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Título
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
Autor
Año del Documento
2022
Editorial
Royal Society of Chemistry
Descripción
Producción Científica
Documento Fuente
Organic Chemistry Frontiers, 2022, vol. 9, n. 2, p. 420-427
Zusammenfassung
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.
Palabras Clave
Pyrazolone
Pirazolona
ISSN
2052-4110
Revisión por pares
SI
Patrocinador
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)
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)
Version del Editor
Propietario de los Derechos
© 2022 Royal Society of Chemistry
Idioma
eng
Tipo de versión
info:eu-repo/semantics/acceptedVersion
Derechos
openAccess
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