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A method for the preparation of chiral amines by asymmetric reductive amination of ketones

A chiral amine, asymmetric technology, applied in the direction of organic chemistry methods, cyanide reaction preparation, chemical instruments and methods, etc., can solve the problems that aliphatic ketones are not applicable, and achieve mild conditions, high atom economy, and high catalytic activity Effect

Active Publication Date: 2022-04-12
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

[0004] In 2003, Yongxiang CHi (Y.X.Chi, Y.G.Zhou, X.M.Zhang J.Org.Chem.2003,68,4120-4122) reported the direct asymmetric reductive amination of aromatic ketones with 4-methoxyaniline as amine source Reaction, can obtain chiral α-arylamine product under Ir-(S, S)-f-Binaphine catalysis, and its product yield is greater than 93%, enantioselectivity reaches 96% at the highest, but this catalytic system is to fat Ketones don't work

Method used

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  • A method for the preparation of chiral amines by asymmetric reductive amination of ketones
  • A method for the preparation of chiral amines by asymmetric reductive amination of ketones
  • A method for the preparation of chiral amines by asymmetric reductive amination of ketones

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Experimental program
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Effect test

Embodiment 1

[0035]

[0036] Under nitrogen protection, [Ir(COD)Cl] 2 (0.0025mmol, 0.5mol%), chiral phosphine-phosphoramidite ligand (shown in the above formula) (0.0055mmol, 1.1mol%) was dissolved in toluene (1.0mL), stirred at room temperature for 10 minutes, added substrate 2 , a solution of 6-dimethylaniline (0.5mmol) and acetophenone (0.6mol) in toluene (1.0mL) and 0.2ml of isopropyl titanate were placed in an autoclave, replaced by hydrogen 3 times, and then Introduce hydrogen to 50 atmospheres, and react at 50°C for 12 hours. Hydrogen gas was released slowly, and the product was separated with a silica gel column after removing the solvent.

[0037] The product is detected and analyzed, and the NMR and HPLC data are as follows:

[0038] 98%yield.97%ee was determined by chiral HPLC (chiralcel OJ-H, n-hexane / i-PrOH=90 / 10, 1.0mL / min, 254nm, 40℃):tR (major)=4.9min,t R (minor) = 5.4min.[α] D 25 =-158 (c=1.42in CHCl 3 ). 1 H NMR (400MHz, CDCl 3 ): δ=1.54(d, J=6.8Hz, 3H), 2.19(s...

Embodiment 2

[0041] Change the reaction condition chiral phosphine-phosphinoamide ligand in embodiment 1 into B, and all the other are the same as embodiment 1, and react to obtain product 2,6-dimethyl-N-(1-phenylethyl) aniline Yield 98%, enantioselectivity 90% ee. Ligand B has the following structure:

[0042]

Embodiment 3

[0044] Change the reaction condition chiral phosphine-phosphinoamide ligand in embodiment 1 into C, and all the other are the same as embodiment 1, and react to obtain product 2,6-dimethyl-N-(1-phenylethyl) aniline Yield 98%, enantioselectivity 80% ee. The structure of Ligand C is as follows:

[0045]

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Abstract

The invention discloses a method for preparing chiral amines by asymmetric reductive amination of ketones. The method uses chiral phosphine-phosphoramidite ligands and metal iridium precursors to prepare complexes in situ as catalysts, and ketones and amines directly Asymmetric reductive amination of chiral amines. The preparation of the ligand of the invention is simple, the dosage of catalyst is low, the operation is simple and continuous operation can be realized, and it is suitable for large-scale preparation of chiral amine. 2-ethyl-6-methylaniline / catalyst (S / C) is 500000 to have better result when the present invention is synthetic to the intermediate of pure metolachlor, reaches 95% yield, 80% enantioselective It has good industrial applicability.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for preparing chiral amines by asymmetric reductive amination of ketones. 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 main methods for the synthesis of chiral amines include asymmetric hydrogenation and asymmetric reductive amination of imines and enamines. Among them, asymmetric reductive amination is a green, environmentally friendly and efficient method for the synthesis of chiral amines. With the help of chiral catalysts and other auxiliary agents, it directly reacts ketone compounds with amine sources to generate chiral amine compounds. This reaction omits the step of preparing imine or enamine intermediates in asymmetric hydrogenation, which improves the yield of chiral amines and...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C209/54C07C211/45C07C211/48C07C211/52C07C213/08C07C215/08C07C227/08C07C229/18B01J31/22
CPCC07C209/54C07C213/08C07C227/08B01J31/2295C07B2200/07B01J2531/827B01J2231/4277C07C211/45C07C211/48C07C211/52C07C215/08C07C229/18
Inventor 胡向平胡信虎
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI