Harnessing Noncovalent π-Type Interactions in Thiourea-Chloride Supramolecular Complexes: Toward the Asymmetric Dearomatization of Diazaheterocycles

Enantioselective dearomatization of diazaheterocycles through anion-binding catalysis has been developed. The process involves the nucleophilic addition of phosphorus nucleophiles to in situ generated N-benzoyliminium chlorides, using a tert-leucine-derived thiourea as an H-bond donor catalyst, ther...

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Detalles Bibliográficos
Autores: Velázquez Muñoz, Marta, Elías Rodríguez, María del Pilar, Tejero, Tomás, Fernández Fernández, Rosario Fátima, Merino, Pedro, Lassaletta, J. M., Monge Fernández, David
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/179998
Acceso en línea:https://hdl.handle.net/11441/179998
https://doi.org/10.1021/acscatal.5c04438
Access Level:acceso abierto
Palabra clave:Anion-binding catalysis
Mechanism
Noncovalent interactions
Supramolecular complex
Thiourea
diazaheterocycle
Dearomatization
Cyclic hydrazino phosphonates
Descripción
Sumario:Enantioselective dearomatization of diazaheterocycles through anion-binding catalysis has been developed. The process involves the nucleophilic addition of phosphorus nucleophiles to in situ generated N-benzoyliminium chlorides, using a tert-leucine-derived thiourea as an H-bond donor catalyst, thereby providing access to appealing cyclic hydrazino phosphonates and their derivatives. Mechanistic investigations suggest that the low solubility of these salts might favor the formation of a supramolecular thiourea−chloride−iminium 2:1:1 complex, which is proposed as the catalytically relevant species accounting for the observed nonlinear effect. Experimental and computational data support a 4H-activation model via this highly ordered ion pair, in which two thiourea molecules are arranged in an antiparallel orientation around the chloride, generating a C2-symmetric groove. Hence, stereodefined insertion of the N-benzoyliminium is ensured by key noncovalent π-type interactions, thereby maximizing the enantioinduction event.