The oxidation of aldehydes is an important process in biological systems. Aldehyde dehydrogenases (ALDHs) are a superfamily of nineteen isozymes that oxidize aldehydes to carboxylic acids, most commonly employing NAD+ as a co-factor. By doing so, organisms can carry out important reactions such as the detoxification of aldehydes in alcohol metabolism and removing reactive aldehydes caused by lipid peroxidation during cellular homeostasis. Although aldehydes are prone to oxidation in the biological system, most aldehydes are generally inert to autoxidation and traditionally require strong oxidants for the catalytic oxidation of aldehydes into corresponding carboxylic acids. Recent studies for developing mild oxidants for catalyzing the oxidation of aldehydes have been reported, but such oxidants still have limitations such as harsh reaction conditions and sluggish reactivity. Therefore, a catalyst system that can oxidize aldehydes efficiently under ambient conditions is in demand.
To date, most oxidation reactions of aldehydes need a good nucleophile to activate the C=O bond by which electron-rich aldehydes often need more reaction time and catalyst. There is a lack of study on the electrophilic oxidation of aldehyde into a carboxylic acid. In the recent work done by Jaeheung Cho and his colleagues from the Ulsan National Institute of Science & Technology, they reported the oxidation of aldehydes by mononuclear manganese (III) iodosylbenzene. In their hypothesis, the C−H bond activation of aldehyde generates the transient (oxo)methylium.
The synthesis of the manganese (III) iodosylbenzene specie was carried out by the reaction of [Mn (TBDAP)(OTf)2] with three equivalences of PhIO in CH3CN/CF3CH2OH at 20 °C. The reactivity of the catalyst system (1) was investigated by using cyclohexane carboxaldehyde (CCA). By the analysis of gas chromatography, the reaction with CCA afforded cyclohexane carboxylic acid (66% yield) as a sole product. This is different from those obtained by the reaction of Metal-Peroxo species with aldehydes, where cyclohexanone or cyclohexene is observed to be a major product.
The synthesis of the manganese (III) iodosylbenzene specie was carried out by the reaction of [Mn (TBDAP)(OTf)2] with three equivalences of PhIO in CH3CN/CF3CH2OH at 20 °C. The reactivity of the catalyst system (1) was investigated by using cyclohexane carboxaldehyde (CCA). By the analysis of gas chromatography, the reaction with CCA afforded cyclohexane carboxylic acid (66% yield) as a sole product. This is different from those obtained by the reaction of Metal-Peroxo species with aldehydes, where cyclohexanone or cyclohexene is observed to be a major product.
Figure 1: A computational electronic energy profile (in kcal mol–1) for the oxidation of CCA by the catalyst complex via the C–H bond activation.
To extend the scope of aldehyde substrates, various aromatic and alkyl aldehydes were employed with the optimized conditions, with all afforded the corresponding carboxylic acids with moderate to good yields.. While the turnover number was moderate, this work did show a novel pathway in aldehyde oxidation. Thus, it will give a good opportunity to develop a better catalyst for the conversion of aldehydes into more valuable products.
Figure 2: Substrate scope of the oxidation of aldehydes into carboxylic acids by the catalyst system with turnover number (TON).
The finding of this work has been published on Journal of American Chemistry Society: Jeong, D.; Kim, H.; Cho, J. Oxidation of Aldehydes into Carboxylic Acids by a Mononuclear Manganese(III) Iodosylbenzene Complex through Electrophilic C–H Bond Activation. J. Am. Chem. Soc. 2023, 145 (2), 888–897. https://doi.org/10.1021/jacs.2c09274.
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