Studies On The Reactivities Of Trifluoromethyl Trifluoromethanesulfonate And Its Derivatives

Trifluoromethyl trifluoromethanesulfonate（CF₃SO₃CF₃）and its derivatives are important trifluoromethoxylation reagents,mainly used in nucleophilic trifluoromethoxylation reactions.But there are few reports on studies of its other aspects.Since the trifluoromethoxy anion originated from CF₃SO₃CF₃ is thermally unstable and quickly decomposes to fluorophosgene and fluoride anion at room temperature,we envisioned that trifluoromethyl trifluoromethanesulfonate would be employed as an excellent carbonylation reagent for amines in the preparation of urea derivatives,heterocycles,and carbamoyl fluorides under additive-free conditions.In addition,reaction of carboxylic acids with CF₃SO₂OCF₃ in the presence of a tertiary amine could achieve directly acyl fluorides through deoxyfluorination of carboxylic acids.In the first part,the reactions of CF₃SO₃CF₃ with amine compounds in CH₃CN at room temperature under ambient atmosphere for 2 minutes to 1 hour provided urea derivatives and carbamoyl fluorides.It was revealed that the click reactions of CF₃SO₃CF₃ with primary amines at room temperature formed ureas in good to high yields,while the same reactions with secondary aliphatic amines provided selectively carbamoyl fluorides in excellent yields.If CF₃SO₃CF₃ reacted with amines bearing adjacent hydroxyl,amino or thiol groups under the standard conditions,a variety of five-and six-membered heterocycles were eventually produced.It was determined that the N-,O-and S-nucleophiles have distinct reaction profiles for 2a and that the N-nucleophiles may possess priority in condensation with 2a under additive-free conditions,compared to the homologous O-and S-nucleophiles.Remarkably,experimental results suggested that CF₃SO₃CF₃ was the best“CO”source under metal-and additive-free conditions by comparing the reactions of the same type of reagents.Advantages of the method include simplicity,speediness,high efficiency,transition-metal-free conditions,good functional group tolerance,a wide range of substrates,excellent yields.In the second part,it has developed a simple method for deoxyfluorination of carboxylic acids with CF₃SO₃CF₃ and organic bases at room temperature.After the reaction,simple treatment could readily remove the byproduct and afford the pure acid fluoride without using column chromatography.Experiments have shown that CF₃SO₃CF₃ and its analogs are all favorable reagents for deoxyfluorination.Compared with the reported synthetic methods,there are many advantages of this approach include simplicity,speediness,high efficiency,ease of handling,good functional group tolerance,a wide range of substrates,and excellent yields,and effortless purification of the products owing to the formation of easily removable byproducts,CF₃SO₃CF₃ has been verified as a safe replacement for difluorophosgene and a promising deoxyfluorination reagent for carboxylic acids.These reactions represent the first example of using CF₃SO₃CF₃ as a viable fluorination reagent and a carbonylation reagent,and mark a favorable breakthrough of CF₃SO₃CF₃ in organic applications.It is significant for further studying of CF₃SO₃CF₃ and broadening its application range.