Studies On Asymmetric Baeyer-villiger Oxidation Reactions Catalyzed By Spirocyclic Pyrrolidine Catalysts And Its Synthetic Application

γ-Butyrolactones and derivatives are the structural cores of many natural products or drug molecules.These products and molecules,especially the chiral compounds,often exhibit particularly excellent biological activities,which are important for the development of new drugs and therapeutic agents.Therefore,the development of asymmetric synthesis of the compounds with γ-butyrolactones skeleton has attracted much attention of many chemists in the past decade.And the Baeyer-Villiger oxidation reaction is one of the concise and convenient approach toward esters from ketones,especially lactones from cycloketones.Spirocyclic pyrrolidine(SPD)has been one of the research priorities of our group since its first synthesis in 2012.It is our research goal to design new catalysts and ligands with stable structure and high catalytic activity based on the structure of SPD and applying these ligands to catalyze asymmetric reactions.In this dissertation,copper-catalyzed asymmetric Baeyer-Villiger oxidation reactions catalyzed by Cu/SPDO(spirocyclic pyrrolidine oxazoline)for synthesis of five-membered lactone compounds efficiently have been introduced.And this reaction has been applied to the asymmetric total synthesis of lignan natural eupomatilones 5 and 6.This dissertation is divided into following three chapters:In the first chapter,the reactions of asymmetric Baeyer-Villiger oxidations to prepare chiral γ-butyrolactones have been reviewed.According to the different reaction strategies,those reactions were divided into two sections: desymmetric reactions and kinetic resolution reactions.Each section was again divided into two subsections,metal catalysis and organic catalysis,according to the different catalysis methods.In addition,the recent research progress of SPDO ligands derived from SPD by our research group was introduced briefly.In the second chapter,some investigations have been made on the desymmetric Baeyer-Villiger oxidation of 3-substituted cyclobutanones with up to 90% yield,66%ee using the Cu(II)/SPDO as catalyst.Moreover,the kinetic resolution reactions of 2-substituted and 2,3-disubstituted cyclobutanones have been achieved with up to 96%ee,>20/1 rs,with the remaining substrates having up to 99% ee.Based on the obtained reaction results and X-ray analysis,reaction mechanism and stereo control models of the above reactions have been proposed.In the third chapter,the reaction of the kinetic resolution of 2,3-disubstituted cyclobutanone catalyzed by Cu(II)/SPDO was applied to the synthesis of natural products eupomatilones 5 and 6,which were completed in nine and eight steps from the commercially available starting material 3-methylcyclobutanone,respectively.