Macrocyclic structures can be synthesized through two simultaneous olefin metathesis reactions: either directly through ring-closing metathesis (RCM) or indirectly through an intermediate formed by acyclic diene metathesis (ADMET). The proclivity of a homologous series of 16 R-but-3-enoate esters to form lactones through one of these two processes is studied at the HF/6-31G(d), B3LYP/6-31G(d), and MP2(full)/6-31G(d) levels of theory. Computed Gibbs free energies are used to determine Delta G(RCM), Delta G(ADMET), and Delta Delta G (Delta G(RCM) - Delta G(ADMET)). Delta Delta G is evaluated to compare the relative favourability of the RCM and ADMET reactions for the various R-but-3-enoate esters, where each system is differentiated by the number of methylene groups (n) added to the ester chain. When n = 0, 1, 10, or 13, cyclic lactone formation by direct RCM is predicted to be thermodynamically favoured, and the indirect synthesis is preferred for all other heterocyclic structures. The same trend holds between 298.15 and 333.15 K, therefore, the gas-phase model is a reasonable approximation of the experimental reaction conditions. The theoretical model is sufficient for smaller systems, but molecules larger than the n = 6 case do not follow experimental results for similar saturated structures. Hence, the assumptions pertaining to straight-chain and cis-ring conformations need to be re-evaluated. In particular, chain flexibility should be further examined.
