Study On The Synthesis Of Trifluoromethyl Vinyl Ethers Based On The New Reaction Of O-Trifluoromethylation Of Ketones

The introduction of fluorine-containing functional groups into organic molecules can often significantly change their physical and chemical properties and biological activities.Therefore,organic fluorides are widely used in medicine,pesticides,materials science and other fields,and also promote the rapid development of related synthesis methodologies.Recently,compounds formed by the bonding of trifluoromethyl（CF₃）with N,O,S and other heteroatoms have attracted much attention.Among them,the research on the synthesis and application of compounds containing OCF₃ has developed rapidly.Among the existing synthesis methods,O-trifluoromethylation,that is,the formation reaction of O-CF₃ bond,is a direct and economic synthesis path.However,the soft and hardness of O nucleophilic and CF₃ electrophilic do not match,and the bonding efficiency between them is poor,resulting in the slow development of O-trifluoromethylation.Although there is a scientific bottleneck in O-trifluoromethylation methodology,the O-trifluoromethylation of alcohol,phenol,ether,carboxylic acid,hydroxylamine and sulfonic acid can be realized by using efficient CF₃ reagent.Ketone is the basic raw material of organic chemical industry.The reported trifluoromethylation reaction of ketone is C-trifluoromethylation reaction,including two types:one is the nucleophilic addition reaction of ketone carbonyl with nucleophilic CF₃ reagent,and the product isα-CF₃ alcohol;The second is the synthesis of ketones using electrophilic CF₃ reagentα-Trifluoromethylation reaction,the product isα-CF₃ ketone.In comparison,the O-trifluoromethylation reaction on carbonyl O with ketone as O source has not been reported.In this paper,the efficient trifluoromethylation reagent Ph ICF₃Cl developed by our research group was used to realize the O-trifluoromethylation-chlorination reaction of ketones for the first time under the activation of aluminum chloride.The intermediate was further dechlorinated to form trifluoromethyl alkenyl ethers.The research contents of this paper are as follows:1.Chapter 1 summarizes three synthesis methods of trifluoromethoxy compounds.In addition,the trifluoromethylation reaction of ketones is summarized,including the nucleophilic addition reaction of trifluoromethyl reagents to carbonyl and theα-Trifluoromethylation reaction.In view of the scientific problem of the soft and hard mismatch between O and CF₃ in the methodology of O-trifluoromethylation,and the potential application of the new reaction mode of O-trifluoromethylation of ketones in the study of compounds containing OCF₃,this research paper,based on the method of activating Ph ICF₃Cl with aluminum chloride,selects the new reaction of O-trifluoromethylation of ketones as the research content,and discusses the significance of the topic.2.In the second chapter,we developed the O-trifluoromethylation of ketones for the first time,and established a new synthesis method of trifluoromethyl vinyl ether.With Ph ICF₃Cl activated by aluminum chloride as the source of trifluoromethyl,the O-trifluoromethylation of ketone can be realized in only 30 minutes under the condition of high temperature reflux.The results showed that the reaction was universal,and ketone substrates including aryl ethyl ketones,aliphatic ketones and cyclic ketones were suitable for the reaction;Through the mechanism verification experiment,a possible mechanism for the reaction was proposed:first,Ph ICF₃Cl and aluminum chloride formed a hypervalent iodine cation species[Ph ICF₃]⁺,then the electrophilic species complexed with carbonyl O,and promoted the addition reaction of Cl^-to carbonyl to form the intermediate[Ph（CF₃）I-O-C-Cl],and finally formed trifluoromethyl vinyl ether products through the elimination of iodobenzene;The potential application value of trifluoromethyl vinyl ether was initially demonstrated through the gram-scale preparation experiment of the product biphenyl trifluoromethyl vinyl ether and the application study of its cyclization and Di functionalization reaction.In short,this paper uses the highly active electrophilic trifluoromethylation reagent Ph ICF₃Cl developed by our research group to realize the carbonyl O-trifluoromethylation reaction of ketones for the first time,and synthesize alkenyl trifluoromethyl ethers,which provides a new strategy for the synthesis of trifluoromethoxy compounds.