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  • Shaping of a Reactive Manganese Catalyst Enables Access to Polyfunctionalized Cyclohexanes via Enantioselective C( sp3)─H Bond Oxidation of 1,3‐ meso Diethers
Title: 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‐mesodiethers 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.  more » « less
Award ID(s):
2154502
PAR ID:
10639362
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley
Date Published:
Journal Name:
Angewandte Chemie International Edition
Volume:
64
Issue:
30
ISSN:
1433-7851
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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