A method for synthesizing carbonyl-containing full-carbon quaternary carbon spiroindoline

Abstract

The present invention discloses a method for synthesizing a carbonyl-containing, all-carbon, quaternary carbon spiroindoline. The method involves a zero-valent palladium catalytic cycle, i.e., oxidative addition of palladium (0) via a carbon-halogen bond, coordination of carbon monoxide and migration insertion to form a carbonyl palladium species, and then dearomatization of the indole ring via nucleophilic attack of indole C3, followed by reduction and elimination to obtain a carbonyl-containing, all-carbon, quaternary carbon spiroindoline derivative. Specifically, compound 1 and carbon monoxide gas are reacted under heating conditions using palladium as a catalyst, an organic phosphine as a ligand, and a sodium salt as an alkaline agent to obtain a carbonyl-containing, all-carbon, quaternary carbon spiroline molecule. The method is a novel method for synthesizing a carbonyl-containing, all-carbon, quaternary carbon spiroindoline, which solves the problems of the prior art, such as the need for multi-step reactions, harsh reaction conditions, a narrow substrate range, and high raw material toxicity.

Description

Technical Field

[0001] The present invention relates to a method for synthesizing a compound, in particular to a method for synthesizing a carbonyl-containing full-carbon quaternary carbon spiroindolenine derivative. Background Art

[0002] Carbonyl-containing, fully quaternary, spiroindoline derivatives are widely distributed in natural products and serve as the core backbones of many pharmaceutical molecules. Furthermore, these derivatives are important synthetic intermediates for pesticides, dyes, and functional materials. Organic chemists are continually searching for simple and direct methods to synthesize these carbonyl-containing spirocycles. However, most reported synthetic methods suffer from drawbacks, making it difficult to effectively integrate the introduction of a carbonyl group with the construction of a fully quaternary, spirocycle. These methods often require separate steps: constructing the spirocycle and introducing the carbonyl group. For example: Franz, AK; Hanhan, NV; Ball-Jones, NRACS Catal. 2013, 3, 540-553; Qiu, B.; Xu, D.; Sun, Q.; Miao, C.; Lee, Y.-M.; Li, X.-X.; Nam, W.; Sun, W.ACS Catal.2018,8,2479-2487;Suzuki,Y.;Vatmurge,N.;Tanaka,S.;Kitamura,M.;Suzuki,Y.;Vatmurge,N.;Tanaka,S.;Kitamura,M. J.Org.Chem. 2016, 5, 729–734; Bera, S.; Daniliuc, G.C.; Studer, A. Angew. Chem. Int. Ed. 2017, 56, 7402–7406; Jiang, H.; Gschwend, B.; Albrecht, L.; Hansen, S.G.; Jorgensen, K.A. Chem.-Eur. J. 2011, 17, 9032–9036. Alternatively, the harsh reaction conditions, narrow substrate range, and high toxicity of the raw materials used are inconsistent with the fundamental principles of green chemistry and sustainable development. Therefore, finding a readily available, rapid, efficient, and simple method to simultaneously introduce a carbonyl group and construct a fully carbonyl-containing quaternary carbonyl spirocycle, thereby achieving the efficient synthesis of indolenine derivatives containing carbonyl-containing quaternary carbonyl spirocycles, remains a pressing challenge in organic chemistry. Summary of the Invention

[0003] Purpose of the invention: The present invention aims to provide a simple and efficient method for synthesizing carbonyl-containing full-carbon quaternary carbon spiroindolenine derivatives.

[0004] Technical Solution: The method for synthesizing carbonyl-containing, all-carbon, quaternary spiroindolenine derivatives of the present invention uses a one-step reaction to simultaneously complete the introduction of the carbonyl group and the construction of the spirocycle. The reaction is carried out according to the following steps: Compound 1 is mixed with carbon monoxide gas, a palladium catalyst, a phosphine ligand, and a base are added, and the reaction is carried out in a solvent to obtain the target compound 2. The reaction formula is as follows:

[0005]

[0006] The present invention relates to a method for preparing a multifunctionalized carbonyl-containing full-carbon quaternary spiroindolenine. The method comprises the following steps: using 2-methyl-3-(o-bromobenzyl)indole as a reaction raw material, adding a palladium catalyst and an appropriate amount of a phosphine ligand in a carbon monoxide atmosphere, stirring the reaction, and synthesizing the functionalized full-carbon quaternary spiroindolenine compound through oxidative addition, carbon monoxide migration insertion, and dearomatization.

