Iridium catalyzed enantiotropic hydrosubstituting process of aromatic pyridine ring and pyrazine ring

An aromatic pyridine ring, enantioselective technology, applied in chemical instruments and methods, organic chemical methods, physical/chemical process catalysts, etc., can solve the problems of severe reaction conditions, destruction of aromaticity, unfavorable energy, etc. Gentle, easy-to-prepare effect

Inactive Publication Date: 2004-01-21
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] One is to destroy the aromaticity during hydrogenation, which is disadvantageous in energy, which makes the reaction conditions more severe. Most of the existing methods in the literature are carried out under high temperature and high pressure conditions
[0010] The second is the lack of coordinating groups (in the asymmetric hydrogenation of C=C bonds, usually only those containing coordinating groups have high activity and enantioselectivity)
The HRh (DIOP) catalyst developed by Japan's Murata has an ee value of only 3% for hydrogenated quinoxaline, and the activity of the catalyst is low

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1: optimization of conditions

[0034] Add [Ir(COD)Cl] to a reaction flask 2 (3.4 mg, 0.005 mmol) and the chiral ligand (0.011 mmol) and five mL of solvent. The reaction mixture was stirred under nitrogen for 30 minutes. Then transfer to the reaction kettle with substrate (1.0mmol) and adduct iodine (12.7mg, 0.05mmol) in advance, and pass through hydrogen (30-50atm) to react for 12 hours. Release hydrogen slowly, remove toluene and obtain pure product directly by column chromatography, the reaction formula is as follows:

[0035] The enantiomeric excess of the product can be determined by chiral HPLC, see Table 1.

[0036] Table 1: Asymmetric hydrogenation of 2-methylquinoline No. H 2 (psi); T solvent conversion ee(%)1 700; 25℃ CH 2 Cl 2 >99 852 700 25°C (ClCH 2 ) 2 >99 853 700; 25℃ MeOH 85 94 700; 25℃ i-PrOH >99 845 700; 25℃ THF >99 856 700; 25℃ Toluene >99 947 700; 25℃ Benzene >99 948 1500; 25℃ Toluene > 99 919 100; 25℃ Toluene 68 9410 700;...

Embodiment 2

[0037] Embodiment 2, the reaction of replacing quinoline substrate in addition

[0038] Add [Ir(COD)Cl] to a reaction flask 2 (3.4 mg, 0.005 mmol) and (R)-MeO-Biphep (6.4 mg, 0.011 mmol) and five mL of toluene. The reaction mixture was stirred under nitrogen for 30 minutes. Then transfer to the reaction kettle with substrate (1.0mmol) and adduct iodine (12.7mg, 0.05mmol) in advance, and pass through hydrogen (30-50atm) to react for 12 hours. Release hydrogen slowly, remove toluene and obtain pure product directly by column chromatography, the reaction formula is as follows: The enantiomeric excess of the product can be determined by chiral HPLC, see Table 2. Table 2. Asymmetric hydrogenation of substituted quinolines No. R' / R of 1 Yield Ee (absolute configuration) 1 H / Me(1a) 94(2a) 94(R)2 H / Et(1b) 88(2b ) 96(R)3 H / n-Pr(1c) 92(2c) 93(R)4 H / n-Bu(1d) 86(2d) 92(R)5 H / 3-Butenyl(1e) 91( 2d) e 92(R)6 H / n-Pentyl(1f) 92(2f) 94(R)7 H / Phenethyl(1g) 94(2g) 93(R)8 88(2h) 94(R)...

Embodiment 3

[0038] Add [Ir(COD)Cl] to a reaction flask 2 (3.4 mg, 0.005 mmol) and (R)-MeO-Biphep (6.4 mg, 0.011 mmol) and five mL of toluene. The reaction mixture was stirred under nitrogen for 30 minutes. Then transfer to the reaction kettle with substrate (1.0mmol) and adduct iodine (12.7mg, 0.05mmol) in advance, and pass through hydrogen (30-50atm) to react for 12 hours. Release hydrogen slowly, remove toluene and obtain pure product directly by column chromatography, the reaction formula is as follows: The enantiomeric excess of the product can be determined by chiral HPLC, see Table 2. Table 2. Asymmetric hydrogenation of substituted quinolines No. R' / R of 1 Yield Ee (absolute configuration) 1 H / Me(1a) 94(2a) 94(R)2 H / Et(1b) 88(2b ) 96(R)3 H / n-Pr(1c) 92(2c) 93(R)4 H / n-Bu(1d) 86(2d) 92(R)5 H / 3-Butenyl(1e) 91( 2d) e 92(R)6 H / n-Pentyl(1f) 92(2f) 94(R)7 H / Phenethyl(1g) 94(2g) 93(R)8 88(2h) 94(R)9 86(2i) 96(R)10 F / Me(1j) 88(2j) 96(R)11 Me / Me(1k) 91(2k) 91(R)12 MeO / Me(1l) 8...

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PUM

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Abstract

The iridium catalyzed enantiotropic hydrosubstituting process of aromatic pyridine ring and pyrazine ring uses catalyst system comprising chiral coordination compound of iridium and additive compound. The reaction conditions includes temperature of 0-80 deg.c; solvent of dichloromethane, toluene, tetrahydrofuaran, 1, 2-dichloro ethane, isopropanol, etc.; additive compound of tetrabutyl ammonium iodide, iodine, amine, etc.; pressure of 1-100 atm; substrate/catalyst ratio up to 5000; and chiral coordination compound of diphosphine, N-P compound, S-P compound, etc. The catalyst system is prepared through reaction of iridium precursor and chiral compound in the said solvent and the addition of the additive compound while stirring; and can produce asymmetrical induction up to 96 %. The process of the present invention is environment friendly.

Description

technical field [0001] The invention relates to a method for highly enantioselective iridium-catalyzed hydrogenation to replace aromatic pyridine rings and pyrazine rings. Background technique [0002] Asymmetric hydrogenation has many advantages: very high catalyst activity, fast reaction speed, convenient separation of products, less side reactions, etc. Asymmetric hydrogenation reaction has been developed from the 1960s to the present and has made great achievements. There are five main types of catalytic systems currently used in asymmetric hydrogenation: [0003] A rhodium catalyst of the Wilkinson catalyst type, this catalyst works best with functionalized alkenes, with some good results also obtained for simple ketones and imines. [0004] The ruthenium / bisphosphorus system has achieved outstanding asymmetric induction for functionalized ketones, and is also very effective for some functionalized alkenes. This system has very high catalytic activity and has been wid...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B01J31/16C07B35/00C07D215/02C07D241/42
Inventor 周永贵卢胜梅杨鹏宇王文波
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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