Novel Organic Catalysts Catalyzed Asymmetric Aldol Reaction Of Aldehyde With Aldehyde

Asymmetric organic synthesis is one of the most attractive research areas in organic synthesis.As a new method for asymmetric synthesis,enantioselective orgaocatalysis is becoming more and more popular.It has been becoming an intriguing challenge to explore novel and effective small-molecule organocatalysts.The Aldol reaction is an important reaction of the C-C bond forming reactions,aldol structural units present in many molecules(including natural products and synthetic molecules),which make up a large family of chiral intermediates for synthesis of many drugs.In previous research,most of the small-molecule catalysts are proline and its derivatives.The most explored organocatalytic Aldol reactions are concentrated in ketones as the nucleotrophiles.Aldols between two different aldehydes are not sufficiently explored.One challenge in using aldehyde electronic donors in direct catalytic enantioselective aldolization lies in the very weak nucleophilicity of aldehyde-derived enamines as compared to those derived from ketones.More importantly,the aldol products,being aldehydes themselves,may undergo further aldolization.This is the main reason for less research of the reaction of aldehydes as the donor.In this thesis,a new series of small organic micromolecular catalysts C1-C9 were synthesized from readily available natural amino acids,which were used to study the Aldol reaction between alkylaldehydes and aldehydes.1.A series of catalysts C1-C9 were synthesized and the effects on the catalytic activity and enantioselectivity were studied.2.The catalytic activity and enantioselectivity of the suitable catalyst C9 have been researched in the Aldol reaction of isobutyraldehyde and ethyl glyoxylate as well as in the influence of the type and amount of additives,temperature,different solvents,and the amount of catalyst etc.3.The results indicated that:different additives have great influences on the enantioselectivity of the products.The Acetic acid is the optimal one which significantly improved the enantioselectivity.The amount of acetic acid and the catalyst C9 make little impact on the ee and yield.Low temperature can improve the enantioselectivity,but markedly reduce the reaction rate.The effect of solvents for this reaction is unapparent.The most important thing is that we used this catalyst to successfully explore the Aldol reaction of the alkyl aldehyde with different aldehydes,with good yield and enantioselectivity.