Determination of enantiomeric excess

This is an important technique for the study of asymmetric chemistry. By having an accurate and reliable method for determining e.e.'s, a given reaction can be tested many times and optimised to give maximum stereocontrol.

The five main ways of determining e.e.'s are:[46]

• Polarimetry
• Isotope dilution
• Gas chromatographic methods
• Liquid chromatographic methods
• NMR resolution with
  • chiral derivatives
  • chiral solvating agents
  • chiral shift reagents

Gas chromatography (g.c.) using an optically active stationary phase has the following advantages:[47]

1. No substrate derivatisation and no work up procedures are required (isolation and purification can lead to accidental enantiomer enhancement or racemisation).
2. A very small sample size is required hence reactions can be done on a small scale.
3. It is suitable for the determination of a wide range of e.e.'s (e.e.ª0% to e.e.>95%).

The disadvantages of g.c. are that the solute must be volatile and thermally stable. GC provides no information on the absolute configuration of the products without previously having a standard.

Other methods (for example lanthanide shift reagents) require the product to be isolated before measurement. Polarimetry is widely used but can be very hard to reproduce e.g. concentration, solvent and temperature must all be rigorously controlled and the compound must have been isolated previously to obtain the absolute rotation values.