[0007] Among them, R 1 is H, F, Cl, alkyl or alkoxy; R 2 is H, F, Cl, NO2, CF3, Ph, alkyl or alkoxy; R 3 is an alkyl, Ph or halogen substituted phenyl. Preferably, the raw material indole derivative substituent R 1 =H, Me, OMe or Cl; R 2 =H, F, Cl, NO2, CF3, Ph, Me or OMe; R 3 =Me,Ph or

[0008]

[0009] Preferably, the molar ratio of the compound 1 to carbon monoxide is 1:2-100, and the pressure of carbon monoxide is 0.1 MPa-5 MPa.

[0010] Preferably, the palladium catalyst is palladium acetate, palladium chloride, tetrakistriphenylphosphine palladium, palladium hydroxide, bis(acetonitrile)palladium chloride, palladium trifluoroacetate, palladium acetylacetonate or tetrakistriphenylphosphine palladium; the solvent is toluene, xylene, fluorobenzene, chlorobenzene or trifluorotoluene; the phosphine ligand is triphenylphosphine, bistriphenylphosphinopropane, bistriphenylphosphinobutane, adamantanephosphine, tricyclohexylphosphine, tri-tert-butylphosphine, tri(o-methylphenyl)phosphine or 1,1'-binaphthyl-2,2'-bisdiphenylphosphine; the base is sodium tert-butoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, n-butyllithium, sodium methoxide, sodium ethoxide, triethylamine or diethylamine.

[0011] Preferably, the reaction is carried out at room temperature to 150° C., the reaction time is 1-48 hours, and the yield of the target compound is 72-91%.

[0012] Preferably, the amount of the base used is 1-20 times the molar number of 2-methyl-3-(o-bromobenzyl)indole.

[0013] Preferably, the molar ratio of the catalyst is 2-methyl-3-(o-bromobenzyl)indole:catalyst=1:0.01-0.3.

[0014] Multifunctionalized carbonyl-containing all-carbon quaternary carbon spiroindolenine compounds can be successfully constructed under the above reaction conditions.

[0015] The post-reaction treatment is simple and only requires a simple column chromatography separation method, using a mixed solvent of petroleum ether and ethyl acetate as an eluent to obtain a pure carbonyl-containing full-carbon quaternary carbon spiroindolenine derivative.

[0016] The present invention utilizes a zero-valent palladium catalytic cycle system, namely, oxidative addition of palladium (0) via a carbon-halogen bond, coordination and migration insertion of carbon monoxide to form an acylpalladium species, and then dearomatization of the indole ring via nucleophilic attack by the indole C3. This method is a novel method for synthesizing carbonyl all-carbon quaternary carbon spiroindolenine derivatives. The present invention is superior to synthetic methods reported in the literature, employing a one-pot process that is simple to operate and avoids the use of highly toxic reagents. 2-methyl-3-(o-bromobenzyl)indole, synthesized from readily available, inexpensive raw materials, is used as the reaction raw material.

