Microwave-assisted copper-catalyzed Sonogashira reaction in PEG solvent

Article abstract of DOI:10.1055/s-2007-980337

A catalytic system composed of copper salt, potassium carbonate and appropriate poly(ethylene glycol) (PEG; liquid or solid, various molecular weight: 300< MW <3400) was developed to perform a Sonogashira arylation under microwave activation. In the prese

Full text of DOI:10.1055/s-2007-980337

LETTER
1279
Microwave-Assisted Copper-Catalyzed Sonogashira Reaction in PEG Solvent
M
E
icrowave-Ass
v
iste
d
Coppe
r
e
-Catalyze
d
l
Sonog
i
R
n
e
action a Colacino, Latifa Daïch, Jean Martinez, Frédéric Lamaty*
Institut des Biomolécules Max Mousseron (IBMM), CNRS-Université Montpellier I et II, Place Eugène Bataillon,
4095 Montpellier Cedex 5, France
3
Fax +33(467)144866; E-mail: frederic.lamaty@univ-montp2.fr
Received 17 January 2007
have already explored the use of copper catalyst in the
Heck reaction22 under microwave activation in these
solvents.
Abstract: A catalytic system composed of copper salt, potassium
carbonate and appropriate poly(ethylene glycol) (PEG; liquid or
solid, various molecular weight: 300< MW <3400) was developed
to perform a Sonogashira arylation under microwave activation.
In the presence of copper(I) iodide, various substituted diphenyl-
acetylenes could be synthesized.
We report herein an alternative catalytic system, phos-
phine- and palladium-free, for C–C coupling in Sonogash-
ira conditions, made of a catalytic amount of copper(I)
iodide (CuI), potassium carbonate and poly(ethylene)gly-
col (of various molecular weight), as organic solvent,
under microwave activation.
Key words: Sonogashira coupling, microwave, arylation, copper,
poly(ethylene glycol)
PEGs are homopolymers that can substitute volatile or-
ganic solvents. They present some interesting characteris-
tics, including high polarity and high boiling points,
special properties arising from its cation complexation
ability and have been used to a certain extent in substitu-
tion, oxidation, reduction and organometallic reactions.23
Furthermore they present low toxicity and they have been
used for biomedical applications, especially in the field of
Discovered in the early 1970s, the Sonogashira reaction1
has become one of the most powerful synthetic method
2
,3
for the carbon–carbon bond formation. Since then, it has
found tremendous developments in synthetic chemistry
for the high-throughput preparation of small organic
molecules, which can be screened for their biological
4
,5
6,7
activity, for the synthesis of organic materials, or the
preparation of complex organic molecules. The Sono-
gashira reaction is associated with palladium catalysis and
as such has also promoted the use of palladium as a
catalyst in several organic transformations especially in
cascade reactions.8
2
4
drug discovery and as soluble polymeric support in or-
25
ganic synthesis. PEGs with low molecular weight (less
than 800 dalton) are liquid at room temperature while high
molecular weight PEGs (more than 800 dalton) are solids,
that melt at a moderate temperature and can therefore be
Despite its efficiency, palladium is an expensive metal,
rendering commercial processes based on Pd less attrac-
tive unless extremely active and/or recyclable catalysts
are available. It has been calculated that 1 mol% of Pd
catalyst for a 200 dalton product adds 112 euros to the
18–22,26
used as solvent.
