Improved palladium-catalyzed sonogashira coupling reactions of aryl chlorides

Article abstract of DOI:10.1002/chem.200802444

The improved palladium-catalyzed Sonogashira coupling reactions of aryl chlorides without the necessity to add copper salts were analyzed for the development of palladacycles, adamantylphosphines, carhene ligands, and 2-phosphino-N-arylin-doles and -pyrro

Full text of DOI:10.1002/chem.200802444

COMMUNICATION
DOI: 10.1002/chem.200802444
Improved Palladium-Catalyzed Sonogashira Coupling Reactions of Aryl
Chlorides
Christian Torborg, Jun Huang, Thomas Schulz, Benjamin Schꢀffner, Alexander Zapf,
Anke Spannenberg, Armin Bçrner, and Matthias Beller*[a]
À
The construction of Csp
N
transformation in organic chemistry. The resulting aryl al-
kynes are building blocks often encountered within natural
products, pharmaceutical products, and molecular materi-
als.[1] Due to the highly conjugated p system, this structural
motif is found in organic semiconductors, and the respective
products act as molecular sensors, light-emitting diodes, or
polarizers for liquid-crystalline displays.[2] In recent years
polyaryleneethynylenes (PAEs) and oligoaryleneethynylenes
(OAEs) such as 1 and 2 (Scheme 1) have become an estab-
lished class of conjugated polymers in addition to poly(p-
phenylenevinylene)s (PPVs) and polyacetylenes. Moreover,
arylene–ethynylene macrocycles (AEMs) (e.g. 3) and macro-
molecules such as 4 possess interesting electronic properties
and lead to defined nanostructures.[3,4] Apart from material
science, the construction of aryl alkynes plays an important
role in the synthesis of complex molecules of pharmaceuti-
cal and agrochemical interest (e.g. 5,[5] 6,[6] 7[7]), even though
the arylene–ethynylene structure itself does not often occur
in natural products, which is in marked contrast to the corre-
sponding vinylene–ethynylene motif.[8] However, the alkyny-
lation of aromatic halides and subsequent cyclization is a
widely used method for the synthesis of carbo-[9] and hetero-
cycles[10] as well as intermediates of natural products.[11] It is
undeniable that the most effective way to form aryl–alkyne
bonds is still palladium-catalyzed coupling reactions of aro-
matic halides with alkynes in the presence of base and
copper co-catalysts. Although this reaction was independent-
ly discovered by Cassar, Heck, and Sonogashira in 1975,[12]
today it is generally known as the Sonogashira reaction, and
numerous catalytic systems have been reported for this
[a] C. Torborg, Dr. J. Huang, T. Schulz, B. Schꢀffner, Dr. A. Zapf,
Dr. A. Spannenberg, Prof. Dr. A. Bçrner, Prof. Dr. M. Beller
Leibniz-Insitut fꢁr Katalyse e. V. an der Universitꢀt Rostock
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
Fax : (+49)381-1281-5000
E-mail: matthias.beller@catalysis.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200802444.
Scheme 1. Examples for structures bearing the arylene–ethynylene motif.
Chem. Eur. J. 2009, 15, 1329 – 1336
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1329

transformation.[13] During the last few years important cata-
lyst developments have been described such as the minimi-
zation of the catalyst amount,[14] the activation of less-reac-
tive starting materials (aryl chlorides, alkyl halides),[15] the
selective transformation of more functionalized substrates,[16]
and the application of cost effective and/or sustainable
methods.[17] With respect to the latter point, aryl–alkyne cou-
pling methods catalyzed by more cost-effective metals such
as iron[18] or copper[19] have become an interesting alterna-
tive to Pd-catalyzed procedures regarding the efficient cou-
pling of aryl iodides. However, so far there is no general
procedure for the efficient coupling of deactivated aryl bro-
mides and inexpensive aryl chlorides with these metals. A
generally accepted mechanism[20] of the Sonogashira reac-
tion consists of two catalytic cycles: a) the ꢃclassicꢄ palladi-
For some years we have been interested in the develop-
ment of palladium catalysts that can be applied for coupling
reactions on both laboratory as well as industrial scale. In
this respect we have developed palladacycles,[28] adamantyl-
phosphines,[29] carbene ligands,[30] and 2-phosphino-N-arylin-
doles and -pyrroles.[31] More recently, we also reported the
synthesis of 2-phosphino-N-arylimidazoles and their applica-
tion in cross-coupling reactions of aryl chlorides and bro-
mides.[32] Importantly, such monodentate N-substituted het-
eroaryl phosphines are conveniently synthesized by selective
metalation at the 2-position of the respective N-substituted
heterocycle (pyrrole, indole, imidazole). Thus, a variety of
novel ligands is easily available and can be efficiently pre-
pared in a modular synthesis. This is an important aspect,
since the application of palladium-catalyzed coupling reac-
tions in the fine chemical and pharmaceutical industry re-
quires in general a fine-tuning of the catalytic system. Here,
we describe for the first time the use of N-aryl-heteroaryl-
phosphines in Sonogashira coupling reactions of aryl chlor-
ides without the necessity to add copper salts. Inspired by
the work of the Buchwald group on XPhos,[33] we synthe-
sized the novel ligand [N-(2,6-diisopropylphenyl)-2-imida-
zolyl]-di-tert-butylphosphine L1 (Figure 1).
