Sulfur(VI) fluoride exchange (SuFEx): Another good reaction for click chemistry

Abstract

Aryl sulfonyl chlorides (e.g. Ts-Cl) are beloved of organic chemists as the most commonly used SVI electrophiles, and the parent sulfuryl chloride, O2SVICl2, has also been relied on to create sulfates and sulfamides. However, the desired halide substitution event is often defeated by destruction of the sulfur electrophile because the S VIï£iCl bond is exceedingly sensitive to reductive collapse yielding SIV species and Cl-. Fortunately, the use of sulfur(VI) fluorides (e.g., R-SO2-F and SO2F 2) leaves only the substitution pathway open. As with most of click chemistry, many essential features of sulfur(VI) fluoride reactivity were discovered long ago in Germany.6a Surprisingly, this extraordinary work faded from view rather abruptly in the mid-20th century. Here we seek to revive it, along with John Hyatt's unnoticed 1979 full paper exposition on CH 2ï£CH-SO2-F, the most perfect Michael acceptor ever found.98 To this history we add several new observations, including that the otherwise very stable gas SO2F2 has excellent reactivity under the right circumstances. We also show that proton or silicon centers can activate the exchange of Sï£iF bonds for Sï£iO bonds to make functional products, and that the sulfate connector is surprisingly stable toward hydrolysis. Applications of this controllable ligation chemistry to small molecules, polymers, and biomolecules are discussed. Old chemistry in new glory: Sulfonyl fluoride exchange (SuFEx) forges rugged inorganic links between carbon centers. Like most click reactions, it is an old process now improved to allow the underappreciated sulfate connection to be made for a variety of purposes. The various exchange events uniquely enabled by the use of fluoride are highlighted here in orange. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.