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Method for preparing optically-active alpha-amino phosphonate derivatives by chiral spiro phosphate catalysis

A technology of amino phosphonate and spirocyclic phosphoric acid, which is applied in the field of chiral preparation of phosphorus-containing compounds, can solve the problems that chiral catalysts cannot be recycled, enantioselectivity is not very high, and reaction substrates are limited, etc. Mild conditions, high purity of optical activity, and good stability

Inactive Publication Date: 2013-05-01
ZHEJIANG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

There are still some limitations in the above methods, for example, the chiral catalyst cannot be recycled, or the enantioselectivity is not very high, or the catalyst is very expensive, or the reaction substrate is very limited, etc.

Method used

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  • Method for preparing optically-active alpha-amino phosphonate derivatives by chiral spiro phosphate catalysis
  • Method for preparing optically-active alpha-amino phosphonate derivatives by chiral spiro phosphate catalysis
  • Method for preparing optically-active alpha-amino phosphonate derivatives by chiral spiro phosphate catalysis

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021]

[0022] The imine (R 1 = H, R 2 =4-OMe; 0.05 mmol), diethyl phosphonite (0.1 mmol) and ( R )-chiral spirocyclic phosphoric acid catalyst [formula (1), 0.05 mmol] was dissolved in xylene (0.8 milliliters), stirred at room temperature for 68 hours, and the reaction was completed. The reaction mixture was purified by silica gel column chromatography to obtain a solid product ( S , E )-α-(4-methoxyphenyl)amino-styrylphosphonic acid diethyl ester, yield 88%, melting point 91-93 °C, chiral purity 87% ee, HPLC analysis: Chiralpak AS -H (hexane / i-PrOH = 85 / 15, 0.6 mL / min), t R (major) 21.3 min, t R (minor) 34.6 min, [α] D 20 = -40.2° (c = 0.70, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.35 (d, J = 7.5 Hz, 2H), 7.32 – 7.22 (m, 3H), 6.80 – 6.64 (m, 5H), 6.22-6.29 (m, 1H), 4.38 (dd, J = 25.4, 6.2 Hz, 1H), 4.21-4.13 (m, 5H), 3.73 (s, 3H), 1.30 (t, J = 7.0 Hz, 6H); 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 152.79, 140.52 (d, J = 12.9 Hz), 136.29, 132.96 (d, ...

Embodiment 2

[0024]

[0025] The imine (R 1 = H, R 2 =4-OMe; 0.05 mmol), diisopropyl phosphonite (0.1 mmol) and ( R )-chiral spirocyclic phosphoric acid catalyst [formula (1), 0.05 mmol] was dissolved in xylene (0.8 milliliters), stirred at room temperature for 168 hours, the reaction was complete, and the reaction mixture was purified by silica gel column chromatography to obtain a solid product ( S , E )-α-(4-methoxyphenyl)amino-styryl phosphonic acid diisopropyl ester, the yield is 85%, the melting point is 76-78 °C, the chiral purity is 88% ee, HPLC analysis: Chiralpak AD-H (hexane / i-PrOH = 50 / 50, 0.5 mL / min), t R (minor) 19.2 min, t R (major) 33.2 min, [α] D 20 = -12.5° (c = 0.58, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.35 (d, J = 7.5 Hz, 2H), 7.31-7.26 (m, 2H), 7.22 (t, J = 7.0 Hz, 1H), 6.76 (d, J = 8.8 Hz, 2H), 6.65 (d, J = 8.5 Hz, 3H), 6.29-6.24 (m, 1H), 4.80 – 4.71 (m, 2H), 4.31 (d, J = 25.8 Hz, 1H), 4.03 (s, 1H), 3.72 (s, 3H), 1.34 (d, J = 6.1 H...

Embodiment 3

[0027]

[0028] The imine (R 1 =2-NO 2 , R 2 =3-Cl; 0.05 mmol), diethyl phosphonite (0.1 mmol) and ( S )-chiral spirocyclic phosphoric acid catalyst [formula (1), 0.05 mmol] was dissolved in xylene (0.8 milliliters), stirred at room temperature for 88 hours, and the reaction was completed. The reaction mixture was purified by silica gel column chromatography to obtain a liquid product ( R , E )-α-(3-chlorophenyl) amino-(2-nitro) styryl phosphonic acid diethyl ester, yield 92%, chiral purity is 97% ee, HPLC analysis: Chiralpak AD-H ( hexane / i-PrOH = 80 / 20, 1.0 mL / min), t R (minor) 16.9 min, t R (major) 18.7 min, [α] D 20 = + 40.0° (c = 0.35, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.93 (d, J = 7.9 Hz, 1H), 7.58 – 7.52 (m, 2H), 7.42 – 7.36 (m, 1H), 7.24 – 7.17 (m, 3H), 6.77 (t, J = 7.3 Hz, 1H), 6.72 (d, J = 7.7 Hz, 2H), 6.29-6.23 (m, 1H), 4.52 (dd, J = 25.8, 5.9 Hz, 1H), 4.41 – 4.08 (m, 5H), 1.33 (td, J = 7.0, 0.7 Hz, 6H); 13 C NMR (101 MHz, CDC...

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Abstract

The invention discloses a method for preparing optically-active alpha-amino phosphonate derivatives by chiral spiro phosphate catalysis. Chiral spiro phosphate serves as a catalyst, imine and dialkyl phosphate are stirred in an organic solvent at room temperature, and high-purity optically-active alpha-amino phosphonate derivatives are prepared by a simple post-treatment purification process. The method is mild in reaction condition, simple in process and convenient in operation. The catalyst is high in stability and can be reused. The prepared optically-active alpha-amino phosphonate derivatives are high in potential biological activity and can be used as organic synthesis intermediates.

Description

technical field [0001] The invention relates to a method for preparing optically active α-aminophosphonate derivatives by catalysis of chiral spirocyclic phosphoric acid ester, and belongs to the technical field of chiral preparation of phosphorus-containing compounds. Background technique [0002] α-Aminophosphonic acid and its ester derivatives, as phosphorus-containing analogs of natural amino acids, have a wide range of biological activities. α-Aminophosphonic acid, as a phosphorus-containing analogue of natural amino acid, is the third type of amino acid found in organisms after aminocarboxylic acid and sulfamic acid]. People have conducted extensive research on its synthesis method and biological activity, and found that it has a variety of biological activities such as herbicidal activity, plant growth regulation activity, anti-plant virus activity, and anti-tumor activity. In particular, the phosphorus atom has a tetrahedral structure, which is very similar to the ...

Claims

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Application Information

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IPC IPC(8): C07F9/40B01J31/02
Inventor 沈小明莫凡李炉航赵彦彦林旭峰
Owner ZHEJIANG UNIV
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