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

Preparation method of gamma-carboline derivative Download PDF

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CN111961052A
CN111961052A CN202010908906.9A CN202010908906A CN111961052A CN 111961052 A CN111961052 A CN 111961052A CN 202010908906 A CN202010908906 A CN 202010908906A CN 111961052 A CN111961052 A CN 111961052A
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carboline derivative
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杨晓博
贾静文
蒋博
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Shenyang Normal University
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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

Preparation method of gamma-carboline derivative
Technical Field
The invention belongs to the field of organic synthetic chemistry, and relates to a preparation method of a gamma-carboline derivative.
Background
Gamma-carbolines are a very important class of alkaloids, the backbone of which is often found in natural products, bioactive molecules and drugs (a: r.s.alekseyev, a.v.kurkin and m.a.yurvskaya, chem.hetrocyc.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.). To date, it has been found to exhibit a variety of biological activities, including antiviral, antibacterial, antitumor activities, and the like (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.compact, 2010,6, 118.). Thus, to meet the need for high throughput screening to prepare a variety of γ -carbolines and the need to study structure-activity relationships (SAR), a number of successful synthetic methods (e.g., transition metal catalyzed coupling, acid catalyzed condensation, and light induced cyclization) have 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:6j.k.laha, s.m.baro, r.a.rossi and g.d.cuny, j.org.chem.,2011,76, 6421.). However, these methods have complicated reaction steps, severe reaction conditions, low efficiency, and poor regioselectivity. In view of this, there is still a great need to develop new strategies to synthesize various substituted γ -carboline scaffolds from readily available substrates rapidly and efficiently.
In recent years, the transition metal direct-catalyzed C-H activation/cyclization has become a simple and convenient method due to the application of the transition metal direct-catalyzed C-H activation/cyclization in the synthesis of nitrogen heterocyclic compounds, wherein the method has high economical efficiency and atom economical efficiency (a: S.H.Cho, J.Y.Kim, J.KWak and S.Chang, chem.Soc.Rev.,2011,40, 5068; b: J.Wencel-Delord, T).
Figure BDA0002662509310000021
Liu and f. glorius, chem.soc.rev.,2011,40, 4740.). In these processes, nitrogen-containing groups play an important role throughout as directing groups to coordinate with the catalyst and as nitrogen source for the product (a: n. yoshikai and y.wei, Asian j. org. chem.,2013,2, 466.). Meanwhile, many coupling reagents have been found to be useful for hydrocarbon functionalization and cyclization reactions to form five-or six-membered azacycles (a: D.H.Es and W.A.Goddard, R.A.Periana, Organometallics,2010,29, 6459.). Of these coupling reagents, alkynes are the most popular and desirable substrates for their ready availability and good reaction properties, such as internal alkynes, terminal alkynes and other alternatives (a: t.satoh and m.miura, chem. -eur.j.,2010,16,11212.). They generally react well and complete the ring-closure reaction with high efficiency. However, in most cases, symmetric internal alkynes are employed to avoid the creation of mixtures due to low regioselectivity after the use of asymmetric internal alkynes (a: K.Parthasarathhy and C. -H.Cheng, J.org.chem.,2009,74, 9359; b: T.K.hyster and T.Rovis, J.Am.chem.Soc.,2010,132,10565.). When asymmetric alkynes and terminal alkynes are used, regioselectivity is often not highAnd often 1, 2-insertions of alkynes, it is not uncommon to obtain opposite regioselectivity schemes.
In view of the importance of the gamma-carboline derivatives and the requirement of regioselective synthesis of the compounds, the development of an efficient rhodium-catalyzed gamma-carboline synthesis method is of great significance.
Disclosure of Invention
In view of the above, the technical problem to be solved by the present invention is to provide an efficient synthesis method of rhodium-catalyzed γ -carboline, which uses alkyne with large steric hindrance as a substrate to realize efficient and regioselective synthesis of C3 unsubstituted γ -carboline, and obtains a regioselectivity different from that of the previous methods.
The invention provides a preparation method of a gamma-carboline derivative, which comprises the following steps:
taking a compound with a ketoxime structure shown in a formula (I) and a compound with an alkynyl silane structure shown in a formula (II) as starting materials, and reacting in air by taking trifluoroethanol as a solvent under the catalysis of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer and silver hexafluoroantimonate to synthesize a gamma-carboline compound with a structure shown in a formula (III):
Figure BDA0002662509310000031
wherein R is1Is one of hydrogen atom, alkyl, alkoxy or halogen, R2Is one of hydrogen atom, alkyl, alkynyl or aryl, R3Is one of hydrogen atom, alkyl or aryl.
