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Method for synthesizing chiral oxygen-containing eight-membered ring compound through palladium-catalyzed asymmetric allyl cycloaddition reaction

An allyl ring, addition reaction technology, applied in asymmetric synthesis, organic chemical methods, chemical instruments and methods, etc., can solve the problems of no reports, etc., and achieve convenient and simple operation, high yield, and mild reaction conditions Effect

Inactive Publication Date: 2021-11-02
SHANDONG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, there is still no report on the asymmetric [4+4] cycloaddition reaction to construct oxygen-containing eight-membered ring compounds

Method used

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  • Method for synthesizing chiral oxygen-containing eight-membered ring compound through palladium-catalyzed asymmetric allyl cycloaddition reaction
  • Method for synthesizing chiral oxygen-containing eight-membered ring compound through palladium-catalyzed asymmetric allyl cycloaddition reaction
  • Method for synthesizing chiral oxygen-containing eight-membered ring compound through palladium-catalyzed asymmetric allyl cycloaddition reaction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] (9S,10S)-9-(3,5-Dichlorophenyl)-7-methylene-10-((E)-styryl)-7,8,9,10-tetrahydro-6H- Synthesis of [1,3]bisoxazol[4',5':4,5]benzo[1,2-b]oxooctanoic acid-9-carboxylic acid methyl ester (Ⅲaa)

[0046] The reaction scheme is as follows:

[0047]

[0048] The operation steps are as follows:

[0049] Under nitrogen protection, add Pd to a dry 5 mL reaction vial 2 (dba) 3 · CHCl 3 (0.005mmol, 5.2mg), chiral ligand (0.022mmol, 12.7mg) and 2mL of ethylbenzene, stirred at room temperature for 15 minutes, then transferred the resulting mixture to a 3-(3,5-dichlorophenyl )-5-methylene-2-oxytetrahydro-2H-pyran-3-carboxylic acid methyl ester Ia (63.0mg, 0.2mmol), (E)-6-((E)-3-phenylene Alkenyl)-benzo[d][1,3]dioxa-5-(6H)-one Ⅱa (50.4mg, 0.2mmol) and In a flask of molecular sieves (300mg), the reaction mixture was stirred and reacted at -20°C for 16h under nitrogen protection; the reaction solution was separated and purified by silica gel column chromatography (eluent: EA / PE=0...

Embodiment 2

[0056] (9S,10S)-9-(3,5-Dibromophenyl)-7-methylene-10-((E)-styryl)-7,8,9,10-tetrahydro-6H- Synthesis of [1,3]bisoxazol[4',5':4,5]benzo[1,2-b]oxoctanoic acid-9-carboxylate methyl ester (Ⅲba)

[0057] The reaction scheme is as follows:

[0058]

[0059] The operation steps are as follows:

[0060] Under nitrogen protection, add Pd to a dry 5 mL reaction vial 2 (dba) 3 · CHCl 3 (0.005mmol, 5.2mg), chiral ligand (0.022mmol, 12.7mg) and 2mL ethylbenzene, stirred at room temperature for 15 minutes, then transferred the resulting mixture to a 3-(3,5-dibromophenyl )-5-methylene-2-oxytetrahydro-2H-pyran-3-carboxylic acid methyl ester Ⅰb (80.8mg, 0.2mmol), (E)-6-((E)-3-phenylene Alkenyl)-benzo[d][1,3]dioxa-5-(6H)-one Ⅱa (50.4mg, 0.2mmol) and In a flask of molecular sieves (300mg), the reaction mixture was stirred and reacted at -20°C for 16h under nitrogen protection; the reaction solution was separated and purified by silica gel column chromatography (eluent: EA / PE=0.03-0.1:1,...

Embodiment 3

[0067] (9S,10S)-9-(4-Trifluoromethylphenyl)-7-methylene-10-((E)-styryl)-7,8,9,10-tetrahydro-6H- Synthesis of [1,3]bisoxazol[4',5':4,5]benzo[1,2-b]oxoctanoic acid-9-carboxylic acid methyl ester (Ⅲca)

[0068] The reaction scheme is as follows:

[0069]

[0070] The operation steps are as follows:

[0071] Under nitrogen protection, add Pd to a dry 5 mL reaction vial 2 (dba) 3 · CHCl 3 (0.005mmol, 5.2mg), chiral ligand (0.022mmol, 12.7mg) and 2mL ethylbenzene, stirred at room temperature for 15 minutes, then transferred the resulting mixture to a 3-(4-trifluoromethylphenyl )-5-methylene-2-oxytetrahydro-2H-pyran-3-carboxylic acid methyl ester Ic (62.8mg, 0.2mmol), (E)-6-((E)-3-phenylene Alkenyl)-benzo[d][1,3]dioxa-5-(6H)-one Ⅱa (50.4mg, 0.2mmol) and In a flask of molecular sieves (300mg), the reaction mixture was stirred and reacted at -20°C for 16h under nitrogen protection; the reaction solution was separated and purified by silica gel column chromatography (eluent: EA...

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Abstract

The invention provides a method for synthesizing a chiral oxygen-containing eight-membered ring compound through palladium-catalyzed asymmetric allyl cycloaddition reaction. The method comprises the following steps: in a solvent, under the catalysis of a palladium catalysis system, carrying out [4 + 4] cycloaddition reaction on a gamma-methylene-delta-valerolactone compound I and an o-quinone methylate II to obtain the chiral oxygen-containing eight-membered ring compound III. The palladium catalysis system is composed of a palladium catalyst and a chiral ligand, and the chiral ligand has a structure as shown in a formula IV. The oxygen-containing eight-membered ring compound constructed through the palladium-catalyzed asymmetric allyl cycloaddition reaction has the advantages that the operation is convenient and simple, the yield is high, the reaction raw materials are low in price and easy to obtain, the catalyst cost is low, the substrate application range is wide, the diastereoselectivity is good, the para-selectivity is high and the like.

Description

technical field [0001] The invention relates to a method for synthesizing a chiral oxygen-containing eight-membered ring compound through palladium-catalyzed asymmetric allyl cycloaddition reaction, belonging to the technical field of organic synthesis. Background technique [0002] Chiral oxygen-containing eight-membered ring structures widely exist in active natural products and drug molecules, such as indole alkaloid Decursivine with antimalarial activity, dibenzocyclooctadiene-type lignans with good antiulcer activity (Isoschizandrin), and retapamulin, an antibacterial drug approved by the FDA. However, obtaining chiral oxygen-containing eight-membered ring structure compounds through natural product isolation or biosynthesis is not only time-consuming and labor-intensive, but also expensive, and the yield is low, which has great limitations. In traditional synthetic methods, due to the unfavorable enthalpy and entropy effects and cross-ring interactions during the synt...

Claims

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Application Information

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IPC IPC(8): C07D493/04C07B53/00B01J31/22
CPCC07D493/04C07B53/00B01J31/186C07B2200/07B01J2531/824
Inventor 刘继田李孝训王训华吕瑞峰
Owner SHANDONG UNIV
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