Surprising Reactivity in NiXantphos/Palladium-Catalyzed α-Arylation of Substituted Cyclopropyl Nitriles

α-Arylations of cyclopropyl and related nitriles provide access to important synthetic intermediates and pharmacophores for biologically active molecules. However, robust methods for coupling of sterically encumbered partners have remained elusive. Through optimization using high-throughput experimentation (HTE), the NiXantphos ligand was found to be effective in the coupling of sterically hindered β-substituted cyclopropyl nitriles with a number of aryl groups and heterocycles, including those containing acidic N–H and O–H bonds.