Department of Chemistry, Northeast Normal University, Changchun, 130024, China.
Department of Chemistry and Sustainable Chemistry, Ghent University, 281 Krijgslaan S-3, 9000, Ghent, Belgium.
Nat Commun. 2022 Mar 30;13(1):1674. doi: 10.1038/s41467-022-29323-3.
The insertion of carbenes into the α-C-H bonds of ethers represents one of the most powerful approaches to access polysubstituted α-branched ethers. However, intermolecular carbene insertions remain challenging, since current approaches are generally limited to the use of toxic and potentially explosive α-diazocarbonyl compounds. We now report a silver-catalyzed α-C-H benzylation of ethers using bench-stable N-triftosylhydrazones as safe and convenient carbene precursors. This approach is well suited for both inter- and intramolecular insertions to deliver medicinally relevant homobenzylic ethers and 5-8-membered oxacycles in good yields. The synthetic utility of this strategy is demonstrated by its easy scalability, broad scope with valuable functional groups, high regioselectivity, and late-stage functionalization of complex oxygen-containing molecules. The relative reactivities of different types of silver carbenes and C-H bonds were also investigated by experments and DFT calculations.
卡宾插入醚的α-C-H 键是构建多取代的α-支链醚的最有力方法之一。然而，分子间卡宾插入仍然具有挑战性，因为目前的方法通常限于使用有毒和潜在爆炸的α-重氮羰基化合物。我们现在报道了一种使用稳定的 N-三氟甲磺酰基腙作为安全方便的卡宾前体的银催化醚的α-C-H 苄基化反应。这种方法非常适合于分子间和分子内的插入，以提供具有医学相关性的同苄基醚和 5-8 元氧杂环，产率良好。该策略的合成实用性通过其易于规模化、具有有价值官能团的广泛范围、高区域选择性以及复杂含氧分子的后期官能化得到了证明。通过实验和 DFT 计算还研究了不同类型的银卡宾和 C-H 键的相对反应活性。
