Iridium/chiral diphosphine system catalyzed imine asymmetric hydrogenation method

A chiral bisphosphine ligand, a technology for catalyzing imines, applied in organic chemistry methods, chemical instruments and methods, catalysts for physical/chemical processes, etc., can solve problems such as high equipment requirements and difficulty in ligand synthesis, and achieve catalytic activity. High, Inexpensive, Mild Effects

Active Publication Date: 2019-12-10
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, the synthesis of ligands used in this reaction is difficult, and a large amount

Method used

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  • Iridium/chiral diphosphine system catalyzed imine asymmetric hydrogenation method
  • Iridium/chiral diphosphine system catalyzed imine asymmetric hydrogenation method
  • Iridium/chiral diphosphine system catalyzed imine asymmetric hydrogenation method

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Experimental program
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Effect test

Embodiment 1

[0038] The ligand synthesis method involved in the present invention is shown in the following reaction equation:

[0039]

[0040] Among them, (R c ,S p )-I a :R=Me, R'=H; (R c ,S p )-I b : R=Et, R'=H; (R c ,S p )-I c :R=Ph,R'=H etc

[0041] 1 Preparation of ligand (R c ,S p )-I a

[0042] Under the condition of argon, 1.32g (R c ,S p )-PPFA(I) and 1.63g of imidazole were dissolved in 15ml of dehydroacetic acid, heated to 80°C for 8 hours. After cooling, it was neutralized with excess saturated sodium bicarbonate solution, then extracted with dichloromethane (3×50ml), the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and desolvated. The crude product was analyzed by column chromatography (n-hexane Alkane / ethyl acetate / triethylamine=10 / 10 / 1) to obtain 1.24 g of brown crystal II, yield 89%.

[0043] Under the condition of argon, 0.23g II was dissolved in 15ml dry ether, and 0.47ml n-BuLi was slowly added dropw...

Embodiment 2

[0063] The hydrogenation reaction was carried out in a 200ml autoclave. First replace the reactor with nitrogen three times, then inject 52g of imine (generated by 2-methyl-6-ethylaniline and methoxyacetone) into the reactor, and then inject 0.5ml of in-situ coordinated catalyst Ir -I a (S / C=5×10 5 ). Then replace with hydrogen three times, pressurize to 50bar with hydrogen, raise the temperature to 80°C for 3h, cool down, release the pressure, open the kettle, and the reaction conversion rate is greater than 99% according to GC analysis, and 50g (S)-NAA is obtained by distillation under reduced pressure. 95%, HPLC analysis ee value is 91%.

[0064] The liquid phase and NMR spectrum data are as follows:

[0065] HPLC (OJ-H, n-hexane / i-PrOH=98 / 2, 1.0ml / min, 254nm, 40°C):t R (minor)=3.9min,t R (major) = 4.3min. 1 H NMR (400MHz, CDCl 3 ):7.02(dd, J=7.6,15.2Hz,2H),6.89(t,J=7.6Hz,1H),3.36-3.40(m,6H),2.67(q,J=7.6Hz,2H),2.31 (s, 3H), 1.25 (t, J = 7.6Hz, 3H), δ = 1.20 (d, J =...

Embodiment 3

[0069] Other conditions are identical with example 2, catalyst Ir-I a Change to Ir-I b , GC analysis reaction conversion rate is greater than 99%, HPLC analysis ee value is 85%.

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Abstract

The invention discloses a method for catalyzing asymmetric hydrogenation of imines by an iridium/chiral diphosphine system, which comprises the following steps: reacting a chiral diphosphine ligand with a metal iridium precursor to prepare a complex in situ as a catalyst, and carrying out asymmetric hydrogenation on imines to prepare a chiral amine. The ligand is simple to prepare; catalyst dosage, simple operation, continuous operation can be realized, the preparation method is simple in process and suitable for large-scale preparation of chiral amine, the enantiomeric excess value of the product reaches 80% or above, and the preparation method has is excellent in effect when the S/C (2-ethyl-6-methylaniline/catalyst) rate is 500,000 during synthesis of the s-metolachlor intermediate, theyield reaches 95%, the enantioselectivity reaches 91%, and good industrial practicability is achieved.

Description

technical field [0001] The invention belongs to the field of organic synthesis, in particular to a method for asymmetric hydrogenation of imines catalyzed by an iridium / chiral bisphosphine system. Background technique [0002] Chiral amine compounds are important intermediates in organic synthesis and can be used to prepare various natural and non-natural compounds with biological activity. In recent years, the preparation of chiral amine compounds by asymmetric catalytic hydrogenation of imines has achieved great success [(a) H.-U. Blaser, F. Spinder in Handbook of Homogeneous Hydrogenation (Eds.: J.G.de Vries, C.J. Elsevier), Wiley-VCH, Weinheim, 2007, pp.1193; (b) C.Claver, E.Fernandez in Morden Reduction Methods (Eds.: P.Anderson, I.Munslow), Wiley-VCH, Weinheim, 2008, pp.237; (c) H.-U. Blaser, F. Spinder in Comprehensive Asymmetric Catalysis (Eds.: E. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, Berlin, 1999, pp.247.] But these The catalytic system has problems such a...

Claims

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Application Information

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IPC IPC(8): C07C217/08C07C213/06C07C229/18C07C227/04C07F17/02C07F19/00B01J31/22
CPCB01J31/2295B01J2231/643B01J2531/0225B01J2531/827B01J2531/842C07B2200/07C07B2200/13C07C213/06C07C227/04C07F17/02C07F19/00C07C217/08C07C229/18
Inventor 胡向平胡信虎
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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