Strain-Release Driven Epoxidation and Aziridination of Bicyclo[1.1.0]butanes via Palladium Catalyzed s-Bond Nucleopalladation
Strain-Release Driven Epoxidation and Aziridination of Bicyclo[1.1.0]butanes via Palladium Catalyzed s-Bond Nucleopalladation
复制标题
通过钯催化 s-键核钯化进行应变释放驱动的双环[1.1.0]丁烷的环氧化和氮丙啶化
DOI：
10.1002/ange.202217064
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发表时间：
2023
影响因子：
--
通讯作者：
Wölfl B
中科院分区：
文献类型：
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作者：
Wölfl B
由于环状化合物在药物化学中的广泛应用，合成四元碳环的制备方法的发展越来越重要。在此，我们报告了一种新的方法的发展，用于生产螺环环氧化物和氮杂环丙烷含有环丁烷基序。在两步一锅法中，将双环[1.1.0]丁基亚砜锂化并加入酮、醛或亚胺中，所得中间体通过C-C σ键烷氧基化或氨基钯化与三氟甲磺酸芳基酯交叉偶联，同时形成环氧化物或氮丙啶。经过仔细的优化，一个非常有效的反应被认为是容忍了各种各样的芳香族和脂肪族底物。最后，通过几个高产率的开环反应，我们证明了产物作为模块化构建块的出色适用性，用于将三维结构引入靶分子。
The development of preparative methods for the synthesis of four‐membered carbocycles is gaining increasing importance due to the widespread utility of cyclic compounds in medicinal chemistry. Herein, we report the development of a new methodology for the production of spirocyclic epoxides and aziridines containing a cyclobutane motif. In a two‐step one‐pot process, a bicyclo[1.1.0]butyl sulfoxide is lithiated and added to a ketone, aldehyde or imine, and the resulting intermediate is cross‐coupled with an aryl triflate through C−C σ‐bond alkoxy‐ or aminopalladation with concomitant epoxide or aziridine formation. After careful optimization, a remarkably efficient reaction was conceived that tolerated a broad variety of both aromatic and aliphatic substrates. Lastly, through several high yielding ring‐opening reactions, we demonstrated the excellent applicability of the products as modular building blocks for the introduction of three‐dimensional structures into target molecules.