Ethynyl-cyclohexanol: an efficient acetylene surrogate in Sonogashira coupling

Article abstract of DOI:10.1016/j.tet.2007.10.031

The Sonogashira coupling of aryl halides in the presence of 1-ethynyl-cyclohexanol as an acetylene source provides an efficient method for the synthesis of diarylacetylenes without the isolation of the appropriate arylacetylenes.

Full text of DOI:10.1016/j.tet.2007.10.031

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 975–982
Ethynyl-cyclohexanol: an efficient acetylene surrogate
in Sonogashira coupling
*
ꢀ
Marton Csekei, Zoltan Novak and Andras Kotschy
ꢀ
ꢀ
ꢀ
ꢀ
´
Institute of Chemistry, Eo€tvo€s Loraꢀnd University, Paꢀzmaꢀny Peter s. 1/A, H-1117 Budapest, Hungary
Received 14 September 2007; accepted 8 October 2007
Available online 10 October 2007
ꢀ
Dedicated to Professor Csaba Szantay on the occasion of his 80th birthday
Abstract—The Sonogashira coupling of aryl halides in the presence of 1-ethynyl-cyclohexanol as an acetylene source provides an efficient
method for the synthesis of diarylacetylenes without the isolation of the appropriate arylacetylenes.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
surrogate and coupled with an aryl halide. Addition of the ap-
propriate reagent—that initiated the release of the acetylene
protecting group—followed by the second aryl halide led to
the formation of the desired diarylacetylenes in a one-pot
process. Extending the results of D’Auria11 Brisbois and
co-workers12 described an efficient method for the prepa-
ration of diarylalkynes along the domino approach using
trimethylsilyl-acetylene derivatives, while our research
group followed a similar strategy using 2-methyl-3-butyn-
2-ol as acetylene source.13
The palladium-catalyzed coupling of terminal acetylenes
with aryl and vinyl halides (Sonogashira reaction) is an
important and widely used carbon–carbon bond forming
reaction in organic synthesis,1 enabling the efficient con-
struction of triple bond containing synthetic intermediates,2
condensed heterocycles,3 and natural products.3c,4 The
Sonogashira coupling is also one of the most frequently
used reactions for the preparation of conjugated oligomers
and polymers5 having interesting optical2l,6 and electronic
properties.7
Sequential Coupling
i
Pd/CuI
Ar
Ar'
Ar
PG
Ar
The primary limitation in the preparation of diarylacetylenes
is the availability of the appropriate monoarylacetylenes,
which is greatly limited by their moderate stability. A conve-
nient solution to this problem is offered by the sequential
cross-coupling of masked arylacetylenes and aryl halides
(Scheme 1),8 where the release of the protecting group is
combined with the Sonogashira coupling of an aryl halide
giving the diarylacetylenes without the need to isolate
the sensitive monoarylacetylene intermediate. The most
frequently used masked acetylene moieties in lab-scale
experiments are trimethylsilyl-acetylene9 and 2-methyl-3-
butyn-2-ol10 derivatives. Since the masked arylacetylenes
are usually also prepared in a Sonogashira coupling, it is
possible to combine their formation with the sequential cou-
pling. In the domino Sonogashira coupling both 2-methyl-3-
butyn-2-ol and TMS-acetylene were applicable as acetylene
Ar'
X
i: deprotecting agent
Domino Coupling
Ar
Ar
PG
i
Pd
/CuI
Ar'
X
+
Ar
Ar'
Ar
X
PG
Scheme 1.
Although both TMS-acetylene and 2-methyl-3-butyn-2-ol
usually work well, there is still a strong demand for the
introduction of new protected acetylenes that would offer
enhanced applicability. Utilizing the working principle of
2-methyl-3-butyn-2-ol, other ethynyl carbinols are expected
to be useful as acetylene sources too. A plausible choice is
1-ethynyl-cyclohexanol, a commercially available chemical,
whose price and ‘mode of action’ is very similar to 2-meth-
yl-3-butyn-2-ol, with the only difference that it releases the
chemically more inert cyclohexanone. The present paper
reports the scope and limitations of the use of this protected
acetylene in sequential and domino coupling reactions
leading to diarylacetylenes.
* Corresponding author. Tel.: +36 1 372 2910; fax: +36 1 372 2909; e-mail:
kotschy@elte.hu
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.10.031

´
M. Csekei et al. / Tetrahedron 64 (2008) 975–982
976
2. Results and discussion
advantageous in certain cases. Since diisopropylamine acts
not only as a solvent but also as a base in the Sonogashira
coupling, for the further studies we chose the KOH–DIPA
combination. It should also be noted that the biphasic condi-
tions introduced by Rossi et al.14 (entry 9) do also work well
on this substrate. The reason for not pursuing this line further
was our finding that under these conditions we also observed
a considerable amount of decomposition with sensitive sub-
strates (e.g., electron deficient heterocycles, halopurines).
In order to obtain some model compounds for our studies
first different aryl halides (1a–i) were coupled with 1-ethy-
nyl-cyclohexanol in diisopropylamine (DIPA) to give the
appropriate products (2a–i) in excellent yield (Table 1) on
the multigram scale.
The first reaction we studied was the release of the protecting
group (cyclohexanone) from the arylethynyl-cyclohexanols
and the subsequent Sonogashira coupling with aryl halides.
The optimal solvent–base combination was determined
using 2a and iodobenzene (1a) as test substrates (Table 2)
and the reactions were monitored by GC–MS.
Having established the optimal conditions for the sequential
coupling we studied the reaction of arylethynyl-cyclohexa-
nols (2a–h) and different aryl halides (1a–j). Since, several
of these combinations are ‘mirror images’ of one another
they also provided an opportunity to establish the influence
of the coupling order on the yield of the process. The results
summarized in Table 3 revealed the following trends. If one
of the aryl groups is electron rich, such as 4-methoxyphenyl
or 4-aminophenyl, then the order of the coupling has a signi-
ficant effect on the yield. Coupling of the arylethynyl-cyclo-
hexanol bearing the electron rich aromatic group with less
electron rich aryl halides gave substantially higher yields
than the other way around (cf. entries 5 and 6, 8 and 9, 10
and 11, 12 and 13, 16 and 17 or 31 and 32).
