Institute of Advanced Synthesis (IAS), School of Chemistry and Molecular Engineering, Nanjing Tech University, 30 South Puzhu Road, 211816, Nanjing, P. R. China.
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA, 19104, USA.
Nat Commun. 2019 Sep 25;10(1):4367. doi: 10.1038/s41467-019-12403-2.
Cyclopropanes represent a class of versatile building blocks in modern organic synthesis. While the release of ring strain offers a thermodynamic driving force, the control of selectivity for C-C bond cleavage and the subsequent regiochemistry of the functionalization remains difficult, especially for unactivated cyclopropanes. Here we report a photoredox-coupled ring-opening oxo-amination of electronically unbiased cyclopropanes, which enables the expedient construction of a host of structurally diverse β-amino ketone derivatives. Through one electron oxidation, the relatively inert aryl cyclopropanes are readily converted into reactive radical cation intermediates, which in turn participate in the ensuing ring-opening functionalizations. Based on mechanistic studies, the present oxo-amination is proposed to proceed through an S2-like nucleophilic attack/ring-opening manifold. This protocol features wide substrate scope, mild reaction conditions, and use of dioxygen as an oxidant both for catalyst regeneration and oxygen-incorporation. Moreover, a one-pot formal aminoacylation of olefins is described through a sequential cyclopropanation/oxo-amination.
环丙烷是现代有机合成中一类用途广泛的构筑模块。尽管环张力的释放提供了热力学驱动力，但对于 C-C 键的选择性断裂和随后的官能团化的控制仍然具有挑战性，特别是对于非活化的环丙烷。在这里，我们报告了一种光电还原耦合的未活化环丙烷的开环氧化氨化反应，该反应能够快速构建一系列结构多样的β-氨基酮衍生物。通过单电子氧化，相对惰性的芳基环丙烷很容易转化为反应性的自由基阳离子中间体，这些中间体继而参与随后的开环官能团化反应。基于机理研究，本研究提出的氧化氨化反应是通过 S2 型亲核进攻/开环机理进行的。该方法具有广泛的底物范围、温和的反应条件，以及使用分子氧作为氧化剂，既可以用于催化剂再生，也可以用于氧原子的引入。此外，还通过顺序环丙烷化/氧化氨化描述了一种烯烃的一锅法形式的氨基酰化反应。
