Copper-Catalyzed Tandem Cyclization Of 1,5-diynes For The Construction Of Oxa-quaternary Carbon-Containing Polycyclic Pyrroles

As the most classic reactive intermediates,carbocations are employed in the synthesis of a wide variety of valuable compounds.Among these compounds,polycyclic compounds,especially polycyclic heterocycles,have important synthetic significance due to their widespread existence in bioactive molecules and natural products.As synthetic chemists turn their attention to the synthesis of complex polycyclic heterocycles especially chiral heterocycles,as well as the development of green chemistry concepts,we have put forward more requirements for such reactions.There are still several problems in the application of carbocation chemistry in polycyclic/heterocyclic compounds synthesis:First,the main method for generating carbocations is the heterocleavage of carbon-heteroatom bonds under catalyst activation,which often requires the substrate to have a leaving group.On one hand,it increases the synthetic steps,on the other hand,it reduces the atom economy,and the leaving group may affect the reaction.Second,carbocation-based asymmetric reactions mainly use two types of noble metal catalysts,palladium and iridium,which lead to high reaction costs.Third,carbocation-based cyclization reactions are mainly carried out by Friedel-Crafts reactions,which involve the formation of a single new bond to generate a simple bicyclic compound.However,there are few reports on the formation of multiple new chemical bonds in one step to construct tricyclic and more complex polycyclic compounds.Tandem cyclization reactions based on 1,5-diynes are a feasible strategy to solve the above problems.In this paper,we use heteroatom-linked 1,5-diynes as substrates and copper as catalysts to generate vinyl cations.It avoids the synthesis of substrates with leaving groups,realizes 100%atom economy.Subsequently,through the ylide rearrangement reaction,two types of polycyclic pyrrole compounds containing oxaquaternary carbons were efficiently constructed,and their asymmetric reactions were realized by adding chiral ligands.This thesis is mainly divided into the following three parts:The first part introduces the method of carbocation generation,the synthetic strategy of polycyclic compounds based on carbocation and the synthetic strategy of chiral quaternary carbon based on ylide rearrangement reactions.Finally,we came up with this research content of paper through a systematic summary of these works.In the second part,the existing acyl migration reactions are introduced.Subsequently,the[1,2]-acyl migration reaction of oxonium ylides via vinyl carbocation intermediates was introduced.This reaction uses 1,5-diyne as a substrate to generate vinyl cation under the activation of the copper catalyst,and then the oxygen on the ester group attacks the vinyl cation to obtain an oxonium ylide intermediate.It undergoes[1,2]-acyl migration to construct oxaquaternary carbon-containing polycyclic pyrrole compounds.By adding chiral ligands,the first asymmetric reaction based on non-noble metal catalysis is realized.This reaction has many advantages like mild reaction condition,high bond forming efficiency,excellent enantioselectivity.It can realize preparative-scale reactions,and can also construct chiral tertiary alcohols through product derivatization,which is very meaningful.In the third part,we further study this kind of ylide rearrangement reaction and try to challenge the more difficult[1,2]-aryl migration reaction.High chemoselectivity,high enantioselectivity,and high yields of chiral benzopyranpyrroles were obtained through the regulation of the reaction system which avoided the occurrence of FriedelCrafts reaction.The first asymmetric[1,2]-aryl transfer reaction via vinyl cations was achieved.