Influence of 1,3-Difluorobenzene Substituents for Palladium-Catalyzed Direct Arylations

The influence of electron‐withdrawing and electron‐donating substituents (nitro, nitrile, chloro, bromo, methoxy or amino) on 1,3‐difluorobenzenes in their palladium‐catalysed direct C2 arylation has been explored. With most substituents, the reaction proceeds nicely using air‐stable palladium catalysts (0.5–2 mol‐%) and KOAc/DMA. In general, very regioselective C2‐arylation was observed. Moreover, a variety of substituents on the aryl bromide coupling partner (ester, acetyl, formyl, nitro, nitrile, trifluoromethyl, chloro, fluoro or methyl) was tolerated. Palladium‐catalysed direct arylation of 4‐ or 5‐substituted 1,3‐difluorobenzenes allows the synthesis of 2‐arylated 1,3‐difluorobenzenes in one step. This regioselective C2‐arylation proceeds with air‐stable palladium catalysts and KOAc/DMA. Both electron‐withdrawing and electron‐donating substituents (chloro, bromo, methoxy or amino) on the 1,3‐difluorobenzenes were tolerated.