Protonation at the nitrogen of 5-spirocyclopropane-isoxazolidines induces clean thermal rearrangement/fragmentation to β-lactams and ethylene. Under the same conditions, homologous 5-spirocyclobutane-isoxazolidines undergo unselective fragmentation to give cyclobutyl derivatives through a completely different mechanism. Experimental data and DFT calculations show that the process is initiated with less-favored protonation at the isoxazolidine oxygen rather than nitrogen. Highly energetic O-protonated isoxazolidines undergo N–O cleavage with concomitant endo- or exocyclic deprotonation to give iminium ions that, in the presence of trifluoroacetate, evolve into 2-(1-hydroxycyclobutyl)ethanones and N-[2-(1- hydroxycyclobutyl)ethyl]trifluoroacetamides, respectively. DFT data validate protonation at oxygen of 5-spirocyclobutane-isoxazolidines, which requires higher energy than protonation at nitrogen, but can trigger the proposed process without any energy barrier. The N-protonated derivatives could rearrange to give oxazaspirooctane, with enlargement of the spirocyclobutane ring, but this process, owing to its high energy barrier, cannot compete with the reaction channel promoted by oxygen protonation and, in fact, is not experimentally observed. Being independent of the presence of a strained spirofused ring, acid-catalyzed fragmentation was also demonstrated to occur in normal isoxazolidines, such as those derived from cycloaddition of C–Ph–N–Me-nitrone to norbornene, suggesting that isoxazolidines, widely used in organic synthesis, should not be heated in the presence of protic acids.
Mechanism of the Acid Mediated Thermal Fragmentation of 5-Spirocyclobutaneisoxazolidines / F. M. Cordero; C. Vurchio; A. Brandi ; R. Gandolfi. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - STAMPA. - 2011:(2011), pp. 5608-5616. [10.1002/ejoc.201100621]
Mechanism of the Acid Mediated Thermal Fragmentation of 5-Spirocyclobutaneisoxazolidines
CORDERO, FRANCA MARIA;VURCHIO, CAROLINA;BRANDI, ALBERTO;
2011
Abstract
Protonation at the nitrogen of 5-spirocyclopropane-isoxazolidines induces clean thermal rearrangement/fragmentation to β-lactams and ethylene. Under the same conditions, homologous 5-spirocyclobutane-isoxazolidines undergo unselective fragmentation to give cyclobutyl derivatives through a completely different mechanism. Experimental data and DFT calculations show that the process is initiated with less-favored protonation at the isoxazolidine oxygen rather than nitrogen. Highly energetic O-protonated isoxazolidines undergo N–O cleavage with concomitant endo- or exocyclic deprotonation to give iminium ions that, in the presence of trifluoroacetate, evolve into 2-(1-hydroxycyclobutyl)ethanones and N-[2-(1- hydroxycyclobutyl)ethyl]trifluoroacetamides, respectively. DFT data validate protonation at oxygen of 5-spirocyclobutane-isoxazolidines, which requires higher energy than protonation at nitrogen, but can trigger the proposed process without any energy barrier. The N-protonated derivatives could rearrange to give oxazaspirooctane, with enlargement of the spirocyclobutane ring, but this process, owing to its high energy barrier, cannot compete with the reaction channel promoted by oxygen protonation and, in fact, is not experimentally observed. Being independent of the presence of a strained spirofused ring, acid-catalyzed fragmentation was also demonstrated to occur in normal isoxazolidines, such as those derived from cycloaddition of C–Ph–N–Me-nitrone to norbornene, suggesting that isoxazolidines, widely used in organic synthesis, should not be heated in the presence of protic acids.File | Dimensione | Formato | |
---|---|---|---|
EJOC_2011_5608_SCB fragm.pdf
Accesso chiuso
Tipologia:
Versione finale referata (Postprint, Accepted manuscript)
Licenza:
Tutti i diritti riservati
Dimensione
887.31 kB
Formato
Adobe PDF
|
887.31 kB | Adobe PDF | Richiedi una copia |
I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.