Zhou Fei, He Xiaochun, Zhou Mi, Li Na, Wang Qingqing, Zhang Xuemei, Lian Zhong
Department of Dermatology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen, China.
Nat Commun. 2025 Jan 2;16(1):23. doi: 10.1038/s41467-024-55310-x.
Unsymmetric disulfides are prevalent in natural products and are essential in medicinal chemistry and materials science, but their robust synthesis poses significant challenges. In this paper, we report an expeditous transition-metal-free methodology for synthesizing unsymmetric disulfides through the addition of perthiyl radicals to alkenes. This study marks the use of generating perthiyl radicals by reacting SO with unactivated alkyl (pseudo)halides (Cl/Br/I/OTs). Various primary, secondary and tertiary alkyl (pseudo)halides substituted with different functional groups successfully function as suitable reactants. The formation of perthiyl radicals and their involvement in the reaction process are verified through mechanistic studies and DFT calculations. Overall, this method leverages readily available alkyl electrophiles and alkenes alongside SO in a single reaction setup to efficiently form both carbon-sulfur and sulfur-sulfur bonds simultaneously.
不对称二硫化物在天然产物中普遍存在，在药物化学和材料科学中至关重要，但其合成难度较大，面临诸多挑战。本文报道了一种无过渡金属的便捷方法，通过过硫自由基与烯烃加成来合成不对称二硫化物。本研究标志着通过将SO与未活化的烷基（伪）卤化物（Cl/Br/I/OTs）反应来生成过硫自由基的方法得到应用。各种被不同官能团取代的伯、仲和叔烷基（伪）卤化物均成功作为合适的反应物。通过机理研究和密度泛函理论（DFT）计算验证了过硫自由基的形成及其在反应过程中的参与情况。总体而言，该方法在单一反应体系中利用易得的烷基亲电试剂、烯烃以及SO，能够同时高效地形成碳 - 硫键和硫 - 硫键。
