Nickel-Catalyzed Suzuki–Miyaura Coupling of Aliphatic Amides

We report the Ni-catalyzed Suzuki–Miyaura coupling of aliphatic amide derivatives. Prior studies have shown that aliphatic amide derivatives can undergo Ni-catalyzed carbon–heteroatom bond formation but that Ni-mediated C–C bond formation using aliphatic amide derivatives has remained difficult. The coupling disclosed herein is tolerant of considerable variation with respect to both the amide-based substrate and the boronate coupling partner and proceeds in the presence of heterocycles and epimerizable stereocenters. Moreover, a gram-scale Suzuki–Miyaura coupling/Fischer indolization sequence demonstrates the ease with which unique polyheterocyclic scaffolds can be constructed, particularly by taking advantage of the enolizable ketone functionality present in the cross-coupled product. The methodology provides an efficient means to form C–C bonds from aliphatic amide derivatives using nonprecious-metal catalysis and offers a general platform for the heteroarylation of aliphatic acyl electrophiles.