title: Dehydrogenative TEMPO-Mediated Formation of Unstable Nitrones: Easy Access to N-Carbamoyl Isoxazolines.
abstract: N-carbamoyl nitrones represent an important class of reagents for the synthesis of a variety of natural and biologically active compounds. These compounds are generally converted into valuable 4-isoxazolines upon cyclization reaction with dipolarophiles. However, these types of N-protected nitrones are highly unstable, which limits their synthesis, storage and practical use, enforcing alternative lengthy or elaborated synthetic routes. In this work, a 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO)-mediated formal "dehydrogenation" of N-protected benzyl-, allyl- and alkyl-substituted hydroxylamines followed by in situ trapping of the generated unstable nitrones into N-carbamoyl 4-isoxazolines is presented. A plausible mechanism is also proposed, in which the dipolarophile shows an important assistant role in the generation of the active nitrone intermediate. This simple protocol avoids the problematic isolation of N-carbamoyl protected nitrones, providing new synthetic possibilities in isoxazoline chemistry.
authors.affiliation: Institute for Organic Chemistry, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg (Germany).|Straubing Center of Science for Renewable Resources (WZS), Schulgasse 16, 94315 Straubing (Germany).
authors.forename: Andrea
authors.initials: A
authors.lastname: Gini
authors.affiliation: Institute of Organic Chemistry, University of Münster, Corrensstrasse 40, 248149 Münster (Germany).
authors.forename: Marwin
authors.initials: M
authors.lastname: Segler
authors.affiliation: Institute for Organic Chemistry, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg (Germany).|Straubing Center of Science for Renewable Resources (WZS), Schulgasse 16, 94315 Straubing (Germany).
authors.forename: Dominik
authors.initials: D
authors.lastname: Kellner
authors.affiliation: Institute for Organic Chemistry, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg (Germany). olga.garcia-mancheno@ur.de.|Straubing Center of Science for Renewable Resources (WZS), Schulgasse 16, 94315 Straubing (Germany). olga.garcia-mancheno@ur.de.
authors.forename: Olga García
authors.initials: OG
authors.lastname: Mancheño
keywords: TEMPO; cycloadditon; dehydrogenative; isoxazolines; unstable N-acyl nitrones