CN111961052A - Preparation method of gamma-carboline derivative - Google Patents

Abstract

The invention discloses a preparation method of gamma-carboline derivatives and compounds thereof, wherein ketoxime and alkynyl silane compounds are used as raw materials in [ Cp ]^*RhCl₂]₂(Pentamethylcyclopentadienyl) rhodium (III) dichloride and AgSbF₆Under the catalytic condition of (silver hexafluoroantimonate), Trifluoroethanol (TFE) is used as a solvent to react to prepare the gamma-carboline derivative. The invention has the advantages that: the method has the advantages of mild reaction conditions, simple operation, cheap and easily-obtained raw materials, wide substrate application range, excellent yield of most substrates, redox neutral conditions, no harsh reaction conditions such as low temperature or high temperature and the like, and unique reverse regioselectivity induced by steric hindrance.

Description

A kind of preparation method of γ-carboline derivative

technical field

The invention belongs to the field of organic synthesis chemistry, and relates to a preparation method of a γ-carboline derivative.

Background technique

γ-Carbolines are a very important class of alkaloids whose backbones often appear in natural products, bioactive molecules and drugs (a: R.S.Alekseyev, A.V.Kurkin and M.A.Yurovskaya, Chem.Heterocycl.Comp., 2009, 45, 889; b: S.R.M.Ibrahim, G.A.Mohamed, M.F.Zayed and H.M.Sayed, Drug Res., 2015, 65, 361; c: J.Dai, W.Dan, Y.Zhang and J.Wang, Eur.J.Med.Chem., 2018 , 157, 447.). So far, it has been found to exhibit various biological activities, including antiviral, antibacterial, antitumor activity, etc. (a: H.Aoyama, K.Sako, S.Sato, M.Nakamura, H.Miyachi, Y.Goto, M. Okamoto, M. Baba and Y. Hashimoto, Heterocycles, 2009, 77, 779; b: H. Aoyama, M. Baba and Y. Hashimoto, Curr. Bioact. Compd., 2010, 6, 118.). Therefore, in order to meet the need for the preparation of a wide variety of γ-carbolines in high-throughput screening and the study of structure-activity relationships (SAR), many successful synthetic approaches (e.g., transition metal-catalyzed coupling, acid-catalyzed condensation, and photosynthesis) induced cyclization) has been widely used (a: H. Zhang and R. C. Larock, Org. Lett., 2001, 3, 3083; b: A. Dagar, S. Biswas and S. Samanta, RSC Adv., 2015, 5, 52497; c: 6 J. K. Laha, S. M. Barolo, R. A. Rossi and G. D. Cuny, J. Org. Chem., 2011, 76, 6421.). However, these methods have cumbersome reaction steps, harsh reaction conditions, low efficiency and poor regioselectivity. With this in mind, there is still a great need to develop new strategies to rapidly and efficiently synthesize various substituted γ-carboline frameworks from readily available substrates.

F.Liu andF.Glorius,Chem.Soc.Rev.,2011,40,4740.)。在这些方法中，含氮基团始终发挥着重要作用，作为导向基团与催化剂配位以及产物的氮源(a:N.Yoshikai and Y.Wei,AsianJ.Org.Chem.,2013,2,466.)。同时，许多偶联试剂被发现可以用来进行碳氢官能化及环化反应，形成五元或六元氮杂环(a:D.H.Ess and W.A.Goddard,R.A.Periana,Organometallics,2010,29,6459.)。在这些偶联试剂中，炔烃因其易得和良好的反应特性，如内部炔烃，末端炔烃和其他替代物成为了最受欢迎和最理想的底物(a:T.Satoh andM.Miura,Chem.-Eur.J.,2010,16,11212.)。它们通常反应良好，并以高效率完成环合反应。但是，在大多数情况下，采用对称的内部炔烃，以避免由于使用非对称内部炔烃后区域选择性低而产生混合物(a:K.Parthasarathy and C.-H.Cheng,J.Org.Chem.,2009,74,9359；b:T.K.Hyster and T.Rovis,J.Am.Chem.Soc.,2010,132,10565.)。采用不对称炔烃以及端炔时，往往区域选择性不高，且往往为炔烃的1,2-插入，获得相反的区域选择性方案还不多见。In recent years, due to the application of transition metal-catalyzed CH activation/cyclization in the synthesis of nitrogen heterocyclic compounds, it has become a facile method with high economy and atom economy (a: SHCho, JYKim, J. Kwakand S. Chang, Chem. Soc. Rev., 2011, 40, 5068; b: J. Wencel-Delord, T.

F. Liu and F. Glorius, Chem. Soc. Rev., 2011, 40, 4740.). In these methods, nitrogen-containing groups always play an important role as the directing group for the coordination of the catalyst and the nitrogen source for the product (a: N. Yoshikai and Y. Wei, Asian J. Org. Chem., 2013, 2, 466. ). At the same time, many coupling reagents have been found to be useful for the functionalization and cyclization of hydrocarbons to form five- or six-membered nitrogen heterocycles (a: DHEss and WA Goddard, RAPeriana, Organometallics, 2010, 29, 6459.). Among these coupling reagents, alkynes have become the most popular and ideal substrates due to their easy availability and good reactivity properties, such as internal alkynes, terminal alkynes and other substitutes (a: T. Satoh and M. Miura, Chem.-Eur. J., 2010, 16, 11212.). They generally react well and complete the cyclization reaction with high efficiency. However, in most cases, symmetric internal alkynes are employed to avoid mixtures due to low regioselectivity after using asymmetric internal alkynes (a: K.Parthasarathy and C.-H.Cheng, J.Org. Chem., 2009, 74, 9359; b: TKHyster and T. Rovis, J. Am. Chem. Soc., 2010, 132, 10565.). When asymmetric alkynes and terminal alkynes are used, the regioselectivity is often not high, and it is often the 1,2-insertion of alkynes, and it is rare to obtain the opposite regioselectivity scheme.

In conclusion, in view of the importance of γ-carboline derivatives and the need for the regioselective synthesis of such compounds, it is of great significance to develop an efficient rhodium-catalyzed synthesis method for γ-carboline.

SUMMARY OF THE INVENTION

In view of this, the technical problem to be solved by the present invention is to provide an efficient method for synthesizing γ-carboline catalyzed by rhodium, which utilizes alkynes with large steric hindrance as substrates to realize C3-position unsubstituted γ-carboline The high-efficiency and regioselective synthesis of morpholino has obtained the opposite regioselectivity that is different from previous methods.

