Copper(I)-catalyzed Caryl-Calkynyl bond formation of aryl iodides with terminal alkynes

Article abstract of DOI:10.1055/s-0029-1216876

A wide range of internal alkynes are synthesized from the corresponding aryl iodides and terminal alkynes by Sonogashira-type cross-coupling reactions through Caryl-Calkynyl bond formation in the presence of a catalytic amount of readily available DBU-CuBr complex under mild reaction conditions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1216876

PAPER
2785
Copper(I)-Catalyzed C –C
aryl
Bond Formation of Aryl Iodides with
alkynyl
Terminal Alkynes
C
K
opper(I)-Catalyz
.
e
d
C
–C
G
nyl Bond Formatio n. Thakur, G. Sekar*
a
ry
l
al
k
y
Department of Chemistry, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600036, India
Fax +91(44)22574202; E-mail: gsekar@iitm.ac.in
Received 6 April 2009; revised 17 April 2009
Recently, the Sonogashira coupling reaction was per-
formed under microwave conditions using poly(ethylene
Abstract: A wide range of internal alkynes are synthesized from
the corresponding aryl iodides and terminal alkynes by
Sonogashira-type cross-coupling reactions through Caryl–Calkynyl
4
h
glycol)s as the solvent. However, these advances in the
bond formation in the presence of a catalytic amount of readily field of Sonogashira coupling are not sufficient as most
available DBU–CuBr complex under mild reaction conditions.
reactions still need dry and oxygen-free reaction condi-
tions due to the use of phosphine ligands and, in some cas-
es, high catalytic loading (even super stoichiometric
amounts of ligands are needed). Therefore a mild, eco-
nomic, and efficient catalytic system is still desirable for
this process.
Key words: copper catalyst, coupling reaction, arylated alkynes,
C–C bond formation, Sonogashira coupling, nitrogen ligands
The coupling reaction of aryl halides with terminal
alkynes catalyzed by palladium complexes is a useful
1
method (Sonogashira coupling) for the preparation of in-
ternal alkynes that play a significant role in a number of
I
Cu complex (cat.)
K2CO3
2
natural products and bioactive molecules. However, the
+
high costs of palladium salts, the requirement for copper
as a co-catalyst, the high oxophilicity associated with
phosphine ligands, and tedious multistep processes in-
volved in the synthesis of these phosphine ligands have
rendered palladium unpopular, particularly for large-scale
reactions.
DMF, 140 °C
R1
R2
R1
R2
6
Scheme 1
As a part of our ongoing research towards copper-cata-
5
lyzed oxidation chemistry, very recently we reported
1,1¢-binaphthyl-2,2¢-diamine–copper (BINAM–Cu) as an
efficient catalyst for the synthesis of diaryl ethers, aryl
6
alkyl ethers, and thioethers via Ullmann coupling. Thus,
N
N
N
N
it is a natural extension for us to investigate Caryl–Calkynyl
bond formation for the synthesis of arylated alkynes 6
using copper-complex-catalyzed Sonogashira coupling
reactions (Scheme 1). This procedure is very simple,
mild, clean, and works efficiently without any additives.
OH HO
N
N
1
2
In preliminary studies, we examined the coupling of 1-
iodo-4-methoxybenzene with phenylacetylene using
Salen ligand 1 (20 mol%) with copper(I) iodide (20
mol%) in N,N-dimethylformamide at 140 °C; the reaction
provided 1-methoxy-4-(phenylethynyl)benzene (7a) in
only 10% isolated yield (Figure 1, Table 1, entry 1)
through Caryl–Calkynyl bond formation. When ligand 1 was
replaced with 2, the reaction gave 7a in 68% yield in 13
hours (entry 2). Replacing ligand 2 by commercially
available (–)-sparteine (3) increased the yield to 70% (en-
try 3). Surprisingly, the same reaction using commercially
available 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 4)
and copper(I) iodide as the catalyst gave 7a in a maximum
yield of 86% (entry 4). Using 1,5-diazabicyclo[4.3.0]non-
N
N
N
N
N
N
3
4
5
Figure 1
It has been known for decades that aryl halides could cou-
3
ple with copper(I) acetylides to give arylacetylenes.
