| The asymmetric Michael addition of ethyl nitroacetate to enones that providesstraightforward access to-nitro-keto esters containing two chiral centres is an effectiveC-C bond-foming method and the resulting multi-functional products can be easilytransformed into many useful compounds such as chiral pyrrolidines in organic synthesis.However, there are only about ten papers relating to the topic of asymmetricorganocatalytic Michael addition of ethyl nitroacetate to enones in the past decade.Although having made some achievements already, there still exist some weaknesses suchas the long reaction time, the narrow substrate scope, the low enantiomeric excess, thehigh catalyst loading, the expensive but single catalyst which is unable to reuse and so on.In this thesis, we mainly focused on the study of chiral primary amines catalyzedasymmetric organocatalytic Michael addition of ethyl nitroacetate to enones in thepresence of acid additives and the work are summarized as follows.Firstly, we chose the asymmetric Michael addition of ethyl nitroacetate to(E)-4-(4-methoxyphenyl)but-3-en-2-one as the model reaction to screen a series of newlydesigned and synthesized chiral primary amine catalysts derived from chiral amine acidsand camphor. It was found that primary amine catalyst of36g gave the best result in termsof both the yield and the enantiselectivity.Secondly, optimizations of the reaction conditions such as solvents and acid additiveswere carried out one by one. The best reaction conditions were established as follows: theasymmetric Michael addition of ethyl nitroacetate to enones in the presence of10mol%ofchiral primary amine catalyst of36g in combination with10mol%of2-nitrobenzoic acidas acid additive in solvent of CH2Cl2at room temperature. Finally, under the optimized reaction conditions, the scope of the reaction wasinvestigated offording the corresponding products in68-97%yield, ee up to94%/94%anddr less than2:1. |
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