The invention provides a preparation method of a γ-carboline derivative, comprising the following steps:

The compound having the ketoxime structure represented by the formula (I) and the compound having the alkynyl silane structure represented by the formula (II) are used as starting materials, in dichloro (pentamethylcyclopentadienyl) rhodium (III) Under the catalysis of dimer and silver hexafluoroantimonate, using trifluoroethanol as solvent, the γ-carboline compound with the structure of formula (III) was synthesized in air:

Wherein, R ¹ is one of hydrogen atom, alkyl group, alkoxy group or halogen, R ² is one of hydrogen atom, alkyl group, alkynyl group or aryl group, R ³ is hydrogen atom, alkyl group or aryl group one of the bases.

Preferably, the starting materials are: a compound having a ketoxime structure represented by formula (I), a compound having a trimethyl(phenylethynyl)silane structure represented by formula (II), and the reaction formula is as follows:

wherein R ² is one of hydrogen atom, ethyl group, n-propyl group, allyl group or benzyl group.

Preferably, the starting materials are: a compound having a ketoxime structure represented by formula (I) and a compound having an aralkynyl silane structure represented by formula (II), and the reaction formula is as follows:

When R ³ is phenyl, R ¹ is H, CH ₃ , OMe, Cl at C-5 position of substrate indole or F, OMe, Cl at C-6 position of substrate indole or substrate indole C-7 bit of Me;

When R ³ is 3,4,5-trimethoxyphenyl, R ¹ is Cl at C-6 position of substrate indole;

When R ¹ is H, R ³ is p-tolyl, p-tert-butylphenyl, p-bromophenyl, biphenyl, methyl p-formate phenyl, p-cyanophenyl, p-aldehyde phenyl, o-methyl Oxyphenyl, o-bromophenyl, m-methylphenyl, 3,5-dimethylphenyl, 3,4,5-trimethoxyphenyl, 6-(2,3-dihydrobenzo[ b] One of [1,4]dioxinyl), 3-thienyl and 2-naphthyl;

When R ¹ is Cl at the C-6 position of the substrate indole, R ³ is one of m-chlorophenyl and 3,4-dimethoxyphenyl.

Preferably, the raw materials are: a compound having a ketoxime structure represented by formula (I) and a compound having an alkylalkynyl silane structure represented by formula (II), and the reaction formula is as follows:

wherein R ³ is one of H, CH ₃ , Et or nPr.

Preferably, the molar ratio of ketoxime to alkynylsilane is 1:1.5.

Preferably, the percentage concentration of the dichloro(pentamethylcyclopentadienyl) rhodium (III) dimer substance is 2.5 mol%, and the percentage concentration of silver hexafluoroantimonate is 10 mol% .

Preferably, the temperature of the reaction in the air is 120°C, and the reaction time is 24 hours.

Beneficial effects of the present invention:

The invention provides a method for synthesizing γ-carboline derivatives. The method has mild reaction conditions, simple operation, cheap and easy-to-obtain raw materials, wide adaptability of substrates, excellent yields of most substrates, and neutral redox conditions. , without harsh reaction conditions such as low or high temperature, and the unique reverse regioselectivity induced by steric hindrance.

The method also has the advantages of short preparation period, stable process conditions, simple and safe operation, and easy product purification, and can be used for large-scale production.

Detailed ways

The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

In the preparation method of the present invention, the specific steps include: at room temperature, mixing ketoxime, alkynyl silane compound, [Cp*RhCl ₂ ] ₂ , AgSbF ₆ and an organic solvent in sequence, and reacting at 120° C. in the air for 24 hours, The corresponding γ-carboline derivatives were obtained.

Example 1:

At room temperature, 0.1 mmol 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, 0.0025 mmol [Cp ^* RhCl ₂ ] ₂ , 0.01 mmol _AgSbF6 , 1 mL TFE, then 0.15 mmol trimethyl(phenylethynyl)silane was added and the tube was sealed. The reaction was quenched by stirring at 120°C for 24 hours, then the mixture was cooled to room temperature and concentrated under reduced pressure to obtain the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column), 22 mg of white solid, and the yield was 79%.

¹ H NMR (500MHz, CDCl ₃ ) δ 8.27(s, 1H), 8.22(d, J=7.9Hz, 1H), 7.56-7.52(m, 1H), 7.51-7.44(m, 5H), 7.42- 7.36(m, 2H), 3.42(s, 3H), 3.11(s, 3H). ¹³ C NMR (126MHz, CDCl ₃ )δ152.56, 145.57, 142.58, 141.78, 137.32, 130.52, 128.34, 127.93, 126.25, 122.56, 122.15, 120.77, 119.65, 117.89, 109.12, 32.49, 24.01. HR-MS(ESI)[M+H] ⁺ m/z calcd for C ₁₉ H ₁₇ N ₂ 273.138625, found 273.138315.

Example 2:

At room temperature, 0.1 mmol 1-(1,5-dimethyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, 0.0025 mmol [ Cp ^* RhCl2] ₂ , 0.01 mmol _AgSbF6 , ₁ mL TFE, then 0.15 mmol trimethyl(phenylethynyl)silane was added and the tube was sealed. The reaction was quenched by stirring at 120°C for 24 hours, then the mixture was cooled to room temperature and concentrated under reduced pressure to obtain the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (white solid 20 mg, yield 70%).

¹ H NMR (600MHz, CDCl ₃ ) δ 8.23(s, 1H), 8.00(s, 1H), 7.51-7.43(m, 5H), 7.37-7.34(m, 1H), 7.29(d, J=8.3 Hz, 1H), 3.39(s, 3H), 3.10(s, 3H), 2.59(s, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ152.48, 145.33, 142.70, 140.10, 137.37, 130.52, 130.14, 128.31 ,127.87,127.53,122.61,122.27,119.59,117.73,108.80,32.52,24.06,21.72.HR-MS(ESI)[M+H] ⁺ m/zcalcd for C ₂₀ H ₁₉ N ₂ 287.154275,found 287.154362.

