Mechanistic and Curtin–Hammett Studies of the 1O2 Oxidation of a Prenyl Phenol and Phenolate Anion

The Curtin–Hammett principle, widely recognized in thermal reactions, has been extended to photosensitization processes in this study, providing new insights into the reactivity of photogenerated singlet oxygen (¹O₂) with phenol and phenolate anion species. Here, we explore mechanistic and Curtin–Hammett studies of the equilibrium between the phenol and phenolate anion forms of a prenylated natural product, prenylphloroglucinol. This study uses density functional theory (DFT) to examine phenol and phenolate anion-quenching pathways of ¹O₂ showing distinct pathways for each form. In the phenolate anion, ¹O₂ is quenched to form a peroxy anion. In contrast, in the phenol form, ¹O₂ leads to a potent epoxidizing agent in a seemingly pro-oxidant path. An iso-hydroperoxyhydrofuran intermediate is proposed to be key in the epoxidation. Meanwhile, the phenolate anion cyclizes and protonates forming a comparatively benign hydroperoxyhydrofuran species. The phloroglucinol is next to the C-prenyated group directs the reaction pathway towards the formation of a dihydrobenzofuran, deviating from the conventional ¹O₂ “ene” reaction mechanism and the production of allylic hydroperoxides typically observed in trisubstituted alkenes.