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Updated: Jan 13, 2026

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Solvent-Controlled Regioselective [3 + 2] Reactions from Benzofuran-Derived Azadienes and N,N'-Cyclic Azomethine
Shuhong Wang1,2, Haojia Zhou2, Wendi Xie2
1Pingyuan Laboratory, State Key Laboratory of Antiviral Drugs, School of Pharmaceutical Sciences, Henan Normal University, Xinxiang, Henan 453007, China.
Abstract:
We report a catalyst-free, regioselective [3 + 2] cycloaddition reaction between benzofuran-derived azadienes (BDAs) and N,N'-cyclic azomethine imines, where regioselectivity is controlled by modulating solvent polarity. Spiro[benzofuran-2,2'-pyrazolo[1,2-a]pyrazole] is obtained in high yields (up to 93%) using acetonitrile as the solvent, while the novel spiro[benzofuran-2,1'-pyrazolo[1,2-a]pyrazole] forms in moderate to good yields (42%-73%) with carbon tetrachloride. This solvent-controlled protocol exhibits excellent diastereoselectivity (dr >20:1) for both products, along with a broad substrate scope. Furthermore, scale-up experiments and derivatization studies have been successfully performed. This protocol provides an efficient strategy for regioselective control in the diversified synthesis of bicyclic pyrazolidines, offering a new approach for constructing bicyclic pyrazolidines with different configurations.
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