Study On Construction Of Polycyclic Compounds Via One-pot Sequential Semipinacol Rearrangement/Michael Addition/Henry Reaction

The efficient construction of fused polycyclic carbocycle organic skeletons has been a sustained significant research topic in the field of organic synthesis and medicinal chemistry,owing to their important pharmaceutical values and bioactivities as well as their attractive structural features.A series of high-efficiency organic ring-formation methods or synthesis strategies have been developed,such as Diels-Alder reaction,cycloaddition reaction,polyene cyclization,which have basically met requirements of simple compounds for ring construction.However,constructing polycyclic skeleton of natural products,most of the present reports are based on key intermediate,and build multiple ring systems step by step,while the reports on the high-efficient construction of fused polycyclic carbocycle organic skeletons via one-pot intermolecular tandem reaction are quite rare.Taking 6/5/5fused polycyclic carbocycle skeleton bearing one quaternary carbon center as an example,due to their rigidity and steric hindrance,the total synthesis of such natural products bearing 6/5/5 fused tricyclic skeletons were reported.To date,however,a few such intermolecular tandem methods have been established to construct fused poly-carbocyclic frameworks.The research content of this thesis is to construct 6/5/5tricyclic compounds via tandem reaction.In order to achieve the efficient construction of 6/5/5 tricyclic compounds,we designed the Sequential Semipinacol rearrangement/Michael addition/Henry reaction.After a lot of conditional screening,a one-pot semipinacol rearrangement/Michael addition/Henry reaction of vinylogous?-ketols with nitroolefins has been achieved through the promotion of two Lewis acids,namely,TMSOTf and TiCl₄.Finally,we designed and synthesized two new types of chiral spiro catalysts on the basis of the1-azaspiro[4,4]nonane skeleton catalysts developed by our research group for the designing the sequential reaction.These catalysts did not achieve the desired sequential reactions.This thesis mainly includes the following four chapters:In the first chapter,the structure of natural products containing 6/5/5 tricyclic framework and their ring construction methods and strategies are briefly reviewed.In the second chapter,the sequential reactions of semipinacol rearrangement involving intermolecular carbon electrophilic reagents and applications of nitroolefin reaction in the construction of polycyclic compounds are briefly reviewed.In the third chapter,we designed and studied the sequential semipinacol rearrangement/Michael addition/Henry reaction in detail.A series of 6-5-5 and 7-5-5fused tricyclic carbocycles bearing up to five continuous stereocenters,including one quaternary carbon center,are constructed rapidly with up to 79%yields and>20:1diastereoselectivities through the promotion of two Lewis acids,namely,TMSOTf and TiCl₄.The reaction featuring broad scope of substrates,and a highly atom-,step-economical procedure.In the fourth chapter,we designed and synthesized two new types of spiropyridine catalysts based on the framework of 1-azaspiro[4,4]nonane,and explored their catalytic properties and chiral control effect.We also designed and synthesized chiral iridium complexes containing spiropyridine ligands.