um-based coupling reaction that involves the oxidative addi-
1
À
tion of an aryl (vinyl) halide (or triflate) R X to a low-co-
ordinate palladium(0) complex, then transmetalation of a
copper-acetylide (formed in the second catalytic cycle) to
1
2
À
generate a R Pd
U
undergoes a cis–trans isomerzation and reductive elimina-
tion to give the aryl (vinyl)–alkyne and the regenerated cat-
alyst; and b) the so-called ꢃcopper-cycleꢄ, in which the
copper–acetylide is generated from the free alkyne in the
presence of a base, which is often an amine. This latter cycle
is poorly understood: for example, the in situ formation of a
copper acetylide is not proven yet, although recently indi-
rect evidence has been found.[21] In fact, most of the amines
used are not basic enough to deprotonate the alkyne to pro-
vide an anionic species which can further react to the corre-
sponding copper acetylide. Therefore, a p-alkyne–Cu com-
plex, which makes the alkyne proton more acidic, is often
proposed as an intermediate. With respect to further catalyst
developments the application of copper-free (and also
amine-free) protocols is of importance due to the environ-
mental and economical advantages. However, to date, only
a few examples of Sonogashira reactions without copper
source have been described. Notably, Gelman and Buchwald
discovered in 2003 a catalyst system consisting of [PdCl2-
Figure 1. Molecular structure of L1. Hydrogen atoms are omitted for
clarity. The thermal ellipsoids correspond to 30% probability.
ACHTUNGTRENNUNG(CH3CN)2] and the so-called XPhos ligand, which allowed a
general coupling of aryl chlorides and aryl tosylates with
various terminal alkynes.[15c,22] Although desilylation of tri-
methylsilylacetylene, an important substrate in the synthesis
of larger molecules, was observed during the reaction, an ex-
cellent substrate scope was demonstrated. Interestingly from
a mechanistic viewpoint, the same authors reported that the
presence of copper iodide in the coupling of aryl chlorides
with alkynes inhibits coupling reactions. Copper-free Sono-
gashira reactions were also described in water.[23] More re-
cently, Yi et al. reported in 2006 the application of [PdCl2-
Advantageously, this ligand is formed straightforwardly
from easily available substrates (2,6-diisopropylamine,
glyoxal, formaldehyde,[34] and chloro-di-tert-butylphosphine)
in two steps. For our catalytic studies we chose the reaction
of 3-chlorothiophene (8) and 1-octyne (9), which is a more
challenging coupling reaction. Propylene carbonate (PC)
was first chosen as solvent for the reaction. Its usage in cou-
pling reactions offers several advantages including the possi-
bility of catalyst recycling a) via extraction of the nonpolar
product with nonpolar solvents from the reaction mixture[35]
or b) as PC can form part of temperature-dependent multi-
component solvent systems (TMS systems).[36] To our delight
ACHTUNGTRENNUNG(PCy3)2] in the coupling of various aryl chlorides with al-
kynes under copper-free conditions with 3 mol% catalyst at
100–1508C.[24] Activation of the alkyne without copper is
supposed to proceed via formation of a (h2-RCꢀCH)Pd0 L2
species.[25,26] However, the term ꢃcopper-freeꢄ should be con-
sidered carefully, since commercially available palladium
salts can contain traces of copper.[27]
the reaction proceeded with 1 mol% [PdCl2ACTHNUTRGNEU(GN CH3CN)2] and
8 mol% of phosphine ligand L1 in 76% yield at 908C
(Table 1, entry 1).[37] Unfortunately, decreasing the Pd/ligand
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Chem. Eur. J. 2009, 15, 1329 – 1336

Pd-Catalyzed Sonogashira Coupling Reactions of Aryl Chlorides
COMMUNICATION
Table 1. Sonogashira coupling of 3-chlorothiophene and 1-octyne without
copper.[a]
Entry Pd
[mol%]
L
Solvent Base
Conv.
