Fundamental to the synthesis of enantioenriched chiral molecules is the ability to assign absolute configuration at each stereogenic center, and to determine the enantiomeric excess for each compound. While determination of enantiomeric excess and absolute configuration is often considered routine in many facets of asymmetric synthesis, the same determinations for enantioisotopomers remains a formidable challenge. Here, we report the first highly enantioselective metal‐catalyzed synthesis of enantioisotopomers that are chiral by virtue of deuterium substitution along with the first general spectroscopic technique for assignment of the absolute configuration and quantitative determination of the enantiomeric excess of isotopically chiral molecules. Chiral tag rotational spectroscopy uses noncovalent chiral derivatization, which eliminates the possibility of racemization during derivatization, to perform the chiral analysis without the need of reference samples of the enantioisotopomer.

The chiral analysis of terpenes in complex mixtures of essential oils, necessary for authentication, has been further developed using chiral tagging molecular rotational resonance (MRR) spectroscopy. One analyte that is of particular interest is linalool (3,7-dimethyl-1,6-octadien-3-ol), a common natural chiral terpene found in botanicals with its enantiomers having unique flavor, fragrance, and aromatherapy characteristics. In this MRR demonstration, resolution of the enantiomers is achieved through the addition of a chiral tag, which creates non-covalent diastereomeric complexes with distinct spectral signatures. The relative stereochemistry of the complexes is identified by the comparison of calculated spectroscopic parameters with experimentally determined parameters of the chiral complexes with high accuracy. The diastereomeric complex intensities are analyzed to determine the absolute configuration (AC) and enantiomeric excess (EE) in each sample. Here, we demonstrate the use of chiral tagging MRR spectroscopy to perform a quantitative routine enantiomer analysis of linalool in complex essential oil mixtures, without the need for reference samples or chromatographic separation.