Reactivity of Strained Compounds: Is Ground State Destabilization the Major Cause for Rate Enhancement?

Reaction and activation energies were computationally determined
for the nucleophilic attacks of OH- on
1-cyanobicyclobutane, 2-cyanobicyclobutane, and propionitrile using ab
initio methods at the RHF/6-31+G* level.
In the first reaction the central bond of the bicyclobutane moiety
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 reaction energies are −38.3,
−34, and −0.1 kcal, and the activation energies 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 point to an early transition
state for the first reaction and a late transition
state for the side bond cleavage. Examination of the computed
geometrical parameters shows the opposite trends.
Detailed analysis of these results suggests that the
destabilization of the ground state cannot 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 entering nucleophile. Thus, the main chain of cause
and effect in rate enhancement is molecular
deformation → rehybridization → lower LUMO → better bonding
capabilities. In bicyclobutane the lowest σ*
orbital is associated with the central bond which therefore is cleaved
much faster than the side bond which in turn
is more reactive than the C−C bond of propionitrile.