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 beta-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 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 two-fold 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.