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A method for the synthesis of chiral amines by iridium-catalyzed asymmetric hydrogenation of pyrrole/indolo[1,2-a]quinoxaline

An asymmetric, 2-a technology, applied in the field of chiral compound synthesis, can solve the problem of inactivity of aryl-substituted substrates, and achieve the effects of environmental friendliness, mild reaction conditions, and practical and easy operation

Active Publication Date: 2020-07-21
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, this system is inactive for aryl-substituted substrates and is only suitable for alkyl-substituted phenanthridine substrates

Method used

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  • A method for the synthesis of chiral amines by iridium-catalyzed asymmetric hydrogenation of pyrrole/indolo[1,2-a]quinoxaline
  • A method for the synthesis of chiral amines by iridium-catalyzed asymmetric hydrogenation of pyrrole/indolo[1,2-a]quinoxaline
  • A method for the synthesis of chiral amines by iridium-catalyzed asymmetric hydrogenation of pyrrole/indolo[1,2-a]quinoxaline

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Experimental program
Comparison scheme
Effect test

Embodiment 1-29

[0029] The optimization of embodiment 1-29 hydrogenation reaction condition-do not add acetic anhydride

[0030] In the glove box, drop 1,5-cyclooctadiene iridium chloride dimer (1mol%-5mol% of substrate consumption) and chiral bisphosphine ligand (2.2mol%-5mol% of substrate consumption) in the reaction bottle 11mol%), add an organic solvent (1.0-2.0mL), stir at room temperature for 5min, then transfer the mixture to a reaction flask containing an additive (3mol%-15mol% of the amount of substrate) with an organic solvent (1.0mL), and stir at room temperature for 5min ; Then use an organic solvent (1.0-2.0mL) to transfer this solution to the reaction flask with the hydrogenation substrate 1a (0.2mmol) in advance, move it to the reaction kettle, and feed hydrogen (10psi-1000psi), 0-80 React at ℃ for 12-48 hours; release hydrogen, remove the solvent under reduced pressure and then directly separate the pure product by column chromatography. The reaction formula and ligand structu...

Embodiment 30-39

[0035] The optimization of embodiment 30-39 hydrogenation reaction condition two adds acetic anhydride

[0036] When acetic anhydride is not added, the substrate cannot be completely converted into hydrogenated products, so acetic anhydride is added to the system to further optimize the reaction.

[0037] In the glove box, drop into 1,5-cyclooctadiene iridium chloride dimer (1.5-2mol% of the substrate consumption) and chiral bisphosphine ligand (3.3-4.4mol% of the substrate consumption) in the reaction bottle ), add organic solvent (1.0mL), after stirring at room temperature for 5min, the mixture is transferred to the reaction flask containing additive NIS (4.5-6mol% of substrate consumption) with organic solvent (1.0mL), and stir at room temperature for 5min; Solvent (1.0mL) This solution was transferred to the reaction flask with hydrogenation substrate 1a (0.2mmol) in advance, and acetic anhydride (0-2000mol%) was added to the system, moved to the reaction kettle, and hydroge...

Embodiment 40-53

[0042] Example 40-53 Synthesis of chiral amine 3 by asymmetric hydrogenation of pyrrolo[1,2-a]quinoxaline

[0043] In the glove box, drop into 1,5-cyclooctadiene iridium chloride dimer (1.5 mol% of substrate consumption) and chiral bisphosphine ligand (3.3mol% of substrate consumption) in reaction bottle, add Organic solvent (1.0mL), after stirring at room temperature for 5min, the mixture was transferred to a reaction flask containing the additive NIS (4.5mol% of the amount of substrate) with an organic solvent (1.0mL), stirred at room temperature for 5min; ) Transfer this solution to the reaction flask with hydrogenation substrate 1 (0.3mmol) in advance, then add acetic anhydride (400mol%) in the system, move to the reaction kettle, feed hydrogen (600psi), at 30°C React for 48 hours; release hydrogen, first remove the acetic acid and excess acetic anhydride produced by the reaction with sodium carbonate solution, extract with dichloromethane (30 mL) three times, dry with anh...

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Abstract

The invention provides a method for synthesizing chiral amine. Catalyzed pyrrole / indol [1,2-a] quinoxaline is prepared through asymmetric hydrogenation reaction, a catalyst is the complex of a metal precursor and chiral bisphosphine ligand of iridium, reaction activity and enantioselectivity are high, two kinds of hydrogenation products, i.e., an in situ protected hydrogenation product and a direct hydrogenation product, can be respectively or simultaneously obtained through regulating and controlling the added quantity and reaction time of acetic anhydride, a corresponding chiral tertiary amine compound is obtained, one or two kinds of high enantiomeric excess pure products can be obtained, and the enantiomeric excess of the pure products can be up to 97% at most. The method is simple, convenient, practical and easy in operation, high in yield and friendly to the environment, the catalyst can be commercially obtained, the reaction conditions are mild, and therefore, the method has a potential practical application value.

Description

technical field [0001] The invention relates to a method for synthesizing chiral amines through the asymmetric hydrogenation of pyrrole / indole[1,2-a]quinoxaline compounds using a homogeneous system of iridium with highly enantioselective catalysis, which belongs to the synthesis technology of chiral compounds field. Background technique [0002] Polycyclic heterocyclic chiral compounds widely exist in natural products and biologically active molecules, and the synthesis of such compounds by asymmetric hydrogenation is a simple, direct and efficient method. At present, the asymmetric hydrogenation of three-membered and four-membered heterocyclic imine compounds has achieved important results, such as: dibenzo[b,f][1,4]thiazepine, dibenzo[b ,f][1,4]oxazoles, etc. can achieve high stereoselective hydrogenation reactions to obtain the corresponding heterocyclic compounds through asymmetric catalysis (Reference 1: (a) Gao, K.; Yu, C.- B.; Li, W.; Zhou, Y.-G.; Zhang, X. Chem. Co...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D487/04C07D221/12B01J31/24
Inventor 胡书博翟小勇孙蕾周永贵
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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