Sulfur(VI) Fluoride Exchange (SuFEx): Another Good Reaction for Click Chemistry

 Angewandte Chemie International Edition, 2014.

Jiajia Dong, Larissa Krasnova, M. G. Finn, K. Barry Sharpless.

Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037 (USA) &

The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037 (USA) &

School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332 (USA).

 

ABSTRACT

Aryl sulfonyl chlorides (e.g. Ts-Cl) are beloved of organic chemists as the most commonly used S^VI electrophiles, and the parent sulfuryl chloride, O₂S^VICl₂, 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^VICl bond is exceedingly sensitive to reductive collapse yielding S^IV species and Cl⁻. Fortunately, the use of sulfur(VI) fluorides (e.g., R-SO₂-F and SO₂F₂) 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. 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 CH₂CH-SO₂-F, the most perfect Michael acceptor ever found. 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 SF bonds for SO 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.

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