Water‐Derived Radical Species Initiate Six‐Electron Oxidation of Cyclic Ketones in Microdroplets

ABSTRACT Direct six‐electron oxidation of cyclohexanone and other cyclic ketones and associated C‐C bond cleavage can be achieved in microdroplets without the need for external oxidants, metal catalysts, or thermal activation. Mechanistic studies indicate that presence of trace amounts of water initiate the oxidative transformation by generating reactive radical species. Isotopic labeling experiments employing D 2 O and H 2 18 O provide evidence for involvement of water radical cation (H 2 O •+ ) as the active oxidant. Experiments using different nebulizing gases suggest that both water radical cation and molecular oxygen are required for the oxidation. Furthermore, the radical trapping agent 2,2,6,6‐tetramethylpiperidone (TEMPO) suppresses product formation, consistent with a radical‐mediated mechanism. The substrate scope of this reaction was verified using different cyclic ketones which yielded dicarboxylic acids/keto acids. In line with the mass spectrometric results, the reaction using cyclohexanone was scaled up using a single sprayer (∼ 12 mg product was collected in 3 h) for characterization by 1 H NMR spectroscopy, which verified the formation of adipic acid in microdroplets. Overall, this study (i) demonstrates the need for trace amounts of water during microdroplet reactions, (ii) showcases the exceptional oxidizing power of water microdroplets, and (iii) introduces a green, energy‐efficient pathway for dicarboxylic acid/keto acid synthesis.