Jiang Hua-Jie, Fang Wei, Chen Xinran, Yu Xin-Ran, Meng Yan-Dong, Fang Li-Ping, Shen Meng-Lan, Yao Chuan-Zhi, Li Qiankun, Hong Xin, Yu Jie
Department of Applied Chemistry, Anhui Province Engineering Laboratory for Green Pesticide Development and Application, and Anhui Province Key Laboratory of Crop Integrated Pest Management, Anhui Agricultural University, Hefei 230036, China.
Center of Chemistry for Frontier Technologies, Department of Chemistry, State Key Laboratory of Clean Energy Utilization, Zhejiang University, Hangzhou 310027, China.
J Am Chem Soc. 2025 Jan 15;147(2):2137-2147. doi: 10.1021/jacs.4c16233. Epub 2025 Jan 2.
Asymmetric catalysis involving a sulfoxide electrophile intermediate presents an efficient methodology for accessing stereogenic-at-sulfur compounds, such as sulfinate esters, sulfinamides, , which have garnered increasing attention in modern pharmaceutical sciences. However, as the aza-analog of sulfoxide electrophiles, the asymmetric issues about electrophilic sulfinimidoyl species remain largely unexplored and represent a significant challenge in sulfur stereochemistry. Herein, we exhibit an anionic stereogenic-at-cobalt(III) complex-catalyzed asymmetric synthesis of chiral sulfinamides via chiral sulfinimidoyl iodide intermediates. Mechanistic investigations reveal that the catalytic cycle is initiated by asymmetric oxidative iodination, generating sulfinimidoyl iodides. These active intermediates subsequently undergo an enantiospecific nucleophilic substitution with water, affording a diverse array of enantioenriched sulfinamides. Notably, these sulfinamides exhibit promising antifungal activities against and serve as ideal platform molecules facilitating the stereospecific transformation into various stereogenic aza-sulfur compounds.
涉及亚砜亲电中间体的不对称催化为获取硫中心手性化合物提供了一种有效方法，比如亚磺酸酯、亚磺酰胺等，这些化合物在现代药物科学中受到越来越多的关注。然而，作为亚砜亲电试剂的氮杂类似物，亲电亚磺酰亚胺物种的不对称问题在很大程度上仍未得到探索，并且是硫立体化学中的一个重大挑战。在此，我们展示了一种通过手性亚磺酰亚胺碘中间体，由阴离子钴（III）中心手性配合物催化的手性亚磺酰胺的不对称合成。机理研究表明，催化循环由不对称氧化碘化引发，生成亚磺酰亚胺碘。这些活性中间体随后与水进行对映体特异性亲核取代反应，得到一系列对映体富集的亚磺酰胺。值得注意的是，这些亚磺酰胺对……表现出有前景的抗真菌活性，并作为理想的平台分子促进向各种手性氮杂硫化合物的立体特异性转化。
