Gold(I)-catalyzed divergent and diastereoselective synthesis of azepines by ammoniumation/ring-expansion reactions
| Autor: | Patrick Pale, Romain Pertschi, Aurélien Blanc, Jean-Marc Weibel, Nicolas Kern, Solène Miaskiewicz |
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| Přispěvatelé: | Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC) |
| Rok vydání: | 2021 |
| Předmět: |
Ammoniumation
Bicyclic molecule [CHIM.ORGA]Chemical Sciences/Organic chemistry 010405 organic chemistry Chemistry Azetidine Gold(I) Azepines [CHIM.CATA]Chemical Sciences/Catalysis 010402 general chemistry Ring (chemistry) 01 natural sciences Combinatorial chemistry Catalysis 0104 chemical sciences Cyclobutane chemistry.chemical_compound Nucleophile Azetidines General Earth and Planetary Sciences Azepine Pharmacophore Ring Expansion General Environmental Science |
| Zdroj: | Chem Catalysis Chem Catalysis, Elsevier, 2021, 1 (1), pp.129-145. ⟨10.1016/j.checat.2021.02.004⟩ |
| ISSN: | 2667-1093 |
| DOI: | 10.1016/j.checat.2021.02.004 |
| Popis: | Summary Gold(I) catalysts enable the chemoselective addition of tailor-made N-sulfonylated azetidine derivatives onto alkynes, affording bicyclic vinyl-ammonium gold intermediates. Intramolecularly intercepted by an adequately positioned nucleophilic carbonate or ester function, these ammoniums efficiently lead to ring-expanded azepine products, which are important pharmacophore fragments. Depending on the substitution pattern of the starting material, divergent deauration pathways occur, stereoselectively producing monomeric or original dimeric nitrogenated seven-membered rings in good to excellent yields, such as cis-tetrahydroazepin-4,5-diol carbonate, (E)-alkylidene tetrahydroazepin-4-yl ester, and cis-bis(azepinyl)cyclobutane derivatives. One of the synthetic methods was extended to the formation of dihydrobenzazepines of high pharmaceutical value. A mechanistic study including kinetics and labeling experiments allowed us to fully understand the origin of the high chemo- and diastereoselectivity of these rearrangements. Overall, this work demonstrates the underlying synthetic potential of the ammoniumation catalyzed by gold for the future development of reaction cascades and preparation of bioactive compounds. |
| Databáze: | OpenAIRE |
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