Copper-Catalyzed,N-Radical Initiated Selective Transformation Of Multiple Inert C-H Bonds

The construction of C-C bond has long been the central topic of organic synthetic chemistry.As one of the most important methods to construct C-C bond,traditionally,transition-metal-catalyzed cross-couplings require functionalized substrates to realize C-C bond formation,which requires specific pre-activation of the substrates.In recent years,considering the reaction economy and green chemistry concept,the C-C bond construction based on C-H/C-H cross-coupling has attracted much of attention from synthetic chemists,which,therefore,attacted us to develop the highly selective cross-coupling between inert C-H bonds.In the first part of our work,we realized copper-catalyzed C(sp3)-H/C(sp2)-H cross-coupling en route to various benzo-fused,7-membered carbocyclic rings.In this reaction,under the catalysis of copper,nitrogen radical was f-ormed through the cleavage of a N-H bond,and activated the remote inert C(sp3)-H bond through[1,5]-hydrogen atom transfer(HAT)process.The produced carbon radical was subsequently captured by an intramolecular arene,achieving the highly selecti-ve cross-coupling between inert C(sp3)-H/C(sp2)-H bonds after oxidation and deprotonation,and producing the benzo-fused,6-membered carbocyclic ring.In the next part,this methodology was successfully applied for the synthesis of benzo-fused,7-membered,aza-heterocycles,which is also called 1-benzazepines,exist extensively as key structural motifs in multitudinous biologically active molecules,including different kinds of natural products,pharmaceuticals,and functional materials.This is the first time that this kind of structure is constructed through C-H/C-H cross-coupling.It is worthnoting that both of the above works showed excellent chemo-,regio-and stereo-selectivities.The reactivity of aliphatic C-H bonds paralleled the thermodynamic stability of the carbon radicals produced and followed the order:tertiary>secondary>primary.And the site-selectivity of C(sp3)-H bond activation on the alkyl chain was determined by 1,5-HAT process,solely.In the last part of this dissertation,we accomplished a novel copper-catalyzed[1,3]-nitrogen shift reaction,involving a unique 4-exo-trig cyclization process,which is not favored in fact and has only been reported once.By enhancing the stability of the carbon radical generated from the formation of the aza-4-membered ring,and releasing the ring-strain of the aza-4-membered ring via retro-[4?]process,this kind of 4-exo-trig cyclization process is promoted.On the other hand,two C(sp3)-H bonds,one C(sp2)-H bond,one N-H bond and one C-N bond were cleaved,and two C-N bonds,one C-C double bond were constructed in one pot during this transformation,producing the final indole product.