Role of curvature in acridone for 1 O 2 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.