The Synthesis Of Quinolines And Dicoumarin-fused [1,5] Diazocines By Tandem Reaction Involving Enamino Esters

Since nitrogen-containing heterocyclic compounds exhibit diverse biological and physical properties,they have always been a hot topic for scientists.How to effectively synthesize various nitrogen-containing heterocyclic compounds is the first issue that scientists must consider and solve.In this dissertation,enamine esters were used as synthesizers to design and synthesize two kinds of nitrogen-containing heterocycle derivatives through tandem reaction.One class is a classical functionalized quinoline derivative,and the other is a novel dicoumarin-fused[1,5]diazocines.First of all,the methods of synthesis of various nitrogenous heterocyclic compounds by enamine esters as synthons were reviewed.Secondly,a novel approach for the synthesis of functionalized quinolines has been developed through the copper-catalyzed C–C bond formation and C–N coupling of enamino esters with ortho-halogen aromatic carbonyls.Through the investigation of the catalysts,solvents,alkali and ligands,25 quinoline derivatives were synthesized after the optimum reaction conditions were established.Compared with the reported literature,this method avoids the use of expensive precious metal catalysts,and has the advantages of easy raw materials and cheap catalysts.Finally,a copper-catalyzed tandem process for the one-step construction of dicoumarin-fused[1,5]diazocines from aryl methyl ketones and 4-aminocoumarins has been described,which is proposed to proceed via unprecedented sequential oxidative cross-coupling,C-C bond cleavage,cyclization.This is also the first report that the eight-membered ring structure of diazocine was introduced into the coumarin skeleton.After screening the types of catalysts,solvents,and oxidants,23 novel dicoumarin-fused[1,5]diazocines were synthesized after the optimal reaction conditions were established.All the products were confirmed by ¹H-NMR,¹³C-NMR,HRMS-ESI,and the reaction mechanism was also investigated.The antitumor activity of some compounds was tested by MTT assay.The results showed that compounds 6b,6g,6i,and 6o had certain inhibitory activity on the growth of human lung cancer cell A-549.