BrettPhos | CAS 1070663-78-3 | ≥97%

BrettPhos (dicyclohexyl(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine) is an electron-rich, sterically demanding dialkyl biaryl monophosphine of the Buchwald ligand family, developed for palladium-catalysed carbon–nitrogen cross-coupling. The ligand combines a dicyclohexylphosphino group with a biphenyl backbone carrying 2′,4′,6′-triisopropyl substitution on the upper ring and 3,6-dimethoxy substitution on the phosphine-bearing ring. This arrangement favours the highly active monoligated palladium species characteristic of Buchwald biarylphosphine catalysis.

Ligand design and reactivity

The strong σ-donation of the dialkylphosphine promotes oxidative addition into challenging aryl–halide and aryl–sulfonate electrophiles, while the bulky upper aryl ring favours monoligated palladium species and productive reductive elimination. Mechanistic studies of BrettPhos-type palladium(II) amido complexes show partitioning between O-bound and C-bound isomers, with the C-bound isomer competent for carbon–nitrogen reductive elimination. Together these features make BrettPhos effective with common aryl electrophiles, with particularly strong support for aryl mesylates and aryl chlorides in C–N coupling.

Buchwald–Hartwig amination

BrettPhos is best known for the highly selective monoarylation of primary amines: paired with palladium, it couples primary aliphatic amines and anilines with aryl electrophiles to give secondary arylamines while suppressing over-arylation, a selectivity that reflects the ligand's pronounced steric bulk disfavouring the second arylation to the tertiary amine. This control extends even to the monoarylation of methylamine. The catalyst system enables aryl mesylates as coupling partners and tolerates a broad range of aryl chlorides, bromides and triflates, including hindered and functionalised substrates, at low palladium loadings with fast reaction times. This makes it a valuable ligand for installing aniline and alkylamine motifs in medicinal-chemistry, agrochemical and materials research.

Catalyst deployment and broader scope

BrettPhos is commonly deployed through Buchwald aminobiphenyl palladacycle precatalysts such as BrettPhos Pd G3 and G4, which generate the active catalyst species efficiently and give controlled ligand:palladium ratios at low loadings. Beyond primary-amine monoarylation, BrettPhos and the wider Buchwald biarylphosphine family support related carbon–nitrogen couplings and other palladium-catalysed bond-forming reactions that require a bulky, electron-rich monophosphine. BrettPhos has also been identified as an optimal ligand for the palladium-catalysed trifluoromethylation of aryl chlorides, extending its utility beyond C–N coupling into C–CF₃ bond formation. The ligand is a frequent reference point in catalyst and ligand screening for C–N cross-coupling method development.