Determination of absolute configuration based on anomalous diffraction is a well established method. It is based on the difference between the values of Fhkl and F-h-k-l for non-centrosymmetric space groups in the presence of anomalous scattering. Anomalous scattering is caused by inelastic interactions between x-ray photons and the electrons of the atoms in a crystal and the strength of the anomalous signal is a function of wavelength (more signal at longer wavelengths) and atomic weight (more signal for heavier atoms). Traditionally, atoms such as sulfur or chlorine were needed to detect sufficient anomalous signal to determine absolute configurations with confidence, however thanks to new methods, such as the Hooft-Spek approach or the Parsons quotient method as well as improved detectors and x-ray sources, it is now possible to confidently determine the absolute configuration with oxygen as the heaviest atom.
This is particularly important for natural compounds which often do not contain atoms heavier than oxygen or for pharmaceutically relevant molecules. In the past, it was necessary to derivatize such light-atom molecules to introduce, for example, a sulfur, chlorine or bromine atom, but now, provide the quality of the crystals is good, the absolute configuration can be determined from oxygen alone.