There have been a few reports concerning the use of cop-
per(I) alone as the catalyst for the coupling of aryl halides
4
with terminal alkynes. Although in these reports copper
is used as catalyst, highly oxophilic phosphines are used
4
a–e,l
as ligands;
were replaced by nitrogen- and oxygen-based ligands.
later, these oxophilic phosphine ligands
4f–k
5
-ene (DBN) as ligand instead of DBU also catalyzed the
reaction, but the yield was reduced to 83% (entry 5). Next,
the reaction was carried out with different ratios of DBU
and copper(I) iodide and it was found that 20 mol% of
SYNTHESIS 2009, No. 16, pp 2785–2789
x
x.
x
x
.
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0
0
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Advanced online publication: 26.06.2009
DOI: 10.1055/s-0029-1216876; Art ID: Z06209SS
Georg Thieme Verlag Stuttgart · New York
©

2
786
K. G. Thakur, G. Sekar
PAPER
Table 1 Copper(I)-Catalyzed Sonogashira Coupling with Different
Ligands
Table 2 Effect of Copper Salt, Solvent, and Base
I
I
DBU (20 mol%)
Cu salt (20 mol%)
ligand (20 mol%)
CuI (20 mol%)
+
MeO
MeO
K CO (3 equiv)
2
3
+
K2CO3 (3 equiv)
DMF, 140–145 °C
solvent, 140–145 °C
7a
OMe
OMe
7a
a
Time (h) Yield (%)
Entry
Copper salt
Solvent
a
b
Yield (%)
Entry
Ligand
Time (h)
1
2
3
4
5
6
7
8
9
0
1
CuI
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
MeCN
THF
16
13
13
16
16
16
16
13
30
30
30
30
20
20
20
24
20
86
91
79
72
99
78
72
81
30
40
38
75
45
80
48
75
47
1
2
3
4
5
1
2
3
4
5
48
13
15
13
13
10
68
70
86
83
Cu(OTf)2
Cu(OAc)2
Cu(SO ) ·5H O
4
2
2
CuBr
CuCl2
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
a
See Figure 1.
Isolated yield.
b
ligand–copper combination was the most effective cata-
lytic system.
b
b
b
1
1
The reaction was screened with several copper salts, sol-
vents, and bases to increase the efficiency of the cross-
coupling reaction for the formation of 7a and the results
dioxane
xylene
toluene
DMF
DMF
DMF
DMF
are summarized in Table 2. Although several copper salts 12
catalyzed the reaction, copper(I) bromide was the copper
b
c
d
e
f
1
3
salt of choice, as it provided 7a in almost quantitative
yield (Table 2, entry 5). Similarly, N,N-dimethylform-
amide was the best solvent among those examined. Potas-
sium carbonate as base gave the best yield of product in
14
1
5
comparison with bases such as sodium carbonate and ce- 16
sium carbonate.
1
7
Using these optimized conditions, we initiated our inves-
tigations into the scope of the DBU–CuBr-catalyzed
Sonogashira-type cross-coupling reaction (Table 3). Var-
ious aryl iodides and terminal alkynes reacted to give the
corresponding arylated acetylenes 7. We found that iodo-
benzenes containing electron-releasing groups, such as
the methoxy group (entries 7–9), as well as electron-with-
drawing groups, such as the trifluoromethyl group (entry
a
b
c
d
e
f
Isolated yield.
Reaction was carried out in a pressure tube.
Na CO was used as base.
Cs CO was used as base.
2
3
2
3
K CO (2 equiv) was used.
2
3
Reaction was carried out without DBU.
In summary, we have developed an efficient, experimen-
tally simple, and economically attractive DBU–CuBr
complex catalyzed C-arylation of terminal alkynes with
aryl iodides through a Caryl–Calkynyl bond forming reaction.
Aryl iodides containing both electron-releasing as well as
electron-withdrawing groups react with terminal alkynes
to provide arylated alkyne products in high isolated
yields. The reaction conditions are very mild as OTHP
ethers are unaffected during the entire reaction time.
