Acid-acid Catalyzed Tandem Reaction Assisted By Additive In The Synthesis Of Heterocyclic Compounds

The tandem reaction has attracted more and more attention because of its simplicity and high efficiency,and the acid-acid catalyzed tandem reaction is an important research field in the tandem reaction.In recent years,considerable progress has been made in the synthesis of five-or six-membered heterocyclic compounds by acid-acid catalyzed tandem reactions.However,most of the reported acid-acid catalyzed tandem reactions are based on substrate design strategies.Complex starting materials often require multiple steps of synthesis,which usually require the use of precious metal catalysts.The acid-acid catalyzed tandem reaction assisted by the additive has the advantages of simple system and high synthesis efficiency.When the additive is added to the reaction,the substrate can be activated or further converted.Therefore,in the acid-acid catalyzed tandem reaction assisted by the additive,there is no need to prepare complex precursor,and it is possible to replace the expensive metal catalyst with some cheap and easily available metal catalysts or even non-metal catalysts.In this thesis,a variety of five-or six-membered heterocyclic compounds were constructed via the acid-acid catalyzed tandem reaction assisted by the additive.AlCl₃-catalyzed facile synthesis of trisubstituted furans from aliphatic aldehydes and1,3-dicarbonyl compounds was developed by using NBS as oxidant.This method was effective for the synthesis of various furan derivatives.We developed a two-step method to produce HHCA by using commercially available precursors,which exhibits a remarkable anti-phytopathogenic activity.2,3-Disubstituted benzofurans derivatives were synthesized from acrolein dimer and1,3-dicarbonyl compounds by using NBS as an oxidizing agent.The method was used to synthesize two commercial drug molecules,benzbromarone and amiodarone.The proposed mechanism of the reaction involves an NBS-assisted auto-tandem catalysis with Lewis acid catalyst.To proof the proposed mechanism,an intermediate was isolated successfully,which can be converted to 4,5,6,7-tetrahydrobenzofurans.1,2,4-Trisubstituted pyrroles were synthesized from enolizable aliphatic aldehydes and primary aliphatic amines by using iodine as dual Lewis acid/mild oxidant.Also,enolizable?,?-unsaturated aldehyde reacted with aromatic primary amines to form N-arylpyrroles.An acetal-containing pyrrole can be converted easily to5,6,7,8-tetrahydroindolizine derivative.An acetal-containing pyrrole was successfully synthesized from2-aminobutyraldehyde diethyl acetal and phenylacetaldehyde catalyzed by I₂,which can be converted easily to indolizine derivatives via[4+2]annulations.A variety of six-membered carbocycles and heterocycles,such as indolizine,indole,naphthalene,carbazole,pyrido[1,2]indole and benzothiophene were successfully synthesized.Inspired by the work of Chapter V,we try to synthesize 1,4-nucleophile-electrophile molecule in situ to construct[4+2]annulation products.A three-component reaction of indoles,?-bromoacetal-dehyde acetals,and ketones was developed by using bismuth?III?triflate as the catalyst to realize a straightforward approach for synthesizing carbazole derivatives.Two carbazole derivatives were successfully constructed,which was used as the intermediate to synthesize a europium complex and an intermediate for synthesizing the nonsteroidal anti-inflammatory animal drug Carprofen.