CN111187266A - Method for regioselective dearomatization of compound containing indole skeleton - Google Patents
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
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Abstract
The invention discloses a method for regioselective dearomatization of a compound containing an indole skeleton by substrate regulation, belonging to the technical field of chemical synthesis. The method can be used for carrying out the reaction under the condition that hexafluoroisopropanol is used as a solvent and the temperature is 25 ℃. The method realizes the dearomatization of the benzene ring of the indole skeleton for the first time, and realizes the respective dearomatization of the benzene ring and the pyrrole ring of the indole compounds by adjusting the difference of substrates. The method is novel and convenient, simple to operate, wide in substrate applicability and high in atom economy.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for regioselective dearomatization of a compound containing an indole skeleton.
Background
Indoles and indole derivatives are a very specific class of heterocyclic compounds that are widely found in many natural products and pharmaceutical compounds. Therefore, the modification of the indole skeleton has been intensively studied over the past decades. However, various proposed synthetic methods are directed to the more nucleophilic pyrrole moiety in the indole nucleus, and the functionalization of the indole backbone in the carbon ring has not yet been developed. Dearomatization is a unique strategy for functionalizing planar aromatic compounds, and provides an intuitive and practical method for synthesizing various valuable three-dimensional molecules. In recent years, dearomatization of indoles has made great progress in the synthesis of various indoles and indole-based compounds (acc. chem. res.,2014,47, 2558; chem. eur. j.,2016,22, 2856). However, at present, there is no example of dearomatization of the carbocyclic indole skeleton. Therefore, it is very necessary to develop a strategy to achieve carbocyclic dearomatization of the indole backbone from readily available substrates to construct a more useful backbone.
Redox neutral C-H functionalization reactions involving the process of hydrogen migration are ideal for the synthesis of many versatile and more complex molecules due to their inherent high efficiency and high atom economy. Over the past few years, many hydrogen acceptors have been reported for hydrogen transport. However, in almost all cases, hydride acceptors must be prepared in advance by lengthy steps (chem. commun.,2018,54, 7928; org. lett.,2017,19, 1566; org. lett.,2017,19, 1334).
Aromatization is an important thermodynamic driving force for various synthetic transformations. The o-phenyleneinone compounds (o-QMs) having a strong aromatization tendency have been widely studied as a nucleophile, a cycloaddition reagent and a synthetic intermediate of an oxa-6 π electrocyclic reaction. The guide group is widely applied to direct C-H bond functionalization reaction catalyzed by transition metal. Hydroxyl genes enjoy their full name for their in situ activation/targeting capabilities in a variety of catalytic systems. To address the problem of dearomatization of the indole backbone in the carbocyclic ring, the present invention contemplates the introduction of an activated/targeted hydroxyl group in the carbocyclic ring to reverse the conventional reaction site in the pyrrole ring.
Disclosure of Invention
The invention provides a method for regioselective dearomatization of a compound containing an indole skeleton, which adopts the following technical scheme:
the selective dearomatization of indole skeleton region is realized by taking a compound (I) and an anthranilic aldehyde compound as reaction substrates through redox neutral hydrogen transfer reaction in a solvent;
the compound (I) is 4-hydroxy carbazole or ethyl (1H-indole-4-acyl) carbonate;
preferably, the compound (I) and the anthranilic aldehyde compound are used in a molar ratio of 1: 1.
On the basis of the scheme, the reaction solvent is hexafluoroisopropanol, and the reaction is carried out at room temperature.
On the basis of the scheme, the structural formula of the anthranilic aldehyde compound is as follows:
wherein the content of the first and second substances,
n is 1 or 3;
R1is any one of hydrogen, methyl, methoxy, fluorine, trifluoromethyl and halogen.
On the basis of the scheme, the specific reaction steps are as follows:
taking 0.1mmol of the compound (I) and 0.1mmol of anthranilic aldehyde compound respectively, adding 2mL of hexafluoroisopropanol as a solvent, and reacting for 8h at room temperature; detecting the reaction by thin-layer chromatography, and carrying out column chromatography to obtain the product.
