Role of curvature in acridone for 1 O 2 oxidation of a natural product homoallylic alcohol: A novel iso-hydroperoxide intermediate.

A density functional theoretical (DFT) study is presented, implicating a 1 O 2 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 1 O 2 'ene' reaction. Instead, the dihydrobenzofuran arises by 1 O 2 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 CH 2 I + -I - and CHI 2 + -I - formed by UV photolysis of CH 2 I 2 and CHI 3 . The iso-hydroperoxide is also structurally reminiscent of carbonyl oxides (R 2 C=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 H 2 O dehydration reactions for new insight into the biosynthesis of dihydrobenzofuran natural products.