Theoretical studies on Electronic effects in organic molecules and reactive intermediates

Abstract

MNDO calculations on a number of model systems reveal the electronic origin of the remarkable acceleration in the Cope rearrangement of a tetracyclic molecule in acidic medium. The methodology was first established to be suitable for the quantitative evaluation of activation parameters for the Cope process by a critical study of the 1,5 hexadiene system. Incorporation of the hexadiene unit into a tetracyclic skeleton (6.3) leads to a large increase in activation energy for the Cope rearrangement. However, the presence of a carbenium ion centre can reduce the barrier in two possible ways. In one low symmetry pathway, the cation 6.4 can rearrange sequentially via classical carbocations to yield the final Cope product. The overall activation enthalpy is nearly 25 kcal·mol?¹ lower than in the corresponding neutral system. In an alternative pathway, the cation rearranges to a novel pyramidal intermediate. The resultant structure, 6.18, is a ? complex between a CH? fragment and a diolefin unit. This nonclassical carbocation is then computed to rearrange to the eventual Cope product. This pathway is also computed to be energetically favoured. A third mechanism, without participation of the carbenium ion centre, is also computed, which provides another measure of the magnitude of homoconjugative interactions in this system. Calculations on the carbonyl compound, 6.5, and its protonated analogue, 6.6, reveal that limited homoconjugation involving the carbonyl ?* orbital exists even in the neutral molecule. In contrast, the reduction in effective charge at the hydroxy substituted cation dilutes the energetic effect of cationic participation in 6.6. Hence, the computed activation barriers in these systems lie between those computed for the unsubstituted models, 6.3 and 6.4. Chloro substitution reduces the activation barrier for the Cope rearrangement dramatically, both in the neutral molecule (6.7) and in the cation (6.19). These computed substituent effects may be combined to obtain realistic estimates of the activation barriers in the experimentally studied tetracyclic system, 6.1, for the uncatalysed and the acid catalysed reactions. The activation parameters for the Cope rearrangement are also dependent on the rigidity of the endocyclic double bonds. The barrier is considerably reduced in the neutral divinyl norbornyl derivatives. Electronic participation by the C 7 cationic centre is feasible even in these systems, although the magnitude of the barrier reduction is smaller. Finally, the norbornyl skeleton is predicted to be critical for cationic participation in the Cope process. Calculations on cyclopentyl derivatives show that multistep as well as ? complex pathways exist, but are not quite favourable energetically. The present study provides a comprehensive understanding of the role of a cationic centre in the mechanism of Cope rearrangements across a number of systems. It has revived interest in the generation and spectral characterisation of pyramidal carbocations. Attempts to isolate ions such as 6.18 under stable ion conditions from precursors like 6.3 are expected to be rewarding. Higher level theoretical studies on related structures-including a second look at degenerate carbon scrambling in the cyclopentyl cation-would also be of interest.