In the above technical scheme, when the compound (i) is 4-hydroxy carbazole, the chemical reaction formula is as follows:
wherein the content of the first and second substances,
n is 1 or 3;
R1is any one of hydrogen, methyl, methoxy, fluorine, trifluoromethyl and halogen;
the dotted line represents the spatial structure of the compound;
the reaction mechanism is as follows: firstly, HFIP aggregates on 4-hydroxycarbazole 4 and benzaldehyde 1, mediating friedel-crafts alkylation/dehydration/hydrogen migration/cyclization processes; thereby providing the final product 5.
Based on the above scheme, when compound (I) is ethyl (1H-indole-4-acyl) carbonate, the chemical reaction formula is as follows:
wherein the content of the first and second substances,
n is 1 or 3;
R1is any one of hydrogen, methyl, methoxy, fluorine, trifluoromethyl and halogen;
the dotted line represents the spatial structure of the compound;
the reaction mechanism is as follows: first, the carbonyl group of 1 is activated by hydrogen bonding clustering of HFIP, promoting friedel-crafts reaction with indole 6 to give intermediate a. Intermediate a is then dehydrated under the promotion of HFIP to form intermediate B. Next, the electron deficient olefin acts as a hydrogen acceptor, initiating hydrogen transfer to yield intermediate C, accompanied by a decarbonylation process. Subsequently, intramolecular cyclization gave product 7.
The invention has the beneficial effects that:
the invention discloses a method for regioselective dearomatization of a compound containing an indole skeleton by substrate regulation. The method can be used for carrying out the reaction under the condition that hexafluoroisopropanol is used as a solvent and the temperature is 25 ℃. The method realizes the dearomatization of the benzene ring of the indole skeleton for the first time, and realizes the respective dearomatization of the benzene ring and the pyrrole ring of the indole compounds by adjusting the difference of substrates. The method is novel and convenient, simple to operate, wide in substrate applicability and high in atom economy.
The present invention aims to build a redox neutral strategy to assemble more complex molecules in one step, which solves the huge challenges in hydrogen transfer and indole chemistry, with the following advantages: (1) hydrogen migration is initiated by the recovered aromatization driving force of in-situ generation of o-QMs without the need of preparing a hydrogen acceptor in advance; (2) selective dearomatization of the indole skeleton in the carbocyclic and pyrrole rings.
Detailed Description
Terms used in the present invention have generally meanings as commonly understood by one of ordinary skill in the art, unless otherwise specified.
The present invention will be described in further detail with reference to the following data in conjunction with specific examples. The following examples are intended to illustrate the invention and are not intended to limit the scope of the invention in any way.
Reaction conditions for the products described in examples 1-9: taking 0.1mmol of each of 4-hydroxy carbazole and anthranilic aldehyde compounds, adding 2mL of hexafluoroisopropanol as a solvent, and reacting for 8h at room temperature; TLC detection, decompression drying after the material consumption (about 8 hr), silica gel column chromatographic separation, eluting petroleum ether: ethyl acetate was 3: 1. The reaction formula is as follows:
example 1
The chemical formula of the product is as follows: c23H21N2O
Molecular weight: 341.16
Structural formula (xvi):
yield: 73 percent
1H NMR(500MHz,DMSO)δ12.13(s,1H),8.04(d,J＝7.0Hz,1H),7.49(d,J＝7.3Hz,1H),7.32–7.17(m,2H),7.09(t,J＝7.5Hz,1H),7.03(d,J＝7.0Hz,1H),6.93(d,J＝9.9Hz,1H),6.55(t,J＝8.8Hz,2H),5.99(d,J＝9.9Hz,1H),3.79(dd,J＝9.2,6.0Hz,1H),3.49(t,J＝7.7Hz,1H),3.31(s,1H),3.12(d,J＝8.2Hz,1H),2.61(d,J＝15.8Hz,1H),1.97–1.78(m,2H),1.78–1.63(m,1H),1.19(d,J＝10.2Hz,1H)；13C NMR(126MHz,DMSO)δ194.9,146.9,143.2,140.5,137.3,129.3,127.9,124.5,124.0,123.0,120.9,119.6,118.1,115.5,112.7,111.0,110.7,64.7,48.7,47.5,40.5,40.4,40.3,40.3,40.2,40.1,39.9,39.8,39.7,39.5,39.1,27.7,23.5.
