Novel Hydrogen Bond Promoted Organocatalytic Asymmetric Michael Reactions

The rganocatalytic asymmetric reaction is an increasingly active area in organic synthesis. The organocatalytic asymmetric Michael addition provides a rapid access to versatile important chiral building blocks and intermediates for the synthesis of bioactive chemicals and pharmaceutical compounds. In this dissertation, the applications of various organocatalysts to asymmetric Michael additions were summarized firstly. The catalytic activity and the asymmetric induction influenced by the structure of organocatalysts and the reaction conditions were also discussed. Based on these, a novel chiral amine-squaramide catalysts were intensively studied on their catalytic performance of asymmetric Michael reactions of 4-hydroxycoumarin, 4-hydroxypyrone and 2-hydroxyl-1, 4- naphthoquinone toβ,γ-unsaturated -keto esters.A novel class of chiral amine-squaramide catalysts which were prepared from 3, 4-dimethoxy-3-cyclobutene-1, 2-dione and quinine with fairly good overall yields exhibited good catalytic perfomance in the asymmetric Michael reactions of 4-hydroxycoumarin, 4-hydroxypyrone toβ,γ-unsaturated -keto esters. The study demonstrated that the organocatalytic process of substitutedβ,γ-unsaturated -keto esters with both 4-hydroxycoumarin and its analogues 4-hydroxypyrone could afford excellently optically enriched compounds (up to >99% ee) in high yields (up to 95%) under low catalyst loading (2.5 mol%). The absolute configuration of the Michael addition product has been confirmed through the X-ray diffraction analysis, and a plausible transition state of the reaction has been proposed.In the following study, the first enantioselective Micheal reaction of 2- hydroxyl-1, 4- naphthoquinone toβ,γ-unsaturated -keto esters has been disclosed by using the chiral amine-squaramide catalysts. It could get the corresponding chiral naphthoquinone derivatives with up to 88% yield and 98% enantioselectivity in 1,4-dioxane at room temperature under low catalyst loading (2.5-5 mol%). The absolute configuration of the Michael addition product also has been confirmed through the X-ray diffraction analysis.In conclusion, the organocatalytic enantioselective Michael reactions of 4-hydroxycoumarin, 4-hydroxypyrone and 2- hydroxyl-1, 4- naphthoquinone toβ,γ-unsaturated -keto esters have been developed firstly by using the novel chiral amine-squaramide catalysts. Furthermore, based on the experimental results, the plausible transition state and the mechanism of the reaction were analyzed and discussed to some extent, which lay a foundation for the further application of this class catalyst in asymmetric catalysis.