Anionic Additions to Glycosyl Iodides: Highly Stereoselective Syntheses of β C-, N-, and O-Glycosides

Jacquelyn Gervay-Hague, Michael J. Hadd

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Classically, glycosyl halides are activated as glycosyl donors by metal chelation under KoenigsKnorr or Helferich conditions. These reactions often proceed through oxonium formation, and the stereochemical outcome is dictated by the anorneric effect and/or the nature of the protecting group on the C2 hydroxyl. Alternatively, glycosyl halides may undergo direct displacement of the halide by an incoming nucleophile in an SN2 mechanism. The latter reaction is far less common, and before this study it was primarily performed with glycosyl bromides. Having recently shown that both α and βglycosyl iodides could be efficiently generated, we embarked upon an investigation of nucleophilic additions to glycosyl iodides. The studies reported herein show that additions of stabilized anions to α-glycosyl iodides proceed with inversion of stereochemistry to give β-glycosides, even in the absence of a C2 participatory group. Glucosyl, galactosyl, and mannosyl iodides were studied, and the combined results indicate that the reactivity of 2,3,4,6-tetra-O-benzyl-α-D-galactosyl iodide > 2,3,4,6-tetra-O-benzyl-α-D-glucosyl iodide > 2,3,4,6-tetra-O-benzyl-α-D-mannosyl iodide. Both the glucosy] and galactosyl iodides are susceptible to E-2 elimination when treated with highly basic anions. In contrast, the mannosyl iodide undergoes substitution to give the 1,2 cis configuration. The overall sequence involves reaction of an anorneric acetate with trimethylsilyl iodide with in vacua removal of the resulting trimethylsilyl acetate. The iodide is then treated with a nucleophile without further characterization. A variety of nucleophiles were stereoselectively added to the glycosyl halides providing β-, C-, N-, and O-glycosides.

Original languageEnglish (US)
Pages (from-to)6961-6967
Number of pages7
JournalJournal of Organic Chemistry
Volume62
Issue number20
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry

Fingerprint Dive into the research topics of 'Anionic Additions to Glycosyl Iodides: Highly Stereoselective Syntheses of β C-, N-, and O-Glycosides'. Together they form a unique fingerprint.

  • Cite this