Application Of Chloro(aryl)trifluoromethyliodane In O-trifluoromethylation Of Alcohols

The introduction of trifluoromethyl group into organic molecules tends to change the physical,chemical and biological properties of the target compounds.Therefore,the methodological research of introducing trifluoromethyl group into molecules with different structures has attracted extensive attention of organic chemists.Compounds generated by introducing trifluoromethyl group to heteroatom have very important applications in medicine,agrochemicals,and materials science.Wherein,the synthesis and application of OCF₃-containing compounds are one of the focused research topics in this field.Among many methods of constructing OCF₃-containing compounds,O-trifluoromethylation is one of the most concise and efficient synthetic strategy.Our research group has been devoted to the synthesis and application of noncyclic hypervalent iodine trifluoromethylation reagents,and the external coordination structuralλ³-phenyl（chloro）trifluoromethyliodane（Ph ICF₃Cl）was prepared for the first time by using direct ligand exchange method in 2018,which provided a breakthrough basis for the synthesis and application research of Ar ICF₃X.Previous studies have indicated that Ph ICF₃Cl showed partially ionic character and could conduct trifluoromethylation reactions directly with various kinds of nucleophiles without activation,the O-trifluoromethylation reactions of alcohols in which could only be carried out when using alcohol substrates themselves as the reaction solvent.In this paper,two new methods for activating hypervalent iodine trifluoromethylation reagents（Ph ICF₃Cl）have been developed to realize the O-trifluoromethylation reactions of alcohols in extra solvents,and a series of trifluoromethyl ethers have been synthesized through this method.The thesis mainly includes as the following:1.The synthesis methods of OCF₃-containing compounds were systematically summarized,and the activation methods of hypervalent iodine trifluoromethylation reagents were briefly reviewed.2.By using zinc chloride（ZnCl₂）as a Lewis acidic catalyst,the hypervalent iodine trifluoromethylation reagent（Ph ICF₃Cl）has been activated to generate a more reactive[Ph ICF₃]⁺species in situ with[ZnCl₃]^-as a counteranion,which effectively improved the ability of transferring the trifluoromethyl group in Ph ICF₃Cl.Accordingly,the O-trifluoromethylation reations of alcohols were realized in extra solvents,and the reactivity of the chloro（aryl）trifluoromethyliodane with different structures were also detailedly studied in this part.3.By using sodium trifluoromethanesulfonate（NaOTf）as an activator,the in situ ligand exchanging strategy has been achieved to activate Ph ICF₃Cl to generate[Ph ICF₃OTf]species in situ,which possesses a stronger capability of transferring trifluoromethyl group and could realize the O-trifluoromethylation reaction of alcohols in extra solvents efficiently.The reaction has mild reaction conditions and wide range of substrates,and could be available for a series of primary,secondary,tertiary alcohols and hydroxyl-containing drug molecules,which shows potential application value.In conclusion,this paper adopts Lewis acid activation and ligand exchange activation strategy respectively to improve the trifluoromethyl transferability of Ph ICF₃Cl.On this basis,the O-trifluoromethylation reaction of primary,secondary,and tertiary alcohols and hydroxyl-containing drug molecules under non-bulk conditions was realized,and a series of OCF₃-containing compounds were prepared.The new catalytic activation method established in the paper provides a direct,gentle,and efficient synthesis method for introducing trifluoromethyl groups into heteroatoms.