Aminoarenethiolato-copper(I) as (pre-)catalyst for the synthesis of diaryl ethers from aryl bromides and sequential C-O/C-S and C-N/C-S cross coupling reactions

Article abstract of DOI:10.1016/j.tet.2010.09.019

A small library of 2-aminoarenethiolato-copper(I) (CuSAr) complexes was tested as (pre-)catalysts in the arylation reaction of phenols with aryl bromides. These copper(I) (pre-)catalysts are thermally stable, soluble in common organic solvents, and allow reactions of 6 h at 160 °C with low catalyst loadings of 2.5 mol %. Among the (pre-)catalysts screened, 2-[(dimethylamino)methyl]benzenethiolato-copper(I) (1c) led to the best results and provided good to excellent yields of various substituted diaryl ethers. Mechanistic studies showed that at early stages of the C-O coupling reaction the CuSAr complex is converted into CuBr(PhSAr) via selective coupling of the monoanionic arenethiolato ligand with phenyl bromide with formation of CuBr. In addition, the first results are shown involving a multi-component reaction (MCR) protocol for the in situ synthesis of propargylamines and their subsequent conversion involving a C-O cross coupling reaction. Furthermore, two examples of sequential C-O/C-S and C-N/C-S cross coupling reactions have been carried out on the same dihalo-pyridine substrate in a one-pot process with the same (CuSAr) (pre-)catalyst (overall yields 40-80%).

Full text of DOI:10.1016/j.tet.2010.09.019

Tetrahedron 66 (2010) 9009e9020
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Aminoarenethiolato-copper(I) as (pre-)catalyst for the synthesis of diaryl ethers
from aryl bromides and sequential CeO/CeS and CeN/CeS cross coupling
reactions
,
Elena Sperotto a, Gerard P.M. van Klink a, Johannes G. de Vries b, Gerard van Koten a
*
a Chemical Biology & Organic Chemistry, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
b DSM Research, Life Science, Advanced Synthesis and Catalysis, PO Box 18, 6160 MD Geleen, The Netherlands
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 March 2010
Received in revised form 14 August 2010
Accepted 6 September 2010
Available online 21 September 2010
A small library of 2-aminoarenethiolato-copper(I) (CuSAr) complexes was tested as (pre-)catalysts in the
arylation reaction of phenols with aryl bromides. These copper(I) (pre-)catalysts are thermally stable,
soluble in common organic solvents, and allow reactions of 6 h at 160 ꢀC with low catalyst loadings of
2.5 mol %. Among the (pre-)catalysts screened, 2-[(dimethylamino)methyl]benzenethiolato-copper(I)
(1c) led to the best results and provided good to excellent yields of various substituted diaryl ethers.
Mechanistic studies showed that at early stages of the CeO coupling reaction the CuSAr complex is
converted into CuBr(PhSAr) via selective coupling of the monoanionic arenethiolato ligand with phenyl
bromide with formation of CuBr. In addition, the first results are shown involving a multi-component
reaction (MCR) protocol for the in situ synthesis of propargylamines and their subsequent conversion
involving a CeO cross coupling reaction. Furthermore, two examples of sequential CeO/CeS and CeN/
CeS cross coupling reactions have been carried out on the same dihalo-pyridine substrate in a one-pot
process with the same (CuSAr) (pre-)catalyst (overall yields 40e80%).
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
available aryl halides as arylating agents and in situ generated
metal ligand complexes as catalysts, using either bulky alkylphos-
The diaryl ether unit is a common structural unit widely en-
countered in biologically active molecules and natural products1 as
well as in monomers for the synthesis of functional polymers.2 This
structural moiety is part of various important pharmaceuticals with
antibiotic activity, such as vancomycin,3 teicoplanin,4 the antiviral
peptide K-13,5 the antitumoral bouvardin6 and many others.7
Common routes for the preparation of these ethers, i.e., through
CeO bond formation, involve the classical Ullmann diaryl synthe-
sis,8 which however has several drawbacks related to harsh
reaction conditions and stoichiometric use of the copper mediator.9
Recently, new approaches have been developed to overcome these
disadvantages, for example, through the use of organobismuth,10
organostannane,11 organotrifluoroborate10b,12 reagents or arylbor-
onic acids.13 However, the applicability of these aryl donors is still
restricted because of their limited accessibility (multi-step syn-
thetic procedures) and other disadvantages (i.e., production of
heavy metal waste).
phines,14 or pyrrol and indole15 based monophosphine ligands.
Nevertheless, there remains a quest for low-cost alternatives in-
volving cheaper and more abundant metals16 and cheaper ligands
(or ideally no ligands or other additives at all)17 for large-scale and
industrial applications. These are offered by copper-based protocols
in which the copper salt is present in a catalytic amount.
A drawback of the use of copper salts and coppereligand com-
plexes is their generally poor solubility and stability in the commonly
usedorganicmedia.18 Theseproblemshavebeenaddressedbytheuse
of suitable ligands,9,19 like for instance aminoacids,20 ketones,21
phenantroline derivatives22 and nitrogen- and oxygen-containing
ligands23 for the in situ generation of soluble, catalytically active
copper complexes. An alternate option is the use of pre-prepared,
soluble and air-stable copper salteligand complexes, for example,
ionic [Cu(MeCN)4]PF624 or neutral [CuBr(neocup)(PPh3)],25 and many
of these have already shown to be good (pre-)catalysts in diaryl ether
synthesis.9
In recent years elegant and efficient palladium-catalyzed ary-
lations of phenols have been reported, employing commercially
In recent years we explored a class of well-defined neutral copper
(I) complexes, i.e., the 2-aminoarenethiolato-copper(I) complexes
(CuSAr, Fig. 1)26 as (pre-)catalysts for various types of CeX bond
forming reactions and have tested these as (pre-)catalyst in allylic
substitution,27 1,4-,28 and 1,6-29 addition reactions and aromatic
N-arylation30 reactions.
* Corresponding author. Fax: þ31 30 252 3615; e-mail address: g.vankoten@uu.nl
(G. van Koten).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.019

9010
E. Sperotto et al. / Tetrahedron 66 (2010) 9009e9020
toluene to afford the desired 2-aminoarenethiolato-copper(I) com-
R = H, t-Bu, SiMe3
NR'R"
S Cu
plexes as pure materials in 67e85% yield.26
R' = R" = Me, Et, -(CH2)n; n = 4, 5
R
This straightforward synthetic protocol allowed easy prepara-
tion of a series of differently substituted complexes. The various
amines were chosen to test the influence of the basicity of the
N-amine centre as well as of the steric constraints of the amino
ortho-substituent in the ligand on the outcome of the CeO coupling
reaction and the catalytic activity. The aryl ring was varied to the
naphthyl ring, in order to check possible steric effects of the back-
bone. Moreover, various substituent patterns, meta- to the CeS
bond, were tested to possibly modify the solubility properties of the
resulting copper (pre-)catalyst.
