Study On Cascade Reactions Of Indoles Initiated By Radical Addition

As a privileged nitrogen heterocycle,indole skeloton occurs extensively in alkaloids and natural products.In recent years,radical process was widely used in the diverse transformations of indoles due to their high tolerance upon functional groups in the substrates as well as generality for the new formation of kinds of chemical bonds.Thus,many indoles and indoline compounds which are hard to be accessed by traditional methods have been synthesized efficiently.In this thesis,diversity-oriented transformation of indoles through radical process would be mainly discussed in order to resolve the important issue found in previous work and establish the novel protocol for the structural diverse synthesis of indole/indoline derivatives.The main content of this thesis involves the following three parts:The first part also contains three sections.a)Copper-catalyzed synthesis of 2arylquinazolin-4-amines from 2-arylindole and TMSN3 under mild conditions was devoloped.The ring expansion reaction of 2-arylindole involving the C2-radical trapping by newly formed C3-azide group was disclosed.b)In the presence of copper catalyst,addition of azide radical to C2-postion in N-Bz indole gives C3-radical,which is captured by molecular dioxygen,and after reduction by P(OEt)3,a series of 2azidoindolin-3-ol derivatives were obtained.c)When N-Bz indole was replaced with NBz-7-azaindole in above reaction,nitrogen-atom-insertion reaction was observed and systematically studied under the absence of copper catalyst.As a good leaving group,7azaindole fragment could be substituted by various amines for the synthesis of structural diverse ureas.To a certain extent,the carboxamide compounds containg 7-azaindole fragment can be employed as a substitute for aryl isocyanate.In the second part,a general photocatalytic platform for the straightforward dual C2-H/C3-H functionalization of indoles with N-aminopyridinium ylides was disclosed.This cascade reaction was initiated by radical addition of bifunctional reagent to indole C2-position,followed by intramolecular trapping the C3-radical and cleavage of the NN bond,syn-stereoselective difuctionalization of indole was realized.With the help of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone(DDQ),2-amidyl-3-pyridyl indole derivatives were synthesized.The protocol shows high levels of step-and atomeconomy.In the third part,we demonstrated a Mn(OAc)3·2H2O promoted radical additionintramolecular transesterification relay between 3-indolylmethanols and phosphites for the synthesis of 1,2-oxaphospholoindole derivatives under mild conditions.In this transformation,3-indolylmethanol was utilized as a four-atom building block in[4+1]annulation which was scarcely reported.This protocol provides an efficient synthetic toolbox for construction of P,O-heterocycle fused indole compounds.