[0017] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages: (1) the introduction of the carbonyl group and the construction of the spiro ring are completed simultaneously in one pot, which is simple and convenient to operate; (2) the functional group compatibility is wide; (3) no polluting by-products are produced; (4) a recyclable palladium catalyst is used to promote the formation of new carbon-carbon bonds under relatively mild conditions, and a multifunctional carbonyl-containing full-carbon quaternary carbon spiro indolenine derivative is constructed through intermolecular carbonylation dearomatization, which is highly practical. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 is the H NMR spectrum of compound 2m;

[0019] Figure 2 is the C NMR spectrum of compound 2m;

[0020] Figure 3 is the H NMR spectrum of compound 2n;

[0021] Figure 4 is the C NMR spectrum of compound 2n;

[0022] Figure 5 is the H NMR spectrum of compound 2o;

[0023] Figure 6 is the C NMR spectrum of compound 2o;

[0024] Figure 7 is the H NMR spectrum of compound 2p;

[0025] Figure 8 is the C NMR spectrum of compound 2p;

[0026] Figure 9 is the H NMR spectrum of compound 2q;

[0027] Figure 10 is the C NMR spectrum of compound 2q;

[0028] Figure 11 is the H NMR spectrum of compound 2r;

[0029] Figure 12 is the C NMR spectrum of compound 2r;

[0030] Figure 13 is the H NMR spectrum of compound 2s;

[0031] Figure 14 is the C NMR spectrum of compound 2s;

[0032] Figure 15 is the H NMR spectrum of compound 2t;

[0033] Figure 16 is the C NMR spectrum of compound 2t;

[0034] Figure 17 is the H NMR spectrum of compound 2u;

[0035] Figure 18 is the C NMR spectrum of compound 2u;

[0036] Figure 19 This is the general reaction process of the inventive method. DETAILED DESCRIPTION

[0037] The technical solution of the present invention will be further described below in conjunction with specific embodiments.

[0038] Figure 19 This is the general reaction process of the method of the present invention.

[0039] Example 1

[0040]

[0041] In a carbon monoxide atmosphere, a 2-methyl-3-(o-bromobenzyl)indole derivative 1a (0.2 mmol) was mixed with 1% palladium acetate (0.002 mmol) and bistriphenylphosphine butane (0.004 mmol) and reacted under heating for 36 hours. The conversion of 1a was 95%, and the yield of 2a was 88%.1 H NMR (500MHz, CDCl3) δ7.85(d,J=7.7Hz,1H),7.74(t,J=7.5,1H),7.66–7.59(m,2H),7.52–7.44(m,1H),7.35(td,J1=7.6Hz,J2=1. 2Hz,1H),7.13(td,J1=7.5Hz,J2=1.1Hz,1H),7.00(d,J=7.5Hz,1H),3.62(d,J=17.7Hz,1H),3.49(d,J=17.7Hz,1H),2.16(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ200.3,179.3,156.4,152.7,140.6,136.4,135.8,128.7, 128.2,126.9,125.8,125.4,121.1,120.3,72.4,35.2,16.4.HRMS(ESI)m / z:[M+H] + Calcd.for C 17 H 14 NO + 248.1070,Found248.1076.

[0042] Example 2

[0043]

[0044] In a carbon monoxide atmosphere, a 2-methyl-3-(o-bromobenzyl)indole derivative 1b (0.2 mmol) was mixed with 10% palladium hydroxide (0.02 mmol) and tricyclohexylphosphine (0.024 mmol) and reacted under heating for 15 hours. The conversion of 1b was 99%, and the yield of 2b was 90%. 1 H NMR(500MHz, CDCl3)δ7.85(d,J=7.7Hz,1H),7.74(t,J=7.5Hz,1H),7.65(d,J=7.6Hz,1H),7.52–7.46(m,2H), 7.14(d,J=7.9Hz,1H),6.80(s,1H),3.60(d,J=17.6Hz,1H),3.47(d,J=17.6Hz,1H),2.28(s,3H),2.13(s,3H). 13 C{ 1H}NMR (125MHz, CDCl3) δ200.7,178.3,154.2,152.8,140.8,136.5,135.78,135.76,12 9.3,128.3,126.9,125.4,121.9,119.8,72.3,35.3,21.3,16.4.HRMS(ESI)m / z:[M+H] + Calcd.for C 18 H 16 NO + 262.1226,Found 262.1235.

[0045] Example 3

[0046]

[0047] In a carbon monoxide atmosphere, a 2-methyl-3-(o-bromobenzyl)indole derivative 1c (0.2 mmol) was mixed with 20% palladium chloride (0.04 mmol) and bistriphenylphosphine propane (0.056 mmol) and reacted under heating for 18 hours. The conversion of 1c was 90%, and the yield of 2c was 87%. 1 H NMR (500MHz, CDCl3) δ7.82(d,J=7.8Hz,1H),7.74–7.69(m,1H),7.63(d,J=7.7Hz,1H),7.50–7.45(m,2H),6.84(dd,J1= 8.5Hz,J2=2.6Hz,1H),6.54(d,J=2.4Hz,1H),3.70(s,3H),3.59(d,J=17.6Hz,1H),3.44(d,J=17.6Hz,1H),2.10(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ200.4,177.1,158.4,152.8,150.0,142.1,136.4,135.8,128 .3,127.0,125.4,120.5,113.3,108.0,72.5,55.7,35.5,16.3.HRMS(ESI)m / z:[M+H] + Calcd.for C 18 H 16 NO2 + 278.1176,Found 278.1183.

[0048] Example 4

[0049]

[0050] In a carbon monoxide atmosphere, a 2-methyl-3-(o-bromobenzyl)indole derivative 1e (0.2 mmol) was mixed with 1% palladium trifluoroacetate (0.002 mmol) and bistriphenylphosphine propane (0.0032 mmol) and reacted under heating for 24 hours. The conversion of 1e was 96%, and the yield of 2e was 83%. 1 H NMR (500MHz, CDCl3) δ7.85 (d, J = 7.7Hz, 1H), 7.75 (t, J = 7.5Hz, 1H), 7.65 (d, J = 7.6Hz, 1H), 7.51 (dd, J1 = 8.1Hz, J2 = 5.5Hz, 2 H),7.31(dd,J1=8.3Hz,J2=2.1Hz,1H),6.97(d,J=2.1Hz,1H),3.62(d,J=17.7Hz,1H),3.48(d,J=17.6Hz,1H),2.15(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ199.4,179.9,155.0,152.5,142.3,136.13,136.08,131.5 ,128.8,128.5,127.0,125.6,121.7,121.1,72.6,35.1,16.4.HRMS(ESI)m / z:[M+H] + Calcd.for C 18 H 16 ClNO + 282.0680,Found282.0691.

[0051] Example 5

[0052]

[0053] In a carbon monoxide atmosphere, a 2-methyl-3-(o-bromobenzyl)indole derivative 1f (0.2 mmol) was mixed with 10% bis(acetonitrile)palladium chloride (0.02 mmol) and triphenylphosphine (0.040 mmol) and reacted under heating for 24 hours. The conversion of 1f was 90%, and the yield of 2f was 86%. 1H NMR(500MHz, CDCl3)δ7.62(s,1H),7.58(d,J=7.8Hz,1H),7.56–7.50(m,2H),7.34–7.30(m,1H),7.11(t,J=7 .5Hz,1H),6.98(d,J=7.4Hz,1H),3.54(d,J=17.5Hz,1H),3.42(d,J=17.5Hz,1H),2.45(s,3H),2.14(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ200.4,179.5,156.4,150.2,140.8,138.4,137.1,136.6,128 .6,126.6,125.8,125.3,121.1,120.2,72.8,34.9,21.1,16.4.HRMS(ESI)m / z:[M+H] + Calcd.for C 18 H 16 NO + 262.1226,Found 262.1235.

[0054] Example 6

[0055]

