Photoinduced Radical Fluoroalkylation Based On Single Electron Transfer Strategy

The introduction of fluorine-containing groups into organic molecules can usually endow compounds with special properties,especially the introductions of fluoroalkyl groups,such as trifluoromethyl and perfluoroalkyl,into drug molecules always lead to drastic enhancement of their solubility,metabolic stability,and bioavailability.In this context,the developments of efficient processes for construction of C-CF₃ and C-R_fbonds by using cheap and easily available raw materials is one of the significant issues in organic synthesis,which has attracted much attention from organic chemists.In the past few decades,this research field has achieved great development,but there is still a lack of efficient and versatile methods to systematically introduce fluorine-containing groups into organic molecules.Light energy is the cleanest source of energy in nature.Compared with traditional transition metal catalysis,photocatalysis featured by mild conditions and good substrate compatibility,which is suitable for the synthesis of functional organic molecules containing sensitive groups,especially for drugs synthesis and modification.Therefore,the development of general,practical and predictable photocatalytic strategies to construct fluorine-containing organic compounds could provide a reliable method for the synthesis of fluorine-containing drug molecules.This dissertation mainly focuses on the photoinduced single electron transfer strategy to realize radical fluoroalkylation.In this work,under light conditions,the cyanofluoroalkylation of alkenes and asymmetric cyanofluoroalkylation of alkenes have been realized using cheap and easily available fluoroalkyl iodide as the fluoroalkylation reagents.In addition,we also realized dearomatization of?-naphthol under metals,oxidants and photosensitizers free condition,which provides a new alternative for the construction of fluoroalkyl substituted cyclic ketene skeletons.This dissertation mainly includes five chapters.The first chapter summarizes the development of photoinduced radical fluoroalkylation.In chapter 2,under UV light condition,using copper as a single-electron redox catalyst to participate in the photoredox cycle,we realized three components cyanofluoroalkylation of alkenes with fluoroalkyl iodides as fluoroalkylation reagents.In chapter 3,on the basis of the research in Chapter 2,we successfully used clean and abundant visible light as the reaction light source to further realize asymmetric cyanofluoroalkylation of alkenes.More importantly,we have also developed a new bifunctional photoredox chiral copper catalyst,which provides a method for the construction of chiral organic molecules and drug molecules.In chapter 4,we realized the first visible-light-promoted dearomatizative fluoroalkylation of?-naphthols via charge transfer within the naphtholate-fluoroalkyl iodide electron-donor-acceptor(EDA)complex induced a single electron transfer electron donor and accepter complex without the assistance of any transition metal catalyst,oxidizing agent and external photosensitizer.To our surprise,this method can also achieve gram-scale preparation,showing the great significant potential and advantages of this strategy in large-scale industrial synthesis.In chapter 5,we made a brief summary of this work and prospects for the future.