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

Studies
into the mechanism of 8-aminoquinoline-directed nickel-catalyzed
C­(sp3)–H arylation with iodoarenes were carried
out, to determine the catalyst resting state and optimize catalytic
performance. Paramagnetic complexes undergo the key C–H activation
step. The ubiquitous base Na2CO3 is found to
hinder catalysis; replacement of Na2CO3 with
NaOtBu gave improved catalytic turnovers
under milder conditions. Deprotonation of the 8-aminoquinoline derivative N-(quinolin-8-yl)­pivalamide (1a) at the amide
nitrogen using NaH, followed by reaction with NiCl2(PPh3)2 allowed for the isolation of complex Ni­([AQpiv]-κN,N)2 (3) with chelating N-donors (where [AQpiv] = C9NH6NCOtBu).
Complex 3 is a four-coordinate disphenoidal high-spin
Ni­(II) complex, excluding short anagostic Ni--tBu hydrogen interactions. Complex 3 reacts
with the paddle-wheel [Ph3PNi­(μ-CO2tBu)2]2 (6·PPh3) or tBuCO2H to give insoluble {[AQpiv]­Ni­(O2CtBu)}2 (5). Dissolution
of 5 in donor solvents L (L= DMSO and DMF) gave a paramagnetic
intermediate assigned by NMR as [AQpiv]­Ni­(O2CtBu)­L (5·L) and equilibrium
reformation of 3 and 6·L. DFT calculations
support this equilibrium in solution. Both 3 and 5 undergo C–H activation at temperatures as low as
80 °C and in the presence of PR3 (PR3 =
PPh3, PiBu3) to
give Ni­(C9NH6NCOCMe2CH2-κN,N,C)­PR3 (7·PR3). The C–H
functionalization reaction orders with respect to 7·PiBu3, iodoarenes, and phosphines were determined. Hammett analysis using
electronically different aryl iodides suggests a concerted oxidative
addition mechanism for the C–H functionalization step; DFT
calculations were also carried out 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
NaOtBu improved catalysis at milder conditions
and made carboxylic acid and phosphine additives unnecessary. Complex 3 and its functionalized analogues were observed as the catalyst
resting state under these conditions.