Design,Synthesis And Application Of New Umemoto's Reagent

The trifluoromethyl?CF₃?group is a useful structural motif in many biologically active molecules because it influences their chemical and metabolic stabilities,lipophilicity,and binding selectivities.Thus,the development of new methodologies for highly efficient introduction of the CF₃group into organic molecules has attracted plenty of attention among organofluorine chemist.Thus,many types of trifluoromethylating agents have been reported to date.Among them,Umemoto's reagents have become one of the most popular reagents.However,the high cost of these reagents limit their wide application in pharmaceutical industry.In this paper,synthesis of novel trifluoromethylating reagents,and incorporation of trifluoromethyl groups into organic compounds using electrophilic trifluoromethylating reagent have been studied.The main research contents are divided into three parts:Part 1:Our idea to substitute fluorine at specific positions on the dibenzothiophenium rings has resulted in massive improvements in the synthesis,properties,reactivity,and applications of these compounds.On the basis of this idea,2,8-difluoro-and2,3,7,8-tetrafluoro-S-?trifluoromethyl?dibenzothiophenium triflates and other salts were developed as powerful,thermally stable,one-pot-preparable,and recyclable reagents for the trifluoromethylation of various types of nucleophilic substrates,such as carbanions,?hetero?aromatics,alkenes,sulfinates,and phosphines.This one-pot and recycled production tremendously decreases the chemical and environmental costs of this process.Because of their higher reactivity and thermal stability,these new reagents may have wider applications than Umemoto's reagents.Part 2:A practical and efficient protocol of one-pot reaction for the synthesis of aryl trifluoromethyl sulfones has been developed by a tandem reaction of sulfonyl chloride with Umemoto's reagent?.The advantageous features of this method are transition-metal-free and mild conditions,wide scope of substrates,and up to 85%yield.Control experiments indicate that this reaction go through a radical-radical cross coupling pathway.Part 3:A four-component intermolecular trifluoromethylation–acyloxylation of arylalkenes induced by visible light has been developed in the presence of the photoredox catalyst Ru?bpy?₃?PF₆?₂under mild reaction conditions.A new Umemoto's reagent was used as a trifluoromethyl radical source,and this redox neutral reaction demonstrated good functional group tolerance for aryl alkenes with high yields up to 91%.The detailed reaction process was investigated based on control,deuterium and O¹⁸-labeling experiments to support that N,N-dimethylformamide?DMF?/H₂O acted as an acyloxyl source.