[%]
Yield
[%][b]
[mol%]
1
2
3
4
5
1
8
3
6
8
3
2
1
3
3
3
1
3
PC
PC
PC
Cs2CO3
Cs2CO3
Cs2CO3
8
3
4
76
25
30
71
68
18
10
87
45
2
1
2
1
1
1
1
1
1
1
1
1
Figure 2. Molecular structure of 10. Hydrogen atoms are omitted for
clarity. The thermal ellipsoids correspond to 30% probability.
toluene Na2CO3 80
toluene Na2CO3 73
toluene Na2CO3 18
toluene Na2CO3 10
toluene Na2CO3 90
toluene Na2CO3 45
toluene Na2CO3 18
toluene Na2CO3 60
toluene Na2CO3 90
6
7
8[c]
9[d]
10[e]
11[f]
12[g]
For the same reasons, an excess of ligand is not necessary
any more. Hence, complex 10 was directly applied in the re-
action (Table 1, entry 11). However, the reaction yielded
only 40% of the coupling product under optimized condi-
tions; with an additional 2 mol% of L1, the same activity of
the catalyst was observed as with 1 mol% of [PdCl2-
40
86
[a] Reaction
conditions:
3-chlorothiophene
(1 equiv),
1-octyne
(1.3 equiv), base (2.6 equiv), solvent (0.5m), 16 h (reaction times not opti-
mized). [b] GC yields (internal standard: hexadecane). [c] 2 equiv of 1-
octyne and 4 equiv of base. [d] PdACHTNUTRGENNG(U OAc)2. [e] 1 mol% of CuI. [f] 2 equiv
AHCTUNGTREN(NGUN CH3CN)2] and 3 mol% of L1 (Table 1, entry 12). In agree-
ment with the observation by Buchwald et al., inhibition of
the reaction is observed when CuI was applied as co-catalyst
(Table 1, entry 10). Next, a series of commercially available
phosphines and novel dialkyl-2-(N-arylimidazolyl)phos-
phines were compared in the model reaction. Selected re-
sults of this ligand screening are shown in Table 2. Not sur-
prisingly, triphenylphosphine (Table 2, entry 1), but also ster-
ically hindered, basic ligands such as tri-tert-butylphosphine
(employed as the HBF4 salt; Table 2, entry 2) and cataCXi-
um A (Table 2, entry 3) showed no reactivity without any
copper co-catalyst, too. Similarly, N-aryl-2-phosphinopyr-
roles and N-aryl-2-phosphinoindoles (Table 2, entries 4–6)
gave no conversion. Unexpectedly, even XPhos (Table 2,
entry 7) showed only low reactivity under these conditions.
However, significant amounts of the desired coupling prod-
uct are obtained in the presence of the tested imidazole-
based phosphine ligands. Among this class of ligands the fol-
lowing trends can be observed: within the applied N-mesi-
tyl-substituted ligands the di-1-adamantyl derivative gave
the best result (Table 2, entry 10, 55% yield), while the
yield drops significantly going over the corresponding 2-(di-
tert- butylphosphino)imidazole ligand (Table 2, entry 9) to
the sterically less demanding 2-(dicyclohexylphosphino)imi-
dazole (Table 2, entry 8). Evidently, the more sterically hin-
dered ligands gave favorable catalytic results probably be-
cause they accelerate the reductive elimination. Comparing
entries 9 and 11 in Table 2, the ligand substituted with two
phenyl rings in the backbone gave a better yield and selec-
tivity (47% yield; 58% conversion). However, ligand L1
(Table 2, entry 12) showed the best performance compared
to all other ligands tested. Interestingly, the corresponding
2-(di-1-adamantyl)phosphine (Table 2, entry 13) gave only
of 1-octyne and 4 equiv of base, 1 mol% of complex 10. [g] 2 equiv of 1-
octyne and 4 equiv of base, 1 mol% of complex 10, 2 mol% L1.
ratio from 1:8 to 1:3 lowered the product yield (Table 1, en-
tries 2 and 3) significantly. Apparently, the reaction in pro-
pylene carbonate needs an excess of ligand, which may be
explained by partial displacement of the ligand by solvent
molecules.[38] In contrast to the reaction in propylene car-
bonate, the Sonogashira coupling in toluene with sodium
carbonate as base yielded the desired 3-octinylthiophene in
good yield at lower ligand concentration (Table 1, entries 4
and 5). However, an excess of ligand is obviously needed
(Table 1, entries 6 and 7). The best yield is obtained by addi-
tion of two equivalents of the alkyne (Table 1, entry 9, 87%
yield); most likely because the PdII species is reduced to the
catalytically active Pd0 species by the alkyne in the first
place. After a standard procedure,[39] complex 10 was pre-
pared from one equivalent of [PdCl2ACTHNUGTRNE(UNG CH3CN)2] and one
equivalent of L1. Remarkably, X-ray analysis showed a h2-
P,N chelation of L1 to the metal center (Figure 2).[40] Time-
dependent 31P NMR experiments showed that this complex
is also formed from a mixture of one equivalent of [PdCl2-
ACHTUNGTRENNUNG(CH3CN)2] and three equivalents of L1 in propylene carbon-
ate as well as in toluene. Therefore it is most likely that it is
also present in the reaction mixture and should act as a pre-
cursor for a monoligated Pd0 species. Monoligated Pd0 spe-
cies are supposed to be the catalyst in coupling reactions, if
bulky biarylphosphines like L1 are applied.[41] With the
phosphine already attached to the metal center, the creation
of the catalytically active species is considered to be easier
from 10 than from a mixture of [PdCl2ACTHNUGTRNE(UNG CH3CN)2] and L1.
