Shaping of a Reactive Manganese Catalyst Enables Access to Polyfunctionalized Cyclohexanes via Enantioselective C( <i> sp ³ </i> )─H Bond Oxidation of 1,3‐ <i>meso</i> Diethers

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 &gt;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.