Endocyclic cleavage in glycosides with 2,3-trans cyclic protecting groups

Hiroko Satoh, Shino Manabe, Yukishige Ito, Hans P. Lüthi, Teodoro Laino, Jürg Hutter

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59 Citations (Scopus)


An endocyclic pathway is proposed as a reaction mechanism for the anomerization from the β (1,2-trans) to the α (1,2-cis) configuration observed in glycosides carrying 2,3-trans cyclic protecting groups. This reaction occurs in the presence of a weak Lewis or Brønsted acid, while endocyclic cleavage (endocleavage) in typical glycosides was observed only when mediated by protic media or strong Lewis acids. To rationalize the behavior of this class of compounds, the reaction mechanism and the promoting factors of the endocleavage are investigated using quantum-mechanical (QM) calculations and experimental studies. We examine anomerization reactions of thioglycosides carrying 2,3-trans cyclic protecting groups, employing boron trifluoride etherate (BF 3 OEt 2) as a Lewis acid. The estimated theoretical reactivity, based on a simple model to predict transition state (TS) energies from the strain caused by the fused rings, is very close to the TS energies calculated by the TS search along the C1-C2 bond rotation after the endo C-O bond breaking. Excellent agreement is found between the predicted TS energies and the experimental reactivity ranking. The series of calculations and experiments strongly supports the predominance of the endocyclic rather than the exocyclic mechanism. Furthermore, these investigations suggest that the inner strain is the primary factor enhancing the endocleavage reaction. The effect of the cyclic protecting group in restricting the pyranoside ring to a 4C 1 conformation, extensively discussed in conjunction with the stereoelectronic effect theory, is shown to be a secondary factor.(Figure Presented)

Original languageEnglish
Pages (from-to)5610-5619
Number of pages10
JournalJournal of the American Chemical Society
Issue number14
Publication statusPublished - 2011 Apr 13


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