We herein report our study about the ring opening of 1,3-diaza-4-oxa-[3.3.1]-nonene derivatives with organometallic reagents leveraging on their inherent ring strain and presence of reactive functionalities. The ring-opening occurs with Grignard reagents at the carbon bearing the two nitrogen atoms affording unconventional functionalized trans-2,3-disubstituted 1,2,3,6-tetrahydropyridines that are important structural frameworks due to their synthetic versatility and presence in bioactive molecules. The possibility to prepare enantioenriched tetrahydropyridines was also formally explored with success. A computational DFT study points to the formation of a transient iminium ion intermediate in which the coordination of magnesium to the oxygen of the carbonyl and the N-O endocyclic oxygen promotes the ring-opening process at the gem-diamine carbon atom.

Synthesis of Highly Functionalized Tetrahydropyridines by Ring Opening of [3.3.1]‐Heterobicyclic Compounds with Grignard Reagents

Lucrezia Margherita Comparini
Investigation
;
Lucilla Favero
Conceptualization
;
Valeria Di Bussolo
Membro del Collaboration Group
;
Sebastiano Di Pietro
Membro del Collaboration Group
;
Mauro Pineschi
Ultimo
Writing – Original Draft Preparation
2025-01-01

Abstract

We herein report our study about the ring opening of 1,3-diaza-4-oxa-[3.3.1]-nonene derivatives with organometallic reagents leveraging on their inherent ring strain and presence of reactive functionalities. The ring-opening occurs with Grignard reagents at the carbon bearing the two nitrogen atoms affording unconventional functionalized trans-2,3-disubstituted 1,2,3,6-tetrahydropyridines that are important structural frameworks due to their synthetic versatility and presence in bioactive molecules. The possibility to prepare enantioenriched tetrahydropyridines was also formally explored with success. A computational DFT study points to the formation of a transient iminium ion intermediate in which the coordination of magnesium to the oxygen of the carbonyl and the N-O endocyclic oxygen promotes the ring-opening process at the gem-diamine carbon atom.
2025
Comparini, LUCREZIA MARGHERITA; Turchi, Giovanni; Sardelli, Francesca; Favero, Lucilla; DI BUSSOLO, Valeria; DI PIETRO, Sebastiano; Pineschi, Mauro...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1303292
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