Studies On Cross-Heterocylization Of Two Different Isocyanides

Heterocycles are a series of organic compounds that are of the greatest amount and numerous species.As an important branch of heterocycles,nitrogen-containing heterocycles are widely used in medicines,pesticides,dyes and materials.Therefore,the development of new methods for the synthesis of nitrogen-containing heterocycles is still highly required.Due to their unique structures and reactivities,isocyanides are versatile building blocks in chemical synthesis.Accordingly,isocyanides are widely employed in the well-known multicomponent Ugi and Passerini reactions as well as isocyanide-based insertion reactions.However,among these transformations,the chemoselective annulations of two different isocyanides has seldom been explored.In this thesis,new annulations of two different isocyanides are investigated,which demonstrate the unprecedented reactivity profiles of isocyanides.These new reactions provide practical and efficient protocols for the construction of highly functionalized nitrogen-containing heterocycles,such as pyrrolo[3,4-b]indoles,quinolones,naphthyridines,and phenanthrolines.The thesis involves four chapters.Chapter 1: Research background and thesis proposalIn this chapter,the general aspects of isocyanide are introducted,such as structure,properties,tranditional reactions and new reactivity profiles.The thesis proposal is also presented in this capter.Chapter 2: Cross-heterocylizations of isocyanides and 2-alkenyl phenylisocyanidesA new cross-heterocylization between isocyanides and 2-alkenyl phenyl isocyanides was developed for the expeditious synthesis of pyrrolo[3,4-b]indoles under thermal conditions.On the basis of the experimental results and DFT calculations,a mechanism for this domino reaction is proposed,involving chemoselective heterodimerization of two different isocyanides to form 1,4-diazabutatriene intermediates,followed by an intramolecular [3+2]-cycloaddition and 1,3-proton shift.This reaction represents the first example of heterodimerization of two different isocyano groups in a ‘head to head’ manner to generate a nonsymmetrical 1,4-diazabutatriene.The reaction also has the advantages of wide range of substrates,metal-free and 100% atomic economy.Chapter 3: Cross-heterocylizations of aryl and heteroaryl isocyanides with α-substituted isocyanoacetamidesAn unprecedented silver-catalyzed chemoselective cross-heterocylization of aryl and heteroaryl isocyanides with α-substituted isocyanoacetamides was developed for the facile and efficient synthesis of quinolones,naphthyridines,and phenanthrolines in this chapter.A mechanism for this multistep domino reaction is proposed on the basis of control experiments,involving heterodimerization of the two different isocyanides to generate an α-amidoketenimine intermediate,which undergoes 1,3-amino migration to form an α-imidoylketene followed by 6π electrocyclization.New reactivity profiles of isocyanides are exhibited by the generation of α-amidoketenimines from heterodimerization of these two isocyanides.Generally,the [3+2] cycloaddition of activated methylene isocyanides with aryl isocyanides has emerged as an efficient protocol for the catalytic synthesis of imidazoles.In this domino reaction,aryl and heteroaryl isocyanides serve as a four-atom component,and thus this transformation can be viewed as a [4+2]-annulation,which provides a general route to pyridone-fused carbo-and heterocycles.Chapter 4: Organocatalyzed aerobic oxidative Robinson-type annulation of 2-isocyanochalcones with active methylene ketonesIn this chapter,a DBU-catalyzed aerobic oxidative Robinson annulation of 2-isocyanochalcones with active methylene ketones was developed for the expedient and practical synthesis of phenanthridines in high to excellent yields under mild metal-free conditions.In this new domino transformation,two rings and three C-C bonds were simultaneously constructed in a single operation.Two reaction intermediates were isolated in the control experiments,which provided favorable evidence for the mechanism of the multistep reaction.The 7-hydroxyl group on the phenanthridines can be used as a handle for further diversity.