Facile and Multistep Synthesis of Functionalized Nitroxide Radicals Containing a Bipyridine Frame

The synthesis of stable bipyridine substituted nitronyl-nitroxide (NIT) or imino-nitroxide (IM) is reported. These methyl or ethynyl functionalized compounds have been prepared from the bromo-substituted analogues by a carboalkoxylation reaction catalyzed by low valent palladium(0) using carbon monoxide in the presence of a primary alcohol as nucleophile and a tertiary amine as base. In the case of the 6,6′-dibromo-2,2′-bipyridine, a quite selective mono-carboethoxylation reaction is achieved under mild conditions (70 °C, 1 atmosphere CO). Stepwise reduction of the resulting esters with sodium borohydride, followed by Swern oxidation, affords the corresponding carbaldehydes in good yield. Furthermore, these derivatives were used in a multistep protocol to prepare hybrid molecules bearing both an ethynyl group and a nitroxide free radical. The synthetic methods reported herein provide a practical methodology to the rational design of ligands bearing different kinds of functionalities.

bipyridine - carboalkoxylation - palladium - alkyne - nitroxide radicals