Mechanistic studies on the stereoselective formation of β-mannosides from mannosyl iodides using α-deuterium kinetic isotope effects

Mohamed H. El-Badri, Dan Willenbring, Dean J. Tantillo, Jacquelyn Gervay-Hague

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

(Chemical Equation Presented) Stereoselective synthesis of β-mannosides is one of the most challenging linkages to achieve in carbohydrate chemistry. Both the anomeric effect and the C2 axial substituent favor the formation of the axial glycoside (α-product). Herein, we describe mechanistic studies on the β-selective glycosidation of trimethylene oxide (TMO) using mannosyl iodides. Density functional calculations (at the B3LYP/6-31+G(d,p):LANL2DZ level) suggest that formation of both β- and β-mannosides involve loose SN2-like transition-state structures with significant oxacarbenium character, although the transition structure for formation of the α-mannoside is significantly looser. α-Deuterium kinetic isotope effects (α-DKIEs) based upon these computed transition state geometries match reasonably well with the experimentally measured values: 1.16 ± 0.02 for the β-linkage (computed to be 1.15) and 1.19 ± 0.05, see table 2 for the α-analogue (computed to be 1.26). Since it was unclear if β-selectivity resulted from a conformational constraint induced by the anomeric iodide, a 4,6-O-benzylidine acetal was used to lock the iodide into a chairlike conformation. Both experiments and calculations on this analogue suggest that it does not mirror the behavior of mannosyl iodides lacking bridging acetal protecting groups.

Original languageEnglish (US)
Pages (from-to)4663-4672
Number of pages10
JournalJournal of Organic Chemistry
Volume72
Issue number13
DOIs
StatePublished - Jun 22 2007

ASJC Scopus subject areas

  • Organic Chemistry

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