Gold-Catalyzed Direct Arylation

Biaryls (two directly connected aromatic rings, Ar-1-Ar-2) are common motifs in pharmaceuticals, agrochemicals, and organic materials. Current methods for establishing the Ar-1-Ar-2 bond are dominated by the cross-coupling of aryl halides (Ar-1-X) with aryl metallics (Ar-2-M). We report that, in the presence of 1 to 2 mole percent of a gold catalyst and a mild oxidant, a wide range of arenes (Ar-1-H) undergo site-selective arylation by arylsilanes (Ar-2-SiMe3) to generate biaryls (Ar-1-Ar-2), with little or no homocoupling (Ar-1-Ar-1/Ar-2-Ar-2). Catalysis proceeds at room temperature and tolerates a broad range of functional groups, including those incompatible with cross-coupling. These features expedite biaryl preparation, as demonstrated by synthesis of the nonsteroidal anti-inflammatory diflunisal.