Mechanism of 8-Aminoquinoline-Directed Ni-Catalyzed C(sp <sup>3</sup> )–H Functionalization: Paramagnetic Ni(II) Species and the Deleterious Effect of Carbonate as a Base
Bibliographic record
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 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.008 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".