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Skeletal Editing via Diastereoselective Ring Expansion Enables Enantioenriched Tetrasubstituted Δ 3 -Oxepenes

Year: 2026

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Seven-membered oxygen heterocycles, particularly Δ 3 -oxepenes, are prevalent motives, found, for example, in natural products, but remain synthetically challenging due to ring strain and limited asymmetric methods. Here, we describe a new strategy that uses Brønsted acid-promoted skeletal editing to convert enantioenriched dihydro-1,2-oxazines─readily prepared via an enantioselective catalytic nitroso-Diels–Alder reaction─into highly substituted Δ 3 -oxepenes bearing four diastereo-controlled stereocenters. As supported by DFT studies, which also provide insight into the origin of the diastereoselectivity, the transformation proceeds via a transient aziridine intermediate and a regioselective nucleophilic ring-opening, enabling the incorporation of diverse nucleophiles, including thiols, alcohols, and indoles. Operating under mild conditions, this methodology delivers tetrasubstituted Δ 3 -oxepenes in decent yields and excellent enantiomeric excesses.

Source: JACS Au

DOI: 10.1021/jacsau.5c01635

Authors: Emma Naulin, Vincent Gandon, Luc Neuville, Géraldine Masson

Institutions: Centre National de la Recherche Scientifique, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, Institut de Chimie Moléculaire et des Matériaux d'Orsay

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $3,500

Funder: Centre National de la Recherche Scientifique