EnT-Mediated N–S Bond Homolysis of a Bifunctional Reagent Leading to Aliphatic Sulfonyl Fluorides

• Published in: Journal of the American Chemical Society 2023-02, Vol.145 (4), p.2364-2374
• Main Authors: Erchinger, Johannes E., Hoogesteger, Reece, Laskar, Ranjini, Dutta, Subhabrata, Hümpel, Carla, Rana, Debanjan, Daniliuc, Constantin G., Glorius, Frank
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.2c11295

Sulfur­(VI) fluoride exchange (SuFEx) gives rise to a plethora of high-valent sulfur linkages; however, the availability of (aliphatic) sulfonyl fluoride manifolds lag behind, owing to the limited sources of introducing the SO2F moiety via a classical two-electron approach. Recently, radical-based methodologies have emerged as a complementary strategy to increase the diversity of accessible click partners. In this work, synthesis of a bench-stable sulfamoyl fluoride reagent is presented, which may undergo sigma-bond homolysis upon visible-light-induced sensitization to form protected β-amino sulfonyl fluorides from alkene feedstocks. Notably, this offers an appealing strategy to access various building blocks for peptido sulfonyl fluorides, relevant in a medicinal chemistry context, as well as an intriguing entry to β-ammonium sulfonates and β-sultams, from alkenes. Densely functionalized 1,3-sultones were obtained by employing allyl alcohols as substrates. Surprisingly, allyl chloride-derived β-imino sulfonyl fluoride underwent S–O bond formation and ring closure to yield rigid cyclopropyl β-imino sulfonate ester under SuFEx conditions. Furthermore, by engaging a thiol-based hydrogen atom donor in the reaction, the reactivity of the same reagent can be tuned toward the direct synthesis of aliphatic sulfonyl fluorides. Mechanistic experiments indicate an energy transfer (EnT)-mediated process. The transient sulfonyl fluoride radical adds to the alkene and product formation occurs upon either radical–radical coupling or hydrogen atom transfer (HAT), respectively.