SO₂F₂‐Promoted Dehydroxylative Fluorination of Alcohols

Abstract

Reported here is the development of a novel, mild and practical protocol for the SO2F2‐promoted dehydroxylative fluorination of readily available alcohols. The advantages of this protocol include an inexpensive and available reagent, and operational simplicity. This method enables the transformation of many kinds of primary, secondary and tertiary (hetero) arene alcohols into the corresponding fluorides and tolerates a range of functional groups. And the reactions occur smoothly to give the desired products in moderate to high yields. And a tentative mechanism was proposed involving formation and elimination of key intermediate, sulfonyl ester.

SO2F2-Mediated Fluorination of P(O)–H and P(O)–OH Compounds under Mild Conditions

“…In 2014, Sharpless and colleagues reported a method for the rapid synthesis of aryl fluorosulfonates (which played an important role in sulfur­(VI) fluoride exchange (SuFEx) click chemistry) by the reaction of phenols and SO 2 F 2 under mild conditions . Recently, the Sanford group and our group have successively reported SO 2 F 2 -promoted deoxyfluorination of phenolics, α-ketoesters, and alcohols. Our group has been working on the application and development of sulfuryl fluoride and found that sulfuryl fluoride can not only deoxygenate but also act as a potential fluorination and oxidation reagent.…”

SO2F2 Promoted Deoxygenhalogenation from Alcohols: A Practical Method for Preparing Halides.

“…In 2022, our group published a mild method for the dehydrofluorination of multiple (hetero)aromatic alcohols involving the generation and elimination of key sulfonyl ester intermediates. [29] We became interested in extending this strategy to a wider range of substrates and to all halogens. Hence, based on our preliminary results and the special properties of SO 2 F 2 , we established new conditions, featuring SO 2 F 2 , NH 4 X, (X = F, Cl, Br, or I), and a base, toward achieving the aforementioned synthetic goal (Scheme 1(3)).…”

“…In 2021, Sammis's group [28] reported SO 2 F 2 ‐mediated alcohol substitution and deoxygenation through the conversion of fluorosulfates to alkyl halide intermediates. In 2022, our group published a mild method for the dehydrofluorination of multiple (hetero)aromatic alcohols involving the generation and elimination of key sulfonyl ester intermediates [29] . We became interested in extending this strategy to a wider range of substrates and to all halogens.…”

eFluorination of Activated Alcohols Using Collidinium Tetrafluoroborate

“…It involves displacing an activated alcohol by a fluoride ion, which is especially challenging on hindered centers. Fluorination techniques are usually carried out with Selectfluor, HF salts such as Et 3 N·3HF and Olah’s reagent (pyridine·9HF), or S–F bond-type reagents (DAST, SF 4 , Deoxo-Fluor, Pyfluor) . However, the handling of those reagents can require additional considerations.…”

“…Fluorination techniques are usually carried out with Selectfluor, HF salts such as Et 3 N•3HF and Olah's reagent (pyridine•9HF), or S−F bond-type reagents (DAST, SF 4 , Deoxo-Fluor, Pyfluor). 9 However, the handling of those reagents can require additional considerations. Selectfluor displays poor solubility in organic solvents; 10 HF salts often require high temperatures to be effective, 2 and the higher the amount of HF, the higher the risk for the user.…”