Annibaletto Julien, Jacob Clément, Thilmany Pierre, Loison Anaïs, Escorihuela Jorge, Evano Gwilherm
Laboratoire de Chimie Organique, Service de Chimie et PhysicoChimie Organiques, Université libre de Bruxelles (ULB), Avenue F. D. Roosevelt 50, CP160/06, Brussels 1050, Belgium.
Organic Synthesis Division, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, Antwerp 2020, Belgium.
ACS Omega. 2024 Dec 17;9(52):51690-51700. doi: 10.1021/acsomega.4c09973. eCollection 2024 Dec 31.
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.
报道了一项深入的实验和计算研究，以阐明金催化的烯酰胺分子内氢烷基化反应生成茚的潜在机理。评估一组氘代烯酰胺和金配合物的反应活性，有助于深入了解该反应的机理，而密度泛函理论（DFT）计算则能够确定这一前所未有的转化反应的合理反应途径。该途径包括烯酰胺的活化，随后是从高反应性的原位生成的烯酮亚胺离子进行的[1,5]-氢迁移，以及在去质子化之前的后续环化，最后是质子脱金反应。根据DFT计算，最初的[1,5]-氢迁移被确定为反应机理的速率决定步骤。此外，计算研究有助于解释各种烯酰胺反应活性的差异以及金配合物在该反应催化中的关键作用。
