Synthesis Of Fluoroalkylated Quinazolinones And Sulfonamides By Radical Cascades Reactions

Chemical and physical properties of the molecules will significantly change when fluorine atom was introduced into the organic molecules.Fluorinated organic compounds are widely used in medicine,pesticide,new materials and other fields.Exploring to introduce efficiently fluorine atoms into organic molecules has been one of the intensest areas in research of organic fluorochemistry.Quinazolinones are a kind of heterocyclic compounds,which are separated from natural products.These types of natural products disclose a wide range of bioactivity and are applicable in the discovery of pharmaceutical candidates and other areas.At present,radical cyclization cascade reaction is the main strategy to synthesize the quinazolinones.However,studies focusing on introducing fluorine atoms into quinazolinones were rarely reported in the past few years.Herein,we describe a photocatalyzed difluoroalkylation/cyclization cascade strategy for construction of difluoroalkylated quinazolinones.Sulfonamides are widely used in medicine,pesticide and other fields.Herein,we describe an oxidation system enabled trifluoromethylation/cyclization cascade strategy for divergent and expedient synthesis of trifluoromethylated sulfonamides.Summary for this dissertation are as following:(1)Radical cyclization cascade of N-cyanamide alkenes for construction of difluoroalkylated quinazolinones:In this part,we have developed a facile access to synthesis of difluoroalkylated quinazolinones with broad substrate scopes in up to 97%isolated yields.An efficient strategy to build difluoroalkylated quinazolinones via visible-light-mediated difluoroalkylation has been developed.This sustainable strategy has attracted special attention due to its commendable functional group tolerance,operational simplicity,and high to excellent yields under mild conditions.Radical cascade reaction of the substrate was conducted on a gram scale under standard conditions.The desired product was achieved in a reasonable isolated yield of 90%.Several transformations of the difluoroalkylation product were achieved and the-CO2Et group underwent postfunctionalizations.(2)Radical cascade of N-cyansulfonamide alkenes for divergent and expedient synthesis of trifluoromethylated sulfonamides:We have developed an efficient strategy for synthesis of trifluoromethylated sulfonamides via oxidation-enabled trifluoromethylation/cyclization cascade of N-cyansulfonamide alkenes.The methods provide an efficient route for the synthesis of trifluoromethylated sulfonamides with broad substrate scopes in up to 80%isolated yields when the metal absent at room temperature.Radical cascade reaction of the substrate was conducted on a gram scale under standard conditions.The desired product was achieved in a reasonable isolated yield of 74%.This reaction features flexible structural modification,a broad substrate scope and high functional group tolerance as well as mild reaction conditions.