Transition-metal-catalyzed Synthesis Of Aza-Heterocyclic Molecules With Potential Pharmacological Activities

Recently,the transition-metal mediated modern organic synthesis have displayed powerful advantageous in preparing natural-product-like or complex molecules.As a result,recently great achievements have been made among the organic chemistry communities.On the other hand,N-containing compouds are very useful substances,because they are widely exist both in nature and in organism.According to statistics,more than 70% of all marketed drugs developed by humans are nitrogen containing compounds.Therefore,it should be quite meaningful in the development of new methods for the synthesis of nitrogen-containing heterocyclic derivatives.This thesis mainly introduced the transition-metal-catalyzed highly efficient organic transformations,to selectively synthesize some series of natural-product-like aza-heterocyclic molecules,which are potentially useful due to their biological or pharmaceutical activities.The main contents are as follows:?1?In the first part,the most recent Rh^?-catalyzed carbene-formation/migratory insertion reactions,as well as the Au/Ag-catalyzed cycloisomerization reactions to build aza-heterocylic compounds are briefly summarized.?2?A Rh^?-catalyzed metallo-carbene formation reaction of simple indoles with triazoles is reported,to prepare alkenylated-tryptamine derivatives with high efficiency and chemoselectivity.We demonstrated that the Rh-carbenes could be formed from 1,2,3-triazoles through denitrogenation process.The resulting metallo-carbene species then react with N-aryl?alkyl?indoles in Csp2-H insertion model to produce the expected indole enamines.It should be noted that the obtained products in this reaction could be easily transformed into pharmaceutically active Tryptamines and biindoles.?3?A Au/Ag-cocatalyzed reaction of NH-sulfoximines with ynamides to synthesize aryl?alkyl?-enamine derivatives is disclosed.The obtanied products then underwent [Ru]/H₂O₂ mediated catalytic oxidation reactions to selectively cleave the C=C double bond,thus open up a new avenue toward unsymmetrical urea-like sulfoximines in excellent yields.?4?We successively achieved a microwave-promoted,Cp*Co?-catalyzed C-H activation/double C-N bond formation reaction of free NH-sulfoximines with1,4,2-dioxazol-5-ones,to highly chemoselectively synthesize thiadiazine-1-oxide derivatives.The preliminary mechanistic studies revealed a radical process is unlikely involved in this reaction.Instead,an electrophilic metallation mechanism is supposedin the initial step.Additionally,upon putative intermediate investigation studies,the NH-benzoyl substituted sulfoximine was found to be a key component in this double C-N bond formation reaction.