Synthesis Of Heterocyclic Compounds By Addition Reactions Involving β,γ-unsaturated Ketoesters

Heterocyclic compounds are the most numerous and diverse class of organic compounds containing heterocyclic structures,which are widely found in nature and have a wide range of biological activities,and are important backbones for a variety of substances with relevant pharmaceutical activities.Among them,nitrogen-containing heterocycles are the core backbone of many drug molecules and are commonly found in many drug molecules and synthetic functional molecules,providing important and valuable molecules that play a crucial role in the metabolism of living cells.Therefore,it is important to investigate the development of more efficient and convenient methods with atomic economy for the synthesis of biologically active heterocyclic compounds.β,γ-unsaturated α-ketoesters are compounds containing a variety of functional groups in their structures,including unsaturated carbon-carbon double bonds,ketocarbonyls and ester groups,which can undergo many types of reactions,such as conjugate addition and Aldol reactions.In particular,the α-carbonyl esters contained therein are capable of further derivatization reactions to synthesize biologically active compounds such as hydroxy esters and amino acids.In view of the specificity of this structure itself and its unique bioactivity,more and more organic synthesizers have started to pay extensive attention to various reactions involving β,γ-unsaturated α-ketoesters.Since catalytic reactions using small-molecule organocatalysts have the advantages of low toxicity and easy availability,this thesis mainly includes the following two parts for the synthesis of heterocyclic compounds via addition reactions involving β,γ-unsaturated α-ketoesters:The reaction in the first part of this paper is the selective addition reaction of β,γ-unsaturated α-ketoesters with 2,3-disubstituted indoles through the occurrence of selective addition reactions for the functionalization of indoles at the C6 position to synthesize a series of indole derivatives in an efficient manner.Since β,γ-unsaturated α-ketoesters have both1,2-addition sites and 1,4-addition sites in their own structures,the formation of by-products is inevitable,so it is significant to investigate the generation of specific target products for the reactions involving β,γ-unsaturated α-ketoesters.In contrast to the previous reactions in which indole C6 selective functionalization was difficult to occur,the method reported in this paper is mild and the reaction can occur smoothly at room temperature without the use of transition metal catalysts and can be catalyzed by commercially available simple Bronsted acids to efficiently and specifically obtain the products of indole C6 site functionalization.The second part of this paper is devoted to the efficient synthesis of indolizines by the authors through the use of base promoted β,γ-unsaturated α-ketoesters with pyrrole formaldehyde derivatives via the occurrence of [4+2] cycloaddition reactions based on previous work.This reaction was used for the direct construction of 5,6-dihydroindolizine derivatives functionalized at C5,C6 and C7 via an intermolecular domino reaction.This reaction has the advantages of mild conditions and wide applicability of substrates.