Research On Asymmetry Reactions Catalyzed By New Chiral Rosin-derived Bifunctional Thiourea Organocatalysts

Organocatalysis is defined as the acceleration of chemical reactions with a substoi-chiometric amount of organic molecules, which do not contain an active metal reaction center. Asymmetric organocatalysis has just received much attention in the past few years as a result of organocatalysis has developed into a practical synthetic paradigm and started to serve as an important segment in common with biocatalysis and metal catalysis.The operational simplicity, ready availability of these mostly inexpensive bench-stable catalysts, which are incomparably more robust than enzymes or other bioorganic catalysts makes organocatalysis an attractive method for the synthesis of complex structures. Organocatalysis is usually fewer toxicity issues. Moreover, there is no risk of metal leakage and also no expensive recovery process is required in the waste treatment. Such protocols are increasingly finding application in the synthesis of both biologically active natural products and therapeutically important synthetic compoundIn recent years urea/thiourea catalysts due to its special characteristics of the structure and chemical reaction have attracted the attention of many chemists.Years of study have provided chemists with a relatively detailed understanding of catalysis by proton donors. Bronsted acids can accelerate organic reactions by either of two fundamental mechanisms:reversible protonation of the electrophile in a pre-equilibrium step prior to nucleophilic attack; or proton transfer to the transition state in the rate-determining step.This thesis includes six parts:In the first part, the progress on the organocatalytic asymmetric reactions catalyzed by chiral urea/thiourea organocatalysts is summarized.In the second part, we designed and synthesized a series of chiral rosin amine thiourea catalysts, and first used natural rosin derivatives in asymmetric catalysis.we hoped that we cound find excellent catalysts with high catalytic efficiency and enantioselectivity through tuning the chira amine backbone or the steric effect of the alkyl group on thiourea moiety.In the third part:Highly enantioselective synthesize γ-nitro heteroaromatic ketones in a doubly stereocontrolled manner catalyzed by bifunctional thiourea catalysts based on dehydroabietic amine. A new class of dehydroabietic amine-substituted primary amine-thiourea bifunctional catalysts were designed and synthesized. The doubly Stereo-controlled organocatalytic conjugate addition of a variety of heterocycles-bearing ketones to nitroalkenes was investigated for the first time, affording (S)-or (R)-γ-nitro heteroaromatic ketones with excellent enantioselectivities (up to ee>99%). Furthermore, the nearly optically pure γ-nitro heteroaromatic ketones can be readily transformed into chiral pyrrolidine carboxylic acids.In the fourth part:Doubly stereocontrolled asymmetric aza-Henry reaction with in situ generation of N-Boc-imines catalyzed by novel rosin-derived amine thiourea catalysts. The doubly stereocontrolled organocatalytic aza-Henry reaction of nitroalkanes to N-Boc-imines generated in situ from a variety of substituted a-amido sulfones was investigated for the first time, in general, affording the corresponding products with high to excellent yields (up to93%yield) and enantioselectivities (up to98%ee), and satisfactory diastereoselectivies (anti/syn up to98:2).In the fifth part:Highly enantioselective synthesis of N-Protected β-amino malonates in a doubly stereocontrolled manner catalyzed by rosin-derived amine thiourea catalysts:a doubly stereocontrolled apporch to β-amino acids. An efficient doubly stereocontrolled organocatalytic method to access chiral β-amino acids via asymmetric Mannich reaction with in situ generation of N-Boc imines by a new class of bifunctional rosin-derived tertiary amine thiourea catalysts has been established. These organocatalysts based on rosin have been proved to be the very effective promoters for this kind of catalytic asymmetric process and the reaction provides a convenient doubly stereocontrolled method to access synthetic useful β-amino acids with high optical purity.In the sixth part:The first asymmetric Vinylogous Mannich reaction of dicyano- alkylidenes with a-amido sulfones catalyzed by bifunctional Thiourea catalysts based on dehydroabietic amine:the reaction was highly regio-,stereoselective and practical for a broad range of substrates(generally93:7->99:1dr,84->99%ee) at room temperature. moreover,δ-amino acid derivatives with multiple chiral centers cound be generated from the adducts.