Research And Application Of Br?nsted Acid-promoted Cyclodimerization Of Indole Ketones And Lewis Base-Catalyzed Allylic Alkylation Reaction Of ?-(Alkylideneamino) Nitriles

Nitrogen containing heterocyclic compounds are widely used in the fields of medicine,materials and chemical industry.Fused indole compounds and1-pyrroline compounds,as two important nitrogen-containing heterocyclic compounds,not only have good biological activities,but also play an important role in organic synthetic chemistry.Consequently,it is of great significance to develop new methods to prepare these scaffolds.Cyclodimerization of indole derivatives is one of the most direct and effective methods for the synthesis of fused-indole compounds,which has received considerable attention due to the advantages of simple operation and high reaction efficiency.9-Oxabicyclo [3.3.1] nonane and cyclooctylene structural units are the core skeletons of many natural products and drug molecules.By combining the indole ring with the above eight-membered ring skeletons,the obtained compounds may have potential application value.In this context,the first part of this thesis carries out the following work.A Br?nsted acid-promoted cyclodimerization reaction of C(3)-,C(2)-,or N(1)-substituted indole ketone derivatives to synthesize a series of bisindolo9-oxabicyclo [3.3.1] nonane derivatives was developed.Other heteroaromatic ketones,such as thiophene,benzothiophene,furan and pyrrolidone analogues have also been investigated.Among them,5-substituted thiophenes tethered ketone moieties at C(3)position can react to deliver dithiopheno 9-oxabicyclo [3.3.1]nonane compounds.A variety of bisindole fused-cyclooctatetraene derivatives can be obtained,when 2-substituted aryl indole ketones were used.On the other hand,1-pyrroline compounds not only have a variety of biological activities,but also are important reaction intermediates,which can be transformed into pyrroles,pyrrolidines and other heterocyclic compounds.Therefore,the synthesis of these compounds has attracted much attention.?-(Alkylideneamino)nitriles contain both nucleophilic and electrophilic centers,which are ideal synthons and widely used in the synthesis of nitrogen-containing five membered heterocyclic compounds such as pyrrolines and pyrrolidines.In view of the above background,the research contents of the second part of this thesis are as follows.A Lewis base-catalyzed allylic alkylation reaction between?-(alkylideneamino)nitriles and MBH adducts to synthesize a series of allylic substituted ?-(alkylideneamino)nitriles was developed.In addition,asymmetric allylic alkylation reaction of ?-(alkylideneamino)nitriles with MBH carbonates catalyzed by chiral Lewis base was also studied.Given the structural characteristics of allylic products,we successfully synthesized functionalized diverse 1-pyrrolines incorporating ?-quaternary carbon centers through a Lewis base-catalyzed1,4/1,2-addition tandem sequence.Finally,the allylic alkylation/cyclization one-pot sequence of ?-(alkylideneamino)nitriles and the cyclization/reduction one-pot sequence of allylic ?-(alkylideneamino)nitriles were also developed.