Preferably, the starting materials are: the reaction formula of the compound with the ketoxime structure shown in the formula (I) and the compound with the trimethyl (phenylethynyl) silane structure shown in the formula (II) is as follows:
Figure BDA0002662509310000032
wherein R is2Is hydrogen atom, ethyl, n-propyl,One of allyl or benzyl.
Preferably, the starting materials are: the reaction formula of the compound with the ketoxime structure shown in the formula (I) and the compound with the aralkynyl silane structure shown in the formula (II) is as follows:
Figure BDA0002662509310000033
R3when it is phenyl, R1H, CH at the C-5 position of indole as substrate3OMe, Cl or F at C-6 of the substrate indole, OMe, Cl or Me at C-7 of the substrate indole;
R3when it is 3,4, 5-trimethoxyphenyl, R1Is Cl at the C-6 position of indole as a substrate;
R1when is H, R3Is p-tolyl, p-tert-butylphenyl, p-bromophenyl, biphenyl, methyl-p-formate phenyl, p-cyanophenyl, p-aldehydiphenyl, o-methoxyphenyl, o-bromophenyl, m-methylphenyl, 3, 5-dimethylphenyl, 3,4, 5-trimethoxyphenyl, 6- (2, 3-dihydrobenzo [ b ] phenyl][1,4]Dioxin group), 3-thienyl, 2-naphthyl;
R1in the case of Cl at the C-6 position of the indole as substrate, R3Is one of m-chlorophenyl and 3, 4-dimethoxyphenyl.
Preferably, the raw materials are as follows: the reaction formula of the compound with the ketoxime structure shown in the formula (I) and the compound with the alkyl alkynyl silane structure shown in the formula (II) is as follows:
Figure BDA0002662509310000041
wherein R is3Is H, CH3Et or nPr.
Preferably, the molar ratio of ketoxime to alkynylsilane is 1: 1.5.
Preferably, the amount percentage concentration of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer species is 2.5 mol% and the amount percentage concentration of silver hexafluoroantimonate species is 10 mol%.
Preferably, the temperature of the reaction in air is 120 ℃ and the reaction time is 24 hours.
The invention has the beneficial effects that:
the invention provides a synthesis method of a gamma-carboline derivative, which 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 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 purification of products, and can be used for large-scale production.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The preparation method comprises the following specific steps: at room temperature, ketoxime, alkynyl silane compound and [ Cp & RhCl ] are sequentially reacted2]2、AgSbF6Mixing with organic solvent, and reacting in air at 120 deg.C for 24 hr to obtain corresponding gamma-carboline derivative.
Example 1:
Figure BDA0002662509310000051
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime, 0.0025mmol of [ Cp ] was added in succession to a 10mL Schlenk reaction tube*RhCl2]2，0.01mmolAgSbF61mL TFE, then 0.15mmol trimethyl (phenylethynyl) silane was added and the tube sealed. Stirring at 120 deg.C for 24 hr, stopping reaction, and mixingThe mixture was cooled to room temperature and concentrated under reduced pressure to give a crude product. Finally, washing the mixture by using a mixed eluent of petroleum ether and ethyl acetate, and carrying out flash column chromatography (silica gel column) to obtain the corresponding gamma-carboline derivative, wherein the white solid is 22mg, and the yield is 79%.
1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)152.56,145.57,142.58,141.78,137.32,130.52,128.34,127.93,126.25,122.56,122.15,120.77,119.65,117.89,109.12,32.49,24.01.HR-MS(ESI)[M+H]+m/z calcd for C19H17N2273.138625,found 273.138315.
Example 2:
Figure BDA0002662509310000052
to a 10mL Schlenk reaction tube was added 0.1mmol of 1- (1, 5-dimethyl-1H-indol-3-yl) ethan-1-one-O-methyloxime, 0.0025mmol of [ Cp ] in that order at room temperature*RhCl2]2，0.01mmolAgSbF61mL TFE, then 0.15mmol trimethyl (phenylethynyl) silane was added and the tube sealed. After stirring at 120 ℃ for 24 hours, the reaction was stopped, and the mixture was cooled to room temperature and concentrated under reduced pressure to give a crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (20 mg of white solid, 70 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(600MHz,CDCl3)8.23(s,1H),8.00(s,1H),7.51-7.43(m,5H),7.37-7.34(m,1H),7.29(d,J＝8.3Hz,1H),3.39(s,3H),3.10(s,3H),2.59(s,3H).13C NMR(151MHz,CDCl3)152.48,145.33,142.70,140.10,137.37,130.52,130.14,128.31,127.87,127.53,122.61,122.27,119.59,117.73,108.80,32.52,24.06,21.72.HR-MS(ESI)[M+H]+m/z calcd for C20H19N2 287.154275,found 287.154362.
