Role of base assisted proton transfer in N-heterocyclic carbene-catalyzed intermolecular Stetter reaction

Manjaly J. Ajitha, Cherumuttathu H. Suresh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The mechanism of the NHC-catalyzed intermolecular Stetter reaction between benzaldehyde and cyclopropene has been investigated using the PCM-M062X/6-311++G(3df,2p)//M062X/6-31+G(d,p) level of DFT. Compared to the direct reaction, a substantial reduction in the activation free energy by 10.6-14.4 kcal/mol is observed when the reaction is performed in the presence of water, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), and 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU). The bases promote the proton transfer step of the reaction to yield the Breslow intermediate. An early concerted transition state has been located for the stereocontrolling C-C bond formation step (ΔG# = 26.6 kcal/mol) which is used to explain the diastereomeric ratio observed in the experiment.

Original languageEnglish (US)
Pages (from-to)7144-7146
Number of pages3
JournalTetrahedron Letters
Volume54
Issue number52
DOIs
StatePublished - Dec 25 2013

Keywords

  • Breslow intermediate
  • Density functional theory
  • N-Heterocyclic carbene
  • Organocatalysis
  • Stetter reaction

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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