Singha Tushar, Bapat Nakul Abhay, Mishra Subrat Kumar, Hari Durga Prasad
Department of Organic Chemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India.
Org Lett. 2024 Aug 2;26(30):6396-6401. doi: 10.1021/acs.orglett.4c02177. Epub 2024 Jul 24.
Spirocyclobutyl oxindoles have garnered substantial attention in drug discovery and pharmaceuticals owing to their wide range of biological activities. Strain-release in small-ring compounds is a powerful strategy to enable efficient access to complex molecules. In this study, we successfully realized a photoredox-catalyzed strain-release radical spirocyclization approach to attain functionalized spirocyclobutyl oxindoles. A diverse array of radicals, such as sulfonyl, phosphonyl, and trifluoromethyl, were added efficiently to the strained C-C σ-bond of bicyclobutanes (BCBs) to afford a library of spirocyclobutyl oxindoles. Furthermore, the obtained products could be transformed into valuable building blocks. The observed reactivity and selectivity have been rationalized based on density functional theory calculations.
由于其广泛的生物活性，螺环丁基氧化吲哚在药物发现和制药领域引起了广泛关注。小环化合物中的应变释放是一种能够有效合成复杂分子的强大策略。在本研究中，我们成功实现了一种光氧化还原催化的应变释放自由基螺环化方法，以获得功能化的螺环丁基氧化吲哚。一系列不同的自由基，如磺酰基、膦酰基和三氟甲基，能够有效地加成到双环丁烷（BCBs）的应变C-C σ键上，从而得到一个螺环丁基氧化吲哚库。此外，所得到的产物可以转化为有价值的结构单元。基于密度泛函理论计算，对观察到的反应活性和选择性进行了合理的解释。