Example 2
The chemical formula of the product is as follows: c24H23N2O
Molecular weight: 355.18
Structural formula (xvi):
yield: 60 percent of
1H NMR(500MHz,DMSO)δ12.12(s,1H),8.04(d,J＝6.8Hz,1H),7.50(d,J＝8.2Hz,1H),7.30–7.19(m,2H),6.96–6.90(m,2H),6.38(d,J＝9.5Hz,2H),6.00(d,J＝9.9Hz,1H),3.78(dd,J＝9.6,5.9Hz,1H),3.49(t,J＝7.7Hz,1H),3.28(d,J＝15.6Hz,1H),3.12(dd,J＝16.7,8.8Hz,1H),2.58(d,J＝15.6Hz,1H),2.25(s,3H),1.87(dd,J＝19.3,8.3Hz,2H),1.77–1.68(m,1H),1.21(dd,J＝21.2,11.8Hz,1H)；13C NMR(126MHz,DMSO)δ195.0,146.9,143.1,140.7,137.3,136.7,129.2,124.5,124.0,122.9,120.9,118.0,116.8,116.4,112.7,111.6,110.7,64.7,49.0,47.5,38.8,27.7,23.5,21.8.
Example 3
The chemical formula of the product is as follows: c24H20F3N2O
Molecular weight: 409.15
Structural formula (xvi):
yield: 82 percent of
1H NMR(500MHz,DMSO)δ12.17(s,1H),8.10–7.97(m,1H),7.51(d,J＝7.2Hz,1H),7.32–7.19(m,3H),6.95(d,J＝9.9Hz,1H),6.84(d,J＝7.7Hz,1H),6.76(s,1H),5.96(d,J＝9.9Hz,1H),3.84(dd,J＝9.9,5.8Hz,1H),3.58(t,J＝7.9Hz,1H),3.33(s,1H),3.17(dd,J＝17.0,8.9Hz,1H),2.73(d,J＝16.2Hz,1H),1.97–1.86(m,2H),1.75(dt,J＝10.0,5.6Hz,1H),1.27–1.17(m,1H).；13C NMR(126MHz,DMSO)δ194.4,147.0,143.5,139.8,137.3,130.0,127.4(d,J＝302.4Hz),124.5,124.2,124.1,123.1,120.9,118.5,112.8,111.3(q,J＝3.8Hz),110.7,106.4(d,J＝3.8Hz),64.7,47.9,47.5,38.8,27.6,23.5.
Example 4
The chemical formula of the product is as follows:C23H20ClN2O
molecular weight: 375.13
Structural formula (xvi):
yield: 50 percent of
1H NMR(500MHz,DMSO)δ12.16(s,1H),8.04(d,J＝7.4Hz,1H),7.50(d,J＝7.7Hz,1H),7.31–7.21(m,2H),7.12(s,2H),6.95(d,J＝9.9Hz,1H),6.60–6.53(m,1H),5.96(d,J＝9.9Hz,1H),3.79(dd,J＝9.6,5.9Hz,1H),3.50(t,J＝8.1Hz,1H),3.29(d,J＝16.0Hz,1H),3.12(dd,J＝16.9,8.7Hz,1H),2.66(d,J＝16.0Hz,1H),1.90(dd,J＝16.7,9.0Hz,2H),1.74(dd,J＝11.7,5.8Hz,1H),1.23–1.16(m,1H).；13C NMR(126MHz,DMSO)δ194.5,146.9,142.1,140.0,137.3,128.8,127.4,124.5,124.1,123.1,121.7,120.9,118.8,118.4,112.8,112.2,110.7,64.7,48.2,47.7,38.7,27.6,23.5.