Initially, we employed the CuI-catalyzed coupling reac-
tion of iodobenzene (1a, R = H) with phenylacetylene (2),
mixed together with PEG3400 and potassium carbonate, as
a model for testing reaction conditions (Scheme 1). The
9
cost. For this reason, the search for other metallic catalyt-
reaction mixture was heated for 30 minutes under micro-
ic systems that could substitute or complement the palla-
dium catalysts tool box, is a valuable task. One cheaper
metal which has proved to be useful in coupling reactions
wave,2
7–30
which is known as a practical heating technique
to reduce reaction times. Then, the mixture was cooled,
dissolved in a small amount of CH Cl , precipitated in
1
0,11
2
2
is copper.
diethyl ether and filtered. The expected product was
Copper catalysis has been mostly applied to the so-called
Ullmann coupling for the formation of carbon–nitrogen
bonds. Surprisingly, only few publications report on the
obtained from the filtrate after evaporation of the solvent
1
and analyzed by H NMR using CH Br as an internal
2
2
standard. The precipitate, after filtration, contained a
mixture of copper salt, the solvent, the inorganic base, and
inorganic by-products.
1
2–17
use of copper
as the only catalyst for the Sonogashira
reaction that is traditionally a bismetallic-mediated pro-
cess (palladium and copper required). Copper can take
part in cross-coupling chemistry in a way strikingly simi-
lar to palladium, but it is more versatile and productive
since it exits in four oxidation states from 0 to +3, while
palladium has at its disposal only two stable oxidation
states 0 and +2. As an ongoing project related to the use of
poly(ethylene glycol)s (PEGs) as organic solvents,1 we
Encouraging results were obtained in the presence of 0.5
equivalent of copper(I) iodide (150 °C, 64% yield), and
only one equivalent of phenylacetylene (2). Since the re-
action was performed under microwave in a sealed tube,
volatile phenylacetylene (2) vaporized and, probably, less
than an equimolar amount of 2 was effectively present in
the reaction mixture. We decided to increase the amount
of alkyne from one to two equivalents with respect to
8–22
SYNLETT 2007, No. 8, pp 1279–1283
1
6.
0
5.
2
0
0
7
22
phenyl iodide. The yields dropped drastically by reduc-
Advanced online publication: 08.05.2007
DOI: 10.1055/s-2007-980337; Art ID: G02607ST
ing the quantity of catalyst to 0.1 equivalent, or lowering
©
Georg Thieme Verlag Stuttgart · New York

1
280
E. Colacino et al.
LETTER
precipitate obtained from the first experiment in the pres-
ence of the base and starting materials. Although satisfy-
ing results were obtained (66% yield), the catalytic system
I
1
0 mol% CuI
+
PEG, K2CO3
MW
R
R
33
needed some induction period to be fully effective. All
2
the reactions have been performed under no special con-
ditions, moisture playing probably a significant role in the
catalytic reaction by improving the base solubility that
otherwise would remain mostly undissolved. Moreover,
the ability of PEG to complex with large alkali metal ions
leading to solubilization of the base is well known.34
1
1
1
1
1
1
1
1
a: R = H
3a: R = H
b: R = 4-OMe
c: R = 4-NO2
d: R = 2-NO2
e: R = 4-Me
f: R = 2-Me
g: R= 4-CN
h: R = 2-OMe
3b: R = 4-OMe
3c: R = 4-NO2
3d: R = 2-NO2
3e: R = 4-Me
3f: R = 2-Me
3g: R= 4-CN
3h: R = 2-OMe
We expanded our initial study of the activity of PEG–CuI
catalytic system to the Sonogashira coupling of 4-iodo-
anisole (1b) in the presence of two equivalents of phenyl-
Scheme 1
the temperature. We also tried to prepare and heat the cop- acetylene, to study the effects of other bases, temperature,
per salt, base and PEG mixture prior to the addition of the solvent and additives on the yield. The results are summa-
two starting materials together, or one after the other,3
but the results did not improve.
1,32
rized in Table 1.
Poor yields were obtained at 150 °C, and no im-
With the aim of studying the recyclability of the system, provements were observed on doubling the reaction time
the reaction was performed in a second cycle by using the (entry 1).
