Serine derived chiral amine compound as well as preparation method and application thereof

Abstract

The invention discloses a serine derived chiral amine compound as well as a preparation method and application thereof. The chiral amine compound contains a primary amine, a secondary amine or a tertiary amine functional group and has the structural formula as shown in the specification; and chiral amine and salts thereof are prepared through simple preparation steps by taking common chiral serine as the raw material to form the chiral amine compound. The chiral amine and the salts thereof can be used for catalyzing the asymmetrical Michael additive reaction between alpha, beta-unsaturated ketone and nitroalkanes, malonic ester, mercaptan, substituted rhodanine, substituted hydantoin or substituted oxazolone and the cyclopropanation between the alpha, beta-unsaturated ketone and sulfur ylide; the serine derived chiral amine compound has very high catalytic activity and stereoselectivity as well as the highest diastereoselectivity of 30 / 1 and the highest enantioselectivity of 99%, and is wide in oligomer range; and the serine derived chiral amine compound disclosed by the invention is a catalyst with high efficiency as well as good selectivity and controllability.

Description

technical field [0001] The invention relates to a novel class of chiral amine compounds derived from serine, and relates to a preparation method and a new application of the chiral amine compounds. Background technique [0002] Chiral amine compounds have a very wide range of uses and can also be used as chiral ligands or catalysts for catalytic reactions. In the past ten years, many new reactions using chiral amine compounds as catalysts have been discovered. Designing and synthesizing new chiral amine compounds or catalysts in the field of organic catalysis has important scientific and practical value. Currently, there are many articles disclosing chiral tertiary amines (Chem. Rev., 2003, 103, 2985, Acc. Chem. Res., 2004, 37, 621, Acc. Chem. Res., 2004, 37, 542), New reactions of chiral secondary amines (Chem. Rev., 2007, 107, 5416, Chem. Rev., 2007, 107, 5471) and chiral primary amines (Chem. Commun., 2009, 1807) in the field of organic catalysts, new synthesis method....

AI Technical Summary

Problems solved by technology

However, it should be pointed out that: ① Although the synthesis of such simple catalysts derived from phenylalanine, tryptophan, and serine is easy, the scope of structural modification and optimization of the catalysts is limited, and the reaction universality is often relatively poor. ②Although the amount of catalyst is large or the enantioselectivity of the reaction is better, its diastereoselectivity is poor; ③The last very important point is that these simple derivative catalysts ignore the large The steric hindrance of the substituent group plays a crucial role in the control of chirality. In fact, the introduction of a large steric hindrance substituent group can effectively force the reaction transition state to be single, reducing the possibility of other transition states that affect the reaction selectivity, thereby achieving Control over reaction stereoselectivity