Role of curvature in acridone for ¹O₂ oxidation of a natural product homoallylic alcohol: A novel iso‐hydroperoxide intermediate

Abstract

A density functional theoretical (DFT) study is presented, implicating a 1O2 oxidation process to reach a dihydrobenzofuran from the reaction of the natural homoallylic alcohol, glycocitrine. Our results predict an interconversion between glycocitrine and an iso‐hydroperoxide intermediate [R(H)O+–O−] that provides a key path in the chemistry which then follows. Formations of allylic hydroperoxides are unlikely from a 1O2 ‘ene’ reaction. Instead, the dihydrobenzofuran arises by 1O2 oxidation facilitated by a 16° curvature of the glycocitrine ring imposed by a pyramidal N‐methyl group. This curvature facilitates the formation of the iso‐hydroperoxide, which is analogous to the iso species CH2I+–I− and CHI2+–I− formed by UV photolysis of CH2I2 and CHI3. The iso‐hydroperoxide is also structurally reminiscent of carbonyl oxides (R2C=O+–O−) formed in the reaction of carbenes and oxygen. Our DFT results point to intermolecular process, in which the iso‐hydroperoxide's fate relates to O‐transfer and H2O dehydration reactions for new insight into the biosynthesis of dihydrobenzofuran natural products.