Asymmetric synthesis of sulfoximines, sulfonimidoyl fluorides and sulfonimidamides enabled by an enantiopure bifunctional S(VI) reagent.
Asymmetric synthesis of sulfoximines, sulfonimidoyl fluorides and sulfonimidamides enabled by an enantiopure bifunctional S(VI) reagent.
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DOI：
10.1038/s41557-023-01419-3
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发表时间：
2024-01
期刊：
影响因子：
21.8
通讯作者：
Shun Teng;Z. Shultz;Chuan Shan;Lukasz Wojtas;J. Lopchuk
中科院分区：
文献类型：
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作者：
Shun Teng;Z. Shultz;Chuan Shan;Lukasz Wojtas;J. Lopchuk
人们对扩展三维化学空间以设计新材料和药物的兴趣日益浓厚，从而产生了对常用分子功能的等排取代基团的需求。与非手性硫基和碳基对应物相比，手性 S(VI) 官能团的结构和化学性质提供了独特的空间和电子特征。通过立体化学控制操纵 S(VI) 中心以引入结构变异仍然是一个综合挑战。磺酰亚胺酰氟的稳定性和硫氟交换化学的效率使得对映体纯双功能S(VI)转移试剂-BuSF的开发能够克服目前的合成限制。在这里，我们公开了一种试剂平台，作为手性硫氟交换模板，用于快速不对称合成70多种亚砜亚胺、磺酰亚胺酰氟和磺酰亚胺，具有优异的对映体过量和良好的总产率。此外，双功能S(VI)转移试剂的实用性在对映体纯药物中间体和类似物的合成中得到了证明。
An increased interest to expand three-dimensional chemical space for the design of new materials and medicines has created a demand for isosteric replacement groups of commonly used molecular functionality. The structural and chemical properties of chiral S(VI) functional groups provide unique spatial and electronic features compared with their achiral sulfur- and carbon-based counterparts. Manipulation of the S(VI) centre to introduce structural variation with stereochemical control has remained a synthetic challenge. The stability of sulfonimidoyl fluorides and the efficiency of sulfur fluorine exchange chemistry has enabled the development of the enantiopure bifunctional S(VI) transfer reagentt-BuSF to overcome current synthetic limitations. Here, we disclose a reagent platform that serves as a chiral sulfur fluorine exchange template for the rapid asymmetric synthesis of over 70 sulfoximines, sulfonimidoyl fluorides and sulfonimidamides with excellent enantiomeric excess and good overall yields. Furthermore, the practical utility of the bifunctional S(VI) transfer reagent was demonstrated in the syntheses of enantiopure pharmaceutical intermediates and analogues.