Enantioselective NHC-Catalyzed Annulation via Umpolung for the Construction of Hydroxylamine Architectures with Variable Ring Sizes.

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.