The Importance of water in a TEMPO-iodobenzene diacetate oxidation

23 April 2004

In 1997, Piancatelli and coworkers reported ( J. Org. Chem., 1997 , 62 , 6974) a TEMPO-iodobenzene diacetate oxidation of alcohols to aldehydes, stating that the reaction "....can be performed in an open flask without any particular precautions, e.g. inert atmosphere or dry solvent...". This apparent robustness turns out to underlie a lack of robustness, as process chemists at Novartis recently discovered* while performing the selective oxidation reaction below, as part of a synthesis of (+)-discodermolide.

The Novartis group found that while this oxidation worked well on 0.3-1g scale, the yield fell to around 10% on scale-up. Given Piancatelli's comments, they explored the possibility that moisture might be facilitating the reaction, and indeed found that addition of 0.1 equivalents of water dramatically accelerated the oxidation and enabled high yields (~90%) to be achieved on kilogram scale.

* S.J. Mickel et al, Org. Proc. Res. Dev. , 2004 , 8 , 113.