Configurational assignments of diastereomeric γ-lactones using vicinal H–H NMR coupling constants and molecular modelling

Abstract

The conformational features of four diastereomers of the γ-lactone 2-ethyl-4-methyl-5-oxotetrahydrofuran-3-carboxylic acid were investigated by calculations which included molecular mechanics (MM3), semiempirical (AM1) and ab initio molecular orbital theory (HF/6-31G), the latter including solvent emulation. Results were compared with those obtained by ¹H NMR spectroscopy of natural and synthetic analogues in which a long aliphatic chain replaces the ethyl side chain. A notable agreement was found between the experimental vicinal ring coupling constants and those computed by the ab initio calculation; MM3 also gave rise to a fair agreement, while AM1 shows large failures to encounter the potential energy surface of these and other five-membered rings.