Can vibrational spectroscopy be used to identify stereoisomers? Medel, Stelbrink, and Suhm have examined the vibrational spectra of (+) and ()αpinene, (±)1, in the presence of four different chiral terpenes 25.^{1} They recorded gas phase spectra by thermal expansion of a chiral αpinene with each chiral terpene.
For the complex of 4 with (+)1 or ()1 and 5 with (+)1 or ()1, the OH vibrational frequency is identical for the two different stereoisomers. However, the OH vibrational frequencies differ by 2 cm^{1} with 3, and the complex of 3/(+)1 displays two different OH stretches that differ by 11 cm^{1}. And in the case of the complex of αpinene with 2, the OH vibrational frequencies of the two different stereoisomers differ by 11 cm^{1}!
The B3LYPD3(BJ)/def2TZVP optimized geometry of the 2/(+)1 and 2/()1 complexes are shown in Figure 2, and some subtle differences in sterics and dispersion give rise to the different vibrational frequencies.


Figure 2. B3LYPD3(BJ)/def2TZVP optimized geometry of the 2/(+)1 and 2/()1
Of interest to readers of this blog will be the DFT study of these complexes. The authors used three different wellknown methods – B3LYPD3(BJ)/def2TZVP, M062x/def2TZVP, and ωB97XD/def2TZVP – to compute structures and (most importantly) predict the vibrational frequencies. Interestingly, M062x/def2TZVP and ωB97XD/ def2TZVP both failed to predict the vibrational frequency difference between the complexes with the two stereoisomers of αpinene. However, B3LYPD3(BJ)/def2TZVP performed extremely well, with a mean average error (MAE) of only 1.9 cm^{1} for the four different terpenes. Using this functional and the larger mayccpvtz basis set reduced the MAE to 1.5 cm^{1} with the largest error of only 2.5 cm^{1}.
As the authors note, these complexes provide some fertile ground for further experimental and computational study and benchmarking.
Reference
1. Medel, R.; Stelbrink, C.; Suhm, M. A., “Vibrational Signatures of Chirality Recognition Between αPinene and Alcohols for Theory Benchmarking.” Angew. Chem. Int. Ed. 2019, 58, 81778181, DOI: 10.1002/anie.201901687.
InChIs
()1, ()αpinene: InChI=1S/C10H16/c1745869(7)10(8,2)3/h4,89H,56H2,13H3/t8,9/m0/s1
InChIKey=GRWFGVWFFZKLTIIUCAKERBSAN
(+)1, ()αpinene: InChI=1S/C10H16/c1745869(7)10(8,2)3/h4,89H,56H2,13H3/t8,9/m1/s1
InChIKey=GRWFGVWFFZKLTIRKDXNWHRSAN
2, ()borneol: InChI=1S/C10H18O/c19(2)74510(9,3)8(11)67/h78,11H,46H2,13H3/t7,8+,10+/m0/s1
InChiKey=DTGKSKDOIYIVQLQXFUBDJGSAN
3, (+)fenchol: InChI=1S/C10H18O/c19(2)74510(3,67)8(9)11/h78,11H,46H2,13H3/t7,8,10+/m0/s1
InChIKey=IAIHUHQCLTYTSFOYNCUSHFSAN
4, (1)isopinocampheol: InChI=1S/C10H18O/c16847(59(6)11)10(8,2)3/h69,11H,45H2,13H3/t6,7+,8,9/m1/s1
InChIKey=REPVLJRCJUVQFABZNPZCIMSAN
5, (1S)1phenylethanol: InChI=1S/C8H10O/c17(9)8532468/h27,9H,1H3/t7/m0/s1
InChIKey=WAPNOHKVXSQRPXZETCQYMHSAN