Application Of The Oxidative Dehydrogenative Aromatization Reaction In The Synthesis Of Pyrroles And Indolizines

Heterocycles widely exist in the skeleton of natural products,show a variety of biological activities and have thus been applied in many fields,such as biology,medicine,pesticide and materials.Synthesis and biological activity research for nitrogen heterocyclic compound has received extensive attention from chemists and biologists.Moreover,pyrroles and indolizines are two kinds of important aromatic heterocyclic compounds with nitrogen.In recent years,the application of oxidative dehydrogenation aromatization reactions has been made great development in the field of organic synthesis.Compared with other methods,dehydrogenation aromatization reaction has more good atom economy,and has thus become one of the research hotspot in the field of organic synthesis.At the same time,the reaction promoted by non-metallic oxidant has good prospect for its environmentally friendly,highpurity product and mild conditions,usually demanding without anhydrous and anaerobic conditions.In this paper,we mainly developed the method of synthesis of pyrroles and3-aryl/3-alkyl indolizines from simple start materials through one-pot process,and the dehydrogenation aromatization reaction was promoted by non-metallic oxidants.The work mainly includes the following three parts.Part ?,the synthesis of multi-substituted pyrroles.Herein,we report the development of a benzoyl peroxide-mediated oxidative dehydrogenative aromatization reaction for the construction of pyrroles.We subsequently developed a one-pot tandem reaction that combined this new method with a well-defined silver-catalyzed 1,3-dipolar cycloaddition reaction,thereby providing a practical method for the synthesis of multisubstituted pyrroles from easy available alkenes.The mechanism of this oxidativedehydrogenative aromatization reaction was also examined in detail.Part ?,the synthesis of 3-aryl indolizines.A transition-metal-free synthetic route to 3-aryl indolizines from electron-deficient alkenes,pyridines and benzyl halogenations is reported using a tandem reaction for the first time.The key step of this method is the oxidative dehydrogenative aromatization of a tetrahydro indolizine intermediate with 2,2,6,6-tetramethylpiperidine-N-oxyl(TEMPO)as the oxidant.A series of synthetic 3-aryl indolizines have been achieved though an one-pot method,the maximum yield up to 100%.At the same time,the reaction was successfully amplified to the scale of gram.Part ?,the synthesis of 3-alkyl Indolizines.Fellowing the study of the synthesis of 3-aryl indolizines,we have also achieved a series of 3-alkyl Indolizines through an one-pot method from pyridines,halogenated alkanes and electron-deficient olefins,the maximum yield up to 97%.There is also an oxidative dehydrogenative aromatization of a tetrahydro indolizine intermediate with TEMPO as the oxidant.