Asymmetric Mannich Reaction Of ?-Diazocarbonyl Compounds And N-sulfonyl Cyclic Ketimines Catalyzed By Complexes Generated From Chiral And Achiral Phosphines With Gold(?)

Many benzosultam compounds have promising biological activities,and they are also the core structure of many drug molecules.For many years,finding more efficient ways to synthesize benzosultams has been a goal for pharmaceutical chemists.In addition,these compounds are important organic reagents,and are often used in complex organic molecule synthesis,such as the introduction of halogens.Thus studies on the chiral synthesis of this class of compounds could help expanding the application of benzosultams in pharmaceutical synthesis,and have a positive impact on the development of synthetic chemistry.In this thesis,the general information on benzocyclo sulfonamides was first introduced,including its integration in the pharmaceutically active molecules and application in organic synthesis.As the diazo carbonyl compounds were used in this study,the background of diazonium compounds was also briefly introduced,focusing on the use of transition metal catalyzed diazonium compounds involved in organic reactions,as well as common diazonium carbene reactions.Finally,the common types of gold catalysis and its applications in organic synthesis were summarized.In this study,the benzosultams and diazo carbonyl compounds were selected as substrates,chiral and achiral ligands ligand were used to prepare the catalyst complex with gold.The Mannich reaction generated ?-amino-?-diazocarbonyl esters with quaternary carbon centers.A total of 16 benzosultams derivatives with chiral quaternary carbon centers were synthesized.The reaction catalyst has a low load,high yield and good stereoselectivity(up to 97% yield,85% ee).Firstly,according to the existing literature on gold catalysis,the catalytic properties of gold catalysts are mainly activated via carbon-carbon triple bonds or ethylenically unsaturated bonds,that is,the catalytic properties of ?-Lewis acid participate in the reaction.In our study,a very rare catalytic mode of gold catalysis was discovered.In this reaction process,gold did not complex with unsaturated bond in the substrate,that is,the catalytic properties of gold ?-Lewis acid are directly reflected during the reaction.Secondly,the diazonium structure of the substrate still remains in the product structure during the reaction.Metal carbene intermediates and other by-products were not formed in the reaction.This phenomanon is different from the common report that transition metals tend to damage the diazo structure and lead to the formation of metal carbene,and new observation has opened new opportunities for gold catalytic reactions.As the diazo structure in the substrate is preserved,the products can be easily converted into a a more complex structures,which are usually difficult to access by conventional methods.The synthesis of these compounds is very efficient,and examples include thesynthesis of spirosuccinimide via a three-step one-pot synthesis process.Finally,this thesis also explored the reaction mechanism involving the designed control experiments,including Operando IR experiments and nuclear magnetic experiments.We proposed that in this reaction,the gold complex catalyst first catalyzes the formation of enolized intermediates of diazo carbonyl compounds,followed by the reaction with benzosultams in an asymmetric Mannich Reaction fashion.Our method has the advantages of simple preparation of reaction substrates,easy availability of starting materials,broad substrate scope,mild reaction conditions,high reaction yield and excellent enantioselectivity.This study exmpanded the scope of gold-catalyzed reactions and provides a simple and effective method for the synthesis of benzosultams with chiral quaternary carbon centers.