Trifluoromethyl Nonaflate: A Practical Trifluoromethoxylating Reagent and its Application to the Regio‐ and Stereoselective Synthesis of Trifluoromethoxylated Alkenes. Issue 29 (17th June 2021)

• Record Type: Journal Article
• Authors: Lu, Zhichao; Kumon, Tatsuya; Hammond, Gerald B.; Umemoto, Teruo
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 29(2021)
• Page Start: 16171
• Page End: 16177
• Publication Date: 2021-06-17
• Subjects: alkynes -- halotrifluoromethoxylation -- hydrotrifluoromethoxylation -- trifluoromethoxylated alkenes -- trifluoromethoxylation; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202104975
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : Trifluoromethyl nonaflate (TFNf), an odorless liquid (bp 87–89 °C), was developed as an easy‐to‐handle, bench‐stable, and reactive trifluoromethoxylating reagent that can be easily and safely prepared in large scale. The synthetic potency of TFNf was demonstrated with the synthesis of various trifluoromethoxylated alkenes, through a highly regio‐ and stereoselective direct hydro(halo)trifluoromethoxylation of various alkyne derivatives.