Shaping of a Reactive Manganese Catalyst Enables Access to Polyfunctionalized Cyclohexanes via Enantioselective C(sp3)−H Bond Oxidation of 1,3-meso Diethers

Chiral polyoxygenated cyclohexanes are valuable constituents of biologically relevant products. Herein, we report a protocol for the direct access to these scaffolds via site- and enantioselective non-directed oxidation of cyclohexyl-3,5-meso-diethers using aqueous H2O2. Structural shaping of a high...

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Detalhes bibliográficos
Autores: Costas Salgueiro, Miquel, Palone, Andrea, Call Quintana, Arnau, Garcia-Roca, Aleria, Luis Luis, Josep Maria, Sigman, Matthew S., Bietti, Massimo, Nevado, Cristina
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2025
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/26834
Acesso em linha:http://hdl.handle.net/10256/26834
Access Level:Acceso aberto
Palavra-chave:Catàlisi asimètrica
Enantioselective catalysis
Catalitzadors
Catalysts
Descrição
Resumo:Chiral polyoxygenated cyclohexanes are valuable constituents of biologically relevant products. Herein, we report a protocol for the direct access to these scaffolds via site- and enantioselective non-directed oxidation of cyclohexyl-3,5-meso-diethers using aqueous H2O2. Structural shaping of a highly reactive chiral Mn-oxo species, achieved through the combination of a sterically encumbered ligand and a bulky carboxylic acid, promotes a precise fit of the substrate within the catalyst pocket, which translate into exceptional enantioselectivity (up to >99% ee). Computational studies reveal that C–H oxidation proceeds via an initial hydrogen atom transfer, followed by electron transfer, leading to the formation of a chiral cationic intermediate. The resulting desymmetrized 3-methoxycyclohexanone products serve as valuable intermediates for the synthesis of bioactive cores, as they can undergo orthogonal chemical modifications to enable further structural diversification