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

Abstract

We report a mechanistic study of C(sp)-H bond activation mediated by nickel. Cyclometalated Ni(II) ureate [(PEt)Ni(κ- C,N,N-(CH)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(sp)-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)-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.

Direct Base-Assisted C‒H Cyclonickelation of 6-Phenyl-2,2′-bipyridine

“…Variation of the substitution pattern of the metalated arene including deuteration and DFT modelling is subject of ongoing work. The high efficiency motivates a future extension to the more challenging cyclometalation of C(sp 3 )-H protoligands, which was elegantly demonstrated recently by Schafer, Love et al for the formation of [Ni(-CH 2 -N(Cy)C(O)N(quinoline-8-yl)(PEt 3 )] [41]. While for the noble metals Ru, Ir, Rh, or Pd, the base-assisted C(sp 2 )-H deprotonation and metalation using acetate/carbonate has been established for a few years [38][39][40] our study represents an important step into the world of the base metals of the 3d series.…”

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

“…[65][66] The paramagnetic intermediate that underwent C-H bond activation, though its identity was not ascertained. 55 Insolubility rendered the determination of solution NMR data for 5 impossible.…”

“…[53][54] Love and co-workers published a study on the C-H activation step using an 8-aminoquinoline (8-AQ) functionalized tertiary urea as the model substrate and isolated a Ni(II) ureate complex with a C-Ni bond, shown in Scheme 1c. 55 The intramolecular C-H activation is suggested to go through a concerted metalation deprotonation mechanism with an electrophilic C-H activation transition state, as supported by Hammett plot and KIE studies; 55 however, no intermediates prior to C-H activation or functionalization steps have been isolated.…”

Intermolecular Oxidative Addition of Aryl Halides to Platinum(II) Alkyl Complexes

“…4,[6][7][8][9][10][11][12][13][14][15][16] Despite the increasing prevalence of M(II)/M(IV) (M = Ni, Pd) catalytic processes invoking Csp 2 -X OA in the literature, 17 few well-defined examples of such reactivity have been reported. [18][19][20][21][22][23] While many Pt(II) complexes undergo facile SN2-type Csp 3 -X OA, these complexes are inactive toward intermolecular Csp 2 -X OA which typically occurs in a concerted fashion. 24 With the exception of a poorly defined example from 1967, 25 efforts to achieve intermolecular C(aryl)-X oxidative addition have necessitated incorporation of the oxidant into the ligand scaffold (intramolecular OA).…”