Study On Tandem Cycloaddition Reactions Based On Alkyne-allene Isomeric Active Intermediates

Oxygen containing heterocyclic compounds are ubiquitous structural units in natural compounds.For a long time,the synthesis of oxygen containing heterocyclic compounds has attracted extensive attention because of their diverse physiological and biological activities.Although many strategy of synthesizing oxygen containing heterocycles have been reported,the development of more efficient and facile synthetic methods is still the diligent pursuit of many researchers.As a class of highly active molecules,allenes have diverse reaction sites and regulable properties.Therefore,there are many types of reactions based on allenes,such as electrophilic addition,nucleophilic addition,cycloaddition and so on.The cycloaddition reaction involving allenes can obtain heterocyclic with different ring systems and various structures according to the different sites participating in the reaction,which can provide important skeleton for the synthesis of natural products and pharmaceutical molecules.This dissertation is mainly based on the study of the tandem reaction involving propargyl-allene isomerization,here we introduce the following two aspects:(a)Synthesis of Disubstituted 1,3-dihydrobenzofurans via Three-Component Reactions of Aryl iodides,Alkynes,and Protic Nucleophiles.We have developed a three-component tandem cycloaddition reaction based on allene that enables the construction of 1,3-dihydroisobenzofuran compounds.The reaction has undergone a series of processes including Sonogashira coupling,base-promoted propargyl-allene isomerization,[4+2] cycloaddition,and nucleophilic attack.Our protocol allows the incorporation of amines and alcohols into highly complex substrates.We believe that this facile and efficient tandem reaction will be applied to the synthesis of natural products,pharmaceutical molecules,etc.(b)The Tandem Reaction of [2+2] Cycloaddition Involving the Isomerization of Propargyl-Allenes Promoted by Bases.On the basis of the above investigation,we further utilized the activity of alkyne to synthesize a novel tricyclic compound through a tandem reaction of Sonogashira coupling,DBU-promoted isomerization,and [2+2] cycloaddition.The reaction has the advantages of facile,high yield and mild reaction conditions,which provides an environmentally friendly and atom-economical methods for the synthesis of such compounds.