Asymmetric Csp <sup>3</sup> –Csp <sup>3</sup> Bond Formation via Ni-Catalyzed Regio- and Enantioselective Hydroalkylation of Linear 1,3-Diene through Carbonyl Umpolung
Bibliographic record
Abstract
Asymmetric Csp 3 –Csp 3 bond formation has been a grand pursuit in synthetic chemistry. The regioselective and enantioselective hydroalkylation of 1,3-diene has emerged as an appealing approach for constructing chiral allylic Csp 3 –Csp 3 bonds. However, this method is presently confined to the use of stabilized Csp 3 nucleophilic substrates. Herein, we present a nickel-catalyzed asymmetric hydroalkylation of 1,3-dienes with simple unstabilized alkyl carbanion enabled by naturally abundant carbonyls’ umpolung under mild reaction conditions. A range of simple alkylated chiral allylic compounds were generated in good to high yields (up to 96%), with an enantiomeric ratio (er) of up to 98:2 to form the Csp 3 –Csp 3 bond. The protocol is applicable to heterocycles, polyenes, and unsaturated hydrazones as well as late-stage functionalization of various complex pharmaceuticals. Density functional theory calculations elucidated the mechanism and enantioselectivity of the reaction. An enantiocontrol model is also proposed, emphasizing the crucial role of a chiral NHC ligand in facilitating this asymmetric reaction, as revealed by the two-layer two-dimensional (2D) contour maps.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.007 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.002 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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".