Substituent effects on the Bergman cyclization of (Z)‐1,5‐hexadiyne‐3‐enes: a systematic computational study

The effects of several substituents (BH2, BF2, AlH2, CH3, C6H5, CN, COCH3, CF3, SiH3, NH2, NH3+, NO2, PH2, OH, OH2+, SH, F, Cl, Br) on the Bergman cyclization of (Z)‐1,5‐hexadiyne‐3‐ene (enediyne, 3) were investigated at the Becke–Lee–Yang–Parr (BLYP) density functional (DFT) level employing a 6‐31G* basis set. Some of the substituents (NH3+, NO2, OH, OH2+, F, Cl, Br) are able to lower the barrier (up to a minimum of 16.9 kcal mol−1 for difluoro‐enediyne 7rr) and the reaction enthalpy (the cyclization is predicted to be exergonic for OH2+ and F) compared to the parent system giving rise to substituted 1,4‐dehydrobenzenes at physiological temperatures.