Active, selective, and stable single-component precatalysts for asymmetric allylic alkylation
Bibliographic record
Abstract
The stereoselective construction of new carbon-element bonds is a crucial aspect of organic synthesis. Among the many strategies developed to date, palladium-catalysed asymmetric allylic alkylation is commonly used to access chiral molecules in natural product and active pharmaceutical ingredient synthesis. The use of modular Trost-type ligands and phosphinooxazoline (PHOX) ligands results in generally high stereoselectivity for a wide range of transformations. However, these reactions nearly always require relatively high catalyst loadings (5-10 mol%), reaction-specific catalyst preactivation protocols, and excess chiral ligand to ensure high yield and selectivity. Here we report the isolation and catalytic evaluation of a series of chiral palladium(0) single-component precatalysts that are active for a variety of asymmetric allylic alkylation reactions. The four Trost-type precatalysts in this work are the first characterized examples of stable, isolable Pd complexes with the diphosphines coordinated in the desired κ2-P,P fashion. All of the palladium(0) complexes are stable for >12 months when stored under nitrogen, and can be handled as solids and even in solution under air for hours without decomposition. A catalytic evaluation of these single-component precatalysts across 9 distinct asymmetric allylic alkylation reactions reveals excellent performance in terms of reactivity, selectivity, practicality, and minimizing palladium and chiral ligand loading. This enables both small-scale multivariate screening studies and preparative scale synthesis of key chiral building blocks, exemplified with the unprecedented enantioselective allylation of hydantoins. The optimized reaction achieves high yield and enantioselectivity with only 0.2 mol% of catalyst (turnover number of 465). These precatalysts will enable development of more efficient and robust asymmetric allylic alkylation reactions toward complex target molecules.
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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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".