Table 1 Reaction Conditions for the Copper-Catalyzed Sonogashira Reaction for 4-Iodoanisole (1b, R = OMe) in Different PEGs
Entry
Base
Solvent
CuI (equiv)
0.1
Temp (°C)
150
220
220
220
220
220
220
220
220
220
220
220
220
220
220
180
180
200
200
220
220
Time (min)
60
Yield (%)a
1
2
3
4
5
6
7
8
9
K CO3
HO-PEG3400-OH
HO-PEG3400-OH
HO-PEG3400-OH
HO-PEG3400-OH
HO-PEG3400-OH
HO-PEG3400-OH
HO-PEG3400-OH
HO-PEG3400-OH
HO-PEG3400-OH–DMF
HO-PEG3400-OHb
HO-PEG3400-OH–DMFb
HO-PEG3400-OH
HO-PEG3400-OH
HO-PEG300-OH
HO-PEG550-OMe
HO-PEG550-OMe
HO-PEG550-OMe
HO-PEG550-OMe
–
14
69
89
0
2
K CO3
0.1
30
2
K CO3
0.1
60
2
K CO3
–
30
2
(n-C H ) N
0.1
30
0
8
18 3
Cs CO3
0.1
30
40
23
2
2
CsOAc
0.1
30
Bu NOAc
0.1
30
4
K CO3
0.1
30
64
66
89
58
63
78
94
2
2
1
1
1
1
1
1
1
1
1
1
2
2
0
1
2
3
4
5
6
7
8
9
0
1
K CO3
0.1
30
2
K CO3
0.1
30
2
K CO3
0.1
30
2
K CO3
cycle 2
0.1
30
2
K CO3
30
2
K CO3
0.1
30
2
K CO3
0.1
60
2
K CO3
0.1
90
92
100
44
62
10
2
K CO3
0.1
60
2
K CO3
cycle 2
0.1
60
2
K CO3
MeO-PEG250-OMe
30
2
K CO3
MeO-PEG250-OMe–H O
0.1
30
2
2
a
1
Yields were calculated by H NMR using CH Br as an internal standard.
2
2
b
PPh (0.2 equiv) was added.
3
Synlett 2007, No. 8, 1279–1283 © Thieme Stuttgart · New York

LETTER
Microwave-Assisted Copper-Catalyzed Sonogashira Reaction
1281
When the temperature was increased to 220 °C, better re- also explored the Sonogashira coupling with liquid
sults were obtained (entry 2) and improved by extending PEG300 (entry 14), PEG550 monomethylether (entries 15–
the reaction time to one hour (entry 3). In the absence of 19) and PEG250 dimethylether (entry 20). Yield was in-
CuI (entry 4), no reaction occurred under microwave irra- creased from 69% (entry 2) to 78% (entry 14) on replacing
diation. Further studies were carried out to study the influ- PEG3400 with PEG300, probably due to a better solubility of
ence of the base and the reaction temperature for assessing the substrates in PEG300. Monomethyl PEG gave better re-
the catalyst performance. The use of other group 1 metal sults than dimethyl PEG or PEG. Most probably, chela-
carbonates, or acetates gave lower conversion with re- tion of cations by the polymer is optimum when one
spect to K CO (entries 5–8). The best results were ob- hydroxyl group is present. One OH group allows at one
2
3
tained with K CO that became the base of choice for this end of the polymer, together with the neighboring ethyl-
2
3
+
+
project. This result can be rationalized considering that ene oxides, stabilization of a cation (K or Cu ) involved
3
5
PEG can form a loose complex with large alkali metal in the reaction. If two OH groups are present both ends
+
ions such as K , leaving the basic anion as a free ion in the may stabilize the cations, provoking repulsive interactions
3
6
medium and increasing the base solubility and strength. resulting in PEG uncoiling and poor results. Dimethoxy
This hypothesis can explain the low yield obtained in PEGs are unable to generate the same synergistic hydrox-
presence of Bu NOAc, dissolved in PEG: the concentra- yl–ethylene oxide stabilizing effect, as in the case of
4
–
37
tion of AcO in the solution is low due to the ion pair monomethoxy PEG. We also tried to recycle the catalyt-
+
formed with Bu N , diminishing the overall catalyst effi- ic system CuI–PEG550 monomethyl ether; n-hexane was
4
ciency. Different solvent–additive–base combinations added to the reaction vessel containing the crude from the
were also tested: DMF as a co-solvent (entry 9), or PPh3 first cycle. The upper layer, containing 3b was separated
as an additive (entry 10) gave comparable results and no and the catalytic system was used in a second run (entries
improvements in the yields. However 89% yield was 18 and 19). The recycling was not efficient in this case. No
achieved through their synergistic effect (entry 11). The improvement was obtained when PEG3400 was replaced by
investigation was completed by recycling the catalytic PEG250 dimethylether (entry 20).
