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 (SOF₄). 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.

来自立构硫（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，现有的以S(VI)为中心的光学活性化合物的制备方法严重依赖于合成手性S(IV)库，并且报道的S(VI)连接体缺乏立体控制。模块化组装方法涉及在 S(VI) 中心进行连续配体交换并精确控制对映选择性，该方法很有吸引力，但仍然难以实现。在这里，我们报道了基于四氟化亚硫酰气体（SOF ₄）的不对称三维硫（VI）氟化物交换（3D-SuFEx）反应。关键步骤涉及使用有机锂试剂对亚氨基硫二氟化物进行手性配体诱导的对映选择性脱氟取代。所得光学活性磺酰亚胺酰氟允许各种亲核试剂进行进一步的立体特异性氟化物交换，从而为不对称 SuFEx 连接和光学活性 S(VI) 功能分子的发散合成建立模块化平台。