Method for preparing chiral amine by asymmetric hydrogenation of imine

Abstract

The invention discloses a method for preparing chiral amine by asymmetric hydrogenation of imine. Chiral ferrocene phosphine-diformamidine imine reacts with a metal iridium precursor in situ to prepare a complex which is used as a catalyst, and asymmetric hydrogenation is carried out on imine under the existence of an iodine salt or elemental iodine and under the combined action of acid, so that the chiral amine is prepared. The proper usage amount of the catalyst is that the molar ratio of the raw material imine to the catalyst (S / C) is 100000-1000000. According to the method, ligand preparation is simple, the use amount of the catalyst is low, operation is simple and convenient, continuous operation can be realized, the method is suitable for large-scale preparation of chiral amine, andthe enantiomer excess value (ee value) of the product reaches 80% or above, so that the requirements that the product serves as a pesticide intermediate can be met. According to the method, an ideal result is obtained for synthesis of (S)-metolachlor intermediates, and the method has very good industrial practicability.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for preparing chiral amine compounds by asymmetrically hydrogenating imines with high activity and high selectivity. 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, organic chemists at home and abroad have done a lot of work to prepare chiral amine compounds by synthesizing chiral ligands with different skeletons to regulate the asymmetric catalytic hydrogenation of imines, and achieved great success (Tang.W., Zhang .X.etc.Chem.Rev., 2003, 103, 3029.). However, these catalysts have problems such as low reactivity, narrow substrate range, and harsh reaction conditions. Patent (EP0691949B1) reported a better catalytic system, using chiral ligand {(R)-1-[(S)-2-diphenylphosphinoferrocenyl]}ethyl-bi...

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Problems solved by technology

However, these catalysts have problems such as low reactivity, narrow substrate range, and harsh reaction conditions.

Patent (EP0691949B1) reported a better catalytic system, using chiral ligand {(R)-1-[(S)-2-diphenylphosphinoferrocenyl]}ethyl-bis-(3 , 5-dimethylphenyl)phosphine and iridium-cyclooctadiene complex in situ formation catalyst, catalytic hydrogenation of MEA-imine in the presence of acid and tetrabutylammonium iodide at 50 degrees and 80 atmospheres of hydrogen Preparation of fine metolachlor intermediate, the highest enantiomeric excess value (ee) is 76%, but the ligands used in this reaction system are difficult to synthesize

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