Example 5
The chemical formula of the product is as follows: c24H23N2O2
Molecular weight: 371.18
Structural formula (xvi):
yield: 56 percent
1H NMR(500MHz,DMSO)δ12.09(s,1H),8.11(d,J＝7.6Hz,1H),7.52(d,J＝7.9Hz,1H),7.25(dt,J＝23.9,7.2Hz,2H),7.11(t,J＝8.1Hz,1H),6.40(d,J＝10.3Hz,1H),6.38–6.26(m,3H),4.13–4.05(m,1H),3.70(d,J＝13.0Hz,3H),3.50(t,J＝7.5Hz,1H),3.33–3.21(m,2H),2.93(d,J＝16.4Hz,1H),1.85(dd,J＝19.2,8.6Hz,2H),1.58–1.49(m,1H),1.22(dd,J＝20.0,9.8Hz,1H)；13C NMR(126MHz,DMSO)δ182.0,157.7,153.7,144.3,143.5,137.1,132.1,128.4,124.3,123.6,122.1,121.0,112.3,112.1,106.3,105.2,99.3,63.5,55.7,48.0,39.0,34.1,27.8,23.3.
Example 6
Product ofThe chemical formula is as follows: c23H20FN2O
Molecular weight: 359.16
Structural formula (xvi):
yield: 67 percent
1H NMR(500MHz,DMSO)δ12.18(s,1H),8.05(d,J＝6.9Hz,1H),7.51(d,J＝7.4Hz,1H),7.31–7.23(m,2H),7.12(dd,J＝15.3,7.9Hz,1H),6.97(d,J＝9.9Hz,1H),6.41(dd,J＝15.8,8.2Hz,2H),5.98(d,J＝9.9Hz,1H),3.76(dd,J＝9.6,5.9Hz,1H),3.52(t,J＝7.6Hz,1H),3.16(dd,J＝16.8,8.8Hz,1H),3.08(d,J＝16.2Hz,1H),2.75(d,J＝16.0Hz,1H),1.94–1.83(m,2H),1.75(dd,J＝11.1,5.5Hz,1H),1.23(dd,J＝19.8,10.1Hz,1H)；13C NMR(126MHz,DMSO)δ194.5,161.3(d,J＝239.4Hz),147.0,144.8(d,J＝5.0Hz),139.8,137.3,128.5(d,J＝11.3Hz),124.5,124.1,123.1,121.0,118.5,112.8,110.7,107.2,106.2(d,J＝20.1Hz),102.0(d,J＝22.4Hz),64.2,47.8,47.8,31.4,27.6,23.4.
Example 7
The chemical formula of the product is as follows: c23H20BrN2O
Molecular weight: 419.08
Structural formula (xvi):
yield: 65 percent of
1H NMR(500MHz,DMSO)δ12.20(s,1H),8.05(d,J＝6.8Hz,1H),7.51(d,J＝7.2Hz,1H),7.35–7.21(m,2H),7.05(t,J＝7.9Hz,1H),6.98(d,J＝9.8Hz,1H),6.85(d,J＝7.7Hz,1H),6.61(d,J＝8.0Hz,1H),6.00(d,J＝9.8Hz,1H),3.81–3.73(m,1H),3.50(d,J＝7.2Hz,1H),3.17(t,J＝13.5Hz,2H),2.81(d,J＝16.4Hz,1H),1.99–1.84(m,2H),1.80–1.71(m,1H),1.29–1.18(m,1H)；13C NMR(126MHz,DMSO)δ194.2,147.0,144.8,139.9,137.3,129.1,125.1,124.5,124.1,123.1,120.9,119.1,118.6,112.8,110.7,110.6,64.2,55.4,48.8,47.7,27.6,23.6.
Example 8
The chemical formula of the product is as follows: c25H24FN2O
Molecular weight: 387.19
Structural formula (xvi):
yield: 85 percent of
1H NMR(500MHz,DMSO)δ12.16(s,1H),8.10–8.02(m,1H),7.51(d,J＝7.4Hz,1H),7.31–7.21(m,2H),7.15–7.07(m,1H),6.97(d,J＝9.9Hz,1H),6.67(d,J＝8.4Hz,1H),6.49(t,J＝8.8Hz,1H),6.24(d,J＝9.9Hz,1H),3.53(t,J＝10.3Hz,2H),3.39(dd,J＝16.7,9.1Hz,1H),3.22(d,J＝16.7Hz,1H),2.60(d,J＝16.4Hz,1H),1.85–1.76(m,1H),1.70(d,J＝5.4Hz,1H),1.63–1.50(m,3H),1.31(dd,J＝14.3,7.4Hz,3H)；13C NMR(126MHz,DMSO)δ195.2,161.3(d,J＝240.6Hz),148.9(d,J＝7.2Hz),147.0,140.8,137.3,127.8(d,J＝10.1Hz),124.4,124.0,123.0,120.9,117.4,112.8,111.2,110.5,108.4(d,J＝19.5Hz),103.3(d,J＝22.0Hz),66.2,50.9,50.7,31.7,30.5,29.0,28.5,26.7.
