Barańska Izabela, Radosińska Monika, Dobrzańska Liliana, Dzieszkowski Krzysztof, Rafiński Zbigniew
Nicolaus Copernicus University in Toruń, Faculty of Chemistry, 7 Gagarin Street, 87-100 Toruń, Poland.
Jagiellonian University, Faculty of Chemistry, Gronostajowa 2, 30-387 Kraków, Poland.
Org Lett. 2025 Aug 29;27(34):9364-9369. doi: 10.1021/acs.orglett.5c02576. Epub 2025 Aug 18.
An efficient and highly enantioselective organocatalytic annulation for the synthesis of chiral hydroxylamine-containing heterocycles is described. The -heterocyclic carbene (NHC)-catalyzed reaction successfully engages traditionally inert keto-oxime ethers as electrophiles in an intramolecular cyclization with in situ generated Breslow intermediates. This protocol overcomes the inherent challenges of this substrate class, such as low C═N bond electrophilicity and potential N-O bond cleavage, to deliver diverse five- and six-membered N-O frameworks in excellent yields (up to 99%) and enantioselectivities (up to >99% ee). This work provides a powerful, metal-free strategy to access valuable chiral building blocks and significantly expands the reactivity scope of keto-oximes in asymmetric catalysis.
本文描述了一种用于合成含手性羟胺杂环的高效且高度对映选择性的有机催化环化反应。该反应通过氮杂环卡宾（NHC）催化，成功地使传统上惰性的酮肟醚作为亲电试剂，与原位生成的布雷斯洛中间体进行分子内环化反应。该方法克服了这类底物固有的挑战，如C═N键亲电性低和潜在的N - O键断裂问题，以优异的产率（高达99%）和对映选择性（高达>99% ee）提供了多种五元及六元N - O骨架。这项工作提供了一种强大的无金属策略来获取有价值的手性构建块，并显著扩展了酮肟在不对称催化中的反应活性范围。