The use of KOH as base worked well to give full conversion
and excellent selectivity in 60 min (entries 1 and 2). Cesium
carbonate was less effective, while sodium hydride led to
side reactions and the use of barium hydroxide resulted
only in decomposition. Both DIPA and toluene work well
as solvent, showing that the reaction is not too sensitive to
the polarity of the media, although the use of DIPA was
Table 1. The preparation of 1-arylethynyl-cyclohexanols
3% (PPh3)2PdCl2
OH
OH
3% CuI
Table 3. The sequential deprotection–Sonogashira coupling of arylethynyl-
cyclohexanols (2a–h) with aryl halides (1a–j)
+
X
Ar
Ar
i
Pr2NH
2a-i
1a-i
5% (PPh3)2PdCl2
OH
5% CuI
+
Ar
Ar'
X
Ar
Ar'
Entry
ArX
Product
Yielda (%)
i
KOH, Pr2NH
2a-h
1a-j
3a-s
1
2
3
4
5
6
7
8
9
Iodobenzene (1a)
4-Iodoanisole (1b)
2a
2b
2c
2d
2e
2f
2g
2h
2i
99
91
87
75
99
98
93
85
97
Entry
2
Ar0X
Product
Yielda (%)
2-Bromonaphtalene (1c)
3-Bromopyridine (1d)
2-Fluoroiodobenzene (1e)
4-Iodoacetophenon (1f)
4-Iodoaniline (1g)
1
2
3
4
5
6
7
8
2a
2a
2a
2d
2b
2b
2b
2b
2c
2b
2d
2b
2e
2b
2g
2b
2h
2c
2c
2c
2d
2c
2e
2d
2e
2d
2e
2e
2e
2f
1a
1jb
1d
1a
1a
1jb
1b
1c
1b
1d
1b
1e
1b
1g
1b
1h
1b
1a
1c
1d
1c
1e
1c
1d
1d
1e
1a
1jb
1e
1a
1f
3a
3a
3b
3b
3c
3c
3d
3e
3e
3f
76
73
73
95
70
54
30
87
57
82
47
84
27
31
33
67
49
70
69
61
63
83
67
72
74
66
71
69
82
77
78
33
2-Bromothiophene (1h)
2-Bromoiodobenzene (1i)
a
Isolated yields.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
Table 2. The sequential deprotection and Sonogashira coupling of 2a and
iodobenzene (1a) under various conditions
3f
3g
3g
3h
3h
3i
3i
3j
3k
3l
3l
3m
3m
3n
3o
3o
3p
3p
3q
3r
3s
5% (PPh3)2PdCl2
OH
5% CuI
+
Ph
Ph
1a
I
Ph
Ph
base, solvent
2a
3a
Entry
Solvent
Base
Conversiona (%)
Time (h)
1
2
3
4
5
6
7
8
9
DIPA
Toluene
DIPA
Toluene
DIPA
Toluene
DIPA
Toluene
Toluene
KOH
KOH
NaH
NaH
Cs2CO3
Cs2CO3
Ba(OH)2
Ba(OH)2
aq NaOHe
100
100
100b
100c
100
100
35d
1
1
1
3.5
3
4.5
3
100d
100
3
1
a
The reactions were run in a 80 ꢀC oil bath. Conversions were determined
by the GC–MS analysis of the reaction mixture.
Containing 10% Z-stilbene as byproduct.
Containing 25% Z-stilbene as byproduct.
Decomposition.
NaOH of 4 equiv in 2 M solution and 3 mol % TBAI.
2b
2f
b
c
d
e
1b
3s
a
Isolated yields.
Compound 1j stands for bromobenzene.
b

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M. Csekei et al. / Tetrahedron 64 (2008) 975–982
977
The only cases where the reaction performs poorly are cou-
plings with two electron rich aryl groups (entries 7, 14 and
15). For most other reactions we observed good to excellent
yields. The use of bromobenzene (1j) instead of iodoben-
zene gave usually comparable yields in longer reactions
(cf. entries 1 and 2, 27 and 28) unless the other aryl group
was electron rich (entries 5 and 6) where the decreased yield
might be attributed to increased decomposition during the
prolonged heating. Except for these limitations the sequen-
tial coupling performed reliably. Neutral and electron defi-
cient aryl bromides and iodides gave comparable yields.
Both five- and six-membered heterocycles can be included
in the process and the presence of an ortho-substituent on
the aryl halide had no significant influence on the efficiency
of the coupling either.
utilizing 2-methyl-3-butyn-2-ol as acetylene surrogate.
There are certain cases where the domino coupling of aryl
halides with 2-methyl-3-butyn-2-ol gave only mediocre
yields.13 Some of these reactions were repeated using 1-ethy-
nyl-cyclohexanol (Table 4, entries 6–9). The coupling of
iodobenzene (1a) and 2-chloro-bromobenzene (1k) pro-
ceeded efficiently, irrespective of the order of the coupling.
Coupling of the same bromobenzene derivative (1k) with
3-iodotoluene (1l) gave also improved yields. It is not only
with bromoaromatics that the use of 1-ethynyl-cyclohexanol
gives higher yields. The domino homocoupling of 4-iodo-
anisole (1b) was also more efficient with this acetylene
surrogate (entry 1).
As a further test to the utility of 1-ethynyl-cyclohexanol
as an acetylene surrogate we attempted to use it in the
preparation of a [12]tribenzannulene derivative (Scheme 2).
The sequential ‘homocoupling’ of (o-bromophenyl-ethynyl)-
cyclohexanol (2i) in toluene gave the desired hexahydrotri-
benzo[12]annulene in 20% yield. Increasing the activity of
the catalyst by using PCy3 as ligand we obtained 4 in 32%
yield, which is in line with the reported synthetic approaches
utilizing 2-methyl-3-butyn-2-ol.15
Having established the scope and limitations of the sequen-
tial coupling of arylethynyl-cyclohexanols and aryl halides
we also tested the possibility of carrying out this transforma-
tion as the domino coupling of two aryl halides and 1-ethy-
nyl-cyclohexanol (Table 4). The test reactions were aimed at
the weak points of the sequential approach, the synthesis of
diarylacetylenes bearing two electron rich aromatic rings
such as 3d and 3h.
Already in the first attempt, in the preparation of bis(p-ani-
syl)-acetylene (3d, entry 1) from 4-iodoanisole and 1-ethy-
nyl-cyclohexanol we observed a substantial improvement
of the yield to 76% from the 30% observed in the sequential
coupling. The coupling of 4-iodoanisole (1b) and 4-iodoani-
line (1g) was also more efficient in the domino fashion
(entries 2 and 3), the yield increasing to 47% from 31%.
When the electron rich 4-iodoanisole (1b) and the electron
deficient 4-iodo-acetophenon (1f) were coupled with
1-ethynyl-cyclohexanol (entries 4 and 5) the yield depended
largely on the coupling order.
5% PdL2Cl2
OH
5% CuI, KOH
toluene
Br
2i
L: PPh3 Y: 20%, PCy3 Y: 32%
4
Scheme 2. Synthesis of tribenzo[12]benzannulene.
In summary, an efficient method is reported for the use of
1-ethynyl-cyclohexanol as acetylene surrogate in Sonogashira
couplings. It was demonstrated that using this reagent diaryl-
acetylenes can be synthesized either in a sequential manner
or in a one-pot domino Sonogashira coupling. In comparison
with the use of the analogous 2-methyl-3-butyn-2-ol this
method was found to work equally well or better on the sub-
strates tested. It was also demonstrated that the order of the
addition of the aryl halides might have a significant effect on
the yield of the process. As a general rule the more electron
rich aryl halides should be coupled first.
