CN112876401A - Synthesis method of chiral 3-allylindole compound - Google Patents
Synthesis method of chiral 3-allylindole compound Download PDFInfo
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- CN112876401A CN112876401A CN202110096648.3A CN202110096648A CN112876401A CN 112876401 A CN112876401 A CN 112876401A CN 202110096648 A CN202110096648 A CN 202110096648A CN 112876401 A CN112876401 A CN 112876401A
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- indole
- allylindole
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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Abstract
The invention discloses a method for synthesizing a chiral 3-allyl indole compound, which comprises the following specific steps: indole and vinyl cyclopropane are used as reaction raw materials, tetrahydrofuran is used as a reaction solvent, chiral iridium, a chiral ligand and cuprous trifluoromethanesulfonate are used as catalysts, the materials are stirred and reacted at the temperature of 50 ℃, TLC (thin layer chromatography) is used for tracking the reaction to be complete, and the chiral 3-allyl indole compound is prepared through filtration, concentration and purification. According to the synthesis method of the chiral 3-allylindole compound, chiral iridium, a chiral ligand and cuprous trifluoromethanesulfonate are used as catalysts, so that extremely high enantioselectivity and atom economy are obtained, and the method is environment-friendly and pollution-free; the method can realize the synthesis of the chiral 3-allylindole compound in one step, has mild reaction process, safety, reliability and low cost, and is suitable for industrial large-scale production; the synthesis method adopts various substrates as reactants, obtains products with various structures, and has high yield.
Description
Technical Field
The invention relates to the field of organic chemical synthesis, in particular to a synthetic method of a chiral 3-allyl indole compound.
Background
The chiral 3-allyl indole compound has wide application prospect in the field of life science, not only is the core skeleton of some natural alkaloids, but also is a key intermediate for synthesizing a plurality of natural products. The existing technology for synthesizing the 3-allylindole compound has the disadvantages of drastic reaction conditions, more steps, lower enantioselectivity, easy misoperation, even safety accidents, high cost and low yield.
Disclosure of Invention
In order to solve the problems, the invention aims to provide a synthesis method of a chiral 3-allylindole compound, which has the advantages of mild reaction conditions, simple steps, safety, reliability, low cost, and extremely high yield and enantioselectivity.
In order to achieve the purpose, the invention adopts the technical scheme that: (the contents are not to be copied here as in the claims)
According to the synthesis method of the chiral 3-allylindole compound, chiral iridium, a chiral ligand and cuprous trifluoromethanesulfonate are used as catalysts, so that extremely high enantioselectivity and atom economy are obtained, and the method is environment-friendly and pollution-free; the method can realize the synthesis of the chiral 3-allylindole compound in one step, has mild reaction process, safety, reliability and low cost, and is suitable for industrial large-scale production; the synthesis method adopts various substrates as reactants, obtains products with various structures, and has high yield.
Detailed Description
The present invention will be described in further detail with reference to examples.
In the examples described below, unless otherwise indicated, the experimental procedures described are generally carried out according to conventional conditions or conditions recommended by the manufacturer.
Example 1
The synthetic route of chiral 3-allylindole compound 3 is as follows:
0.1mmol of indole 1a compound and 0.2 mmol of vinylcyclopropane 2a compound are added into 1ml of tetrahydrofuran as reactants, 0.005 mmol of [ Ir (cod) Cl ]2, 0.01 mmol of ligand and 0.01 mmol of cuprous trifluoromethanesulfonate as catalysts, the mixture reacts at 50 ℃ for 36 hours, the TLC tracking reaction is completed, and the mixture is concentrated and then separated by silica gel column chromatography (eluent is mixed solution of petroleum ether and acetone in a volume ratio of 10: 1) to obtain chiral 3-allylindole derivative 3 aa.
The structural characterization data for product 3aa in example 1 is as follows:
72％yield(16.9mg)；yellow solid；m.p.39-40℃；[α]D 20＝-6.1(c 0.33,acetone)；1H NMR(400MHz,CDCl3)δ8.17(s,1H),7.61(d,J＝7.4Hz,1H),7.41(d,J＝8.2Hz,1H),7.28–7.21(m,1H),7.19–7.12(m,1H),7.09(d,J＝2.8Hz,1H),6.15–5.99(m,1H),5.37–5.19(m,2H),3.97–3.85(m,1H),3.64–3.54(m,1H),2.69–2.43(m,2H)；13C NMR(100MHz,CDCl3)δ138.0,136.8,125.6,123.0,122.1,120.2,119.2,117.0,114.0,112.8,112.7,111.8,38.9,35.4,21.1；IR(KBr):3402,3083,2901,1579,1447,1228,937,786cm-1；HRMS(ESI-TOF)m/z:[M-H]-Calcd for C15H12N3 234.1036,found m/z 234.1035；The enantiomeric ratio:95:5,determined by HPLC(Daicel Chiralpak IB,hexane/isopropanol＝70/30,flow rate 1.0mL/min,T＝30℃,254nm):tR＝9.650min(minor),tR＝6.847min(major).