Example 9
The chemical formula of the product is as follows: c25H24ClN2O
Molecular weight: 403.16
Structural formula (xvi):
yield: 78 percent of
1H NMR(500MHz,DMSO)δ12.18(s,1H),8.14–8.00(m,1H),7.51(d,J＝7.2Hz,1H),7.30–7.22(m,2H),7.12(t,J＝8.1Hz,1H),6.98(d,J＝9.9Hz,1H),6.83(d,J＝8.4Hz,1H),6.79(d,J＝7.8Hz,1H),6.24(d,J＝9.9Hz,1H),3.53(dd,J＝15.3,6.4Hz,1H),3.47(dd,J＝9.4,4.7Hz,1H),3.39(dd,J＝20.1,10.8Hz,2H),3.26(d,J＝17.0Hz,1H),2.66(d,J＝17.0Hz,1H),1.85–1.78(m,1H),1.74–1.67(m,1H),1.64–1.57(m,2H),1.57–1.50(m,1H),1.34–1.25(m,3H)；13C NMR(126MHz,DMSO)δ195.0,146.9,140.8,137.3,128.0,124.0,123.0,120.9,117.7,117.4,113.7,112.7,66.0,51.9,50.8,36.7,30.5,28.9,28.4,26.6.
Reaction conditions for the products described in examples 10-16: taking 0.1mmol of ethyl (1H-indole-4-acyl) carbonate and 0.1mmol of anthranilic aldehyde compound respectively, adding 2mL of hexafluoroisopropanol serving as a solvent, and reacting for 8H at room temperature; the reaction formula is as follows:
example 10
The chemical formula of the product is as follows: c19H19N2O
Molecular weight: 291.15
Structural formula (xvi):
yield: 64 percent
1H NMR(500MHz,DMSO)δ9.72(s,1H),7.77(s,1H),7.19(t,J＝7.6Hz,1H),7.14–7.04(m,2H),7.02(d,J＝7.0Hz,1H),6.75(d,J＝8.0Hz,1H),6.57(d,J＝6.8Hz,2H),4.45–4.31(m,1H),3.86(d,J＝16.2Hz,1H),3.42(s,1H),3.27(q,J＝7.9Hz,1H),2.45(d,J＝16.2Hz,1H),1.86(s,2H),1.54(d,J＝5.7Hz,1H),0.92–0.80(m,1H)；13C NMR(126MHz,DMSO)δ175.4,157.2,154.1,144.2,129.5,128.7,127.9,125.1,119.7,115.8,114.4,112.7,111.4,59.4,58.0,47.5,32.4,27.7,23.2.
Example 11
The chemical formula of the product is as follows: c19H18ClN2O
Molecular weight: 325.11
Structural formula (xvi):
yield: 81 percent of
1H NMR(500MHz,DMSO)δ9.75(s,1H),7.76(s,1H),7.19(t,J＝7.8Hz,1H),7.16–7.02(m,3H),6.75(d,J＝8.1Hz,1H),6.55(d,J＝8.6Hz,1H),4.37(dd,J＝9.6,6.1Hz,1H),3.81(d,J＝16.4Hz,1H),3.42(d,J＝10.4Hz,1H),3.24(q,J＝8.3Hz,1H),2.48(d,J＝16.6Hz,1H),1.86(d,J＝5.1Hz,2H),1.58–1.49(m,1H),0.91–0.80(m,1H)；13C NMR(126MHz,DMSO)δ175.0,157.3,154.1,143.1,129.7,128.2,127.5,124.8,121.7,119.1,114.5,112.7,112.6,59.4,57.6,47.7,32.1,27.8,23.3.
