Assignment of absolute configuration of sulfinyl dilactones: Optical rotations and 1H NMR experiment and DFT calculations

In previous work, two sulfinyl dilactone compounds were synthesized as key intermediates in the development of new proteasome inhibitors. Two stereogenic centers were introduced during synthesis, including one chiral sulfoxide in a five-membered ring. The absolute configurations (AC) of these two compounds were hard to determine just based on experimental techniques. Therefore, theoretical calculations of chiro-optical and spectroscopic features were used to determine stereochemistry. Ab initio calculations at DFT/B3LYP/6-31G (d, p) level of theory obtained satisfactory agreement with the experimental results. Furthermore, there was good agreement between the calculations of optical rotations and hydrogen chemical shifts in 1H NMR spectra for the final AC assignment as (1′S, 2R, 5R)- and (1′S, 2S, 5S)-5-[1′-(t-Boc-amino)-3′-methylbutyl]-1,3,2-dioxathiolane-2-oxide. This is a successful application of ab initio calculations for the AC assignment for small flexible molecules.