A Convenient New Route to Piperidines, Pyrrolizidines, Indolizidines, and Quinolizidines by Cyclization of Acetylenic Sulfones with β- and γ-Chloroamines. Enantioselective Total Synthesis of Indolizidines<b>(</b><b>−</b><b>)-167B</b>,<b>(</b><b>−</b><b>)-209D</b>,<b>(</b><b>−</b><b>)-209B</b>, and<b>(</b><b>−</b><b>)-207A</b>
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
The methyl esters of (L)-phenylalanine and (L)-methionine underwent conjugate additions via their free amino groups to 1-(p-toluenesulfonyl)hexyne, followed by intramolecular acylation of the corresponding enamide anions and tautomerization to afford 2-benzyl-5-n-butyl-3-hydroxy-4-(p-toluenesulfonyl)pyrrole and 5-n-butyl-3-hydroxy-2-(2-methylthioethyl)-4-(p-toluenesulfonyl)pyr role, respectively. The conjugate additions of a series of acyclic and cyclic secondary beta- and gamma-chloroamines to acetylenic sulfones proceeded similarly under mild conditions. The resulting adducts were deprotonated with LDA in THF at -78 degrees C, and the resulting sulfone-stabilized carbanions underwent intramolecular alkylation to afford cyclic enamine sulfones. Thus, acyclic gamma-chloroalkyl-benzylamines afforded the corresponding 2- or 2,6-disubstituted piperidines, while 2-(chloromethyl)pyrrolidines, 2-(2-chloroethyl)pyrrolidines, 2-(chloromethyl)piperidines, and 2-(2-chloroethyl)piperidines produced the corresponding 3-substituted pyrrolizidines, 5- or 3-substituted indolizidines, and 4-substituted quinolizidines, respectively. 8-Methyl-5-substituted indolizidines were also prepared from the appropriate methyl-substituted chloroamine precursor. Enantioselective syntheses were achieved by employing chiral chloroamines derived from amino acids or other enantiopure precursors. Further transformations of several of the products provided concise syntheses of four dendrobatid alkaloids. Thus, reduction of (8aS)-5-n-propyl-6-(p-toluenesulfonyl)-delta5,6-indolizidine with sodium cyanoborohydride in trifluoroacetic acid, followed by reductive desulfonylation, afforded (-)-indolizidine 167B. The corresponding 5-n-hexyl derivative similarly produced (-)-indolizidine 209D, while (-)-(8R, 8aS)-8-methyl-5-n-pentyl-6-(p-toluenesulfonyl)-delta5,6-indo lizidine furnished (-)-indolizidine 209B. Finally, the similar reduction and debenzylation of (-)-(8R,8aS)-5-(2-benzyloxyethyl)-8-methyl-6-(p-toluenesulfo nyl)-delta5,6-indolizidine produced the corresponding 5-hydroxyethyl indolizidine. This was subjected to chlorination of the alcohol group with thionyl chloride and substitution with a higher order allyl cuprate reagent to afford (-)-indolizidine 207A.
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.
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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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