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CO2/DMSO-Catalyzed Oxidation of Benzylic and Allylic Alcohols

DMSO oxidations of alcohols are well known (e.g., Swern, Pfitzner-Moffatt, and Parikh-Doering) and widely used. These methods, however, require activation of the alcohol with large excesses of promoters that are often both toxic and relatively difficult to handle. Therefore, DMSO oxidation techniques are often not amenable to large scale reactions. Das and co-workers have recently reported a significant advance in DMSO oxidation methods using cheap, abundant, atom-economical, and nontoxic carbon dioxide to promote the oxidation reaction (Scheme 1).1

As shown in Scheme 1, the optimized conditions were tried with a variety of primary and secondary alcohols to yield aldehydes and ketones. When using primary alcohols, no overoxidation to the corresponding carboxylic acid was seen, and the reaction solely yielded the aldehyde (entries 1-14).

Scheme 1: Oxidation of primary and secondary alcohols using the CO2/DMSO method.

 

The reaction also works well with cyclic alcohols (Scheme 2) under the same conditions.

Scheme 2: Oxidation of cyclic alcohols using the CO2/DMSO method.

This CO2/DMSO oxidation was demonstrated to be a useful step in the synthesis of the potent micro-tubule-targeting and vascular-damaging agent combretastatin A4 and in the synthesis of the breast cancer treatment pharmaceutical agent DMU-212 (Scheme 3).

Scheme 3: Synthesis of pharmaceutically-active molecules featuring the CO2/DMSO oxidation.

In summary, the first CO2/DMSO-catalyzed oxidation of alcohols has been demonstrated by the Das group. This reaction does not require metal catalysts or toxic promoters. A wide variety of functional groups tolerate the mild conditions of this reaction. Because of the simple conditions and reagents required in this oxidation, it should be of interest to the synthesis community.

Debra D. Dolliver, Ph.D.

1 Riemer, D.; Mandaviya, B.; Schilling, W.; Götz, A. C.; Kühl, T.; Finger, M.; Das, S. ACS Catalysis 2018, 8, 3030.

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