Direct a-Oxygenation Reactions of Aldehydes and Ketones

The hydroxy group in the a-position to a carbonyl group is a common feature of many natural and biologically active compounds. Furthermore, this functionality is an obvious precursor in the synthesis of other important building blocks such as diols. 

The first electrophilic source of oxygen introduced for the proline-catalyzed a-oxygenation of aldehydes and ketones was nitrosobenzene, based on the use of this reagent in the asymmetric metal-catalyzed oxidation of tin enolates [12]. A number of research groups, including those of Zhong [12a], MacMillan [13b], 

Also for this transformation, Blaclcmond and co-workers [15] detected a rate acceleration and amplification of the enantiomeric excess. 

The a-oxidation of aldehydes was later further extended to the use of ketones as nucleophiles. In order to develop this reaction into a useful process, a considerable effort was made to optimize the reaction conditions as several different problems arose these included a lower reaction rate and yields because of the formation of the di-addition product at the two enolizable carbon atoms and lower 0/N-selectivity. Hayashi et al. [16a] and Cordova et al. [16c] partly solved these problems by using a relatively large excess of ketone and by applying the slow addition method leading to good chemical yields (44-91%), with near-enantiopure products being obtained (96-99% ee). 

The addition of nitrosobenzene to ketones catalyzed by proline has been applied by Ramachary and Barbas in the desymmetrization of meso-cyclohexanone derivatives [17]. 

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