system (entries 12 and 13) and good yields were obtained
in a second run.
To determine the scope of the Sonogashira cross-coupling
reaction in different PEGs (solid or liquid), we performed
Low-molecular-weight liquid PEGs can be regarded as the reaction with other substrates, at 150 °C for 2.5
protic solvents with aprotic binding sites constituted by hours.38
the ethylene oxide units. Several organic substrates are
As summarized in Table 2, we found that electron-defi-
2
3
soluble in low-molecular-weight liquid PEG.
cient (1c,d,g) or electron-rich aryl iodides (1b,e,f,h) react-
Different factors affect the phase catalytic activity, such ed with phenylacetylene (2) to give the corresponding
as PEG molecular weight, chain end effects, and nature of substituted diphenylacetylenes 3b–h with moderate to
the associated cations and anions. For these reasons we
Table 2 Yield of Copper-Catalyzed Sonogashira Reaction with Different Aryl Iodides in Different PEGsa
Aryl iodide
1a
1b
1c
1d
1e
1f
1g
1h
Entry Physical state of 1
l
s
s
s
s
l
s
s
1
2
3
4
5
6
7
8
9
0
MeO-PEG250-Me (liquid)
–
50
70
–
13
49
87
74b
–
27
9
15
1
19
35
50
–
83
88
80
–
–
10
42
15
–
HO-PEG300-OH (liquid)
HO-PEG550-OMe (liquid)
18
41
5
3
–
–
100c
99d
–
–
–
–
–
–
–
MeO-PEG2000-OMe (solid)
HO-PEG3400-OH (solid)
52
56
–
24
50
–
47
57
–
4
36
36
15d
–
55
92
–
48
24
–
2
5.1
5d
80d
–
–
–
–
2e
6
–
–
1
HO-PEG2000-OMe (solid)
67
20
58
53
69
11
34
a
b
c
d
e
1
Yields were calculated by H NMR using CH Br as an internal standard; ‘–’ indicates reaction not performed.
2
2
Yield is given for a second cycle.
Reaction was carried out at 200 °C for 60 min.
Reaction was carried out at 220 °C for 30 min.
Reaction was carried out at 220 °C for 60 min.
Synlett 2007, No. 8, 1279–1283 © Thieme Stuttgart · New York

1
282
E. Colacino et al.
LETTER
good yields depending on the physical states of both the Acknowledgment
PEG and the substrates, that seem to play a key role.
We thank the CNRS and the Ligue Contre le Cancer for financial
When liquid phenyl iodide (1a) was used, all conditions support.
yielded good results: small or large PEGs afforded aver-
age yields of diphenylethyne (3a).
References and Notes
PEG550 monomethylether (entries 3–5) or PEG3400 (entry
(
1) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
975, 4467.
8
) were the best solvents for the synthesis of 1-(4-
1
cyanophenyl)-2-phenylethyne (3g), with yields ranging
from 41% (entry 3) up to 99% at 200 °C (entry 4) or at 220
(
2) Sonogashira, K. Comprehensive Organic Synthesis, Vol. 3;
Trost, B. M., Ed.; Pergamon Press: Oxford, 1999, 521.
