Palladium on carbon-catalyzed cross-coupling of aryl halides with potassium p-tolyltrifluoroborate in air

Article abstract of DOI:10.1080/00397910802419698

Palladium supported on carbon (Pd/C) has been shown to be an effective catalyst for the cross-coupling of potassium p-tolyltrifluoroborate with a variety of aryl bromides and iodides. Yields ranging from moderate to good were obtained using Pd/C in ethano

Full text of DOI:10.1080/00397910802419698

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Palladium on Carbon-Catalyzed
Cross-Coupling of Aryl
Halides with Potassium p-
Tolyltrifluoroborate in Air
Carl R. LeBlond a , Kaycie M. Butler a , Marc W.
Ferrington a & Matthew A. Browe a
a Chemistry Department , Indiana University of
Pennsylvania , Indiana, Pennsylvania, USA
Published online: 28 Jan 2009.
To cite this article: Carl R. LeBlond , Kaycie M. Butler , Marc W. Ferrington &
Matthew A. Browe (2009) Palladium on Carbon-Catalyzed Cross-Coupling of Aryl
Halides with Potassium p-Tolyltrifluoroborate in Air, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 39:4,
636-640, DOI: 10.1080/00397910802419698
To link to this article: http://dx.doi.org/10.1080/00397910802419698
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Synthetic Communications1, 39: 636–640, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802419698
Palladium on Carbon-Catalyzed Cross-Coupling
of Aryl Halides with Potassium
p-Tolyltrifluoroborate in Air
Carl R. LeBlond, Kaycie M. Butler, Marc W. Ferrington, and
Matthew A. Browe
Chemistry Department, Indiana University of Pennsylvania,
Indiana, Pennsylvania, USA
Abstract: Palladium supported on carbon (Pd=C) has been shown to be an
effective catalyst for the cross-coupling of potassium p-tolyltrifluoroborate with
a variety of aryl bromides and iodides. Yields ranging from moderate to good
were obtained using Pd=C in ethanol=water mixtures with potassium carbonate
as base at 50 ꢀC under an air atmosphere.
Keywords: Cross-coupling reaction, palladium catalysis, potassium p-tolyltri-
fluoroborate, Suzuki–Miyaura reaction
INTRODUCTION
The palladium-catalyzed Suzuki–Miyaura cross-coupling reaction of aryl
halides with arylboronic acids is arguably one of the most important C-C
bond formation reactions.[1] Mainly because of its high functional group
tolerance, the Suzuki–Miyaura reaction is often used in the final steps of
complex convergent syntheses. However, in the pharmaceutical industry
the amount of residual palladium contaminating final products is strictly
limited, and often times extra chromatographic, crystallization, or carbon
treatment steps are required to reduce palladium levels to allowed limits.
EMEA guidelines categorize palladium as a Class 1A metal with an oral
Received May 19, 2008.
Address correspondence to Carl R. LeBlond, 975 Oakland Avenue, Indiana,
PA 15705. E-mail: Carl.leblond@iup.edu
636

