Polonovski-Type N-Demethylation of N-Methyl Alkaloids Using Substituted Ferrocene Redox Catalysts

Various substituted ferrocenes have been trialed as catalysts in the nonclassical Polonovski reaction for N-demethylation of N -methyl alkaloids. Earlier studies suggest that conditions facilitating a higher ferrocenium ion concentration lead to superior outcomes. In this regard, the bifunctional ferrocene FcCH 2 CO 2 H, with electron donor and acceptor moieties in the same molecule, has been shown to be advantageous for use as a catalyst in the N-demethylation of a number of tertiary N -methylamines such as codeine, thebaine, and oripavine. These substrates are readily N-demethylated under mild conditions, employing sub-stoichiometric amounts of the substituted ferrocene at ambient temperature. These reactions are equally efficient in air and may also be carried out in one pot.