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 i nvestigated at the Becke-Lee-Yang Parr (BLYP) density functional (DFT) leve l 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 c yclization is predicted to be exergonic for -OH2+ and -F) compared to the p arent system giving rise to substituted 1,4-dehydrobenzenes at physiologica l temperatures. (C) 2001 John Wiley & Sons, Inc.