Starting with the electron rich aryl halide in the domino
coupling gave a yield that is comparable with the appropriate
sequential coupling, while the reversal of the order led to
diminished yields (alike in the analogous sequential cou-
pling). It was also of interest to compare the efficiency
of the present methodology with the analogous process
Table 4. The domino Sonogashira coupling of aryl halides using 1-ethynyl-
cyclohexanol as acetylene surrogate
3. Experimental
3.1. General
1, 3% (PPh3)2PdCl2
OH
i
3% CuI, Pr2NH
+
X
Ar
Ar
Ar'
2, Ar'-X, KOH
Unless otherwise indicated, all starting materials were
obtained from commercial suppliers (Aldrich, Fisher, Merck),
and were used without further purification. All reactions
were performed under an atmosphere of argon. Analytical
thin-layer chromatography (TLC) was performed on Merck
Entry
1
10
Product
Yielda (%)
1
2
3
4
5
6
7
8
9
1b
1b
1g
1b
1f
1a
1k
1k
1l
1b
1g
1b
1f
1b
1k
1a
1l
3d
3h
3h
3s
3s
3t
3t
3u
3u
76 (66)
47
40
64
24
86 (47)
83 (71)
70 (59)
43 (40)
DC pre-coated TLC plates with 0.25 mm Kieselgel 60 F254
.
Visualization was performed with a 254 nm UV lamp. Silica
gel column chromatography was carried out with Flash silica
1
gel (0.040–0.063 mm) from Merck. The H and 13C NMR
1k
spectra were recorded on a Brucker DRX-250 spectrometer
in CDCl3. Chemical shifts are expressed in parts per million
(d) using residual solvent protons as internal standards
a
Isolated yields. Numbers in parentheses refer to the highest yield of the
same product obtained by using 2-methyl-3-butyn-2-ol.

´
M. Csekei et al. / Tetrahedron 64 (2008) 975–982
978
1
(d 7.26 for H, d 77.0 for 13C). Coupling constants (J) are
reported in hertz (Hz). Splitting patterns are designated as
s (singlet), d (doublet), t (triplet), m (multiplet), dd (doublet
of doublets), dt (doublet of triplets), td (triplet of doublets).
Combination of gas chromatography and low resolution
mass spectrometry was obtained on an Agilent 6890 N
Gas Chromatograph (30 mꢁ0.25 mm column with 0.25 mm
HP-5MS coating, He carrier gas) and Agilent 5973 Mass
NMR (CDCl3; 250 MHz): d 8.72 (d, 1H, J¼1.3 Hz), 8.47
(dd, 1H, J¼4.9 Hz, J¼1.5 Hz), 7.69 (dt, 1H, J¼7.9 Hz,
J¼1.8 Hz), 7.22 (dd, 1H, J¼7.9 Hz, J¼4.9 Hz), 4.28 (m,
1H), 1.99–1.95 (m, 2H), 1.74–1.54 (m, 7H), 1.33–1.25 (m,
1H); 13C NMR (CDCl3, 62.5 MHz): d 151.9, 148.0, 138.8,
123.0, 120.4, 97.4, 80.4, 68.5, 39.8, 25.1, 23.2. IR (solid,
cmꢂ1): 3223, 2948, 2934, 2854, 2159, 2030, 1977, 1626,
1596, 1498, 1447, 1353, 1343, 1293, 1266, 1186, 1155,
1070, 1033, 976, 858, 819, 747; MS (EI, 70 eV) m/z (% rel-
ative intensity, ion): 201 (8, [M+]), 200 (23), 172 (16), 158
(100), 145 (36), 130 (57), 117 (13), 103 (14), 93 (16), 55
(33). Analysis calculated for C13H15NO: C 77.58; H 7.51;
N 6.96. Found: C 77.21; H 7.50; N 6.63.
Spectrometer (Ion source: EI+, 70 eV, 230 ꢀC; interface:
ꢀ
apparatus and are uncorrected.
€
300 C). All melting points were measured on Buchi 501
3.2. General procedure for the synthesis of arylethynyl-
cyclohexanols
3.2.5. 1-(20-Fluorophenyl)ethynyl-cyclohexanol (2e).
Beige solid (2152 mg, 9.86 mmol, 99% yield). Mp:
60–61 ꢀC. 1H NMR (CDCl3; 250 MHz): d 7.40 (t, 1H,
J¼7.2 Hz), 7.30–7.22 (m, 1H), 7.08–7.00 (m, 2H), 2.64 (s,
1H), 2.06–1.97 (m, 2H), 1.75–1.55 (m, 7H), 1.31–1.24 (m,
1H); 13C NMR (CDCl3, 62.5 MHz): d 164.7, 160.7, 133.3,
133.3, 130.0, 129.7, 123.8, 123.7, 115.5, 115.1, 111.5,
111.3, 98.2, 98.1, 77.7, 77.7, 69.2, 39.9, 25.1, 23.3. IR (solid,
cmꢂ1): 3343, 2926, 2855, 1572, 1488, 1443, 1391, 1340,
1297, 1263, 1241, 1208, 1187, 1100, 1063, 1029, 963,
903, 857, 845, 815, 754; MS (EI, 70 eV) m/z (% relative
intensity, ion): 218 (13, [M+]), 217 (15), 199 (7), 190 (8),
175 (100), 162 (37), 147 (74), 133 (56), 122 (24), 120
(24), 109 (15), 81 (31), 55 (43). Analysis calculated for
C14H15OF: C 77.04; H 6.93. Found: C 76.83; H 7.14.
Aryl halide (1) (10 mmol), 1.49 g of 1-ethynyl-cyclohexanol
(12 mmol), 211 mg of PdCl2(PPh3)2 (0.3 mmol, 3%), and
57 mg of CuI (0.3 mmol, 3%) were placed into a flame-dried
Schlenk flask. Diisopropylamine of 20 mL was added, and
the mixture was stirred under argon at 80 ꢀC. The reaction
was followed by TLC and GC–MS. When the coupling
was complete (typically less than 30 min), the product (2)
was separated by column chromatography, using hexane–
ethylacetate eluent.
3.2.1. 1-Phenylethynyl-cyclohexanol (2a).16 Pale yellow
solid (1978 mg, 9.89 mmol, 99% yield). Mp: 57–59 ꢀC. 1H
NMR (CDCl3; 250 MHz): d 7.44–7.39 (m, 2H), 7.31–7.25
(m, 3H), 2.28 (s, 1H), 2.03–1.94 (m, 2H), 1.79–1.55 (m,
7H), 1.33–1.25 (m, 1H); 13C NMR (CDCl3, 62.5 MHz):
d 131.6, 128.2, 128.1, 122.9, 92.8, 84.3, 69.0, 40.0, 25.2,
23.4; MS (EI, 70 eV) m/z (% relative intensity, ion): 200
(20, [M+]), 199 (43), 157 (100), 144 (30), 129 (70), 115
(61), 102 (64), 55 (48).
