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

作者：Lei Wang, Panpan Zhou, Dong Xie, Qian Yue, Hao-Zheng Sun, Shang‐Dong Yang, Gang‐Wei Wang · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.4c15003 · 被引用次数：23 · 研究领域：Synthesis and Catalytic Reactions、Catalytic C–H Functionalization Methods、Radical Photochemical Reactions

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.