[0056] In a carbon monoxide atmosphere, 1 g (0.2 mmol) of a 2-methyl-3-(o-bromobenzyl)indole derivative was mixed with 2.5% palladium acetate (0.005 mmol) and bistriphenylphosphine butane (0.01 mmol) and reacted under heating for 24 hours. The conversion rate for 1 g was 99%, and the yield for 2 g was 90%. 1 H NMR (500 MHz, CDCl3) 1 H NMR (500MHz, CDCl3) δ7.73(d,J=7.8Hz,1H),7.59(d,J=7.7Hz,1H),7.44(s,1H),7.36–7.28(m,2H),7.12(t,J =7.5Hz,1H),7.00(d,J=7.3Hz,1H),3.56(d,J=17.6Hz,1H),3.43(d,J=17.6Hz,1H),2.52(s,3H),2.15(s,3H). 13 C{ 1H}NMR (125MHz, CDCl3) δ199.7,179.6,156.4,153.3,147.4,140.8,134.2,129.6,128 .6,127.3,125.8,125.3,121.1,120.3,72.6,35.1,22.2,16.4.HRMS(ESI)m / z:[M+H] + Calcd.for C 18 H 16 NO + 262.1226,Found 262.1234.

[0057] Example 7

[0058]

[0059] In a carbon monoxide atmosphere, 2-methyl-3-(o-bromobenzyl)indole derivative 1h (0.2 mmol) was reacted with 10% palladium acetate (0.02 mmol) and Ad2P n The mixture was mixed with Bu (0.032 mmol) and reacted under heating for 10 hours. The conversion rate in 1 hour was 94%, and the yield in 2 hours was 89%. 1 H NMR (500MHz, CDCl3) δ7.58(d,J=7.7Hz,1H),7.51(d,J=8.4Hz,1H),7.35–7.30(m,2H),7.25(d,J=2.5Hz,1H),7.12 (t,J=7.5Hz,1H),7.00(d,J=7.4Hz,1H),3.85(s,3H),3.51(d,J=17.3Hz,1H),3.39(d,J=17.3Hz,1H),2.14(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ200.3,179.4,160.1,156.4,145.6,140.7,137.7,128.7,127 .6,125.8,125.3,121.1,120.3,106.4,73.2,55.7,34.5,16.4.HRMS(ESI)m / z:[M+H] + Calcd.for C 18 H 16 NO2 + 278.1176,Found 278.1184.

[0060] Example 8

[0061]

[0062] In a carbon monoxide atmosphere, 2-methyl-3-(o-bromobenzyl)indole derivative 1m (0.2 mmol) was mixed with 1% palladium acetate (0.002 mmol) and bis(triphenylphosphine)butane (0.004 mmol) and reacted under heating for 36 hours. The conversion rate of 1m was 95%, and the yield of 2m was 85%. The H NMR and C NMR spectra are shown in Figure 2. Figure 1-2 shown. 1 H NMR (500MHz, CDCl3) δ7.76(d,J=8.2Hz,1H),7.64(s,1H),7.59(d,J=Hz,1H),7.48-7.46(m,1H),7.34(dt,J1=7.6Hz,J2=1.2Hz ,1H),7.12(dt,J1=8.7Hz,J2=1.1Hz,1H),6.98(d,J=7.4Hz,1H),3.57(d,J=17.9Hz,1H),3.45(d,J=17.9Hz,1H),2.15(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ198.8,178.7,156.3,154.1,142.5,140.2,134.8,129.1, 128.8,127.1,126.3,125.9,121.0,120.3,72.3,34.7,16.3.HRMS(ESI)m / z:[M+H] + Calcd.for C 17 H 13 ClNO + 282.0680, Found 282.0689.

[0063] Example 9

[0064]

[0065] In a carbon monoxide atmosphere, a 2-methyl-3-(o-bromobenzyl)indole derivative 1n (0.2 mmol) was mixed with 10% palladium hydroxide (0.02 mmol) and tricyclohexylphosphine (0.024 mmol) and reacted under heating for 15 hours. The conversion of 1n was 99% and the yield of 2n was 81%. The H-NMR and C-NMR spectra are shown in Figure 1. Figure 3-4 shown. 1H NMR (500MHz, CDCl3) δ7.64-7.52(m,3H),7.44(d,J=7.6Hz,1H),7.34(dt,J1=7.7Hz,J2=1.3Hz,1H),7.1 2(t,J=7.6Hz,1H),6.98(d,J=7.4Hz,1H),3.58(d,J=17.7Hz,1H),3.42(d,J=17.7Hz,1H),2.18(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ196.8,178.8,156.2,154.8,140.4,135.9,133.4,132.4, 129.9,128.8,125.8,125.2,121.0,120.3,72.7,34.4,16.5.HRMS(ESI)m / z:[M+H] + Calcd.for C 17 H 13 ClNO + 282.0680, Found 282.0683.

