Studies On The Condensation Of Secondary Amides With Isocyanides:Synthesis And Asymmetric Mannich Reaction Of 3-iminoindoles

Organic synthetic methodology is one of important branche of organic chemistry,which directly promote the development of chemistry,drug R&D and relative fields.Amides are a kind of highly stable and easily avalable carboxylic acid derivative with a high oxidation state.These features make it not only a kind of important synthetic intermediate,also the main structure characteristic of the protein.In addition,amides also serve as protecting group of amine and powerful directing groups in C-H activation reactions.Nonetheless,it is textbook knowledge that the low reactivity of amides is a result of resonance stabilization.This stabilization reduces the susceptibility of amides towards nucleophilic attack.Consequently,the development of general and step-economical methods for the direct transformation of amides in C-C bond formation is both a highly desirable and a challenging objective.Indoles are a class of significant nitrogen-containing heterocyclic aromatic compounds,and they are the most pervasive heterocycles in nature.As derivatives of indoles,3-iminoindoles and indoleones are key intermediates in organic synthesis,indoleones as well as show high biological activity and reactivity.It is meaningful to develop a new and efficient protocol to synthesize indoles.Chiral aza-quaternary carbon center widely present in natural products and drug molecules.And the chiral aza-quaternary carbon center could be obtained from asymmetric addition of ketmines.3-iminoindoles include two ketmines,nucleophiles regioselectivly attack 2-position imine would be obtained an indole skeleton chiral with aza-quaternary carbon center.This strategy is a challenging and meaningful issue.This dissertation contains the following two parts:1.Developed a general method for metal-free tandem reaction of isocyanides with secondary amides.(Chapter 2)Based on amide activation,a metal-free tandem reaction of isocyanides with secondary amides has been developed.This one-pot reaction of activated secondary amides by Tf2O with isocyanides directly access to 3-Iminoindole compounds.And hydrolysis of the 3-iminoindoles from this strategy leaded to diversity indoleones.It is important that this is the first case of isocyanides with activated secondary amides.This protocol is characterized by its mild reaction conditions,efficient,excellent functional group tolerance and chemoselectivity.2.Developed a general method for L-proline catalyzed asymmetric Mannich reaction of 2-position imine of 3-Iminoindole(Chapter 3)A general method for L-proline catalyzed asymmetric Mannich reaction of 2-position imine of 3-iminoindoles has been developed.L-proline as catalyst,ketone as nucleophile,the regioselectivly attack of the 2-position cyclic ketmine obtained the aza-quaternary carbon center.This protocol is characterized by its mild reaction conditions,efficient,excellent functional group tolerance and enantioselectivity.