A comprehensive computational examination of transannular Diels-Alder reactions of unsubstituted C14 trienes - Barriers, template effects, and the Curtin-Hammett principle

A combination of MM3-level molecular mechanics calculations and PM3-level s emiempirical molecular orbital calculations has been employed, in conjuncti on with an algorithm for the comprehensive conformational analysis of cycli c compounds, to obtain 1202 unique 1,3,9-cyclotetradecatriene conformations , distributed over the six possible geometrical isomers, and 70 unique tran sannular Diels-Alder transition structures leading to the six possible ster eoisomeric tricyclic olefins. A kinetic analysis that takes into account al l minima of a given geometrical isomer and all transition structures leadin g to the same tricyclic product leads to a free energy of activation that i s almost the same as the free energy difference between the lowest minimum and the lowest transition structure (the Curtin-Hammett principle). A subst antial template effect, mainly entropic in origin, is found when the transa nnular reactions are compared to the Diels-Alder reactions of the cognate 2 ,4-hexatrienes with the 2-butenes. Although the cyclization of the trans-ci s-trans triene favours the cis-anti-cis over the trans-anti-trans product b y more than 20 kcal mol(-1), the situation is reversed in the acyclic react ion. A cyclic triene that can cyclize directly to a trans-anti-trans tricyc le can therefore be proposed.