3.2.6. 1-(40-Acetylphenyl)ethynyl-cyclohexanol (2f).17
Pale brown solid (2380 mg, 9.83 mmol, 98% yield). Mp:
80–81 ꢀC. 1H NMR (CDCl3; 250 MHz): d 7.87 (d, 2H,
J¼8.5 Hz), 7.48 (d, 2H, J¼8.5 Hz), 2.58 (s, 3H), 2.35 (s,
1H), 2.04–1.98 (m, 2H), 1.77–1.55 (m, 7H), 1.35–1.25 (m,
1H); 13C NMR (CDCl3, 62.5 MHz): d 197.4, 136.1, 131.7,
128.1, 127.8, 96.3, 83.5, 69.0, 39.8, 26.5, 25.1, 23.3; MS
(EI, 70 eV) m/z (% relative intensity, ion): 242 (34, [M+]),
199 (100), 171 (50), 143 (19), 129 (23), 115 (21), 55 (47).
3.2.2. 1-(40-Methoxyphenyl)ethynyl-cyclohexanol (2b).16
Yellow solid (2095 mg, 9.10 mmol, 91% yield). Mp:
60–61 ꢀC. 1H NMR (CDCl3; 250 MHz): d 7.35 (d, 2H,
J¼8.7 Hz), 6.81 (d, 2H, J¼8.7 Hz), 3.79 (s, 3H), 2.40 (s,
1H), 2.02–1.92 (m, 2H), 1.77–1.54 (m, 7H), 1.28–1.24 (m,
1H); 13C NMR (CDCl3, 62.5 MHz): d 159.4, 133.0, 115.0,
113.8, 91.4, 84.1, 69.0, 55.2, 40.0, 25.2, 23.4; MS (EI,
70 eV) m/z (% relative intensity, ion): 230 (46, [M+]), 201
(33), 187 (100), 174 (33), 159 (39).
3.2.7. 1-(40-Aminophenyl)ethynyl-cyclohexanol (2g). Pale
brown solid (2000 mg, 9.29 mmol, 93% yield). Mp:
1
117–118 ꢀC. H NMR (CDCl3; 250 MHz): d 7.22 (dt, 2H,
J¼8.6 Hz, J¼2.2 Hz), 6.58 (dt, 2H, J¼8.7 Hz, J¼2.2 Hz),
3.79 (s, 2H), 2.27 (s, 1H), 2.0–1.91 (m, 2H), 1.73–1.51 (m,
7H), 1.28–1.24 (m, 1H); 13C NMR (CDCl3, 62.5 MHz):
d 146.5, 132.9, 114.6, 112.2, 90.5, 84.8, 69.1, 40.1, 25.2,
23.4. IR (solid, cmꢂ1): 3374, 3237, 2929, 2853, 2213,
1605, 1509, 1446, 1337, 1269, 1179, 1156, 1134, 1058,
958, 901, 854, 834, 805; MS (EI, 70 eV) m/z (% relative in-
tensity, ion): 215 (30, [M+]), 197 (100), 186 (31), 172 (74),
169 (63), 159 (21), 144 (51), 130 (53), 117 (76), 106 (31),
55 (81). Analysis calculated for C14H17NO: C 78.10; H
7.96; N 6.51. Found: C 78.35; H 8.13; N 6.14.
3.2.3. 1-(20-Naphthyl)ethynyl-cyclohexanol (2c). White
solid (2175 mg, 8.70 mmol, 87% yield). Mp: 120–121 ꢀC.
1H NMR (CDCl3; 250 MHz): d 7.97 (s, 1H), 7.82–7.74
(m, 3H), 7.51–7.46 (m, 3H), 2.62 (s, 1H), 2.12–2.08 (m,
2H), 1.80–1.59 (m, 7H), 1.33–1.30 (m, 1H); 13C NMR
(CDCl3, 62.5 MHz): d 132.8, 132.6, 131.4, 128.4, 127.8,
127.6, 127.6, 126.5, 126.4, 120.1, 93.2, 84.6, 69.1, 40.0,
25.2, 23.4. IR (solid, cmꢂ1): 3240, 2931, 2854, 2158,
2033, 1604, 1568, 1507, 1446, 1412, 1342, 1302, 1285,
1244, 1182, 1170, 1157, 1134, 1105, 1067, 1038, 963,
828; MS (EI, 70 eV) m/z (% relative intensity, ion): 250
(61, [M+]), 249 (50), 232 (19), 207 (100), 194 (23), 179
(64), 165 (63), 152 (80), 141 (20), 128 (17), 55 (83). Analy-
sis calculated for C18H18O: C 86.36; H 7.25. Found: C 86.59;
H 7.08.
3.2.8. 1-(20-Thienyl)ethynyl-cyclohexanol (2h). Pale
yellow solid (1750 mg, 8.49 mmol, 85% yield). Mp: 97–
1
99 ꢀC. H NMR (CDCl3; 250 MHz): d 7.26–7.17 (m, 2H),
6.95 (dd, 1H, J¼4.9 Hz, J¼3.6 Hz), 2.36 (s, 1H), 2.02–1.97
(m, 2H), 1.75–1.55 (m, 7H), 1.31–1.25 (m, 1H); 13C NMR
(CDCl3, 62.5 MHz): d 131.8, 126.9, 126.8, 122.8, 96.6,
77.5, 69.2, 39.8, 25.1, 23.2. IR (solid, cmꢂ1): 3213, 2931,
2853, 1515, 1446, 1423, 1344, 1285, 1256, 1229, 1183,
3.2.4. 1-(30-Pyridyl)ethynyl-cyclohexanol (2d). White
solid (1510 mg, 7.50 mmol, 75% yield). Mp: 75–76 ꢀC. 1H

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M. Csekei et al. / Tetrahedron 64 (2008) 975–982
979
1069, 964, 938, 902, 851, 826, 731, 702, 694; MS (EI,
70 eV) m/z (% relative intensity, ion): 206 (26, [M+]), 177
(17), 163 (100), 150 (37), 135 (63), 121 (23), 110 (27), 55
(40). Analysis calculated for C12H14OS: C 69.86; H 6.84.
Found: C 69.54; H 7.04.
62.5 MHz): d 152.2, 148.5, 138.4, 131.6, 128.8, 128.4,
123.0, 122.5, 120.4, 92.6, 85.9; MS (EI, 70 eV) m/z (%
relative intensity, ion): 179 (100, [M+]), 178 (22), 151
(14), 126 (21).
