Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Rd., Shanghai, 200062, P. R. China.
School of Pharmacy and Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai, 200237, P. R. China.
Angew Chem Int Ed Engl. 2022 Nov 2;61(44):e202207100. doi: 10.1002/anie.202207100. Epub 2022 Oct 5.
Sulfur(VI) fluoride cleavage and exchanging linkage, a new generation of linkage chemistry, exhibits enormous potential for combining a range of functional molecules in an increasing number of fields. Herein, we established a metal-free linkage of unactivated alkenes and sulfonimidoyl fluorides via hydrosulfonimidoylation to construct sulfoximines within minutes. An intermolecular hydride transfer process is the key step, and it occurs via overlap of the LUMO in the sulfonimidoyl cation and HOMO in the unactivated alkene, which was confirmed via control experiments with deuterated compounds. DFT calculations further demonstrated the concerted process involving formation of the S-C(sp ) bond and hydride transfer. Remarkably, abundant natural products and pharmaceuticals with multiple heteroatoms and sensitive functional groups have been subjected to the current linkage reaction to achieve various sulfoximine linkages, furnishing the basis for drug discovery and drug conjugation.
硫（六）氟化物的断裂和交换键合，作为新一代的键合化学，在将各种功能分子结合到越来越多的领域方面展现出巨大的潜力。在此，我们通过氢磺酰亚胺化反应，在无需活化的烯烃和磺酰亚胺氟化物之间建立了一种无金属键合，从而在数分钟内构建了亚砜亚胺。分子间的氢转移过程是关键步骤，它通过磺酰亚胺阳离子的 LUMO 和未活化烯烃的 HOMO 的重叠发生，这一点通过氘代化合物的对照实验得到了证实。DFT 计算进一步证明了涉及 S-C(sp ) 键形成和氢转移的协同过程。值得注意的是，大量含有多种杂原子和敏感官能团的天然产物和药物已被用于当前的键合反应，以实现各种亚砜亚胺键合，为药物发现和药物偶联提供了基础。
