Endocyclic Cleavage in Glycosides with 2,3-trans Cyclic Protecting Groups

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• 作者：Hiroko Satoh ; Shino Manabe ; Yukishige Ito ; Hans P. L眉thi ; Teodoro Laino ; J眉rg Hutter
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：April 13, 2011
• 年：2011
• 卷：133
• 期：14
• 页码：5610-5619
• 全文大小：1124K
• 年卷期：v.133,no.14(April 13, 2011)
• ISSN：1520-5126

文摘

An endocyclic pathway is proposed as a reaction mechanism for the anomerization from the 尾 (1,2-trans) to the 伪 (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 Br酶nsted 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 (BF₃路OEt₂) 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鈭扖2 bond rotation after the endo C鈭扥 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 ⁴C₁ conformation, extensively discussed in conjunction with the stereoelectronic effect theory, is shown to be a secondary factor.