Direct Aziridine Synthesis from Amines and Styrene Derivatives via a Base-Promoted Oxidative Cascade Reaction

We report a base-promoted protocol for direct aziridine synthesis from primary amines and styrene derivatives. The reaction proceeds via base-promoted styrene hydroamination to generate a β-arylamine intermediate that undergoes deprotonative benzylic halogenation followed by cyclization to an aziridine. A Curtin-Hammett oxidative scenario underpins this cascade process, where 2-halothiophenes selectively transfer a halogen to transient benzylic carbanionic species generated in the presence of amine anions. This unique oxidative strategy provides new and complementary synthetic capabilities over established aziridination methods that rely on alkene or amine oxidation. Most importantly, abundantly available primary anilines and alkylamines are used to directly access aziridines with diverse N-substituents in a modular fashion. The anionic and mild nature of this oxidative approach is further distinguished by its suitability for difficult-to-oxidize vinyl(hetero)arene substrates and the tolerance of groups that are classically prone to oxidation (e.g., weak C-H bonds and nucleophilic π-systems). Quantum chemical modeling is used to rationalize the selective X-transfer of 2-halothiophenes over more traditional electrophilic halogen sources, which further inspired the development of a protocol to transform β-phenethylamines into N-H aziridine derivatives. This work thus illustrates the utility and broad potential of incorporating base-promoted X-transfer within cascade processes to build complex products from simple precursors.