Synthesis Of Chiral Pyrrolidine-Binaphthyl Carboxamides And Their Application On Enantioselective Michael Addition

The Michael addition reaction is one of the most important carbon-carbon bond-forming reactions in organic synthesis. Asymmetric organocatalytic Michael addition has attracted intense interests in the recent years due to its environmental friend-liness, stability, cheapness and the generation of multiple chiral centers in a single step. Recently, many researchers have focused on the design and synthesis of new and highly efficient organocatalysts. This thesis include the following parts:Firstly, introduced some general examples of Michael addition and applacations in synthesis, meanwhile, we also introduced organocatalyzed Michael addition in details.Secondly, designed and synthesized chiral pyrrolidine-binaphthyl carboxamides organocatalysts. In this paper, after we carefully studied the structural characteristics of excellent pyrrolidine-based catalysts which had been reported previously and the research of optically active 1, 1'-bi-2-naphthol(BINOL) and its derivatives which have been extensively used in asymmetric catalysis and chiral recognition, we designed a series of pyrrolidine-binaphthyl carboxamides catalysts. Through the protection of hydroxyls using MOM; under the action of n-BuLi. we got the (R)-3,3'-dicarboxylicacid BINOL and (S)-3,3'-dicarboxylicacid BINOL; then remove the MOM protection; synthesis pyrolidine-amide. Then, using trifluoroacetic acid to remove the Boc protection we obtained the target catalysts.Thirdly. In this context. we document the asymmetric Michael addition of nitroolefins and cyclohexanone with the use of R and S as organocatalysts. The influence of catalysts'structure, catalyst loading, additives and solvents to the yields and enantioselectivities of the adducts was investigated, and a series of encouraging results were obtained. At 20℃, toluene as solvent,10 mol% of catalyst, adding 10 mol% of benzoic acid which is the optimized conditions. Michael addition product yield up to 95%, ee value> 99%. dr value (syn:anti) up to 99:1, syn type is the main Michael product. We successfully achieved highly enantioselective catalysis for asymmetric carbon-carbon bond formation reactions. However, according to the catalytic results, the catalytic center of the designed catalyst on the two sides didn't play a catalytic role at the same time.Under the optimized conditions, we also studied the asymmetric nitro-Michael addition reaction of different (3-nitroolefins and cyclohexanone. The reactions of differentβ-nitroolefins and cyclohexanone proceeded smoothly in excellent enantioselectivities and diastereoselectivity (yield up to 87%, ee value up to 94%, dr value>99:1) to furnish the Michael adducts. At the same time, we also accumulated a lot of data and experience for the asymmetric catalysis of Michael addition in the future.Via the researching work of this dissertation, we hope that we can provide preliminary theoretical basis for design of new organocatalysts for Michael additions and provide reference for development of catalyst diversity.