Chem. Eur. J. 2009, 15, 1329 – 1336
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1331

M. Beller et al.
Table 2. Reaction of 3-chlorothiophene and 1-octyne using different
phosphine ligands.[a]
detail. Table 3 demonstrates that good to excellent results
can be obtained under mild conditions in the case of activat-
ed aryl and heteroaryl chlorides using 1 mol% catalyst
Table 3. Sonogashira coupling of various aryl and heteroaryl chlorides
with different alkynes.[a]
Entry
Ligand
PPh3
PACHTUNGTRENNUNG(tBu)3*HBF4
BuPAd2
Conversion [%]
Yield [%][b]
1
2
3
0
3
0
0
0
0
Entry Aryl chloride Alkyne
Product
Yield [%][b]
97
4
5
2
3
0
0
1
6
7
7
0
6
2
3
93
75
34
8
19
76
63
1
21
55
4
97
5[c]
42
87
64
9
6
10
7
11
12
58
47
68
8
9
31
87
73
31
10
73
77
83
45
11
13
25
12[c]
13[c]
[a] Reaction
conditions:
3-chlorothiophene
(1 equiv),
1-octyne
(1.3 equiv), Na2CO3 (2.6 equiv), [PdCl2ACHNUTTGRENNG(NU CH3CN)2] (1 mol%), ligand
(3 mol%), toluene (0.5m), 908C, 16 h (reaction times not optimized).
[b] GC yields (internal standard: hexadecane).
[a] Reaction conditions: 3-chlorothiophene (1 equiv), 1-octyne (2 equiv),
Na2CO3 (4 equiv), [PdCl2A(CH3CN)2] (1 mol%), L1 (3 mol%), toluene
(0.5m), 908C, 16 h (reaction times not optimized). [b] Yield of isolated
CTHUNGTRENNUNG
25% yield, even though it is considered to be more bulky.
Finally, the Sonogashira reaction without added copper co-
catalyst in the presence of ligand L1 was studied in more
product. [c] 0.5 mol% [PdCl
halide, 1 equiv alkyne.
2ACHTUNGTERN(NUNG CH3CN)2], 1.5 mol% L1. [d] 2 equiv aryl
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Pd-Catalyzed Sonogashira Coupling Reactions of Aryl Chlorides
COMMUNICATION
(if liquid) (1 mmol), and the alkyne (2 mmol) were added successively
under argon atmosphere. The reaction mixture was heated up to 908C
for 16 h (reaction times not optimized) while it was stirred vigorously.
After cooling to room temperature, the mixture was then quenched with
water (3 mL), and the aqueous phase was extracted with diethyl ether
(3ꢅ4 mL). The organic phases were combined, concentrated, and the de-
sired product was isolated by column chromatography (cyclohexane or
cyclohexane/ethyl acetate mixtures). Alternatively, the reaction mixture
was quenched with water (3 mL) and diluted with diethyl ether (8 mL).
Hexadecane was then added as an internal standard and quantitative
analysis was performed by gas chromatography.
(Table 3, entries 1–4; 75–97% yield). Moreover, electron-
rich aryl chlorides such as 4-chloroanisole react readily with
1-octyne in 87% yield (Table 3, entry 6). Notably, amino
groups are tolerated under these conditions as shown by the
reaction of 2-bromo-6-chloro-4-fluoroaniline, which is con-
verted into the corresponding 2-subsituted product (Table 3,
entry 7). The reaction of 2-chlorostyrene with 1-octyne gave
an interesting highly conjugated coupling product (Table 3,
entry 8). This reaction also shows that the catalyst system is
chemoselective for the coupling of the alkyne, as no stilbene
or stilbene oligomers are observed. Finally, 3-chlorothio-
phene was allowed to react with various alkynes. In addition
to the reaction of 1-octyne (87%; Table 3, entry 9) also reac-
tions with cyclopentyl-, triethylsilyl-, and phenylacetylene
proceeded smoothly (73–83%; Table 3, entries 10–12).
In summary, palladium-catalyzed Sonogashira couplings
have been performed in the presence of N-substituted heter-
oaryl phosphines without copper co-catalysts for the first
time. In general, good to excellent coupling results of a vari-
ety of aryl and heteroaryl chlorides—including challenging
substrates—have been obtained in the presence of [N-(2,6-
diisopropylphenyl)-2-imidazolyl]-di-tert-butylphosphine L1
at low catalyst loading. Various functional groups including
amino, silyl, and vinyl groups are tolerated under these con-
ditions, in contrast to previously reported copper-free proce-
dures. The novel procedure is cost effective and benign with
respect to solvent, base, and avoiding the addition of copper
salts.
