Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, UK.
Nat Rev Chem. 2022 Feb;6(2):146-162. doi: 10.1038/s41570-021-00352-8. Epub 2022 Jan 19.
The advent of sulfur(VI)-fluoride exchange (SuFEx) processes as transformations with click-like reactivity has invigorated research into electrophilic species featuring a sulfur-fluorine bond. Among these, sulfonyl fluorides have emerged as the workhorse functional group, with diverse applications being reported. Sulfonyl fluorides are used as electrophilic warheads by both medicinal chemists and chemical biologists. The balance of reactivity and stability that is so attractive for these applications, particularly the resistance of sulfonyl fluorides to hydrolysis under physiological conditions, has provided opportunities for synthetic chemists. New synthetic approaches that start with sulfur-containing substrates include the activation of sulfonamides using pyrilium salts, the deoxygenation of sulfonic acids, and the electrochemical oxidation of thiols. Employing non-sulfur-containing substrates has led to the development of transition-metal-catalysed processes based on palladium, copper and nickel, as well as the use of SOF gas as an electrophilic hub. Selectively manipulating molecules that already contain a sulfonyl fluoride group has also proved to be a popular tactic, with metal-catalysed processes again at the fore. Finally, coaxing sulfonyl fluorides to engage with nucleophiles, when required, and under suitable reaction conditions, has led to new activation methods. This Review provides an overview of the challenges in the efficient synthesis and manipulation of these intriguing functional groups.
硫（六）氟交换（SuFEx）反应作为类似点击反应的转化，极大地促进了对具有硫-氟键的亲电物种的研究。在这些亲电物种中，砜基氟化物已成为主力官能团，其应用也层出不穷。药物化学家与化学生物学家均将砜基氟化物用作亲电弹头。这些应用中，反应性与稳定性之间的平衡极具吸引力，尤其是砜基氟化物在生理条件下对水解的抗性，为合成化学家提供了机会。以含硫底物为起始原料的新合成方法包括使用吡咯鎓盐激活磺酰胺、磺酸的脱氧以及硫醇的电化学氧化。使用不含硫的底物则导致基于钯、铜和镍的过渡金属催化过程的发展，以及 SOF 气体作为亲电中心的应用。选择性地操纵已经含有砜基氟化物的分子也被证明是一种流行策略，其中金属催化过程再次占据主导地位。最后，在需要时并在合适的反应条件下，促使砜基氟化物与亲核试剂反应，从而产生了新的激活方法。本文综述了有效合成和操纵这些有趣官能团所面临的挑战。
