Trifluoromethyl Nonaflate: A Practical Trifluoromethoxylating Reagent and its Application to the Regio‐ and Stereoselective Synthesis of Trifluoromethoxylated Alkenes

Abstract

The trifluoromethoxy group has elicited much interest among drug and agrochemical discovery teams because of its unique properties. We developed trifluoromethyl nonafluorobutanesulfonate (nonaflate), TFNf, an easy‐to‐handle, bench‐stable, reactive, and scalable trifluoromethoxylating reagent. TFNf is easily and safely prepared in a simple process in large scale and the nonaflyl part of TFNf can easily be recovered as nonaflyl fluoride after usage and recycled. The synthetic potency of TFNf was showcased with the underexplored synthesis of various trifluoromethoxylated alkenes, through a high regio‐ and stereoselective hydro(halo)trifluoromethoxylation of alkyne derivatives such as haloalkynes, alkynyl esters, and alkynyl sulfones. The synthetic merits of TFNf were further underscored with a high‐yielding and smooth nucleophilic trifluoromethoxylation of alkyl triflates/bromides and primary/secondary alcohols.

Trifluoromethoxylation of Arynes Using 2,4‐Dinitro‐1‐(trifluoromethoxybenzene) as Trifluoromethoxide Anion Source

“…Trifluoromethyl triflate (TFMT), [9a,b] largely used to generate trifluoromethoxide salts, [9a–b,d−f,i,o] is an expensive reagent and low boiling point liquid (bp 19 °C), which limits its applications. Trifluoromethyl nonaflate (TFNf) was developed to overcome this boiling point issue but it has to be prepared from the Umemoto II reagent [9n] . Trifluoromethyl aryl sulfonates (TFMS) [9g] have been developed as a substitute of the latters but they have to be prepared from explosive and expensive Togni's reagent [10] .…”