RT info:eu-repo/semantics/article
T1 NHC-catalysed [3+2]-asymmetric annulation between pyrazolin-4,5-diones and enals: Synthesis of novel spirocyclic pyrazolone γ-butyrolactones and computational study of mechanism and stereoselectivity
A1 Gil Ordóñez, Marta
A1 Maestro Fernández, Alicia
A1 Ortega, Pablo
A1 Jambrina, Pablo G.
A1 Andrés García, José María
K1 Pyrazolone
K1 Pirazolona
AB Chiral pyrazolones with a spirocyclic centre at the C4-position are widely found in a large family of medically relevant compounds. In recent years, organocatalysis, particularly that performed with quiral N-heterocyclic carbenes (NHCs), has allowed the enantioselective synthesis of these spirocyclic compounds despite its inherent difficulty. In this work, we describe the fully diastereo- and highly enantioselective synthesis of novel spirocyclic pyrazolone γ-butyrolactones via NHC-catalysed [3+2] annulation reaction of enals and 1H-pyrazol-4,5-diones. To understand the catalytic mechanism and origin of stereoselectivity, electronic structure calculations were carried out. After considering various pathways, we concluded that stereoselectivity-determining step is the formation of the lactone that proceeds after addition of the NHC derived homoenolate to the electrophilic carbonyl group of pyrazolin-4,5-dione. Our calculations predict that the free energy barrier is lower for the (RS) product, which is also the main product experimentally obtained.
PB Royal Society of Chemistry
SN 2052-4110
YR 2022
FD 2022
LK https://uvadoc.uva.es/handle/10324/50776
UL https://uvadoc.uva.es/handle/10324/50776
LA eng
NO Organic Chemistry Frontiers, 2022, vol. 9, n. 2, p. 420-427
NO Producción Científica
DS UVaDOC
RD 24-abr-2024