°
C (entry 5) for shorter reaction times. The coupling prod-
(3) Sonogashira, K. Metal-Catalysed Cross-Coupling
Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-VCH:
Weinheim, 1998, Chap 5.
uct 1-(4-nitrophenyl)-2-phenylethyne (3c) was obtained
in 47–58% yields in solid PEGs (entries 6, 7 and 10). Poor
yields and extensive degradation was observed in liquid
PEGs (entries 1–3). When 2-nitroiodobenzene (1d) was
the substrate, very poor yields of 1-(2-nitrophenyl)-2-phe-
nylethyne (3d) were obtained in any PEG (entries 1–3 and
(
(
4) Hegedus, L. S. J. Organomet. Chem. 1992, 422, 301.
5) Nicolaou, K. C.; Dai, W.-M. Angew. Chem., Int. Ed. Engl.
1991, 30, 1387.
(6) Bunz, U. H. F. Chem. Rev. 2000, 100, 1605.
(7) Wu, R.; Schumm, J. S.; Pearson, D. L.; Tour, J. M. J. Org.
Chem. 1996, 61, 6906.
6
–10). Probably, the nitro group in ortho position to the
1
6,39
(
8) Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E.-i., Ed.; Wiley: New York, 2002.
9) Zapf, A.; Beller, M. Chem. Eur. J. 2001, 7, 2908.
alkyne moiety is not tolerated under these conditions.
Moderate yields of 1-(4-methylphenyl)-2-phenylethyne
(
(
(
3e) could be obtained only in PEG550 (entry 3) or PEG2000
entry 10) monomethylether, and higher temperatures
(
(
10) Hassan, J.; Sevignon, M.; Gozzi, C.; Schultz, E.; Lemaire,
M. Chem. Rev. 2002, 102, 1359.
11) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem. Rev. 2004,
248, 2337.
with shorter reaction time afforded even lower conversion
of the starting materials. The isomeric 1-(2-methylphe-
nyl)-2-phenylethyne (3f) could be obtained with good
yields in every type of PEG (entries 1–3, 6, 7 and 10).
However the reaction did not proceed in the absence of
PEG, clearly showing that the PEGs play a key role in the
catalytic system. Very poor yields were obtained in DMF
(12) Okuro, K.; Furuune, M.; Miura, M.; Nomura, M.
Tetrahedron Lett. 1992, 33, 5363.
13) Dawei, M.; Feng, L. Chem. Commun. 2004, 17, 1934.
14) Thathagar, M. B.; Beckers, J.; Rothenberg, G. Green Chem.
(
(
2004, 6, 215.
(
15) Okuro, K.; Furuune, M.; Enna, M.; Miura, M.; Nomura, M.
(
9%). In the case of 4-iodoanisole (1b), 1-(4-methoxy-
J. Org. Chem. 1993, 58, 4716.
phenyl)-2-phenylethyne (3b) could be obtained in moder-
ate yields in DMF (44%) or PEG3400 (entry 7). Better
results were obtained in PEG550 monomethylether and
recycling was also possible (entries 3 and 4). On the
(16) He, H.; Wu, Y.-J. Tetrahedron Lett. 2004, 45, 3237.
(17) Trofimov, B. A.; Stepanova, Z. V.; Sobenina, L. N.;
Mikhaleva, A. I.; Ushakov, I. A. Tetrahedron Lett. 2004, 45,
6513.
(
(
18) Sauvagnat, B.; Lamaty, F.; Lazaro, R.; Martinez, J.
Tetrahedron Lett. 2000, 41, 6371.
19) Ribière, P.; Yadav-Bhatnagar, N.; Martinez, J.; Lamaty, F.
QSAR Comb. Sci. 2004, 23, 911.
contrary, the yield of the isomeric cross-coupling product
0
1
-(2-methoxyphenyl)-2-phenylethyne (3h)4 under our
standard conditions was compromised by a competitive
4
1
reaction affording 2-phenylbenzo[b]furan.
PEG2000 dimethylether afforded 3h in a moderate yield
entry 6).
