kcal/mol). 18 Absolute stereochemistry of (aR)-6, (aS)-6, (aR)-iso-6 and (aS)-iso-6, were determined using vibrational circular dichroism (VCD) (Scheme 3). VCD is a technique which evaluates CD spectra in the IR range, and can be used in combination with density functional theory-based modelling to determine not only absolute stereochemistry, and to provide insight into conformations in solution. Molecular modelling of both (aR) and (aS)-6 yielded 20 unique conformations within 7 kcal/mol of one-another, each of which underwent further DFT optimization at several levels of theory to calculate VCD. 31 Although many of the methods gave computed VCD spectra that closely matched the experimental spectra, optimization at B3LYP/cc-pVTZ provided the best match, and in these studies 6 conformers were identified that contributed 1% or greater to the Boltzmann weighted average. While most of the conformational flexibility was coming from the methoxy groups, there was some small variation of the dihedral angle defining the chiral axis (93-100°), with 98.6° contributing to 60.5% of the spectra (Scheme 3A). A similar treatment was given to iso-6, with the B3PW91/cc-pVTZ combination this time yielding slightly better results than the other methods. Unexpectedly, the VCD spectra were considerably different than that of 6 on account of the greater , iso-6 had two ground state minima -one at 70° and one at 100° -consistent with these findings. These two conformations are roughly equidistant from the perpendicular conformation, and consequently, many of their VCD peaks are equal and opposite in signal strength, weakening the observed signal. One potential explanation for these observed differences may lie in the electronic preference the AC ring to adopt the isocolchicine-type pose to juxtapose dipoles of the aromatic rings (Scheme 3C). In the case of 6, this conformer would also provide steric relief as there would be greater distance between the methyl appendages. In the case of iso-6, these electronic and steric differences are conflicting, and could lead to the observed mixture of the two conformers.