Suzuki-Miyaura coupling of aryl tosylates and mesylates in water

Article abstract of DOI:10.1002/ejoc.201000251

The palladium complex (0.5 mol-%) of a water-soluble sulfonated fluorenylphosphane (cataCXium Fsulf) enables the facile Suzuki-Miyaura coupling of various (heterocyclic) aryl tosylates and aryl mesylate with various (heterocyclic) boronic acids in excellent yields (> 95%) using water as the reaction solvent.

Full text of DOI:10.1002/ejoc.201000251

RETRACTION
DOI: 10.1002/ejoc.201001176
Retraction: Suzuki–Miyaura Coupling of Aryl Tosylates and Mesylates in
Water
Jan Pschierer[a] and Herbert Plenio*[a]
Keywords: C-C coupling / Palladium / Water / Suzuki–Miyaura reactions / Phosphanes
The following article from the European Journal of Organic Chemis-
try, “Suzuki–Miyaura Coupling of Aryl Tosylates and Mesylates in
Water”, published online on April 15, 2010 in Wiley Online Library
(www.onlinelibrary.wiley.com, doi: 10.1002/ejoc.201000251) and in
print (Eur. J. Org. Chem. 2010, 2934–2937), has been retracted by
agreement between the corresponding author, the journal Editor,
Dr. Haymo Ross, and Wiley-VCH. The retraction has been agreed
1
because several H and 13C NMR spectroscopic data listed in the
manuscript are incorrect, and the original mass spectra cannot be
located. Attempts to repeat the synthesis of several representative
products under the conditions reported in this manuscript have
failed.
Received: August 20, 2010
Published Online: September 2, 2010
[a] Organometallic Chemistry, Chemistry, TU Darmstadt,
Petersenstr. 18, 64287 Darmstadt, Germany
E-mail: Plenio@tu-darmstadt.de
View this journal online at
wileyonlinelibrary.com
 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

