Organicatalysis Asymmetric Vinylogous Cyclization Reaction Of β,γ-unsaturated Pyrazolamide

In the past two decades,asymmetric organocatalytic has developed rapidly and has been widely used in the synthesis of various chiral compounds.The development of simple and efficient methods to synthesize a variety of chiral compounds has been a central issue in the field of chemical synthesis.The field of asymmetric vinylogous reactions is one of the most dynamic and strongest fields in organic synthesis.At present,a wide range of high regioselectivity and stereoselective addition reactions have been successfully established.The asymmetric vinylogous reactions can provide a simple method to product a chiral center at the y-position or even further away from the functional group of the substrate.Unsaturated carbonyl compounds can form dienamines or dienols and other intermediates under the condition of chiral amine catalysts to carry out asymmetric insertion reaction at the γ position,which can be used to construct various chiral multi-components and heterocyclic compounds.This may have implications for the synthesis of natural products or the development of new drugs.In addition,the dienol intermediate formed by the unsaturated pyrazole amide under the bifunctional catalyst is used for the y-position vinylogous addition reaction,and the pyrazole group is used as the easy leaving group and controlled guiding group can be used to construct chiral four-membered rings and chiral indole spiro derivatives.Therefore,in this thesis,theβ,γ-unsaturated pyrazole amide is used as a nucleophile for the vinylogous Michael reactions/cyclization and Diels-Alder reaction at the y position.This paper is divided into four chapters.The first chapter mainly summarizes the introduction of asymmetric organocatalytic,classical catalysis mode,asymmetric vinylogous reactions and the asymmetric vinylogous reactions of unsaturated carbonyl compounds at the γ position.In chapter 2,we first introduced the vinylogous Michael addition reaction.Secondly,we report the asymmetric Michael addition/cyclization reaction of β,γ-unsaturated pyrazole amides and nitroalkenes,which provides a novel method for the construction of chiral cyclobutane derivatives.In the presence of 15 mol%cinchona catalyst QNSA,using toluene as the solvent and first carry out the vinylogous Michael addition reaction of β,γ-unsaturated pyrazole amide at y-position,and then in the presence of organic base,the vinylogous product uses CHCl3 as the solvent and intramolecular cyclization to obtain cyclobutane derivatives with high yields and excellent enantioselectivities,and the reaction can be prepared on a gram scale.In chapter 3,we first introduce the Diels-Alder reaction of organocatalysis,and give a brief overview of chiral indole spiro compounds.Subsequently,we studied the catalyst derived from cinchona base to catalyze the asymmetric inverse-electron-demand oxa-Diels-Alder reaction of β,γ-unsaturated pyrazole amides and isatin derivatives,providing a basis for the construction of chiral indole spiro skeletons..The Diels-Alder reaction was catalyzed by 10 mol%cinchona base catalyst,trifluorotoluene was used as the solvent,and the β,γ-unsaturated pyrazole amide and the[4+2]ring of the isatin derivative were carried out at 0℃.The chiral indole spiro skeleton compounds were obtained with highly yields and enantioselectivities.In summary,we have developed reaction which usedβ,γ-unsaturated pyrazole amide to achieve the asymmetric vinylogous Michael addition reaction involving and the asymmetric asymmetric inverse-electron-demand oxa-Diels-Alder reaction.Cyclobutane derivatives and chiral indole spiro derivatives provide a basis for subsequent research and applications.