Four-Component Reactions of [n.1.1]Propellanes (n = 1 or 3) Triggered by Electrophilic Activation
Bibliographic record
Abstract
Exposure of [n.1.1]propellanes (n = 1 or 3) to acidic nucleophiles typically gives decomposition products due to the instability of bicyclo[n.1.1]alkyl carbocations. This instability makes the synthesis of functionalized bicyclo[n.1.1]alkanes from protic nucleophiles by electrophilic activation of [n.1.1]propellanes particularly challenging. In stark contrast, we now report a four-component reaction between [n.1.1]propellanes (n = 1 or 3), N-iodosuccinimide, nine cyclic ethers and ten classes of protic nucleophiles, that maintains the structural integrity of the bicyclo[n.1.1]alkyl motif in the products. Crucially, this reaction gives one-step access to 4-hydroxy thalidomide derivatives that enabled us to demonstrate in a whole cell assay that a n-butoxy-bicyclo[1.1.1]pentyl linker is tolerated by cereblon, a component of E3 ligase, which is an important target of proteolysis-targeting chimeras. Experimental rate law and theoretical calculations with a model nucleophile suggest that the four-component reaction relies on the attack by THF of a halogen bond complex formed between N-iodosuccinimide and the propellane, which is assisted by hydrogen bonding of the protic nucleophiles to the succinimide component.
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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 | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 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".