An Oxidative Palladium-Catalyzed Remote <i>meta</i> -Selective Homo-Biaryl Coupling Assisted by Nitrile Directing Templates

Remote <i>meta</i>-C-H functionalization has emerged as a transformative approach in organic synthesis, allowing for the selective functionalization of inactive <i>meta</i>-C-H bonds. While considerable progress has been made in <i>meta</i>-C-H functionalization strategies, including olefination, cyanation, acetoxylation, and arylation, regioselective <i>meta</i>-C-H homo-biaryl coupling remains unexplored. In this study, we report the first palladium-catalyzed oxidative protocol for regioselective <i>meta</i>-C-H homo-biaryl coupling, targeting substrates such as 3-phenylpropanoic acid, 2-phenylethan-1-ol, phenylacetic acid, and phenylmethanesulfonic acid derivatives. This method significantly enhances the synthetic tool box for the construction of complex biaryl frameworks with exceptional precision. The reaction proceeds efficiently under ambient conditions, with copper trifluoromethanesulfonate identified as a critical additive for driving the process. Furthermore, this strategy has been extended to the synthesis of complex trimeric and diolefination products. The protocol delivered the desired products in good yields with excellent regioselectivity and demonstrated broad applicability across a range of substrates bearing diverse aliphatic and aromatic nitrile-based directing group templates.