SuFEx-enabled, chemoselective synthesis of triflates, triflamides and triflimidates†
a
Lauren
Voets,
a
Ruben
Van Lommel,
ab
Fien
Hoppenbrouwers,
a
Mercedes
Alonso,
b
Steven H. L.
Verhelst,
cd
Wim M.
De Borggraeve
*a
and
Joachim
Demaerel
*ac
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 (CF3SO2F) 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 SVI–F connector with a S![[double bond, length as m-dash]](https://www.rsc.org/images/entities/char_e001.gif)
O → SNR replacement furnished the analogous triflimidoyl fluorides as SuFEx electrophiles, which were engaged in the synthesis of rarely reported triflimidate esters. Notably, experiments showed H2O 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 CF3SO2F triflylation of amines.
- This article is part of the themed collection: 2022 Chemical Science HOT Article Collection
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