COMPUTATIONAL MODELING OF STEREOSELECTIVITY IN THE DIELS-ALDER REACTIONS OF DIENOL ESTERS OF O-METHYLMANDELIC ACID AND THE QUESTION OF PI-STACKING

Ab initio calculations have been performed to determine the conformational energy profiles of methoxyacetic acid and vinyl formate. Methoxyacetic acid prefers approximately coplanar arrangements of its C̳O and Cα-O bonds, with the syn arrangement favored over the anti by 0.9 kcal/mol. Vinyl formate is most stable in the conformation having a syn-periplanar C-O-O̳O array and an anti-periplanar C̳C-O-C array. The results of these calculations were incorporated as torsional parameters in the MM2 force field in order to assess the possible role of π-stacking interactions in the stereoselective Diels-Alder reactions of chiral diene 1,3-butadienyl O-methylmandelate (1). These force-field calculations predict that, in the lowest energy conformation of 1, the dienyl carbons, the carbonyl group, and the Cα-0 bond are approximately coplanar, and the phenyl ring is approximately perpendicular to this plane, as proposed recently by Thornton and Siegel. Conformations having a π-stacking arrangement of the dienyl and phenyl groups of 1 are predicted to lie at least 6.8 kcal/mol higher in energy. The stereoselectivity observed in this reaction can be fully understood in terms of the calculated ground-state conformational preferences of 1, without invoking special π-π interactions between the phenyl and dienyl groups in the transition state. © 1990, American Chemical Society. All rights reserved.