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

We report a mechanistic study of C(sp(3))-H bond activation mediated by nickel. Cyclometalated Ni(II) ureate [(PEt3)Ni(kappa(3)-C,N,N-((C) under barH(2))N(Cy)(CO)(N) under bar(((N) under bar)-quinolin-8-y1))] was synthesized and isolated from the urea precursor, (Me)(Cy)N(CO)N(H)(quinolin-8-yl), via C(sp(3))-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(sp(3))-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.