Peng Zhiyuan, Sun Shoujun, Zheng Meng-Meng, Li Yangyang, Li Xixi, Li Suhua, Xue Xiao-Song, Dong Jiajia, Gao Bing
State Key Laboratory of Chemo/BioSensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha, China.
Institute of Translational Medicine, National Facility for Translational Medicine (Shanghai), Shanghai Jiao Tong University, Shanghai, China.
Nat Chem. 2024 Mar;16(3):353-362. doi: 10.1038/s41557-024-01452-w. Epub 2024 Feb 14.
Linkage chemistry and functional molecules derived from the stereogenic sulfur(VI) centre have important applications in organic synthesis, bioconjugation, drug discovery, agrochemicals and polymeric materials. However, existing approaches for the preparation of optically active S(VI)-centred compounds heavily rely on synthetic chiral S(IV) pools, and the reported linkers of S(VI) lack stereocontrol. A modular assembly method, involving sequential ligand exchange at the S(VI) centre with precise control of enantioselectivity, is appealing but remains elusive. Here we report an asymmetric three-dimensional sulfur(VI) fluoride exchange (3D-SuFEx) reaction based on thionyl tetrafluoride gas (SOF). A key step involves the chiral ligand-induced enantioselective defluorinative substitution of iminosulfur oxydifluorides using organolithium reagents. The resulting optically active sulfonimidoyl fluorides allow for further stereospecific fluoride-exchange by various nucleophiles, thereby establishing a modular platform for the asymmetric SuFEx ligation and the divergent synthesis of optically active S(VI) functional molecules.
源自手性硫（VI）中心的连接化学和功能分子在有机合成、生物共轭、药物发现、农用化学品和高分子材料中具有重要应用。然而，现有的制备光学活性硫（VI）中心化合物的方法严重依赖于合成手性硫（IV）库，并且所报道的硫（VI）连接基团缺乏立体控制。一种模块化组装方法，即在硫（VI）中心进行顺序配体交换并精确控制对映选择性，很有吸引力但仍然难以实现。在此，我们报道了一种基于亚硫酰四氟气体（SOF）的不对称三维硫（VI）氟交换（3D-SuFEx）反应。关键步骤涉及使用有机锂试剂在手性配体诱导下对亚胺基硫酰二氟进行对映选择性脱氟取代。所得的光学活性磺酰亚胺基氟化物允许各种亲核试剂进一步进行立体特异性氟交换，从而建立了一个用于不对称SuFEx连接和光学活性硫（VI）功能分子发散合成的模块化平台。