2
1), reacted with terminal acetylenes to provide arylated
products 7 in high isolated yields. Highly sterically hin-
dered ortho-substituted iodobenzenes (entries 12–14 and
1
7–19) also provided arylated alkynes 7k–m and 7p–r
with excellent yields by reacting with terminal alkynes in
the presence of the DBU–CuBr complex. The reaction
condition tolerated acid-sensitive functional groups. For
example, a tetrahydro-2H-pyran-2-yl ether containing ter-
minal alkyne [2-(prop-2-ynyloxy)tetrahydro-2H-pyran]
reacted with several iodobenzenes to provide correspond-
ing arylated products 7d,f,j,m,o,r in good yield without
cleavage of the acid sensitive OTHP ether group (entries
All the reactions were carried out in reaction tube under an N atmo-
2
sphere. Commercially available DBU and terminal acetylenes were
purchased from Sigma Aldrich chemical company. CuI and iodo
3
, 6, 11, 14, 16, and 19). A terminal alkyne containing a benzenes were purchased from Alfa Aesar. K CO was purchased
2 3
heterocycle also reacted with 1-iodo-4-methoxybenzne in from Merck, India. All of these reagents were used without further
purification. DMF was purchased from SRL India and dried over
CaH . Reaction temperatures were controlled by Varivolt tempera-
ture modulator, melting points were determined using a Guna 230
the presence of DBU–CuBr complex to provide corre-
sponding arylated product 7h in excellent isolated yield
entry 9).
2
(
Synthesis 2009, No. 16, 2785–2789 © Thieme Stuttgart · New York

PAPER
Copper(I)-Catalyzed Caryl–Calkynyl Bond Formation
2787
Table 3 Cross-Coupling Reaction of Aryl Iodides with Terminal
Alkynes in the Presence of DBU–CuBr Catalyst
was heated to 140–145 °C. Phenylacetylene (65.9 mL, 0.6 mmol)
was added to the mixture at 140–145 °C in 2 portions (33 mL each)
at 10 min intervals. The septum was replaced with a glass stopper
and the mixture was heated for 16 h (the progress of the reaction
was followed by TLC). After complete disappearance of 1-iodo-4-
methoxybenzene, the mixture was allowed to cool to r.t. (~30 °C)
and the solvent was evaporated. The crude residue was purified by
DBU (20 mol%)
CuBr (20 mol%)
K2CO3 (3 equiv)
DMF, 140–145 °C
ArI
+
R
Ar
R
7
column chromatography (silica gel, EtOAc–hexanes) to afford 7a
(
7
103 mg, 99%) as a white solid; mp 59 °C; R = 0.37 (hexane).
f
a
Time Product Yield
Entry Ar
R
–1
IR: 1173, 1247, 2181, 2853, 2923, 2954 cm .
b
(
h)
(%)
99
97
80
84
98
75
99
75
81
97
86
93
96
78
99
60
81
88
65
95
85
1
H NMR (400 MHz, CDCl ): d = 3.82 (s, 3 H), 6.87 (dd, J = 7.2, 2
3
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
Ph
Ph
Ph
4-MeC H
6
20
11
20
14
20
20
16
14
20
11
20
20
14
20
14
20
20
14
20
20
15
7b
7c
7d
7b
7e
7f
Hz, 2 H), 7.27–7.39 (m, 3 H), 7.42–7.56 (m, 4 H).
4
1
3
C NMR (100 MHz, CDCl ): d = 55.5, 88.2, 89.5, 114.2, 115.6,
3
Ph
1
23.8, 128.1, 128.5, 131.6, 133.2, 159.8.
CH OTHP
2
+
HRMS: m/z [M + H] calcd for C H O: 209.0966; found:
1
5
13
2
09.0960.
4-MeC H4
6
Ph
7
1-Methyl-4-(phenylethynyl)benzene (7b)
White solid; mp 64 °C; R = 0.53 (hexane).
