Stereo- and Regioselective Synthesis of Polysubstituted Chiral 1,4-Oxazepanes
Bibliographic record
Abstract
The number of cyclic molecular scaffolds available to medicinal chemists remains limited, and simple structures such as oxazepanes are still made using multistep procedures, including a number of protection/deprotection steps and purifications. We report herein an expedient and efficient synthesis of chiral polysubstituted oxazepanes. The developed method relies on a regio- and stereoselective 7-endo cyclization through haloetherification. Mechanistic studies using a combination of computations and experiments confirmed the expected role of the asymmetry of the chiral bromonium intermediate on the haloetherification regioselectivity. Computations also suggested that the bromonium intermediate is formed with no transition state; hence, the stereoselectivity is controlled primarily by the conformation of the substrate. Applied to a set of 16 substrates, tetra- and pentasubstituted oxazepanes were prepared with good yields and moderate to excellent regio- and stereoselectivities.
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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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".