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Updated: Sep 11, 2025

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Enantioselective NHC-Catalyzed Annulation via Umpolung for the Construction of Hydroxylamine Architectures with
Izabela Barańska1, Monika Radosińska1, Liliana Dobrzańska1
1Nicolaus Copernicus University in Toruń, Faculty of Chemistry, 7 Gagarin Street, 87-100 Toruń, Poland.
Abstract:
An efficient and highly enantioselective organocatalytic annulation for the synthesis of chiral hydroxylamine-containing heterocycles is described. The N-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.
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