4-MeC H4
6
4-MeC H
4
6
f
4-MeC H4
6
CH OTHP
2
–1
IR: 2168, 2856, 2919, 3030, 3050 cm .
1
4-MeOC H4
6
Ph
7a
7g
7h
7i
H NMR (400 MHz, CDCl ): d = 2.37 (s, 3 H), 7.16 (d, J = 8 Hz, 2
3
H), 7.28–7.38 (m, 3 H), 7.43 (d, J = 8.4 Hz, 2 H), 7.47–7.59 (m, 2
H).
4-MeOC H4
6
4-MeC H
6
4
1
3
C NMR (100 MHz, CDCl ): d = 21.6, 88.9, 89.7, 120.3, 123.6,
3
4-MeOC H4
6
3-pyridyl
Ph
1
28.2, 128.4, 129.2, 131.6, 131.7, 138.5.
1
1
1
1
1
1
1
1
1
1
2
2
3-MeOC H4
6
+
GC-MS (EI ): m/z = 192.950.
3-MeOC H4
6
CH OTHP
2
7j
7
1
,2-Diphenylethyne (7c)
2-MeC H4
6
Ph
7k
7l
Yellow solid; mp 60 °C; R = 0.57 (hexane).
f
–
IR: 2342, 2359, 2852, 2924, 3056 cm .
1
2-MeC H4
6
4-MeC H
4
6
1
H NMR (400 MHz, CDCl ): d = 7.34–7.46 (m, 6 H), 7.55–7.66 (m,
3
2-MeC H4
6
CH OTHP
2
7m
7n
7o
7p
7q
7r
7s
4 H).
1
3
C NMR (100 MHz, CDCl ): d = 89.6, 123.5, 128.4, 128.5, 131.8.
3
3,5-Me C H
3
Ph
2
6
+
GC-MS (EI ): m/z = 178.7603.
3,5-Me C H
2
CH OTHP
2
6
3
8
2
-(3-Phenylprop-2-ynyloxy)tetrahydro-2H-pyran (7d)
Light yellow liquid; R = 0.64 (5% EtOAc–hexane).
2-MeOC H4
6
Ph
f
2-MeOC H4
6
4-MeC H
6
–1
IR: 1118, 1200, 1441, 2341, 2852, 2941 cm .
4
1
2-MeOC H4
6
CH OTHP
2
H NMR (400 MHz, CDCl ): d = 1.48–1.93 (m, 6 H), 3.54–3.61 (m,
3
1 H), 3.86–3.94 (m, 1 H), 4.49 (dd, J = 27.2, 15.6 Hz, 2 H), 4.90 (t,
J = 3.2 Hz, 1 H), 7.28–7.33 (m, 3 H), 7.42–7.48 (m, 2 H).
1-naphthyl
4-F CC H
4
Ph
Ph
1
3
C NMR (100 MHz, CDCl ): d = 19.2, 25.5, 30.4, 54.9, 62.2, 85.2,
3
7t
3
6
8
5.9, 97.0, 128.3, 128.5, 132.0.
a
All alkynes gave satisfactory spectral data.
Isolated yield.
+
HRMS: m/z [M + H] calcd for C H O : 217.1229; found:
b
14 17
2
2
17.1225.
volts apparatus. TLC was performed using Merck silica gel 60 F254
precoated plates (0.25 mm) and visualized by UV fluorescence
lamp. Silica gel (100–200 mesh) purchased from SRL India, was
used for chromatography. H and C NMR spectra were recorded
1
on a Bruker 400 MHz instrument. H NMR spectra were reported
7
Di-4-tolylacetylene (7e)
White solid; mp 125 °C; R = 0.69 (hexane).
f
1
13
–1
IR: 2728, 2855, 2921, 3024 cm .
1
H NMR (400 MHz, CDCl ): d = 2.38 (s, 6 H), 7.19 (d, J = 8 Hz, 4
3
using TMS (d = 0.0) as internal standard or the residual CHCl peak
3
H), 7.46 (d, J = 8 Hz, 4 H).
1
3
(
d = 7.26). C NMR were reported relative to CDCl (d = 77.16).