The coupling of bromobenzene with phenol was chosen as
a model reaction mediated by 2.5 mol % of 1c as (pre-)catalyst
(Scheme 2). The solvent of choice appeared to be N-methyl-
pyrrolidinone (NMP) at a reaction temperature of 160 ꢀC. Indeed,
other solvents as dioxane, toluene, acetonitrile, which were tested at
90e110 ꢀC, and in all cases afforded the ethers in yields lower than
30% (calculated on bromobenzene) within 16 h. Only DMSO and
DMF gaveresults comparable tothose obtained for reactions in NMP,
probably due tothe needtoachieve a reaction temperature of 160 ꢀC.
Fig. 1. 2-Aminoarenethiolato-copper(I) complexes.
The complexes have excellent solubility in a range of useful
solvents.26 In addition, electronic and physical properties can easily
be fine-tuned by introducing substituents at the arene ring or the
amino-functionality.
In the present study the reactivity of a small library of differently
substituted 2-aminoarenethiolatoecopper(I) complexes as (pre-)
catalysts in the O-arylation of phenols with aryl bromides is
reported. The copper complexes studied show good catalytic ac-
tivity in CeO coupling reactions affording diaryl ethers, at a catalyst
loading of only 2.5 mol % within relatively short reaction times. The
fate of the CuSAr pre-catalyst during initial stages of the reaction
has also been studied. Moreover, we report the first experiments
making use of the versatility of the CuSAr pre-catalyst to combine
diverse sequential reactions on the same substrate molecule cata-
lyzed by a single catalyst in a one-pot procedure. These experi-
ments provided promising results for the synthesis of target
molecules with interesting combinations of (hetero)aryl building
blocks, starting from 2-bromo-5-iodopyridine.
O
2.5 mol% [Cu]
+
Br
HO
base, NMP, 160 o
C
2. Results
Scheme 2. Coupling reaction of bromobenzene with phenol.
A series of 2-aminoarenethiolato-copper(I) complexes, see Fig. 2,
was prepared through a synthesis involving a one-pot procedure of
the four steps (Scheme 1), i.e., a heteroatom directed ortho-lithiation,
insertion of sulfur in the formed carbon-lithium bond, a quench with
trimethylsilyl chloride resulting in the formation of the trimethylsilyl
thioester, which subsequently was used in a reaction with CuCl in
The search for an appropriate base led to a choice of cesium
carbonate after a series of organic and inorganic bases had been
screened (Table 1). Soluble organic bases, for example, NEt3,
Hunig’s base, pyridine and 2,6-luitidine gave poor product yields.
Likewise, moderate results were obtained with either potassium
N
N
N
N
X
X
X
3
X
1
2
4
N
N
N
N
X
X
X
X
7
8
6
5
N
N
N
X
X
X
11
9
10
Si
Si
N
N
N
Si
X
X
X
13
12
14
a. X = H; b. X = SSiMe3; c. X = SCu
Fig. 2. Library of 2-aminoarenethiolato-copper(I) complexes used in this study.
NMe2
NMe2
NMe2
NMe2
SCu
i
ii, iii
iv
Li
[1Li]
H
SSiMe3
1a
1b
1c
i. t-BuLi, pentane, -78 oC; ii. 1/8 S8, THF, -78 oC to -20 oC; iii. SiMe3Cl, -20 oC to rt; iv. CuCl,
toluene, rt
Scheme 1. General procedure for the synthesis of aminoarenethiolato-copper(I) complexes exemplified by the synthesis of 1c.

E. Sperotto et al. / Tetrahedron 66 (2010) 9009e9020
9011
Table 1
the various substrates were obtained by comparison of the yield
of the respective CeO coupling products by interrupting each
reaction after 6 h (Table 3). In all reactions total selectivity was
accomplished and formation of biaryl products or isomeric diaryl
ethers was never observed, while dehalogenated arenes
(reduction product) appeared to be present in the reaction mix-
tures in amounts below 2%.
Effect of the nature of the base on the CeO coupling of phenol with aryl bromide
Entry
Base
Yielda
%
1
2
3
4
K2CO3
43
98
89
52
Cs2CO3
KO-t-Bu
K3PO4
Reaction conditions: phenol (6.5 mmol), aryl bromide (5 mmol), base (5.5 mmol),
CuSAr catalyst 1c (2.5 mol %), solvent (1 mL), 16 h, 160 ꢀC, under N2.
a
Table 3
Determined by GC using dihexyl ether as internal standard, based on phenyl
Etherification of aryl bromides catalyzed by CuSAr 1c after 6 h
bromide.
O
2.5 mol% [Cu]
+
Br
HO
carbonate or phosphate (Table 1; entries 1 and 4), whereas quite
good yields of diphenyl ether were achieved in the presence of
potassium tert-butoxide (Table 1; entry 3) as a base. Notably, with
Cs2CO3 the CeO coupling product was obtained in almost quanti-
tative yield (98%, Table 1; entry 2). The latter excellent results
possibly relate to the good solubility characteristics of cesium
phenolate formed as intermediate in polar aprotic solvents, cf. the
so-called ‘cesium-effect’.31
R'
Cs2CO3, NMP, 160 oC, 6 h
R
R
R'
NMe2
S Cu
[Cu] =
Entry
ArBr
Phenol
Yielda
90b
%
Different aryl halides were tested under the chosen reaction
conditions, but fluoro and chlorobenzene did not react (notably no
formation of the arene reduction product was detected), whereas in
the reaction with iodobenzene the maximum yield of diphenyl
ether amounted to only 36%. Consequently further investigations
were concentrated on the use of bromoarene derivatives. The library
of 2-aminoarenethiolato-copper(I) complexes was tested under the
optimized conditions established for the CeO coupling reaction
between bromobenzene and phenol. The yield of diphenyl ether for
each CuSAr (pre-)catalyst was monitored after 16 h (Table 2). Parent
complex 1c gave excellent results (Table 2; entry 1), while an in-
crease of the basicity of the nitrogen atom in the catalyst resulted in
a slight decrease of the yield (87e90%, entries 2e4). Good to ex-
cellent yields were achieved with 2-[(dimethylamino)methyl]
naphthalene-3-thiolato-copper(I) 5c (74% entry 5), while the re-
placement of the dimethylamino group in 5c by diethylamine (6c)
or pyrrolidinyl (7c) caused an increase in the yield of diphenyl ether
to 93%. Introduction of substituents, on either the phenyl or the
naphthyl ring did increase the solubility of the complexes but did
not affect the catalytic activity in a substantial way (entries 9e14).
