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Method for synthesizing chiral amine through palladium catalyzed asymmetric hydrogenolysis of racemic oxazirine

A technology of oxaziridine and aziridine, which is applied in the field of catalytic hydrogenolysis, racemization and substitution of oxaziridine to synthesize chiral sulfonamide, which achieves convenient preparation, mild reaction conditions, high reactivity and enantioselectivity Effect

Active Publication Date: 2016-06-22
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, expanding the substrate scope of asymmetric hydrogenolysis reactions remains a challenge due to the fragility and variability of substrates in the hydrogenolysis environment.

Method used

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  • Method for synthesizing chiral amine through palladium catalyzed asymmetric hydrogenolysis of racemic oxazirine
  • Method for synthesizing chiral amine through palladium catalyzed asymmetric hydrogenolysis of racemic oxazirine
  • Method for synthesizing chiral amine through palladium catalyzed asymmetric hydrogenolysis of racemic oxazirine

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Embodiment 1: optimization of conditions

[0033] Drop into palladium trifluoroacetate (3mol% of substrate consumption in formula 1) and chiral phosphine ligand (3.3mol% of substrate consumption in formula 1) in reaction bottle, add 1 milliliter of acetone after nitrogen replacement, room temperature stirs 1 Hour. Concentrate in vacuo then, add 3 milliliters of dichloromethane under nitrogen, this solution is transferred to the reaction kettle that has put substrate 1a (51.8 mg, 0.2 mmol) and camphorsulfonic acid (10mol% of substrate consumption in formula 1) in advance , 600 psi of hydrogen was passed through, and the reaction was carried out at 50° C. for 20 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:

[0034]

[0035] The yield was determined from the reaction crude product with 1,3,5-trimethoxybenzene as the internal standard 1 HNM...

Embodiment 2

[0040] Example 2: Synthesis of various chiral sulfonamides by palladium-catalyzed asymmetric hydrogenolysis 2

[0041] Drop into palladium trifluoroacetate (3mol% of substrate consumption in formula 1) and (S, S, R, R)-TangPhos (3.3mol% of substrate consumption in formula 1) in reaction bottle, add 1 after nitrogen replacement mL of acetone and stirred at room temperature for 1 hour. Concentrate in vacuo then, add 3 milliliters of dichloromethane under nitrogen, this solution is transferred in the reaction kettle that has substrate (0.2 mmol) and L-CSA (10mol% of substrate consumption in formula 1) in advance, feeds Hydrogen to 600psi, react at 50°C for 15-24 hours, release hydrogen slowly. Direct column chromatography after removing solvent obtains pure product, and reaction formula is as follows:

[0042]

[0043] The yield is the separation yield, and the enantiomeric excess of the product is determined by chiral liquid chromatography, see Table 2.

[0044] Table 2. Pal...

Embodiment 3

[0048] Example 3: Synthesis of various chiral sulfonamides by palladium-catalyzed asymmetric hydrogenolysis 4

[0049] Drop into palladium trifluoroacetate (3mol% of substrate consumption in formula 1) and (S, S, R, R)-TangPhos (3.3mol% of substrate consumption in formula 1) in reaction bottle, add 1 after nitrogen replacement mL of acetone and stirred at room temperature for 1 hour. Concentrate in vacuo then, add 3 milliliters of dichloromethane under nitrogen, this solution is transferred in the reaction kettle that has substrate (0.2 mmol) and L-CSA (10mol% of substrate consumption in formula 1) in advance, feeds Hydrogen to 1000psi, react at 70°C for 15-24 hours, release hydrogen slowly. After removing solvent, direct column chromatography separates and obtains pure product, and reaction formula is as follows:

[0050]

[0051] The yield is the isolated yield, and the enantiomeric excess of the product is determined by chiral liquid chromatography, see Table 3.

[00...

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Abstract

A catalysis system used in a method for synthesizing chiral amine through palladium catalyzed asymmetric hydrogenolysis of racemic oxazirine is a chiral diphosphine complex of palladium. The racemic substituted oxazirine is hydrogenolyzed to obtain corresponding chiral sulfonamide, and the enantiomeric excess can reach 99%. The method has the advantages of simple, practical and easy operation, commercially available catalyst and mild reaction conditions. The method for synthesizing the chiral sulfonamide through asymmetric hydrogenolysis also has the advantages of high antipodal selectivity, good yield, environmentally-friendly and atomically-economic reaction, and environmental protection.

Description

technical field [0001] The invention relates to a method for synthesizing chiral sulfonamide by using palladium homogeneous system to catalyze hydrogenolysis and racemization to replace oxaziridine with high enantioselectivity. Background technique [0002] Hydrogenolysis occupies a very important position in organic synthesis and industrial applications (references one: (a) Arnold, M.R.Chem.Eng.Rev.1956,48,1629. (b) Martin, A.; Armbruster, U. ; Gandarias, I.; Arias, P.L.Eur.J.LipidSci.Technol.2013,115,9.(c)Chaudhari,RaghunathV.;Torres,A.;Jin,X.Ind.Eng.Chem.Res.2013, 52, 15226.). Most hydrogenolysis reactions are mainly used to synthesize racemic or achiral compounds, and there are very few examples of asymmetric hydrogenolysis so far. Early explorations of asymmetric hydrogenolysis focused on the desymmetrization of symmetrical epoxides and geminal dihalides (Reference 2: (a) Chan, A.S.C.; Coleman, J.P.J.Chem.Soc.Chem.Commun.1991, 535. (b) Bakos, J.; Orosz, A.; Cserépi, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D275/02C07D275/06
Inventor 周永贵宋波余长斌黄文学陈木旺
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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