Example 3:

At room temperature, 0.1 mmol of 1-(5-methoxy-1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime was sequentially added to a 10 mL Schrock reaction tube, 0.0025 mmol [Cp ^* RhCl2] ₂ , 0.01 mmol ₁ mL _AgSbF6 , TFE, then 0.15 mmol trimethyl(phenylethynyl)silane was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (white solid 24 mg, yield 80%).

¹ H NMR (600MHz, CDCl ₃ ) δ 8.22 (s, 1H), 7.70 (d, J=2.4Hz, 1H), 7.51-7.43 (m, 5H), 7.31 (d, J=8.8Hz, 1H) , 7.17(dd, J=8.8, 2.5Hz, 1H), 3.96(s, 3H), 3.39(s, 3H), 3.09(s, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ154.79, 152.55, 145.40 ,142.97,137.29,136.79,130.51,128.34,127.91,122.68,119.70,117.82,114.59,109.69,106.40,56.32,32.57,23.98.HR-MS(ESI)[M+H] ⁺ m/z 0 calcd for C ₂ H ₁₉ N ₂ O 303.149190, found 303.149529.

Example 4:

At room temperature, 0.1 mmol of 1-(5-chloro-1-methyl-1H-indol-3-yl)ethan-1-one-O-methyl oxime, 0.0025 mmol was sequentially added to a 10 mL Schrock reaction tube [Cp ^* RhCl2] ₂ , 0.01 mmol _AgSbF6 , ₁ mL TFE, then 0.15 mmol trimethyl(phenylethynyl)silane was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column), 19 mg of pale yellow solid, and the yield was 62%.

¹ H NMR (600 MHz, CDCl ₃ ) δ 8.27 (s, 1H), 8.09 (d, J=8.4 Hz, 1H), 7.52-7.43 (m, 5H), 7.38 (d, J=1.6 Hz, 1H) ,7.32(dd,J=8.4,1.8Hz,1H),3.38(s,3H),3.06(s,3H).

¹³ C NMR (151MHz, CDCl ₃ )δ152.49,145.90,142.98,142.43,136.89,132.30,130.49,128.45,128.12,123.30,121.25,120.73,119.86,117.45,109.30 M+H] ⁺ m/z calcd for C ₁₉ H ₁₆ ClN ₂ 307.099653, found 307.099359.

Example 5:

At room temperature, 0.1 mmol of 1-(6-fluoro-1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl2] ₂ (0.0025 mmol), _AgSbF6 0.01 mmol, TFE ₁ mL, then trimethyl(phenylethynyl)silane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 18 mg, yield 61%).

¹ H NMR (600 MHz, CDCl ₃ ) δ 8.25 (s, 1H), 8.12 (dd, J=8.6, 5.3 Hz, 1H), 7.52-7.42 (m, 2H), 7.09 (qd, J=9.9, 9.5 , 2.1Hz, 2H), 3.37(s, 3H), 3.07(s, 3H). ¹³ C NMR(151MHz, CDCl ₃ )δ162.30(d, J=243.5Hz), 152.04, 145.42, 143.21, 142.74( d, J＝11.7Hz), 136.99, 130.51, 128.42, 128.08, 123.56(d, J＝10.4Hz), 119.78, 118.50, 117.60, 108.83(d, J＝23.9Hz), 96.30(d, J＝26.8Hz ), 32.71, 23.88. HR-MS(ESI)[M+H] ⁺ m/z calcd for C ₁₉ H ₁₆ FN ₂ 291.129203, found 291.129705.

Example 6:

At room temperature, 0.1 mmol of 1-(6-chloro-1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl(phenylethynyl)silane 0.15 mmol was added and the tube was sealed. The reaction was quenched by stirring at 120°C for 24 hours, then the mixture was cooled to room temperature and concentrated under reduced pressure to obtain the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) to obtain 21 mg of white solid with a yield of 69%.

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.27 (s, 1H), 8.09 (d, J=8.4 Hz, 1H), 7.52-7.45 (m, 5H), 7.38 (d, J=1.6 Hz, 1H) ,7.33(dd,J=8.4,1.7Hz,1H),3.38(s,3H),3.07(s,3H).

¹³ C NMR (126MHz, CDCl ₃ ) δ152.43, 145.78, 143.01, 142.46, 136.86, 132.35, 130.49, 128.46, 128.15, 123.31, 121.30, 120.73, 119.89, 117.47, 238.44, 32

HR-MS(ESI)[M+H] ⁺ m/z calcd for C ₁₉ H ₁₆ ClN ₂ 307.099653, found 307.099297.

Example 7:

At room temperature, 0.1 mmol of 1-(6-methoxy-1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime was sequentially added to a 10 mL Schrock reaction tube, [Cp ^* RhCl ₂ ] ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl(phenylethynyl)silane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 23 mg, yield 77%).

¹ H NMR (500MHz, CDCl ₃ ) δ 8.21 (s, 1H), 8.06 (d, J=8.7Hz, 1H), 7.50-7.43 (m, 5H), 6.97 (dd, J=8.6, 2.2Hz, 1H), 6.84(d, J=2.2Hz, 1H), 3.93(s, 3H), 3.36(s, 3H), 3.06(s, 3H). ¹³ C NMR (126MHz, CDCl ₃ )δ159.46, 151.17, 144.50 ,143.31,142.74,137.28,130.49,128.34,127.91,123.27,119.55,118.00,115.86,109.00,93.76,55.83,32.54,23.68.HR-MS(ESI)[M+H] ⁺ m/z calcd for C ₂₀ H ₁₉ N ₂ O 303.149190, found 303.149471.

Example 8:

At room temperature, 0.1 mmol of 1-(6-chloro-1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl((3,4,5-trimethoxyphenyl)ethynyl)silane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 27 mg, yield 68%).

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.28 (s, 1H), 8.08 (d, J=8.4 Hz, 1H), 7.40 (d, J=1.5 Hz, 1H), 7.33 (dd, J=8.4, 1.7Hz, 1H), 6.66(s, 2H), 3.95(s, 3H), 3.88(s, 6H), 3.46(s, 3H), 3.06(s, 3H). ¹³ C NMR (126MHz, CDCl ₃ ) ^{δ153.16,152.52,145.53,142.89,142.40,137.97,132.39,132.24,123.29,121.33,120.67,119.81,117.42,109.46,107.78,61.19,56.38,32.47,2} m/z calcd for C ₂₂ H ₂₂ ClN ₂ O ₃ 397.131347, found 397.130630.

