Nitrene C–H Bond Insertion Approach to Carbazolones and Indolones. Formal Total Synthesis of (–)-Methyl N-Decarbomethoxychanofruticosinate, (–)-Aspidospermidine and (+)-Kopsihainanine A
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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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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it