Manifold Design And Construction Study On Acid–acid Catalyzed Tandem Reaction

Domino reactions have been paid more and more attention because they are concise and efficient in organic synthesis.Auto-tandem catalysis with acid is a great mean to develop domino reaction.The established tandem reactions have been widely used in the synthesis of valuable and complex molecule by using simple components as starting materials.However,developing acid-acid catalyzed tandem reaction heavily relied on the substrate-designing strategy.Due to the tedious experimental procedure to prepare complex precursor,it is urgent to find new strategies to make the acid-acid catalyzed tandem reaction more practical.In this thesis,three appraches were used to develop tandem reaction,including additive assisted(the second and third chapter),concomitant assisted(the fourth chapter),and liquid/liquid biphasic system assisted(the fifth chapter)strategies:1.5-Hydroxy-2-arylbenzofurans were synthesized by Michael addition/intramolecular cyclization reaction of acetophenone and 1,4-benzoquinones with the aid of a system composed of Sc(OTf)3 and additive orthoformate.The tandem reaction could be completed because of strong nucleophilic property of vinyl ethyl ether,which was in situ formed by the interaction between acetophenone and triethyl.It could occur in mild reaction conditions and had wide substrate scope.In addition,this method was also used to prepare some important 2-phenylbenzofuran derivatives,including important medicinal intermediate,natural product precursor,and liquid crystal meterials monomer,displaying clearly the efficient and concise ness.2.The system "Al(OTf)3/additive NBS" could be used to realize the cascade reaction of atropaldehyde acetals and alkyl acetoacetates to synthesize aryl slicylates.Mechanistically,The reaction is a tandem Robinson cyclization and oxidative aromatization reaction,and the oxidative ability of NBS was the key to render the whole reaction possible.The reaction conditions was mild,and the substrate scope of this reaction is very good.This method could be also applied for synthesis of carbozole,quinoline,1H-pyrazolo[3,4-b]pyridine,and pyrazolo[1,5-a]pyrimidine.Notably,when this method was utilized to prepare an important anti-inflammatory drug diflunisal,clear advantages could be observed,such as simple synthetic procedure and high yield.3.By using reaction concomitant HBr as a component of catalyst,a relay catalysis system was established,which can carry out some acid-acid catalyzed tandem reaction.BiCl3 mediated the Friedel-Crafts reaction of 2-phenylindoles and a-bromoacetaldehyde to give the intermediate 2-(2-phenyl-1H-indol-3-yl)acetaldehyde,along with the generation of HBr.And then,benzo[?]carbazoles were formed through intramolecular aldol reaction of this intermediate with the aid of relay catalysis of HBr;Also,based on the same method mechnism,a three-component reaction of indole,?-bromoacetaldehyde and 1,3-dicarbonyl compound was also established to synthesize carbazoles under the same reaction.This three-component reaction could be completed in a short time and had broad scope of substrate.4.In a biphasic system composed of nitroethane and sulfone-containing betaine-type salt,TfOH can catalize the reaction between a-hydroxyketones and 2-phenyl indoles to generate benzo[a]carbazoles.The reaction mechanism includes cascade Henys-type rearrangenment and intermolecular aldol reaction.The method was also employed to prepare N-methyl indole substituted 1,2-dihydronaphthalene and carbazole,showing great effectiveness.