Construction Of Diversified Nitrogen-Containing Heterocyclic Compounds Based On Azaallyl Anions

Nitrogen-containing heterocycles are one of the most prevalent building blocks in natural products,pharmaceuticals,agrochemicals,and organic materials.In particular,more than 75%of FDA-approved commercial drug molecules possess nitrogen-containing heterocycle rings.Among them,five-membered and six-membered nitrogen-containing heterocyclic compounds,such as isoquinoline,1-pyrroline and dihydroquinazoline,have a wide range of biological activities and important application value in the pharmaceutical industry.With the development of the concept of green chemistry,transition metal-free construction of nitrogen-containing heterocyclic compounds has always been a hot area of research in organic synthetic chemistry.In this dissertation,three nitrogen-containing heterocyclics,isoquinoline,1-pyrroline and dihydroquinoline,were constructed via transition-metal-free synthesis based on the azaallyl anion,including 1)the synthesis of isoquinoline compounds by tandem radical cyclization/intermolecular coupling reaction;2)transition-metal-free synthesis of 1-pyrroline derivatives via cyclization of terminal alkynes with2-azaallyls;3)transition-metal-free synthesis of 1.2-dihydroquinazoline derivatives from 2-iodoaniline with 2-azaallyls.This dissertation is divided into five chapters.In the first chapter,the research progress on synthesis of three nitrogen-containing heterocyclic compounds,isoquinoline,1-pyrroline and quinazoline,was described briefly.In the second chapter,a new transition-metal-free synthesis of isoquinoline derivatives was developed by the super electron donor 2-azallyl anion.The isoquinoline compounds were synthesized through tandem reduction/radical cyclization/radical coupling/aromatization under mild conditions.The method has good scope of substrates.Both aryl ketimines and alkyl aldimines led to isoquinoline derivatives.A series of products were synthesized with 24 targets and up to 94%yields.Gram-scale reaction proved the scalability of this method.In the third chapter,a synthetic method of 1-pyrroline derivatives though cyclization of terminal alkynes with 2-azallyls was developed.In this reaction,ketimines were deprotonated to form 2-azallyl anion with a base,then attacked the terminal alkynes,and followed by obtaining a proton to provide coupling products,which further underwent deprotonation,isomerization.and cyclization to give theproduct 1-pyrroline derivatives.This method enables the cyclization of terminal alkynes and 2-azallyls to proceed efficiently under mild and transition-metal-free conditions by a simple combination of base and solvent.The method can tolerate a variety of terminal alkynes and imines.A series of products were synthesized with 26targets and up to 98%yields.This cyclization reaction will provide an efficient method for the synthesis of pharmaceutical-relevant polysubstituted and multifunctional pyrrolines.In the fourth chapter,a synthetic method of 1,2-dihydroquinazoline derivatives from 2-azallyls and 2-iodoanilines was developed.This method enables the synthesis of 1,2-dihydroquinazolines by tandem reduction/radical coupling/S_N2/oxidation.The reaction conditions are mild,no transition metals and oxidants are involved,and oxygen in the air was used as the oxidant.The reaction has good scope of substrates.In addition to dihydroquinazolines obtained from aryl ketimines with different substituents,spiro ring dihydroquinazolines also were obtained from aldimines with different substituents in moderate or good yields.A series of products were synthesized with 31 targets and up to 86%yields.The synthesized dihydroquinazoline derivatives will be of great significance in the field of medicinal chemistry.In the fifth chapter,the research work of this dissertation was summarized.