Tf2O

Tf2O, or triflic anhydride, is a highly reactive sulfonylating reagent used in organic synthesis. Its formula is (CF3SO2)2O, and it is the anhydride of triflic acid (CF3SO3H). Tf2O is valued for its ability to convert substrates into highly reactive triflate derivatives, which serve as excellent leaving groups in cross-coupling and other transformations.

As a strong electrophile, Tf2O is typically employed to activate alcohols and related nucleophiles by forming alkyl or aryl triflate esters (ROSO2CF3). These triflates are commonly used to enable nucleophilic substitutions, palladium- and nickel-catalyzed cross-couplings, and various rearrangements. Tf2O can also activate carbonyl compounds under appropriate conditions, generating acyl triflate intermediates that facilitate acylation reactions or conversion of carboxylic acids to more reactive derivatives.

Preparation and availability: Tf2O is commercially available and is commonly prepared by the dehydration of triflic acid or through other dehydration routes that remove water from two molecules of CF3SO2OH to yield (CF3SO2)2O. Because of its high reactivity, Tf2O is typically handled under strictly anhydrous conditions and stored in appropriate containers under inert atmosphere and at low temperature.

Handling and safety: Tf2O is moisture-sensitive and reacts exothermically with water, releasing heat and forming triflic acid. It is corrosive and can cause severe chemical burns; inhalation or skin contact should be avoided. Appropriate personal protective equipment and dry, inert solvents are recommended when working with Tf2O.

See also: triflic acid, triflate, sulfonylation.