Nickel-Catalyzed Reductive Arylation of Redox Active Esters for the Synthesis of α-Aryl Nitriles: Investigation of a Chlorosilane Additive.

A nickel-catalyzed reductive cross-coupling of redox active -hydroxyphthalimide (NHP) esters and iodoarenes for the synthesis of α-aryl nitriles is described. The NHP ester substrate is derived from cyanoacetic acid, which allows for a modular synthesis of substituted α-aryl nitriles, an important scaffold in the pharmaceutical sciences. The reaction exhibits a broad scope, and many functional groups are compatible under the reaction conditions, including complex highly functionalized medicinal agents.

Design of an Electron-Withdrawing Benzonitrile Ligand for Ni-Catalyzed Cross-Coupling Involving Tertiary Nucleophiles.

The design of new ligands for cross-coupling is essential for developing new catalytic reactions that access valuable products such as pharmaceuticals. In this report, we exploit the reactivity of nitrile-containing additives in Ni catalysis to design a benzonitrile-containing ligand for cross-coupling involving tertiary nucleophiles. Kinetic and Hammett studies are used to elucidate the role of the optimized ligand, which demonstrate that the benzonitrile moiety acts as an electron-acceptor to promote reductive elimination over β-hydride elimination and stabilize low-valent Ni.