Example 3:
Figure BDA0002662509310000061
at room temperature, 0.1mmol of 1- (5-methoxy-1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime, 0.0025mmol of [ Cp ] was added in succession to a 10mL Schlenk reaction tube*RhCl2]2，0.01mmol 1mL AgSbF6TFE, then 0.15mmol of trimethyl (phenylethynyl) silane is added and the tube is sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (24 mg of white solid, 80 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)154.79,152.55,145.40,142.97,137.29,136.79,130.51,128.34,127.91,122.68,119.70,117.82,114.59,109.69,106.40,56.32,32.57,23.98.HR-MS(ESI)[M+H]+m/z calcd for C20H19N2O 303.149190,found 303.149529.
Example 4:
Figure BDA0002662509310000071
at room temperature, 0.1mmol of 1- (5-chloro-1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime, 0.0025mmol of [ Cp ] was added in succession to a 10mL Schlenk reaction tube*RhCl2]2，0.01mmol AgSbF61mL TFE, then 0.15mmol trimethyl (phenylethynyl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally washing with mixed eluent of petroleum ether and ethyl acetate, and performing flash column chromatography (silica gel column) to obtain corresponding gamma-carboline derivative19mg of a yellow solid, yield 62%.
1H NMR(600MHz,CDCl3)8.27(s,1H),8.09(d,J＝8.4Hz,1H),7.52-7.43(m,5H),7.38(d,J＝1.6Hz,1H),7.32(dd,J＝8.4,1.8Hz,1H),3.38(s,3H),3.06(s,3H).
13C NMR(151MHz,CDCl3)152.49,145.90,142.98,142.43,136.89,132.30,130.49,128.45,128.12,123.30,121.25,120.73,119.86,117.45,109.42,32.63,23.94.HR-MS(ESI)[M+H]+m/z calcd for C19H16ClN2 307.099653,found 307.099359.
Example 5:
Figure BDA0002662509310000072
at room temperature, 1- (6-fluoro-1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime 0.1mmol, [ Cp ] was sequentially added to a 10mL Schlenk reaction tube*RhCl2]2(0.0025mmol)，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl (phenylethynyl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (18 mg of light yellow solid, 61 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(600MHz,CDCl3)8.25(s,1H),8.12(dd,J＝8.6,5.3Hz,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).13C NMR(151MHz,CDCl3)162.30(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 C19H16FN2291.129203,found 291.129705.
Example 6:
Figure BDA0002662509310000081
at room temperature, 1- (6-chloro-1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime 0.1mmol, [ Cp ] was added in sequence to a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl (phenylethynyl) silane was added and the tube sealed. After stirring at 120 ℃ for 24 hours, the reaction was stopped, and the mixture was cooled to room temperature and concentrated under reduced pressure to give a crude product. And finally, washing the mixture by using a mixed eluent of petroleum ether and ethyl acetate, and carrying out flash column chromatography (silica gel column) to obtain the corresponding gamma-carboline derivative, wherein 21mg of white solid is obtained, and the yield is 69%.
1H NMR(500MHz,CDCl3)8.27(s,1H),8.09(d,J＝8.4Hz,1H),7.52-7.45(m,5H),7.38(d,J＝1.6Hz,1H),7.33(dd,J＝8.4,1.7Hz,1H),3.38(s,3H),3.07(s,3H).
13C NMR(126MHz,CDCl3)152.43,145.78,143.01,142.46,136.86,132.35,130.49,128.46,128.15,123.31,121.30,120.73,119.89,117.47,109.44,32.64,23.88.
HR-MS(ESI)[M+H]+m/z calcd for C19H16ClN2 307.099653,found 307.099297.
Example 7:
Figure BDA0002662509310000091
at room temperature, 1- (6-methoxy-1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime 0.1mmol, [ Cp ] was added in sequence to a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl (phenylethynyl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally washing with mixed eluent of petroleum ether and ethyl acetate, and performing fast column chromatography (silica gel column) to obtain corresponding gamma-carboline derivativesOrganism (light yellow solid 23mg, 77% yield).
1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)159.46,151.17,144.50,143.31,142.74,137.28,130.49,128.34,127.91,123.27,119.55,118.00,115.86,109.00,93.76,55.83,32.54,23.68.HR-MS(ESI)[M+H]+m/z calcd for C20H19N2O 303.149190,found 303.149471.
