Mechanistic insights into the origin of substituent-directed product Z–E selectivity for gold-catalyzed [4+1]-annulations of 1,4-diyn-3-ols with isoxazoles: A DFT study

Kaifeng Wang, Yuxia Liu, Qiao Wu, Lingjun Liu, Yulin Li, Tony D. James, Guang Chen, Siwei Bi

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Density functional theory (DFT) calculations were used to explore the Au(I)-catalyzed selective [4 + 1] annulations of cyclopropyl- and H-substituted 1,4-diyn-3-ols with isoxazole. The results indicated that after the N-nucleophilic attack of isoxazole, instead of obtaining the α–hydroxy gold carbene intermediate proposed experimentally, a concerted three-step forward product by isoxazole O[sbnd]N cleavage, 1,2-phenylalkyne shift and the hydroxyl H shift was identified as the key intermediate, for the reaction proceeding either via an Au-assisted C[dbnd]C double-bond rotation to produce the Z-isomeric enone or via two different Au-assisted C[dbnd]C rotations to furnish the E-configured enone depending on the substituents used. Further theoretical investigations indicated that the chemoselective step is the nucleophilic cyclization but not the C[dbnd]C double-bond rotation. The chemoselective preference for the Z-configured product using the cyclopropyl substitutent was attributed to two factors: i) the additional O[tbnd]H[sbnd]N hydrogen bonding interaction stabilizes the rate-determining cyclization TS leading to the Z-product, and ii) further Z-E product-isomerization is blocked due to significant structural deformation being involved. In contrast, using the H substituent results in a reversed chemoselectivity with exclusive formation of the E-configured enone, which is closely related to the smaller entropy effects involved.

Original languageEnglish
Article number110647
Pages (from-to)1-9
Number of pages9
JournalMolecular Catalysis
Early online date4 Oct 2019
Publication statusPublished - 1 Jan 2020


  • 1,4-diyn-3-ols
  • Au(I)-catalysis
  • DFT
  • Selectivity
  • [4+1] annulation

ASJC Scopus subject areas

  • Catalysis
  • Process Chemistry and Technology
  • Physical and Theoretical Chemistry

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