1
(4-Acetylphenylethynyl)trimethylsilane: H NMR (300 MHz, CDCl3): d=
7.75–7.71 (m, 2H, 2ꢅHarom), 7.41–7.35 (m, 2H, 2ꢅHarom), 2.43 (s, 3H,
CH
197.5 (CH
(Carom), 104.2 (Cacetyl–Carom), 98.3 (C-Si
0.00 ppm (Si
(CH3)3); MS (70 eV): m/z (%): 216 (18) [M+], 201 (100), 158
3A
(CH3)3); 13C NMR (75 MHz, CDCl3): d=
ACHTUNGTRENNUNG
CTHUNGTRENNUNG
A
CHTUNGTRENNUNG
AHCTUNGTRENNUNG
(9), 143 (7); HRMS: calcd for C13H16OSi: 216.09649; found: 216.09620.
3-(Phenylethynyl)thiophene: 1H NMR (300 MHz, CDCl3): d=7.49–7.39
(m, 3H, 3ꢅHarom), 7.33–7.19 (m, 4H, 4ꢅHarom), 7.16–7.09 ppm (m, 1H,
2ꢅHarom); 13C NMR (75 MHz, CDCl3): d=131.6 (Carom), 129.9 (Carom),
128.6 (Carom), 128.4 (Carom), 128.3 (Carom), 125.4 (Carom), 123.2 (Carom), 122.3
(Carom), 88.9 (Cacetyl), 84.5 ppm (Cacetyl); MS (70 eV): m/z (%): 184 (100)
[M+], 152 (11), 139 (24); HRMS: calcd for C12H8S: 184.03412; found:
184.03381.
3-(Cyclopentylethynyl)thiophene: 1H NMR (300 MHz, CDCl3): d=7.36–
7.28 (m, 1H, Harom), 7.23–7.16 (m, 1H, Harom), 7.08–7.01 (m, 1H, Harom),
2.78 (quin, J=8.0 Hz, 1H, CH), 2.07–1.85 (m, 2H), 1.84–1.43 ppm (m,
6H); 13C NMR (75 MHz, CDCl3): d=130.1 (Carom), 127.4 (Carom), 124.9
(Carom), 123.1 (Carom), 94.1 (Cacetyl), 75.1 (Cacetyl), 33.9 (CH-CH2), 30.8
(CH), 25.1 ppm (CHACTHNUTRGNEUNG
(CH2)CH2);. MS (70 eV): m/z (%): 176 (87) [M+],
161 (13), 147 (100), 134 (30) 128 (18), 121 (18), 115 (18), 108 (23), 97
(10), 91 (11), 77 (9), 69 (8), 63 (11), 45 (10); HRMS: calcd for C11H12S:
176.06542; found: 176.06560.
3-(1-Octynyl)thiophene: 1H NMR (300 MHz, CDCl3): d=7.35–7.29 (m,
1H, Harom), 7.23–7.16 (m, 1H, Harom), 7.07–7.01 (m, 1H, Harom), 2.36 (t,
J=7.0 Hz, 2H, Cacetyl-CH2), 1.65–1.19 (m, 8H, (CH2)4CH3), 0.89 ppm (t,
J=7.0 Hz, 3H, (CH2)4CH3); 13C NMR (75 MHz, CDCl3): d=130.1
(Carom), 127.5 (Carom), 125.0 (Carom), 123.1 (Carom), 90.0 (Cacetyl-Carom), 75.6
(Cacetyl-CH2), 31.4, 28.8, 28.7, 22.6, 19.4 (Cacetyl-CH2), 14.1 ppm
((CH2)4CH3); MS (70 eV): m/z (%): 192 (54) [M+], 163 (22), 149 (45),
135 (61), 123 (100), 115 (52), 108 (22), 97 (32), 91 (17), 77 (26), 63 (13),
45 (17); HRMS: calcd for C12H16S: 192.09644; found: 192.09672.
Experimental Section
General: All reactions were performed under an argon atmosphere using
standard Schlenk techniques. All starting materials and reactants were
used as received from commercial suppliers, except toluene, which was
distilled from sodium and stored under argon before use. Phosphine li-
gands and complexes were stored in Schlenk flasks but weighed under
air. NMR spectra were recorded on an ARX300 (Bruker) spectrometer;
chemical shifts are given in ppm and are referenced to the residual sol-
vent peak. Mass spectra were recorded on an AMD 402 double-focusing,
magnetic sector spectrometer (AMD Intectra). GC-MS spectra were re-
corded on a HP 5989A (Hewlett Packard) chromatograph equipped with
a quadropole analyzer. Gas chromatography analyses were realized on a
HP 6890 (Hewlett Packard) chromatograph using a HP 5 column. Melt-
ing points were measured on a SMP3 (Stuart) and are not corrected.
