Chiral isothiocyanates – An approach to determination of the absolute configuration using circular dichroism measurement

Chiral alkyl 2-isothiocyanates have been obtained from enantiopure, aliphatic amines. ECD measurements allowed us to correlate an absolute configuration at C-2 with a sign of the Cotton effect (CE) observed for n–π* transition at the longer-wavelength range of the spectrum. Chirooptical data calculated for all enantiomers were consistent with the measured CE values and indicated that the weak absorption band at 240 nm could give an important information concerning the stereochemistry of simple, chiral isothiocyanates. Optically active esters of 2-isothiocyanatocarboxylic acids, prepared from α-amino acids, showed two absorption bands located over 195 nm. The more intensive band near 200 nm and the weak absorption located at 250 nm were related to n–π* transitions in NCS group. TD DFT calculations carried out for methyl esters of 2-isothiocyanatocarboxylic acids showed the correlation between signs of CE determined for both absorption bands, and the absolute configuration on C-2.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Several chiral 2-isothiocyanates were synthesized and their ECD spectra were measured. ► TD DFT calculations (B3LYP/6-311+G(2d,p), PCM) reproduced all observed Cotton effects. ► Cotton effect in the range of 210–230 nm depends on the configuration of C-2. ► Correlation between CE at 210–230 nm and configuration of C-2 was observed also in presence of other stereogenic centers.