Determination of the absolute configurations of bicyclo[3.1.0]hexane derivatives via electronic circular dichroism, optical rotation dispersion and vibrational circular dichroism spectroscopy and density functional theory calculations.

The electronic circular dichroism (ECD), optical rotation dispersion (ORD), and vibrational circular dichroism (VCD) spectra of a pair of enantiomers, i.e. 3 and 4, of a bicyclo[3.1.0]hexane derivative have been measured in acetonitrile and acetonitrile-d(3), respectively. Extensive conformational searches at the B3LYP/6-311++G** level have been carried out for 3, which has four OH and one N(3) functional groups. For the bicyclo[3.1.0]hexane ring of 3, the boat-like conformers have been found to be much more stable than the chair-like conformers, while the number and the strength of the intramolecular hydrogen bonds have been identified as the dominant factors in the relative stability among the boat-like and among the chair-like conformers. DFT simulations of the ECD, ORD and VCD spectra have been performed for all low energy conformers at the B3LYP/6-311++G** and B3LYP/aug-cc-pVDZ level. Implicit continuum polarization model has been used to account for solvent effects in all these chiroptical measurements. Comparison of the DFT simulations with the experimental data shows that all three chiroptical properties yield the same absolute configuration assignment for . This work demonstrates that using multiple chiroptical spectroscopic methods in combination with DFT calculations allows one to determine absolute configurations with high confidence for chiral carbohydrates and their analogues, which possess a large number of rotatable bonds.