ArOTf

ArOTf, or aryl triflate, denotes aryl triflate esters in which an aryl group is bonded to a triflate leaving group (trifluoromethanesulfonate, –OTf). The triflate moiety is one of the best leaving groups known in organic synthesis, which makes aryl triflates versatile substrates for cross-coupling and related transformations.

Preparation: The common method is triflation of phenols with triflic anhydride (Tf2O) in the presence of a base such as pyridine, DIPEA, or lutidine, typically at 0–25 °C. The reaction Ar–OH + Tf2O → Ar–OTf + HOTf converts a relatively unreactive phenol into a reactive electrophile. Aryl triflates can also be installed in situ during a coupling sequence or prepared from other aryl precursors using Tf2O-based reagents.

Reactivity: Ar–OTf undergoes oxidative addition to Pd(0) or Ni(0) catalysts, enabling cross-coupling reactions such as Suzuki–Miyaura, Negishi, Kumada, and Stille to form C–C bonds, as well as C–N bond-forming processes in Buchwald–Hartwig amination. In many cases aryl triflates offer advantages over aryl halides, especially for substrates that are difficult to convert to halides. They can be hydrolyzed back to the parent phenol upon exposure to water or base.

Applications and limitations: Aryl triflates are widely used in pharmaceutical and natural product synthesis, allowing late-stage diversification of complex molecules. Their formation requires care to avoid hydrolysis; they can be moisture-sensitive and Tf2O is corrosive and lachrymatory, requiring proper handling and inert atmosphere.

See also: triflate, cross-coupling reactions, aryl halides.