Yang Hui-Yi, Du Hai-Bao, Bai Yong-Ping, Ding Ya-Hui, Ma Yi-Fan, Wu Gang, Zhang Ning, Szymczak Nathaniel K, Guo Shuo
College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, China.
College of Chemistry, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071,China.
Sci Adv. 2025 Jul 25;11(30):eadw8408. doi: 10.1126/sciadv.adw8408.
Fluorine-containing allyl compounds are prevalent in drugs and bioactive molecules. Here, we report a straightforward and efficient radical pentafluorosulfanylation of allyl sulfones using sulfur chloride pentafluoride (SFCl) to synthesize structurally diverse pentafluorosulfanyl allylic compounds. This transformation exhibits excellent functional group tolerance and achieves an impressive isolated yield of up to 98% in just 1 minute under ultraviolet light. Mechanistic studies suggest that the sulfonyl group acts as a free radical leaving group, with the capability of abstracting the chlorine atom from SFCl. This radical chain propagation pathway facilitates the rapid regeneration of the sulfur pentafluoride radical, resulting in a notably high quantum yield. Moreover, this light-driven radical pentafluorosulfanylation simplifies the synthetic pathway to modify complex and bioactive molecules. In addition, the drug-modified pentafluorosulfanyl compounds exhibited promising effects in inhibiting cancer cell proliferation, both in vitro and in vivo. Therefore, this protocol provides a practical synthetic route to radical pentafluorosulfanylation, highlighting its potential in drug discovery.
含氟烯丙基化合物在药物和生物活性分子中普遍存在。在此，我们报道了一种使用五氟化硫氯（SFCl）对烯丙基砜进行直接且高效的自由基五氟硫烷基化反应，以合成结构多样的五氟硫烷基烯丙基化合物。该转化反应表现出优异的官能团耐受性，并且在紫外光下仅需1分钟就能实现高达98%的可观分离产率。机理研究表明，砜基作为自由基离去基团，能够从SFCl中夺取氯原子。这种自由基链增长途径促进了五氟化硫自由基的快速再生，从而产生显著高的量子产率。此外，这种光驱动的自由基五氟硫烷基化反应简化了修饰复杂生物活性分子的合成途径。另外，经药物修饰的五氟硫烷基化合物在体外和体内均表现出有前景的抑制癌细胞增殖的效果。因此，该方案为自由基五氟硫烷基化提供了一条实用的合成路线，突出了其在药物发现中的潜力。
