Understanding Ni(II)-Mediated C(sp3)–H Activation: Tertiary Ureas as Model Substrates

We report a mechanistic study of C­(sp3)–H bond activation mediated by nickel. Cyclometalated Ni­(II) ureate [(PEt3)­Ni­(κ3-C,N,N-(CH2)­N­(Cy)­(CO)­N­((N)-quinolin-8-yl))] was synthesized and isolated from the urea precursor, (Me)­(Cy)­N­(CO)­N­(H)­(quinolin-8-yl), via C­(sp3)–H activation. We investigated the effects of solvents and base additives on the rate of C–H activation. Kinetic isotope effect experiments showed that C–H activation is rate determining. Through deuterium labeling and protonation studies, we also showed that C–H activation can be reversible. We extended this reaction to a range of ureas with primary and secondary C­(sp3)–H bonds, which activate readily to form analogous nickelated products. Finally, we showed that carboxylate additives assist with both ligand dissociation and initial N–H bond activation, consistent with a concerted metalation–deprotonation mechanism.