Influence of Benzothiophene C2-Substituents in Palladium-Catalyzed Direct C3-Arylation

Abstract

In the context of Pd-catalyzed CH bond arylation, the C2-position of benzothiophenes has been demonstrated to exhibit the highest reactivity. However, when the C2-position is not available, studies have shown that CH bond activation of the C3-position becomes a viable alternative. This study investigates the influence of several C2-substituents on benzothiophenes in the palladium-catalyzed CH C3-arylation reaction. The reaction was found to be compatible with hydroxymethyl, formyl, and acetyl substituents. Conversely, the desired coupling product was obtained in low yield in the presence of an ester substituent. For these reactions, a variety of aryl bromides bearing useful substituents, such as fluoro, trifluoromethyl, chloro, acetyl, nitrile, and ester, as well as heteroaryl bromides, were tolerated. Furthermore, a commercially available, air-stable palladium catalyst and a cost-effective base were utilized in these coupling reactions.