Through Space π‐Electrons Communication in [2,2]‐Paracyclophanes: Unprecendented Stabilization of Radicals

Efforts to understand radical stability have led to considerable progress in radical chemistry. In this article, we investigated a novel approach to enhancing the radical stability of carbon-centered radicals through space electron delocalization within [2,2]-paracyclophanes. Alkoxyamines possessing a paracyclophane scaffold exploit face-to-face π-π-interactions between the aromatic rings to effectively lower bond dissociation energy (BDE) for NO-C bond homolysis. Electron spin resonance (ESR) experiments and computational modeling have confirmed a better stability compared to the analogues without the paracyclophane core. Theoretical analyses further elucidate the role of through-space electron communication in enhancing radical stability. This study highlights promising applications in fields such as organic synthesis, material science, and drug design. By achieving a low BDE for homolysis, the alkoxyamines efficiently release radicals, enabling successful application in nitroxide-mediated polymerization (NMP) of styrene, which provides high control over polymer architecture. Additionally, preliminary anti-proliferative assays reveal that the alkoxyamines exhibit promising anti-cancer activities against lung, breast, and prostate cells, which is correlated to their ability to release radicals upon homolysis.