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Catalytic asymmetric hydrogenation synthesis method for chiral gamma-sultam

A sultam, asymmetric technology is applied in the field of catalyzing hydrogenated imine to synthesize chiral γ-sultam, achieving the effects of complete reaction, convenient preparation, high reactivity and enantioselectivity

Inactive Publication Date: 2012-04-18
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, there are still relatively few effective methods for synthesizing them for stereoselectivity, especially so far, there are only few examples for the synthesis of chiral sultams.

Method used

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  • Catalytic asymmetric hydrogenation synthesis method for chiral gamma-sultam
  • Catalytic asymmetric hydrogenation synthesis method for chiral gamma-sultam
  • Catalytic asymmetric hydrogenation synthesis method for chiral gamma-sultam

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Embodiment 1: optimization of conditions

[0032] Put palladium precursor (0.005mmol) and chiral ligand (0.006mmol) into the reaction flask, add 1ml of acetone after nitrogen replacement, and stir at room temperature for 1 hour. Then concentrate in vacuo, add 2 milliliters of 2,2,2-trifluoroethanol under nitrogen, transfer this solution to the reaction kettle with substrate 1a (45mg, 0.25mmol) in advance, feed hydrogen at 40 atmospheres, and react at room temperature 12 hours. Slowly release hydrogen, remove the solvent and directly separate the pure product by column chromatography, the reaction formula and ligand structure are as formula 5:

[0033] Formula 5

[0034] The conversion rate was determined by proton nuclear magnetic resonance spectroscopy, and the enantiomeric excess of the product was determined by chiral liquid chromatography, as shown in Table 1.

[0035] Table 1. Asymmetric hydrogenation of cyclic sulfonimides 1a

[0036]

Embodiment 2

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

[0038] Put palladium trifluoroacetate (1.7mg, 0.005mmol) and (S)-SegPhos (3.7mg, 0.006mmol) into the reaction flask, add 1ml of acetone after nitrogen replacement, and stir at room temperature for 1 hour. Then concentrate in vacuo, add 2 milliliters of 2,2,2-trifluoroethanol under nitrogen, transfer this solution to the reaction kettle with substrate (0.25 mmol) in advance, feed hydrogen to 40 atmospheres, and react at room temperature for 12 hours , releasing hydrogen gas slowly. After removing solvent, direct column chromatography separation obtains pure product, and reaction formula is as formula 6:

[0039] Formula 6

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

[0041] Table 2. Synthesis of various chiral γ-sultams by palladium-catalyzed asymmetric hydrogenation 2

[0042]

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Abstract

The invention discloses a method using palladium to catalyze asymmetrical hydrogen to compound into chiral gamma-sultam, wherein, a catalytic system used by the invention is a chiral diphosphine complex of palladium. The reaction can be made within the following conditions: temperature: 25 to 75 DEG C; solvent: 2, 2, 2-trifluoroethanol; pressure: 35 to 40 atmospheric pressures; time: 10 to 12 hours. The proportion of substrate and catalyst is 50:1, a metal precursor of the catalyst is palladium trifluoroacetate; a chiral ligand is a chiral diphosphine ligand; the preparation method for the catalyst is that: the metal precursor of the palladium and the chiral diphosphine ligand are stirred in acetone at room temperature, and then are made a vacuum condensation to obtain the catalyst. To hydrogenise cyclic sulfimide can obtain corresponding chiral 3-substituted gamma-sultam, and enantiomeric excess thereof can reach 93 percent. The method has simple and practical operation, easy-obtaining raw materials, high enantioselectivity and good yield; the reaction has green atomic economy and is environment-friendly.

Description

technical field [0001] The invention relates to a method for synthesizing chiral gamma-sultam by using palladium homogeneous system to catalyze hydrogenation imine with high enantioselectivity. technical background [0002] Many compounds containing cyclic sulfonamide functional groups, also known as sulphonamides, have certain physiological activities, so they are found to be an important class of drugs and agricultural reagents. The three common drugs of the following formula 1 all contain sulphonic acid Lactam structural unit: [0003] Formula 1 [0004] In addition to attracting people's attention as drugs, sultam compounds have also been successfully applied as chiral auxiliary agents and chiral reagents. [0005] Due to the importance of sultams in the fields of medicine and synthetic chemistry, several methods for the synthesis of such heterocycles have been explored. But there are still relatively few effective methods for synthesizing them with stereoselectivit...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D275/02
Inventor 周永贵汪游清卢胜梅
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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