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Heteroatom-Activated Cyclization: A Unified Route to Diverse Six-Membered N-Heterocycles from Homopropargylic Amines
Zhaoxia Zhong1, Aorou Song1, Xuejie Liu2
1School of Pharmacy and Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education), Yantai University, Yantai 264005, China.
Abstract:
We report a unified, metal-free strategy that employs terminal heteroatom (chalcogen or halogen)-substituted homopropargylic amines as key substrates. Their cyclization with heteroallenes (e.g., CO2, CS2, isocyanates) under mild conditions efficiently affords three classes of six-membered N-heterocycles. The protocol is scalable and the products feature a versatile exocyclic vinyl-heteroatom handle for diversification. Mechanistic studies, supported by DFT calculations, highlight the heteroatom's essential function in activating the alkyne for the pivotal 6-exo-dig cyclization.
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