Research On The Synthesis Of Nitrogen Heterocycles With Vinyl Azides

There are many kinds of nitrogen heterocycles,such as pyrroles,pyrazoles,imidazoles,thiazoles,triazoles,pyridines,pyrimidine,pyrazine,indole,quinoline,isoquinoline,phenanthridine etc.Since these skeletons construct the basic units of many natural products,drugs,materials and ligands,the development of their synthesis method has always been a hot research direction in organic synthesis.In recent years,with the promotion of the concept of green chemistry,green and efficient methods for the assembly of various N-heterocycles have emerged one after another.However,vinyl azides have been regarded as “sleepers” among the reactive azido species,and have drawn little attention over the last century.As more and more safe and efficient methods for the synthesis of vinyl azides have been reported,the application and research of using vinyl azides as synthons in organic synthesis had been increased.Because of the abundant reaction sites and reaction modes of vinyl azides,chemists can flexibly use the fragments of vinyl azides as needed to synthesize a series of complex nitrogen-containing heterocycles.In addition,the synergy of the azides group and the alkene makes vinyl azides exhibit unique reactivity which is not found in azides or alkene alone.For example,vinyl azides can function as electrophiles,nucleophiles,radical acceptors,metal imine radical precursors and 2H-azirine precursors.Furthermore,vinyl azides can be compatible with diverse catalytic systems,such as Lewis acid-mediated system,base-promoted system,transition-metal-catalyzed system,photocatalyzed system and so on.In this context,on the basis of a systematic summary of the previous studies on the transformation of vinyl azides,two important N-heterocyclic skeletons were successfully synthesized by taking vinyl azides as a platform molecule to construct C-C and C-N bonds through the exploration of green and efficient catalytic system.The research details are summarized as follows:In the chapter two,an unprecedented Lewis acid-promoted selective cleavage of vinyl azides for the synthesis of 4-substituted quinolines is developed.In this conversion,vinyl azides function as a dual synthon via C=C and C-N bond cleavage with two C=C bonds and one C=N bond formation in a one-step manner.The reaction is appreciated for its readily accessible substrates,high step economy,mild conditions,and use of air as the sole oxidant.In the chapter three,a novel nano copper-catalyzed substrate-dependent chemodivergent transformation of vinyl azides with terminal alkyne is disclosed.2,5-Disubstituted pyrroles were selectively obtained in high yield with aryl alkynes and aliphatic alkynes,whereas 2,3,4-trisubstituted pyrroles were formed with silylated alkynes.This switchable method provides a controllable and facile access to both multisubstituted pyrrole scaffolds with high efficiency,excellent regioselectivity,and good functional group compatibility.