Synthesis Of Nitrogen (Oxygen) Heterocycles Via Fe/Cu-catalyzed C(sp~3)-H Functionalization Of Saturated Cyclic Amines

Due to their wide presence in nature,rich and diverse reaction patterns and remarkable biological activities,nitrogen（oxygen）-containing heterocyclic compounds have a broad application prospect in organic synthesis and drug research&development.Therefore,the development of simple and efficient methods for the synthesis of nitrogen（oxygen）heterocyclic compounds is a hot spot in organic synthesis.On the other hand,the direct functionalization of inert C（sp³）–H bond has the advantages of elimination of substrate（s）pre-activation and minimization of byproduct（s）production,and has thus been considered as on of the most prominent and promising strategies in organic synthesis.Inspired by the above facts,this thesis has studied the cascade reactions of cyclic amines with 2-oxo-2-arylacetic acids under the catalysis of some inexpensive metal catalysts.From these studies,some novel,efficient and selective syntheses of furanone fused N-heterocyclic compounds and acylated N-heterocycles featuring with an inert C（sp³）–H bond functionalization have been developed.The main results are summarized in the following two parts:Firstly,an efficient synthesis of furanone fused N-heterocycles via the cascade reactions of cyclic amines with 2-oxo-2-arylacetic acids is developed.Mechanistically,the formation of the title compounds is initiated by the in situ formation of a cyclic enamine intermediate via FeCl₃/di-tert-butyl peroxide/oxygen（O₂）–promoted C（sp³）–H dehydrogenation of saturated cyclic amine.Nucleophilic addition of the cyclic enamine intermediate onto 2-oxo-2-arylacetic acid followed by cyclization and dehydration gives the targated products.Compared with literature protocols,this new method has the advantages of simple and easily obtainable starting materials,high efficiency and excellent atom-economy.Secondly,a highly regioselective synthesis of acylated N-heterocycles from the cascade reactions of saturated cyclic amines with 2-oxo-2-arylacetic acids is developed.Mechanistically,the formation of the title compounds involves firstly a C（sp³）–H bond dehydrogenation of cyclic amine to give an enamine intermediate followed by its cross coupling with the acyl species in situ generated through the decarboxylation of 2-oxo-2-arylacetic acid.Interestingly,in this cascade process the copper catalyst is believed to play a crucial role not only in dehydrogenation,but also in decarboxylation and the cross coupling reaction.This is the example in which acylated N-heterocycles were directly prepared from the readily available saturated cyclic amines by using 2-oxo-2-arylacetic acids as the non-corrosive and easy to handle acylating reagents.In summary,through thorough screening of different inexpensive metal catalysts and various reaction conditions,selective and efficient syntheses of the synthetically and biologically valuable furanone fused N-heterocycles and acylated N-heterocycles have been realized in this dissertation.The studies accomplished herein not only provides some novel methods for the synthesis of the above mentioned heterocyclic compounds,but also help to reveal the reactivities of inert C（sp³）–H bond in saturated amines and extend their applications in organic synthesis.