Substituent effects in the Nicholas epimerization of glycosides

Abstract

The Nicholas reaction is a proven and versatile tool in glycoside chemistry. Its application is less clear-cut, if the intermediate Nicholas cation has two reactive sides that enable different reactions. Density functional theory (DFT) calculations are used to rationalize the observed difference in product yields for the Nicholas epimerization and substitution obtained from experiments with very similar glycosides. Substituents, which can increase the rigidity of the backbone, should be avoided in epimerization reactions as they can slow down reorientation of the intramolecular ion pair so that the substitution reaction dominates.

Reaction of Alkynyl- and Alkenyltrifluoroborates with Propargyldicobalt Cations: Alkynylation, Alkenylation, and Cyclopropanation Product Pathways

“…The energy diagram for these transformations is provided as Scheme . In all cases, the initial step involves substrate activation by BF 3 ( INT1 Me ), followed by the dissociation of the BF 3 ·OAc group . In all studied cases, the generation of this Nicholas cation is our rate-determining step.…”

“…All structures were calculated using the Gaussian 09 suite of programs at the B3LYP functional using the Gen basis set (the small 6-31G* basis set for all atoms and the much larger def2-TZVP set for Co) and employing the conductor-like polarizable continuum solvation model to account for solvent effects (default solvent parameters for dichloromethane were used). The success of the B3LYP/Gen­(6-31G*/def2-TZVP) method combined with a polarizable continuum model for CH 2 Cl 2 as a solvent for similar systems has been reported . All minima were confirmed by real vibrational frequencies, and transition states were confirmed with one imaginary frequency.…”