Computational And Experimental Studies On Copper-Catalyzed Selective Cascade C-H/N-H Annulation Of Electron-Deficient Acrylamide With Arynes:Efficient Synthesis Of 2-Quinolinone

Nitrogen-containing heterocyclic skeletons are widely found in natural products and drug molecules with biological and pharmaceutical activities.Compared with the traditional synthesis methods,the transition metal catalyzed C-H bond functionalization method for the construction of nitrogen-containing heterocyclic skeleton has attracted widespread attentions in recent years due to its advantages of short synthesis steps,high atomic economy and mild reaction conditions.Attentions have been devoted to copper-catalyzed construction of nitrogen-containing heterocyclic skeletons by our group,and copper-cata-lyzed sp~2 C-H/N-H cascade annulations of benzamide and indolecarbox-amide have been achieved.This dissertation is aimed to further extend the copper-catalyzed sp~2 C-H/N-H cascade annulation reaction to electron-de-ficient olefin,and realize one-step synthesis of 2-quinolone skeleton.We assume that the activity of C-H activation of electron-deficient olefins can be effectively improved by N,N-bidentate directing group,and the feasibility of the reaction is confirmed by density functional theory calculation.After the optimization of reaction conditions,one-step synthesis of 2-quinolone skeleton using acrylamide and 2-trimethylsilyl phenyltrifluoro-methanesulfonate as substrates,copper acetate as catalyst and oxygen as oxidant are achieved.A broad range of subsrates,including terminal double bond,nonterminal double bond and various symmetrical benzyne precursors,are applied to the reaction successfully to obtain corresponding products with moderate to good yields.The preliminary experimental verification of mechanism is consistent with the results of density functional theory calculations.