3.3.3. 4-Phenylethynyl-anisole (3c).20 White solid. Com-
pounds 2b and 1a yielded 145 mg (0.70 mmol, 70% yield),
while 2b and 1j gave 112 mg (0.54 mmol, 54% yield). Mp:
3.2.9. 1-(20-Bromophenyl)ethynyl-cyclohexanol (2i).18
Pale yellow solid (2720 mg, 9.74 mmol, 97% yield). Mp:
1
1
67–68 ꢀC. H NMR (CDCl3; 250 MHz): d 7.48 (dd, 1H,
59–60 ꢀC. H NMR (CDCl3; 250 MHz): d 7.42–7.34 (m,
J¼8.0 Hz, J¼0.9 Hz), 7.37 (dd, 1H, J¼7.7 Hz, J¼1.6 Hz),
7.18–7.03 (m, 2H), 2.35 (s, 1H), 1.99–1.95 (m, 2H),
1.75–1.48 (m, 7H), 1.22–1.12 (m, 1H); 13C NMR (CDCl3,
62.5 MHz): d 133.2, 132.3, 129.3, 126.9, 125.6, 125.0,
97.5, 83.0, 69.3, 39.9, 25.2, 23.3; MS (EI, 70 eV) m/z (%
relative intensity, ion): 280 (3, [M+]), 278 (3, [M+]), 237
(17), 235 (17), 222 (4), 220 (4), 209 (7), 207 (7), 200 (13),
199 (100), 182 (7), 180 (6), 143 (7), 128 (19), 115 (23),
101 (9), 55 (43).
4H), 7.23–7.18 (m, 3H), 6.74 (d, 2H, J¼8.9 Hz), 3.65 (s,
3H); 13C NMR (CDCl3, 62.5 MHz): d 159.5, 133.0, 131.4,
128.2, 127.8, 123.5, 115.3, 113.9, 89.4, 88.0, 55.1; MS
(EI, 70 eV) m/z (% relative intensity, ion): 209 (44), 208
(100, [M+]), 193 (100), 165 (82), 139 (11).
3.3.4. Di-(4-methoxyphenyl)-acetylene (3d).13 Pale yellow
solid. Compounds 2b and 1b gave 71 mg (0.30 mmol, 30%
yield). The domino coupling yielded 180 mg (0.76 mmol,
76% yield). Mp: 139–140 ꢀC. 1H NMR (CDCl3;
250 MHz): d 7.46 (dt, 4H, J¼8.8 Hz, J¼2.5 Hz), 6.87 (dt,
4H, J¼9.1 Hz, J¼2.4 Hz), 3.82 (s, 6H); 13C NMR (CDCl3,
62.5 MHz): d 159.4, 132.8, 115.7, 113.9, 87.9, 55.3; MS
(EI, 70 eV) m/z (% relative intensity, ion): 238 (100,
[M+]), 223 (86), 195 (28), 180 (17), 152 (38).
3.3. General procedure for the synthesis of diaryl-
acetylenes
Sequentialcoupling: arylethynyl-cyclohexanol (2) (1 mmol),
aryl halide (1) (1 mmol), 35 mg of PdCl2(PPh3)2 (0.05 mmol,
5%), 9.5 mg of CuI (0.05 mmol, 5%), and 224 mg of KOH
(4 mmol) were placed into a flame-dried Schlenk flask.
Diisopropylamine of 7 mL was added, and the mixture
was stirred under argon at 80 ꢀC. The reaction was followed
by TLC and GC–MS. When the coupling was complete the
product (3) was separated by column chromatography using
hexane–ethylacetate mixtures (100:0–80:20) as eluent.
3.3.5. 2-(40-Methoxyphenyl)ethynyl-naphthalene (3e).
Yellow solid. Compounds 2b and 1c yielded 224 mg
(0.87 mmol, 87% yield), while 2c and 1b gave 147 mg
(0.57 mmol, 57% yield). Mp: 122–124 ꢀC. 1H NMR
(CDCl3; 250 MHz): d 8.07 (s, 1H), 7.86–7.81 (m, 3H),
7.63–7.49 (m, 5H), 6.93 (d, 2H, J¼8.9 Hz), 3.84 (s, 3H);
13C NMR (CDCl3, 62.5 MHz): d 159.6, 133.1, 133.0,
132.6, 131.6, 131.1, 128.4, 127.9, 127.7, 127.7, 126.4,
120.9, 115.3, 114.0, 89.8, 88.5, 55.2. IR (solid, cmꢂ1):
3054, 2996, 2836, 2213, 1592, 1566, 1508, 1464, 1436,
1303, 1283, 1269, 1243, 1172, 1137, 1106, 1030, 946,
899, 862, 829, 819, 741; MS (EI, 70 eV) m/z (% relative in-
tensity, ion): 258 (100, [M+]), 243 (51), 215 (45), 213 (34),
189 (11). Analysis calculated for C19H14O: C 88.34; H
5.46. Found: C 88.78; H 5.03.
Domino coupling: aryl halide (1) (1 mmol), 149 mg of
1-ethynyl-cyclohexanol (1.2 mmol), 21 mg of PdCl2(PPh3)2
(0.03 mmol, 3%), and 5.7 mg of CuI (0.03 mmol, 3%) were
placed into a flame-dried Schlenk flask. Diisopropylamine
of 7 mL was added, and the mixture was stirred under argon
at 80 ꢀC. The reaction was followed by TLC and GC–MS.
When the first coupling was complete (typically less than
30 min), the appropriate aryl halide (10) (1 mmol), 21 mg of
PdCl2(PPh3)2 (0.03 mmol, 3%), 5.7 mg of CuI (0.03 mmol,
3%) and 224 mg of KOH (4 mmol) were added. The mixture
was stirred under argon at 80 ꢀC, until the reaction was com-
plete. The product (3) was separated by column chromato-
graphy, using hexane–ethylacetate mixtures (100:0–80:20)
as eluent.
3.3.6. 3-(40-Methoxyphenyl)ethynyl-pyridine (3f).13 Pale
yellow solid. Compounds 2b and 1d gave 172 mg
(0.82 mmol, 82% yield), while 2d and 1b yielded 98 mg
1
(0.47 mmol, 47% yield). Mp: 46–48 ꢀC. H NMR (CDCl3;
250 MHz): d 8.75 (d, 1H, J¼1.9 Hz), 8.51 (dd, 1H,
J¼4.9 Hz, J¼1.6 Hz), 7.77 (dt, 1H, J¼7.9 Hz, J¼1.9 Hz),
7.48 (d, 2H, J¼8.8 Hz), 7.25 (dd, 1H, J¼8.0 Hz,
J¼5.0 Hz), 6.88 (d, 2H, J¼8.8 Hz), 3.82 (s, 3H); 13C
NMR (CDCl3, 62.5 MHz): d 159.9, 152.0, 148.1, 138.1,
133.1, 122.9, 120.7, 114.5, 114.0, 92.7, 84.7, 55.2; MS
(EI, 70 eV) m/z (% relative intensity, ion): 209 (100,
[M+]), 194 (42), 166 (28), 139 (28), 113 (14).
