The discovery of chemical methods enabling the construction of carbocycle-fused uracils which embody a three-dimensional and functional-group-rich architecture is a useful tool in medicinal chemistry oriented synthesis. In this work, an unprecedented amine-catalyzed [4+2] cross-cycloaddition is documented; it involves remotely enolizable 6-methyluracil-5-carbaldehydes and β-aryl enals, and chemoselectively produces two novel bicyclic and tricyclic fused uracil chemotypes in good yields with a maximum level of enantiocontrol. In-depth mechanistic investigations and control experiments support an intriguing homo-synergistic organocatalytic approach, where the same amine organocatalyst concomitantly engages both aldehyde partners in a stepwise eliminative [4+2] cycloaddition, whose vinylogous iminium ion intermediate product may diverge—depending upon conditions—to either bicyclic targets by hydrolysis or tricyclic products by a second homo-synergistic trienamine-mediated stepwise [4+2] cycloaddition.

Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross-Cycloadditions: DFT-Supported Homo-Synergistic Organocatalytic Approach / Curti, C.; Rassu, G.; Lombardo, M.; Zambrano, V.; Pinna, L.; Battistini, L.; Sartori, A.; Pelosi, G.; Zanardi, F.. - In: ANGEWANDTE CHEMIE. INTERNATIONAL EDITION. - ISSN 1433-7851. - 59:45(2020), pp. 20055-20064. [10.1002/anie.202007509]

Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross-Cycloadditions: DFT-Supported Homo-Synergistic Organocatalytic Approach

Pinna L.;
2020

Abstract

The discovery of chemical methods enabling the construction of carbocycle-fused uracils which embody a three-dimensional and functional-group-rich architecture is a useful tool in medicinal chemistry oriented synthesis. In this work, an unprecedented amine-catalyzed [4+2] cross-cycloaddition is documented; it involves remotely enolizable 6-methyluracil-5-carbaldehydes and β-aryl enals, and chemoselectively produces two novel bicyclic and tricyclic fused uracil chemotypes in good yields with a maximum level of enantiocontrol. In-depth mechanistic investigations and control experiments support an intriguing homo-synergistic organocatalytic approach, where the same amine organocatalyst concomitantly engages both aldehyde partners in a stepwise eliminative [4+2] cycloaddition, whose vinylogous iminium ion intermediate product may diverge—depending upon conditions—to either bicyclic targets by hydrolysis or tricyclic products by a second homo-synergistic trienamine-mediated stepwise [4+2] cycloaddition.
Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross-Cycloadditions: DFT-Supported Homo-Synergistic Organocatalytic Approach / Curti, C.; Rassu, G.; Lombardo, M.; Zambrano, V.; Pinna, L.; Battistini, L.; Sartori, A.; Pelosi, G.; Zanardi, F.. - In: ANGEWANDTE CHEMIE. INTERNATIONAL EDITION. - ISSN 1433-7851. - 59:45(2020), pp. 20055-20064. [10.1002/anie.202007509]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11388/238836
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 6
social impact