2026-04-26T07:15:22Zhttps://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

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 Gil Ordóñez, Marta Maestro Fernández, Alicia Ortega, Pablo Jambrina, Pablo G. Andrés García, José María Pyrazolone Pirazolona Producción Científica 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. Junta de Castilla y León (projects FEDER-VA115P17 and VA149G18) Junta de Castilla y León (predoctoral fellowship EDU/556/2019) Junta de Castilla y León - Fondo Social Europeo (grant EDU/601/2020) Ministerio de Ciencia, Innovación y Universidades - Agencia Estatal de Investigación - Fundación Salamanca City of Culture and Knowledge (grant PID2020-113147GA-I00) 2021-12-09T12:32:53Z 2021-12-09T12:32:53Z 2022 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Organic Chemistry Frontiers, 2022, vol. 9, n. 2, p. 420-427 2052-4110 https://uvadoc.uva.es/handle/10324/50776 10.1039/D1QO01462E eng https://pubs.rsc.org/en/Content/ArticleLanding/2022/QO/D1QO01462E Attribution-NonCommercial-NoDerivatives 4.0 Internacional info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ © 2022 Royal Society of Chemistry application/pdf Royal Society of Chemistry https://uvadoc.uva.es/bitstream/10324/50776/4/NHC-Catalysed-%5b3%2b2%5d-Asymmetric-Annulation.pdf.jpg Hispana TEXT http://creativecommons.org/licenses/by-nc-nd/4.0/ UVaDOC. Repositorio Documental de la Universidad de Valladolid https://uvadoc.uva.es/handle/10324/50776