Only
(20) Ribière, P.; Enjalbal, C.; Aubagnac, J.-L.; Yadav-Bhatnagar,
N.; Martinez, J.; Lamaty, F. J. Comb. Chem. 2004, 6, 464.
(
21) Ribière, P.; Declerck, V.; Nédellec, Y.; Yadav-Bhatnagar,
N.; Martinez, J.; Lamaty, F. Tetrahedron 2006, 62, 10456.
22) Declerck, V.; Martinez, J.; Lamaty, F. Synlett 2006, 3029.
(
In conclusion, a palladium- and phosphine-free reaction
condition for Sonogashira-type coupling was developed
that used PEG–CuI–K CO as the catalyst system under
(
(23) Chen, J.; Spear, S. K.; Huddleston, J. G.; Rogers, R. D.
Green Chem. 2005, 7, 64.
2
3
(
24) Poly(ethylene glycol): Chemistry and Biological
Applications; Harris, J. M.; Zalipsky, S., Eds.; American
Chemical Society: Washington, 1997.
microwave activation. This reaction was applicable to a
range of aryl iodides. In spite of the fact that higher tem-
peratures were required than with palladium-based cata-
(
(
25) Gravert, D. J.; Janda, K. D. Chem. Rev. 1997, 97, 489.
26) Declerck, V.; Ribière, P.; Nédellec, Y.; Allouchi, H.;
Martinez, J.; Lamaty, F. Eur. J. Org. Chem. 2007, 201.
1
,42,43
lyst systems,
the catalyst system had the advantage of
using available and less expensive reagents that were eas-
ily removable (by simple precipitation). The reaction we
have set up is operationally simple and cross-coupling
products could be obtained in good yields, depending on
the physical state of the aryl iodide–PEG combination. In
general, liquid substrates afforded cleaner reactions and
better yields. The pivot role of PEG for this catalytic sys-
tem has been widely demonstrated and no homocoupling
products were detected in the crude. Since the recovery of
the PEG-based catalytic system is based on a precipitation
step, this system is a very practical alternative to the other
catalytic system for the Sonogashira reaction.
(27) Microwaves in Organic Synthesis; Loupy, A., Ed.; Wiley-
VCH: Weinheim, 2006.
(
(
28) Kappe, C. O. Angew. Chem. Int. Ed. 2004, 43, 6250.
29) Deshayes, S.; Liagre, M.; Loupy, A.; Luche, J. L.; Petit, A.
Tetrahedron 1999, 55, 10851.
(
(
30) Caddick, S. Tetrahedron 1995, 51, 10403.
31) Thathagar, M. B.; Rothenberg, G. Adv. Synth. Catal. 2005,
347, 1965.
(32) Le Bars, J.; Specht, U.; Bradley, J. S.; Blackmond, D. G.
Langmuir 1999, 15, 7621.
(
33) Yang, Y.; Zhou, R.; Zhao, S.; Li, Q.; Zheng, X. J. Mol.
Catal. A: Chem. 2003, 192, 303.
Synlett 2007, No. 8, 1279–1283 © Thieme Stuttgart · New York

LETTER
Microwave-Assisted Copper-Catalyzed Sonogashira Reaction
1283
1
(
(
(
(
34) Santaniello, E.; Mazzocchi, A.; Sozzani, P. Tetrahedron
Lett. 1979, 19, 4581.
35) Hakem, I. F.; Lal, J.; Bockstaller, M. R. Macromolecules
(measured by H NMR using CH Br as internal standard).
2
2
When PEG550-monomethylether was the solvent of choice,
the workup was achieved by adding cyclohexane (0.5 mL) to
the reactor containing the crude, and the supernatant was
recovered and evaporated, affording 1-(4-methoxyphenyl)-
2-phenylethyne (3g) in 44% yield (measured by H NMR
using CH Br as an internal standard). The lower phase was
2004, 37, 8431.
36) Capuano, F.; Vergara, A.; Paduano, L.; Annunziata, O.;
Sartorio, R. J. Phys. Chem. B 2003, 107, 12363.
