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

Abstract

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. (C) 2001 John Wiley & Sons, Inc.