Elucidating the Origin of Conformational Energy Differences in Substituted 1,3-Dioxanes: A Combined Theoretical and Experimental Study.
13C NMR spectroscopy, ab initio quantum mechanics, and molecular mechanics have been used to investigate the trans-4-(trifluoromethyl)-2,2,6-trimethyl-1,3-dioxane chair/twist-boat equilibrium. The molecular mechanics calculations were based upon the MM3 and AMBER force fields. A 6-31G basis set was used for the ab initio calculations, and MP2 correlation corrections were applied. Both the ab initio and AMBER molecular mechanics calculations are consistent with the (13)C NMR chemical shift differences for the trans-4-(trifluoromethyl)-2,2,6-trimethyl-1,3-dioxane conformers. The predicted chair to twist-boat equilibrium suggested by the MM3 calculations is not consistent with the experimental data. These results support the suggestion by Howard et al. (Howard, A. E.; Cieplak, P.; Kollman, P. A. J. Comput.Chem. 1995, 16, 243-261) on the critical role of electrostatic interactions in determining the chair/twist-boat equilibrium.
Cieplak
Piotr
P
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, California 94143, and Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455.
Howard
Allison E.
AE
Powers
Jay P.
JP
Rychnovsky
Scott D.
SD
Kollman
Peter A.
PA