1
Br
HO
2
3
4
5
6
7
85b
85b
81b
13c
64
Br
Br
Br
Br
HO
HO
OMe
tBu
HO
HO
NO2
Ac
Br
HO
HO
77b
MeO
Br
Table 2
8
87b
Br
HO
Screening of the reactivity of 2-aminoarenethiolato-copper(I) complexesa in
reaction of Scheme 2
Complex
Aryl
R
R0, R00
Yieldb
%
1
2
3
4
5
6
7
8
Phenyl
Phenyl
Phenyl
Phenyl
Naphthyl
Naphthyl
Naphthyl
Naphthyl
Phenyl
H
H
H
H
H
H
H
H
Me, Me
Et, Et
e(CH2)4e
e(CH2)5e
Me, Me
98
87
90
89
74
96
96
87
89
83
71
9
85
Br
HO
HO
HO
50d
63e
10
11
Br
Br
Et, Et
e(CH2)4e
e(CH2)5e
Me, Me
e(CH2)4e
e(CH2)5e
79b
Br
9
10
11
5-t-Bu
5-t-Bu
5-t-Bu
Phenyl
Phenyl
12
13
14
Phenyl
Phenyl
Naphthyl
3-TMS
5-TMS
3-TMS
Me, Me
Me, Me
Me, Me
81
87
84
12
79b
Br
HO
HO
a
For R, R0, R00 see Figs. 1 and 2. Reaction conditions: phenol (6.5 mmol), bromo-
benzene (5 mmol), Cs2CO3 (5.5 mmol), [Cu] (2.5 mol %), solvent (1 mL), 16 h, under
N2, 160 ꢀC.
13
14
82b
64
b
Determined by GC using dihexyl ether as internal standard, based on phenyl
MeO
Br
bromide.
Further studies were carried out with 1c as the (pre-)catalyst
of choice. The scope of the reaction was studied by reacting
a variety of combinations of functionalized bromoarenes and
phenols as coupling partners. Comparisons of the reactivity of
Br
HO
(continued on next page)

9012
Table 3 (continued)
E. Sperotto et al. / Tetrahedron 66 (2010) 9009e9020
bromide-functionality to form a new CeO bond and then, after
addition of the second set of reagents, reacts on the iodide-func-
tionality with thiophenol to form the new CeS bond. The optimized
reaction conditions for the two separate couplings, CeO and CeS,
respectively, appeared to be suitable for the CeO/CeS combination
as well. Although the reagents were added in sequence to favor the
chemoselectivity of the two coupling processes, the overall reaction
was conducted in one-pot without isolation/purification of in-
termediates and the desired product 15 was isolated in 80% yield.
Two additional side products, identified by GC/MS analysis, are the
dietherification (<5%) and the dithioetherification (<10%) prod-
ucts, respectively.
A second example is shown in Scheme 4, following the same
strategy for the synthesis of 15. At first, the CeN bond is formed
between pyridine and benzylamine with high chemoselectivity at
the CeBr bond. The following step is then initiated by the addition
of thiophenol and a fresh portion of catalyst 1, to give the desired
CeN/CeS coupled product 16 in 60% overall yield. As detected by
GC/MS, the dithioetherification side-product was present in the
reaction mixture in low amounts <5%. A second product was
identified as N-benzyl-benzylideneamine, oxidation product of
benzylamine and the reason for its formation was already recog-
nized.34 It is worthwhile to note that in both examples of Schemes 3
and 4, the presence of copper catalyst is required to obtained for-
mation of products.
Entry
ArBr
Phenol
Yielda
65
%
15
Br
Br
HO
16
2
HO
Reaction conditions: phenol (6.5 mmol), bromoarene (5 mmol), Cs2CO3 (5.5 mmol),
[Cu] (2.5 mol %), NMP (1 mL), 160 ꢀC, 6 h, under N2.
a
Determined by GC and GCeMS using dihexyl ether as internal standard, based
on aryl bromide.
b
Isolated yield; see supporting information for analytical data.
Reaction time (16 h).
Using 1.3 equiv of phenol, yield of monosubstituted product.
Using 2.6 equiv of phenol, yield of disubstituted product.
c
d
e
Reaction of bromobenzene with electron-rich phenols resulted
in the formation of the corresponding asymmetric diaryl ethers in
good yields (81e90%, entries 1e4), both for para- and meta-
substituted phenols.
Following a general trend in the field of CeO coupling re-
actions,21 4-nitrophenol, which bears a strong electron-withdraw-
ing NO2-group proved to be a less efficient substrate for the desired
O-arylation reaction, even after 16 h when the product was present
in a yield of 13% (entry 5), and conversion was 15% based on the
starting bromobenzene.
When the arylating reagent was changed from bromobenzene to
meta- or para-substituted aryl bromides, just a slight decrease in
reactivity and yield in product was noticed. The etherification of
electron-rich bromoarene derivatives with 3,5-dimethylphenol
afforded the respective diaryl ethers in good yields (79e82%, entries
11e13). The coupling of aryl bromides with either electron-donating
or-withdrawing substituents, i.e., 4-bromoanisole, 4-bromotoluene
and 4-bromoacetophenone, with phenol gave rise to the formation
of the diaryl ethers in good yields (64e87%, entries 6e9).
More sterically hindered aryl bromides and phenols are chal-
lenging substrates which are not often tested but highly important
with respect to the scope of the diaryl ether reaction.28 Coupling
partners such as ortho-disubstituted arenes or phenols commonly
give quite poor results. The reactivity of the present 2-amino-
arenethiolato-copper(I) (pre-)catalyst was investigated employing
some of these starting materials but produced moderate results
(64e65%, entries 14 and 15), in concert with results obtained with
other copper(I) catalysts.32,33 Only traces of product were detected
in the mixture of the reaction of 2,6-dimethylbromobenzene with
2,6-dimethylphenol in the presence of 1c (2%, entry 16).
1) BnNH2, CuSAr 2.5 mol%
I
S
K2CO3, NMP, 160 oC, 16 h
N
Br
N
N
H
2) PhSH, CuSAr 2.5 mol%
K2CO3, 160 oC, 16 h
16
yield 60 %
Scheme 4. Sequential CeN/CeS coupling reactions on 2-bromo-5-iodopyridine.
In preliminary experiments CuSAr (2.5 mol %) was added only at
the beginning of the reaction sequences (see Schemes 3 and 4),
which were carried out in one-pot without isolation or purification
of the intermediates. However in these set-ups, yields of the de-
sired products, 15 and 16, respectively, never exceeded 30%, while
the yield of side products, i.e., dietherification and dithioether-
ification products, increased to 15e20%.
2.2. Study of the (pre-)catalyst
Analysis of the reaction mixtures had revealed the presence of
a compound which could be identified as 2-[(dimethylamino)
methyl]phenyl phenyl sulfide (PhSAr in Scheme 5). The formation
of PhSAr results from the reaction of CuSAr with bromobenzene.
This reaction was proven by an independent experiment, per-
formed under the same conditions as the catalytic reaction, in-
volving the reaction in NMP of bromobenzene with CuSAr in 1: 1 M
ratio (see experimental). Exclusively PhSAr (and CuBr) was formed
which was isolated in 80% yield. Consequently, it can be concluded
that PhSAr is formed in the reaction mixture through S-arylation of
the SAr-anion with bromobenzene, which is present in the reaction
mixture in large excess. Experiments conducted at different tem-
peratures (80e160 ꢀC) showed that PhSAr is only formed at re-
action temperatures ꢁ100 ꢀC.
