2,5-Dihydro-1,3,4-oxadiazoles and Bis(heteroatom-substituted)carbenes.
Bibliographic record
Abstract
2,5-Dihydro-1,3,4-oxadiazoles with heteroatom substituents at C-2 (also known as corresponding Delta(3)-1,3,4-oxadiazolines) are very useful materials for the thermal generation of acetoxy(alkoxy)-, dialkoxy-, alkoxy(aryloxy)-, diaryloxy-, alkoxy(alkylthio)-, bis(alkylthio)- and alkoxy(amino)-carbenes. Such carbenes are relatively nucleophilic and react with a variety of electrophilic functional groups. This Account reviews our work to prepare 2,5-dihydro-1,3,4-oxadiazoles and apply them to the synthesis of other target molecules. Carbenes bearing alkoxy substituents at the carbene carbon can be looked upon as acetals of carbon monoxide. Their reactions with electron-deficient alkenes or alkynes can afford acetals of cyclopropanones or cyclopropenones. Although such products may be formed by concerted cycloaddition, initial formation of one bond to produce zwitterions is likely in some cases. In addition, the reactions of these molecules with carbonyl compounds could involve acetals of alpha-lactones as intermediates. Although we have isolated some acetals of cyclopropanones, we have not isolated the other intermediates. However, some of the products we observe probably resulted from these intermediates. For example, dimethoxycarbene reacts with maleic anhydrides to generate six-membered rings by apparent carbonyl addition followed by an acyloxy group transfer. Similarly, dimethoxycarbene reacts with thiocarbonyl compounds, such as xanthates, by apparent carbonyl addition and transfer of the alkylthiyl group to the erstwhile carbene carbon. Reaction of ROC:(OR)' with an alcohol R''OH or a phenol should generate chiral (racemic) orthoformates. Similarly, reaction of alkoxy(alkylthiyl) carbenes with alcohols could generate chiral (racemic) dialkyl thiyl orthoformates. 2,5-Dihydro-1,3,4-oxadiazoles are particularly useful for synthetic applications because they are easily prepared and reasonably stable, thermal sources of bis(heteroatom)carbenes. Such carbenes react with a variety of electrophilic functional groups, often with rearrangement of initial products. Those products, many of them new, could be used as starting materials toward other synthetic targets. Isolation of products from the reaction is relatively simple because the coproducts of thermolysis of the oxadiazoles are primarily N(2) and a ketone, such as acetone. Thus, 2,5-dihydro-1,3,4-oxadiazoles should be part of every synthesis chemist's toolbox.
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 | 0.000 | 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".