Qi Jing, Wang Chu, Wang Gan, O'Neill Patrick, Reddy Dubbaka Srinivas, Ting Ang Hwee, Chen Xuebo, Wu Jie
Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, Singapore, 117544, Republic of Singapore.
Theoretical and Computational Photochemistry of the Chinese Ministry of Education, Chemistry College, Beijing Normal University, Beijing, 100875, P. R. China.
Angew Chem Int Ed Engl. 2025 Jan 2;64(1):e202413723. doi: 10.1002/anie.202413723. Epub 2024 Oct 30.
Capitalizing the inherent strain energy within molecules, strain-release-driven reactions have been widely employed in organic synthesis. Small cycloalkanes like cyclopropanes and cyclobutanes, with their moderate ring strain, typically require dense functionalization to induce bias or distal activation of (hetero) aromatic rings via single-electron oxidation for relieving the tension. In this study, we present a pioneering direct activation of alkyl cyclopropanes/butanes through electrochemical oxidation. This approach not only showcases the potential for ring-opening of cyclopropane/butane under electrochemical conditions but also streamlines the synthesis of diverse oxazolines and oxazines. The applicability of our method is exemplified by its broad substrate scopes. Notably, the products derived from cyclobutanes undergo a formal ring contraction to cyclopropanes, introducing an intriguing aspect to our discoveries. These discoveries mark a significant advancement in strain-release-driven skeletal rearrangement reactions of moderately strained rings, offering sustainable and efficient synthetic pathways for future endeavours.
利用分子内固有的应变能，应变释放驱动的反应已在有机合成中广泛应用。像环丙烷和环丁烷这样的小环烷烃，由于其适度的环张力，通常需要密集的官能团化，以通过单电子氧化诱导（杂）芳环的偏向或远端活化来缓解张力。在本研究中，我们展示了一种通过电化学氧化对烷基环丙烷/丁烷进行开创性直接活化的方法。这种方法不仅展示了在电化学条件下环丙烷/丁烷开环的潜力，还简化了多种恶唑啉和恶嗪的合成。我们方法的适用性通过其广泛的底物范围得到例证。值得注意的是，源自环丁烷的产物经历了向环丙烷的形式上的环收缩，为我们的发现引入了一个有趣的方面。这些发现标志着适度张力环的应变释放驱动的骨架重排反应取得了重大进展，为未来的研究提供了可持续且高效的合成途径。
