Nitrene C–H Bond Insertion Approach to Carbazolones and Indolones. Formal Total Synthesis of (–)-Methyl N-Decarbomethoxychanofruticosinate, (–)-Aspidospermidine and (+)-Kopsihainanine A
Bibliographic record
Abstract
A new, modular platform for access to 1,2,3,9-tetrahydro-4H-carbazol-4-ones (H4-carbazolones) and 3,4-dihydrocyclopenta[b]indol-1(2H)-ones (H2-indolones) is disclosed from readily accessed 2-arylcycloalkane-1,3-diones (6- and 5-membered). These precursors were prepared through a Cu-catalyzed arylation of 1,3-cyclohexanediones with aryl iodides or via a ring-expansion of aryl succinoin derivatives. Activation of a single carbonyl group in the diones, a highly regioselective reaction with unsymmetrical 2-arylcyclohexane-1,3-diones, and subsequent azidation gave 3-azido-2-aryl-cycloalk-2-en-1-ones. The regioselectivity was computationally assessed. Finally, a Rh-catalyzed nitrene/nitrenoid insertion into the ortho-C–H bond of the aryl moiety, gave the H4-carbazolones and H2-indolones, products that are of high synthetic value. One carbazolone synthesized was elaborated to a key intermediate for the formal total synthesis of N-decarbomethoxychanofruticosinate, (–)-aspidospermidine, (+)-kopsihainanine A. With 2-aryl-1,3-cycloheptanedione, prepared from cyclohexanone and benzaldehyde, the azidation reaction was accomplished in a facile manner. However, the Rh-catalyzed reaction led to some unusual observations, with an azirine as a major product. DFT computations were performed in order to understand the differences in reactivities of the 5- and 6-membered -azido enones in comparison to the 7-membered analogue.
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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".