A vibrational circular dichroism (VCD) methodology for the measurement of enantiomeric excess in chiral compounds in the solid phase and for the complementary use of NMR and VCD techniques in solution: The camphor case

For the first time, the success of a methodology for the determination of enantiomeric excess (% ee) in chiral solid samples by vibrational circular dichroism (VCD) spectroscopy is reported. We have used camphor to determine the % ee in a blind sample constituted by a mixture of its two enantiomers as a test for the validity of our approach. IR and VCD spectra of different enantiomeric mixtures of R/S-camphor in Nujol mulls were recorded and linear regressions of VCD intensities (ΔAbs.) vs. % ee for selected bands were found. Finally, the VCD intensities of a blind sample were interpolated in these linear regressions, obtaining its % ee with a rms of 2.4. These results in the solid phase were complemented with the determination of % ee in the liquid phase by VCD and NMR techniques, which are proved to be complementary techniques to carry out this kind of analysis. In the same way as in the VCD solid phase, linear regressions of ΔAbs. vs. % ee for selected bands were established, obtaining a rms of 1.1 in the % ee determination of a blind sample. H NMR experiments at 600 MHz using the chiral solvating agent, (S,S)-ABTE, allow the determination of the proportions of enantiomers in CDCl solution with great accuracy. C CPMAS NMR spectra prove that this technique cannot be used for conglomerates and/or solid solutions.This work was carried out with financial support from the Ministerio de Economía y Competitividad (Project No. CTQ2012-32436, CTQ2014-56833-R and CTQ2015-63997-C2-2- P), CICE/JA-FEDER-UJA:Plan de Fortalecimiento de las Capacidades de I+D+i/2014–15 (UJA2013/08/03) and Comunidad Autónoma de Madrid (Project FOTOCARBON, ref. S2013/MIT-2841). Authors thank the University of Jaén for continuing financial support, for bridge projects (UJA2015/08/07 and UJA2016/08/15), for Acción 2: Financiación de Incentivos a la Excelencia de I+D+i de la UJA 2014–15 in 2014 and 2015 calls and to its CICT for instrumental facilities. M. M. Q. M. thanks the University of Jaén for both pre- and post-doctoral fellowships. We also thank the Servei de Ressonància Magnètica Nuclear, Universitat Autònoma de Barcelona, for allocating instrument time to this projectPeer Reviewe