Mechanistic studies of thiol reactivity can be challenging because electrophilic reaction intermediates, such as sulfenic acids (RSOH) and sulfenyl chlorides (RSCl), are generally too reactive to be observed directly. Herein we report the design and synthesis of a sterically-encumbered fluorinated triptycene thiol to enable direct observation of reaction intermediates in aqueous buffer by 19F NMR, as demonstrated in reactions with hydrogen peroxide and hypochlorous acid. Reactions with H2O2 resulted in the formation of a persistent RSOH species, which was subsequently converted to a sulfinic acid (RSO2H) and then a sulfonic acid (RSO3H), while RSCl was found to be the intermediate in reactions with HOCl. Utilizing the same scaffold, reactions of thiol with thermally and photochemically generated singlet oxygen afforded RSO2H as the primary product. The stark difference in product profile from sterically-unencumbered thiols – which yield disulfides – implies that the reaction proceeds through a sulfenyl hydroperoxide (RSOOH) intermediate. Sulfenic acids, which were not observed in reactions of thiols with singlet oxygen, were also found to rapidly react with singlet oxygen to afford sulfinic acids, which is proposed to involve initial formation of an analogous sulfinyl hydroperoxide (RS(O)OOH). The formation and reactions of RSOOH are explored by computations. Use of the water-soluble fluorinated triptycene scaffold to probe reductive processes on RSOH (e.g., with ascorbate and/or iron) is also illustrated, wherein it was found that RSOH are surprisingly resistant to reductive heterolysis – in stark contrast with hydroperoxides – owing to their strong S-O bond.

中文翻译：

---

直接用 19F NMR 监测水溶液中硫醇反应中的亲电中间体


硫醇反应性的机理研究可能具有挑战性，因为亲电反应中间体，如亚磺酸 （RSOH） 和次磺酰氯 （RSCl），通常反应性太强，无法直接观察。在本文中，我们报道了空间位阻氟三苯硫醇的设计和合成，以便能够通过 19F NMR 直接观察水性缓冲液中的反应中间体，如与过氧化氢和次氯酸的反应所示。与 H 2 O 2 反应导致形成持久性 RSOH 物质，随后转化为亚磺酸 （RSO2H），然后转化为磺酸 （RSO3H），而 RSCl 被发现是与 HOCl 反应的中间体。利用相同的支架，巯基与热和光化学生成的单线态氧反应得到 RSO2H 作为主要产物。与产生二硫化物的空间无阻碍硫醇在产物特性上的明显差异意味着反应通过次磺酰过氧化氢 （RSOOH） 中间体进行。在硫醇与单线态氧的反应中未观察到的亚磺酸也被发现与单线态氧迅速反应以产生亚磺酸，这涉及类似亚磺酰过氧化氢 （RS（O）OOH） 的初始形成。通过计算探索 RSOOH 的形成和反应。还说明了使用水溶性氟化三苯支架探测 RSOH 上的还原过程（例如，使用抗坏血酸和/或铁），其中发现 RSOH 对还原异解具有惊人的抵抗力 - 与氢过氧化物形成鲜明对比 - 由于它们的强 S-O 键。