Finding reliable methodology for optical rotation and correct predictions of (s)-methyloxirane and 1R,5R)-β-pinene

Theoretical calculations of optical rotation (OR), although important to predict absolute configurations (ACs) and corroborate experiments, require efficient methodology able to reproduce enantiomer specificity and real OR values. Also, troublesome molecules are recurring in the literature, such as (S)methyloxirane and (1R,5R)-beta-pinene. This study evaluates DFT functionals B3LYP, CAM-B3LYP, omega B97X-D, M06-2X, and PBEO considering basis sets aug- cc-pVDZ, aug-cc-pVTZ, 6-311 ++G(2d,p), and 6-311 ++G(3df,2p) in OR predic- tion of 42 rigid organic molecules assessing cases with wrong enantiomeric determination comparing to available experimental data at wavelengths 355, 589, and 633 nm. Functionals CAM-B3LYP and omega B97X-D with augcc-pVTZ are indicated here to reproduce experimental values more accurately considering fewer number of wrong AC predictions, normalized RIV1SD values below 0.70, and a good approximation to experimental values in hierarchical cluster analysis. Methyloxirane AC was reproduced in CAM-B3LYP and PBEO, with [alpha](355) = 6.94 for CAM-B3LYP/aug-cc-pVTZ close to experimental value [alpha](355) 7.49 +/- 0.30. Good results were found for AC of beta-pinene in M06-2X, CAM-B3LYP, and wB97X-D while the latter in 6-311 G(3df,2p) obtained OR values of [alpha](589) = 3.44 and [alpha](689) 4.20 close to experimental values [alpha](589) = 2.8 and [alpha](689) 4.66 +/- 0.60. The two molecules aforementioned are, for the first time, reported to give valid theoretical OR values in such simple methodologies. OR calculations were all performed after geometry optimization at the same level of theory, and analysis of different functional combinations for each step in beta-pinene showed it can interfere with AC prediction even in rigid molecules.

Automated summary

This study evaluates the accuracy of different DFT functionals and basis sets in predicting optical rotation of 42 rigid organic molecules. The results show that the combination of CAM-B3LYP and omega B97X-D with augcc-pVTZ can accurately reproduce experimental values and perform well in AC prediction.