Method for synthesizing chiral fluoroamine by palladium catalytic asymmetric hydrogenation

An asymmetric, chemical synthesis technology, applied in chemical instruments and methods, preparation of organic compounds, preparation of amino compounds, etc., to achieve mild conditions, high reactivity and enantioselectivity, and simple and practical reaction operations.

Active Publication Date: 2012-02-01
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, literature reports are mainly through substrate induction [Ni, C.F.;. Liu, J.; Zbang, L.J.; Hu, J.B. Angew. Chem. Int. Ed. Gosselin, F.; O'Shea, P.D.; Roy, S.; Reamer, R.A.; Chen, C.-Y.;

Method used

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  • Method for synthesizing chiral fluoroamine by palladium catalytic asymmetric hydrogenation
  • Method for synthesizing chiral fluoroamine by palladium catalytic asymmetric hydrogenation
  • Method for synthesizing chiral fluoroamine by palladium catalytic asymmetric hydrogenation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1: optimization of conditions

[0031] Put palladium trifluoroacetate (0.0025 mmol, 0.85 mg) and the chiral ligand L in the diagram below into the reaction flask 1 -L 6 One of them (0.003 mmol), after nitrogen replacement, 1 ml of acetone was added, and stirred at room temperature for 1 hour. It was then concentrated in vacuo, and 3 ml of 2,2,2-trifluoroethanol was added under nitrogen, and the solution was transferred to pre-placed substrate 1a (35 mg, 0.125 mmol) and In the reaction kettle of MS molecular sieves (40 mg), 41 atmospheres of hydrogen gas was introduced, and the reaction was carried out at 25° C. for 16 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:

[0032]

[0033] 2a: (R)-4-Methoxy-N(2,2,2-trifluoro-1-phenylethyl)aniliee. 99% yield, 93% ee, [α] RT D =-53.6 (c0.60, CHCl 3 ); 1 H NMR (400MHz, CDCl 3 )δ7.4...

Embodiment 2

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

[0038] Palladium trifluoroacetate (0.85 mg, 0.0025 mmol) and (R)-Cl-MeO-BiPhep (2.0 mg, 0.003 mmol) were put into the reaction flask, 1 ml of acetone was added after nitrogen replacement, and stirred at room temperature for 1 hour. It was then concentrated in vacuo, 3 ml of 2,2,2-trifluoroethanol was added under nitrogen, and the solution was transferred to a pre-placed substrate 1 (0.125 mmol) and In the reactor of MS (40 mg), feed hydrogen to 41 atmospheres, react at room temperature for 15-24 hours, and release hydrogen slowly. After removing solvent, direct column chromatography separates and obtains pure product, and reaction formula is as follows:

[0039]

[0040] The enantiomeric excess of the product was determined by chiral liquid chromatography, see Table 2.

[0041] Table 2. Synthesis of various chiral fluoroamines by palladium-catalyzed asymmetric hy...

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Abstract

The invention discloses a method for synthesizing chiral fluoroamine by palladium catalytic asymmetric hydrogenation, wherein, the used catalysis system comprises a palladium chiral diphosphite complex. The reaction is carried out under the following conditions that: the temperature is 0-50 DEG C, the solvent is a 2,2,2-trifluoroethyl alcohol, the pressure is 1-42 atm, the ratio of the substrate to the catalyst is 50 : 1, the used metal precursor is palladium trifluoroacetate, the used chiral ligand is a chiral diphosphite ligand. The catalyst is prepared by stirring the palladium metal precursor and the chiral diphosphite ligand in acetone at room temperature, and then carrying out vacuum condensation. According to the invention, by the hydrogenation of imine containing trifluoromethyl, corresponding chiral amine containing trifluoromethyl is obtained, the enantiomeric excess can reach to 94 %; by the hydrogenation of imine containing perfluoroalkyl, corresponding chiral amine containing perfluoroalkyl is obtained, and the enantiomeric excess can reach to 86 %. The present invention has the advantages of simple and practical operation, high enantioselectivitiy, good yield, green atom economy of the reaction, and no environmental pollution.

Description

technical field [0001] The invention relates to a method for synthesizing chiral fluoroamine by catalyzing hydrogenation of fluoroimine with high enantioselectivity in homogeneous system of palladium. Background technique [0002] Fluorine-containing imines are very important building blocks and are widely used in the synthesis of material chemistry, pesticides and pharmaceutical intermediates [a) Prakash, G.K.S.; Yudin, A.Chem.Rev.1997, 97, 757-786; b ) Ruano, J.L.G.; Alemán, J.; .Catalán, S.; Marcos, V; Monteagudo, S.; , 7941-7944.]. However, due to the strong electron-withdrawing effect of trifluoromethyl or polyfluoroalkyl, it is difficult to synthesize such compounds by traditional methods [a) Nelson, D.W.; Easley, R.A.; Pintea, B.N.V.Tetrahedron Lett.1999,40,25- 28; b) , B.; Abid, M.; London, G.; Esquibel, J.; , M.; Mhadgut, S.C.; Yan, P.; Prakash, G.K.S.; Angew. Chem. Int. Ed 2005, 44, 3086-3089.]. We refer to [a) Uneyama, K.; Amii, H.; Katagiri, T.; Kobayashi,...

Claims

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Application Information

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IPC IPC(8): C07B43/04C07C209/52C07C211/45C07C211/47C07C213/02C07C217/84B01J31/24
Inventor 周永贵陈木旺
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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