[0066] Example 10

[0067]

[0068] In a carbon monoxide atmosphere, 2-methyl-3-(o-bromobenzyl)indole derivative 1o (0.2 mmol) was mixed with 20% palladium chloride (0.04 mmol) and bistriphenylphosphine propane (0.056 mmol) and reacted under heating for 18 hours. The conversion of 1o was 90% and the yield of 2o was 86%. The H NMR and C NMR spectra are shown in Figure 1. Figure 5-6 shown. 1 H NMR (500MHz, CDCl3) δ7.76-7.73(m,2H),7.61(d,J=7.8Hz,1H),7.48(t,J=7.7Hz,1H),7.36(dt,J1=7.7Hz,J2=1.2 Hz,1H),7.15(t,J=7.5Hz,1H),7.0(d,J=7.5Hz,1H),3.59(d,J=18.3Hz,1H),3.48(d,J=18.3Hz,1H),2.17(s,3H). 13 C{ 1H}NMR (125MHz, CDCl3) δ199.4,178.6,156.3,150.3,140.2,138.2,135.4,133.2, 129.9,128.9,126.0,123.6,121.1,120.4,72.1,34.1,16.4.HRMS(ESI)m / z:[M+H] + Calcd.for C 17 H 13 ClNO + 282.0680, Found 282.0686.

[0069] Example 11

[0070]

[0071] In a carbon monoxide atmosphere, 2-methyl-3-(o-bromobenzyl)indole derivative 1p (0.2 mmol) was mixed with 1% palladium trifluoroacetate (0.002 mmol) and bistriphenylphosphine propane (0.0032 mmol) and reacted under heating for 24 hours. The conversion of 1p was 96% and the yield of 2p was 84%. The H NMR and C NMR spectra are shown in Figure 2. Figure 7-8 shown. 1 HNMR (500MHz, CDCl3) δ7.96-7.94(m,2H),7.76(d,J=8.0Hz,1H),7.61(d,J=7.8Hz,1H),7.36(dt,J1=7.8Hz,J2=1.3 Hz,1H),7.14(t,J=7.5Hz,1H),6.94(d,J=7.4Hz,1H),3.68(d,J=17.9Hz,1H),3.55(d,J=17.9Hz,1H),2.16(s,3H). 13 C{ 1 H}NMR(125MHz,CDCl3)δ199.4,178.3,156.3,152.8,140.0,138.9,137.0(q,J C-F =32.5Hz),129.0,126.0,125.9,125.4(q,J C-F =3.8Hz),124.1,(q,J C-F =3.8Hz),123.4(q,J C-F =271.3Hz),121.0,120.5,72.4,35.1,16.4.HRMS(ESI)m / z:[M+H] + Calcd.for C 18 H 13F3NO + 316.0944,Found 316.0952.

[0072] Example 12

[0073]

[0074] In a carbon monoxide atmosphere, 2-methyl-3-(o-bromobenzyl)indole derivative 1q (0.2 mmol) was mixed with 10% bis(acetonitrile)palladium chloride (0.02 mmol) and triphenylphosphine (0.040 mmol) and reacted under heating for 24 hours. The conversion rate of 1q was 90%, and the yield of 2q was 73%. The H NMR and C NMR spectra are shown in Figure 1. Figure 9-10 shown. 1 H NMR (500MHz, CDCl3) δ8.51(s,1H),8.36-8.33(m,1H),7.99(d,J=8.3Hz,1H),7.61(d,J=7.8Hz,1H),7.39-7.36(m ,1H),7.15(t,J=7.15Hz,1H),6.97(d,J=7.4Hz,1H),3.59(d,J=18.0Hz,1H),3.72(d,J=18.0Hz,1H),2.17(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ198.8,177.9,156.2,153.4,152.4,140.3,139.7,129.2, 126.3,126.1,123.7,122.3,120.9,120.6,72.6,35.0,16.5.HRMS(ESI)m / z:[M+H] + Calcd.for C 17 H 13 N2O3 + 293.0921,Found293.0929.

