Intrinsic Optical Activity and Large-Amplitude Displacement: Conformational Flexibility in (R)-Glycidyl Methyl Ether

Abstract

The dispersive optical activity of (R)-(-)-glycidyl methyl ether (R-GME) has been interrogated under ambient vapor-phase and solution-phase conditions, with quantum-chemical analyses built on density functional (B3LYP and CAM-B3LYP) and coupled-cluster (CCSD) implementations of linear-response theory exploited to interpret experimental findings. Inherent flexibility of the heavy atom skeleton leads to nine low-lying structural isomers that possess distinct chiroptical and physicochemical properties, as evinced by marked changes in the magnitude and the sign of rotatory powers observed in various media. These species are interconverted by independent motion along two large-amplitude torsional coordinates and are stabilized differentially by interaction with the surroundings, thereby reapportioning their relative contributions to the collective response evoked from a thermally equilibrated ensemble. The intrinsic behavior exhibited by isolated (vapor-phase) R-GME molecules was calculated through use of both conformer-averaging and restricted vibrational-averaging procedures, the former affording moderately good agreement with measurements of optical rotatory dispersion (ORD) and the latter providing strong evidence for sizable effects arising from vibrational degrees of freedom. A similar conformer-averaging ansatz based on the polarizable-continuum model (PCM) for implicit solvation was deployed to elucidate R-GME specific-rotation parameters acquired for six dilute solutions. This approach gave reasonable predictions for sodium D-line (589.3 nm) experiments performed in the extremes of solvent polarity represented by cyclohexane and acetonitrile but failed to reproduce the overall shape of ORD profiles and suggested more complex processes might be involved in the case of an aromatic medium.

Absolute Configurations of Naturally Occurring [5]- and [3]-Ladderanoic Acids: Isolation, Chiroptical Spectroscopy, and Crystallography

“…(b) The solvent influence in the experimental measurements was represented by the polarizable continuum model (PCM), , and explicit inclusion of solvent molecules in the calculations is not possible for molecules of the size considered here. (c) Vibrational contributions to calculated specific rotations are known to be important, − and these contributions can only be incorporated for small molecules. (d) Aggregation at the concentrations employed might occur via stacking of concatenated cyclobutanes, but this cannot be realistically modeled in our calculations.…”

Synthetic routes for a variety of halogenated (chiral) acetic acids from diethyl malonate

“…7,8 Due to the small number of atoms, they are also well suited to high-quality ab initio calculations [9][10][11][12] that are relevant for a detailed understanding of the spectroscopic investigations of chiral molecules.…”

Absolute Configuration of Bromofluoroiodomethane after Preparative Gas Chromatographic Separation

“…[2][3][4] This underlines the importance of chiral molecules in many areas related to chemistry and biology, [5] however, these molecules are more likely large compared to the small molecules which are of particular interest here. Small chiral halomethanes and oxiranes are ideal prototype molecules for the investigation of chiroptical properties (rotational angle, [6] (vibrational) circular dichroism, [7] photo-electron circular dichroism, [8,9] etc.). The synthesis of small, halogen containing chiral molecules (C 1 and C 2 ) is difficult and has not been performed with high versatility in the past, however, we devised a versatile and efficient synthetic route to achieve this for chiral halogenated acetic acids.…”