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Tridentate Nitrophosphine Ligands and Their Complexes, and Their Applications in Asymmetric Catalytic Hydrogenation of Ketones

A technology of tridentate nitrogen and phosphine ligands, applied in organic compound/hydride/coordination complex catalysts, catalytic reactions, preparation of organic compounds, etc., can solve the problems of chiral alcohols that need to be improved, and achieve convenient storage and Use, high activity, high conversion effect

Active Publication Date: 2020-05-22
SHENZHEN CATALYS SCI & TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the efficient asymmetric hydrogenation of ketones to chiral alcohols still needs to be improved

Method used

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  • Tridentate Nitrophosphine Ligands and Their Complexes, and Their Applications in Asymmetric Catalytic Hydrogenation of Ketones
  • Tridentate Nitrophosphine Ligands and Their Complexes, and Their Applications in Asymmetric Catalytic Hydrogenation of Ketones
  • Tridentate Nitrophosphine Ligands and Their Complexes, and Their Applications in Asymmetric Catalytic Hydrogenation of Ketones

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Synthesis of tridentate nitrogen phosphine ligand

[0043]

[0044] 0°C, N 2 Add 7mL of tBuLi's n-hexane solution (1.6mol / L, 11.2mmol) dropwise into anhydrous ether (20mL) solution of compound 1 (2.57g, 10mmol) under stirring, and naturally rise to room temperature and stir 2h. Then the temperature was lowered to -78°C, and redistilled PCl was slowly added dropwise. 3 (11.46 mmol, 1 mL), the mixture was warmed to room temperature and reacted overnight. Then the temperature was lowered to -78°C again, and R was slowly added dropwise with a constant pressure funnel. 2 MgBr solution (by 30mmol R 2 Br and 0.8g, 33.3mmol magnesium chips were prepared in tetrahydrofuran). After the dropwise addition, the temperature was slowly raised to react overnight, and then 20 mL of saturated NH 4 Cl solution. The oily phase was extracted three times with ether, each time with 20 mL of ether. The oil phase was dried with anhydrous sodium sulfate, spin-dried, and chromatographe...

Embodiment 2

[0060] Preparation of 1-phenylethyl alcohol from acetophenone (S / C=10 000)

[0061]

[0062] Under high-purity argon atmosphere, [Ir(COD)Cl] 2 (3.4mg, 0.005mmol) and chiral ligand L6 (9.2mg, 0.011mmol) were dissolved in isopropanol (1mL) and stirred at room temperature for 3 hours to obtain a clear orange solution. Take 20 μL (0.001 mol%) of the orange solution with a microsyringe and add it to a mixed system of acetophenone (2 mmol), isopropanol (2 mL) and lithium tert-butoxide (1 mol %). The reaction system was placed in an autoclave at room temperature and H 2 (20atm) and stirred for 12 hours. The solvent was removed under reduced pressure and separated by column chromatography (using silica gel column, eluent: ethyl acetate) to obtain pure product 1-phenylethanol. The product was analyzed by HPLC and the measured ee value was 98%. Determination of enantiomeric excess by HPLC, Chiralcel OD-H column, n-hexane:isopropanol=95:5; flow rate=1.0mL / min; UV detection at 210nm...

Embodiment 3

[0064] Preparation of 1-phenylpropanol from propiophenone (S / C=10 000)

[0065]

[0066] Under high-purity argon atmosphere, [Ir(COD)Cl] 2 (3.4mg, 0.005mmol) and chiral ligand L6 (9.2mg, 0.011mmol) were dissolved in isopropanol (1mL) and stirred at room temperature for 3 hours to obtain a clear orange solution. Take 20 μL (0.001 mol%) of the orange solution with a microsyringe and add it to a mixed system of propiophenone (2 mmol), isopropanol (2 mL) and lithium tert-butoxide (1 mol %). The reaction system was placed in an autoclave at room temperature and H 2 (20atm) and stirred for 12 hours. The solvent was removed under reduced pressure and separated by column chromatography (using silica gel column, eluent: ethyl acetate) to obtain pure 1-phenylpropanol. The product was analyzed by HPLC, and the measured ee value was 99%. Determination of enantiomeric excess by HPLC, Chiralcel OJ-H column, n-hexane:isopropanol=95:5; flow rate=1.0mL / min; UV detection at 210nm; t R (S...

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Abstract

The invention belongs to the field of organic and medicine synthetic chemistry, and discloses a tridentate nitrogen phosphine ligand. The tridentate nitrogen phosphine ligand has a structure shown ina formula I which is shown in the attached figure, wherein R1 is toluene sulfonyl or 2,4,6-triisopropylbenzenesulfonyl, and R2 is aryl or substituted aryl. The invention also discloses a complex of the tridentate nitrogen phosphine ligand; the complex is prepared by mixing the tridentate nitrogen phosphine ligand and a transition metal complex; the complex is used for asymmetric catalytic hydrogenation of ketone. The tridentate nitrogen phosphine ligand has the advantages that 1, the synthesizing is easy, and the chiral ligand can be prepared by only two to three reaction steps; 2, the ligandis stable, the series of ligand is not sensitive to water and oxygen, and the convenience in storage and use is realized; 3, the catalyzing effect is good, and the catalyst can be used for realizing 100% of conversion and 99% of stereo selectivity on most of suitable primers; 4, the atom economy is high, and the activity of the catalysis system is higher; for most of suitable primers, the conversion number reaches more than 10000, and the maximum conversion number reaches 200000.

Description

technical field [0001] The invention belongs to the field of organic and pharmaceutical synthesis chemistry, and specifically relates to a tridentate nitrogen phosphine ligand and its complex, and its application in the asymmetric catalytic hydrogenation of ketones. Background technique [0002] Chiral alcohol is an important fragment that widely exists in drug molecules and natural products, such as Ezetimine, Duloxetine, Aprepitant, Crizotinib, etc. [0003] [0004] Due to the great industrial value of chiral alcohols in pharmaceutical and other fields, people have conducted in-depth research on the methodology of synthesizing chiral alcohols. Ultimately, asymmetric hydrogenation proved to be the most direct and efficient method for the synthesis of chiral alcohols. In the past few decades, the technology of asymmetric hydrogenation of ketones by using catalysts obtained by complexing palladium, rhodium, ruthenium and other metals with chiral phosphine ligands to obta...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07F17/02B01J31/24C07C29/145C07C33/20C07C33/46C07C33/18C07C41/26C07C43/23C07D333/16C07D307/42
CPCB01J31/2404B01J2231/643B01J2531/0205B01J2531/0225B01J2531/827B01J2531/842C07C29/145C07C41/26C07D307/42C07D333/16C07F17/02C07C33/20C07C33/46C07C33/18C07C43/23
Inventor 张绪穆梁志钦
Owner SHENZHEN CATALYS SCI & TECH CO LTD
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