Cyclopropanes to Spirocyclic Amine-Boranes: Merging Metal Free C‒H Bond Activation and C‒C Bond Cleavage
Bibliographic record
Abstract
Abstract Spirocyclic motifs often require multi-step syntheses but are of high value to medicinal chemists due to frequent improvements in potency, selectivity, and physicochemical properties over their planar parent drug molecules. Due to the ubiquity of C‒H and C‒C bonds, an extremely challenging, yet incredibly attractive way to achieve molecular diversity and complexity is through the tandem and predictable activation of inert C‒H and C‒C bonds. Tandem activation/cleavage of these bonds in readily accessible cyclopropanes to access complex motifs is challenging and has only been reported using transition metals. The merging of C‒H activation and C‒C bond cleavage strategies for the regioselective transformation of unactivated cyclopropane building blocks into spirocyclic scaffolds in a metal-free manner could be a valuable addition to the organic chemist’s synthetic toolbox. Here, we demonstrate a regioselective C‒H bond activation and subsequent C‒C bond cleavage of unactivated cyclopropane amine-boranes (CABs) to form spirocyclic amine-boranes (SABs) possessing a rare N-spiroatom in an intramolecular manner using 5 mol% of Tf2NH. The one-pot transformation yields SABs that are amenable to downstream modification and provides access to potential pharmacophores that may have applications in drug discovery.
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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) | 0.002 | 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".