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Method for synthesizing chiral phosphoramidate by carrying out asymmetric hydrogenation on palladium-catalyzed imine phosphate

A technology for catalyzing imine phosphonate and amino phosphonate, which is applied in the direction of chemical instruments and methods, catalytic reactions, physical/chemical process catalysts, etc., can solve problems such as the inability to synthesize amino phosphonic acid and its derivatives, Achieve the effects of simple and practical reaction operation, high reactivity and enantioselectivity, and chiral value-added

Inactive Publication Date: 2017-06-20
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

However, the main defect of this method is that it is impossible to synthesize aminophosphonic acid and its derivatives with quaternary carbon in the β-position; in 2008, the Goulioukina group developed a homogeneous rhodium-catalyzed asymmetric Hydrogenation reaction (reference four, (a) Goulioukina, N.S.; Bondarenko, G.N.; Lyubimov, S.E.; Davankov, V.A.; Gavrilov, K.N.; Beletskaya, I.P. Adv. Synth. Catal. N.S.; Shergold, I.A.; Bondarenko, G.N.; Ilyin, M.M.; Davankov, V.A.; Beletskaya, I.P. Adv. Synth. Catal. new method

Method used

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  • Method for synthesizing chiral phosphoramidate by carrying out asymmetric hydrogenation on palladium-catalyzed imine phosphate
  • Method for synthesizing chiral phosphoramidate by carrying out asymmetric hydrogenation on palladium-catalyzed imine phosphate
  • Method for synthesizing chiral phosphoramidate by carrying out asymmetric hydrogenation on palladium-catalyzed imine phosphate

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Embodiment 1: optimization of conditions

[0032] Drop into palladium trifluoroacetate (2mol% of the substrate consumption in formula 1) and chiral phosphine ligand (2.4mol% of the substrate consumption in formula 1) in reaction bottle, add 1mL acetone after nitrogen replacement, room temperature stirs 1- After 3 hours, the catalyst was obtained. Then concentrate in vacuo, add 1.5mL organic solvent under nitrogen, transfer this solution to pre-placed substrate 1a (39.5mg, 0.1mmol) and In a reactor containing molecular sieves (50 mg-100 mg relative to 0.1 mmol of the substrate molecular sieve in Formula 1), 600 psi of hydrogen gas was passed through, and the reaction was carried out at 40° C. for 24 hours. Slowly release hydrogen, remove the solvent and directly separate the pure product by column chromatography. The reaction formula and ligand structure are as follows:

[0033]

[0034] The yield is the separation yield, and the enantiomeric excess of the product ...

Embodiment 2

[0037] Example 2: Synthesis of various chiral aminophosphonates by palladium-catalyzed asymmetric hydrogenation 2

[0038] Drop into palladium trifluoroacetate (2mol% of the substrate consumption in formula 1) and chiral phosphine ligand (2.4mol% of the substrate consumption in formula 1) in reaction bottle, add 1mL acetone after nitrogen displacement, room temperature stirs 1- After 3 hours, the catalyst was obtained. Then concentrate in vacuo, add 1.5mL trifluoroethanol / dichloromethane=volume ratio 2 / 1 mixed solvent under nitrogen, transfer this solution to pre-placed substrate 1 (0.1mmol) and In the reaction kettle of molecular sieve (the amount of molecular sieve is 50mg-100mg relative to 0.1mmol of the substrate molecular sieve in Formula 1), 600psi of hydrogen gas was passed through, and the reaction was carried out at 40°C for 24 hours. Slowly release hydrogen, remove the solvent and directly separate the pure product by column chromatography. The reaction formula and...

Embodiment 3

[0043] Example 3: Synthesis of various chiral aminophosphonates by palladium-catalyzed asymmetric hydrogenation 4

[0044] Drop into palladium trifluoroacetate (2mol% of the substrate consumption in formula 1) and chiral phosphine ligand (2.4mol% of the substrate consumption in formula 1) in reaction bottle, add 1mL acetone after nitrogen displacement, room temperature stirs 1- After 3 hours, the catalyst was obtained. Then concentrate in vacuo, add 1.5mL trifluoroethanol / dichloromethane=volume ratio 2 / 1 mixed solvent under nitrogen, transfer this solution to pre-placed substrate 1 (0.1mmol) and In a reactor containing molecular sieves (50 mg-100 mg relative to 0.1 mmol of the substrate molecular sieve in Formula 1), 600 psi of hydrogen gas was passed through, and the reaction was carried out at 40° C. for 24 hours. Slowly release hydrogen, remove the solvent, and directly separate the pure product by column chromatography. The reaction formula and ligand structure are as fo...

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Abstract

The invention discloses a palladium-catalyzed method for asymmetric hydrogenation of imine phosphonate to synthesize chiral amino phosphonate. The catalyst system used is palladium chiral bisphosphorus complex. Asymmetric hydrogenation of a series of imine phosphonates can give the corresponding chiral amino phosphonates with an enantiomeric excess of 99%. The invention is simple and practical to operate, the catalyst is commercially available, and the reaction conditions are mild. In addition, the synthesis of chiral aminophosphonates by asymmetric hydrogenation has high enantioselectivity and good yield, and the reaction has green atom economy and is environmentally friendly.

Description

technical field [0001] The invention relates to a method for synthesizing chiral amino phosphonate through the asymmetric hydrogenation of imine phosphonate catalyzed by palladium homogeneous system with high enantioselectivity. Background technique [0002] Optically active aminophosphonic acid has structural similarity with amino acids, and also has 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.; Maier, L.; Diel, P.J.Phosphorous, Sulfur Silicon Relat.Elem.1994, 90, 259. (c) Grembecka, J.; Mucha, A.; Cierpicki, T.Kafarski, P.J.Med.Chem. 2641. Yao, G.; Ye, M.; Huang, R.; Li, Y.; Pan, Y.; Xu, Q.; , 24, 501.). Based on this, the asymmetric synthesis of aminophosphonic acid and its derivatives has attracted extensive attention of researchers. According to the different bonding methods...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/40C07F9/6541C07F9/6547B01J31/24
CPCC07F9/4056B01J31/2447B01J2231/341B01J2531/824C07F9/6541
Inventor 周永贵严忠吴波高翔孙蕾
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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