Non-Symmetrical Bis-Azine Biaryls from Chloroazines: A Strategy Using Phosphorus Ligand-Coupling

Distinct approaches to synthesize bis-azine biaryls are in demand as these compounds have multiple applications in the chemical sciences and are challenging targets for metal-catalyzed cross-coupling reactions. Most approaches focus on developing new reagents as the formal nucleophilic coupling partner that can function in metal-catalyzed processes. We present an alternative approach using pyridine and diazine phosphines as nucleophilic partners and chloroazines where the heterobiaryl bond is formed via a tandem S_NAr-phosphorus ligand-coupling sequence. The heteroaryl phosphines are prepared from chloroazines and are bench stable solids. Using this strategy, a range of bis-azine biaryls can be formed from abundant chloroazines that would be challenging using traditional approaches and a one-pot cross-electrophile coupling of two chloroazines is feasible.