Determination of enantiomeric excess in samples of chiral molecules using fourier transform vibrational circular dichroism spectroscopy: simulation of real-time reaction monitoring.

The first use of Fourier transform vibrational circular dichroism (FT-VCD) to follow changes in the percent enantiomeric excess (% EE) of chiral molecules in time using a flow cell sampling apparatus is reported. FT-VCD, as opposed to dispersive scanning VCD, eliminates the need to scan the VCD spectrum in time to monitor the % EE at more than one spectral location. The first use of partial least-squares chemometric analysis to determine % EE values from kinetic sets of VCD spectral data is also reported. These two advances have been used to monitor simultaneously changes in the fractional composition and the % EE of a mixture of two different chiral molecules. This simulates the progress of the chemical reaction from a chiral reactant to a chiral product where the % EE of both molecules can change with time. For the molecules studied, alpha-pinene, camphor, and borneol, the accuracy of following % EE changes for one species alone is approximately 1%, while for simultaneously following % EE changes in two species is approximately 2% for 10-20-min sampling periods at 4 cm(-)(1) spectral resolution. This accuracy can be increased for the same collection times or maintained for shorter periods of collection by lowering the spectral resolution. These findings demonstrate the potential for VCD to be used for real-time monitoring of the composition and % EE of chemical reactions involving the synthesis chiral molecules.