2-Methyl-4-(3-thiophenyl)-3-butyn-2-ol: 1H NMR (300 MHz, CDCl3): d=
7.36–7.32 (m, 1H, Harom), 7.20–7.14 (m, 1H, Harom), 7.04–6.99 (m, 1H,
H
arom), 2.19 (br s, 1H, OH), 1.53 ppm (s, 6H, 2ꢅ CH3); 13C NMR
(75 MHz, CDCl3): d=129.9 (Carom), 128.7 (Carom), 125.3 (Carom), 121.8
(Carom), 93.4 (Cacetyl-CACHTUNTGRNE(GNU CH3)2OH), 77.3 (Cacetyl-Carom), 65.7 (C-(CH3)2OH),
31.5 ppm ((CH3)2); MS (70 eV): m/z (%): 166 (33) [M+], 151 (100), 135
(7), 123 (10), 108 (13), 89 (6), 75 (6), 69 (6), 63 (11) 43 (59); HRMS:
calcd for C9H10OS: 166.04469; found: 166.04494.
X-ray structure determinations: Data were collected with a STOE-IPDS
diffractometer using graphite-monochromated MoKa radiation. The struc-
tures were solved by direct methods [SHELXS-97: G. M. Sheldrick, Uni-
versity of Gçttingen, Germany, 1997] and refined by full-matrix least-
squares techniques against F2 [SHELXL-97: G. M. Sheldrick, University
of Gçttingen, Germany, 1997]. XP (Bruker AXS) was used for graphical
representations.
1-Methoxy-4-(oct-1-ynyl)benzene: 1H NMR (300 MHz, CDCl3): d=7.35–
7.27 (m, 2H, 2ꢅHarom), 6.83–6.75 (m, 2H, 2ꢅHarom), 3.78 (s, 3H, OCH3),
2.36 (t, J=6.9 Hz, 2H, CH
0.88 ppm (t, J=6.9 Hz, 3H, CH CTHGNUTRENNUNG
G
2ACHTUNGRTNE(NUNG C4H8)CH3),
(C4H8)CH3); 13C NMR (75 MHz,
CDCl3): d=159.0, 132.9, 116.3, 113.8, 88.9, 80.2, 55.3, 31.4, 28.9, 28.7,
22.6, 19.5, 14.1 ppm; MS (70 eV): m/z (%): 216 (51) [M+], 187 (19), 173
(38), 159 (38), 145 (100), 130 (15), 115 (29), 102 (28); HRMS: calcd for
C15H20O: 216.15087; found: 216.15080.
CCDC-712744 (L1) and CCDC-712745 (10) contain the supplementary
crystallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Methyl-4-(oct-1-ynyl)benzoate: 1H NMR (300 MHz, CDCl3): d=7.95–
7.87 (m, 2H, 2ꢅHarom), 7.44–7.37 m, 2H, 2ꢅHarom), 3.86 (s, 3H, CH
O)), 2.38 (t, J=7.0 Hz, 2H, CH2A(C5H11)), 1.64–1.20 (m, 8H, CH2-
(C4H8)CH3), 0.87 ppm (t, J=7.0 Hz, 3H, CH2A
(C4H8)CH3); 13C NMR
(75 MHz, CDCl3): d=166.6 (CH3O(C=O)), 131.5 (Carom), 129.4 (Carom),
129.0 (Carom), 128.8 (Carom), 94.0 (Cacetyl-CH2), 80.1 (Cacetyl-Carom), 52.1
(CH3O(C=O)), 31.4, 28.6, 28.6, 22.6, 19.5 (Cacetyl-CH2), 14.1 ppm
((CH2)4CH3); MS (70 eV): m/z (%): 244 (36) [M+], 213 (29), 201 (45),
3ACHTUNGTRENNUNG(C=
CTHUNGTRENNUNG
A
CHTUNGTRENNUNG
Sonogashira reaction of aryl chlorides: A 25 mL Schlenk tube was evacu-
ated and backfilled with argon. It was charged with [PdCl2ACTHNUTRGNEN(UG CH3CN)2]
(2.59 mg, 0.01 mmol), L1 (11.2 mg, 0.03 mmol), and Na2CO3 (424 mg,
4 mmol). If it was a solid, the (hetero)aryl chloride was also added at
that point. Then, toluene (2 mL), the corresponding (hetero)aryl chloride
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
Chem. Eur. J. 2009, 15, 1329 – 1336
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1333

M. Beller et al.
173 (35), 143 (52), 129 (100), 115 (43); HRMS: calcd for C16H20O2:
244.14578; found: 244.14578.
Acknowledgements
3-Chloro-5-fluoro-2-(oct-1-ynyl)aniline: 1H NMR (300 MHz, CDCl3): d=
6.98–6.86 (m, 2H, 2ꢅHarom), 4.60–4.00 (br s, 2H, 2ꢅNH2), 2.48 (t, J=
We thank Dr. W. Baumann, Dr. C. Fischer, Dipl. Ing. A. Koch, S. Buch-
holz, S. Schareina, A. Kammer, and S. Rossmeisl (all LIKAT) for excel-
lent analytical assistance. We also acknowledge helpful comments from
Dr. A. Sergeev. Generous financial support from the state of Mecklen-
burg-Vorpommern, the Bundesministerium fꢁr Bildung und Forschung
(BMBF) and the Deutsche Forschungsgemeinschaft (GRK 1231 and
Leibniz-prize) is gratefully acknowledged.