37) Dygas, J. R.; Misztal-Faraj, B.; Florjanczyk, Z.; Krok, F.;
Marzantowicz, M.; Zygadlo-Monikowska, E. Solid State
Ionics 2003, 157, 249.
1
2
2
reused in a similar reaction with finely powdered K CO
2
3
(0.047 g, 0.34 mmol, 1.5 equiv), 4-iodoanisole (0.053 g, 0.23
mmol, 1.0 equiv) and phenylacetylene (0.046 g, 0.46 mmol,
2.0 equiv) to give 1-(4-methoxyphenyl)-2-phenylethyne
(
38) Copper-Catalyzed Sonogashira Reaction of 4-
Iodoanisole (1g) with Phenylacetylene (2): Microwave-
assisted reactions were performed with a Biotage Initiator 60
1
(3b) in 100% yield (measured by H NMR using CH Br as
2
2
®
EXP instrument. Temperature was measured with an IR
an internal standard); TLC [cyclohexane–Et O (50:50), l =
2
sensor on the outer surface of the reaction vial. In a typical
experiment, to a mixture of CuI (0.0043 g, 0.023 mmol, 0.1
equiv), finely powdered K CO (0.047 g, 0.34 mmol, 1.5
254 nm]: R = 0.66; mp 58–61 °C; HPLC (l = 214 nm): t =
f
R
14.253 min. IR (CCl ): 2210 (w), 1500 (s), 1435 (m), 1242
4
–
1 1
(s), 1168 (m), 1030 (s), 825 (s) cm . H NMR (CDCl ,
2
3
3
equiv) and PEG3400-OH (0.25 g) were added 4-iodoanisole
1b; 0.053 g, 0.23 mmol, 1.0 equiv) and phenylacetylene (2;
.046 g, 0.46 mmol, 2.0 equiv). The resulting mixture was
Me Si): d = 7.46–7.53 (m, 4 H), 7.32–7.34 (m, 3 H), 6.87 (d,
4
1
3
(
0
J = 8.8 Hz, 2 H), 3.83 (s, 3 H). C NMR (CDCl , Me Si):
3 4
d = 159.61, 113.06, 131.46, 128.32, 127.94, 123.59, 115.37,
114.00, 89.36, 88.06, 55.32. MS (ESI+): m/z = 435 [(2 × M
heated by microwave irradiation at 220 °C (initial power 400
W) for 30 min. After cooling, the reaction mixture was
solubilized in CH Cl and precipitated in Et O. Filtration and
+
+
+
+ H O) + H] , 417 [2 × M + H] , 209 [M + H] . HRMS: m/z
2
calcd for C H O: 208.0888; found: 208.0882.
2
2
2
15 12
evaporation afforded 1-(4-methoxyphenyl)-2-phenylethyne
(39) Corma, A.; Garcìa, H.; Leyva, A. J. Catal. 2006, 240, 87.
(40) Stephens, R. D.; Castro, C. E. J. Org. Chem. 1963, 31, 4071.
(41) Yue, D.; Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70,
10292.
(42) Dieck, H. A.; Heck, R. F. J. Organomet. Chem. 1975, 93,
259.
1
(
3b) in 58% yield (measured by H NMR using CH Br as an
2 2
internal standard). HPLC analysis did not detect the presence
of by-products. The precipitate was reused in a similar
reaction with finely powdered K CO (0.047 g, 0.34 mmol,
2
3
1
.5 equiv), 4-iodoanisole (0.053 g, 0.23 mmol, 1.0 equiv)
and phenylacetylene (0.046 g, 0.46 mmol, 2.0 equiv) to give
-(4-methoxyphenyl)-2-phenylethyne (3b) in 88% yield
(43) Cassar, L. J. Organomet. Chem. 1975, 93, 253.
1
Synlett 2007, No. 8, 1279–1283 © Thieme Stuttgart · New York

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