Design, Synthesis Of Multi-functional Organocatalysts And Their Application In The Asymmetric Michael/Mannich Cascade Reactions Of Nitroolefins

Over the past years, organocatalysts bearing hydrogen bonding activating group has received rapid development. In2003, the bifunctional urea and thiourea catalysts were firtst synthesized by Takemoto’s group. Then, a series of thiourea-based organocatalysts have been developed and widely applied in various enantioselective transformations. In2008, a class of bifunctional amine-thiourea-bearing multiple hydrogen bonding donors were synthesized by Wang’s group. In which the nitro group was activated by the multiple hydrogen bonding donors.In this thesis, we have designed and synthesized a series of multi-functional organocatalysts and further successfully applied in the asymmetric Michael/Mannich cascade reaction of nitroolefins, in which, the nucleophilic substrate and the electrophilic nitro group and imine group were activated simultaneously by the multi-functional catalysts. This thesis is composed of the following three parts:Part Ⅰ:Three kinds of novel multifunctional organocatalysts were designed and synthesized, which were containing the functional groups of tertiary amines, thiourea and sulfonamide. Those organocatlysts were composed of1,2-cyclohexane-diamine derivatives,9-amino-cinchona derivatives and6-amino-quinine derivatives.Part Ⅰ:The first kind of multifunctional organocatalysts was applied for the asymmetric "two components" oxa-Michael/Mannich cascade reaction of salicylaldimines with nitroolefins. After screening the catalysts and the sulfonyl groups at the N-terminal of the salicylaldimine and optimizing the reaction conditions, such as temperature, solvent, catalyst loading, it was found that the catalyst Ih was capable of promoting the reaction with excellent results. Under the optimized reaction conditions, this approach provides a simple and efficient entry to polysubstituted chiral4-aminobenzopyrans with three consecutive stereocenters, and in high yield (up to97%) with excellent stereoselectivity (up to98%Ee and>99:1Dr). Facile access to the non-symmetric optically pure3,4-diamino chromanes was also obtained.Part Ⅲ:The asymmetric "three components" sulfa-Michael/Mannich cascade reaction of thiophenol, nitroolefins and imine was researched. After screening these three kinds of multifunctional catalysts and optimizing the reaction conditions, it was found that the6-aminoquinine derivatives, especially the catalyst Ⅲf, were capable of promoting the reaction with excellent results, under the conditions of the dichloromethane as a solvent to give the product in a high yield (94%), moderate enantioselectivity (75:25) and a high enantioselectivity (97%).