Studies On Asymmetric Reaction Catalyzed By Bifunctional Hydrogen Bonding Catalysts

This thesis mainly focused on the design, synthesis of chiral bifunctional hydrogen bonding organocatalysts and their application in asymmetric transformations. The details are summarized below:In Chapter1, the significant progress of bifunctinal organocatalysis in the past ten years has been briefly reviewed. Representative catalysts and types of reactions were listed. New directions and challenges in this field were also proposed.In Chapter2, an efficient asymmetric N-Nitroso Aldol reaction of1,3-dicarbonyl derivatives and nitrosobenzene using bifunctional squaramide organanocatalysts was described. A briefly survey of various bifunctional organocatalysts revealed that the catalyst bearing squaramide moity showed great activity and stereoselectivity in the asymmetric N-Nitroso Aldol reaction. Under optimized conditions, the corresponding adducts was obtained with up to98%ee. Moreover, conversion of these adducts to the corresponding N-phenyl α-amino acid derivatives could be realized by using acetic acid and zinc dust as the reducing agent.In Chapter3, a family of novel chiral aminoalcohol bifuncational organocatalysts has been designed and synthesized start from (IS,2S)-2-amino-l-(p-nitrophenyl) propane-1,3-diol which is a by-product in the industrial production of chloramphenicol. These catalysts were tested by asymmetric alcoholysis of a series of bi-and tricyclic succinic anhydrides and monocyclic glutaric anhydrides, and corresponding hemiesters were obtained in high yield with good enantioselectivity (up to93%ee). The hemiester could be reduced to afford a lactone with good yield and enantioselectivity. In addition, the usefulness of this methodology was demonstrated in the asymmetric synthesis of the key intermediate of P2X7receptor antagonists.In Chapter4, a highly enantioselective thiolysis of a range of anhydrides has been achieved in84-94%yield with81-92%ee using these catalysts above derived from a inexpensive aminoalcohol. Thiols other than benzyl mercaptan also were effective nucleophlies in the desymmtrization reaction and gave excellent enantioselectivities. In addition, a synthetic application of this methodology was demonstrated in the asymmeric synthesis of pregabalin.