Example 12
The chemical formula of the product is as follows: c19H18BrN2O
Molecular weight: 369.06
Structural formula (xvi):
yield: 62 percent of
1H NMR(500MHz,DMSO)δ9.75(s,1H),7.76(s,1H),7.26–7.17(m,3H),7.06(d,J＝7.5Hz,1H),6.75(d,J＝8.1Hz,1H),6.51(d,J＝8.6Hz,1H),4.36(dd,J＝9.8,6.0Hz,1H),3.81(d,J＝16.4Hz,1H),3.42(td,J＝9.0,3.5Hz,1H),3.23(q,J＝8.5Hz,1H),2.48(d,J＝16.8Hz,1H),1.91–1.82(m,2H),1.57–1.47(m,1H),0.91–0.81(m,1H)；13C NMR(126MHz,DMSO)δ174.5,156.8,153.6,142.9,130.4,129.9,129.2,124.3,121.7,114.0,112.6,112.3,106.1,58.9,57.0,47.2,31.6,27.3,22.8.
Example 13
The chemical formula of the product is as follows: c19H18FN2O
Molecular weight: 309.14
Structural formula (xvi):
yield: 76 percent of
1H NMR(500MHz,DMSO)δ9.78(s,1H),7.80(s,1H),7.21(t,J＝7.8Hz,1H),7.16–7.09(m,1H),7.07(d,J＝7.5Hz,1H),6.76(d,J＝8.1Hz,1H),6.42(t,J＝8.5Hz,2H),4.33(dd,J＝9.3,6.3Hz,1H),3.61(d,J＝16.7Hz,1H),3.43(d,J＝8.0Hz,1H),3.32–3.25(m,1H),2.55(s,1H),1.86(s,2H),1.59–1.50(m,1H),0.87(t,J＝9.5Hz,1H)；13C NMR(126MHz,DMSO)δ174.9,160.9(d,J＝240.7Hz),159.9,157.3,154.2,145.9,145.8(d,J＝8.8Hz),129.8,128.7(d,J＝11.3Hz),124.7,114.5,112.8,107.5,106.3(d,J＝20.3Hz),102.3(d,J＝22.2Hz),58.9,57.2,47.8,27.7,25.1,23.2.
Example 14
The chemical formula of the product is as follows: c19H18ClN2O
Molecular weight: 325.11
Structural formula (xvi):
yield: 76 percent of
1H NMR(500MHz,DMSO)δ9.81(s,1H),7.82(s,1H),7.21(t,J＝7.9Hz,1H),7.10(dd,J＝17.9,7.9Hz,2H),6.78(d,J＝8.1Hz,1H),6.68(d,J＝7.8Hz,1H),6.55(d,J＝8.2Hz,1H),4.33(dd,J＝9.6,6.2Hz,1H),3.67(d,J＝17.0Hz,1H),3.40(dt,J＝10.5,7.2Hz,1H),3.31(dd,J＝16.8,8.2Hz,1H),2.60(d,J＝17.0Hz,1H),1.93–1.76(m,2H),1.62–1.49(m,1H),0.93–0.79(m,1H)；13C NMR(126MHz,DMSO)δ175.0,157.3,154.2,145.7,133.4,129.9,128.8,124.6,117.1,116.2,114.6,112.8,110.4,58.8,57.9,47.7,30.2,27.7,23.3.
Example 15
The chemical formula of the product is as follows: c19H18BrN2O
Molecular weight: 369.06
Structural formula (xvi):
yield: 78 percent of
1H NMR(500MHz,DMSO)δ9.81(s,1H),7.83(s,1H),7.22(t,J＝7.9Hz,1H),7.11–7.01(m,2H),6.85(d,J＝7.8Hz,1H),6.77(d,J＝8.1Hz,1H),6.60(d,J＝8.2Hz,1H),4.33(dd,J＝9.5,6.3Hz,1H),3.65(d,J＝16.9Hz,1H),3.42(dd,J＝11.9,8.7Hz,1H),3.34–3.28(m,1H),2.55(d,J＝16.9Hz,1H),1.92–1.83(m,2H),1.57(dd,J＝10.6,5.2Hz,1H),0.92–0.82(m,1H)；13C NMR(126MHz,DMSO)δ174.8,157.1,154.0,145.7,129.7,129.1,124.4,124.3,119.1,118.4,114.4,112.6,110.8,58.7,58.0,47.5,33.0,27.5,23.2.