3.3.1. Diphenylacetylene (3a).12 White solid. Compounds
2a and 1a yielded 136 mg (0.76 mmol, 76% yield), while
2a and 1j gave 130 mg (0.73 mmol, 73% yield). Mp:
1
54–55 ꢀC. H NMR (CDCl3; 250 MHz): d 7.55–7.51 (m,
4H), 7.37–7.30 (m, 6H); 13C NMR (CDCl3, 62.5 MHz):
d 131.1, 127.8, 127.7, 122.7, 88.9; MS (EI, 70 eV) m/z (%
relative intensity, ion): 178 (100, [M+]), 176 (21), 152
(17), 126 (8).
3.3.7. (40-Methoxyphenyl)ethynyl-fluorobenzene (3g).
White solid. Compounds 2b and 1e yielded 190 mg
(0.84 mol, 84% yield), while using 2e and 1b gave 61 mg
3.3.2. 3-Phenylethynyl-pyridine (3b).19 Pale brown solid.
Compounds 2a and 1d yielded 130 mg (0.73 mmol, 73%
yield), while 2d and 1a gave 170 mg (0.95 mmol, 95%
yield). Mp: 48–49 ꢀC. 1H NMR (CDCl3; 250 MHz): d 8.69
(d, 1H, J¼1.3 Hz), 8.47 (dd, 1H, J¼4.9 Hz, J¼1.7 Hz),
7.73 (dt, 1H, J¼7.9 Hz, J¼2.0 Hz), 7.49–7.45 (m, 2H),
7.31–7.28 (m, 3H), 7.23–7.17 (m, 1H); 13C NMR (CDCl3,
1
(0.27 mmol, 27% yield). Mp: 56–57 ꢀC. H NMR (CDCl3;
250 MHz): d 7.37–7.32 (m, 3H), 7.16–7.07 (m, 1H), 6.97–
6.90 (m, 2H), 6.72 (d, 2H, J¼8.8 Hz); 13C NMR (CDCl3,
62.5 MHz): d 164.4, 160.4, 159.8, 133.2, 133.2, 133.1,
129.6, 129.5, 123.9, 123.8, 115.5, 115.2, 114.8, 113.9,
112.2, 112.0, 94.5, 94.5, 81.3, 81.3, 55.1. IR (solid, cmꢂ1):

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M. Csekei et al. / Tetrahedron 64 (2008) 975–982
980
1598, 1566, 1508, 1488, 1448, 1286, 1265, 1244, 1220,
1195, 1172, 1097, 1024, 940, 864, 835, 819, 751; MS (EI,
70 eV) m/z (% relative intensity, ion): 226 (100, [M+]),
211 (52), 183 (72), 157 (18). Analysis calculated for
C15H11OF: C 79.63; H 4.90. Found: C 79.85; H 4.91.
IR (solid, cmꢂ1): 3054, 2215, 1594, 1557, 1498, 1477,
1402, 1270, 1242, 1183, 1107, 1019, 951, 902, 865, 830,
803, 741, 701; MS (EI, 70 eV) m/z (% relative intensity,
ion): 229 (100, [M+]), 200 (13), 176 (13), 88 (21). Analysis
calculated for C17H11N: C 89.06; H 4.84; N 6.11. Found: C
88.55; H 4.73; N 5.83.
3.3.8. 4-(40-Methoxyphenyl)ethynyl-aniline (3h).21 Pale
yellow solid. Compounds 2b and 1g yielded 70 mg
(0.31 mmol, 31% yield), while using 2g and 1b gave
74 mg (0.33 mmol, 33% yield). The domino coupling ac-
cording to Method B gave 105 mg product (0.47 mmol,
47% yield) when 1b reacted first; 90 mg (0.40 mmol,
40% yield) product was obtained when 1g reacted first.
3.3.13. 2-(Naphth-2-yl)ethynyl-fluorobenzene (3m).
White solid. Compounds 2c and 1e yielded 204 mg
(0.83 mmol, 83% yield), while using 2d and 1c gave
1
165 mg (0.67 mmol, 67% yield). Mp: 90–91 ꢀC. H NMR
(CDCl3; 250 MHz): d 8.12 (s, 1H), 7.87–7.83 (m, 3H),
7.66–7.51 (m, 4H), 7.39–7.30 (m, 1H), 7.19–7.12 (m, 2H);
13C NMR (CDCl3, 62.5 MHz): d 164.7, 160.7, 133.5,
133.4, 132.9, 131.7, 130.0, 129.9, 128.3, 128.0, 127.8,
127.8, 126.8, 126.6, 124.0, 123.9, 120.2, 120.2, 115.7,
115.4, 112.0, 111.8, 94.9, 94.8, 83.0, 83.0. IR (solid,
cmꢂ1): 3051, 2159, 1592, 1573, 1492, 1466, 1444, 1345,
1309, 1264, 1238, 1219, 1139, 1116, 1093, 1028, 951,
940, 906, 867, 822, 753, 744; MS (EI, 70 eV) m/z (% relative
intensity, ion): 247 (18), 246 (100, [M+]), 244 (28), 123 (11).
Analysis calculated for C18H11F: C 87.78; H 4.50. Found: C
87.77; H 4.14.
1
Mp: 138–139 ꢀC. H NMR (CDCl3; 250 MHz): d 7.35 (d,
2H, J¼8.4 Hz), 7.24 (d, 2H, J¼8.1 Hz), 6.77 (d, 2H,
J¼8.3 Hz), 6.54 (d, 2H, J¼8.2 Hz), 3.73 (s, 5H); 13C
NMR (CDCl3, 62.5 MHz): d 159.1, 146.3, 132.7, 116.0,
114.7, 113.9, 112.9, 88.6, 87.1, 55.2; MS (EI, 70 eV) m/z
(% relative intensity, ion): 223 (100, [M+]), 208 (92), 180
(35), 152 (32).
3.3.9. 2-(40-Methoxyphenyl)ethynyl-thiophene (3i).22
White solid. Compounds 2b and 1h yielded 144 mg
(0.67 mmol, 67% yield), while using 2h and 1b gave
1
105 mg (0.49 mmol, 49% yield). Mp: 53–54 ꢀC. H NMR
3.3.14. Di-(3-pyridyl)-acetylene (3n).25 White solid. Com-
pounds 2d and 1d yielded 130 mg (0.72 mmol, 72% yield).
Mp: 59–60 ꢀC. 1H NMR (CDCl3; 250 MHz): d 8.72 (s, 2H),
8.51 (d, 2H, J¼2.7 Hz), 7.75 (dt, 2H, J¼7.9 Hz, J¼1.7 Hz),
7.24 (dd, 2H, J¼7.6 Hz, J¼4.7 Hz); 13C NMR (CDCl3,
62.5 MHz): d 152.2, 149.0, 138.4, 123.0, 119.7, 89.1; MS
(EI, 70 eV) m/z (% relative intensity, ion): 180 (100,
[M+]), 179 (27), 152 (11), 127 (17), 100 (10), 74 (18).
