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. [ABSTRACT FROM AUTHOR]