Branched-Selective Cross-Electrophile Coupling of 2-Alkyl Aziridines and (Hetero)aryl Iodides Using Ti/Ni Catalysis

The arylation of 2-alkyl aziridines by nucleophilic ring-opening or transition-metal-catalyzed cross-coupling enables facile access to biologically relevant β-phenethylamine derivatives. However, both approaches largely favor C–C bond formation at the less-substituted carbon of the aziridine, thus enabling access to only linear products. Consequently, despite the attractive bond disconnection that it poses, the synthesis of branched arylated products from 2-alkyl aziridines has remained inaccessible. Herein, we address this long-standing challenge and report the first branched-selective cross-coupling of 2-alkyl aziridines with aryl iodides. This unique selectivity is enabled by a Ti/Ni dual-catalytic system. We demonstrate the robustness of the method by a twofold approach: an additive screening campaign to probe functional group tolerance and a feature-driven substrate scope to study the effect of the local steric and electronic profile of each coupling partner on reactivity. Furthermore, the diversity of this feature-driven substrate scope enabled the generation of predictive reactivity models that guided mechanistic understanding. Mechanistic studies demonstrated that the branched selectivity arises from a Ti III -induced radical ring-opening of the aziridine.