Lewis Acid Catalyzed Cascade Reactions Of Indoles

Indole scaffolds are important structural units of many pharmaceuticals and natural products.Consequently,it is of great significance to develop efficient approaches for the construction of polyindole-substituted and indole-fused compounds with complex and novel architectures.In this thesis,initially,we summarized the recent development on the methods for the synthesis of polyindole-substituted and indole-fused compounds.Based on the literatures,subsequently,we designed new strategies for the construction of these useful compounds and detailed investigations were then conducted.1)A FeCl₃-catalyzed 1,2-addition/substitution cascade of indoles and 3-acetylcoumarins was developed.And a series of highly hindered tetrasubstituted bis（indolyl）methanes bearing a biologically useful coumarin motif were obtained in up to 99%yields.The attractive features of the reaction involve easily available and green catalyst,operational simplicity,broad substrate scope and excellent regioselectivity.2)The Friedel-Crafts alkylation/substitution sequence of indoles and 3-acetylindoles catalyzed by CuBr₂ was realized.Under the optimized reaction condition,a series of highly hindered triindoles with a quaternary carbon center were obtained in up to 97%yields.3)A FeCl₃-catalyzed cascade reaction between indoles and ortho-hydroxyl chalcones was firstly developed.With CH₃CN as the solvent,a series of indole-fused chromans with diverse and complex structures were obtained in moderate to excellent yields.Further investigation revealed that solvents had significant effect on the reaction processes.The reaction proceeded in different manners in CH₃CN,MeOH and CHCl₃.By using methanol as solvent,a series of monoindole-substituted chromans with a ketal skeleton were obtained via Michael addition/ketalization sequence.In addition,by switching the reaction media to CHCl₃,bisindole-substituted chromans were generated.But these two indole substituents were the same.Besides,we can synthesize bisindole-substituted chromans bearing two different indoles by a simple two-step process.This reaction represents the first example for the divergent synthesis of indole-substituted and-fused chromans with novel and complex architectures by simply changing the reaction solvents,which may pave the way for the design of new reactions.