Example 9:

At room temperature, 0.1 mmol of 1-(1,7-dimethyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl2] _{2 (} 0.0025 mmol), _AgSbF6 (0.01 mmol), TFE (1 mL), then trimethyl(phenylethynyl)silane (0.15 mmol) was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 23 mg, yield 80%).

¹ H NMR (500MHz, CDCl ₃ ) δ 8.29(s, 1H), 8.11-8.06(m, 1H), 7.55-7.49(m, 4H), 7.49-7.44(m, 1H), 7.29-7.27(m , 2H), 3.65(s, 3H), 3.12(s, 3H), 2.82(s, 3H). ¹³ C NMR (126MHz, CDCl ₃ )δ152.09, 145.25, 144.47, 141.57, 137.60, 130.06, 129.87, 128.56, 127.82,123.45,121.44,121.25,120.66,119.85,118.58,36.59,23.94,20.72.HR-MS(ESI)[M+H] ⁺ m/zcalcd for C ₂₀ H ₁₉ N ₂ 287.154275,found 287.154412.

Example 10:

At room temperature, 1-(1H-indol-3-yl)ethan-1-one-O-methyloxime 0.1 mmol, [Cp ^* RhCl ₂ ] ₂ 0.0025 mmol, AgSbF were successively added to a 10 mL Schrock reaction tube. ₆ 0.01 mmol, TFE 1 mL, then trimethyl(phenylethynyl)silane 0.15 mmol and tube sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (white solid 12 mg, yield 46%).

¹ H NMR (600 MHz, CDCl ₃ ) δ 8.82 (s, 1H), 8.42 (s, 1H), 8.21 (d, J=7.9 Hz, 1H), 7.66 (d, J=7.4 Hz, 2H), 7.55 (t, J＝7.6Hz, 2H), 7.50(d, J＝3.8Hz, 2H), 7.45(t, J＝7.4Hz, 1H), 7.40-7.35(m, 1H), 3.10(s, 3H) . ¹³ C NMR (101MHz, CDCl ₃ ) δ152.50, 142.98, 142.12, 139.32, 135.96, 129.61, 128.51, 128.21, 126.56, 122.74, 122.70 MS, 121.18, 119.14, 118.13, 111.4. +H] ⁺ m/z calcd for C ₁₈ H ₁₅ N ₂ 259.122975, found 259.122479.

Example 11:

At room temperature, 0.1 mmol of 1-(1-ethyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl(phenylethynyl)silane (0.15 mmol) was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 13 mg, yield 45%).

¹ H NMR (500MHz, CDCl ₃ ) δ 8.23 (d, J=9.7Hz, 2H), 7.53 (t, J=7.7Hz, 1H), 7.49 (s, 5H), 7.43 (d, J=8.2Hz) , 1H), 7.38(t, J=7.5Hz, 1H), 3.96(q, J=7.1Hz, 2H), 3.11(s, 3H), 1.01(t, J=7.1Hz, 3H). ¹³ C NMR (126MHz, CDCl ₃ )δ152.68,145.54,141.67,140.64,137.55,130.28,128.34,128.13,126.20,122.77,122.55,120.70,119.61,118.11,109.39,38.2.HR-MS(ESI[118.11,109.39,128.95,24ESI. +H] ⁺ m/z calcd for C ₂₀ H ₁₉ N ₂ 287.154275, found 287.153412.

Example 12:

At room temperature, 0.1 mmol of 1-(1-propyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl(phenylethynyl)silane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 19 mg, yield 63%).

¹ H NMR (400MHz, CDCl ₃ ) δ 8.27-8.18 (m, 2H), 7.56-7.45 (m, 6H), 7.42 (d, J=8.2Hz, 1H), 7.39-7.34 (m, 1H), 3.86-3.79(m, 2H), 3.12(s, 3H), 1.45(h, J=7.5Hz, 2H), 0.49(t, J=7.4Hz, 3H). ¹³ C NMR (101MHz, CDCl ₃ )δ152 .66,145.52,141.85,140.98,137.50,130.42,128.30,128.04,126.14,122.71,122.35,120.67,119.65,117.99,109.54,45.80,24.13,22.36,10.94 ⁺ m /z calcd for C ₂₁ H ₂₁ N ₂ 301.169925, found 301.168759.

Example 13:

At room temperature, 1-(1-allyl-1H-indol-3-yl)ethan-1-one-O-methyloxime 0.1mmol, [Cp ^* RhCl ₂ ] ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl(phenylethynyl)silane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 25 mg, yield 83%).

¹ H NMR (600MHz, CDCl ₃ ) δ 8.25-8.22 (m, 2H), 7.53-7.49 (m, 1H), 7.45 (s, 5H), 7.38 (t, J=7.7Hz, 2H), 5.60 ( ddt, J=17.1, 10.4, 4.5Hz, 1H), 5.03-4.99(m, 1H), 4.64-4.59(m, 1H), 4.55-4.48(m, 2H), 3.12(s, 3H). ¹³ C NMR(101MHz,CDCl ₃ )δ152.67,145.72,142.02,141.12,137.10,132.26,130.37,128.24,128.14,126.25,122.61,122.37,120.93,119.70,118.07,116.56,109.96,46.61,24.10.HR-MS(ESI )[M+H] ⁺ m/z calcd for C ₂₁ H ₁₉ N ₂ 299.154275, found 299.153392.

Example 14:

At room temperature, 0.1 mmol of 1-(1-benzyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube. ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl(phenylethynyl)silane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 27 mg, yield 78%).

¹ H NMR (500MHz, Chloroform-d) δ 8.27(d, J=7.8Hz, 1H), 8.22(s, 1H), 7.48-7.44(m, 1H), 7.41-7.37(m, 1H), 7.37 -7.32(m,1H),7.30(d,J=8.2Hz,1H),7.26-7.22(m,2H),7.22-7.18(m,2H),7.15-7.13(m,1H),7.12-7.08 (m, 2H), 6.56 (d, J=7.1Hz, 2H), 5.17 (s, 2H), 3.16 (s, 3H). ¹³ C NMR (126 MHz, CDCl ₃ ) δ 152.62, 145.67, 142.24, 141.49, 136.77 ,136.67,130.28,128.52,128.12,127.93,127.19,126.50,125.66,122.70,122.38,121.15,119.98,118.22,109.97,47.87,24.02.HR-MS(ESI for calc for [M+H] ⁺ m/m C ₂₅ H ₂₁ N ₂ 349.169925, found 349.168733.

