National Institute of Informatics (NII), Tokyo 101-8430, Japan.
J Am Chem Soc. 2011 Apr 13;133(14):5610-9. doi: 10.1021/ja201024a. Epub 2011 Mar 21.
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 (4)C(1) conformation, extensively discussed in conjunction with the stereoelectronic effect theory, is shown to be a secondary factor.
提出了一个内型环途径作为反应机制，用于解释在带有 2,3-反式环保护基的糖苷中观察到的从β(1,2-反式)到α(1,2-顺式)构型的差向异构化。该反应发生在弱路易斯酸或布朗斯特酸存在下，而在典型的糖苷中，仅在内型环断裂（endo 断裂）由质子介质或强路易斯酸介导时才观察到。为了合理化这一类化合物的行为，使用量子力学（QM）计算和实验研究来研究 endocleavage 的反应机制和促进因素。我们研究了带有 2,3-反式环保护基的硫代糖苷的差向异构化反应，使用三氟化硼乙醚（BF(3)·OEt(2)）作为路易斯酸。基于从融合环引起的应变来预测过渡态（TS）能量的简单模型，估计的理论反应性非常接近通过内 C-O 键断裂后沿 C1-C2 键旋转进行的 TS 搜索计算的 TS 能量。预测的 TS 能量与实验反应性排序之间存在极好的一致性。该系列计算和实验强烈支持内型环而不是外型环机制的主导地位。此外，这些研究表明，内环应变是增强 endocleavage 反应的主要因素。与立体电子效应理论结合广泛讨论的环保护基限制吡喃糖苷环至（4）C(1)构象的影响，被证明是次要因素。
