SYNthesis OF CYCLOHEPTA[DE]NAPHTHALENES VIA NICHOLAS REACTIONS. THE FIRST TOTAL SYNthesis OF MICROSTEGIOL, A REARRANGED ABIETANE
Bibliographic record
Abstract
The Nicholas reaction is one of the important organometallic transformations in organic chemistry. The facile synthesis of its precursors, complexation of alkyne with the Co2(CO)6 unit, and straightforward demetallation after the completion of the reaction has made this reaction a tool of first choice for the synthetic chemist. Due to its versatile applications in organic syntheses, Nicholas reaction chemistry was considered to be well suited to the preparation of a cyclohepta[de]naphthalenes. Natural products such as microstegiol, oxomicrostegiol, salvibretol and oxosalvibretol are important examples of compounds possessing cyclohepta[de]naphthalene carbon skeleton, and to date, no synthesis of any of these compounds appears in the literature. In a model study for the synthesis of cyclohepta[de]naphthalenes, the reactivity pattern of propargyldicobalt cations with derivatives of naphthalene-2,7-diol, such as 2,7-dimethoxy- and dibenzyloxynaphthalene, were investigated under conventional Nicholas reaction conditions. Predominantly C-1 monocondensation and 1,6-dicondensation reaction products were formed, while in selected instances C-3 monocondensation or 1,8-dicondensation products were favoured. The mono- and dicondensation Nicholas reaction products were employed to synthesize cyclohepta[de]naphthalenes via ring closing metathesis and Friedel Crafts reactions. The application of Nicholas reaction chemistry of a selectively protected 2,7-naphthalenediol in the synthesis of the natural product (▒)-microstegiol was investigated. The differentially protected 2,7-naphthalenediol allowed the selective replacement of one of oxygen functions by a methyl group, and facile deprotection of other oxygen function allowed tautomerization to a cyclohepta[de]naphthalene-1-one upon seven membered ring closure in most cases. Ultimately the total synthesis of ()-microstegiol was accomplished in 15 steps with 7.2% overall yield from 2,7-dihydroxynaphthalene.
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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) | 0.004 | 0.002 |
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".