BrettPhos

BrettPhos is a bulky, electron-rich biaryl phosphine ligand widely used to accelerate palladium-catalyzed cross-coupling reactions. It is part of the family of Buchwald ligands and is particularly valued for enabling challenging transformations, such as the coupling of aryl chlorides and heteroaryl electrophiles, under relatively mild conditions. The design of BrettPhos emphasizes steric bulk around the palladium center and high electron donation from the phosphine, which together promote fast oxidative addition and facilitate reductive elimination in catalytic cycles.

In typical applications, BrettPhos is employed with palladium precursors to form active catalytic species for C–N, C–O, and C–C bond-forming couplings. It is frequently used in Buchwald–Hartwig amination (arylation of amines with aryl halides), as well as in cross-couplings of aryl chlorides with phenols, amines, boron, and zinc reagents. The ligand’s performance is noted for broad substrate scope, tolerance of various functional groups, and effectiveness with less reactive electrophiles compared to many other ligands.

Operational considerations include its occasional sensitivity to air and moisture, requiring standard inert-atmosphere handling. Conditions vary by substrate, but typical systems pair BrettPhos with a palladium source such as Pd2dba3 or a Pd(II) precatalyst, a base such as Cs2CO3 or KOtBu, and a coordinating solvent like toluene or dioxane at elevated temperatures.

See also: SPhos, XPhos, t-BuXPhos, and other Buchwald ligands.