A DFT study of NHC-catalyzed reactions between 2-bromo-2-enals and acylhydrazones: mechanisms, and chemo- and stereoselectivities. (25th April 2022)

• Record Type: Journal Article
• Authors: Li, Yan; Geng, Lina; Song, Zhiyi; Zhang, Zhiqiang
• Is Part Of: New journal of chemistry. Volume 46:Number 19(2022)
• Page Start: 9146
• Page End: 9154
• Publication Date: 2022-04-25
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/d2nj01078j
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : The reaction mechanisms and origins of the chemo- and stereoselectivities of NHC-catalyzed [4 + 2] annulation of 2-bromo-2-enals and acylhydrazones. Abstract : The mechanistic features, and chemo- and stereoselectivities of the [4 + 2] cycloaddition between 2-bromo-2-enal and acylhydrazone catalyzed by a chiral N-heterocyclic carbene (NHC) catalyst were derived from density functional theory calculations. In the energetically most favored pathway, the activation of 2-bromo-2-enal by the NHC catalyst occurs first, followed by a proton transfer promoted by HCO3 −, and the resulting Breslow intermediate then undergoes successive debromination and HCO3 − -mediated proton transfer leading to an acylazolium ion, which in turn undergoes γ-deprotonation to yield the vinyl enolate intermediate. The next crucial step is the [4 + 2] cycloaddition and affords the six-membered zwitterionic intermediate, which upon expulsion of NHC provides access to ( R )-δ-lactam. The computational results are in good agreement with the experimental observations. Distortion/interaction and non-covalent interaction (NCI) analyses were conducted to disclose the origins of the stereoselectivity. Furthermore, global reactivity indexes (GRIs) analysis was also performed to investigate the role of NHC.