3
1
3
FT-IR spectra were recorded on a Nicolet 6700 spectrophotometer.
HRMS were recorded on Q-Tof Micro mass spectrometer.
C NMR (100 MHz, CDCl
138.3.
): d = 21.6, 89.0, 120.5, 129.2, 131.6,
3
+
GC-MS (EI ): m/z = 207.0151.
1
1
1
-Methoxy-4-(phenylethynyl)benzene (7a); Typical Procedure
-Iodo-4-methoxybenzene (117 mg, 0.5 mmol), K CO (207.3 mg,
.5 mmol), and CuBr (14.4 mg, 0.1 mmol) were added to a 15-mL
9
2
3
2-[3-(4-Tolyl)prop-2-ynyloxy]tetrahydro-2H-pyran (7f)
Yellow liquid; R = 0.60 (5% EtOAc–hexane).
f
reaction tube capped with a septum. The tube was evacuated and
back-filled with N . DMF (3 mL) and DBU (14.95 mL, 0.1 mmol)
were added to the mixture at r.t. (~30 °C) and the resulting mixture
–
IR: 1200, 1440, 2165, 2851, 2940 cm .
1
2
Synthesis 2009, No. 16, 2785–2789 © Thieme Stuttgart · New York

2
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K. G. Thakur, G. Sekar
PAPER
1
13
H NMR (400 MHz, CDCl ): d = 1.5–1.93 (m, 6 H), 2.34 (s, 3 H),
3
C NMR (100 MHz, CDCl ): d = 20.8, 88.5, 93.5, 123.2, 123.7,
3
3
2
.53–3.61 (m, 1 H), 3.85–3.94 (m, 1 H), 4.48 (dd, J = 28, 15.6 Hz,
H), 4.90 (t, J = 3.6 Hz, 1 H), 7.11 (d, J = 8.4 Hz, 2 H), 7.34 (d,
J = 8.4 Hz, 2 H).
125.7, 128.3, 128.4, 128.5, 129.6, 131.6, 132.0, 140.3.
+
GC-MS (EI ): m/z = 191.2857.
1
3
13
1-Methyl-2-(4-tolylethynyl)benzene (7l)
White solid; mp 122 °C; R = 0.63 (hexane).
C NMR (100 MHz, CDCl ): d = 19.2, 21.6, 25.5, 30.4, 55.0, 62.2,
3
8
4.5, 86.1, 97.0, 119.8, 129.2, 131.9, 138.6.
f
+
HRMS: m/z [M + Na] calcd for C H NaO : 253.1204; found:
–1
IR: 2853, 2919, 3023 cm .
1
5
18
2
2
53.1205.
1
H NMR (400 MHz, CDCl ): d = 2.45 (s, 3 H), 2.55 (s, 3 H), 7.16–
3
7.22 (m, 3 H), 7.23–7.28 (m, 2 H), 7.47 (d, J = 8 Hz, 2 H), 7.52 (d,
J = 7.6 Hz, 1 H).
1
0
1-Methoxy-4-(4-tolylethynyl)benzene (7g)
Yellow liquid; R = 0.26 (hexane).
f
1
3
C NMR (100 MHz, CDCl ): d = 20.9, 21.6, 87.8, 93.7, 120.7,
3
–
IR: 1174, 1247, 2211, 2840, 2917, 3005, 3030 cm .
1
1
23.4, 125.7, 128.3, 129.3, 129.6, 131.5, 131.9, 138.4, 140.2.
1
H NMR (400 MHz, CDCl ): d = 2.24 (s, 3 H), 3.68 (s, 3 H), 6.73–
3
.78 (m, 2 H), 7.03 (d, J = 8 Hz, 2 H), 7.27–7.33 (m, 2 H), 7.33–7.38
m, 2 H).
+
GC-MS (EI ): m/z = 205.5543.
6
(
2-[3-(2-Tolyl)prop-2-ynyloxy]tetrahydro-2H-pyran (7m)
Light yellow liquid; R = 0.55 (5% EtOAc–hexane).
