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Updated: Apr 10, 2026

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Cascade Azide-Alkyne Cycloaddition/Azetidine Ring-Opening Reactions for Accessing Aminomethyl-Functionalized
Cong Fu1, Jingyi Jiang1, Qicai Ma1
1State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Abstract:
This study presents an efficient transition-metal-free method for the synthesis of aminomethyl-decorated 1,2,3-triazole-fused bicyclic heterocycles via a tandem azide-alkyne cycloaddition and azetidine ring-opening reaction. The tandem process proceeds with broad functional group compatibility and high atom economy. Mechanistic studies indicate that the transformation involves an initial [3 + 2] cycloaddition followed by intramolecular triazole-mediated azetidine ring opening. The resulting aminomethyl motif provides a versatile handle for further functionalization, enabling the synthesis of structurally complex, biologically relevant heterocycles including bioactive conjugates.
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