Palladium on Carbon-Catalyzed Cross-Coupling
637
exposure limit of 10 ppm. (See www.emea.europa.eu/pdfs/human/swp/
444600.pdf.) One solution is to use a heterogeneous palladium catalysts
(e.g., Pd=C), allowing the Pd and support to be easily filtered from the
product mixture.[2,3] These heterogeneous cross-couplings have the addi-
tional advantage that no ancillary ligands (e.g., phosphine) are required,
further simplifying product isolation and purification. More recent advances
in the Suzuki–Miyaura cross-coupling have focused on using potassium
aryltrifluoroborates as coupling partners.[4] These substrates are easily pre-
pared in a monomeric form from readily available and inexpensive starting
materials and exhibit exceptional stability to air and moisture.
In the course of our studies aimed at elucidating boron to palladium
transmetalation pathways we examined the Pd supported on carbon
catalyzed cross-coupling of aryl bromides with potassium aryltrifluoro-
borates. A number of arylbromides have been shown to cross-couple with
potassium p-tolyltrifluoroborate using K2CO3 as base in ethanol–water
mixtures to provide biaryls in moderate to good yields.
RESULTS AND DISCUSSION
The cross-coupling of bromobenzene with potassium p-tolyltrifluoro-
borate was chosen as a model system. A variety of conditions were
screened to optimize this Pd=C catalyzed cross-coupling reaction.
A range of bases (KOH, K3PO4, K2CO3, Na2CO3) and solvents
(ethanol, methanol, NMP, THF) were examined under anhydrous condi-
tions. In all cases, only a trace yield of biaryl products was observed. The
importance of water in homogeneous catalytic reactions of aryltrifluoro-
borates has been established and appears to be important with Pd=C
catalyzed reactions as well.[5] Once water was added to the reaction mix-
tures, the yields were observed to increase substantially. Thus conditions
similar to those developed for arylboronic acids were found to be optimal
for potassium aryltrifluoroborates.[6]
Furthermore, these cross-couplings can be performed under an air
atmosphere. Provided in Table 1 are examples of the cross-coupling of
1 with a variety of aryl bromides. Aryl bromides with either electron-
releasing or electron donating groups can be efficiently coupled. The
cross-coupling of 4-iodotoluene did not proceed to high conversion,
resulting in low yield (42%). Earlier studies have indicated CsF or KF

638
C. R. LeBlond et al.
Table 1. Cross-coupling of potassium p-tolytrifluoroborate with substituted aryl
halides
Aryl Halide
Product
Yield (%)
65
63
85
65
42
Note. Conditions: ethanol=water (5=1), Pd=C (10 mol%), and K2CO3 (2 eq.) at
50 ꢀC for 24 h.
provide higher yield for cross-coupling aryl iodides; however, these bases
were not used in this study.[7]
EXPERIMENTAL
Typical Procedure for Pd/C Catalyzed Cross-Coupling of Potassium
p-Tolyltrifluoroborate with Aryl Bromides
Under a standard air atmosphere, 0.5 mmol (99 mg) of potassium p-tolyl-
trifluoroborate was combined with 0.5 mmol of aryl bromide, 110 mg of

Palladium on Carbon-Catalyzed Cross-Coupling
639
Pd=C (0.05 mmol Engelhard Escat 172 5% Pd=C dry), and 1 mmol
(138 mg) K2CO3 in a scintillation vial. To this, 3 mL of ethanol=water
(5=1 volume ratio) were added along with a magnetic stirrer bar. The
capped scintillation vial was heated in an oil bath at 50 ꢀC for 24 h under
constant stirring. At the end of the 24 h, the reaction mixture was diluted
with 25 mL of ethyl acetate or dichloromethane and then gravity filtered
to remove the Pd=C catalyst. The filtrate was washed with water
(4.0 mL), then the organic layer was dried over anhydrous sodium sulfate.
Evaporation of the solvent yielded the biphenyl product. Reaction
screening for conversion was performed using gas chromatography–mass
spectrometry. All products are known compounds, and the structures
1
were confirmed by comparison of their H NMR spectra with that of
the known compounds.
CONCLUSIONS
Palladium on carbon has been shown to be an effective catalyst system
for the cross-coupling of aryl bromides and potassium p-tolyltrifluoro-
borate. This cross-coupling can be accomplished using common solvents
(ethanol=water) and base (K2CO3) at 50 ꢀC under an air atmosphere.
REFERENCES
1. (a) Miyaura, N.; Suzuki, A. Palladium-catalyzed cross-coupling reactions of
organoboron compounds. Chem. Rev. 1995, 95, 2457–2483; (b) Suzuki, A.
Recent advances in the cross-coupling reactions of organoboron derivatives
with organic electrophiles, 1995–1998. J. Organomet. Chem. 1999, 576,
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Springer-Verlag: Berlin, 2002; vol. 219, p. 11; (d) Kotha, S.; Lahiri, K.;
Kashinath, D. Recent applications of the Suzuki–Miyaura cross-coupling
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old catalyst for new applications—Its use for the Suzuki–Miyaura reaction.
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geneous catalysis: A critical review. Adv. Synth. Catal. 2006, 348, 609–679.
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C. R. LeBlond et al.
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