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

Abstract

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 NaO t Bu 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] = C9NH6NCO t Bu). Complex 3 is a four-coordinate disphenoidal high-spin Ni­(II) complex, excluding short anagostic Ni-- t Bu hydrogen interactions. Complex 3 reacts with the paddle-wheel [Ph3PNi­(μ-CO2 t Bu)2]2 (6·PPh 3 ) or t BuCO2H to give insoluble {[AQpiv]­Ni­(O2C t Bu)}2 (5). Dissolution of 5 in donor solvents L (L= DMSO and DMF) gave a paramagnetic intermediate assigned by NMR as [AQpiv]­Ni­(O2C t Bu)­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, P i Bu3) to give Ni­(C9NH6NCOCMe2CH2-κN,N,C)­PR3 (7·PR 3 ). The C–H functionalization reaction orders with respect to 7·P i Bu 3 , 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 NaO t Bu 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.

Salt‐Stabilized Silylzinc Pivalates for Nickel‐Catalyzed Carbosilylation of Alkenes

“…These findings demonstrated that nickel catalyst enables regioselective 1,2‐addition of PhMe 2 Si−ZnOPiv to alkene (Scheme 4b). In order to further unravel the mechanistic intricacies of the 8‐aminoquinoline, we decided to examine the reactivity of the paramagnetic Ni II species of [AQ piv ] 2 Ni [25] ( 68 ). Interestingly, catalytic amount of [AQ piv ] 2 Ni was found to be a suitable catalyst, as 6 and 7 were invariably formed in moderate to good yields (Scheme 4c).…”

Electronic Directing Group Modification for Improved Ni(II)-Mediated C(sp3)–H Activation: A Hammett Investigation of 8-Aminoquinoline

“…Also, it was observed that the addition of carboxylate additives has a synergistic effect with carbonate bases and increases the rate of C–H activation in the proposed CMD pathway. Following our work, the Johnson group published the first detailed mechanistic investigation for an amide system where a paramagnetic bis -AQ ligated Ni­(II) species was isolated and shown to be a productive species in achieving C­(sp 3 )–H activation (Figure a, ii) . Even more recently, the Baik and Chang groups reported the Ni­(II) catalyzed C­(sp 3 )–H amidation of AQ amides and computationally investigated the influence of 5-substituted AQs for improving catalytic turnover (Figure a, iii) …”

“…Following our work, the Johnson group published the first detailed mechanistic investigation for an amide system where a paramagnetic bis-AQ ligated Ni(II) species was isolated and shown to be a productive species in achieving C(sp 3 )−H activation (Figure 1a, ii). 42 Even more recently, the Baik and Chang groups reported the Ni(II) catalyzed C(sp 3 )−H amidation of AQ amides and computationally investigated the influence of 5-substituted AQs for improving catalytic turnover (Figure 1a, iii). 43 Through a series of kinetic experiments and a Hammett analysis, which we have previously disclosed with para-benzyl ureas (Figure 2a), the rates of C−H activation were determined.…”

Coordination-Induced Weakening of a C(sp3)–H Bond: Homolytic and Heterolytic Bond Strength of a CH–Ni Agostic Interaction

“…Ni- and Pd-catalyzed C­(sp 3 )–H functionalization typically involves a rate-limiting C­(sp 3 )–H activation step, where the chelating ligands direct the C–H bond near the metal center before generating the M–C covalent bond. It is generally accepted that this crucial step proceeds through a transient intermediate containing a C–HM agostic interaction (i.e., 3-center-2-electron M–H–C bond) that reacts with internal or exogenous base through a concerted-metalation deprotonation (CMD) pathway (Figure , left) . However, since one-pot synthetic protocols assemble the active species in situ, it is difficult to quantify the magnitude of C–H bond weakening prior to M–C bond formation in this elementary step.…”