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Method for synthesizing chiral aminophosphonates through organocatalytic Friedel-Crafts reactions

A technology of amino phosphonate and Friedel-Crafts reaction, applied in organic chemistry methods, organic chemistry, chemical instruments and methods, etc., can solve problems such as abundant nucleophilic reagents, achieve simple and practical reaction operation, complete reaction, and excellent reaction conditions mild effect

Inactive Publication Date: 2018-06-05
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

It is worth mentioning that in the nucleophilic addition strategy, the nucleophiles are limited to acetone, acetylcyanide, nitromethane and aryl boronic acid, etc., in order to meet the synthesis needs of various quaternary carbon-centered chiral aminophosphonates, Nucleophiles still need to be further enriched

Method used

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  • Method for synthesizing chiral aminophosphonates through organocatalytic Friedel-Crafts reactions
  • Method for synthesizing chiral aminophosphonates through organocatalytic Friedel-Crafts reactions
  • Method for synthesizing chiral aminophosphonates through organocatalytic Friedel-Crafts reactions

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Experimental program
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Effect test

Embodiment 1

[0024] Embodiment 1: optimization of conditions

[0025] In the air, add five-membered cyclic imine phosphonate 2a (33mg, 0.1mmol), chiral phosphoric acid (10mol% of the amount of substrate in formula 1) and organic solvent (2mL) to the reaction flask successively, stir at room temperature for ten minutes, then added indole 3 (35mg, 0.3mmol), reacted at 30°C, and monitored the progress of the reaction by TLC. After the reaction, the pure product was obtained by direct column chromatography separation. The reaction formula and chiral phosphoric acid structure are as follows:

[0026]

[0027] The yield is the separation yield, and the enantiomeric excess of the product is determined by chiral liquid chromatography, see Table 1 for details.

[0028] Table 1. Asymmetric addition reaction of imidophosphonate 2a with indolea

[0029]

[0030]

Embodiment 2

[0031] Example 2: Chiral Phosphoric Acid Catalyzed Friedel-Crafts Reaction Synthesis of Various Chiral Amino Phosphonates 4

[0032] In the air, add five-membered cyclic imine phosphonate 2 (0.1 mmol), chiral phosphoric acid (5 mol% of substrate consumption in formula 1) and organic solvent (2 mL) to the reaction flask successively, stir at room temperature for ten minutes, Then add indole 3 (35mg, 0.3mmol), react at 30°C, and monitor the progress of the reaction by TLC. After the reaction, the pure product was obtained by direct column chromatography separation. The reaction formula and chiral phosphoric acid structure are as follows:

[0033]

[0034] The yield is the separation yield, and the enantiomeric excess of the product is determined by chiral liquid chromatography, see Table 2.

[0035] Table 2. Chiral phosphoric acid catalyzed Friedel-Crafts reaction for the synthesis of various chiral aminophosphonates4a

[0036]

[0037]

[0038] (R)-diisopropyl

[00...

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Abstract

The invention provides a method for synthesizing chiral aminophosphonates through organocatalytic Friedel-Crafts reactions. An organic catalyst used in the method is chiral phosphoric acid. Corresponding chiral aminophosphonates with quaternary carbon centers can be prepared by catalyzing asymmetric Friedel-Crafts reactions of a series of imidophosphonates with indole, and enantiomeric excess is up to 98%. The method provided by the invention is simple, practical and feasible; the catalyst is commercially available; and reaction conditions are mild. In addition, since the chiral aminophosphonates is synthesized through the asymmetric Friedel-Crafts reactions, high enantioselectivity and good yield are realized, and the reactions have the advantages of atomic economy, environmental friendliness and the like.

Description

technical field [0001] The invention relates to a method for synthesizing chiral amino phosphonate by catalyzing the asymmetric Friedel-Crafts reaction of imine phosphonate and indole with high enantioselectivity in a homogeneous system of chiral phosphoric acid. Background technique [0002] Optically active aminophosphonic acids have structural similarities with amino acids, and also have a wide range of physiological activities, and can be used as enzyme inhibitors, antifungal agents, antibacterial agents and anticancer agents (Reference 1: (a) Senten, K.; L.; Van der Veken, P.; De Meester, I.; Lambeir, A.-M.; Scharpé, S.; L.; Diel, P.J. Phosphorous, Sulfur Silicon Relat. Elem. 1994, 90, 259. (c) Grembecka, J.; Mucha, A.; Cierpicki, T. Kafarski, P.J. Med. Chem. Yao, G.; Ye, M.; Huang, R.; Li, Y.; Pan, Y.; .). Based on this, the asymmetric synthesis of aminophosphonic acid and its derivatives has attracted extensive attention of researchers. According to the different...

Claims

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Application Information

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IPC IPC(8): C07F9/6558C07B53/00
CPCC07F9/65583C07B53/00C07B2200/09
Inventor 周永贵严忠高翔孙蕾
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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