Example 16
The chemical formula of the product is as follows: c21H22BrN2O
Molecular weight: 396.08
Structural formula (xvi):
yield: 76 percent of
1H NMR(500MHz,DMSO)δ9.75(s,1H),7.92(s,1H),7.24–7.15(m,2H),7.11(d,J＝2.2Hz,1H),7.05(d,J＝7.4Hz,1H),6.71(dd,J＝14.1,8.5Hz,2H),4.37–4.28(m,2H),3.76(d,J＝16.3Hz,1H),3.40(t,J＝4.8Hz,1H),2.35(d,J＝16.4Hz,1H),1.72(dd,J＝12.1,6.1Hz,1H),1.69–1.61(m,1H),1.41(ddd,J＝24.7,13.6,5.4Hz,4H),1.31(d,J＝8.6Hz,1H),0.94(dd,J＝9.2,4.6Hz,1H)；13C NMR(126MHz,DMSO)δ174.9,156.7,153.3,145.9,130.3,129.8,129.2,125.2,122.8,114.3,113.9,112.2,106.8,60.5,59.6,49.3,31.6,29.2,29.1,28.8,25.7.
The above-mentioned embodiments only provide several embodiments of the present invention, but should not be construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (8)
1. A method for regioselective dearomatization of a compound containing an indole skeleton is characterized in that a compound (I) and an anthranilic aldehyde compound are used as reaction substrates, and the regioselective dearomatization of the indole skeleton is realized through a redox neutral hydrogen transfer reaction in a solvent;
the compound (I) is 4-hydroxy carbazole or ethyl (1H-indole-4-acyl) carbonate.
2. The process according to claim 1 for the regioselective dearomatization of compounds containing an indole skeleton, characterized in that the anthranilaldehyde compounds have the following structural formula:
wherein the content of the first and second substances,
n is 1 or 3;
R1is any one of hydrogen, methyl, methoxy, fluorine, trifluoromethyl and halogen.
3. The process for the regioselective dearomatization of indole-skeleton-containing compounds according to claim 1 or 2, characterized in that the solvent is hexafluoroisopropanol.
4. The process for the regioselective dearomatization of compounds containing an indole skeleton according to claim 3, characterized in that the compound (I) is used in a molar ratio to the anthranilic aldehyde compound of 1: 1.
5. The process of selective dearomatization of a zone containing an indole skeleton compound according to claim 3, characterized in that the reaction temperature is room temperature.
6. The process for the selective dearomatization of a zone containing indole skeleton compounds according to any of claims 1 to 5, characterized by the steps of:
taking 0.1mmol of the compound (I) and 0.1mmol of anthranilic aldehyde compound respectively, adding 2mL of solvent, and reacting for 8h at room temperature.
7. The process for the regioselective dearomatization of indole skeleton-containing compounds according to claim 6, wherein, when the compound (I) is 4-hydroxycarbazole, the chemical reaction is represented by the following formula:
wherein the content of the first and second substances,
n is 1 or 3;
R1is any one of hydrogen, methyl, methoxy, fluorine, trifluoromethyl and halogen;
the dotted lines represent spatial structures.
8. The process for the regioselective dearomatization of compounds having an indole skeleton according to claim 6, wherein when compound (I) is ethyl (1H-indol-4-yl) carbonate, the chemical reaction is represented by the following formula:
wherein the content of the first and second substances,
n is 1 or 3;
R1is any one of hydrogen, methyl, methoxy, fluorine, trifluoromethyl and halogen;
the dotted lines represent spatial structures.
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| CHUNQI CHEN ET AL.: "Efficient construction of tetrahydroquinolines via fluorinated alcohol mediated cascade [1,5]-hydride transfer/cyclization", 《ORG. BIOMOL. CHEM.》 * |
| YAO-BIN SHEN ET AL.: "Redox-Neutral Cascade Dearomatization of Indoles via Hydride Transfer: Divergent Synthesis of Tetrahydroquinoline-Fused Spiroindolenines", 《J. ORG. CHEM.》 * |
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