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

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 substitution pattern starting material, divergent deauration pathways occur, stereoselectively producing monomeric original dimeric nitrogenated seven-membered rings in good excellent yields, such as cis-tetrahydroazepin-4,5-diol carbonate, (E)-alkylidene tetrahydroazepin-4-yl ester, and cis-bis(azepinyl)cyclobutane derivatives. One synthetic methods was extended formation dihydrobenzazepines high pharmaceutical value. A mechanistic study including kinetics labeling experiments allowed us fully understand origin chemo- diastereoselectivity rearrangements. Overall, this work demonstrates underlying potential ammoniumation catalyzed for future development reaction cascades preparation bioactive compounds.