SuFEx-enabled, chemoselective synthesis of triflates, triflamides and triflimidates. Issue 8 (17th January 2022)

• Record Type: Journal Article
• Authors: Li, Bing-Yu; Voets, Lauren; Van Lommel, Ruben; Hoppenbrouwers, Fien; Alonso, Mercedes; Verhelst, Steven H. L.; De Borggraeve, Wim M.; Demaerel, Joachim
• Is Part Of: Chemical science. Volume 13:Issue 8(2022)
• Page Start: 2270
• Page End: 2279
• Publication Date: 2022-01-17
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1sc06267k
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Triflyl fluoride gas (CF3 SO2 F) and its aza analogues are reported as new SuFEx activators. These S VI –F reagents react efficiently with a variety of nucleophiles, yet the presence of water grants complete chemoselectivity to phenols. Abstract : Sulfur(vi ) Fluoride Exchange (SuFEx) chemistry has emerged as a next-generation click reaction, designed to assemble functional molecules quickly and modularly. Here, we report the ex situ generation of trifluoromethanesulfonyl fluoride (CF3 SO2 F) gas in a two chamber system, and its use as a new SuFEx handle to efficiently synthesize triflates and triflamides. This broadly tolerated protocol lends itself to peptide modification or to telescoping into coupling reactions. Moreover, redesigning the S VI –F connector with a SO → SNR replacement furnished the analogous triflimidoyl fluorides as SuFEx electrophiles, which were engaged in the synthesis of rarely reported triflimidate esters. Notably, experiments showed H2 O to be the key towards achieving chemoselective trifluoromethanesulfonation of phenols vs. amine groups, a phenomenon best explained—using ab initio metadynamics simulations—by a hydrogen bonded termolecular transition state for the CF3 SO2 F triflylation of amines.