Example 8:
Figure BDA0002662509310000092
at room temperature, 1- (6-chloro-1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime 0.1mmol, [ Cp ] was added in sequence to a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl ((3,4, 5-trimethoxyphenyl) ethynyl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (27 mg of light yellow solid, 68 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)8.28(s,1H),8.08(d,J＝8.4Hz,1H),7.40(d,J＝1.5Hz,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).13C NMR(126MHz,CDCl3)153.16,152.52,145.53,142.89,142.40,137.97,132.39,132.24,123.29,121.33,120.67,119.81,117.42,109.46,107.78,61.19,56.38,32.47,23.89.HR-MS(ESI)[M+H]+m/z calcd for C22H22ClN2O3 397.131347,found 397.130630.
Example 9:
Figure BDA0002662509310000101
at room temperature, 1- (1, 7-dimethyl-1H-indol-3-yl) ethan-1-one-O-methyloxime 0.1mmol, [ Cp ] was added in sequence to a 10mL Schlenk reaction tube*RhCl2]2(0.0025mmol)，AgSbF6(0.01mmol), TFE (1mL), then trimethyl (phenylethynyl) silane (0.15mmol) was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (23 mg of light yellow solid, the yield is 80%) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)152.09,145.25,144.47,141.57,137.60,130.06,129.87,128.56,127.82,123.45,121.44,121.25,120.66,119.85,118.58,36.59,23.94,20.72.HR-MS(ESI)[M+H]+m/z calcd for C20H19N2 287.154275,found 287.154412.
Example 10:
Figure BDA0002662509310000111
at room temperature, 1- (1H-indol-3-yl) ethan-1-one-O-methyloxime 0.1mmol, [ Cp ] was added in sequence to a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl (phenylethynyl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (12 mg of white solid, 46 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(600MHz,CDCl3)8.82(s,1H),8.42(s,1H),8.21(d,J＝7.9Hz,1H),7.66(d,J＝7.4Hz,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).13C NMR(101MHz,CDCl3)152.50,142.98,142.12,139.32,135.96,129.61,128.51,128.21,126.56,122.74,122.70,121.18,119.14,118.13,111.15,23.74.HR-MS(ESI)[M+H]+m/z calcd for C18H15N2 259.122975,found 259.122479.
Example 11:
Figure BDA0002662509310000112
at room temperature, 0.1mmol of 1- (1-ethyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then trimethyl (phenylethynyl) silane (0.15mmol) was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture is washed by mixed eluent of petroleum ether and ethyl acetate, and the corresponding gamma-carboline derivative (13 mg of light yellow solid, 45 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)152.68,145.54,141.67,140.64,137.55,130.28,128.34,128.13,126.20,122.77,122.55,120.73,119.61,118.11,109.39,38.95,24.12,14.02.HR-MS(ESI)[M+H]+m/z calcd for C20H19N2 287.154275,found 287.153412.
Example 12:
Figure BDA0002662509310000121
at room temperature, 0.1mmol of 1- (1-propyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl (phenylethynyl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture is washed by mixed eluent of petroleum ether and ethyl acetate, and the corresponding gamma-carboline derivative (19 mg of light yellow solid, 63 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)152.66,145.52,141.85,140.98,137.50,130.42,128.30,128.04,126.14,122.71,122.35,120.67,119.65,117.99,109.54,45.80,24.13,22.36,10.94.HR-MS(ESI)[M+H]+m/z calcd for C21H21N2 301.169925,found 301.168759.
Example 13:
Figure BDA0002662509310000131
at room temperature, 0.1mmol of 1- (1-allyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl (phenylethynyl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (25 mg of light yellow solid, 83 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(600MHz,CDCl3)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).13C NMR(101MHz,CDCl3)152.67,145.72,142.02,141.12,137.10,132.26,130.37,128.24,128.14,126.25,122.61,122.37,120.93,119.70,118.07,116.56,109.96,46.61,24.10.HR-MS(ESI)[M+H]+m/z calcd for C21H19N2299.154275,found 299.153392.
Example 14:
Figure BDA0002662509310000132
at room temperature, 0.1mmol of 1- (1-benzyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl (phenylethynyl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (27 mg of light yellow solid, 78% yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,Chloroform-d)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).13C NMR(126MHz,CDCl3)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)[M+H]+m/z calcd for C25H21N2349.169925,found 349.168733.
Example 15:
Figure BDA0002662509310000141
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]2(0.0025mmol)，AgSbF6(0.01mmol), TFE1mL, then trimethyl (p-tolylethynyl) silane 0.15mmol was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (20 mg of white solid, 70 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)152.34,145.61,142.68,141.77,137.72,134.24,130.37,129.04,126.20,122.54,122.15,120.72,119.63,117.83,109.10,32.48,23.98,21.41.HR-MS(ESI)[M+H]+m/z calcd for C20H19N2 287.154275,found 287.154551.
