A General Approach for Strained Ring Functionalization via Nucleophilic Catalysis
Bibliographic record
Abstract
High Resolution Image Download MS PowerPoint Slide Nucleophilic addition to strained rings offers an efficient route to small aliphatic rings, which serve as valuable bioisosteres in drug development. However, these reactions often require external stoichiometric bases, additives, or strong nucleophiles, limiting their practicality, compatibility, and scope. Moreover, achieving diastereocontrol in these reactions remains challenging, and direct addition of sp 3 C–H bonds continues to be difficult owing to their lack of electron lone pairs and weak acidity. Here, we present, for the first time, a nucleophilic catalysis strategy that addresses these challenges, enabling not only the direct and diastereoselective addition of a wide range of sp 3 C–H bonds, but also diverse heteroatom-based nucleophiles, including carboxylic acids, amides, phosphine oxides, and thiols, to strained rings without the need for external bases or additives. Mechanistic studies suggest the involvement of a covalent intermediate, generated through the nucleophilic addition of the catalyst to the strained ring substrate.
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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) | 0.001 | 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 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".