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Regiodivergent Nucleophilic Fluorination under Hydrogen Bonding Catalysis: A Computational and Experimental Study

[Image: see text] The controlled programming of regiochemical outcomes in nucleophilic fluorination reactions with alkali metal fluoride is a problem yet to be solved. Herein, two synergistic approaches exploiting hydrogen bonding catalysis are presented. First, we demonstrate that modulating the ch...

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Detalles Bibliográficos
Autores principales: Horwitz, Matthew A., Dürr, Alexander B., Afratis, Konstantinos, Chen, Zijun, Soika, Julia, Christensen, Kirsten E., Fushimi, Makoto, Paton, Robert S., Gouverneur, Véronique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10161234/
https://www.ncbi.nlm.nih.gov/pubmed/37079853
http://dx.doi.org/10.1021/jacs.3c01303
Descripción
Sumario:[Image: see text] The controlled programming of regiochemical outcomes in nucleophilic fluorination reactions with alkali metal fluoride is a problem yet to be solved. Herein, two synergistic approaches exploiting hydrogen bonding catalysis are presented. First, we demonstrate that modulating the charge density of fluoride with a hydrogen-bond donor urea catalyst directly influences the kinetic regioselectivity in the fluorination of dissymmetric aziridinium salts with aryl and ester substituents. Moreover, we report a urea-catalyzed formal dyotropic rearrangement, a thermodynamically controlled regiochemical editing process consisting of C–F bond scission followed by fluoride rebound. These findings offer a route to access enantioenriched fluoroamine regioisomers from a single chloroamine precursor, and more generally, new opportunities in regiodivergent asymmetric (bis)urea-based organocatalysis.