Synthesis Of2-acylpyrroles And Fused Pyrroles Based On The Domino Reactions Of Methyl Isocyanide

Pyrroles are an important class of heterocyclic compounds. Many drugs, natural productsand synthetic materials contain pyrrole structural unit. In the past century, therefore, synthesisof pyrrole and its derivatives has been a research focus in organic synthesis. However, newand straightforward methods to access these compounds from simple starting materials arestill highly desirable, in particular the approach has the advantage of being amenable tostructural diversification.In this thesis, we have developed novel and efficient domino reactions for the synthesisof polysubstituted pyrroles, fused pyrrole and indolizidine derivatives. These methods haveapparent advantages, such as readily available starting materials, mild reaction conditions,atom and step economy and diversification of product structure. Mechanisms of these newreactions are also investigated in details.The thesis is divided into six chapters. In chapter one, the development of tandemreactions, heterocyclization based on methyl isocyanide and pyrrole synthesis in recent yearsare reviewed. The thesis proposal is presented in chapter two.Chapter three describes an efficient and atom-economic strategy for the synthesis ofcyclopenta[b]pyrroles under extremely mild and transition metal-free conditions. In thetandem reaction, a new paradigm for trapping of the incipient imidoyl anion by intramolecularγ-carbon electrophile is realized, and two C–C sigma bonds are formed.Chapter four shows a tandem Michael addition/isocyanide insertion reaction ofα,β-unsaturated ketone and tosyl methyl isocyanide. A concise and efficient methodology forthe one-pot synthesis of a variety of functionalized2-acylpyrroles is developed. For the fristtime, we have realized the isocyanide insertion into C–C bond reactions.In chapter five, a synthetic method of indole-4,7-quinones, seven-andeight-membered-ring fused pyrroles from cyclic α,β-unsaturated ketone and tosyl methylisocyanide, which went through Michael addition/isocyanide insertion into acyl C–C bondprocess, is described. The initial carbon rings are expanded by one-carbon-atom while thepyrrole rings were constructed.Chapter six, under catalysis of alkali, we have developed a new tandem [7+1]annulation/intramolecular cyclization reaction from the reaction of ethyl isocyanoacetate with-dialkenoyl ketene dithioacetals. This reaction features high to excellent yields, mildtransition metal-free conditions, high diastereoselectivity and perfect atom-economy.Furthermore, a series of8-azabicyclo[5.2.1]dec-8-enes and tricyclic indolizidine derivativeswith six adjacent stereocenters were synthesized in excellent yields in one-step.