Imine As An Intermediate For The Coupling Reactions Of Nitrogen Heterocyclic Compounds

Mono-and poly-nitrogen heterocyclic structural motifs are frequently found in various bioactive molecules and natural products.The bis-or poly-N-heterocycles,arising from the coupling of single N-heterocyclic compounds,not only possess the biological activities that are superior to those of the original substrates,but also exhibit unexpected new properties.Hence,the development of straightforward approaches to access bis-N-heterocycle has become a topic of immense importance in organic synthesis.In this doctoral thesis,by employing hydrogen transfer and dehydrogenation as the substrate-activating strategies,the N-heterocycles are activated to form the imine intermediates,which are then captured by another molecule of nucleophilic nitrogen heterocycle and furnish the desired bis-N-heterocycles.The main content of the thesis is composed of following four sections:?1?By a hydrogen transfer-mediated activation mode,we have demonstrated a new palladium-catalyzed direct?,?-coupling of different types of N-heteroarenes.Such a selective coupling reaction proceeds with the advantages of operational simplicity,high atom-economic efficiency,and use of safe and abundant i-propanol as the activating agent,offering a practical way to access bi-N-heteroarenes.Preliminary exploration has revealed that the obtained bis-1,10-phenanthroline 2qq'as a ligand is capable of improving copper catalyst for C-C bond formation and 2qq'reveals its capability as a fluorescent sensor to detect Ni²⁺ion.The work of this paper has built an important basis for the creation of extended?-conjugated systems that are of important significance in biological,medicinal,material and synthetic organic chemistry as well as catalysis.?2?By a hydrogen transfer-mediated activation mode for the non-activated pyridyl nucleus,a general catalytic hydrogen transfer-mediated?-functionalization of1,8-naphthyridines is reported for the first time.The first step is most likely the formation of an imine intermediate,its?-site selectively couples with the C₈-site of various tetrahydroquinolines?THQs?to afford novel?-functionalized tetrahydro 1,8-naphthyridines,a class of synthetically useful building blocks and potential candidates for the discovery of therapeutic and bio-active products.The utilization of THQs as inactive hydrogen donors?HDs?appears to be a key strategy to overcome the over-hydrogenation barrier and address the chemo-selectivity issue.The developed chemistry features operational simplicity,readily available catalyst and good functional tolerance,and offers a significant basis for further development of new protocols to directly transform or functionalize inert N-heterocycles.?3?Aruthenium/Br?nstedacid-CocatalyzedTransferHydrogenative Para-Aminoalkylation of Aniline Derivatives with N-Heteroarenes has been demonstrated.The developed transfer hydrogenative Friedel-Crafts reaction of aniline derivatives with1,8-naphthyridines enables to elaborate bis-N-heterocycles in an efficient manner.In such a process,the utilization of THQs as inactive hydrogen donors?HDs?appears to be a key strategy for the coupling step.Its para-site of an?-site of various 1,8-?-functionalized tetrahydro1,8-naphthyridines.The reaction exhibits excellent functional group compatibility and broad substrate scope.?4?In this chapter,a Iridium-catalyzed dehydrogenative?-functionalization of?hetero?aryl-fused cyclic secondary amines with indoles is presented.By employing dehydrogenation as a substrate-activating strategy,the imine serves as a key reactive intermediate,which is traped by the indole nucleophiles,thus affording the?-functionalized?hetero?aryl-fused cyclic secondary amines in a straightforward manner together with the merits of high a step-and atom-efficiency.