FULL PAPER
DOI: 10.1002/ejoc.201000251
Suzuki–Miyaura Coupling of Aryl Tosylates and Mesylates in Water
Jan Pschierer[a] and Herbert Plenio*[a]
Keywords: C-C coupling / Palladium / Water / Suzuki–Miyaura reactions / Phosphanes
The palladium complex (0.5 mol-%) of a water-soluble sulfon-
ated fluorenylphosphane (cataCXium Fsulf) enables the
facile Suzuki–Miyaura coupling of various (heterocyclic) aryl
tosylates and aryl mesylate with various (heterocyclic) bor-
onic acids in excellent yields (Ͼ 95%) using water as the
reaction solvent.
Up until now our work was focused on cross coupling
reactions utilizing aryl chlorides as the substrates.[7–8] The
excellent performance of catalysts based on palladium com-
plexes of sulfonated and water soluble fluorenylphosphanes,
motivated us to test the activity of such complexes in reac-
tions utilizing much less reactive aryl tosylates and the ra-
rely utilized mesylates in Suzuki–Miyaura coupling.[9]
These substrates, derived from the respective phenols, are
much cheaper than triflates or nonaflates. Recently signifi-
cant progress in the Suzuki transformations of tosylates/
mesylate substrates was reported by Kwong et al. utilizing
tert-butyl alcohol and between 1–2 mol-% of Pd/indolyl-
phosphane complex for aryl mesylate coupling[10] and be-
tween 0.5–2 mol-% for tosylates.[11] More recently Buch-
wald et al. reported Suzuki reactions with the same pseu-
dohalide substrates utilizing ca. 2 mol-% of [Pd] and two
equivalents of Brettphos in amyl alcohol solvent.[12] We
would like to report here on the Suzuki–Miyaura reactions
in water utilizing aryl tosylate and mesylate substrates.
Introduction
Traditionally for organic transformations a large number
of different organic solvents are used as the reaction me-
dium. However, the use of volatile organics also has some
drawbacks, as these liquids tend to be toxic and flammable.
The search for alternative solvents or solvent mixtures with
special properties led to the development of numerous ad-
vanced solvent concepts involving ionic liquids, supercriti-
cal phases or perfluorinated solvents.[1] Water, on the other
hand, appears to be less sophisticated.[2] However, the use
of water as the reaction solvent for organic transformations
has a number of advantages: It is widely available in excel-
lent purity, it is non-flammable, non-toxic and it normally
has a low, but nonetheless significant solubility for many
organic compounds.[3] The same holds true for chemical
transformations catalyzed by late transition metals, such as
palladium-catalyzed cross coupling reactions[4] or ruthe-
nium-mediated olefin metathesis.[5] However, apart from a
potential benign effect of using water, we have demon-
strated recently that water is an excellent solvent for pro-
moting the catalytic activity in Suzuki–Miyaura and Sono-
gashira coupling reactions as compared to that of the same
catalysts in traditional organic solvents.[6] Specifically we
have shown that catalysts for Suzuki–Miyaura reactions, es-
pecially for heterocyclic substrates are much more efficient
in water or aqueous/organic solvent mixtures than in or-
ganic solvents. One explanation for the usefulness of water
for such transformation, was that the potentially inhibiting
(i.e., palladium-coordinating) heterocycles prefer to form
hydrogen bonds with water molecules rather than coordi-
nate to palladium.[7] Furthermore formation of less reactive
boroxines occurs easily in the absence of water and the for-
mation of aryl boronates intermediates is more facile in
water than in less polar solvents.[6]
Results and Discussion
We first optimized the catalytic transformation by vary-
ing the nature of the base, the Pd source, the Pd/phosphane
ratio and the solvent composition (Table 1). As noted be-
fore, the nature of the base does not have a strong influence
on the coupling reactions in water.[7] The use of water-solu-
ble Na2PdCl4 gives much better results than with PdCl2.
Despite the fact that a monoligated PdL1 species is the
likely active species, two equivalents of phosphane ligand
are required for efficient catalysis.[6] For a few highly water
insoluble substrates, the use of n-butanol/water mixtures in-
stead of pure water was found to be advantageous.[7] For
the test reaction this did not turn out to be the case, since
most of the heterocyclic substrates possess a reasonable sol-
ubility in hot water. The mono and disulfonated fluorenyl-
phosphane are equally efficient (Scheme 1). We therefore
chose cataCXium F sulf since it is commercially available
or can be synthesized easily.[13] It is convenient to use
K2CO3 as the base and water as the reaction solvent.
[a] Organometallic Chemistry, Chemistry, TU Darmstadt,
Petersenstr. 18, 64287 Darmstadt, Germany
E-mail: Plenio@tu-darmstadt.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000251.
2934
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 2934–2937