[0075] Example 13

[0076]

[0077] In a carbon monoxide atmosphere, 2-methyl-3-(o-bromobenzyl)indole derivative 1r (0.2 mmol) was mixed with 2.5% palladium acetate (0.005 mmol) and bis(triphenylphosphine)butane (0.01 mmol) and reacted under heating for 24 hours. The conversion of 1r was 99% and the yield of 2r was 91%. The H NMR and C NMR spectra are shown in Figure 2. Figure 11-12 shown. 1H NMR(500MHz, CDCl3)δ7.60(d,J=7.8Hz,1H),7.34(dt,J1=7.6Hz,J2=1.3Hz,1H),7.24(s,1H),7.14(t,J=7.5Hz, 1H),7.04-7.02(m,2H),4.04(s,3H),3.94(s,3H),3.51(d,J=17.5Hz,1H),3.40(d,J=17.5Hz,1H),2.15(s,3H). 13 C{ 1 H}NMR (125MHz, CDCl3) δ198.6,179.7,156.4,156.3,150.1,148.2,140.7,129.3,128.6 ,125.8,121.1,120.2,107.5,105.5,72.7,56.4,56.2,34.9,16.2.HRMS(ESI)m / z:[M+H] + Calcd.for C 19 H 18 NO3 + 308.1281,Found308.1286.

[0078] Example 14

[0079]

[0080] In a carbon monoxide atmosphere, 2-methyl-3-(o-bromobenzyl)indole derivative 1s (0.2 mmol) was reacted with 10% palladium acetate (0.02 mmol) and Ad2P n Bu (0.032 mmol) was mixed and reacted under heating for 10 hours. The conversion rate of 1s was 94% and the yield of 2s was 82%. The H-NMR and C-NMR spectra are shown in Figure 2. Figure 13-14 shown. 1 H NMR (500MHz, CDCl3) δ9.02(d,J=8.3Hz,1H),8.20(dJ=8.4Hz,1H),7.98(d,J=8.2Hz,1H),7.71-7.41(m,4H),7.36(dt,J1=7.8 Hz,J2=1.3Hz,1H),7.13(t,J=7.5Hz,1H),7.03(d,J=7.4Hz,1H),3.71(d,J=18.1Hz,1H),3.59(d,J=18.0Hz,1H),2.19(s,3H) 13 C{ 1H}NMR(125MHz, CDCl3)δ200.2,179.5,156.5,156.4,140.6,137.0,133.0,130.8,129.8,129.6, 128.6,128.3,127.3,125.8,124.0,123.7,121.0,120.2,72.8,35.4,16.3.HRMS(ESI)m / z:[M+H] + Calcd.for C 21 H 16 NO + 298.1226,Found 298.1234.

[0081] Example 15

[0082]

[0083] In a carbon monoxide atmosphere, 2-phenyl-3-(o-bromobenzyl)indole 1t (0.2 mmol) was mixed with 5% palladium acetylacetonate (0.01 mmol) and tricyclohexylphosphine (0.016 mmol) and reacted under heating for 48 hours. The conversion of 1t was 90% and the yield of 2t was 72%. The H NMR and C NMR spectra are shown in Figure 1. Figure 15-16 shown. 1 H NMR (500MHz, CDCl3) δ7.96 (d, J=7.7Hz, 1H), 7.81-7.76 (m, 2H), 7.69-7.66 (m, 3H), 7.57 (t, J=7.8Hz, 1H), 7.43-7.3 3(m,4H),7.13(dt,J1=7.5Hz,J2=1.1Hz,1H),6.91(d,J=7.4Hz,1H),3.84(d,J=17.7Hz,1H),3.51(d,J=17.7Hz,1H) 13 C{ 1 H}NMR (125MHz, CDCl3) δ200.2,177.2,155.8,152.5,142.0,136.4,135.8,131.7,131.1,128. 9,128.8,128.4,127.9,127.3,126.3,125.9,121.3,120.1,70.5,37.6.HRMS(ESI)m / z:[M+H] + Calcd.for C 22 H 16 NO + 310.1226,Found 310.1232.