Example 15:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ (0.0025 mmol), AgSbF6 (0.01 mmol), TFE ₁ mL, then trimethyl(p-tolueneethynyl)silane 0.15 mmol and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (white solid 20 mg, yield 70%).

¹ H NMR (500MHz, CDCl ₃ ) δ 8.26 (s, 1H), 8.21 (d, J=7.9Hz, 1H), 7.56-7.51 (m, 1H), 7.40 (d, J=8.2Hz, 1H) , 7.39-7.34(m, 3H), 7.30(d, J=7.9Hz, 2H), 3.44(s, 3H), 3.11(s, 3H), 2.47(s, 3H). ¹³ C NMR(126MHz, CDCl) ₃ )δ152.34,145.61,142.68,141.77,137.72,134.24,130.37,129.04,126.20,122.54,122.15,120.72,119.63,117.83,109.10,32.48,23.98,21.411111HR-MS(ESI.98)[M ⁺ H] m/z calcd for C ₂₀ H ₁₉ N ₂ 287.154275, found 287.154551.

Example 16:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ (0.0025 mmol), AgSbF6 0.01 mmol, TFE ₁ mL, then ((4-(tert-butyl)phenyl)ethynyl)trimethylsilane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 25 mg, yield 75%).

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.27 (s, 1H), 8.22 (d, J=7.9 Hz, 1H), 7.55 (t, J=7.7 Hz, 1H), 7.51 (d, J=8.2 Hz) , 2H), 7.43-7.36(m, 4H), 3.45(s, 3H), 3.11(s, 3H), 1.41(s, 9H). ¹³ CNMR(126MHz, CDCl ₃ )δ152.39,151.01,145.75,142.72, 141.81,134.17,130.19,126.21,125.25,122.58,122.22,120.73,119.66,117.85,109.13,34.85,32.55,31.59,24.06.HR-MS(ESI)[M+H] ⁺ m/z calcd for C _{23 25} N ₂ 329.201225, found 329.200531.

Example 17:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then ((4-bromophenyl)ethynyl)trimethylsilane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 25 mg, yield 72%).

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.24-8.19 (m, 2H), 7.63 (d, J=8.3 Hz, 2H), 7.55 (t, J=7.7 Hz, 1H), 7.41 (d, J= 8.2Hz, 1H), 7.40-7.33(m, 3H), 3.44(s, 3H), 3.10(s, 3H).

¹³ C NMR (126MHz, CDCl ₃ )δ152.93,145.40,142.38,141.74,136.31,132.06,131.55,126.41,122.59,122.25,122.05,120.93,118.35,117.99,104.68.17,32

HR-MS(ESI)[M+H] ⁺ m/z calcd for C ₁₉ H ₁₆ BrN ₂ 351.049137, found 351.049639.

Example 18:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then ([1,1'-biphenyl]-4-ylethynyl)trimethylsilane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 27 mg, yield 78%).

¹ H NMR (500MHz, CDCl ₃ ) δ 8.32(s, 1H), 8.24(d, J=7.9Hz, 1H), 7.76-7.72(m, 2H), 7.72-7.69(m, 2H), 7.58- 7.54(m, 3H), 7.50(t, J=7.7Hz, 2H), 7.44(d, J=8.2Hz, 1H), 7.42-7.38(m, 2H), 3.51(s, 3H), 3.13(s ,3H). ¹³ C NMR(126MHz,CDCl ₃ )δ152.62,145.56,142.70,141.86,140.83,140.60,136.26,130.94,129.07,127.74,127.24,127.04,126.35,122.63,122.20,120.87,119.33,117.99,109.21 , 32.72, 24.02.

HR-MS(ESI)[M+H] ⁺ m/z calcd for C ₂₅ H ₂₁ N ₂ 349.169925, found 349.170541.

Example 19:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then methyl 4-((trimethylsilyl)ethynyl)benzoate 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 26 mg, yield 73%).

¹ H NMR (600 MHz, CDCl ₃ ) δ 8.26 (s, 1H), 8.22 (d, J=7.9 Hz, 1H), 8.17 (d, J=8.2 Hz, 2H), 7.58-7.53 (m, 3H) , 7.42(d, J=8.2Hz, 1H), 7.39(t, J=7.5Hz, 1H), 3.98(s, 3H), 3.42(s, 3H), 3.11(s, 3H). ¹³ C NMR( 101MHz,CDCl ₃ )δ166.93,153.15,145.32,142.37,142.27,141.79,130.51,129.73,129.62,126.46,122.62,122.06,120.99,118.64,118.06,109.23,52.42,32.79,24.08.HR-MS(ESI)[ M+H] ⁺ m/z calcd for C ₂₁ H ₁₉ N ₂ O ₂ 331.144104, found331.143458.

Example 20:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then 4-((trimethylsilyl)ethynyl)benzonitrile 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (white solid 24 mg, yield 80%).

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.22 (d, J=5.9 Hz, 2H), 7.80 (d, J=8.2 Hz, 2H), 7.61 (d, J=8.2 Hz, 2H), 7.59-7.54 (m, 1H), 7.44 (d, J=8.2Hz, 1H), 7.41 (t, J=7.6Hz, 1H), 3.43 (s, 3H), 3.11 (s, 3H). ¹³ C NMR (126MHz, CDCl ₃ )δ153.59,145.22,142.48,142.20,141.80,132.18,131.13,126.68,122.68,122.00,121.23,118.69,118.23,117.81,111.92,109.30,32.96,2H]-HR(ESI) ⁺ m/z calcd for C ₂₀ H ₁₆ N ₃ 298.133874, found 298.134252.

Example 21:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then 4-((trimethylsilyl)ethynyl)benzaldehyde 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (white solid 14 mg, yield 45%).

¹ H NMR (600 MHz, CDCl ₃ ) δ 10.13 (s, 1H), 8.27 (s, 1H), 8.23 (d, J=7.9 Hz, 1H), 8.03 (d, J=8.1 Hz, 2H), 7.68 (d, J＝8.0Hz, 2H), 7.59-7.55(m, 1H), 7.44(d, J＝8.2Hz, 1H), 7.41(t, J＝7.6Hz, 1H), 3.44(s, 3H) _The ^_ , 24.09.HR-MS(ESI)[M+H] ⁺ m/z calcd for C ₂₀ H ₁₇ N ₂ O301.133540,found 301.132693.

