The determination of absolute structure with both Mo and Cu radiation

The ability to quickly and easily change between molybdenum and copper radiation with imaging plate system like the RAPID II (with no loss of performance from phosphor optimisation, as is observed in comparable CCD machines) is particularly beneficial in determining the absolute configuration of a particular molecule.

As chiral starting materials are often very expensive either to make or to extract from natural products, the ability to produce a chiral product with a known absolute stereochemistry from an achiral starting material is highly prized financially by both academic and industrial chemists around the world. Though the level of enantiomeric excess achieved in a chemical reaction can be determined by other methods, the determination of single crystal structures is required to identify which hand has been formed.

Compound I		Compound II

Good quality single crystals of compounds I and II were successfully grown and their structures determined. In the case of compound I, which has the empirical formula C₁₁H₁₀FNO₃, the use of copper radiation combined with careful data collection was required to allow the determination of the absolute structure. Copper was required not only because of the presence of only light atoms, but also because of the extra flux available from a copper tube; the crystals were of reasonable quality, but quite small at 0.12 x 0.10 x 0.10 mm³. The data were collected overnight and gave a structure with a conventional R-factor of 2.6%. The absolute structure was determined by refinement of the Flack parameter to 0.05, with a standard uncertainty of 0.12; this is sufficient to be sure of the absolute configuration of the molecule.

In the case of compound II, which has the empirical formula C₁₁H₉Br₂NO₃, molybdenum radiation was used to determine the absolute configuration. This was desirable as the presence of two bromine atoms in each formula unit ensured sufficient anomalous dispersion with molybdenum radiation, and was considered better than copper radiation as the effects of absorption would be reduced using molybdenum. The crystal structure was collected in a few hours on a crystal measuring 0.15 x 0.10 x 0.10 mm³ and resulted in a refinement with a conventional R-factor of 2.06%. Again, the Flack parameter was refined to 0.013 with a standard uncertainty of 0.010, which clearly distinguishes the absolute configuration of the molecule.

The ability to collect data using copper radiation in addition to molybdenum radiation was required to be able to be sure of the results of this work, and the financial advantages of not requiring a dedicated diffractometer with copper radiation are clear. With an imaging plate diffractometer, there is no loss of detector sensitivity from the detector phosphor. In the case of molecule I, the anomalous dispersion was slight enough that such a loss in sensitivity might have prevented the refinement of the standard uncertainty on the Flack parameter to a value where it was possible to be confident in the assignment of the absolute structure.

Results courtesy of Andy Parkin, Lynne H Thomas and Chick C Wilson, Structural Chemistry Group,  University of Glasgow. This work has been submitted for publication in Angewandte Chemie.

Tags:  absolute structure determination, Flack parameter, copper radiation, molybdenum radiation, anomalous dispersion