Studies On The Tandem Reactions Of Ethyl Isocyanoacetate With Polysubstituted 1,4-dien-3-ones

Tandem reactions, which result from the combination of multiple transformations in a single pot, could efficiently afford complex products from simple, readily available starting materials. Such processes are both economically and ecologically beneficial and environmentally benign, which could minimize the requisite reagents, solvents, costs, time, and separation processes for the desired transformation and also minimize the formation of waste. Therefore, the development of novel tandem reactions is particularly attractive in modern organic chemistry.This dissertation is devoted to develop novel strategies for the construction of biologically active fused and -bridged pyrrole compounds through highly efficient multisteps tandem reactions between isocyanoacatate and 1,4-dien-3-ones. Mechanisms of these new reactions were also investigated in details.The dissertation is divided into five chapters. In chapter one, the progresses on both tandem reactions and isocyanide chemistry were reviewed. Based on chapter one and combined with our group's research works, the dissertation proposal was presented.Chapter three describes a novel strategy for the synthesis of pyrrolizidines through an organocatalytic quadruple tandem reaction. Catalyzed by DBU, polyfunctionalized pyrrolizidines were stereoselectively constructed by a tandem double-Michael-addition/cyclization/acyl migration of 1,4-dien-3-ones and ethyl isocyanoacetate. A possible mechanism of this reaction is proposed based on the isolated intermediates.Chapter four involves a novel strategy for the synthesis of 6-azabicyclo[3.2.1]octanes by an organocatalytic triple domino reaction. Catalyzed by DBU, polyfunctionalized 6-azabicyclo[3.2.1]octanes with up to five adjacent stereocenters were stereoselectively constructed by a tandem double-Michael -addition/cyclization of 1,4-dien-3-ones and ethyl isocyanoacetate.Chapter five shows a new strategy for the stereoselective synthesis of 4,5,7,7a-tetrahydrobenzo[d]oxazol-6(3aH)-ones by tandem Michael addition/1,3- dipolar cycloaddition reactions ofα-alkenoyl-α-benzoyl ketene-(S,S)-acetals and isocyanoacetate.The benefits of the tandem reactions in this dissertation are summarized as below: (1) novel mechanism; (2) high efficiency, up to four bonds and two rings were formed in one-pot operation; (3) up to four adjacent stereocenters were formed; (4) perfectly atom-economy; (5) excellent regio- and diastereoselectivity. The studies in this dissertation discovered novel and efficient domino reactions to form azabicyclic skeleton, found in natural alkaloids, and paved the way to synthesis such natural-like product libraries under simple, mild and environmentally benign conditions.