Determination of the Stereochemistry of 3-Hydroxymethyl-2,3-dihydro-[1,4]dioxino[2,3-b]- pyridine by Vibrational Circular Dichroism and the Effect of DFT Integration Grids

Abstract

Vibrational circular dichroism (VCD) spectra are presented for 3-hydroxymethyl-2,3-dihydro-[1,4]dioxino-[2,3-b]pyridine. The assignment of the stereochemistry has been done by comparison between the experimental spectra and theoretically calculated spectra for both enantiomers. The DFT calculations were found capable to correctly assign absolute configurations. The influence of the basis set used in the DFT calculations on the extent of the agreement between the theoretical and experimental findings was investigated by use of different Pople-style basis sets and correlation consistent basis sets, showing that 6-31G* is an acceptable basis set, and that cc-pVTZ yields the best agreement. Similarly, the effect of DFT integration grids was examined. A quantitative measure for the similarity between experimental and theoretical spectra is used.

A vibrational circular dichroism implementation within a Slater-type-orbital based density functional framework and its application to hexa- and hepta-helicenes

“…We have thus demonstrated that our implementation is correct and therefore can be applied for theoretical predictions of VCD spectra, which, as already shown [32,33,37,[41][42][43][44][45], is an important pre-requisite for interpretations of complicated experimental spectra of larger molecules, the assignment of absolute configurations of chiral substances, and the detection of specific interactions in chiral super-molecular aggregates, which manifest themselves in molecular vibrations.…”

A Confidence Level Algorithm for the Determination of Absolute Configuration Using Vibrational Circular Dichroism or Raman Optical Activity

“…The similarity measure, used in this study for the quantification of the agreement between the calculated, ( ) f ν , and measured, ( ) g ν , IR or VCD spectra, is a fairly straightforward adaptation of a cosine based similarity measure as will be demonstrated in detail below and as was also used by Kuppens et al [13][14][15][16] , following up on work by De Gelder et al [17] for comparing powder diffraction spectra. Instead of such a generalized cosine in a multidimensional vector space, one can also use the arithmetic mean as normalizing term or, in fact, any other similarity measure, including the Tanimoto one as recently used by Shen et al [18] .…”

“…Kuppens et al [13][14][15][16] suggested the difference between the neighbourhood similarities of the measured VCD spectra versus each of the corresponding calculated spectra of both enantiomers as a criterion to assess the degree of success of a VCD assignment of the AC.…”

“…Such an approach is rather tedious because individual bands need to be crosslinked between theory and experiment and because choosing a reduced number of bands in establishing the absolute configuration may introduce some arbitrariness. In search of a more direct and immediate quantification of the agreement, a neighbourhood similarity (NS) measure has previously been introduced for VCD [13][14][15][16] . This similarity measure, based on the overlap between measured and calculated spectra, takes into account the neighbourhood in the direct proximity of the bands.…”

“…This similarity measure, based on the overlap between measured and calculated spectra, takes into account the neighbourhood in the direct proximity of the bands. Despite earlier fruitful applications of such NS measures [13][14][15][16] , no test of such measures has been performed over a wider set of molecules for which the AC is known from other approaches such as explicitly correlating VCD bands between theory and experiment or other experimental techniques such as X-ray diffraction. Moreover, no confidence level has yet been established for VCD assignments.…”