A Unified Approach to Couple Aromatic Heteronucleophiles to Azines and Pharmaceuticals

Abstract

Abstract Coupling aromatic heteronucleophiles to arenes is a common way to assemble drug‐like molecules. Many methods operate via nucleophiles intercepting organometallic intermediates, via Pd‐, Cu‐, and Ni‐catalysis, that facilitate carbon‐heteroatom bond formation and a variety of protocols. We present an alternative, unified strategy where phosphonium salts can replicate the behavior of organometallic intermediates. Under a narrow set of reaction conditions, a variety of aromatic heteronucleophile classes can be coupled to pyridines and diazines that are often problematic in metal‐catalyzed couplings, such as where (pseudo)halide precursors are unavailable in complex structures with multiple polar functional groups.