Ligand-controlled β-selective C(sp3)–H arylation of N-Boc-piperidines

We report a general palladium-catalyzed β-arylation of Boc-piperidines, which yields a variety of valuable 3-arylpiperidines in a simple and direct manner. The β- vs. α-arylation selectivity was controlled by the ligand, with flexible biarylphosphines providing mainly the desired β-arylated products whereas more rigid biarylphosphines mainly furnished the more classical α-arylated products. The computed reaction mechanism (DFT), studied from the common α-palladated intermediate, indicated that the reductive elimination steps leading to the α- and β-arylated products are selectivity-determining. Moreover, the experimental trend obtained with different ligands was well reproduced by the calculations.