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A method for the synthesis of chiral tertiary amines by asymmetric hydrogenation of ruthenium catalyzed arylamine compounds

A compound and synthesis technology, applied in the field of ruthenium-catalyzed asymmetric hydrogenation of arylamine compounds to synthesize chiral tertiary amines

Active Publication Date: 2021-06-15
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

[0005] However, the asymmetric hydrogenation of heteroatom-free aromatic compounds and their functionalized derivatives has always been a challenging direction compared to aromatic heterocyclic compounds.

Method used

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  • A method for the synthesis of chiral tertiary amines by asymmetric hydrogenation of ruthenium catalyzed arylamine compounds
  • A method for the synthesis of chiral tertiary amines by asymmetric hydrogenation of ruthenium catalyzed arylamine compounds
  • A method for the synthesis of chiral tertiary amines by asymmetric hydrogenation of ruthenium catalyzed arylamine compounds

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment 1: Optimization of reaction conditions for hydrogenation of monosubstituted substrates

[0027] Drop into two-(2-methallyl) cyclooctyl-1,5-diene ruthenium (2mol%-5mol% of substrate consumption) and chiral bisphosphine ligand (2.2% of substrate consumption) in the reaction flask mol%-5.5mol%), after nitrogen replacement, add organic solvent (1.0-2.0mL) and fluoroboric acid (4mol%-10mol% of the amount of substrate), stir at room temperature for 0.5 hours; then use organic solvent (1.0-2.0mL) Transfer this solution to the reaction flask with arylamine substrate 1a (0.1 mmol) in advance, move it to the reaction kettle, feed hydrogen (600psi-1000psi), and react at 0-50°C for 24 hours; release hydrogen, After removing the solvent, direct column chromatography separates and obtains the pure product, and the reaction formula and the ligand structure are as follows:

[0028]

[0029] The yield is the conversion rate, and the enantiomeric excess of the product is d...

Embodiment 2

[0033] Example 2: Synthesis of chiral tertiary amine 2 by ruthenium-catalyzed asymmetric hydrogenation

[0034] Put bis-(2-methallyl) cyclooctyl-1,5-diene ruthenium (5 mol% of substrate consumption) and (S, S)- i PrDuPhos (5.5mol% of substrate consumption), after nitrogen replacement, add organic solvent (1.0mL) and fluoboric acid (10mol% of substrate consumption), stir at room temperature for 0.5 hour; then use organic solvent (1.0mL) to turn this solution Put the arylamine substrate 1 (0.2mmol) in the reaction flask in advance, move it to the reaction kettle, feed hydrogen gas (1000psi), and react at 30°C for 24 hours; release the hydrogen gas, remove the solvent and separate directly by column chromatography Obtain pure product, reaction formula is as follows:

[0035]

[0036] The yield is the separation yield, and the enantiomeric excess of the product is determined by chiral liquid chromatography, see Table 2.

[0037] Table 2. Ruthenium-catalyzed asymmetric hydroge...

Embodiment 3

[0040] Embodiment 3: Optimization of reaction conditions for hydrogenation of disubstituted substrates

[0041] Drop into two-(2-methallyl) cyclooctyl-1,5-diene ruthenium (5 mol% of substrate consumption) and chiral bisphosphine ligand (5.5mol% of substrate consumption) in the reaction flask , add organic solvent (1.0mL) and fluoroboric acid (10mol% of the substrate amount) after nitrogen replacement, and stir at room temperature for 0.5 hours; then use organic solvent (1.0mL) to transfer this solution to pre-placed arylamine (0.1mmol) in the reaction flask, moved to the reaction kettle, feed hydrogen (1000psi), reacted 24 hours under 30 ℃; Release hydrogen, remove the direct column chromatography separation after solvent to obtain pure product, reaction formula is as follows:

[0042]

[0043] The yield is the conversion rate, and the enantiomeric excess of the product was determined by chiral liquid chromatography, see Table 3.

[0044] Table 3. Optimization of asymmetri...

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Abstract

The invention discloses a method for synthesizing chiral tertiary amine by asymmetric hydrogenation of 9-amidophenanthrene compound catalyzed by ruthenium-bisphosphine ligand. Using 2-5mol% ruthenium catalyst, adding 4-10mol% fluoboric acid, asymmetric hydrogenation of 9-amide phenanthrene compound to obtain the corresponding chiral tertiary amine compound, and its enantiomeric excess can reach 98%. The invention has the advantages of simple and practical operation, high yield, environmental friendliness, commercially available catalyst, mild reaction conditions and potential practical application value.

Description

technical field [0001] The invention relates to a method for synthesizing chiral tertiary amine by catalyzing the asymmetric hydrogenation of arylamine compound with highly enantioselective ruthenium homogeneous system. Background technique [0002] In recent years, great progress has been made in the asymmetric hydrogenation of aromatic heterocycles. A variety of aromatic heterocyclic compounds, such as: indole, pyridine, pyrrole, quinoline, etc., can be hydrogenated with high stereoselectivity through asymmetric catalysis to obtain the corresponding heterocyclic compounds (Reference 1: (a) Wang, D.S. ; Chen, Q.A.; Li, W.; Yu, C.-B.; Zhou, Y.-G.; , M.-W.; Chen, Q.-A.; Shi, L.; Duan, Y.; Zhou, Y.-G.Angew.Chem.Int.Ed.2012,51,10181.(c)Wang ,D.-S,;Ye,Z.-S.;Chen,Q.-A.;Zhou,Y.-G.J.Am.Chem.Soc.2011,133,8866.(d)Wang,W.-B .; Lu, S-M.; Yang, P.-Y.; Han, X.-W.; Zhou, Y.-G.J. Am. Chem. Soc. 2003, 125, 10536.). However, compared with heteroatom-free aromatic compounds, their asymmet...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C231/12C07C233/06C07C233/65C07C233/23C07F9/6509C07F9/6568C07F17/02B01J31/24
CPCB01J31/2414B01J31/2433B01J31/2452B01J2231/646B01J2531/0205B01J2531/821C07B2200/07C07C231/12C07F9/650994C07F9/65683C07F17/02C07C233/06C07C233/65C07C233/23
Inventor 严忠谢焕平孙蕾周永贵
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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