Walters Jennifer C, Tierno Anthony F, Dubin Aimee H, Wengryniuk Sarah E
Department of Chemistry, Temple University, 1901 N. 13 St. Philadelphia, PA 19122.
European J Org Chem. 2018 Mar 29;2018(12):1460-1464. doi: 10.1002/ejoc.201800118. Epub 2018 Jan 31.
Herein, we report a simplified approach to the synthesis of medium-ring ethers through the electrophilic activation of secondary alcohols with (poly)cationic λ-iodanes (-HVI). Excellent levels of selectivity are achieved for C-O bond migration over established α-elimination pathways, enabled by the unique reactivity of a novel 2-OMe-pyridine-ligated -HVI. The resulting HFIP-acetals are readily derivatized with a range of nucleophiles, providing a versatile functional handle for subsequent manipulations. The utility of this methodology for late-stage natural product derivatization was also demonstrated, providing a new tool for diversity-oriented synthesis and complexity-to-diversity (CTD) efforts. Preliminary mechanistic investigations reveal a strong effect of alcohol conformation on reactive pathway, thus providing a predictive power in the application of this approach to complex molecule synthesis.
在此，我们报道了一种通过用（聚）阳离子λ-碘烷（-HVI）对仲醇进行亲电活化来合成中环醚的简化方法。通过一种新型的2-甲氧基吡啶连接的-HVI的独特反应性，在C-O键迁移方面相对于已确立的α-消除途径实现了优异的选择性水平。所得的六氟异丙醇缩醛很容易用一系列亲核试剂进行衍生化，为后续操作提供了一种通用的官能团处理方法。还展示了这种方法在后期天然产物衍生化中的实用性，为多样性导向合成和复杂性到多样性（CTD）研究提供了一种新工具。初步的机理研究揭示了醇构象对反应途径有很强的影响，从而为将该方法应用于复杂分子合成提供了预测能力。
