Biaryl Ligands for C–N Coupling

Key words

palladium catalysis - Buchwald–Hartwig amination - Suzuki coupling

Significance

Aryl carbon–nitrogen bonds are ubiquitous in nature and important pharmaceuticals; however, a mild and catalytic method for their formation has been a major hurdle for organic chemistry. In the late 1990s Buchwald described a new series of dialkylbiaryl phosphine ligands that allowed for mild and efficient palladium-catalyzed cross-couplings. Further work led to the development of JohnPhos, which enabled room temperature palladium-catalyzed intermolecular amination. This seminal work set the stage for widespread adoption of Buchwald ligands in both industry and academia. Herein, Buchwald reports the discovery of JohnPhos, a bulky biaryl ligand, for amination and Suzuki coupling under mild conditions.

Comment

The reported ligand, JohnPhos, contains bulky tert-butyl groups, which were crucial to facilitate the difficult reductive elimination of the aryl carbon–nitrogen bond. A variety of amines including anilines and alkylamines were tolerated in the reaction. Notably, very low loadings of palladium could be employed for the C–N coupling; however, the reaction required higher temperature. The capability of the new ligand was also explored in Suzuki coupling. The Suzuki coupling could also be run under similarly mild conditions with a variety of aryl halides and aryl boronic acids.