Synthesis Of Aryltrifluoromethyl-?~3-Iodane

Fluorinated Organic compounds have significant physiological and pharmacological activities,and are widely used in the fields of medicine and pesticides.Currently,fluorine-containing drugs account for a large proportion in the listed drugs,especially those containing trifluoromethyl groups.The introduction of trifluoromethyl group into organic compounds has been important subject in the field of fluorine chemistry.The key to the study of trifluoro-methylation methodology is the development and utilization of novel trifluoromethylation reagents.One of the most challenging research topic in the field of organic fluorine chemistry is the development of trifluoromethyl-?³-iodane as electrophilic trifluoromethylating reagent.However,several attempts made by Yagupolskii,Umemoto,Togni,etc.towards the synthesis for phenyl?trifluoromethyl?iodide failed.In 2006,Togni and co-workers successfully synthesized two cyclic aryltrifluoromethyl hypervalent iodine compounds?later called Togni reagents?,which are widely used under the activation of Lewis acid or Br?nsted acids.However,the only few types of available hypervalent iodine trifluoromethylation reagents remain the problems of high synthesis costs and complicated synthesis steps.Some scientists are committed to developing inexpensive,simple,and efficient methods for synthesizing trifluoromethyl hypervalent iodine reagents.Recently,our group has synthesized phenyltrifluoromethyl-?³-iodine using simple operated and low-cost continuous ligand exchange method.However,aryltrifluoromethyl-?³-iodine with diverse substituents cannot be synthesized because of the poorfunctional group tolerance.The synthesis of aryltrifluoro-methyl-?³-iodane makes it possible to develop chiral trifluoromethylation reagents and to study novel stereoselective trifluoromethylation reactions.This dissertation focuses on the synthesis of aryltrifluoromethyl-?³-iodane,the main contents include:1.The first chapter introduces the development,synthesis and application of trifluoro-methylation reagents and focusing on the development and utilization of electrophilic trifluoromethylation reagents.In the early days,the development of chalcogenophilic electro-philic trifluoromethylation reagents has been relatively mature,and the synthesis of trifluoro-methyl hypervalent iodine reagents has been limited by the instability of aryltrifluoromethyl iodonium until the synthesis of Togni reagents begins the prologue of hypervalent iodine compounds as electrophilic trifluoromethylation reagents.Afterwards,our group detect the in-situ generated PhI⁺CF₃ species and successfully synthesized phenyl-trifluoromethyl-?³-iodane.2.Based on previous work,we synthesized aryltrifluoromethyl-?³-iodane by a simple ligand exchange strategy.First,the aryl iodine was oxidized by Na₂S₂O₈ and chlorinated subsequently by concentrated hydrochloric acid to form ArICl2.Then,by using TMSCF3 and TBAA,aryl trifluoromethyl-?³-iodane was generated from ArICl₂ in acetonitrile at room temperature,which includes the first chiral trifluoromethyl reagent.The method has the advantages of mild reaction conditions,low-cost and wide range of substrates,which is significant for the development of chiral trifluoromethyl reagents.We simply evaluate the reaction activity of the reagents with well-known trifluoromethylation reactions.It has been preliminarily estimated that the electron-donating group has a tendency to enhance the reactivity of the reagent.