Regio‐, enantio‐, peri‐, and stereo‐selectivities of the reactions of five‐membered cyclodiene derivatives with itaconic anhydride toward the formation of norbornene lactones

Abstract

AbstractThe reactions of five‐membered cyclodiene derivatives with itaconic anhydride could proceed via four plausible pathways: two pathways involving initial Diels–Alder cycloaddition reactions followed by lactonization, and two pathways involving direct ring‐opening esterification reactions followed by intramolecular Diels–Alder cycloaddition, all to afford five‐ and six‐membered norbornene lactones, which are key intermediates in the synthesis of biologically interesting molecules as well as polymers such as polyelectrolytes. There are several regio‐, enantio‐, peri‐, and stereo‐chemical possibilities in these reactions, leading to several potential pathways, and these pathways are studied with density functional theory calculations in this work. The results reveal that the initial Diels–Alder reaction pathways have lower activation barriers than esterification reaction pathways. Generally, the activation barriers for the formation of S‐enantiomers are lower compared with the formation of R‐enantiomers. The reactions are stereo‐selective toward endo‐cycloadducts over exo‐cycloadducts, and this is as a result of steric interaction. The analysis of the electrophilic (Pk+) and nucleophilic (Pk−) Parr functions at the reactive centers shows that the cycloaddition will happen in such a way as to unite the atoms with the highest molecular orbital coefficients because this would lead to the greatest stabilization, and this is in good agreement with the energetic trends and the experimental outcome.