Methodology For The Synthesis Of Nitrogen-containing Heterocycles Based On The Tandem Cyclization Reaction Of Conjugated Allenic Aldehydes/Ketones

Nitrogen-containing polycyclic compounds are commonly found in natural and biologically active compounds,which are regarded as a very important class of functional molecules for the agrochemical,pharmaceutical and fine chemical industries.The needs of social development and the requirements of environmental protection have led to the continuous development of methodology for building such compounds.That highly efficient,rapid and controllable conversation,are the only requirement for organic synthetic chemistry in the new era.Due to their characters of simple synthesis from raw materials,multiple reaction sites,and high conversion efficiency,conjugated alkynyl aldehydes/ketones have been continuously displayed their unique chemical fascination in the field of tandem reactions in the past decade.After decades of development,a systematic synthesis methodology with these compounds have formed,which provides a rich and realistic theoretical support for the efficient and rapid construction of diverse nitrogen heterocyclic compounds.The first chapter in the introduction systematically summarized the tandem cyclization of conjugated allynaldehydes/ketones and their applications in the construction of polycyclic compounds.Based on the differences in the cyclization patterns of alkynes and the differences in the intermediates of different cyclization modes,the recent advances in the chemistry of conjugated allynaldehydes/ketones were reviewed.In the second chapter,the synthesis of indolinone and 2-methylenepyrroline compounds was reported in synergistic catalytic of cuprous chloride/triethylamine.In this reaction system,The conversion of the conjugated allynal is efficient and rapid.The reaction can continuously form four chemical bonds,and a series of aza tricyclic compounds are constructed.The mechanism study found that the addition of triethylamine is a key factor in the tandem reaction.The addition of stoichiometric triethylamine not only effectively suppresses side reactions but also promotes further conversion of the reaction.Based on the suggestion of the control experiments results,triethylamine not only acted as a ligand to coordinate with copper to form a catalytic species,but also acted as Lewis base to promote the cyclization of propargyne in the later stage.The reaction conditions are mild,wide-applicable,and well-compatible even with heterocyclic substituted substrates.Further,the propargylamine substrate containing the internal alkyne(Cona-ene cyclization challenge substrate)can also be successfully performed.In the third chapter,the synthesis of indenone and tetrahydrooxazole nitrone compounds by enolone and nitrosobenzene is introduced.The reaction can be used to synthesize a series of aza polycyclic products quickly and efficiently without the need of a catalyst.Interestingly,in this reaction,the substrate alkynyl group is attacked by two molecules of nitrosobenzene,followed by the capture of the olefins in the molecule,resulting in the polyfunctionalization of the inert internal acetylene.The stereoselectivity and functional group compatibility of the reaction is good,and the reaction conditions are simple and mild.Based on the comprehensive experiments and literature,we believe that the reaction process is as follows: The two molecules of nitrosobenzene in the system and the alkynes of acetylenic ketones form a reversible intermediate dinitrone,where [2+3] cycloaddition occurs with olefins under heating conditions converting the final product.