Synthesis of Enantioenriched Aryl-tert-Butylphenylphosphine Oxides via Cross-Coupling Reactions of tert-Butylphenylphosphine Oxide with Aryl Halides

A series of enantiomerically enriched tertiary phosphine oxides have been prepared via the Pd-catalyzed cross-coupling reactions of enantiomerically pure tert-butylphenylphosphine oxide, with a variety of aryl iodides and bromides. This new protocol under optimized reaction conditions [toluene, 110 C-0, Pd(PPh3)(4), K2CO3 (or Et3N)] afforded highly functionalized P-chiral phosphine oxides with a yield of 78% to 95% and with enantiomeric excesses above 98%. The stereoretentive outcome of the cross-coupling reactions was proved by X-ray crystallography of selected phosphine oxides: (S)-(2-aminophenyl)(tert-butyl)(phenyl)phosphine oxide (3a) and (S)-anthracen-9-yl(tert-butyl)(phenyl)phosphine oxide (3i). When attempting to convert the enantiomerically pure phosphine oxide 3a to the corresponding borane by the treatment with the borane dimethyl sulfide complex partial stereoerosion at a stereogenic phosphorus atom was observed. Racemic tert-butyl (2-(dimethylamino)phenyl)(phenyl)phosphine (7a) was isolated in a quantitative yield upon deprotection of the corresponding borane (8a) and converted to a palladium crystalline complex (9), the structure of which has been proved by X-ray crystallography.