7.0 Hz, 2H, CH
(t, J=7.0 Hz, 3H, CH CTHUNGTRENNUNG
G
2ACHTUNGTRNE(UNNG C4H8)CH3), 0.88 ppm
(C4H8)CH3); 13C NMR (75 MHz, CDCl3): d=
155.6, 152.4, 141.1 (d, J=2.4 Hz), 118.6 (d, J=11.5 Hz), 116.6 (dd, J=
39.4 Hz, 24.5 Hz), 110.3 (d, J=10.1), 97.8, 75.9 (d, J=3.6), 31.4, 28.7,
28.7, 22.6, 19.6, 14.1 ppm; IR (ATR): n˜ =3484, 3385, 3082, 2955, 2928,
2857, 2223, 1589, 1572, 1469, 1301, 1201, 1157, 1069, 850, 793, 728 cmÀ1
;
MS (70 eV): m/z (%): 253 (87) [M+], 224 (20), 210 (18), 196 (26), 182
(100), 175 (19), 158 (29), 149 (44), 126 (23); HRMS: calcd for
C14H17ClFN: 253.10281; found: 253.10287.
À
Keywords: aryl chlorides · C C coupling · homogeneous
catalysis · palladium · phosphane ligands · Sonogashira
reaction
4-(3,3-Dimethylbut-1-ynyl)benzonitrile: 1H NMR (300 MHz, CDCl3): d=
7.56–7.49 (m, 2H, 2ꢅHarom), 7.55–7.38 (m, 2H, 2ꢅHarom), 1.29 ppm (s,
(CH3)3); 13C NMR (75 MHz, CDCl3): d=132.1, 131.9, 129.2, 118.7,
9H, CACHTUNGTRENNUNG
110.7, 103.5, 78.0, 30.8, 28.2. MS (70 eV): m/z (%): 183 (20) [M+], 168
(100), 153 (31), 140 (13); HRMS: calcd for C13H13N: 183.10425; found:
183.10477.
1-(Oct-1-ynyl)-2-vinylbenzene: 1H NMR (300 MHz, CDCl3): d=7.58–
7.52 (m, 1H, 1ꢅHarom), 7.43–7.35 (m, 1H, 1ꢅHarom), 7.30–7.12 (m, 3H,
2ꢅHarom, 1ꢅHvinyl), 5.78 (dd, J=17.7 Hz, 1.2 Hz, 1H, 1ꢅHvinyl), 5.32 (dd,
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1974, 27, 1491; b) D. W. Knight, G. Pattenden, J. Chem. Soc. Perkin
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D. Kim, J. Org. Chem. 2005, 70, 8723; b) Y. Koyama, M. J. Lear, F.
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267; c) V. Fiandanese, D. Bottalico, C. Cardellicchio, G. Marchese,
A. Punzi, Tetrahedron 2005, 61, 4551; d) P. Kumar, V. Naidu, P.
Gupta, J. Org. Chem. 2005, 70, 2843; e) S. Lopꢆz, F. Fernandꢆz-
Trillo, P. Midꢇn, L. Castedo, C. Saꢈ, J. Org. Chem. 2006, 71, 2808;
f) G. Sabitha, C. S. Reddy, P. Srihari, J. S. Yadav, Synthesis 2003,
2699.
J=11.0 Hz, 1.2 Hz, 1H, 1ꢅHvinyl), 2.46 (t, J=6.9 Hz, 2H, CH
1.70–1.20 (m, 8H, CH2A(C4H8)CH3), 0.91 ppm (t, J=6.9 Hz, 3H, CH2-
ACHTUNGTRENNUNG
(C4H8)CH3); 13C NMR (75 MHz, CDCl3): d=138.8, 135.2, 132.5, 127.7,
127.4, 124.5, 122.9, 115.0, 95.4, 78.9, 31.4, 28.8, 28.7, 22.6, 19.6, 14.1 ppm;
MS (70 eV): m/z (%): 212 (1) [M+], 169 (16), 155 (59), 141 (100), 128
(44), 115 (67); HRMS: calcd for C16H20: 212.15595; found: 212.15596.
1-(Oct-1-ynyl)-4-(trifluoromethyl)benzene: 1H NMR (300 MHz, CDCl3):
d=7.54–7.42 (m, 4H, 4ꢅHarom), 2.40 (t, J=7.1 Hz, 2H, 2ꢅCacetyl-CH2),
1.67–1.21 (m, 8H, (CH2)4CH3), 0.89 ppm (t, J=4.6 Hz, 3H, (CH2)4CH3);
13C NMR (75 MHz, CDCl3): d=131.8, 129.2 (q, J=23.6 Hz), 128.0, 125.2
(q, J=3.8 Hz), 124.1 (q, J=272.1 Hz), 93.4, 79.5, 31.4, 28.6, 28.5, 22.6,
19.5, 14.1 ppm; MS (70 eV): m/z (%): 254 (44) [M+], 235 (26), 225 (81),
211 (98), 197 (45), 183 (100), 170 (37), 159 (62), 129 (78) 115 (40);
HRMS: calcd for C15H17F3: 254.12769; found: 254.12722.
