Comparative conformational studies of 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxyhex-1-enitols at the DFT level

• Published in: Carbohydrate research 2018-06, Vol.462, p.13-27
• Main Authors: Nowacki, Andrzej, Liberek, Beata
• Format: Article
• Language: English
• Subjects: Allylic effect; B3LYP; Conformation; Galactose - analogs & derivatives; Galactose - chemistry; Glycal; M06–2X; Molecular Conformation; Quantum Theory; Quasi 1,3-diaxial interactions; Vinylogous anomeric effect
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/j.carres.2018.03.013

B3LYP and M06–2X optimization and MP2 single point calculations are reported for the 4H5 and 5H4 conformations of 3,4,6-tri-O-acetyl-D-allal, 3,4,6-tri-O-acetyl-D-galactal, 3,4,6-tri-O-acetyl-D-glucal, and 3,4,6-tri-O-acetyl-D-gulal. Significant discrepancies in predictions of relative energies and conformers' population for B3LYP and M06–2X optimized geometries are observed. Generally, B3LYP overestimates the conformers' energies with respect to MP2, whereas M06–2X slightly underestimates the conformers' energies. B3LYP failed to estimate the 4H5⇄5H4 conformational equilibrium for 3,4,6-tri-O-acetyl-D-galactal and 3,4,6-tri-O-acetyl-D-glucal. The M06–2X functional showed good agreement with experimental results for all glycals studied. The 4H5⇄5H4 conformational equilibrium for 3,4,6-tri-O-acetyl-D-allal and 3,4,6-tri-O-acetyl-D-gulal is governed by the vinylogous anomeric effect (VAE), whereas competition between the VAE and quasi 1,3-diaxial interactions influence this equilibrium for 3,4,6-tri-O-acetyl-D-galactal and 3,4,6-tri-O-acetyl-D-glucal. The orientation of the 4-OAc group influences the strength of the quasi 1,3-diaxial interactions between the 3-OAc and 5-CH2OAc groups. AIM analysis shows weak bonding interaction between the 3-OAc and 5-CH2OAc groups. [Display omitted] •DFT and MP2 calculations are reported for the 4H5 and 5H4 conformations four glycals.•B3LYP overestimates and M06–2X underestimates the rotamers' energies compared to MP2.•B3LYP failed to estimate the conformational equilibrium for D-galactal and D-glucal.•M06–2X showed good agreement with experimental results for all glycals studied.•AIM analysis shows weak bonding interaction between the 3-OAc and 5-CH2OAc groups.