Suzuki–Miyaura Coupling in Water
Table 1. Optimization of Suzuki–Miyaura conditions.
Table 2. Suzuki–Miyaura coupling of aryl tosylates.[a]
Ligand Pd/ligand Pd source
Base
Solvent
Conv.[a]
1
1
2
2
1
2
–
2
2
1
1:2
1:2
1:2
1:2
1:1
1:1
Na2PdCl4
PdCl2
PdCl2
Na2PdCl4
Na2PdCl4
Na2PdCl4
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
NaOH
water
water
water
water
water
water
water
water
89%
9%
7%
80%
10%
13%
–
no ligand Na2PdCl4
1:2
1:2
1:2
Na2PdCl4
Na2PdCl4
Na2PdCl4
78%
K2CO3 water/n-butanol, 1:3 81%
NaOH water 82%
[a] Conversion determined via gas chromatography (heptadecane,
internal standard). Average of two runs.
Scheme 1. Sulfonated and water-soluble fluorenylphosphanes.
We first tested a number of aryl tosylates in the Suzuki–
Miyaura coupling with aryl boronic acids. In general the con-
versions are facile at 95 °C for overnight reactions; in water
0.5 mol-% of [Pd] complex are sufficient for excellent sub-
strate conversion with isolated yields in excess of 90%. The
only two exceptions are the sterically highly demanding 2,4,6-
trimethyl-tosylates with slightly lower yield (Table 2, entry 6
(89%) and entry 9 (87%). It is also remarkable that thiophene
boronic acid and furan boronic acid, produce the cross cou-
pling products in water as the solvent in excellent yields –
even in combination with a sterically hindered substrate
(Table 2, entry 6). Ferrocene boronic acid, a substrate rarely
[a] Conditions: 1.0 mmol aryl tosylate, 1.2 mmol boronic acid,
2.5 mmol K2CO3, degassed water (5.0 mL), 95 °C, reaction time:
16 h, catalyst stock solution in water, c(Pd) = 1.0 mol-%/mL,
Na2PdCl4/cataCXium Fsulf, 1:2. Yields correspond to isolated ma-
terial after chromatography (silica), cyclohexane/EtOAc, 4:1.
Somewhat to our surprise the reactions of aryl mesylates,
used in Suzuki coupling reactions,[9d,14] also gives the desired which are considered to be less reactive in cross coupling
coupling products under the normal reaction conditions.
reactions,[10] turned out to be equally or even slightly more
The isolation of the coupling products is facile. For large efficient than cross coupling involving the aryl tosylates
scale reactions the poorly water-soluble product “swims” (Table 3). For all reactions done at a 0.5 mol-% loading,
on the surface of the water reaction mixture. It can be easily virtually quantitative reactant conversion with isolated
separated in good purity from the water without the use of yields of 99% are observed for the mesylate reactions. Even
additional solvents. For small scale reactions during the at 0.25 mol-% [Pd] loading respectable yields for the mesyl-
work-up a second solvent (n-butanol) is added to enable ate reactions in the range of 59–89% are found, with most
isolation of the product following phase separation and transformations providing yields in excess of 70%, which
evaporation. For both work-up techniques inorganic salts were slightly, but significantly lower for the tosylate conver-
and boron containing species remain in the aqueous phase sions.
and consequently the isolated crude products are of good
For the mesylate reactions we screened a few simple sub-
purity since all of the aryl tosylates and mesylates are con- strates (entries 1, 2 and 5, Table 3), several reactions involv-
sumed during the reaction.
ing heterocyclic substrates (entries 3, 4, 6, 8–13), labile bor-
Eur. J. Org. Chem. 2010, 2934–2937
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2935

J. Pschierer, H. Plenio
FULL PAPER
Table 3. Suzuki–Miyaura coupling of aryl mesylates.[a]
excellent catalytic activity for Suzuki–Miyaura coupling of
aryl tosylates and mesylates. Water rather than organic sol-
vents appear to be the better solution.
Experimental Section
Suzuki–Miyaura Coupling of Aryl Tosylates/Mesylates with Pd/
cataCXium® F sulf
Preparation of the Catalyst Stock Solution: [Na2PdCl4] (14.7 mg,
0.05 mmol), phosphonium salt (0.1 mmol) and K2CO3 (56 mg,
0.4 mmol) were placed in a Schlenk tube under argon. Degassed
water (5.0 mL) was added and the mixture was stirred at 45 °C for
3 h. This stock solution had a Pd concentration of 0.01 molL–1.
General Procedure for Suzuki–Miyaura Coupling: Boronic acid
(1.2 mmol), aryl tosylate or mesylate (1.0 mmol) and K2CO3
(345 mg, 2.5 mmol) were placed in a 25 mL Schlenk tube and evac-
uated and backfilled with Ar twice. Degassed water (5.0 mL) was
added together with the appropriate volume of catalyst stock solu-
tion. The reaction mixture was stirred for 16 h at 100 °C and then
cooled to room temperature. The reaction mixture was extracted
with n-butanol (5.0 mL) twice. The combined organic layers were
dried with MgSO4, filtered and the volatiles evaporated. The resi-
due normally consists of pure product (Ͼ99%), which was further
purified by column chromatography (cyclohexane/EtOAc, 4:1) to
afford the analytically pure corresponding cross coupling product.
Supporting Information (see also the footnote on the first page of
this article): Analytical and spectroscopic data for the cross cou-
pling products.
Acknowledgments
Support of this work by the Deutsche Forschungsgemeinschaft
(DFG) is gratefully acknowledged. Additional support was pro-
vided by Dr. R. Kadyrov/Evonik.
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