2.1. Sequential CeX cross coupling reactions on 2-bromo-5-
iodopyridine
In this section the starting material of choice was 2-bromo-5-
iodopyridine, because of its commercial availability and good
reactivity. One example is shown in Scheme 3, in which initially
2-bromo-5-iodopyridine reacts selectively with phenol on its
1) PhOH, CuSAr 2.5 mol%
I
S
Cs2CO3, NMP, 160 oC, 16 h
NMe2
Br
T > 100 o
C
NMe2
S Cu
CuSAr
+
+
CuBr
N
Br
N
O
S
2) PhSH, CuSAr 2.5 mol%
K2CO3, 160 oC, 16 h
15
yield 80 %
PhSAr
Scheme 5. Formation of 2-[(dimethylamino)methyl]phenyl phenyl sulfide (PhSAr).
Scheme 3. Sequential CeO/CeS couplings on 2-bromo-5-iodopyridine in one pot.

E. Sperotto et al. / Tetrahedron 66 (2010) 9009e9020
9013
This result shows that in fact the 2.5 mol % of the 2-amino-
arenethiolato-copper(I) complex is converted into an equimolar
mixture of PhSAr and CuBr. Obviously, this in situ formation of the
CeS coupling product PhSAr (and consequently CuBr) leads to
a copper salteligand combination, which affects positively the cat-
alytic CeO coupling process. The CeO coupling reaction was also
performed with pure CuBr (2.5 mol %) and additional, preformed,
PhSAr (2.5 mol %) instead of the pre-catalyst CuSAr. Under the same
conditions, the reaction gave a lower yield of diaryl ether of 87% (vs
98% with CuSAr). This underlines the positive influence of PhSAr as
a ligand, and the presence of a more complicated catalytic system as
well. Indeed it shows that the in situ formation of the [CuBrePhSAr]
complex from the pre-catalyst CuSAr and the substrate PhBr is more
efficient than the combination reached via pure CuBr and PhSAr
separately.
The different results of the CuSAr- and CuBr-catalyzed reactions
strongly suggest that the S-coupling product PhSAr apparently acts
as suitable N,S-ligand for the CuBr formed in early stages of the
reaction. To verify this hypothesis and study in more detail the
effect of PhSAr, we sought independent proof for the formation of
possible complexes between PhSAr and copper.
A mixture of only CuSAr (2.5 mol % respect to bromobenzene)
with bromobenzene (reaction of 30 min, 120 ꢀC, Scheme 5) was
studied by mass spectrometry (FIA-ESI-MS, Flow Injection Analy-
sis-Electrospray Ionization-Mass Spectrometry). The main peaks
displayed by the positive ESI-MS spectrum matched with those in
the spectrum of pure PhSAr confirming the presence and formation
of the S-coupling product. In addition the presence of two adducts
was observed, one with a 1:1 [CuPhSAr]þ and another one with
a 2:1 [Cu(PhSAr)2]þ ligand-to-copper molar ratio, each displaying
the characteristic isotopic distributions for their molecular cations
(Scheme 6).
spectrum of
a
solution of [Cu(PhSAr)2]BF4 in methanol-d4
showed, when compared to the spectrum of free PhSAr, a down-
field shift for both benzylic (Dd¼0.20 ppm) and methyl protons
(
Dd¼0.24 ppm), which indicates a coordination of the ligand to
the metal centre. The methyl and benzylic proton resonances of
[Cu(PhSAr)2]BF4 appeared as broad singlets under the conditions
employed (methanol-d4, 298 K). The temperature dependency of
the 1H NMR spectra of [Cu(PhSAr)2]BF4 could not be studied for
temperatures below 298 K, because of its poor solubility in
methanol-d4, whereas at higher temperature (328 K) no change
was observed. Analysis of the MALDI-TOF MS (Matrix Assisted
Laser Desorption Ionization-Time of Flight Mass Spectrometry)
spectrum of authentic [Cu(PhSAr)2]BF4 showed the presence of
the ions [CuPhSAr]þ (m/z 306.3092) and [Cu(PhSAr)2]þ (m/z
549.3817) with the characteristic isotopic patterns, confirming
the nature and coordination of PhSAr to Cu(I) in the species 17
and 18 found in the reaction mixture.
These data do not provide information about the coordination
geometry around the metal centre of the complex in solution.
However, it is known that copper(I) adopt preferentially a tetrahe-
dral or a square planar configuration, which can be achieved via the
complexation of tetradentate ligands or two bidentate ligands.37
These cationic complexes are generally represented by the formula
[CuIL2] [Y] and in particular, when CuIBr salt is present, the anion Y
can also be [CuBr2]ꢂ. Structures reported in literature, which in-
volved N2S2-ligands,38 and extensive studies related to metal-con-
taining proteins, i.e., blue copper proteins,39 showed the frequent
tetrahedral geometry of coordination around Cu(I). In view of the
close similarity of the donor atoms of these complexes with the ones
used in this report, we expect for complex [Cu(PhSAr)2]BF4 a similar
tetrahedral structure for the cation, with two neutral N,S-bidentate
coordinating ligands PhSAr and BF4 as counter anion. Correspond-
ingly, complex 18 is expected to present an analogous structure [Cu
(PhSAr)2][CuBr2], with [CuBr2]ꢂ as counter anion. In the case of a 1:1
coordination of the N,S-ligand PhSAr, as expected for complex 17, an
additional mode of coordination can be involved, which includes the
formation of CueX bridges, where X is Brꢂ in our case. Similar
structures have been reported, including N,N-,40aec S,S-,40d and N,S-
ligands.40e Therefore, complex 1 is most likelypresentas a species, in
which the N,S-ligated copper maintains a tetrahedral/square planar
configuration via two bridging bromide anions, with a general for-
mula of [Cu2L2]X2.
NMe2
NMP
120 o
S
+
+
+
[Cu(PhSAr) ]
2
[CuPhSAr]
+
CuBr
C
18
17
PhSAr
Scheme 6. Complexes 17 and 18.
Attempts to prepare independently and isolate these 1:1 (17)
and 2:1 (18) ligand-to-copper complexes appeared to be difficult
and in the case of the 1:1 complex did not result in the isolation of
a distinct, pure complex. Therefore the nature of the 1:1 complex
(17) was studied on in situ formed material.
3. Discussion
The present study shows that, with 2-aminoarenethiolato-
copper(I) complexes as (pre-)catalyst and starting from aryl bro-
mides, the desired diaryl ethers are formed in yields of 50e98%. The
scope of the reaction is quite broad, and tolerates arene sub-
stituents ranging from electron-withdrawing to electron-donating
groupings in ortho-, meta- and para-positions, on both the phenol
and the aryl bromide derivatives. The protocol developed involves
a low loading of the cheap metal copper (only 2.5 mol %) and leads
to a clean and selective formation of the diaryl ether product, as no
side products were detected beside starting materials, which could
be recovered at the end of the reaction. Limitations of the present
protocol regard the rather high reaction temperature (160 ꢀC) and
lack of coupling when the phenol bears an electron-withdrawing
group on the ring.
