Mechanistic Investigation of the Ruthenium–N-Heterocyclic-Carbene-Catalyzed Amidation of Alcohols and Amines

Ilya Makarov, Peter Fristrup, Robert Madsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The mechanism of the ruthenium–N-heterocyclic-carbene-catalyzed formation of amides from alcohols and
amines was investigated by experimental techniques (Hammett studies, kinetic isotope effects) and by a computational study by using dispersion-corrected density functional theory (DFT/
M06). The Hammett study indicated that a small positive charge builds-up at the benzylic position in the transition
state of the turnover-limiting step. The kinetic isotope effect was determined to be 2.29ACHTUNGTRENUNG(!0.15), which suggests that the breakage of the C"H bond is not the rate-limiting step, but that it is one of several slow steps in the catalytic cycle. Rapid scrambling of hydrogen and deuterium at the a position of the alcohol was observed with
deuterium-labeled substrates, which implies that the catalytically active species is a ruthenium dihydride. The experimental results were supported by the characterization of a plausible catalytic cycle by using DFT/M06. Both cisdihydride and trans-dihydride intermediates were considered, but when the theoretical turnover frequencies
(TOFs) were derived directly from the calculated DFT/M06 energies, we found that only the trans-dihydride
pathway was in agreement with the experimentally determined TOFs.
Original languageEnglish
JournalChemistry: A European Journal
Volume18
Issue number49
Pages (from-to)15683–15692
Number of pages11
ISSN0947-6539
DOIs
Publication statusPublished - 2012

Keywords

  • Amides
  • Density functional calculations
  • Isotope effect
  • Reaction mechanisms
  • Ruthenium

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