Dynamic Kinetic Activation of Aziridines Enables Radical-Polar Crossover (4 + 3) Cycloaddition with 1,3-Dienes

The cycloaddition of aziridines with unsaturated compounds is a valuable method for synthesizing nitrogen heterocycles. However, this process is predominantly substrate-controlled, posing significant challenges in regulating the regioselectivity of the C–N bond cleavage. In this study, we report a nickel-catalyzed dynamic kinetic activation strategy that enables catalyst-controlled activation of aziridines. Various types of aziridines, including 2-phenyl, 2-carbonyl, 2-alkyl, and disubstituted aziridines, consistently cleave their more sterically hindered C–N bonds to generate 1,3-radical anion intermediates. These intermediates participate in a highly regioselective 1,4-Heck/allylic substitution cascade with aromatic branched 1,3-dienes, resulting in a radical-polar crossover (4 + 3) cycloaddition that produces seven-membered azepine products. This approach not only complements traditional dipolar cycloaddition, in which aziridines typically act as zwitterionic 1,3-dipoles, but also introduces an unusual cycloaddition mode for 1,3-dienes. Experimental investigations and density functional theory (DFT) calculations provide insight into the reaction mechanism.