Mechanistic Studies on the Gold-Catalyzed Intramolecular Hydroalkylation of Ynamides to Indenes
Julien Annibaletto1, Clément Jacob1,2, Pierre Thilmany1
1Laboratoire de Chimie Organique, Service de Chimie et PhysicoChimie Organiques, Université libre de Bruxelles (ULB), Avenue F. D. Roosevelt 50, CP160/06, Brussels 1050, Belgium.
Abstract:
An in-depth experimental and computational study to rationalize the mechanism underlying the gold-catalyzed intramolecular hydroalkylation of ynamides to indenes is reported. Evaluating the reactivity of a set of deuterated ynamides and gold complexes allowed to get valuable insights into the mechanism of this reaction, while DFT calculations allowed to determine a plausible reaction pathway for this unprecedented transformation. This pathway involves the activation of the ynamide followed by a [1,5]-hydride shift from the highly reactive, in situ generated keteniminium ion, and a subsequent cyclization before deprotonation followed by a final protodeauration. According to DFT calculations, the initial [1,5]-hydride shift was identified as the rate-determining step of the reaction mechanism. Additionally, computational studies allowed to rationalize the differences in reactivity of various ynamides and the pivotal role of gold complexes in the catalysis of this reaction.
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