Study On The Synthesis Of Benzo[b]azepines Based On Palladium(Ⅱ)/Lewis Acid Cocatalyzed Oxidative Annulation Of 2-alkenylanilines And Propargylic Esters

Nitrogen heterocyclic compounds are important structural elements of many natural products,biologically active molecules,pharmaceutical preparations and other functional molecules;in the field of catalysis,nitrogen-containing heterocycles are also widely used as auxiliary ligands for catalysts.Among them,seven-membered nitrogen heterocycles play an important role in nitrogen-containing compounds.Therefore,the efficient construction of aza seven-membered ring is one of the important research hotspots in the field of modern organic synthetic chemistry.In recent years,the transition metal-catalyzed C(sp~2)-H bond activation has achieved vigorous development,especially in the synthesis of seven-membered aza ring,which drives more and more researchers to adopt more concise and efficient C(sp~2)-H bond activation strategy to synthesize azepines.Based on the previous work,we developed the[5+2]cyclization reaction of 2-vinylaniline and propargyl ester co-catalyzed by palladium and Lewis acid to achieve the efficient construction of benzoazepine compounds.The novelty of this method is that Lewis acid is used as a co-catalyst,which improves the reaction efficiency.It is also importantly expandsion the scope of[5+2]cyclization reaction using propargyl esters as a cyclization partner.This article mainly includes two parts:In the first chapter,the research progress of 2-vinylaniline and its analogues 2-vinylphenol in the preparation of nitrogen-containing or oxygen-containing heterocycles was briefly reviewed,including direct cyclization,cyclization[5+1]and cyclization[5+2],which provided some guidance for the study of synthesis methods of benzoazepines.In Chapter 2,we developed a new method for the synthesis of benzoazepines by the oxidative coupling cyclization of 2-vinylaniline and propargyl ester co-catalyzed by palladium and Lewis acid.This method is characterized by using readily available propargyl ester and2-vinylaniline as staring materials,mild conditions,and good functional group tolerance.In addition,the reaction mechanism was elucidated.This method has successfully expanded the scope of the[5+2]cyclization reaction of 2-vinylaniline and alkyne derivatives.