Organocatalytic Asymmetric Addition Reaction Of ?,?-unsaturated N-acylpyrazoles

Acyclic ?,?-unsaturated N-acylpyrazole compounds can combine with chiral tertiary amine catalysts and transform to the dienolate intermediates to achieve selective a-or y-functionalization in the reactions.Therefore,?,?-unsaturated N-acylpyrazoles is often used as dienolate nucleophiles in asymmetric organocatalytic carbon-carbon and carbon-heteroatom bond forming reactions.The N-acylpyrazole group in the structure can be used as a directing group to enhance stereocontrol and facilitate the activation of reaction sites.Moreover,N-acylpyrazole can also be used as a good leaving group for subsequent transformations.This dissertation mainly studies the asymmetric y-or a-selective addition reactions of the acyclic nucleophile ?,?-unsaturated N-acylpyrazoles activated to dienolate intermediates under the action of bifunctional tertiary amine catalysts.This dissertation was divided into four chapters.The first chapter introduces the research of different kinds of nucleophiles participating in the direct asymmetric addition reaction through the catalytic pathway of dienamine and dienolates respectively.In the second chapter,we first discuss the participation of dienolates in asymmetric organocatalytic inverse-electron demand Diels-Alder reaction.Secondly,we reported the asymmetric organocatalytic inverse-electron-demand oxa-Diels-Alder reaction of 2,3-dioxopyrrolidines with ?,?-unsaturated N-acylpyrazoles,which provided a fast and efficient method for the construction of pyralopyrroline-2-one bicyclic skeleton.The reaction carried out in tetrahydrofuran with 5 mol%cinchona alkaloid-derived squaramide catalyst at 10?.What's more,the different substituted dioxopyrrolidines and unsaturated N-acylpyrazoles substrates were expanded.Bicyclic pyrroline-2-keto-pyran compounds were obtained with high yields(up to 99%)and excellent diastereoselectivities and enantioselectivities(up to>99:1 dr,>99%ee),and the corresponding products could be easily converted into functional groups,and the enantioselectivities results were good.In chapter three,firstly,we introduce the asymmetric catalytic synthesis of chiral ?-amino acid derivatives.Then we studied the asymmetric direct Mannich reaction of N-Ts aldimines with ?,?-unsaturated N-acylpyrazoles,which provided a simple and effective method for the synthesis of ?-amino acids.The reaction prodeeded in cyclohexane with 10 mol%bifunctional tertiary amine-squaramide catalyst at the designation(40?)temperature.A series of substituted aldimines and unsaturated N-acylpyrazoles substrates were investigated.The products could obtained in good yields(up to 99%)with good enantioselectivities and excellent diastereoselectivities(up to 98%ee,>99:1 dr).In summary,we studied the asymmetric organocatalytic inverse-electron-demand oxa-Diels-Alder reaction and direct Mannich reaction involving dienolates intermediates,and synthesized chiral pyralopyrroline-2-one derivatives and ?-amino acid derivatives,which laid the foundation for the follow-up researches and applications.