Dearomative 1,4-Difunctionalization of Non-Activated Arenes Enabled by Boryl Radical-Mediated Halogen-Atom Transfer

Given the widespread presence of spirocyclic scaffolds in natural products and pharmacologically relevant synthetic compounds, the development of efficient methodologies for their construction holds great importance in medicinal chemistry and pharmaceutical research. In this study, a general photoch...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Congling Deng (20523059) (author)
مؤلفون آخرون: Hao Wu (65943) (author), Sheng Li (107261) (author), Li Chen (5749) (author), Xiaozu Liu (2078776) (author), Peijun Liu (563547) (author)
منشور في: 2025
الموضوعات:
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الوصف
الملخص:Given the widespread presence of spirocyclic scaffolds in natural products and pharmacologically relevant synthetic compounds, the development of efficient methodologies for their construction holds great importance in medicinal chemistry and pharmaceutical research. In this study, a general photochemical dearomative spirocyclization of nonactivated arenes has been established. The key to this method lies in the ability of amine-borane radicals to activate aryl bromides and iodides via halogen-atom transfer, thereby allowing for the conversion of aryl halides into the corresponding aryl radicals for subsequent chemodivergent transformations. The remarkable compatibility and versatility of this dearomative 1,4-difunctionalization is showed by the rapid assembly of structurally diverse 1,4-cyclohexadiene-based spirocycles incorporating oxindole, indoline, or dihydrobenzofuran subunits. Moreover, the potential utility of this protocol is exemplified by a formal total synthesis of the vasopressin V2 receptor antagonist Satavaptan.