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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
[3 + 2] Cycloaddition of Iminyl Radicals and 2-Azaallyl Anions for the Synthesis of Multisubstituted 2-Imidazolines
Kaili Yu1, Canli Zhang1, Haitao Yang1,2
1Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, and School of Pharmacy, Yunnan University, Kunming 650500, P. R. China.
Abstract:
A unique transition-metal-free cascade cyclization method has been developed for the synthesis of multisubstituted 2-imidazoline derivatives. The reaction is initiated via single-electron transfer (SET) between 2-azaallyl anions and oximes, generating 2-azaallyl radicals and iminyl radicals that undergo radical-radical coupling to construct a C-N bond. Subsequent base-mediated deprotonation affords 2,4-diazapentadienyl anions that undergo 6π electrocyclization to give 2-imidazoline products. This method exhibits broad functional group tolerance and provides the products in moderate yields (36 examples, up to 81%). The proposed mechanism, which involves the coupling of iminyl radicals and 2-azaallyl radicals, is corroborated by radical trapping experiments. Several synthesized 2-imidazoline derivatives showed potent in vitro antitumor activity against A549, HCT116, and MDA-MB-231 human cancer cell lines.
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