[0084] Example 16

[0085]

[0086] In a carbon monoxide atmosphere, 2-(4-fluorophenyl)-3-(o-bromobenzyl)indole 1u (0.2 mmol) was mixed with 4% tetrakistriphenylphosphine palladium (0.008 mmol) and (0.024 mmol) and reacted under heating for 40 hours. The conversion rate of 1u was 95% and the yield of 2u was 81%. The H NMR and C NMR spectra are shown in Figure 2. Figure 17-18 shown. 1 H NMR (500MHz, CDCl3) δ7.95 (d, J = 7.7Hz, 1H), 7.81-7.56 (m, 5H), 7.57 (t, J = 7.3Hz, 1H), 7.39 (dt, J1 = 7.8Hz, J2 = 1.2Hz, 1H), 7 .13(dt,J1=7.5Hz,J2=1.1Hz,1H),7.05-7.02(m,2H),6.91(d,J=7.3Hz,1H),3.79(d,J=17.7Hz,1H),3.52(d,J=17.7Hz,1H). 13 C{ 1 H}NMR(125MHz,CDCl3)δ200.0,175.9,164.5(d,J C-F =251.3Hz),155.7,152.4,141.9,136.2,136.0,130.0(d,J C-F =8.8Hz),128.9,128.5,128.1(d,J C-F =2.5Hz),127.3,126.3,125.9,121.2,120.1,116.1(d,J C-F =21.3Hz),70.4,37.6.HRMS(ESI)m / z:[M+H] + Calcd.for C 22 H 15 FNO + 328.1132,Found328.1143.

Claims

1. A method for synthesizing a carbonyl-containing full-carbon quaternary carbon spiroindolenine derivative, characterized in that: The introduction of the carbonyl group and the construction of the spiro ring are simultaneously completed in a one-step reaction. The reaction is carried out according to the following steps: Compound 1 is mixed with carbon monoxide gas, a palladium catalyst, a phosphine ligand, and a base are added, and the target compound 2 is obtained after reaction in a solvent. The reaction formula is as follows: ， Among them, R 1 is H, F, Cl, alkyl or alkoxy; R 2 is H, F, Cl, NO2, CF3, Ph, alkyl or alkoxy; R 3 is an alkyl group, a Ph or halogen-substituted phenyl group; the palladium catalyst is palladium acetate, palladium chloride, tetrakistriphenylphosphine palladium, palladium hydroxide, bis(acetonitrile)palladium chloride, palladium trifluoroacetate or palladium acetylacetonate; the solvent is toluene, xylene, fluorobenzene, chlorobenzene or trifluorotoluene; the phosphine ligand is triphenylphosphine, bistriphenylphosphinopropane, bistriphenylphosphinobutane or tricyclohexylphosphine; the base is sodium tert-butoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, n-butyllithium, sodium methoxide, sodium ethoxide, triethylamine or diethylamine; the reaction is carried out at room temperature to 150°C.

2. The method for synthesizing the carbonyl-containing all-carbon quaternary carbon spiroindolenine derivative according to claim 1, characterized in that: The molar ratio of the compound 1 to carbon monoxide is 1:2-100, and the pressure of carbon monoxide is 0.1 MPa-5 MPa.

3. The method for synthesizing the carbonyl-containing all-carbon quaternary carbon spiroindolenine derivative according to claim 1, wherein: The reaction time of this reaction is 1 to 48 hours.

4. The method for synthesizing the carbonyl-containing full-carbon quaternary carbon spiroindolenine derivative according to claim 1, characterized in that: The yields of the target compounds were 72-91%.

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