Competitive reduction of the aryl halide to the corresponding
dehalogenated arene, the formation of isomeric biaryl compounds
via substitution through an eliminationeaddition mechanism and
the reductive homocoupling of the aryl halide (Scheme 7)13a,21a,41
are commonly encountered features in the Ullmann biaryl ether
synthesis. However, it is worth mentioning that in our studies
(Tables 2 and 3) using the optimized protocol, high selectivities
Pure PhSAr and the reaction mixture of the reaction of PhSAr
35
with CuBr in 1:1 M ratio (reaction of 180 min, 120 ꢀC) in DMSO-d6
were both analyzed by 1H NMR spectroscopy (see Experimental).
The 1H NMR spectrum for PhSAr showed a clear pattern, with
a singlet resonance at 2.13 ppm for the methyl protons, another
singlet resonance at 3.48 ppm for the benzylic protons and a mul-
tiplet pattern for the aromatic protons (7.15e7.43 ppm). The 1H
NMR spectrum of the reaction mixture of PhSAr with CuBr showed
a similar pattern to the previous spectrum, but revealed down-field
shifts, commonly observed upon ligand coordination to a metal, for
the methyl protons (Dd¼0.17 ppm), for the benzylic protons
(
Dd¼0.05 ppm) and a different pattern for the aromatic protons.
These NMR data pointed to the presence of a [CuBrePhSAr] species
in solution (Scheme 6).
Independent preparation of the 2:1 complex (18) was ach-
ieved through addition of a solution of ligand PhSAr to a sus-
pension of [Cu(MeCN)4]BF4 in benzene, in 2:1 M ratio.36 The
isolated off-white powder analyzed as [Cu(PhSAr)2]BF4 showed
poor solubility in common organic solvents. However, 1H NMR

9014
E. Sperotto et al. / Tetrahedron 66 (2010) 9009e9020
Br
HO
Cu catalyst
O
O
O
+
+
+
+
R
R
R
R
R
a
b
c
d
Scheme 7. Possible competitive reactions besides the cross-coupling product formation (a: desired product, b: biphenyl, c: isomeric biaryl ether, d: dehalogenated arene).
were accomplished. Formation of biphenyls and isomeric diaryl
ethers were not observed, while dehalogenated arenes were
detected only in trace amounts (<2%).
product AreOR.13a,46 The role of the S- and N-donor atoms of the
PhSAr ligand during the coupling process is not clear yet but it is
obvious that the PhSAr is a versatile ligand that can act as mono-
or bidentate ligand supporting the switches of the oxidation state
of the copper centre during this coupling process.
Up to now the reported copper-catalyzed biaryl ether syntheses
use a copper source in amount of 5e10 mol % and a suitable ligand
in 10e20 mol % with reaction temperatures ranging from 80 to
150 ꢀC and reaction times from 16 to 24 h22,23,32 An obvious dif-
ference is the fact that whereas our catalytic protocol tolerates
a lower loading of 2.5 mol % of the copper-catalyst, a reaction
temperature as high as 160 ꢀC is still needed. Moreover, while
commonly aryl iodides show higher reactivity than bromides and
chlorides, in our case aryl bromides are the most reactive partners
for the coupling. This can be an indication that the use of 2-ami-
noarenethiolato-copper(I) complexes as (pre-)catalyst causes
a substantial shift in the mechanistic pathway of the CeO coupling
process.32a,42
As the coupling reaction shows a preference for bromide anions,
the nature of the halide anion present in the reaction mixture also
plays a fundamental role. It is noteworthy that in contrast to bro-
mide (and chloride), iodide ions stabilize the copper atom in its þ1
oxidation state.18,43 These observations seem to support a mecha-
nistic pathway in which the oxidation state of the copper changes
throughout the catalytic cycle, rather than a mechanistic proposal
in which the copper centre maintains its þ1 oxidation state.44
4. Conclusions
In the present report the preparation of a new library of
aminoarenethiolato-copper(I) complexes was described, in-
cluding a variety of thiolato-ligands derived from diverse amine
derivatives and aryl and naphthyl backbones. It was found that
prior to the CeO coupling reaction the CuSAr catalyst is con-
verted into a CuBr(PhSAr) complex via selective coupling of the
monoanionic arenethiolato ligand with phenyl bromide.
A
mechanistic sequence in which this complex subsequently cata-
lyzes the CeO coupling reaction has been proposed. The present
results also show that CuSAr 1c is an interesting pre-catalyst for
one-pot sequential reactions. Indeed, its high solubility, good
catalytic activity and chemoselectivity towards Br- or I- func-
tionalities in CeO/CeN and CeS couplings, respectively, are im-
portant features. In these sequential multistep reactions there
was no need for work-up after the first step, allowing a simple
synthesis of the products.
3.1. Proposed mechanism
5. Experimental
In Scheme 8 a reaction sequence for the present reactions
between arene alcohols and arene bromides is proposed fol-
lowing the proposal put forward by Buchwald et al.45 The cata-
lytic cycle starts with the formation of the PhSAr ligand and CuBr.
The arene alcohol is then converted into a metal phenolate/
cuprate-like intermediate [Cu(OR)L]. Activation of the aryl bro-
mide occurs via its coordination to the copper centre allowing
inner electron transfer from the copper(I) centre to the aryl
moiety. Concomitant CeO coupling via a concerted process inside
the aggregate would then lead to the formation of the coupling
5.1. General remarks
All reactions were performed using Schlenk techniques under
an inert atmosphere unless stated otherwise. Chemicals were
purchased from Across or Aldrich. Solvents used in the catalyst
syntheses were carefully dried and distilled prior to use. Solvents
used for catalytic tests were used as received. Chloro-
trimethylsilane was distilled and passed through basic alumina
prior to use.1H and 13C{1H} NMR spectra were recorded on a Varian
Inova 300 MHz spectrometer at 298 K unless stated otherwise. The
chemicals shifts (d) are presented in parts per million referenced to
residual solvent resonances. Gas chromatography analyses were
performed on a PerkineElmer Clarus 500 GC equipped with an
CuSAr
Alltech EC-5 column (30 mꢃ0.32 mm IDꢃ0.25
mm). Elemental
analyses were performed by Kolbe, Mikroanalytisches Labo-
ratorium, Mühlheim/Ruhr, Germany. MS measurements were
carried out on an Applied Biosystems Voyager DE-STR MALDI-TOF
MS and on SCIEX API 150 EX FIA-ESI mass spectrometer with
positive ion electrospray.