Example 16:
Figure BDA0002662509310000151
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]2(0.0025mmol)，AgSbF60.01mmol, TFE1mL, then ((4- (tert-butyl) phenyl) ethynyl) trimethylsilane 0.15mmol was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture is washed by mixed eluent of petroleum ether and ethyl acetate, and the corresponding gamma-carboline derivative (light yellow solid 25mg, yield 75%) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)8.27(s,1H),8.22(d,J＝7.9Hz,1H),7.55(t,J＝7.7Hz,1H),7.51(d,J＝8.2Hz,2H),7.43-7.36(m,4H),3.45(s,3H),3.11(s,3H),1.41(s,9H).13C NMR(126MHz,CDCl3)152.39,151.01,145.75,142.72,141.81,134.17,130.19,126.21,125.25,122.58,122.22,120.73,119.66,117.85,109.13,34.85,32.55,31.59,24.06.HR-MS(ESI)[M+H]+m/z calcd for C23H25N2 329.201225,found 329.200531.
Example 17:
Figure BDA0002662509310000152
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then ((4-bromophenyl) ethynyl) trimethylsilane 0.15mmol was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (25 mg of light yellow solid, 72 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)8.24-8.19(m,2H),7.63(d,J＝8.3Hz,2H),7.55(t,J＝7.7Hz,1H),7.41(d,J＝8.2Hz,1H),7.40-7.33(m,3H),3.44(s,3H),3.10(s,3H).
13C NMR(126MHz,CDCl3)152.93,145.40,142.38,141.74,136.31,132.06,131.55,126.41,122.59,122.25,122.05,120.93,118.35,117.99,109.17,32.68,24.03.
HR-MS(ESI)[M+H]+m/z calcd for C19H16BrN2 351.049137,found 351.049639.
Example 18:
Figure BDA0002662509310000161
at room temperature, in a 10mL Schlenk reaction tubeAdding 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime in turn, [ Cp [ -1H-indol-3-yl ] methyl-oxime*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then ([1,1' -biphenyl) was added]-4-ylethynyl) trimethylsilane 0.15mmol and the tube was sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (27 mg of light yellow solid, 78% yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)152.62,145.56,142.70,141.86,140.83,140.60,136.26,130.94,129.07,127.74,127.24,127.04,126.35,122.63,122.20,120.87,119.33,117.99,109.21,32.72,24.02.
HR-MS(ESI)[M+H]+m/z calcd for C25H21N2 349.169925,found 349.170541.
Example 19:
Figure BDA0002662509310000171
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of methyl 4- ((trimethylsilyl) ethynyl) benzoate was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (26 mg of light yellow solid, 73 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(600MHz,CDCl3)8.26(s,1H),8.22(d,J＝7.9Hz,1H),8.17(d,J＝8.2Hz,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).13C NMR(101MHz,CDCl3)166.93,153.15,145.32,142.37,142.27,141.79,130.51,129.73,129.62,126.46,122.62,122.06,120.99,118.64,118.06,109.23,52.42,32.79,24.08.HR-MS(ESI)[M+H]+m/z calcd for C21H19N2O2 331.144104,found 331.143458.
Example 20:
Figure BDA0002662509310000172
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 4- ((trimethylsilyl) ethynyl) benzonitrile 0.15mmol was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (24 mg of white solid, 80 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)8.22(d,J＝5.9Hz,2H),7.80(d,J＝8.2Hz,2H),7.61(d,J＝8.2Hz,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).13C NMR(126MHz,CDCl3)153.59,145.22,142.48,142.20,141.80,132.18,131.13,126.68,122.68,122.00,121.23,118.69,118.23,117.81,111.92,109.30,32.96,24.04.HR-MS(ESI)[M+H]+m/z calcd for C20H16N3 298.133874,found 298.134252.
Example 21:
Figure BDA0002662509310000181
at room temperature under0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL schlock reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of 4- ((trimethylsilyl) ethynyl) benzaldehyde are added and the tube is sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (14 mg of white solid, 45 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(600MHz,CDCl3)10.13(s,1H),8.27(s,1H),8.23(d,J＝7.9Hz,1H),8.03(d,J＝8.1Hz,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),3.12(s,3H).13C NMR(101MHz,CDCl3)191.86,153.40,145.29,143.95,142.35,141.83,135.83,131.12,129.74,126.59,122.68,122.07,121.13,118.41,118.18,109.29,32.94,24.09.HR-MS(ESI)[M+H]+m/z calcd for C20H17N2O 301.133540,found 301.132693.
