; The 3-arylindol-2-one compounds have the structure shown in Formula II; Formula II; In the structure shown in Formula I or Formula II, R 1 For Me, H, Et, Bn, Pr, Ph, Ac, or Boc; R 2 It is 5-Cl, 4-Cl, 4-Me, 5-MeO, 5-NH2, or H; R 3 It can be 4-F, 4-Cl, 4-Me, 4-Bu, 2-Me, 3-Me, 4-Ph, 4-MeO, 3-MeO or H.

2. The preparation method according to claim 1, characterized in that, The molar ratio of the compound having the structure shown in Formula I to the palladium catalyst is 1:0.02~0.

06.

3. The preparation method according to claim 1, characterized in that, The molar ratio of the palladium catalyst precursor to the Lewis acid is 1~3:4~6.

4. The preparation method according to claim 1, characterized in that, The molar ratio of the compound having the structure shown in Formula I to the volume ratio of the polar organic solvent is 1 mmol: 5~15 mL.

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