Studies On The In-Situ Generation Of Phenyl(Trifluoromethyl) Iodonium And Electrophilic Trifluoromethylation

Organo-fluorine compounds have wide applications in diverse areas for their significant enhanced bioactivities than non-fluorine-containing analogues. Approximately 30% of modern medicines and agricultural chemicals contain at least one fluorine atom in molecules, among them, trifluoromethyl group occupies a large portion. Therefore, studies on the methodology for incorporation of CF3 into organic structures has emerged as one of the most attactive areas of organic synthesis in recent years. To this end, development and application of the trifluoromethylating reagents are crucial and necessary.Phenyl(trifluoromethyl)iodide is one of the simplest electrophilic trifluoromethylating reagents. However, several attempts made by Yagupolskii, Umemoto, Togni and other groups from 1978 to 2013 towards the synthesis or detection for Phenyl(trifluoromethyl)iodide failed. In 2006, Togni's group successfully synthesized cyclic I-trifluoromethylated iodine(III) compounds (called Togni's reagents later) which has been now commercially available and widely used. However, several drawbacks are really concerning such as higher cost and multi-step synthesis. Obviously, the development of low cost and simple trifluoromethylated hypervalent iodine compound, such as the corresponding acyclic anologues suitable for electrophilic trifluoromethylation, would be more applicable and practical.This dissertation consists of three parts:Part 1:The first chapter introduces the history and applications of electrophilic trifluoromethylating reagents, as well as recent advances of trifluoromethylating reactions. The second chapter elaborates the basis and strategy of my study.Part 2:The first chapter introduces how to detect the in-situ generated [PhICF3]+ species and the application of this species in direct a-C trifluoromethylation of ketene dithioacetals. The second chapter describes that [PhIC2F5]+ can also be detected in-situ based on the previous work. And using [PhIC2F5+ , the direct a-C pentafluoroethylation of ketene dithioacetals is successful. The third chapter focuses on expanding the application of these reactive species. The direct trifluoromethylation and pentafluoroethylation of indoles and electron rich arenes are successful.Part 3:The first chapter is inspired by the classical iododecarboxylation reactions of a-oxo ketene dithioacetals induced by iodium ion. The decarboxylative trifluoromethylation of a-oxo ketene dithioacetals based on the in-situ generation of [PhICF3]+ is realized. Meanwhile, the side product, a-iodo ketene dithioacetals, is important to prove the proposed cationic mechnism. The second chapter introduces how to detect [PhICF3]+ and [PhIC2F5]+ by HRMS and 19F-NMR analysis. The third chapter examines the reactivity of [ArICF3]+which have different substituents on the aryl ring.