Asymmetric Synthesis Of Spirooxindole δ-lactones And α-amino Acid Derivatives Via Organocatalysis

Synthesis of spirocyclic compounds via asymmetric organocatalysis is studied in this thesis which is composed of three parts:Part 1:Asymmetric catalysis for the synthesis of spirocyclic compoundsFirstly, this part briefly summarizes the importance, classification, problems and possible solutions of asymmetric catalysis. In generally, asymmetric catalysis can be divided into three types:enzymatic catalysis, metal-ligand catalysis, organocatalysis. They all have their own merits and drawbacks. There are three main directions of asymmetric catalysis:looking for catalysts with high selectivity, increasing the efficiency of chiral catalysts, recycling and reusing the chiral catalysts.Secondly, a review featuring recent developments of asymmetric catalysis is presented. Spirocycles provide an exciting platform to develop and understand the reactivity and selectivity for a wide variety of catalysts while affording diverse strategies to access molecules with important applications. " Privileged" routes for the efficient construction of spirocenters:cyclization catalyzed by Pd, Rh, Ir complexes, NHC-catalyzed cycloaddition reactions, metal- and acid-catalyzed cycloaddition, thiourea-catalyzed cycloaddition reactions, pyrrolidine catalysts for cycloaddition reactions, asymmetric catalysis for rearrangement and ring-expansion reactions.Part 2:Hydrogen-bond-directed formal [5+1] annulations of oxindoles with ester-linked bisenones:facile access to chiral spirooxindole δ-LactonesA novel bifunctional thiourea catalyzed formal [5+1] cycloaddition of oxindoles and ester-linked bisenones was successfully developed. This strategy involves two sequential Michael additions, leading to spirooxindole δ-lactones with three contiguous stereocenters including an all-carbon quaternary center with high diastereoselectivities and enantioselectivites. In addition, a remarkable N-substituent effect was observed on the reactivity and selectivity.Part 3:Organocatalyzed asymmetric vinylogous allylic-allylic alkylation of Morita-Baylis-Hillman carbonates with olefinic azlactones:facile access to chiral multifunctional a-amino acid derivativesVinylogous reactivity of olefinic azlactones was realized through the development of a chiral amine-catalyzed highly stereooselective allylic-allylic alkylation with Morita-Baylis-Hillman (MBH) carbonates. The Lewis base-activation of electrophile and Br(?)nsted base-activation of nucleophile were efficiently combined, giving access to multifunctional acyclic α-amino acid derivatives in a highly stereocontrolled manner. The synthetic utility of these versatile synthons was further demonstrated by the facile synthesis of cyclic quaternary α-amino acid derivatives.