Mechanism of 8-Aminoquinoline Directed Ni-Catalyzed C(sp3)-H Functionalization: Paramagnetic Ni(II) Species, and the Deleterious Effect of Na2CO3 as a Base

Studies into the mechanism of 8-aminoquinoline-directed nickel-catalyzed C(sp³)–H arylation with iodoarenes are described, in an attempt to determine the catalyst resting state and optimize catalytic performance. Paramagnetic complexes are identified that are undergo the key C–H activation step. Hammett analysis using electronically different aryl iodides suggests a concerted oxidative addition mechanism for the C–H functionalization step; DFT calculations were also performed to support this finding. When Na₂CO₃ is used as the base the rate determination step for C–H functionalization appears to be 8-aminoquinoline deprotonation and binding to Ni. The carbonate anion was also observed to provide a deleterious NMR inactive low-energy off-cycle resting state in catalysis. Replacement of Na₂CO₃ with NaO^tBu not only improved catalysis at milder conditions but also eliminated the need for carboxylic acid and phosphine additives.