REACTIVITY OF STRAINED COMPOUNDS - IS GROUND-STATE DESTABILIZATION THE MAJOR CAUSE FOR RATE ENHANCEMENT

Reaction and activation energies were computationally determined for t he nucleophilic attacks of OH- on 1-cyanobicyclobutane, 2-cyanobicyclo butane, and propionitrile using ab initio methods at the RHF/6-31+G l evel. In the first reaction the central bond of the bicyclobutane moie ty is cleaved. In the second reaction a side bond is fissioned, and in the third reaction an unstrained reference C-C bond is cleaved. The r eaction energies are -38.3, -34, and -0.1 kcal, and the activation ene rgies are 4.4, 30.6, and 41.6 kcal, respectively. Based on these data, traditional analysis suggests that the percent of strain relieved at the transition states of the first two reactions which have nearly the same thermodynamic driving force is 97% and 32%, respectively. These values, according to the linear free energy relationship approach poin t to an early transition state for the first reaction and a late trans ition state for the side bond cleavage. Examination of the computed ge ometrical parameters shows the opposite trends. Detailed analysis of t hese results suggests that the destabilization of the ground state can not be considered as the major cause for the rate enhancement observed for strained substrates. Rather, an early transition state, which is usually accompanied by a low activation energy, results from a better capability of the frontier orbitals of the substrate to bond the enter ing nucleophile. Thus, the main chain of cause and effect in rate enha ncement is molecular deformation --> rehybridization --> lower LUMO -- > better bonding capabilities. In bicyclobutane the lowest sigma orbi tal is associated with the central bond which therefore is cleaved muc h faster than the side bond which in turn is more reactive than the C- C bond of propionitrile.