Study On Hydrogen Transfer-mediatd Cyclization Of N-heteroarenium Salts

N,O-fused heterocycles are widely used in the fields of natural products,functional materials,medicines and agricultural products.Thus,it is of great significance to develop green and efficient chemical methods for the synthesis of N,O-fused heterocycles.Pyridyl is extensively distributed in many functional molecules,but the pyridyl-containing aromatic heterocycles have high thermal stability and reaction kinetic inertness.So it is an important but challenging research subject that utilizes pyridine-based N-heteroarenes as raw materials to construct N,O-fused heterocycles.The hydrogen transfer coupling reaction is a new organic synthetic method that meets the needs of green and sustainable development,and is expected to solve some synthetic issues that are difficult to address with conventional methods.However,the development of hydrogen transfer-mediated one-pot multicomponent reactions still remains a challenge,as it is hard to selectively transer hydrogen to one or more specific sites among different substrates.In this paper,a series of fused pyrano[2,3-b]pyridyl derivatives with promising applications have been synthesized by hydrogen transfer-mediatd cyclization.The specific content includes the following three parts:In chapter 1,we have described the research advances of N,O-heterocycles in the development of bioactive and drug-relevant molecules.Then,we summarized not only the N-heteroarenium salt and its application in organic synthesis,but also the construction of N-heterocycles through hydrogen transfer-mediated cyclization strategy.Base on these descriptions,we raised the research purpose and content of this thesis.In chapter 2,by employing iridium/sodium tert-butoxide as the catalytic system,the N-heteroarenium salts is activated by hydrogen transfer to form imine intermediate,which is then captured by paraformaldehyde and 1,3-cyclohexanediones to give new N,O-fused heterocycles with a quaternary carbon at theβposition.This hydrogen transfer multicomponent reaction provides a new method to the construction of fused pyrano[2,3-b]pyridyl derivatives.Through the developed synthetic method,we synthesized 34 substrates with a yield of 48%-85%.Thus,this transformation has the advantages of using the readily available feedstocks,broad substrate scope,good functional group tolerance,high diastereoselectivity,and high step and atom efficiency.Noteworthy,paraformaldehyde is not only a hydrogen source but also a coupling agent in this reaction,so no need to add additional hydrogen source.In addition,the obtained product can be further transformed into a high-value N,O-heterocyclic compound.In chapter 3,we have described an Iridium-catalyzed hydrogen transfer-mediated three-component cyclization reaction of N-heteroarenium salts,paraformaldehyde and 4-hydroxycoumarins.Under N₂ protection and with the use of a[Ir Cp*Cl₂]₂/KOH catalyst system,we synthesized 29 substrates with a yield of 50%-90%.Thus,the developed hydrogen transfer multicomponent reaction allows to flexibly construct a series of novel fused pyrano[2,3-b]pyridyl derivatives.Thus,this reaction has laid the foundation for the further synthesis of biomedical active molecules.In summary,we have developed an Iridium-catalyzed multi-component hydrogen transfer cyclization of N-heteroarenium salt,paraformaldehyde and different cyclic 1,3-diketones,which provides a new effective synthetic method for the direct construction pyrano[2,3-b]pyridyl derivatives.The present work laids the foundation for the further design of hydrogen transfer-mediated multicomponent reactions,and enriched the methods of organic synthetic chemistry.