PhBr
L = PhSAr-ligand
PhOR
ROH + Cs2CO3
CsHCO3 + CsBr
CuBrL
5.2. General procedure for the etherification-catalytic tests
Br
CuII
L
The catalytic tests were performed using standard Schlenk tech-
niques. In a generalprocedure, the Schlenktubewascharged withthe
base (5.50 mmol) and solid substrate. Liquid reagents (aryl halide:
5.00 mmol; phenol: 6.50 mmol) and solvent (1 mL) were then added
and finally the copper(I)catalystwasadded (0.125mmol). The reactor
was kept under inert atmosphere and placed, under stirring, in a pre-
heated oil bath at 160 ꢀC for 6e16 h. Subsequently, the reaction
mixture was allowed to cool to room temperature and diluted with
Cu(OR)L
RO
Br
CuI
RO
L
Scheme 8. Proposed mechanism for the copper-catalyzed etherification reaction.47
acetonitrile (5 mL) and dihexyl ether (100 ml, 0.425 mmol) was added

E. Sperotto et al. / Tetrahedron 66 (2010) 9009e9020
9015
as external standard. All samples were analyzed by gas chromatog-
raphy to obtain the data presented. The reaction mixture was filtered
through a plug of Celite, the solvent removed in vacuo to yield the
crude product, which was purified by silica gel chromatography.
For the library of (pre-)catalysts, see: Sperotto, E.; van Klink,
G.P.M.; de Vries, J.G.; van Koten, G. Tetrahedron. 2010, 66,
3478e3484.
chromatography on silica gel (eluent: ethyl acetate/hexane 1:5), to
give the product as colorless oil (yield 54%).
1H NMR (399.9 MHz, CDCl3):
d 8.21 (br s, 1H, PyrCH), 7.54 (d, 1H,
J¼8.8 Hz, PyrCH), 7.36e7.35 (m, 3H, Ar), 7.33e7.28 (m, 2H, Ar),
7.26e7.21 (m, 2H, Ar), 7.15e7.11 (m, 3H, Ar), 6.42 (d, 1H, J¼8.8 Hz,
PyrCH), 5.52 (br s, 1H, NH), 4.53 (d, 2H, J¼5.6 Hz, CH2); 13C NMR
(100.6 MHz, CDCl3):
d 158.2, 152.8, 144.6, 138.6, 138.5, 129.2, 129.0,
127.89, 127.6, 126.0, 124.7, 116.9, 108.1, 46.5; nmax (liquid film) 3437,
3054, 2986, 1657, 1595, 1265, 738 cmꢂ1; MS (EI) m/z (relative in-
tensity): 292.05 ([M]þ, 80%), 215.07 (25%), 187.08 (25%), 147.02
(15%), 106.11 (50%), 91.09 (100%), 65.08 (35%); HR-ESI-MS: MHþ,
found 293.1087. C18H16N2S requires 293.1112.
S
N
O
5.2.3. 2-[(Dimethylamino)methyl]phenyl phenyl sulphide, PhSAr
(Scheme 5). (a)A solution of t-BuLi (17.0 mL, 1.5 M in pentane,
25.5 mmol, 1.1 equiv) was added to a solution of N,N-dime-
thylbenzylamine (3.00 g, 22.18 mmol, 1 equiv) in dry pentane
(60 mL) at room temperature, under nitrogen atmosphere. After
stirring the orange solution overnight, the solvent was removed in
vacuo and cold THF (0 ꢀC, 40 mL) was added an ice bath was used to
maintain the low temperature. The resulting brown solution was
stirred for 1.5 h, then 1,2-diphenyl disulfane (5.567 g, 25.5 mmol,
1.1 equiv) was added and the reaction mixture turned to a grey
turbid colour. The stirring was kept for 1.5 h, when the ice bath was
removed. The reaction mixture was stirred for additional 30 min,
after that 15 mL of demineralized water were added and the stir-
ring maintained for 30 min. The mixture was washed first with
brine, extracted with diethyl ether, dried over MgSO4 and con-
centrated in vacuum to obtain orange oil. Crude yield: 5.6 g, 90%.
The crude product was purified via silica gel column chromatog-
raphy (eluent: hexane/ethylacetate 5:1) to obtain the pure product
as yellow oil. Isolated yield: 85%.
5.2.1. 2-Phenoxy-5-phenylsulfanylpyridine (15). A reaction vessel
was first charged with Cs2CO3 (0.36 g 1.1 mmol), 2-bromo-5-
iodopyridine (0.284 g, 1.00 mmol), phenol (94 mg, 1.00 mmol)
and DMSO (0.5 mL) was then added. The aminoarenethiolato-
copper(I) complex 1 (6.0 mg, 0.025 mmol, 2.5 mol %) was then
added and the reaction mixture heated at 160 ꢀC for 16 h, with
good stirring. Afterwards, the heating was stopped, the reaction
vessel cooled down and K2CO3 (0.152 g, 1.1 mmol), thiophenol
(0.11 g, 1 mmol) and a fresh portion of 1 (0.006 g, 0.025 mmol,
2.5 mol %) were added to the reaction mixture. The heating
(160 ꢀC) and stirring were again started for 16 h, after which the
reaction was stopped. Isolation of the crude product (yield 80%)
was performed by washing the mixture with NaHCO3 (1 N)/
pentane (4ꢃ50 mL), drying over MgSO4 and, after filtration, re-
moving the solvent in vacuo. The product was purified by column
chromatography on silica gel (eluent: ethyl acetate/hexane 1:4),
to give the product as colorless oil (yield 75%).
1H NMR (399.94 MHz, CDCl3):
CH2), 7.15e7.19 (m, 1H, Ar), 7.23e7.35 (m, 7H, Ar), 7.45e7.47 (d, 1H,
Ar); 13C NMR (100.576 MHz, CDCl3):
139.9, 136.6, 136.1, 132.3,
d 2.29 (s, 6H, N(CH3)2), 3.61 (s, 2H,
1H NMR (399.9 MHz, CDCl3):
d 8.25 (br s, 1H, PyrCH), 7.79e7.68
d
(m, 1H, PyrCH), 7.45e7.39 (m, 3H, Ar), 7.29e7.22 (m, 5H, Ar),
7.19e7.14 (m, 2H, Ar), 6.85 (br s, 1H, PyrCH); 13C NMR (100.6 MHz,
131.2, 130.4, 129.4, 128.1, 127.2, 127.1, 62.27, 45.63. MS (EI) m/z
(relative intensity): 195 (72), 194 (68), 117 (34), 89 (100), 65 (70).
Anal. Calcd for C15H17NS: C 74.03, H 7.04, N 5.76. Found: C 73.94, H
7.10, N 5.69.
(b) Following the general procedure for a catalytic test, a re-
action mixture was prepared, which contained NMP (1 mL), bro-
CDCl3):
d 153.7, 143.9, 136.2, 135.0, 130.8, 129.8, 129.7, 129.5, 129.3,
129.2, 127.44, 126.82, 121.28; nmax (liquid film) 3059, 2925, 1577,
1457,1268, 691 cmꢂ1; MS (EI) m/z (relative intensity): 279.02 ([M]þ,
100%), 250.03 (20%), 176.05 (46%), 115.09 (37%), 104.05 (50%), 77.09
(30%), 65.08 (18%); HR-ESI-MS: MHþ, found 280.0810. C17H13NOS
requires 280.0796.
mobenzene: (5 mmol, 527
ml), internal standard dihexyl ether
(100 l, 0.42 mmol) and CuSAr complex (5 mmol, 1.149 g). Product:
m
2-[(dimethylamino)methyl]phenyl phenyl sulphide (PhSAr). GC
yield: 80%.