examples 2 to 16
The reaction synthetic route is shown as follows:
the synthesis of examples 2-16 was the same as in example 1, except that indoles of different structures were used as starting materials.
The reaction raw materials and yields are shown in table 1:
TABLE 1 reaction starting materials and yields for examples 2-16
Note: in Table 1, er is the enantiomeric ratio.
Examples 16 to 23
The reaction synthetic route is shown as follows:
the synthesis of examples 16-23 was carried out in the same manner as in example 1, except that indole having a different structure and vinylcyclopropane b (the specific structure of which is shown as 2b in the synthesis scheme) were used as starting materials.
The reaction raw materials and yields are shown in table 2:
TABLE 2 reaction starting materials and yields for examples 17-23
Note: in Table 2, er is the enantiomeric ratio.
As can be seen from tables 1 and 2, the method of the present invention not only can realize the synthesis of chiral 3-allylindole compounds in one step, and obtain extremely high enantioselectivity and excellent yield, but also has the advantages of high atom economy, environmental friendliness, wide application range, easily available raw materials, simple and safe operation, mild reaction conditions, short reaction time, simple post-treatment, and diversified product structures, thereby having great implementation value and potential social and economic benefits.
Claims (4)
1. A synthetic method of a chiral 3-allyl indole compound is characterized by comprising the following specific steps:
indole and vinyl cyclopropane are used as reaction raw materials, tetrahydrofuran is used as a reaction solvent, chiral iridium, a chiral ligand and cuprous trifluoromethanesulfonate are used as catalysts, the materials are stirred and reacted at the temperature of 50 ℃, TLC tracks the reaction to be complete, and the chiral 3-allyl indole compound is prepared after filtration, concentration and purification;
the molar ratio of the indole to the vinylcyclopropane to the chiral iridium to the chiral ligand to the cuprous trifluoromethanesulfonate is 1:2:0.05:0.1: 0.1; the dosage ratio of the indole to the tetrahydrofuran is 0.1 mmol: 1 mL;
the chemical structure of the chiral 3-allyl indole compound is shown as formula 1:
in the formula 1, R is selected from one of hydrogen, C1-C3 alkyl, C1-C3 alkoxy, halogen and nitro; r1One selected from hydrogen, C1-C3 alkyl and benzene; r2One selected from hydrogen, C1-C3 ester group and cyano;
the structural formula of the indole is shown in the specification
Wherein R is selected from one of hydrogen, C1-C3 alkyl, C1-C3 alkoxy, halogen and nitro; r1One selected from hydrogen, C1-C3 alkyl and benzene;
the structural formula of the vinyl cyclopropane is shown in the specification
In the formula, R2One selected from hydrogen, C1-C3 ester group and cyano.
2. The method for synthesizing chiral 3-allylindole compound according to claim 1, wherein the chiral ligand is selected from one or two of the following ligands;
3. the method of claim 2, wherein the chiral ligand is a chiral 3-allylindole compoundStructure is as
4. The method for synthesizing chiral 3-allylindole compound according to any of claims 1-3, wherein the purification is silica gel column chromatography, and the eluent is a mixture of petroleum ether and acetone, wherein the volume ratio of petroleum ether to acetone is 10: 1.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202110096648.3A CN112876401A (en) | 2021-01-25 | 2021-01-25 | Synthesis method of chiral 3-allylindole compound |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202110096648.3A CN112876401A (en) | 2021-01-25 | 2021-01-25 | Synthesis method of chiral 3-allylindole compound |
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2021
- 2021-01-25 CN CN202110096648.3A patent/CN112876401A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| FENG SHI等: "Regio- and enantioselective ring-opening reaction of vinylcyclopropanes with indoles under cooperative catalysis", 《ORG. CHEM. FRONT.》, vol. 8, 17 August 2020 (2020-08-17), pages 2 - 3 * |
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