Carbohydrate-based oxepines are powerful intermediates for the synthesis of septanose carbohydrates. We report the characterization of the preferred conformation of oxepines synthesized from D-glucose- and D-mannose (1 and 2, respectively) using computational chemistry and NMR spectroscopy. The conformations of 1 and 2 are governed by trans-annular interactions and the vinylogous anomeric effect (VAE). A Monte Carlo conformational search for 1 and 2 was performed with an OPLSe force field. DFT optimization and single-point energy calculations were performed on all conformations at a B3LYP/6-31G(d,p) level of theory. Calculated 3JHH coupling constants were performed for all unique conformations at a B3LYP/6-31G(d,p)u+1s[H] level of theory and weighted based on a Boltzmann distribution. These values were compared to the experimental values collected using NMR experiments. Additionally, VT-NMR was implemented to probe the conformational dynamics. A range of solvents along the dielectric continuum were examined theoretically and spectroscopically. Ultimately, we found that 1 and 2 adopt a conformation that minimizes substituent interactions and maximizes the VAE. Oxepines with conformations heavily governed by the VAE display increased reactivity for rearrangement reactions.

Interactions driving the preferred conformations and reactivity of carbohydrate-based oxepines

ACS Spring Meeting 2021

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