Diastereoselective Synthesis of 1-Aza-spiro[5.5]undecane Skeleton
Bibliographic record
Abstract
The synthesis of various bicyclic enamines (5), bearing a side chain with a multiple C-C bond or a furan ring, was performed from racemic pipecolic acid through sulfone (1c).Cyclization of these derivatives (5), via the corresponding in situ generated N-acyliminium ions, was studied in various acidic conditions to afford, in some cases, spiro intermediates (2) which possess the backbone of the histrionicotoxin family of alkaloids.We have recently demonstrated that bicyclic N-acyliminium ion (A) (Scheme 1) reacted with various πtype nucleophiles to exclusively afford trans-disubstituted 2,6-piperidines. 1 This methodology was successfully applied to the total synthesis of tricyclic alkaloid (-)-porantheridine. 2 Based on these results, we next envisioned the stereoselective preparation of trisubstituted piperidines (2) containing a spirocyclohexane moiety, via an intramolecular nucleophilic addition on a bicyclic iminium ion of type (B) (Scheme 1).Herein, we wish to report some promising preliminary results concerning a stereoselective approach towards the 1-aza-spiro[5.5]undecaneskeleton.Such azaspirocyclic substructures constitute actually the main core of histrionicotoxins (HTX), a family of alkaloids isolated from the skin secretions of the Colombian frog Dendrobates histrionicus. 3 summarized in Scheme 2, our strategy relies on an intramolecular nucleophilic addition of an unsaturated C-C bond on a tetrasubstituted bicyclic iminium ion.The generation of the required iminium ion was envisioned from derivatives (1), via tetrasubstituted intermediates of type (C).The R group of compound (1) must fulfill two requirements, i.e. to be nucleofugal enough to generate the iminium ion, and to be an efficient electron withdrawing group to allow the introduction of the alkyl chain.To this end,
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".