title: O-2 Substituted pyranosyl oxacarbenium ions are C-2-O-2 2-fold rotors with a strong syn preference.
abstract: The substituent at O-2 of glycopyranosides is known to have a pronounced effect on both the formation and the cleavage of glycosides at C-1. This is primarily attributed to stereoelectronic effects on the formation and stability of the related glycopyranosyl oxacarbenium ions. Previous QM studies of 2-O-methyl substituted manno and gluco configured pyranosyl oxacarbenium ions found a preference for the methyl carbon to be syn to the CH-2 methine. This study examines the conformational preference of variously substituted O-2 tetrahydropyranosyl oxacarbenium ions and confirms this syn preference. Neutral analogues are shown to have the expected 3-fold rotation whereas the charged species exhibit 2-fold rotation about C-2-O-2. Natural bond order (NBO) calculations suggest that the dominant stabilizing interaction is a unimodal O-2 lone pair to C-1-O-5 pi-bond hyperconjugative interaction. This syn conformational preference has important implications for mimics of glycopyranosyl oxacarbenium ion transition states. It also suggests a conformational based mechanism that can be exploited to tune the reactivity of glycopyranosyl donors in the glycosylation reaction.
authors.affiliation: Steacie Institute for Molecular Sciences, NRC Canada, 100 Sussex Drive, Ottawa, ON, Canada K1A 0R6.
authors.forename: Andrei R
authors.initials: AR
authors.lastname: Ionescu
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Whitfield
authors.forename: Marek Z
authors.initials: MZ
authors.lastname: Zgierski
mesh_terms: D002236:Carbohydrate Conformation; D006027:Glycosides / Q000737:chemistry*; D006031:Glycosylation; D007477:Ions; D012399:Rotation; D013237:Stereoisomerism
chemical_list: D006027:Glycosides; D007477:Ions