AB-INITIO STUDY OF THE BERGMAN REACTION - THE AUTOAROMATIZATION OF HEX-3-ENE-1,5-DIYNE

The Bergman reaction of the hex-3-ene-1,5-diyne molecule (enediyne) to form the singlet biradical p-benzyne structure under ring closure has been studied by ab initio methods. The complete active space (CAS) SC F method was used for geometry optimizations at five points along the reaction path of the Bergman reaction. Subsequent calculations using t he multireference second-order perturbation theory based on a CASSCF r eference (CASPT2) established the energetics along the reaction path, especially for the reactant, transition state, and product. The energe tics were further corrected for zero point vibrational energy at the C ASSCF level of theory. The study incorporated four different basis set s: a double-zeta plus polarization (DZP), a triple-zeta plus double po larization (TZ2P), and two different average atomic natural orbital (A NO) basis sets. The study predicts the energy barrier to ring closure to be 25.0 +/- 3.1 kcal/mol and the enthalpy of reaction to be 4.9 +/- 3.2 kcal/mol. The latter value deviates significantly from the value estimated on the basis of group additivity and the Born-Haber cycle. T he enediyne moiety is the main functional group of a new class of anti cancer agents. The activation of the Bergman reaction in these drugs h as been argued to be due to a small structural change in the terminal- terminal carbon distance of about -0.5 Angstrom originating from an ep oxide conversion in the rest of the drug. The present study indicates that such a structural change is not sufficient for the Bergman autoar omatization to proceed at an appreciable rate. A new reaction path inv olving no biradical formation, resulting in the same products, is sugg ested.