Studies On The Synthesis And Asymmetric Catalytic Behaviors Of Novel Isosteviol Based Chiral Bifunctional Organocatalysts

Organocatalysis is the third important asymmetric catalytic method followingorganometallic catalysis and enzyme catalysis. Over the past decade, the research ofthis area has grown rapidly to become one of the most exciting current fields inorganic chemistry and much interest has been devoted to the development of highlyefficient organocatalysts for a variety of reactions. Since the "single molecule, dualactivation" concept was developed, a number of thiourea-based andsquaramide-based organocatalysts have been designed and widely applied in variousstereoselective transformations and exhibited excellent asymmetric catalyticactivities. Base on the new concept of organic asymmetric catalysis “bifunctionalorganocatalyst” and isostiviol, an inexpensive and readily available natural productpossessing a hydrophobic skeleton, design and synthesis of novel organocatalystsand their catalytic activities in asymmetric C-C bond forming reactions wereinvestigated.In the first part of the dissertation, the concept of chirality, the meaning ofasymmetric synthesis, as well as asymmetric organocatalysis were briefly introduced.The recent progress on chiral amine-thiourea and amine-squaramide catalyzedstereoselective Michael addition has also been summarized.In the second part, based on the “bifunctional catalyst” concept, two novel kinds ofchiral thiourea and squaramide organocatalysts were designed and synthesizedstarting from isosteviol and DACH.In the third part of the thesis, highly doubly stereocontrolled enantioselectiveMichael addition of isobutyraldehyde to nitroalkenes and aldehyde to N-substitutedmaleimides were developed by using the chiral amine-thiourea catalysts.Furthermore, the reactions of isobutyraldehyde and nitroalkenes proceeded smoothlyboth in organic solvents and in water under mild conditions. High isolated yields (upto98%) and enantioselectivities (up to99%ee) were obtained using our catalyticsystem. In addition, combined with the computer simulation and theoretical calculation, the proposed reaction mechanism and working model of transition statewere suggested. Furthermore, the catalytic system of aldehyde and N-substitutedmaleimides can be used efficiently in large-scale reactions with the yields andenantioselectivities being maintained at the same level.In the following study, we described two highly efficient oaganocatalyticasymmetric Michael additions of acetylacetone to nitroolefins and ?-substitutedcyanoacetates to maleimides promoted by novel isosteviol-derived bifunctionalthiourea. Doubly stereocontrolled organosyntheses were achieved in the Michaeladdition of acetylacetone and nitroolefins, comparable isolated yields (up to95%)and enantioselectivities (up to97%ee) were obtained. While in the reaction of?-substituted cyanoacetates and maleimides, thiourea the catalysts obtained from(S,S)-DACH showed better asymmetric catalytic activities.In the next part, we reported, for the first time, the asymmetric catalytic behaviorsof the novel chiral bifunctional primary amine-squaramide organocatalysts based onisostiviol. Their successful applications in the doubly stereocontrolledenantioselective Michael addition of isobutyraldehyde to nitroalkenes (up to98%yield and up to99%ee) as well as the aldehyde to N-substituted maleimides (up to98%yield and up to99%ee) were described. The possible reaction mechanism andtransition state were also proposed.In the six part of the dissertation, we presented the highly enantioselectiveMichael addition of acetylacetone to nitroolefins catalyzed by the novelisosteviol-based thiral amine-squaramide organocatalyst. It is worth mentioning thatthe reactions carried out smoothly both in neat conditions and in CHCl3, and bothgave high isolated yields (up to95%in neat condition; up to97%in CHCl3) andenantioselectivities (up to97%in neat condition; up to99%in CHCl3).