Details of the Mechanism of the Asymmetric Transfer Hydrogenation of Acetophenone Using the Amine(imine)diphosphine Iron Precatalyst: The Base Effect and The Enantiodetermining Step
Bibliographic record
Abstract
Abstract The excellent ketone asymmetric transfer hydrogenation (ATH) systems using the precatalysts (S,S)-trans-[FeCl(CO)(PPh2CH2CH2NHCHPhCHPhNCHCH2PAr2)]BPh4 (Ar = Ph (1), p-tolyl (2)) have a fascinating dependence of activity on the base concentration, which is investigated here. The reaction of complex 1 or 2 with 1 equiv of the strong base potassium tert-butoxide in THF for 2?7 days produces the neutral amine(ene-amido) complexes [FeCl(CO)(PPh2CH2CH2NHCHPhCHPhNCHCHPAr2)] (8 and 9). These monodeprotonated complexes have been completely characterized by NMR, EA, and FT-IR spectroscopy and mass spectrometry, and the structure of 9 has been further confirmed by single-crystal X-ray diffraction to reveal a structure with the NH and FeCl bonds parallel and the proton and chloride ligands next to each other. The structures of 8 and 9 and their 1H NMR patterns are similar to those of the active catalyst for the ATH of ketones that is postulated to have NH and FeH bonds parallel with the protonic and hydridic hydrogens adjacent. Identical key nuclear Overhauser effect (NOE) correlations in both 8 and the hydrido complex provide further evidence for the postulated structure of the amine iron hydride intermediate. The catalyst system is not active for the transfer hydrogenation of acetophenone, unless greater than 2 equiv of base is added to activate the precatalyst. The addition of base (up to 8 equiv per iron) increases the reaction rate, while a further increase of the base concentration shows a reduction of activity. The loss of activity with less than 2 equiv of base results from a side reaction of the active amido(ene-amido) complexes with 2-propanol to form an inactive neutral bis(amido) iron complex, which was characterized by NMR spectroscopy. Structural evidence for this was provided by the X-ray crystal structure determination of an analogous bis(amino) iron(II) complex, generated from the reaction of the amine(ene-amido) iron complex with methanol in C6D6 in the presence of BF4?. The presence of excess base prevents this side reaction, thereby favoring the reaction which forms the active amine iron hydride species that is in the catalytic cycle. The structure of the transition state for the reaction of the amine hydrido iron catalyst with acetophenone has been successfully modeled using density functional theory (DFT) calculations. The (R) configuration of the product 1-phenylethanol is induced by the position of the phenyl groups on the catalyst and a ??? stabilizing interaction between the aryl ring on the ketone and the ene-amido moiety on the ligand.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".