Kinetically-driven reactivity of sulfinylamines enables direct conversion of carboxylic acids to sulfinamides.
Kinetically-driven reactivity of sulfinylamines enables direct conversion of carboxylic acids to sulfinamides.
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DOI：
10.1039/d3sc04727j
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发表时间：
2023-11-29
期刊：
影响因子：
8.4
通讯作者：
Larionov, Oleg V.
中科院分区：
文献类型：
--
作者：
Dang, Hang T.;Porey, Arka;Nand, Sachchida;Trevino, Ramon;Manning-Lorino, Patrick;Hughes, William B.;Fremin, Seth O.;Thompson, William T.;Dhakal, Shree Krishna;Arman, Hadi D.;Larionov, Oleg V.
亚砜酰胺是一些最重要的四价硫化合物，是一系列新兴药物官能团、生物偶联分子工具和合成中间体的关键切入点，包括亚砜亚胺、磺胺酰亚胺和磺胺酰卤化物，以及广泛的其他S（iv）和S（vi）官能团。然而，亚砜胺的化学空间仍然有限，亚砜胺的方法主要局限于双电子亲核取代反应。我们在此报道了一种直接自由基介导的脱羧亚胺化反应，首次使人们能够从羧酸的广泛和结构多样的化学空间中获得亚胺。我们的研究表明，尽管氮原子的自由基加成具有固有的热力学偏好，但亚砜酰胺的形成仍然普遍存在，而基于计算生成的潜在自由基反应活性描述符的机器学习衍生模型有助于预测反应效率。由于亚胺的动力学反应活性和吖啶光催化作用，现在可以很容易地从羧酸和胺中通过直接脱羧反应获得亚胺。
Sulfinamides are some of the most centrally important four-valent sulfur compounds that serve as critical entry points to an array of emergent medicinal functional groups, molecular tools for bioconjugation, and synthetic intermediates including sulfoximines, sulfonimidamides, and sulfonimidoyl halides, as well as a wide range of other S(iv) and S(vi) functionalities. Yet, the accessible chemical space of sulfinamides remains limited, and the approaches to sulfinamides are largely confined to two-electron nucleophilic substitution reactions. We report herein a direct radical-mediated decarboxylative sulfinamidation that for the first time enables access to sulfinamides from the broad and structurally diverse chemical space of carboxylic acids. Our studies show that the formation of sulfinamides prevails despite the inherent thermodynamic preference for the radical addition to the nitrogen atom, while a machine learning-derived model facilitates prediction of the reaction efficiency based on computationally generated descriptors of the underlying radical reactivity. Sulfinamides can now be readily accessed from carboxylic acids and amines in a direct decarboxylative reaction enabled by the kinetically-driven reactivity of sulfinylamines and acridine photocatalysis.
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影响因子：
64.8
作者：
Bayeh L;Le PQ;Tambar UK
通讯作者：
Tambar UK
影响因子：
15
作者：
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通讯作者：
Bolm, Carsten
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Davies, Thomas Q.;Hall, Adrian;Willis, Michael C.
通讯作者：
Willis, Michael C.