Control of Chemo‐Selectivity via Alcohol‐Affected Kinetics in Cu‐Hydroxylamine Catalyzed Aerobic Oxidation of Mesitol

Chemo-selectivity control is a critical challenge in aerobic C-H oxidations, particularly in preventing overoxidation. In this work, we present an alcohol-tunable strategy to control the oxidation degree of CuCl₂/NH₂OH·HCl-catalyzed mesitol oxidation in alcohols. In ^tBuOH, the reaction efficiently yields the aldehyde product with high selectivity, whereas in MeOH, the ether intermediate turned out to be the predominant product. Further kinetic analysis and mechanistic studies revealed that the reactivity is driven by the in-situ formation of protonated alkyl nitrate ([RON(O)OH]⁺), highlighting the critical role of ROH solvents. The differing responses of mesitol and the ether intermediate to the reaction conditions result in distinct kinetics across different alcohols, enabling precise control over the final products. These findings provide mechanistic insights into the origins of alcohol-dependent chemo-selectivity and pave the way for advancing protocols for selectivity control.