Example 22:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then ((2-methoxyphenyl)ethynyl)trimethylsilane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 25 mg, yield 83%).

¹ H NMR (600MHz, CDCl ₃ ) δ 8.24-8.18 (m, 2H), 7.55 (t, J=7.7Hz, 1H), 7.47 (td, J=8.3, 1.6Hz, 1H), 7.42 (d, J=8.2Hz, 1H), 7.40-7.36(m, 2H), 7.11(t, J=7.4Hz, 1H), 7.02(d, J=8.3Hz, 1H), 3.72(s, 3H), 3.46( s, 3H), 3.12(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ )δ157.90, 151.99, 144.77, 143.36, 141.62, 132.16, 130.04, 126.29, 125.90, 122.56, 122.06, 120.83, 116.36, 117.36, 116.680 ,110.59,109.09,55.49,30.69,23.54.HR-MS(ESI)[M+H] ⁺ m/zcalcd for C ₂₀ H ₁₉ N ₂ O 303.149190,found 303.149471.

Example 23:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then ((2-bromophenyl)ethynyl)trimethylsilane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 22 mg, yield 64%).

¹ H NMR (600MHz, CDCl ₃ ) δ 8.23(d, J=7.9Hz, 1H), 8.19(s, 1H), 7.76-7.72(m, 1H), 7.57-7.53(m, 1H), 7.48- 7.44(m, 2H), 7.42(d, J=8.2Hz, 1H), 7.39(t, J=7.5Hz, 1H), 7.37-7.33(m, 1H), 3.42(s, 3H), 3.13(s ,3H). ¹³ C NMR(151MHz,CDCl ₃ )δ153.21,145.08,142.35,141.46,138.36,132.64,132.58,129.98,127.48,126.29,126.02,122.62,122.08,120.80,118.58,117.67,109.07,30.90,24.13 .HR-MS(ESI)[M+H] ⁺ m/z calcd for C ₁₉ H ₁₆ BrN ₂ 351.049137, found 303.351.049628.

Example 24:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl(m-tolylethynyl)silane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 24 mg, yield 84%).

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.26 (s, 1H), 8.22 (d, J=7.9 Hz, 1H), 7.57-7.52 (m, 1H), 7.42 (d, J=8.2 Hz, 1H) , 7.38(t, J=7.6Hz, 2H), 7.31-7.26(m, 3H), 3.44(s, 3H), 3.11(s, 3H), 2.45(s, 3H). ¹³ C NMR(126MHz, CDCl ₃ )δ152.47,145.55,142.61,141.79,138.04,137.21,131.22,128.66,128.20,127.65,126.23,122.58,122.18,120.74,119.78,117.85,109.12,32.53,24.06,21.65.HR-MS(ESI)[M +H] ⁺ m/z calcd for C ₂₀ H ₁₉ N ₂ 287.154275, found 287.154498.

Example 25:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then ((3-chlorophenyl)ethynyl)trimethylsilane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 25 mg, yield 83%).

¹ H NMR (500MHz, CDCl ₃ ) δ 8.26-8.20(m, 2H), 7.57(t, J=7.7Hz, 1H), 7.49(s, 1H), 7.48-7.44(m, 2H), 7.43( d, J=3.2Hz, 1H), 7.41(d, J=8.2Hz, 1H), 7.39-7.37(m, 1H), 3.46(s, 3H), 3.12(s, 3H). ¹³ C NMR(126MHz) ,CDCl ₃ )δ152.78,144.90,142.47,141.83,138.97,134.41,130.47,129.67,128.70,128.26,126.61,122.64,122.02,121.13,118.34,118.09,109.30,32.74,23.81.HR-MS(ESI)[M +H] ⁺ m/z calcd for C ₁₉ H ₁₆ ClN ₂ 307.099653, found307.099347.

Example 26:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then ((3,5-dimethylphenyl)ethynyl)trimethylsilane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 22 mg, yield 73%).

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.26 (s, 1H), 8.22 (d, J=7.9 Hz, 1H), 7.54 (t, J=7.7 Hz, 1H), 7.41 (d, J=8.2 Hz , 1H), 7.37(t, J=7.5Hz, 1H), 7.09(s, 3H), 3.45(s, 3H), 3.11(s, 3H), 2.41(s, 6H). ¹³ C NMR(126MHz, CDCl ₃ )δ152.29,145.41,142.63,141.80,137.85,137.07,129.52,128.34,126.19,122.55,122.18,120.69,119.90,117.81,109.10,32.51,23.90.9,21 ⁺ m/z calcd for C ₂₁ H ₂₁ N ₂ 301.169925, found 301.169980.

Example 27:

At room temperature, 0.1 mmol of 1-(6-chloro-1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then ((3,4-dimethoxyphenyl)ethynyl)trimethylsilane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 25 mg, yield 68%).

¹ H NMR (500MHz, CDCl ₃ ) δ 8.27(s, 1H), 8.07(d, J=8.4Hz, 1H), 7.39(d, J=1.4Hz, 1H), 7.35-7.29(m, 1H) , 7.02-6.97(m, 2H), 6.95(s, 1H), 3.97(s, 3H), 3.90(s, 3H), 3.42(s, 3H), 3.05(s, 3H). ¹³ C NMR(126MHz) ,CDCl ₃ )δ152.14,149.10,148.77,145.59,143.15,142.42,132.38,129.05,123.27,122.87,121.32,120.66,119.71,117.40,113.68,111.05,109.45,56.14,56.12,32.47,23.72.HR-MS( ESI)[M+H]+m/z calcd for C ₂₁ H ₂₀ ClN ₂ O ₂ 367.120782, found 367.120191.

Example 28:

At room temperature, 0.1 mmol of 1-(6-methoxy-1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime was sequentially added to a 10 mL Schrock reaction tube, [Cp ^* RhCl ₂ ] ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then (3,4-dimethoxyphenyl)ethynyl)trimethylsilane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (pale yellow solid 30 mg, yield 83%).

