Sulfonyl Fluoride Synthesis through Electrochemical Oxidative Coupling of Thiols and Potassium Fluoride

Abstract

Sulfonyl fluorides are valuable synthetic motifs for a variety of applications, among which sulfur(VI) fluoride exchange-based “click chemistry” is currently the most prominent. Consequently, the development of novel and efficient synthetic methods to access these functional groups is of great interest. Herein, we report a mild and environmentally benign electrochemical approach to prepare sulfonyl fluorides using thiols or disulfides, as widely available starting materials, in combination with KF, as an inexpensive, abundant and safe fluoride source. No additional oxidants nor additional catalysts are required and, due to mild reaction conditions, the reaction displays a broad substrate scope, including a variety of alkyl, benzyl, aryl and heteroaryl thiols or disulfides.

Accelerating sulfonyl fluoride synthesis through electrochemical oxidative coupling of thiols and potassium fluoride in flow

“…Next, we investigated the influence of the fluoride source on the reaction outcome ( Table 3). As shown in our previous work [15], the reaction worked well with alkali fluorides but also with Selectfluor. The use of Selectfluor was not further considered due to low atom efficiency and its higher price compared to alkali fluorides.…”

“…It is possible that pyridine functions either as an electron mediator [23] or a as phase transfer catalyst. From our mechanistic investigations [15], we believe that at least pyridine functions partly as a phase transfer catalyst (Table 4). Screening the concentration of pyridine, we found that the best results were obtained with 0.6-0.7 M pyridine ( Table 4, Entries 6 and 9).…”

“…While the reaction required 24-36 h in batch to reach full conversion [15], the reaction can be completed in only 5 min in flow ( Figs. 4 and 5).…”

“…While the CuAAC has served as a benchmark reaction for flow chemistry in the past two decades, SuFEx has received much less scrutiny. Recently, our group developed an electrochemical approach to access the key sulfonyl fluoride starting materials [15]. The method involves an anodic oxidation process and uses widely available thiols or disulfides and KF as a cheap, safe and widely available fluorine source.…”

Cyclic Alkenylsulfonyl Fluorides: Palladium‐Catalyzed Synthesis and Functionalization of Compact Multifunctional Reagents

“…Unsurprisingly, these latter two reports focus exclusively on planar arene and heteroarene substrates. A recent report has described the electrochemical coupling of thiols and potassium fluoride as a route to sulfonyl fluorides …”