AshPhos Ligand: Facilitating Challenging Aminations in Five- and Six-Membered Heteroaryl Halides Using Cyclic Secondary and Bulky Amines.

Our newly developed AshPhos ligand represents a significant advancement in Buchwald-Hartwig aminations, overcoming many limitations of existing ligands. Created from affordable and accessible materials, AshPhos enhances catalytic performance, especially for extremely difficult substrates, by emphasizing the principles of ligand chelation and cooperativity. Its successful synthesis and application in catalytic aminations underscore its potential for use in the sustainable synthesis of compounds important to medicinal chemistry, materials, and energy. Further studies validated AshPhos's effectiveness in coupling challenging heteroaryl bromides and chlorides with various amines, including hindered amines and those with multiple heteroatoms. Slightly elevated temperatures were essential to avoid forming inactive species, ensuring consistent catalytic turnover. A control nuclear magnetic resonance spectroscopy study suggests the formation of catalytically dormant species or deligation of AshPhos from palladium at room temperature due to the coordination of multiple substrate molecules with the palladium species. Analyses showed cost-effectiveness of AshPhos, making it a significant advancement in catalytic amination for more efficient and sustainable chemical processes. The diverse substrate scope, covering challenging coupling partners and forming over 55 substrates in good-to-excellent yields, further demonstrated the efficiency of AshPhos.