Evaluating the Feasibility of DHPM-γ-Chalcogenolactones synthesis via DFT

Following the synthesis of DHPM-γ-thiolactones, this study investigated the feasibility of obtaining DHPM-γ-chalcogenolactones containing O, S, Se, and Te through DFT calculations at the M06-2X/def2-TZVP level of theory. For the oxygen and sulfur derivatives, transition structures consistent with the classical esterification mechanism were identified, with activation free energies of 3.5/7.4 and 3.0/15.6 kcal mol⁻¹ for the addition and elimination steps, respectively. In contrast, no tetrahedral intermediates were located for the selenium and tellurium analogues. Instead, a concerted addition-elimination pathway was found, with activation free energies of 31.6 and 36.8 kcal mol⁻¹, respectively. These substantially higher barriers indicate that the reaction mechanism is strongly dependent on the chalcogen atom and explain the greater synthetic difficulty associated with Se- and Te-containing DHPM-γ-lactones. These findings provide mechanistic insights that will guide future experimental studies toward the synthesis of these challenging heterocycles.