S
N
N
H
5.2.4. Catalytic test with CuBr and PhSAr. Following the general
procedure for a catalytic test, the reaction mixture was prepared
using freshly prepared CuBr (17.9 mg, 0.125 mmol) and PhSAr
(28.7 mg, 0.125 mmol) instead of CuSAr as pre-catalyst. All the
other conditions were kept (160 ꢀC, 16 h, base Cs2CO3, PhBr and
PhOH) as previously described. The reaction mixture was analyzed
by GC (dihexyl ether as internal standard) and showed a yield of
diaryl ether of 87% (vs 98% with CuSAr pre-catalyst).
5.2.2. N-(5-Phenylsulfanylpyridin-2-yl)benzylamine (16). A reaction
vessel was first charged with K2CO3 (0.45 g, 3.57 mmol), 2-bromo-
5-iodopyridine (0.85 g, 2.98 mmol), benzylamine (0.38 g,
3.57 mmol) and DMSO (1 mL) was then added. At last, the ami-
noarenethiolato-copper(I) complex 1 (17.0 mg, 0.0739 mmol,
2.5 mol %) was added and the reaction mixture heated at 160 ꢀC for
16 h, under good stirring. Afterwards, the heating was stopped, the
reaction vessel cooled down and K2CO3 (0.45 g, 3.57 mmol), thio-
phenol (393 mg, 3.57 mmol) and a fresh portion of CuSAr 1
(17.0 mg, 0.0739 mmol, 2.5 mol %) were added to the reaction
mixture. The heating and stirring were started again for 16 h, after
which the reaction was stopped. Isolation of the crude product
(yield 60%) was performed by washing the mixture with NaHCO3
(1 N)/pentane (4ꢃ50 mL), drying over MgSO4 and, after filtration,
removing the solvent in vacuo. The product was purified by column
5.2.5. Preparation of samples for mass-spectrometry analysis. A
mixture of CuSAr (200 mg, 0.874 mmol) and bromobenzene (5.49 g,
35 mmol) in NMP (7 mL) was prepared in a round-bottomed flask
under a positive pressure of nitrogen. The mixture was heated at
120 ꢀC for 30 min, afterwards a sample was taken and analysed by
FIA-ESI-MS (positive ionization).
Identified ions signals: PhSAr, [MþH]þ m/z found: 244.30; calcd:
244.38; complex 1, m/z found: 306.10 (100%), 307.00 (20%), 308.02
(51%), 309.00 (8%), 310.10 (1%), calcd: 306.04; complex 2, m/z
found: 549.30 (100%), 550.00 (35%), 551.30 (65%), 552.00 (20%),
553.20 (4%), calcd: 549.15. A mixture of PhSAr (0.86 mmol) and

9016
E. Sperotto et al. / Tetrahedron 66 (2010) 9009e9020
+Q1: 0.083 to 2.002 min from Sample 1 (Cu Br benzene) of 70626-09 Cu Br-benzene.wiff (Turbo Spray)
Max. 8.8e6 cps.
244.3
8.8e6
8.5e6
8.0e6
7.5e6
7.0e6
6.5e6
6.0e6
5.5e6
5.0e6
4.5e6
4.0e6
3.5e6 199.2
3.0e6
2.5e6
2.0e6
1.5e6
1.0e6
306.1
549.3
552.3
363.4
200.3
5.0e5
208.4
220
405.5
309.2
301.3
693.2
700
247.2
240
507.1
500 520
256.4
260 280
366.3
360
631.2
620 640
450.1
440 460
200
300
320
340
380
400
420
480
540
560
580
600
660
680
m/z, amu
Cu(MeCN)4BF4 (0.43 mmol) in methanol (10 mL) was prepared in
a round-bottomed flask under a positive pressure of nitrogen. The
mixture was heated at 120 ꢀC for 30 min, afterwards a sample was
taken, and analysed by MALDI-TOF-MS (DHB Matrix).
Identified ions signals: PhSAr [MþH]þ m/z found: 244.3694;
calcd: 244.3730; complex 1, m/z found: 306.3092 (100%), 307.3129
(20%), 308.3099 (50%), calcd: 306.04; complex 2, m/z found: 549.38
(100%), 550.3785 (40%), 551.3837 (57%), calcd: 549.15.

E. Sperotto et al. / Tetrahedron 66 (2010) 9009e9020
9017
A reaction mixture was prepared (as described in Kinetic ex-
periments in HEL auto-MATE working station section), a sample
was taken and analysed by FIA-ESI-MS (positive ionization).
Identified ions signals: PhSAr [MþH]þ m/z found: 244.40; calcd:
244.38; complex 1, m/z found: 306.30 (100%), 307.00 (20%), 308.20
(45%), calcd: 306.04; complex 2, m/z found: 549.30 (100%), 550.00
(40%), 551.20 (60%), 552.30 (23%), 553.00 (7%), 554.30 (4%), calcd:
549.15; complex C29H30CuN2S [Cu(PhSAr)BBA]þ m/z found: 501.30
(100%), 502.00 (40%), 503.20 (60%), calcd: 501.15. Non-identified
ions signals: m/z 269.30, 395.20, 419.30, 539.0.
+Q1: 0.083 to 2.002 min from Sample 1 ( Cu 30 minmin) of 70626-14 Cu reaction 30 min.wiff (Turbo Spray)
Max. 4.0e6 cps.
207.4
3.6e5
3.4e5
3.2e5
395.2
3.0e5
2.8e5
2.6e5
2.4e5
2.2e5
2.0e5
1.8e5
1.6e5
1.4e5
1.2e5
1.0e5
8.0e4
6.0e4
4.0e4
2.0e4
244.4
397.3
269.3
306.3
419.3
335.3
221.4
363.3
365.1
396.3
271.1
261.2
333.3
308.2
208.4
203.3
421.2
337.4
289.2
277.2
268.3
263.2
256.4
399.4
225.5
216.4 229.2
320.2
318.2
405.4
246.3
336.3
302.3
205.2
273.4
427.2
366.3
357.2
360
413.3
429.2
237.3
240
290.4
290
350.2
340 350
259.2
287.2
280
406.4
410
401.3
321.2
368.4
299.2
300
339.2
375.2
310.1
310
393.3
390
249.1
250
210
220
230
260
270
320
m/z, amu
330
370
380
400
420
430

9018
E. Sperotto et al. / Tetrahedron 66 (2010) 9009e9020
+Q1: 0.083 to 2.002 min from Sample 1 ( Cu 30 minmin) of 70626-14 Cu reaction 30 min.wiff (Turbo Spray)
Max. 4.0e6 cps.
