[3 + 2] Cycloaddition of Iminyl Radicals and 2-Azaallyl Anions for the Synthesis of Multisubstituted 2-Imidazolines

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.