Mechanism of the Ullmann Biaryl Ether Synthesis Catalyzed by Complexes of Anionic Ligands: Evidence for the Reaction of Iodoarenes with Ligated Anionic CuI Intermediates

Ramesh Giri, Andrew Brusoe, Konstantin Troshin, Justin Y. Wang, Marc Font, John F. Hartwig

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A series of experimental studies, along with DFT calculations, are reported that provide a detailed view into the mechanism of Ullmann coupling of phenols with aryl halides in the presence of catalysts generated from Cu(I) and bidentate, anionic ligands. These studies encompass catalysts containing anionic ligands formed by deprotonation of 8-hydroxyquinoline, 2-pyridylmethyl tert-butyl ketone, and 2,2,6,6-tetramethylheptane-3,5-dione. Three-coordinate, heteroleptic species [Cu(LX)OAr]- were shown by experiment and DFT calculations to be the most stable complexes in catalytic systems containing 8-hydroxyquinoline or 2-pyridylmethyl tert-butyl ketone and to be generated reversibly in the system containing 2,2,6,6-tetramethylheptane-3,5-dione. These heteroleptic complexes were characterized by a combination of 19F NMR, 1H NMR, and UV-vis spectroscopy, as well as ESI-MS. The heteroleptic complexes generated in situ react with iodoarenes to form biaryl ethers in high yields without evidence for an aryl radical intermediate. Measurements of 13C/12C isotope effects showed that oxidative addition of the iodoarene occurs irreversibly. This information, in combination with the kinetic data, shows that oxidative addition occurs to the [Cu(LX)OAr]- complexes and is turnover-limiting. A Hammett analysis of the effect of phenoxide electronic properties on the rate of the reaction of [Cu(LX)OAr]- with iodotoluene also is consistent with oxidative addition of the iodoarene to an anionic phenoxide complex. Calculations by DFT suggest that this oxidative addition is followed by dissociation of I- and reductive elimination of the biaryl ether from the resulting neutral Cu(III) complex.

Original languageEnglish (US)
Pages (from-to)793-806
Number of pages14
JournalJournal of the American Chemical Society
Volume140
Issue number2
DOIs
StatePublished - Jan 17 2018

Fingerprint

Oxyquinoline
Ketones
Discrete Fourier transforms
Ether
Ethers
Ligands
Phenols
Nuclear magnetic resonance
Isotopes
Spectrum Analysis
Deprotonation
Catalysts
Ultraviolet spectroscopy
Electronic properties
Kinetics
dipivaloylmethane
Experiments
Proton Magnetic Resonance Spectroscopy

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

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title = "Mechanism of the Ullmann Biaryl Ether Synthesis Catalyzed by Complexes of Anionic Ligands: Evidence for the Reaction of Iodoarenes with Ligated Anionic CuI Intermediates",
abstract = "A series of experimental studies, along with DFT calculations, are reported that provide a detailed view into the mechanism of Ullmann coupling of phenols with aryl halides in the presence of catalysts generated from Cu(I) and bidentate, anionic ligands. These studies encompass catalysts containing anionic ligands formed by deprotonation of 8-hydroxyquinoline, 2-pyridylmethyl tert-butyl ketone, and 2,2,6,6-tetramethylheptane-3,5-dione. Three-coordinate, heteroleptic species [Cu(LX)OAr]- were shown by experiment and DFT calculations to be the most stable complexes in catalytic systems containing 8-hydroxyquinoline or 2-pyridylmethyl tert-butyl ketone and to be generated reversibly in the system containing 2,2,6,6-tetramethylheptane-3,5-dione. These heteroleptic complexes were characterized by a combination of 19F NMR, 1H NMR, and UV-vis spectroscopy, as well as ESI-MS. The heteroleptic complexes generated in situ react with iodoarenes to form biaryl ethers in high yields without evidence for an aryl radical intermediate. Measurements of 13C/12C isotope effects showed that oxidative addition of the iodoarene occurs irreversibly. This information, in combination with the kinetic data, shows that oxidative addition occurs to the [Cu(LX)OAr]- complexes and is turnover-limiting. A Hammett analysis of the effect of phenoxide electronic properties on the rate of the reaction of [Cu(LX)OAr]- with iodotoluene also is consistent with oxidative addition of the iodoarene to an anionic phenoxide complex. Calculations by DFT suggest that this oxidative addition is followed by dissociation of I- and reductive elimination of the biaryl ether from the resulting neutral Cu(III) complex.",
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Mechanism of the Ullmann Biaryl Ether Synthesis Catalyzed by Complexes of Anionic Ligands : Evidence for the Reaction of Iodoarenes with Ligated Anionic CuI Intermediates. / Giri, Ramesh; Brusoe, Andrew; Troshin, Konstantin; Wang, Justin Y.; Font, Marc; Hartwig, John F.

In: Journal of the American Chemical Society, Vol. 140, No. 2, 17.01.2018, p. 793-806.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mechanism of the Ullmann Biaryl Ether Synthesis Catalyzed by Complexes of Anionic Ligands

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AU - Giri, Ramesh

AU - Brusoe, Andrew

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AU - Hartwig, John F.

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