Example 22:
Figure BDA0002662509310000191
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then ((2-methoxyphenyl) ethynyl) trimethylsilane 0.15mmol was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (25 mg of light yellow solid, 83 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(600MHz,CDCl3)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).13C NMR(101MHz,CDCl3)157.90,151.99,144.77,143.36,141.62,132.16,130.04,126.29,125.90,122.56,122.06,120.83,120.80,117.56,116.13,110.59,109.09,55.49,30.69,23.54.HR-MS(ESI)[M+H]+m/z calcd for C20H19N2O 303.149190,found 303.149471.
Example 23:
Figure BDA0002662509310000192
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then ((2-bromophenyl) ethynyl) trimethylsilane 0.15mmol was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (22 mg of light yellow solid, 64 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(600MHz,CDCl3)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).13C NMR(151MHz,CDCl3)153.21,145.08,142.35,141.46,138.36,132.64,132.58,129.98,127.48,126.29,126.02,122.62,122.08,120.80,118.58,117.67,109.07,30.90,24.13.HR-MS(ESI)[M+H]+m/z calcd for C19H16BrN2351.049137,found 303.351.049628.
Example 24:
Figure BDA0002662509310000201
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl (m-tolylethynyl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (24 mg of light yellow solid, 84 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)8.26(s,1H),8.22(d,J＝7.9Hz,1H),7.57-7.52(m,1H),7.42(d,J＝8.2Hz,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).13C NMR(126MHz,CDCl3)152.47,145.55,142.61,141.79,138.04,137.21,131.22,128.66,128.20,127.65,126.23,122.58,122.18,120.74,119.78,117.85,109.12,32.53,24.06,21.65.HR-MS(ESI)[M+H]+m/z calcd for C20H19N2 287.154275,found 287.154498.
Example 25:
Figure BDA0002662509310000211
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then ((3-chlorophenyl) ethynyl) trimethylsilane 0.15mmol was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (25 mg of light yellow solid, 83 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)152.78,144.90,142.47,141.83,138.97,134.41,130.47,129.67,128.70,128.26,126.61,122.64,122.02,121.13,118.34,118.09,109.30,32.74,23.81.HR-MS(ESI)[M+H]+m/z calcd for C19H16ClN2 307.099653,found 307.099347.
Example 26:
Figure BDA0002662509310000212
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then ((3, 5-dimethylphenyl) ethynyl) trimethylsilane 0.15mmol was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (22 mg of light yellow solid, 73 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)8.26(s,1H),8.22(d,J＝7.9Hz,1H),7.54(t,J＝7.7Hz,1H),7.41(d,J＝8.2Hz,1H),7.37(t,J＝7.5Hz,1H),7.09(s,3H),3.45(s,3H),3.11(s,3H),2.41(s,6H).13C NMR(126MHz,CDCl3)152.29,145.41,142.63,141.80,137.85,137.07,129.52,128.34,126.19,122.55,122.18,120.69,119.90,117.81,109.10,32.51,23.99,21.50.HR-MS(ESI)[M+H]+m/z calcd for C21H21N2 301.169925,found 301.169980.
Example 27:
Figure BDA0002662509310000221
sequentially adding into a 10mL Schlenk reaction tube at room temperature1- (6-chloro-1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime 0.1mmol, [ Cp [*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then ((3, 4-dimethoxyphenyl) ethynyl) trimethylsilane 0.15mmol was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture is washed by mixed eluent of petroleum ether and ethyl acetate, and the corresponding gamma-carboline derivative (25 mg of light yellow solid, 68 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)152.14,149.10,148.77,145.59,143.15,142.42,132.38,129.05,123.27,122.87,121.32,120.66,119.71,117.40,113.68,111.05,109.45,56.14,56.12,32.47,23.72.HR-MS(ESI)[M+H]+m/z calcd for C21H20ClN2O2367.120782,found 367.120191.
Example 28:
Figure BDA0002662509310000231
at room temperature, 1- (6-methoxy-1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime 0.1mmol, [ Cp ] was added in sequence to a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then (3, 4-dimethoxyphenyl) ethynyl) trimethylsilane 0.15mmol was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (30 mg of light yellow solid, 83 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)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).13C NMR(126MHz,CDCl3)159.48,151.05,148.95,148.72,144.51,143.31,142.89,129.67,123.28,122.86,119.34,117.96,115.87,113.81,111.05,109.06,93.73,56.14,55.85,32.38,23.63.HR-MS(ESI)[M+H]+m/z calcd for C22H23N2O3363.170319,found 363.170919.
Example 29:
Figure BDA0002662509310000232
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl ((3,4, 5-trimethoxyphenyl) ethynyl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (27 mg of light yellow solid, 75 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(600MHz,CDCl3)8.28(s,1H),8.22(d,J＝7.9Hz,1H),7.57-7.53(m,1H),7.43(d,J＝8.2Hz,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).13C NMR(101MHz,CDCl3)153.11,152.68,145.29,142.48,141.74,137.85,132.74,126.34,122.58,122.12,120.84,119.59,117.86,109.15,107.84,61.20,56.38,32.36,24.04.HR-MS(ESI)[M+H]+m/z calcd for C22H23N2O3 363.170319,found 363.170887.