¹ H NMR (500MHz, CDCl ₃ ) δ 8.21(s, 1H), 8.06(d, J=8.7Hz, 1H), 7.03-7.00(m, 1H), 7.00-6.96(m, 3H), 6.86( d, J=2.1Hz, 1H), 3.97(s, 3H), 3.94(s, 3H), 3.90(s, 3H), 3.41(s, 3H), 3.05(s, 3H). ¹³ C NMR(126MHz) ,CDCl ₃ )δ159.48,151.05,148.95,148.72,144.51,143.31,142.89,129.67,123.28,122.86,119.34,117.96,115.87,113.81,111.05,109.06,93.73,56.14,55.85,32.38,23.63.HR-MS( ESI)[M+H] ⁺ m/z calcd for C ₂₂ H ₂₃ N ₂ O ₃ 363.170319, found 363.170919.

Example 29:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl((3,4,5-trimethoxyphenyl)ethynyl)silane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 27 mg, yield 75%).

¹ H NMR (600 MHz, CDCl ₃ ) δ 8.28 (s, 1H), 8.22 (d, J=7.9 Hz, 1H), 7.57-7.53 (m, 1H), 7.43 (d, J=8.2 Hz, 1H) , 7.40-7.36(m, 1H), 6.68(s, 2H), 3.95(s, 3H), 3.88(s, 6H), 3.50(s, 3H), 3.10(s, 3H). ¹³ C NMR(101MHz) , CDCl ₃ )δ153.11,152.68,145.29,142.48,141.74,137.85,132.74,126.34,122.58,122.12,120.84,119.59,117.86,109.15,107.84,61.20,24.6.HR-MS(ESI)[56.38,32 +H] ⁺ m/z calcd for C ₂₂ H ₂₃ N ₂ O ₃ 363.170319, found363.170887.

Example 30:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then ((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethynyl)trimethylsilane 0.15 mmol and sealed Tube. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 20 mg, yield 60%).

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.23 (s, 1H), 8.20 (d, J=7.9 Hz, 1H), 7.56 (t, J=7.7 Hz, 1H), 7.43 (d, J=8.2 Hz ,1H),7.39(t,J＝7.5Hz,1H),7.00-6.96(m,2H),6.94-6.90(m,1H),4.34(s,4H),3.51(s,3H),3.11( s,3H). ¹³ C NMR(126MHz,CDCl ₃ )δ151.65,144.36,143.73,143.41,142.86,141.91,129.75,126.59,123.70,122.56,122.01,121.10,119.44,119.26,117.95,117.23,109.33,64.58, 64.56, 32.52, 23.35. HR-MS(ESI)[M+H] ⁺ m/z calcd for C ₂₁ H ₁₉ N ₂ O ₂ 331.144104, found 331.142593.

Example 31:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl(thiophen-3-ylethynyl)silane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 17 mg, yield 61%).

¹ H NMR (400MHz, CDCl ₃ ) δ 8.36 (s, 1H), 8.21 (d, J=7.9Hz, 1H), 7.58-7.53 (m, 1H), 7.47 (dd, J=4.7, 1.6Hz, 1H), 7.44(d, J=8.2Hz, 1H), 7.41-7.36(m, 1H), 7.19-7.15(m, 2H), 3.54(s, 3H), 3.10(s, 3H). ¹³ C NMR _[ ] ⁺ m/z calcd for C ₁₇ H ₁₅ N ₂ S, 279.095046found 279.094281.

Example 32:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl(naphthalen-2-ylethynyl)silane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 23 mg, yield 72%).

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.34 (s, 1H), 8.28 (d, J=7.9 Hz, 1H), 7.99 (d, J=7.8 Hz, 1H), 7.96 (d, J=8.2 Hz ,1H),7.63-7.57(m,2H),7.56-7.49(m,2H),7.44(d,J=8.4Hz,1H),7.40(t,J=7.4Hz,1H),7.37-7.32( m, 2H), 3.19(s, 3H), 3.08(s, 3H).

¹³ C NMR(126MHz,CDCl ₃ )δ152.98,145.98,143.48,141.56,134.74,133.80,133.44,128.75,128.68,128.46,126.76,126.35,126.33,126.27,125.42,122.64,122.16,120.80,117.61,117.27,109.08 , 31.04, 24.10. HR-MS(ESI)[M+H] ⁺ m/z calcd for C ₂₃ H ₁₉ N ₂ 323.154275, found 323.154461.

Example 33:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then add ethynyltrimethylsilane 0.15 mmol and seal the tube. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 18 mg, yield 92%).

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.44 (d, J=5.9 Hz, 1H), 8.16 (d, J=7.9 Hz, 1H), 7.58-7.53 (m, 1H), 7.47 (d, J= 8.2Hz, 1H), 7.37(t, J=7.5Hz, 1H), 7.21(d, J=5.9Hz, 1H), 3.85(s, 3H), 3.06(s, 3H). ¹³ C NMR(126MHz, CDCl ₃ )δ153.02,145.40,143.61,140.97,126.43,122.61,122.21,120.83,117.69,109.01,102.41,29.34,23.49.HR-MS(ESI)[M+H] ⁺ m/zcalcd for C ₁₃ H ₁₃ N ₂ 197.107325, found 197.107821.

Example 34:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then but-1-yn-1-yltrimethylsilane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, it was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 20 mg, yield 89%).

¹ H NMR (600MHz, CDCl ₃ ) δ 8.20 (s, 1H), 8.17 (d, J=7.9Hz, 1H), 7.56-7.52 (m, 1H), 7.46 (d, J=8.2Hz, 1H) ,7.37-7.33(m,1H),4.09(s,3H),3.15(q,J=7.5Hz,2H),3.03(s,3H),1.40(t,J=7.6Hz,3H) ^.13C NMR (151MHz, CDCl ₃ ) δ 151.69, 145.21, 143.38, 141.45, 126.03, 122.50, 122.39, 120.57, 119.75, 117.85, 108.91, 31.92, 23.98, 23.67, 17.02. HR-MS (ESI) [M+H] ⁺ m /z calcd for C ₁₅ H ₁₇ N ₂ 225.138625, found 225.138150.

Example 35:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl(prop-1-yn-1-yl)silane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, rinse with a mixed eluent of petroleum ether and ethyl acetate, and flash column chromatography (silica gel column) to obtain the corresponding γ-carboline derivatives. The ratio of the two configurations is 1:1 (light yellow solid 19 mg, yield 89%).

