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Updated: May 22, 2025

Accessing Valuable Ligand Supports for Transition Metals: A Modified, Intermediate Scale Preparation of 1,2,3,4,5-Pentamethylcyclopentadiene
Published on: March 20, 2017
Shaping of a Reactive Manganese Catalyst Enables Access to Polyfunctionalized Cyclohexanes via Enantioselective
Miquel Costas1, Andrea Palone1, Arnau Call2
1Institut de Química Computacional i Catàlisi (IQCC) and Departament de Química, Universitat de Girona, Campus Montilivi, Girona, Catalonia, E-17071, Spain.
Abstract:
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 translates 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.
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