Synthesis Of Indoles And Their Derivatives Based On Annulation Reactions Of 1-Alkynylnaphthalen-2-ols

Cyclic molecules including carbocyclic,heterocyclic and spirocyclic as well as bridged rings are widely present in natural products,biologically active substances,and drug molecules.In addition,cyclic molecules are used as important intermediates in organic synthesis to synthesize the desired target compounds through suitable derivatization.Annulation reactions are an important and powerful synthetic strategy for building up various cyclic compounds,where the key is to make the coupling among the multiple reactive sites of organic building blocks through suitable catalytic systems.To realize this goal,in this thesis,1-alkynyl naphthalen-2-ols and ortho-arylalkynylanilines were used as the key building blocks,enabling three different types of annulation strategies to give 82 examples of four functionalized indole derivatives in a atom-econimic fashion.The detail research contents are as follows:In the first part,the significance and application of the annulation reactions are briefly introduced,and the current research progress of 1-alkynyl naphthalen-2-ols and ortho-arylalkynylanilines are highlighted.On the basis of the above document survey,the innovation aspects of this thesis are provided.In the second section,Yb（OTf）₃-catalyzed alkyne-carbonyl metathesis/oxa-Michael addition relay reaction of isatins with 1-alkynyl naphthalen-2-ols was described,and used to produce different substituted naphtho[2,1-b]furan-3-ones with good to excellent yields and high diastereoselectivity through an intermolecular[2+2]cycloaddition-retroelectrocyclization（CA-RE）cascade.By utilizing the characteristic of the[2+2]cyclization between electron-rich alkynes and carbonyl groups,this protocol enabled the cleavage/recombination of carbon-oxygen double bonds,thereby enriching the methodology of the alkynes-carbonyl metathesis chemsitry and thus providing an efficient and convenient way to synthesize naphtho[2,1-b]furan-3-ones.In the third part,a new quinine-catalyzed bicyclization reaction of 1-alkynyl naphthalen-2-ols with nitrones was reported,leading to highly regioselective formation of a series of functionalized oxazino[3,4-a]indoles with moderate to good yields through the cleavage of the N-O bond.This approach accommodates a wide range of substrates and good functional group tolerance,providing a new synthetic pathway for the difunctionalization of internal alkynes.Based on literature reports and our experimental results,a possible mechanism is proposed,which involves[3,3]-rearrangement,intramolecular isomerization and nucleophilic addition cascade.In the fourth part,Zn I₂-promoted cyclization/Friedel-Crafts alkylation cascade of ortho-arylalkynylanilines was developed,and chromeno[4,3-b]indoles and naphthyl-C₂-indoles were selectively synthesized.From experimental outcomes,the chemoselectivity of the reaction depends on the substituents from substrates.For example,O-methyl-protected or unsubstituted ortho-arylalkynylanilines generated rotation hindered naphthalene-substituted indoles wheares hydroxyl-substituted ortho-arylalkynylanilines were converted into chromo[4,3-b]indoles.In addition,this reaction not only tolerated various substituents such as methyl,ethyl,tert-butyl,fluorine,chlorine,and bromine from the substrates but also has controllable chemo-and regio-selectivities,thereby opening new avenues for the synthesis of chromeno[4,3-b]indoles and naphthyl-C2-indoles derivatives.Based on literature reports and our experimental results,a possible mechanism was proposed,which involved intramolecular cyclization,Friedel-Crafts alkylation,intramolecular oxa-Michael addition cascade.