¹ H NMR (600MHz, DMSO-d ₆ ) δ 8.14 (d, J=7.9Hz, 1H), 8.11 (d, J=7.8Hz, 1H), 8.06 (s, 1H), 7.69 (d, J= 8.2Hz, 1H), 7.64(d, J=8.2Hz, 1H), 7.56-7.49(m, 2H), 7.34-7.29(m, 3H), 4.12(s, 3H), 3.84(s, 3H), 2.89(s, 6H), 2.75(s, 3H), 2.58(s, 3H).

¹³ C NMR(101MHz,DMSO-d ₆ )δ152.01,151.15,150.50,145.89,144.97,143.24,140.83,140.62,125.88,125.65,121.96,121.73,121.29,121.00,120.22,120.18,116.36,114.49,113.52,109.50 ,109.40,101.35,31.64,28.98,24.27,23.30,23.04,16.32.HR-MS(ESI)[M+H] ⁺ m/z calcd for C ₁₄ H ₁₅ N ₂ 211.122975,found 211.122108.

Example 36:

At room temperature, 0.1 mmol of 1-(1-methyl-1H-indol-3-yl)ethan-1-one-O-methyloxime, [Cp ^* RhCl ₂ ] were successively added to a 10 mL Schrock reaction tube. ₂ 0.0025 mmol, AgSbF ₆ 0.01 mmol, TFE 1 mL, then trimethyl(pent-1-yn-1-yl)silane 0.15 mmol was added and the tube was sealed. Stir at 120°C for 24 hours. The reaction was quenched, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture was washed with a mixed eluent of petroleum ether and ethyl acetate, and the corresponding γ-carboline derivative was obtained by flash column chromatography (silica gel column) (light yellow solid 22 mg, yield 92%).

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.20-8.14 (m, 2H), 7.55 (t, J=7.7 Hz, 1H), 7.47 (d, J=8.1 Hz, 1H), 7.36 (t, J= 7.5Hz, 1H), 4.08(s, 3H), 3.10-3.01(m, 5H), 1.77(dq, J=14.7, 7.7, 7.1Hz, 2H), 1.06(t, J=7.3Hz, 3H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ 151.39, 145.36, 143.44, 141.42, 126.10, 122.43, 122.22, 120.64, 118.15, 117.88, 108.92, 32.45, 31.84, 25.62, 23.66 HR-MS(ESI9, 13.88). H]+m/z calcd for C ₁₆ H ₁₉ N ₂ 239.1543, found 239.1548.

The invention utilizes rhodium to catalyze the carbon-hydrogen bond activation reaction, and realizes the efficient and regioselective synthesis of C3-position unsubstituted γ-carboline by using simple and readily available raw materials. The valuable γ-carboline derivatives are synthesized through simple operations and cheap and readily available raw materials, the reaction conditions are mild, the economy is efficient, and the atom economy and step economy are high.

The above-disclosed preferred embodiments of the present invention are provided only to help illustrate the present invention. The preferred embodiments do not exhaust all the details, nor do they limit the invention to only the described embodiments. Obviously, many modifications and variations are possible in light of the contents of this specification. These embodiments are selected and described in this specification in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can well understand and utilize the present invention. The present invention is to be limited only by the claims and their full scope and equivalents.

Claims (7)

1. a preparation method of γ-carboline derivative, is characterized in that, comprises the following steps: The compound having the ketoxime structure represented by the formula (I) and the compound having the alkynyl silane structure represented by the formula (II) are used as starting materials, in dichloro (pentamethylcyclopentadienyl) rhodium (III) Under the catalysis of dimer and silver hexafluoroantimonate, using trifluoroethanol as solvent, the γ-carboline compound with the structure of formula (III) was synthesized in air:

Wherein, R ¹ is one of hydrogen atom, alkyl group, alkoxy group or halogen, R ² is one of hydrogen atom, alkyl group, alkynyl group or aryl group, R ³ is hydrogen atom, alkyl group or aryl group one of the bases. 2. the preparation method of a kind of γ-carboline derivative according to claim 1, is characterized in that, The starting materials are: a compound having a ketoxime structure represented by formula (I), a compound having a trimethyl (phenylethynyl) silane structure represented by formula (II), and the reaction formula is as follows:

wherein R ² is one of hydrogen atom, ethyl group, n-propyl group, allyl group or benzyl group. 3. the preparation method of a kind of γ-carboline derivative according to claim 1, is characterized in that, The starting materials are: a compound having a ketoxime structure represented by formula (I) and a compound having an aralkynyl silane structure represented by formula (II), and the reaction formula is as follows:

When R ³ is phenyl, R ¹ is H, CH ₃ , OMe, Cl at C-5 position of substrate indole or F, OMe, Cl at C-6 position of substrate indole or substrate indole C-7 bit of Me; When R ³ is 3,4,5-trimethoxyphenyl, R ¹ is Cl at C-6 position of substrate indole; When R ¹ is H, R ³ is p-tolyl, p-tert-butylphenyl, p-bromophenyl, biphenyl, methyl p-formate phenyl, p-cyanophenyl, p-aldehyde phenyl, o-methyl Oxyphenyl, o-bromophenyl, m-methylphenyl, 3,5-dimethylphenyl, 3,4,5-trimethoxyphenyl, 6-(2,3-dihydrobenzo[ b] One of [1,4]dioxinyl), 3-thienyl and 2-naphthyl; When R ¹ is Cl at the C-6 position of the substrate indole, R ³ is one of m-chlorophenyl and 3,4-dimethoxyphenyl. 4. The preparation method of a γ-carboline derivative according to claim 1, wherein the raw materials are: a compound having a ketoxime structure represented by formula (I), and a compound having a ketoxime structure represented by formula (II) The compound showing the structure of alkylalkynylsilane, the reaction formula is as follows:

wherein R ³ is one of H, CH ₃ , Et or nPr. 5. The preparation method of a γ-carboline derivative according to claim 1-4, wherein the molar ratio of the ketoxime to the alkynyl silane is 1:1.5. 6. the preparation method of a kind of γ-carboline derivative according to claim 1-4 is characterized in that, The mass percentage concentration of the dichloro(pentamethylcyclopentadienyl) rhodium (III) dimer substance is 2.5 mol%, and the mass percentage concentration of the silver hexafluoroantimonate substance is 10 mol%. 7 . The method for preparing a γ-carboline derivative according to claim 1 , wherein the reaction temperature in the air is 120° C. and the reaction time is 24 hours. 8 .