Enantioselective Access To Ring-Fused Compounds Bearing An All-Carbon Quaternary Stereocenter Via Palladium-Catalytzed Desymmetrization

Catalytic desymmetrization refers to enantiofacial discrimination of prochiral or meso-compounds to synthesize chiral products with high optical purity.Enantioselective desymmetrization reactions to furnish quaternary carbon stereocenters have been widely studied.In this thesis,based on the palladium-catalyzed intramolecular desymmetrization arylation strategy,we have developed two types of desymmetrization reactions to construct two different kinds of ring-fused compounds bearing an all-carbon quaternary stereocenters,including desymmetrization of ?-quaternary carbon-containing cyclohexanones and1,4-dihydropyridines to synthesize bicyclo[3.3.1]nonanones and indenodihydropyridines,respectively.1)An efficient desymmetrization of ?-quaternary carbon-containing cyclohexanones using readily available palladium and benzylamine as dual catalysts is developed.A wide range of bicyclo[3.3.1]nonanones containing a bridgehead quaternary carbon were formed in good yields with high enantioselectivities.Furthermore,aryl and alkenyl bromides,aryl iodide and triflates could also perform this reaction very well.This methodology exhibits good functional group tolerance and broad substrate scope.Notably,the products could be transformed into high-value building blocks such as quaternary center-containing dihydronaphthalenes,ring-fused indoles and lactones,tetralones,and 6,6,5-tricycles.Control experiments and computational calculations demonstrated the important role of benzylamine in accelerating the reaction rate and enhancing the enantioselectivities.2)An efficient desymmetrization of ?-quaternary carbon-containing dihydropyridines by palladium catalysis is disclosed,accessing a series of chiral indenodihydropyridines with high enantioselectivities.Notably,by modifying the reduction conditions,the indenodihydropyridine compounds can be further transformed to chiral tetrahydropyridines and piperidines,respectively.