(CDCl3; 250 MHz): d 7.44 (dt, 2H, J¼9.0 Hz, J¼2.4 Hz),
7.26–7.23 (m, 2H), 6.98 (dd, 1H, J¼4.9 Hz, J¼3.9 Hz),
6.86 (dd, 2H, J¼8.8 Hz, J¼2.4 Hz), 3.80 (s, 3H); 13C
NMR (CDCl3, 62.5 MHz): d 159.7, 132.9, 131.4, 127.0,
126.8, 123.7, 114.9, 114.0, 93.0, 81.2, 55.2; MS (EI,
70 eV) m/z (% relative intensity, ion): 214 (100, [M+]),
199 (85), 171 (37), 127 (20).
3.3.10. 2-Phenylethynyl-naphthalene (3j).23 White solid.
Compounds 2c and 1a yielded 160 mg (0.70 mmol, 70%
yield). Mp: 113–114 ꢀC. 1H NMR (CDCl3; 250 MHz):
d 8.09 (s, 1H), 7.86–7.82 (m, 3H), 7.63–7.60 (m, 3H),
7.54–7.50 (m, 2H), 7.44–7.37 (m, 3H); 13C NMR (CDCl3,
62.5 MHz): d 133.0, 132.8, 131.6, 131.4, 128.4, 128.4,
128.3, 128.0, 127.8, 127.8, 126.6, 126.5, 123.3, 120.5,
89.8, 89.7; MS (EI, 70 eV) m/z (% relative intensity, ion):
228 (100, [M+]), 226 (32), 207 (8), 114 (11).
3.3.15. 3-(20-Fluorophenyl)ethynyl-pyridine (3o). Color-
less liquid. Compounds 2d and 1e yielded 130 mg
(0.66 mmol, 66% yield), while using 2e and 1d gave
145 mg (0.74 mmol, 74% yield). 1H NMR (CDCl3;
250 MHz): d 8.79 (d, 1H, J¼1.3 Hz), 8.55 (dd, 1H,
J¼4.9 Hz, J¼1.4 Hz), 7.80 (dt, 1H, J¼7.9 Hz, J¼1.9 Hz),
7.52 (td, 1H, J¼7.3 Hz, J¼1.7 Hz), 7.37–7.23 (m, 2H),
7.15–7.06 (m, 2H); 13C NMR (CDCl3, 62.5 MHz):
d 164.4, 160.4, 152.0, 148.6, 138.3, 133.2, 133.2, 130.4,
130.3, 123.9, 123.8, 122.8, 119.8, 115.6, 115.2, 111.1,
110.8, 90.7, 90.7, 85.8, 85.8. IR (oil, cmꢂ1): 3031, 2224,
1560, 1492, 1472, 1450, 1406, 1263, 1221, 1186, 1145,
1120, 1098, 1022, 942, 864, 801, 753, 700; MS (EI,
70 eV) m/z (% relative intensity, ion): 197 (100, [M+]),
170 (13), 144 (30). Analysis calculated for C13H8FN: C
79.18; H 4.09; N 7.10. Found: C 79.30; H 4.11; N 7.17.
3.3.11. Di-(naphth-20-yl)acetylene (3k).24 White solid.
Compounds 2c and 1c yielded 192 mg (0.69 mmol, 69%
yield). Mp: 215–216 ꢀC. 1H NMR (CDCl3; 250 MHz):
d 8.11 (s, 2H), 7.86–7.83 (m, 6H), 7.40 (dd, 2H, J¼8.3 Hz,
J¼1.3 Hz), 7.53–7.49 (m, 4H); 13C NMR (CDCl3,
62.5 MHz): d 133.1, 132.9, 131.5, 128.4, 128.0, 127.8,
127.8, 126.7, 126.6, 120.6, 90.2; MS (EI, 70 eV) m/z (% rel-
ative intensity, ion): 278 (100, [M+]), 276 (30), 139 (26), 138
(26), 125 (9).
3.3.16. 2-Phenylethynyl-fluorobenzene (3p).26 White
solid. Compounds 2e and 1a yielded 140 mg (0.71 mmol,
71% yield), while using 2e and 1j gave 135 mg
1
3.3.12. 3-(Naphth-20-yl)ethynyl-pyridine (3l). White solid.
Compounds 2c and 1d yielded 140 mg (0.61 mmol, 61%
yield), while using 2d and 1c gave 144 mg (0.63 mmol,
(0.69 mmol, 69% yield). Mp: 45–46 ꢀC. H NMR (CDCl3;
250 MHz): d 7.60–7.51 (m, 3H), 7.40–7.28 (m, 4H), 7.17–
7.08 (m, 2H); 13C NMR (CDCl3, 62.5 MHz): d 164.6,
160.6, 133.4, 133.4, 131.7, 130.0, 129.9, 128.6, 128.3,
124.0, 123.9, 122.9, 115.7, 115.3, 112.0, 111.8, 94.4, 94.4,
82.7, 82.6; MS (EI, 70 eV) m/z (% relative intensity, ion):
197 (17), 196 (100, [M+]), 194 (13), 170 (11), 98 (11).
1
63% yield). Mp: 70–72 ꢀC. H NMR (CDCl3; 250 MHz):
d 8.71 (d, 1H, J¼1.4 Hz), 8.42 (dd, 1H, J¼4.8 Hz, J¼
1.4 Hz), 7.94 (s, 1H), 7.70–7.66 (m, 4H), 7.45 (dd, 1H,
J¼8.6 Hz, J¼1.5 Hz), 7.39–7.33 (m, 2H), 7.12 (dd, 1H,
J¼7.8 Hz, J¼4.9 Hz); 13C NMR (CDCl3, 62.5 MHz):
d 152.1, 148.4, 138.3, 132.9, 132.8, 131.7, 128.0, 128.0,
127.7, 127.7, 126.8, 126.6, 122.9, 120.4, 119.6, 93.0, 86.2.
3.3.17. Di-(2-fluorophenyl)-acetylene (3q).12 White solid.
Compounds 2e and 1e yielded 175 mg (0.82 mmol, 82%

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M. Csekei et al. / Tetrahedron 64 (2008) 975–982
981
yield). Mp: 50–52 ꢀC. 1H NMR (CDCl3; 250 MHz): d 7.59–
7.52 (m, 2H), 7.39–7.30 (m, 2H), 7.18–7.08 (m, 4H); 13C
NMR (CDCl3, 62.5 MHz): d 164.6, 160.6, 133.5, 133.5,
130.4, 130.3, 124.0, 123.9, 115.7, 115.4, 111.7, 111.4,
87.7, 87.6; MS (EI, 70 eV) m/z (% relative intensity, ion):
214 (100, [M+]), 193 (10), 144 (6), 107 (13), 94 (8).
separated by column chromatography, using hexane as elu-
ent. Yellow solid, using 35 mg of Pd(PPh3)2Cl2 yielded
20 mg product (0.066 mmol, 20% yield), while using
37 mg Pd(PCy3)2Cl2 gave 32 mg product (0.107 mmol,
32% yield). Mp: 202–204 ꢀC (decomp.). 1H NMR (CDCl3;
250 MHz): d 7.31–7.23 (m, 6H), 7.14–7.07 (m, 6H); 13C
NMR (CDCl3, 62.5 MHz): d 132.0, 128.5, 126.6, 92.8; MS
(EI, 70 eV) m/z (% relative intensity, ion): 301 (25), 300
(100, [M+]), 298 (36), 150 (26), 149 (33), 136 (13).
