Molecular structure determination using chiroptical spectroscopy: where we may go wrong?

Chiroptical spectroscopy is being widely used for determining the three-dimensional molecular structures (i.e., absolute configurations and conformations) of chiral molecules. The general procedure used with any of the chiroptical spectroscopic methods is to analyze the experimental data using corresponding quantum chemical predictions. Such analysis involves multiple steps, including consideration of conformations, solvent effects, electronic transitions, stereoisomers, and experimental artifacts, each of which possesses certain limitations. These limitations, when not recognized or properly taken into account, may lead to incorrect conclusions. This review emphasizes on selected examples that illustrate the potential limitations in utilizing the chiroptical spectroscopic methods. The examples used include hibiscus acid dimethylester, hibiscus acid disodium salt, 3,3'-diphenyl-[2,2'-binaphthalene]-1,1'-diol, tartaric acid esters, and 6,6'-dibromo-[1,1'-binaphthalene]-2,2'-diol.