Example 30:
Figure BDA0002662509310000241
at room temperature, at 10mSequentially adding 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethyl-1-one-O-methyl oxime and [ Cp ] into an L schlock reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then ((2, 3-dihydrobenzo [ b ]][1,4]Dioxin-6-yl) ethynyl) trimethylsilane 0.15mmol and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture is washed by mixed eluent of petroleum ether and ethyl acetate, and the corresponding gamma-carboline derivative (20 mg of light yellow solid, 60 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)8.23(s,1H),8.20(d,J＝7.9Hz,1H),7.56(t,J＝7.7Hz,1H),7.43(d,J＝8.2Hz,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).13C NMR(126MHz,CDCl3)151.65,144.36,143.73,143.41,142.86,141.91,129.75,126.59,123.70,122.56,122.01,121.10,119.44,119.26,117.95,117.23,109.33,64.58,64.56,32.52,23.35.HR-MS(ESI)[M+H]+m/z calcd for C21H19N2O2 331.144104,found 331.142593.
Example 31:
Figure BDA0002662509310000251
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl (thiophen-3-ylethynyl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (17 mg of light yellow solid, 61 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)153.54,146.79,143.23,141.73,137.67,129.35,127.23,126.77,126.43,122.62,122.01,120.97,117.88,111.75,109.20,31.82,24.09.HR-MS(ESI)[M+H]+m/z calcd for C17H15N2S,279.095046found 279.094281.
Example 32:
Figure BDA0002662509310000252
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl (naphthalen-2-ylethynyl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (23 mg of light yellow solid, 72 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)8.34(s,1H),8.28(d,J＝7.9Hz,1H),7.99(d,J＝7.8Hz,1H),7.96(d,J＝8.2Hz,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).
13C NMR(126MHz,CDCl3)152.98,145.98,143.48,141.56,134.74,133.80,133.44,128.75,128.68,128.46,126.76,126.35,126.33,126.27,125.42,122.64,122.16,120.80,117.61,117.27,109.08,31.04,24.10.HR-MS(ESI)[M+H]+m/z calcd for C23H19N2323.154275,found 323.154461.
Example 33:
Figure BDA0002662509310000261
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of ethynyltrimethylsilane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (18 mg of light yellow solid, 92 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(500MHz,CDCl3)8.44(d,J＝5.9Hz,1H),8.16(d,J＝7.9Hz,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).13C NMR(126MHz,CDCl3)153.02,145.40,143.61,140.97,126.43,122.61,122.21,120.83,117.69,109.01,102.41,29.34,23.49.HR-MS(ESI)[M+H]+m/z calcd for C13H13N2 197.107325,found 197.107821.
Example 34:
Figure BDA0002662509310000271
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then but-1-yn-1-yltrimethylsilane 0.15mmol was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture of petroleum ether and ethyl acetate is used for washing, and the corresponding gamma-carboline derivative (20 mg of light yellow solid, 89 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(600MHz,CDCl3)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,CDCl3)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 C15H17N2 225.138625,found 225.138150.
Example 35:
Figure BDA0002662509310000272
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl (prop-1-yn-1-yl) silane was added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally washing with mixed eluent of petroleum ether and ethyl acetate, and performing flash column chromatography (silica gel column) to obtain corresponding gamma-carboline derivative with the ratio of two configurations being 1:1 (light yellow solid 19mg, yield 89%).
1H NMR(600MHz,DMSO-d6)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).
13C NMR(101MHz,DMSO-d6)152.01,151.15,150.50,145.89,144.97,143.24,140.83,140.62,125.88,125.65,121.96,121.73,121.29,121.00,120.22,120.18,116.36,114.49,113.52,109.50,109.40,101.35,31.64,28.98,24.27,23.30,23.04,16.32.HR-MS(ESI)[M+H]+m/z calcd for C14H15N2 211.122975,found 211.122108.
Example 36:
Figure BDA0002662509310000281
at room temperature, 0.1mmol of 1- (1-methyl-1H-indol-3-yl) ethan-1-one-O-methyloxime and [ Cp ] are sequentially added into a 10mL Schlenk reaction tube*RhCl2]20.0025mmol，AgSbF60.01mmol, TFE1mL, then 0.15mmol of trimethyl (pent-1-yn-1-yl) silane were added and the tube sealed. Stirring was carried out at 120 ℃ for 24 hours. The reaction was stopped, then the mixture was cooled to room temperature and concentrated under reduced pressure to give the crude product. Finally, the mixture is washed by mixed eluent of petroleum ether and ethyl acetate, and the corresponding gamma-carboline derivative (22 mg of light yellow solid, 92 percent of yield) is obtained by flash column chromatography (silica gel column).
