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2,3-disubstituted boron-containing indole compounds with high enantioselectivity and preparation method of 2,3-disubstituted boron-containing indole compounds

An enantioselective, disubstituted technology, applied in the field of high enantioselective 2,3-disubstituted boron-containing indole compounds and their preparation, can solve the problems that have not been reported in the literature

Inactive Publication Date: 2018-06-22
NORTHEAST NORMAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

So far, the reaction of 2,3-disubstituted indoles with highly enantioselective borylation has not been reported in the literature

Method used

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  • 2,3-disubstituted boron-containing indole compounds with high enantioselectivity and preparation method of 2,3-disubstituted boron-containing indole compounds
  • 2,3-disubstituted boron-containing indole compounds with high enantioselectivity and preparation method of 2,3-disubstituted boron-containing indole compounds
  • 2,3-disubstituted boron-containing indole compounds with high enantioselectivity and preparation method of 2,3-disubstituted boron-containing indole compounds

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preparation example Construction

[0042] The present invention also provides a method for preparing highly enantioselective 2,3-disubstituted boron-containing indole compounds, the method comprising:

[0043] Under the protection of nitrogen, add catalyst, ligand (S, S)-Ph-BPE, alkali and solvent into the reaction vessel, and stir at room temperature. The stirring time is preferably 8-15 min, more preferably 10 min, and then add the coupling The pinacol borate is stirred continuously, the stirring time is preferably 8-15 min, more preferably 10 min, and then functionalized o-iminostyrene is added, preferably after stirring for 5 min, and then methanol is added to react at room temperature. The reaction time is 6-8h, and the completion of the reaction is detected by TLC. Then, after extraction, the organic phases are combined, dried with anhydrous sodium sulfate, filtered with suction, and distilled under reduced pressure to remove the organic solvent, and finally subjected to silica gel column chromatography to ob...

Embodiment 1

[0051]

[0052] Under the protection of nitrogen, add cuprous chloride (2mol%), (S,S)-Ph-BPE (3mol%) and NaOtBu (0.30mmol) to a 10mL pressure-resistant sealed tube with a stir bar, and then add tetrahydrofuran ( 2mL), stirring at room temperature for 10 min. After stirring for 10 min, add pinacol diboronic acid (0.30 mmol) to the system, continue to stir for 10 min, then add 1a (0.20 mmol), stir for 5 min, then add methanol (0.20 mmol), leave the reaction at room temperature, stir for 8 h, and use TLC detects the completion of the reaction. The reaction was quenched with water (10ml), extracted with dichloromethane (3×10mL), the organic phases were combined, dried with anhydrous sodium sulfate, filtered with suction, and distilled under reduced pressure to remove the organic solvent, and finally subjected to silica gel column chromatography to obtain 2,3 -Disubstituted indole compound 2a, with a yield of 96%.

[0053] figure 1 For the 2,3-disubstituted indole 2a prepared in Exa...

Embodiment 2

[0057] Replace 1a in the example with 1b, and other conditions are the same as in Example 1, to obtain 2,3-disubstituted indole compound 2b with an ee value of 98%. .

[0058]

[0059] The hydrogen nuclear magnetic spectrum data, the carbon nuclear magnetic spectrum data and the high performance liquid chromatography data of the product 2b prepared in Example 2 are as follows:

[0060] White solid.NMR Spectroscopy: 1 H NMR(500MHz, CDCl 3 )δ=7.17(d,J=8.0Hz,3H), 7.07(d,J=8.0Hz,2H), 7.04(d,J=7.5Hz,1H), 6.72(t,J=7.5Hz,1H) ,6.66(d,J=7.5Hz,1H), 4.93(d,J=8.5Hz,1H),4.01(s,1H),3.66(q,J 12 =8.5Hz, J 13 = 15.5Hz, 1H), 2.31 (s, 3H), 1.20 (d, J = 5.0 Hz, 12H), 0.90-0.85 (m, 1H), 0.58-0.54 (m, 1H); 13 C NMR(125MHz, CDCl 3 )δ=150.66,137.82,136.88,134.19,128.82,127.46,127.26,124.28,118.53,108.60,83.60,67.87,42.35,25.02,24.80,21.07.Mass Spectrometry:HRMS(ESI-TOF)(m / z): Calcd for C 22 H 29 BNO 2 ([M+H] + ),350.2290,found,350.2290.[α] D 19 =+15.8,(c=1,CHCl 3 ).HPLC analysis(AD-H,5%IPA / hexane,1mL / min...

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Abstract

The invention provides 2,3-disubstituted boron-containing indole compounds with high enantioselectivity and a preparation method of the 2,3-disubstituted boron-containing indole compounds, and belongsto the technical field of organic synthesis chemistry. The general structural formula of the compounds are shown in formula I. The invention also provides a preparation method of the 2,3-disubstituted boron-containing indole compounds with high enantioselectivity. The method comprises the following steps: adding a catalyst, a ligand (S, S)-Ph-BPE, base and a solvent to a reaction vessel, performing stirring at the room temperature, then adding bis(pinacolato)diboron for continuous stirring, adding functionalized o-iminostyrene for a reaction at the room temperature to obtain the 2,3-disubstituted boron-containing indole compounds. The 2,3-disubstituted boron-containing indole compounds have high enantioselectivity, and high-performance liquid chromatography experiments prove that the ee value of the compound can reach the highest value of 99%.

Description

Technical field [0001] The invention belongs to the technical field of organic synthetic chemistry, and specifically relates to a high enantioselective 2,3-disubstituted boron-containing indole compound and a preparation method thereof. Background technique [0002] Optically active 2,3-disubstituted indole has a very wide range of applications in organic synthesis and medicinal chemistry. This heterocyclic structure exists in many natural products and pharmaceutical active molecules. In addition, this kind of chiral heterocyclic framework is also the key basis for drug discovery, and many natural molecular libraries are based on the indole structural framework. Therefore, the asymmetric synthesis strategy of nitrogen heterocyclic structure has been studied and reported one after another. Among these methods, The acid-catalyzed asymmetric hydrogenation of indole is perhaps the most important method. Although this method is very attractive, the need to provide a strong acid env...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F5/02C07F5/04
CPCC07B2200/07C07F5/025C07F5/04
Inventor 熊涛张前张鸽
Owner NORTHEAST NORMAL UNIVERSITY
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