XPhos

XPhos is a bulky, electron-rich biaryl monophosphine ligand used to accelerate palladium-catalyzed cross-coupling reactions. It was developed to enable challenging transformations, particularly those involving aryl chlorides and heteroaryl substrates, and has become a widely employed ligand in modern Pd-catalyzed coupling and amination chemistry.

The ligation environment provided by XPhos combines a large steric demand with strong electron donation, properties that stabilize reactive palladium intermediates and facilitate oxidative addition, transmetalation, and reductive elimination. The biaryl framework places the phosphine in a geometry that promotes rapid turnover and increases tolerance to a variety of substrates and bases. These features contribute to activity under relatively mild conditions and often with low catalyst loadings.

XPhos is commonly used in Suzuki–Miyaura and related cross-couplings, including Buchwald–Hartwig amination and C–N, C–O, and some C–C bond-forming processes. It is compatible with a broad range of bases, solvents, and palladium sources, and supports reactions with aryl chlorides, bromides, and a wide array of functional groups. Typical systems pair XPhos with Pd precursors such as Pd(OAc)2 or Pd2(dba)3 and may employ bases like Cs2CO3 or K3PO4 in solvents such as toluene, dioxane, or mixed aqueous-organic media.

XPhos is part of a family of Buchwald-type ligands that includes SPhos and BrettPhos, designed to enable efficient, broadly applicable Pd-catalyzed couplings. It is commercially available from multiple suppliers and is widely cited in the literature for improving reactivity and substrate scope in modern cross-coupling protocols.