2026-04-28T21:13:04Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/507762022-12-04T22:15:28Zcom_10324_1187com_10324_931com_10324_894com_10324_28542com_10324_952col_10324_1408col_10324_28543

00925njm 22002777a 4500 dc Gil Ordóñez, Marta author Maestro Fernández, Alicia author Ortega, Pablo author Jambrina, Pablo G. author Andrés García, José María author 2022 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. Organic Chemistry Frontiers, 2022, vol. 9, n. 2, p. 420-427 2052-4110 https://uvadoc.uva.es/handle/10324/50776 10.1039/D1QO01462E 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