Absolute Configuration of Chiral Natural Products
Within the past few years it has been conclusively demonstrated that vibrational circular dichroism (VCD) is a reliable method for AC determinations. VCD offers a novel alternative to X-ray crystallography, permitting AC determinations on neat liquid, oil, and solution samples. VCD requires no derivatization of the sample or growth of a pure single crystal. VCD is defined as the difference in infrared (IR) absorption for left versus right circular polarization for a chiral molecule during a vibrational transition. VCD combines the structural specificity of vibrational IR absorption spectroscopy with the stereochemical sensitivity of a chi-roptical spectroscopy such as CD. The absolute stereochemistry is established by comparing the solution-phase VCD spectrum to the results of an ab initio quantum chemistry calculation. The calculations are easily carried out in commercial packages such as Gaussian (Gaussian, Inc., Pittsburgh, Pennsylvania).