Electronic Control of Mechanistic Divergence in Iron-Catalyzed Olefin Carboamidation to β- and γ-Lactams

Abstract Regiodivergent synthetic strategies employing common precursors provide a powerful means of accessing structurally distinct molecular scaffolds. Herein, we report an electronically controlled, regiodivergent iron-catalyzed intramolecular olefin carboamidation of styrenyl dioxazolones that selectively affords either β- or γ-lactams using a range of carbon nucleophiles, including electron-rich arenes, allylsilanes, and propargylsilanes, thereby providing access to arylated, allylated, and allenylated products, respectively. Combined Hammett analysis, experimental mechanistic studies, and density functional theory (DFT) calculations support the involvement of a common azabicyclo[2.1.0]pentanone intermediate and reveal two electronically differentiated pathways: 1) strain-releasing SN2-type aziridine ring-opening promoted by electron-withdrawing substituents to deliver five-membered γ-lactams and 2) solvent-assisted aziridine ring-opening promoted by electron-donating substituents to generate a benzylic carbocation intermediate, followed by SN1-type trapping with a carbon nucleophile to furnish four-membered β-lactams.