2ACHTUGNTERN(NUNG C5H11)),
CHTUNGTRENNUNG
Triethyl(thiophen-3-ylethynyl)silane: 1H NMR (300 MHz, CDCl3): d=
7.46 (dd, J=3.0 Hz, 1.1 Hz, 1H, 1ꢅHarom), 7.22 (dd, J=5.0 Hz, 3.0 Hz,
1H, 1ꢅHarom), 7.11 (dd, J=5.0 Hz, 1.2 Hz, 1H, 1ꢅHarom), 1.03 (t, J=
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126, 3108; d) T. A. Zeidan, S. V. Kovalenko, M. Manoharan, I. V.
Alabugin, J. Org. Chem. 2006, 71, 962; e) T. Yao, M. A. Campo,
R. C. Larock, Org. Lett. 2004, 6, 2677; f) D. Rodrꢉguez, M. Martꢉnez-
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Org. Chem. 2004, 69, 3842.
7.9 Hz, 9H, SiACHTUNGTRENNUNG(CH2CH3)3), 0.66 ppm (t, J=4.9 Hz, 6H, SiACHTUNTGREN(NNGU CH2CH3)3);
13C NMR (75 MHz, CDCl3): d=130.3, 129.5, 125.1, 122.6, 101.1, 91.4, 7.5,
4.5 ppm; IR (ATR): n˜ =3109, 2953, 2934, 2910, 2873, 2151, 1005, 945,
869, 779, 722, 680 cmÀ1; MS (70 eV): m/z (%): 222 (13) [M+], 193 (99),
165 (100), 137 (83), 111 (16); HRMS: calcd for C12H18SSi: 222.08930;
found: 222.08877.
4-(Oct-1-ynyl)quinoline: 1H NMR (300 MHz, CDCl3): d=8.79 (d, J=
4.5 Hz, 1H, 1ꢅHarom), 8.29–8.01 (m, 2H, 2ꢅHarom), 7.75–7.48 (m, 2H, 2ꢅ
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H
arom), 7.39 (d, J=4.5 Hz, 1H, 1ꢅHarom), 2.53 (t, J=7.1 Hz, 2H, Cacetyl-
CH2), 1.74–1.23 (m, 8H, (CH2)4CH3), 0.95–0.79 ppm (m, 3H,
(CH2)4CH3); 13C NMR (75 MHz, CDCl3): d=149.8, 148.1, 130.8, 129.8,
129.7, 128.2, 126.9, 126.1, 123.6, 101.1, 31.4, 28.7, 28.5, 22.6, 19.8,
14.1 ppm; MS ( 70 eV): m/z (%): 237 (100) [M+], 208 (34), 194 (52), 180
(59), 166 (71), 153 (45), 139 (36); HRMS: calcd for C17H19N: 237.15120;
found: 237.15135.
Complex 10: m.p.>2458C (decomp); 1H NMR (300 MHz, CD2Cl2): d=
7.57 (dd, J=2.6 Hz, 1.5 Hz, 1H, Himid), 7.49 (t, J=7.8 Hz, 1H, 4-Harom),
7.27 (d, J=7.8 Hz, 2H, 3-Harom, 5-Harom), 7.02 (dd, J=1.5 Hz, 0.6 Hz, 1H,
H
imid), 2.29 (sep, J=6.8 Hz, 2H, 2ꢅCH
1.37 (s, 9H, C(CH3)3), 1.23 (d, J=6.9 Hz, 6H, CH
J=6.9 Hz, 6H, CH
(CH3)2); 13C NMR (75 MHz, CD2Cl2): d=146.6, 132.5,
U
ACHTUGNRTNE(NUNG CH3)3),
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
131.9, 128.2, 128.1, 127.7, 125.0, 38.9 (d, J=9.6 Hz), 30.0 (d, J=3.8 Hz),
29.4, 27.6, 21.3 ppm; 31P NMR (120 MHz, CD2Cl2): d=53.7; IR (ATR):
n˜ =3162, 3140, 2962, 2923, 2866, 1457, 1444, 1173, 1132, 813, 805, 787,
770, 763 cmÀ1; HRMS (ESI, [M+ Na+]): calcd for C23H37Cl2N2NaPPd:
573.10026; found: 573.09955.
1334
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Chem. Eur. J. 2009, 15, 1329 – 1336

Pd-Catalyzed Sonogashira Coupling Reactions of Aryl Chlorides
COMMUNICATION
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