Chem Catalysis [LASYROC]

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.

Graphical Abstract:

Reference :

Romain Pertschi, Solène Miaskiewicz, Nicolas Kern, Jean-Marc Weibel, Patrick Pale, Aurélien Blanc

Gold(I)-catalyzed divergent and diastereoselective synthesis of azepines by ammoniumation/ring-expansion reactions

Chem Catalysis, Volume 1, Issue 1, 17 June 2021, Pages 129-145 - DOI : https://doi.org/10.1016/j.checat.2021.02.004, Comment: https://www.sciencedirect.com/science/article/pii/S2667109321000166?via%3Dihub

Contacts :

A. Blanc and P. Pale, équipe LASYROC, Institut de Chimie (UMR 7177).