A total synthesis of toddaquinoline exposes a dual role for cobalt in radical additions to pyridines

This paper describes the first total synthesis of toddaquinoline, an alkaloid from the root bark of Formosan Toddalia asiatica. Importantly, the synthesis has exposed a dichotomy in radical reactions mediated by tin and cobalt(I) that involve additions to pyridines. Our observations suggest that cobalt plays a dual role in such reactions: firstly initiating homolysis of the carbon to halogen bond, then acting as a Lewis acid to promote radical additions to the carbon centre adjacent to nitrogen.