Leveraging azides in the synthesis of cyclobutenes and the conversion of arenes to pyridines
Abstract/Contents
- Abstract
- Four-membered rings are rapidly becoming sought-after scaffolds in pharmaceuticals due to their rigid structure and well-defined exit vectors. Towards this goal, we developed a method to enantioselectively form cyclobutenes from simple olefins and N-sulfonyl-1,2,3-triazoles. While these triazoles are known to act as diazo precursors via ring-chain tautomerization, we recognized them as vicinal dicarbene equivalents. Thus, alkynes are reacted in [3+2] cycloadditions with azides to form triazoles, which are then reacted with alkenes in a formal [2+2] cycloaddition. A host of enantioenriched cyclobutenes were synthesized, several of which were carried on to assemble the carbon skeletons of several natural products. The ability to selectively delete, insert, or exchange atoms in the core scaffolds of molecules is of fundamental interest to synthetic chemists and could be of great use to medicinal chemists seeking to rapidly modulate the parameters of lead compounds. Though atom deletions and insertions have garnered much interest in the form of ring contractions and expansions, atom exchanges have seen considerably less development. One notable exchange that has eluded chemists is the conversion of benzene to pyridine, which is of interest due to the "necessary nitrogen atom" effect, which describes the enhancement of key pharmacological properties when an arene in a lead compound was replaced with a pyridine. To this end, we found that azides serve as effective nitrene precursors to engage arenes in a C to N atom exchange sequence featuring nitrogen atom insertion and carbon atom deletion.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Patel, Sajan |
|---|---|
| Degree supervisor | Burns, Noah |
| Thesis advisor | Burns, Noah |
| Thesis advisor | Du Bois, Justin |
| Thesis advisor | Xia, Yan, 1980- |
| Degree committee member | Du Bois, Justin |
| Degree committee member | Xia, Yan, 1980- |
| Associated with | Stanford University, Department of Chemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Sajan Patel. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/zt672cb0703 |
Access conditions
- Copyright
- © 2023 by Sajan Patel
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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