Characterization and Fate of a Septanosyl Ferrier Cation in the Gas and Solution Phases.

Ferrier reactions follow a mechanistic pathway whereby Lewis acid activation of a cyclic enol ether facilitates departure of an allylic leaving group to form a glycosyl Ferrier cation. Attack on the Ferrier cation provides a new acetal linkage concurrent with the transposition of the alkene moiety. The idiosyncratic outcomes of Ferrier reactions of seven-membered ring carbohydrate-based oxepines prompted an investigation of its corresponding septanosyl Ferrier cation. Experiments that characterized the ion, including gas-phase cryogenic IR spectroscopy matched with density functional theory-calculated spectra of candidate cation structures, as well as product analysis from solution-phase Ferrier reactions, are reported here. Results from both approaches revealed an inclination of the seven-membered ring cation to contract to five-membered ring structures. Gas-phase IR spectra matched best to calculated spectra of structures in which five-membered dioxolenium formation opened the oxepine ring. In the solution phase, an attack on the ion by water led to an acyclic enal that cyclized to a C-methylene-aldehydo arabinofuranoside species. Attack by allyl trimethylsilane, on the other hand, was diastereoselective and yielded a C-allyl septanoside.

Characterization of the low energy conformations and differential reactivities of D-glucose and D-mannose based oxepines.

Carbohydrate-based oxepines are valuable intermediates for the synthesis of septanose carbohydrates. Here we report the characterization of the preferred conformations of D-glucose and D-mannose based oxepines 1 and 2 using computational chemistry and NMR spectroscopy. Monte Carlo conformational searches on 1 and 2 were performed, followed by DFT optimization and single-point energy calculations on the low energy conformations of each oxepine. Coupling constants were computed for all unique conformations at a B3LYP/6-31G(d,p)u+1s level of theory and weighted based on a Boltzmann distribution. These values were then compared to the experimental values collected using 3JH,H values collected from 1H NMR spectra. Information from the MC/DFT approach was then used in a least squares method that correlated DFT calculated and observed 3JH,H coupling constants. The conformations of 1 and 2 are largely governed by a combination of the rigidifying enol ether element in combination with the reduction of unfavorable interactions. The vinylogous anomeric effect (VAE) emerged as a consequence, rather than a driver of conformations. Oxepine 1 showed greater reactivity in Ferrier rearrangement reactions relative to oxepine 2, in line with its greater %VAE.