Study On The Reaction And Transformation Of Acetylenic Amide And Nitrogen Heterocyclic Compound

Ynamides are one class of important organic building blocks,which can be converted into various nitrogen-containing heterocyclic skeletons under transition-metal catalysis and metal-free catalysis conditions,such as enamides,imidazoles,oxazolidinones,pyrroles,pyrrolidines,amino acids,piperazines and so on.These skeletons could be found in a large number of natural products and pharmaceutically compounds,thus having potential applications for drug discovery.Therefore,the research on the transformations of ynamides is great significance in the organic synthetic community.Based on the ynamide chemistry,this project combines the highly active alkynyl group of ynamides and the nucleophilic nitrogen-containing heterocyclic compounds,designing and developing some nucleophilic addition and tandem cyclization reactions,which provides a variety of functional enamides and polysubstituted pyrroles,respectively.And it will promote the development of ynamide chemistry and silver carbene chemistry.In part one,we describe the direct reaction of ynamides with 2H-tetrazoles which could proceed under metal-free conditions to provide a variety of functionalized?Z?-?-tetrazol enamide products in high yields,including the N-2 and N-1 adducts that are easily separated.The reaction could undergo a key keteniminium ion intermediate,generated in situ from ynamides with acidic2H-tetrazoles,leading to the formation of C-N bonds efficiently.The present reaction features simple experimental operations and mild reaction conditions,high chemo-,regio-and stereo-selectivities,and high reaction efficiencies.Without using any catalyst,the reaction protocol should facilitate the modification of tetrazole-containing molecules for the discovery of new potentially bioactive compounds.In part two,a formal[3+2]cycloaddition between ynamides and unprotected isoxazol-5-amines has been developed in the presence of catalytic Ag NTf₂ in an open flask.By the protocol,a variety of functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives can be obtained in up to 99%yield.The reaction mechanism might involve the generation of an unusual?-imino silver carbene intermediate?or a silver-stabilized carbocation?and subsequent cyclization/isomerization to build the significant pyrrole-3-carboxamide motif.The reaction features the use of an inexpensive catalyst,simple reaction conditions,simple work-up without column chromatographic purification for most of products and high yields.