Diversification of 2,2’-Bipyridines and Azaheterocycles via Nucleophilic Displacement of Trimethylaminiums

Bipyridines and azaarenes are an important class of ligands that impart unique and tunable properties to transition metal complexes and catalysts. While some derivatives are commercially available, noncommercial analogues are often challenging to prepare and purify. Herein we report a general nucleophilic aromatic substitution reaction that converts cationic trimethylaminated bipyridines into a series of functionalized bipyridines. Our method showcases a series of C–O, C–S, and C–F bond forming reactions as well as a selective monodemethylation that converts the electron-deficient trimethylaminium to an electron-rich dimethylamine. The approach was further applied to diversification of pharmaceuticals and natural products, and was applied to the total synthesis of Graveolinine and the preparation of Graveolinine derivatives.