Nucleophilic substitution reactions of 2-phenylthio-substituted carbohydrate acetals and related systems: Episulfonium ions vs. oxocarbenium ions as reactive intermediates

A powerful approach for controlling the stereochemistry of glycosylation reactions involves using a directing group at an adjacent carbon to influence the stereochemistry of nucleophilic attack. The use of substituents such as I, PhS, and PhSe has proven to be especially valuable because it enables the preparation of 2-deoxysugars after reductive removal of the directing group. The mechanisms of these reactions are generally considered to involve nucleophilic opening of bridged onium ions and to proceed with inversion. Onium ions, however, equilibrate with open cations, and these open forms can be favored when the cation is highly stabilized. Although the selectivities of reactions of carbohydrate-derived cations are consistent with the intermediacy of onium ions, the reactions of acyclic cations are not. Instead, consideration of the preferred conformations of the oxocarbenium ions and stereoelectronically favored additions to these intermediates provides a predictive model to explain the diastereoselectivities observed in reactions of oxocarbenium ions bearing proximal heteroatoms.