C–ON Bond Homolysis of Alkoxyamines, Part 11: Activation of the Nitroxyl Fragment

A few years ago, Bagryanskaya and
colleagues (J. Org. Chem. 2011) showed
that protonation of the nitroxyl fragment
deactivated the alkoxyamine C–ON bond. Conversely, our group
showed that protonation (Chem. Commun. 2011), as well as other chemical reactions such as oxidation or amine
quaternization (Org. Lett. 2012), of
the pyridyl moiety carried by the alkyl fragment was suitable to activate
the homolysis of the C–ON bond. To pursue our goal of applying
alkoxyamines as theranostic agents (Org. Biomol. Chem. 2014 and Mol. Pharmaceutics 2014) by activation of the C–ON bond homolysis, we
turned our interest to the chemical activation of the nitroxyl fragment
by oxidation/reduction of selected functions. Conversion of a hydroxyl
group located close to the nitroxyl moiety successively into aldehyde,
then acid, and eventually into ester, led to a successive decrease
in kd.