Heterocyclization Based On Alkenoyl Acetamides

Traditionally, heterocyclic chemistry is the largest branch in organic chemistry. A widevariety of heterocyclic compounds (about half of the total organic compounds), widely usedin medicine, agricultural chemicals etc., and is closely related to life science and materialscience. Heterocyclic compounds in organic synthesis accounts for a sizeable proportion ofvoluminous literature. Heterocyclic compounds, especially aza-heterocycles (eg alkaloids)posses a wide range of biological activity and structural diversity, making it the main goal ofthe synthesis. Exploring the synthetic methodology of heterocyclic compounds, especially ina simple, efficient, and atom economy fashion, is very desirable.In the past several decades, α-acyl acetamide compounds have been extensively andsuccessfully used as synthetic precursors for the synthesis of polyfunctionalized heterocycles.The study in this thesis focuses on the discovery of new synthetic methods of the syntheses ofseveral novel heterocycles including two-carbon-tethered heterocyclic pairs,tetrahydroindole,piperidone, tetramic acids and succinimide derivatives by tandem reaction, intramolecularcyclization and oxidative rearrangemen, respectively, starting from the easily availablealkenoyl acetamide derivatives on the other hand, the related reaction mechanisms arediscussed.The thesis is divided into six chapters. In the first chapter, a review for the research onthe use of alkenoyl acetamide compounds for the synthesis of several heterocyclics in recentyears. And the thesis proposal is presented in chapter two. In chapter three, it is describes thata new strategy for the synthesis of C2-tethered pyrrole/oxazole pairs in good to high yieldsunder mild reaction conditions from alkenoyl acetamides and ethyl isocyanoacetate. Thistandem reaction comprises two [3+2] cycloadditions and allows the construction of twodiferent heterocycles in a single step. This new strategy involves the formation of four C-Cand one C-O bonds in a regio-and diastereoselective manner with the chemoselectivefragmentation.Chapter four describes a new strategy for the synthesis of various highlyfunctionalized7-aza-tetrahydroindoles from α-alkenoyl acetamide and ethylisocyanoacetate in a single step under mild conditions. A new reaction mechanism isproposed based on the observation that isocyanide carbon plays the role of a1,1-dielectrophile.Chapter five introduces a new concept, polarity-reversible conjugate addition and showedhow the regioselectivity of a conjugate addition can be reversed with a simple and subtlechange in a remote substituent. This concept provides new insights into the conjugate addition chemistry.In Chapter six, an oxidative rearrangemen pathway to succinimide derivatives fromtetramic acids is described. This new oxidative rearrangement reaction is unique in severalrespects including the use of triplet oxygen as oxidant without activation (metal-free systemswithout photoexcitation), and it is a noteworthy new tandem reaction.