549.3
6.8e4
6.5e4
6.0e4
5.5e4
5.0e4
4.5e4
4.0e4
3.5e4
3.0e4
2.5e4
2.0e4
1.5e4
1.0e4
501.3
551.2
503.2
507.0
539.0
509.2
505.0
540.9
552.3
545.2
537.2
530.1
456.2
445.3
438.2
477.2
479.2
485.4
510.3
475.3
542.1
580.4
621.4
554.3
5000.0
515.1
520
459.1
695.2
609.3
685.0
448.1
571.2
496.3
659.2
660
681.0
589.2
462.3
592.3
600
499.3
626.3
638.2
640
568.4
624.9
620
534.0
540
585.3
580
688.5
700
440
460
480
500
560
680
m/z, amu
5.2.6. Coordination evidences for complex 17, [CuPhSAr]þ. A mixture
of PhSAr (0.125 mmol) and freshly synthesised CuBr (0.125 mmol)
in DMSO-d6 (1 mL) was prepared in a schlenk tube under nitrogen
atmosphere. The mixture was heated at 120 ꢀC for 180 min,
afterwards a sample was taken and analysed by 1H NMR.
1H NMR (399.94 MHz, DMSO-d6):
d 2.29 (s, 6H, N(CH3)2), 3.53 (s,
2H, NCH2), 7.18e7.20 (m, 1H, Ar), 7.30e7.44 (m, 8H, Ar).
(For comparison to) PhSAr: 1H NMR (399.94 MHz, DMSO-d6):
d
2.12 (s, 6H, N(CH3)2), 3.48 (s, 2H, NCH2), 7.14e7.34 (m, 8H, Ar), 7.43
(d, 1H, Ar).

E. Sperotto et al. / Tetrahedron 66 (2010) 9009e9020
9019
1H NMR spectra in DMSO-d6, at room temperature. (a) Spectrum
of PhSAr; (b) spectrum of PhSAr and CuBr in 1:1 M ratio, after 3 h at
120 ꢀC in DMSO-d6.
13. (a) Evans, D. A.; Katz, J. L.; West, T. R. Tetrahedron Lett. 1998, 39, 2937e2940; (b)
Lam, P. Y. S.; Clark, C. G.; Saubern, S.; Adams, J.; Winters, M. P.; Chan, D. M. T.;
Combs, A. Tetrahedron Lett. 1998, 39, 2941e2944.
14. For selected examples: (a) Burgos, C. H.; Barder, T. E.; Huang, X.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2006, 45, 4321e4326; (b) Aranyos, A.; Old, D. W.; Kiyo-
mori, A.; Wolfe, J. P.; Sadighi, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121,
4369e4378; (c) Mann, G.; Incarvito, C.; Rheingold, A. L.; Hartwig, J. F. J. Am.
Chem. Soc. 1999, 121, 3224e3225; (d) Shelby, Q.; Kataoka, N.; Mann, G.; Hart-
wig, J. J. Am. Chem. Soc. 2000, 122, 10718e10719; (e) Fleckenstain, C. A.; Plenio,
H. Chem. Soc. Rev. 2010, 39, 694e711; (f) Hu, T.; Schulz, T.; Torborg, C.; Chen, X.;
Wang, J.; Beller, M.; Huang, J. Chem. Commun. 2009, 7330e7332.
15. Harkal, S.; Kumar, K.; Michalik, D.; Zapf, A.; Jackstell, R.; Rataboul, F.; Riermeier,
T.; Monsees, A.; Beller, M. Tetrahedron Lett. 2005, 46, 3237e3240.
16. For iron-catalyzed CeO coupling examples: (a) Bistri, O.; Correa, A.; Bolm, C.
Angew. Chem., Int. Ed. 2008, 47, 586e588; (b) Bonnamour, J.; Bolm, C. Org. Lett.
2008, 10, 2665e2667; (c) Xia, N.; Taillefer, M. Chem.dEur. J. 2008, 14,
6037e6039.
17. (a) Sperotto, E.; de Vries, J. G.; van Klink, G. P. M.; van Koten, G. Tetrahedron Lett.
2007, 48, 7366e7370; (b) Chang, J. W. W.; Chee, S.; Mak, S.; Buranaprasertsuk,
P.; Chavasiri, W.; Chan, P. W. H. Tetrahedron Lett. 2008, 49, 2018e2022; (c)
He, H.; Wu, Y.-J. Tetrahedron Lett. 2003, 3445e3446; (d) Chauhan, S. M. S.; Jain,
N.; Kumar, A.; Srinivas, K. A. Synth. Commun. 2003, 33, 3607e3614; (e) Zhang, J.;
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18. Cotton, F. A.; Wilkinson, G.; Murillo, C. A.; Bochmann, M. Advanced Inorganic
Chemistry; John Wiley: New York, NY, 1999, pp 854e876.
5.2.7. Preparation of complex [Cu(PhSAr)2]BF4. A solution of 2(N,N-
dimethyl benzylamino)-phenyl sulfide (0.211 g, 0.86 mmol,
2 equiv) in distilled and deoxygenated benzene (10 mL) was
transferred under nitrogen via cannula to a suspension of Cu
(MeCN)4BF4 (136 mg, 0.43 mmol, 1 equiv) in distilled and de-
oxygenated benzene (15 mL). The mixture was stirred under ni-
trogen at room temperature overnight, while a yellow solid
precipitated. The pale yellow precipitate was then filtered and
washed with dry Et2O (2ꢃ5 mL). The solvent was then removed and
the off-white powder dried under reduced pressure (yield 76%,
0.21 g, 0.326 mmol).
1H NMR (399.94 MHz, CD3OD):
d 2.49 (s, 6H, CH3), 3.81 (br s, 2H,
CH2), 7.20 (s, 3H, Ar), 7.33e7.46 (m, 6H, Ar).
FT-IR (ATR, cmꢂ1): 3062.90, 2886.15, 2846.50, 1588.11, 1473.95,
1463.94, 1440.34, 1045.59, 1032.90, 976.85, 873.94, 837.10, 752.48,
707.71, 693.83, 681.42.
Anal. Calcd for C30H34BCuF4N2S2: C 56.56, H 5.38, N 4.40. Found:
C 55.55; H 5.03, N 4.10.
19. Saphier, M.; Burg, A.; Sheps, S.; Cohen, H.; Meyerstein, D. J. Chem. Soc., Dalton
Trans. 1999, 1845e1850.
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Acknowledgements
We thank the Dutch Ministry of Economic Affairs, NWO/CW,
NRSC-C and Chemspeed Technologies for the financial support
given to the CW/CombiChem programme and Dr. T. Jerphagnon for
help and discussions.
23. (a) Cristau, H.-J.; Cellier, P. P.; Hamada, S.; Spindler, J.-F.; Taillefer, M. Org. Lett.
2004, 6, 913e916 and references therein; (b) Ouali, A.; Spindler, J.-F.; Jutand, A.;
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Jaseer, E. A.; Sekar, G. J. Org. Chem. 2009, 74, 3675e3679; (f) Benyahya, S.;
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2010, 75, 1791e1794.
Supplementary data
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.09.019.
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