3.3.18. 4-Phenylethynyl-acetophenone (3r).27 Pale yellow
solid. Compounds 2f and 1a yielded 170 mg (0.77 mmol,
1
77% yield). Mp: 95–96 ꢀC. H NMR (CDCl3; 250 MHz):
d 7.83 (d, 2H, J¼8.7 Hz), 7.52–7.44 (m, 4H), 7.28–7.25
(m, 3H), 2.50 (s, 3H); 13C NMR (CDCl3, 62.5 MHz):
d 197.2, 136.1, 131.7, 131.6, 128.7, 128.4, 128.2, 128.1,
122.5, 92.6, 88.6, 26.5; MS (EI, 70 eV) m/z (% relative inten-
sity, ion): 220 (55, [M+]), 205 (100), 176 (61), 151 (25), 102
(11), 88 (20).
Acknowledgements
The authors thank Dr. K. Torkos for providing the necessary
analytical background. The financial support of the Hunga-
rian Scientific Research Fund (OTKA F047125/2004 and
D048657) and KPI (GVOP-3.2.1.-0358/2004) is gratefully
acknowledged.
3.3.19. 4-(40-Methoxyphenyl)ethynyl-acetophenone
(3s).28 Pale yellow solid. Compounds 2b and 1f yielded
195 mg (0.78 mmol, 78% yield), while using 2f and 1b
gave 83 mg (0.33 mmol, 33% yield). The domino coupling
according to Method B obtained 160 mg (0.64 mmol, 64%
yield) product when 1b reacted first, and 60 mg
(0.24 mmol, 24% yield) product when 1f reacted first. Mp:
References and notes
1. (a) Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E., de Meijere, A., Eds.; John Wiley &
Sons: New York, NY, 2002; (b) Metal-Catalyzed Cross-
Coupling Reactions; de Meijere, A., Diederich, F., Eds.; Wiley-
VCH: Weinheim, 2004; (c) Palladium Reagents and Catalysts:
New Perspectives for the 21st Century; Tsuji, J., Ed.; John
Wiley & Sons: Chichester, UK, 2004; (d) Sonogashira, K.;
Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467; (e)
Sonogashira, K. Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3,
Chapter 2.4, p 521; (f) Bumagin, N. A.; Sukhomlinova, L. I.;
Luzikova, E. V.; Tolstaya, T. P.; Beletskaya, I. P. Tetrahedron
Lett. 1996, 37, 897; (g) Hundertmark, T.; Littke, A. F.;
Buchwald, S. L.; Fu, G. C. Org. Lett. 2000, 2, 1729; (h)
Erdelyi, M.; Gogoll, A. J. Org. Chem. 2001, 66, 4165; (i)
Doucet, H.; Hierso, J.-C. Angew. Chem., Int. Ed. 2007, 46, 834;
(j) Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874.
1
123–124 ꢀC. H NMR (CDCl3; 250 MHz): d 7.91 (d, 2H,
J¼8.4 Hz), 7.57 (d, 2H, J¼8.2 Hz), 7.48 (d, 2H,
J¼8.7 Hz), 6.88 (d, 2H, J¼8.7 Hz), 3.82 (s, 3H), 2.59 (s,
3H); 13C NMR (CDCl3, 62.5 MHz): d 197.2, 160.0, 135.8,
133.2, 131.4, 128.5, 128.2, 114.6, 114.0, 92.9, 87.5, 55.2,
26.5; MS (EI, 70 eV) m/z (% relative intensity, ion): 250
(94, [M+]), 235 (100), 207 (20), 192 (17), 176 (14), 164
(50), 163 (58), 117 (18).
3.3.20. (20-Chlorophenylethynyl)-benzene (3t).13 Pale yel-
low liquid. The domino coupling according to Method B
yielded 183 mg (0.86 mmol, 86%), when 1a reacted first,
1
and 83% (177 mg, 0.83 mmol) when 1k reacted first. H
NMR (CDCl3; 250 MHz): d 7.58–7.51 (m, 3H), 7.41–7.37
(m, 1H), 7.35–7.30 (m, 3H), 7.23–7.15 (m, 2H); 13C NMR
(CDCl3, 62.5 MHz): d 135.8, 133.1, 131.7, 129.2, 129.2,
128.6, 128.3, 126.4, 123.1, 122.8, 94.5, 86.1; MS (EI,
70 eV) m/z (% relative intensity, ion): 212 (100, [M+]),
176 (50), 151 (21), 88 (19).
ꢀ
2. (a) Novak, Z.; Szabo, A.; Repasi, J.; Kotschy, A. J. Org. Chem.
2003, 68, 3327; (b) Novak, Z.; Kotschy, A. Org. Lett. 2003, 5,
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3495; (c) Draper, T. L.; Bailey, T. R. J. Org. Chem. 1995, 60,
748; (d) Gomtsyan, A.; Didomenico, S.; Lee, C.-H.;
Matulenko, M. A.; Kim, K.; Kowaluk, E. A.; Wismer, C. T.;
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Sotelo, E. Synlett 2002, 2062; (f) Samaritani, S.; Menicagli,
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3.3.21. 3-(20-Chlorophenylethynyl)-toluene (3u).13 Yellow
solid. Domino coupling yielded 70% (160 mg, 0.70 mmol)
when 1k reacted first, and 97 mg (0.43 mmol, 43%), when 1l
1
reacted first. Mp: 39–41 ꢀC. H NMR (CDCl3; 250 MHz):
d 7.54–7.49 (m, 1H), 7.40–7.31 (m, 3H), 7.24–7.10 (m,
4H), 2.31 (s, 3H); 13C NMR (CDCl3, 62.5 MHz): d 137.9,
135.8, 133.1, 132.2, 129.5, 129.2, 129.1, 128.7, 128.2,
126.4, 123.2, 122.6, 94.7, 85.8, 21.1; MS (EI, 70 eV) m/z
(% relative intensity, ion): 226 (100, [M+]), 189 (65), 165
(17), 94 (23).
3.3.22. Hexadehydrotribenzo[12]annulene (4).29 1-(20-
Bromophenylethynyl)-1-cyclohexanol (2i) (279 mg, 1 mmol),
5% of PdCl2L2 (0.05 mmol), 9.5 mg of CuI (0.05 mmol,
5%), and 224 mg of KOH (4 mmol) were placed into
a flame-dried Schlenk flask. Absolute toluene of 7 mL was
added, and the mixture was stirred under argon at 80 ꢀC.
The reaction was followed by TLC and GC–MS. When the
sequential coupling was complete, the product (4) was
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