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Method for synthesizing chiral sultam containing hetero atom unsymmetrical hydrogenation using Pd as catalyst

A sultone and asymmetric technology, which is applied in the field of catalytic hydrogenation of cyclic imines to synthesize chiral heteroatom-containing sultams, can solve the problems of low ee value and achieve the effects of convenient separation, complete reaction and convenient preparation

Inactive Publication Date: 2009-05-06
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

[0010] In 2004, Fruit and Muller also reported the synthesis of chiral benzosultams containing oxythiazepine rings (formula 3) through intramolecular amination reactions using chiral Rh catalysts. The chiral ligands used were α-amino acids. Derivatives, but the obtained ee values ​​are relatively low

Method used

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  • Method for synthesizing chiral sultam containing hetero atom unsymmetrical hydrogenation using Pd as catalyst
  • Method for synthesizing chiral sultam containing hetero atom unsymmetrical hydrogenation using Pd as catalyst
  • Method for synthesizing chiral sultam containing hetero atom unsymmetrical hydrogenation using Pd as catalyst

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Experimental program
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Effect test

Embodiment 1

[0036] Example 1: Optimization of conditions

[0037] Put palladium trifluoroacetate (0.005 mmol, 1.7 mg) and chiral ligand (0.006 mmol) into the reaction flask, add 1 ml of acetone after nitrogen replacement, and stir at room temperature for 1 hour. Then it was concentrated in vacuo, and 2 ml of 2,2,2-trifluoroethanol was added under nitrogen. The solution was transferred to a reaction kettle with substrate 1a (45mg, 0.25mmol) in advance, and hydrogen was introduced to 40 atmospheres at room temperature. React for 12 hours. Slowly release hydrogen gas, remove the solvent, and directly separate by column chromatography to obtain a pure product. The reaction formula and ligand structure are as shown in formula 4:

[0038]

[0039] Formula 4

[0040] The conversion rate was determined by proton nuclear magnetic resonance spectroscopy, and the enantiomeric excess of the product was determined by chiral liquid chromatography. See Table 1.

[0041] Table 1. Asymmetric hydrogenation o...

Embodiment 2

[0043] Example 2: Palladium-catalyzed asymmetric hydrogenation to synthesize various chiral sultams containing oxygen and sulfur nitrogen heterocycles 2

[0044] Put palladium trifluoroacetate (1.7 mg, 0.005 mmol) and (S, S)-f-Binaphane (4.8 mg, 0.006 mmol) into the reaction flask, replace with nitrogen, add 1 ml of acetone, and stir at room temperature for 1 hour. Then it was concentrated in vacuo, and 2 ml of 2,2,2-trifluoroethanol was added under nitrogen. The solution was transferred to a reaction kettle with a substrate (0.25 mmol) in advance, and hydrogen was introduced to 40 atmospheres, and reacted at room temperature for 12 hours. , Slowly release hydrogen. After removing the solvent, the pure product can be obtained by column chromatography and the reaction formula is shown in formula 5:

[0045]

[0046] Formula 5

[0047] The enantiomeric excess of the product was determined by chiral liquid chromatography, as shown in Table 2.

[0048] Table 2. Palladium-catalyzed a...

Embodiment 3

[0050] Example 3: Palladium-catalyzed asymmetric hydrogenation to synthesize various chiral benzosultams 4

[0051] Put palladium trifluoroacetate (1.7 mg, 0.005 mmol) and (S, S)-f-Binaphane (4.8 mg, 0.006 mmol) into the reaction flask, replace with nitrogen, add 1 ml of acetone, and stir at room temperature for 1 hour. Then it was concentrated in vacuo, and 2 ml of 2,2,2-trifluoroethanol was added under nitrogen. The solution was transferred to a reaction kettle with a substrate (0.25 mmol) in advance, and hydrogen was introduced to 40 atmospheres, and reacted at room temperature for 12 hours. , Slowly release hydrogen. After the solvent is removed, the pure product is obtained by column chromatography and the reaction formula is as shown in formula 6:

[0052]

[0053] Formula 6

[0054] The enantiomeric excess of the product was determined by chiral liquid chromatography, see Table 3.

[0055] Table 3. Palladium-catalyzed asymmetric hydrogenation to synthesize various chiral su...

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Abstract

The invention provides a method for synthesizing chiral sultam containing hetero atoms by palladium-catalyzed asymmetric hydrogenation, wherein the catalyst is a chiral diphosphine ligand of palladium. The reaction is carried out at a temperature of between 25 and 60 DEG C and at a pressure of 40 atmosphere for 12 hours in solvent of 2, 2, 2-trifluoroethanol. Sulfonyl oxathiazinane heterocycle five-membered cyclic imide is hydrogenated to obtain corresponding chiral sultam containing oxathiazinane heterocycles with enantiomeric which excessively reaches 97 percent; and benzo N-sulfonyl oxathiazinane heterocycle six-membered cyclic imide is hydrogenated to obtain corresponding chiral sultam containing oxathiazinane heterocycles with enantiomeric which excessively reaches 99 percent; and benzo N-sulfonyl benzothiazinane heterocycle six-membered cyclic imide is hydrogenated to obtain corresponding chiral sultam containing benzothiazinane heterocycles with enantiomeric which excessively reaches 98 percent. The method has the advantages of simple and practical operation, high enantiomeric selection and good yield, and the reaction has green atomic economy and is friendly to environment.

Description

Technical field [0001] The invention relates to a method for synthesizing chiral heteroatom-containing sultams by using a homogeneous system of palladium to highly enantioselectively catalyze the hydrogenation of cyclic imines. Background technique [0002] Many compounds containing cyclic sulfonamide functional groups, also known as sultams, are an important class of compounds. For sultams whose structural unit is oxathiazinane heterocycles, they can interact with a variety of nucleophiles. The reagent reacts to obtain the corresponding amine derivative. As shown in formula 1, X can be a substituent such as Bn, Ph, Cbz, etc. The presence of X is conducive to better attack by nucleophiles. If the compound containing the oxathione heterocyclic sultam is enantiopure, then the corresponding enantiopure chiral amine can be obtained. Therefore, heterocyclic sultam compounds containing oxygen sulfa nitrogen are an important intermediate for the synthesis of chiral amines. [0003] ...

Claims

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Application Information

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IPC IPC(8): C07D291/04C07D291/06B01J31/24B01J31/28C07B53/00
Inventor 周永贵汪游清余长斌
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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