1H NMR(400MHz,CDCl3)8.20-8.14(m,2H),7.55(t,J＝7.7Hz,1H),7.47(d,J＝8.1Hz,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).13C NMR(101MHz,CDCl3)151.39,145.36,143.44,141.42,126.10,122.43,122.22,120.64,118.15,117.88,108.92,32.45,31.84,25.62,23.69,13.88.HR-MS(ESI)[M+H]+m/z calcd for C16H19N2 239.1543,found 239.1548.
The invention utilizes rhodium to catalyze carbon-hydrogen bond activation reaction, and uses simple and easily obtained raw materials to realize high-efficiency and regioselective synthesis of C3-site unsubstituted gamma-carboline. The gamma-carboline derivative with important value is synthesized by simple operation and cheap and easily-obtained raw materials, and the method has the advantages of mild reaction conditions, economy, high efficiency, high atom economy and step economy.
The preferred embodiments of the invention disclosed above are intended to be illustrative only. The preferred embodiments are not intended to be exhaustive or to limit the invention to the precise embodiments disclosed. Obviously, many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the invention and the practical application, to thereby enable others skilled in the art to best utilize the invention. The invention is limited only by the claims and their full scope and equivalents.

Claims (7)

1. The preparation method of the gamma-carboline derivative is characterized by comprising the following steps:
taking a compound with a ketoxime structure shown in a formula (I) and a compound with an alkynyl silane structure shown in a formula (II) as starting materials, and reacting in air by taking trifluoroethanol as a solvent under the catalysis of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer and silver hexafluoroantimonate to synthesize a gamma-carboline compound with a structure shown in a formula (III):
Figure FDA0002662509300000011
wherein R is1Is one of hydrogen atom, alkyl, alkoxy or halogen, R2Is one of hydrogen atom, alkyl, alkynyl or aryl, R3Is one of hydrogen atom, alkyl or aryl.
2. The method for producing a γ -carboline derivative according to claim 1,
the starting materials are as follows: the reaction formula of the compound with the ketoxime structure shown in the formula (I) and the compound with the trimethyl (phenylethynyl) silane structure shown in the formula (II) is as follows:
Figure FDA0002662509300000012
wherein R is2Is one of hydrogen atom, ethyl, n-propyl, allyl or benzyl.
3. The method for producing a γ -carboline derivative according to claim 1,
the starting materials are as follows: the reaction formula of the compound with the ketoxime structure shown in the formula (I) and the compound with the aralkynyl silane structure shown in the formula (II) is as follows:
Figure FDA0002662509300000021
R3when it is phenyl, R1H, CH at the C-5 position of indole as substrate3OMe, Cl or F at C-6 of the substrate indole, OMe, Cl or Me at C-7 of the substrate indole;
R3when it is 3,4, 5-trimethoxyphenyl, R1Is Cl at the C-6 position of indole as a substrate;
R1when is H, R3Is p-tolyl, p-tert-butylphenyl, p-bromophenyl, biphenyl, methyl-p-formate phenyl, p-cyanophenyl, p-aldehydiphenyl, o-methoxyphenyl, o-bromophenyl, m-methylphenyl, 3, 5-dimethylphenyl, 3,4, 5-trimethoxyphenyl, 6- (2, 3-dihydrobenzo [ b ] phenyl][1,4]Dioxin group), 3-thienyl, 2-naphthyl;
R1in the case of Cl at the C-6 position of the indole as substrate, R3Is one of m-chlorophenyl and 3, 4-dimethoxyphenyl.
4. The method for preparing a γ -carboline derivative according to claim 1, wherein the raw materials are: the reaction formula of the compound with the ketoxime structure shown in the formula (I) and the compound with the alkyl alkynyl silane structure shown in the formula (II) is as follows:
Figure FDA0002662509300000022
wherein R is3Is H, CH3Et or nPr.
5. The method for preparing a γ -carboline derivative according to claims 1 to 4, wherein the molar ratio of ketoxime to alkynylsilane is 1: 1.5.
6. The method for producing a γ -carboline derivative according to claims 1 to 4,
the weight percentage concentration of dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer substance is 2.5 mol%, and the weight percentage concentration of hexafluoroantimonate substance is 10 mol%.
7. The method for preparing a γ -carboline derivative according to claims 1 to 4, wherein the reaction temperature in air is 120 ℃ and the reaction time is 24 hours.
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