1
3
C NMR (100 MHz, CDCl ): d = 21.6, 55.4, 88.3, 88.8, 114.1,
3
f
1
15.8, 120.7, 129.2, 131.5, 133.1, 138.2, 159.6.
–1
IR: 1117, 1200, 1440, 2186, 2852, 2940 cm .
+
HRMS: m/z [M + H] calcd for C H O: 223.1123; found:
2
1
6
15
1
H NMR (400 MHz, CDCl ): d = 1.50–1.93 (m, 6 H), 2.43 (s, 3 H),
3
23.1119.
3
2
.53–3.61 (m, 1 H), 3.86–3.94 (m, 1 H), 4.54 (dd, J = 18.8, 15.6 Hz,
H), 4.94 (t, J = 3.6 Hz, 1 H), 7.09–7.15 (m, 1 H), 7.16–7.24 (m, 2
1
1
3-[(4-Methoxyphenyl)ethynyl]pyridine (7h)
Yellow-colored semisolid; R = 0.43 (hexane).
H), 7.42 (d, J = 7.6 Hz, 1 H).
f
1
3
C NMR (100 MHz, CDCl ): d = 19.3, 20.8, 25.5, 30.5, 55.0, 62.3,
3
–
IR: 1144, 1246, 1440, 2216, 2836, 2930, 3000 cm .
1
8
4.8, 89.1, 96.8, 122.6, 125.6, 128.5, 129.5, 132.3, 140.5.
1
H NMR (400 MHz, CDCl ): d = 3.76 (s, 3 H), 6.82 (d, J = 8.4 Hz,
3
+
HRMS: m/z [M + Na] calcd for C H NaO : 253.1204; found:
1
5
18
2
2
(
H), 7.20 (dd, J = 8, 4.4 Hz, 1 H), 7.38–7.45 (m, 2 H), 7.69–7.76
m, 1 H), 8.42–8.49 (m, 1 H), 8.67 (s, 1 H).
2
53.1204.
1
3
14
C NMR (100 MHz, CDCl ): d = 55.3, 84.6, 93.0, 114.1, 114.6,
3
1,3-Dimethyl-5-(phenylethynyl)benzene (7n)
Slightly yellow liquid; R = 0.84 (hexane).
1
21.0, 123.0, 133.2, 138.4, 147.9, 160.1, 171.0.
f
+
HRMS: m/z [M + H] calcd for C H NO: 210.0919; found:
–1
IR: 2210, 2734, 2916 cm .
1
4
12
2
10.0915.
1
H NMR (400 MHz, CDCl ): d = 2.39 (s, 6 H), 7.04 (s, 1 H), 7.26
3
(
s, 2 H), 7.36–7.46 (m, 3 H), 7.57–7.65 (m, 2 H).
1
2
1-Methoxy-3-(phenylethynyl)benzene (7i)
Light yellow liquid; R = 0.37 (hexane).
1
3
C NMR (100 MHz, CDCl ): d = 21.2, 88.8, 89.9, 123.0, 123.6,
3
f
1
28.2, 128.4, 129.4, 130.3, 131.7, 138.0.
–
IR: 1222, 1442, 2212, 2834, 2923, 3002 cm .
1
+
HRMS: m/z [M + H] calcd for C H : 207.1174; found: 207.1175.
1
16 15
H NMR (400 MHz, CDCl ): d = 3.72 (s, 3 H), 6.77–6.83 (m, 1 H),
3
6
1
.96–7.00 (m, 1 H), 7.05 (dd, J = 7.6, 0.8 Hz, 1 H), 7.16 (t, J = 8 Hz,
H), 7.22–7.30 (m, 3 H), 7.41–7.48 (m, 2 H).
2-[3-(3,5-Dimethylphenyl)prop-2-ynyloxy]tetrahydro-2H-pyr-
an (7o)
1
3
C NMR (100 MHz, CDCl ): d = 55.4, 89.3, 89.5, 115.1, 116.5,
3
Light yellow liquid; R = 0.57 (5% EtOAc–hexane).
f
1
23.3, 124.3, 124.4, 128.4, 128.5, 129.5, 131.8, 159.5.
–1
IR: 1118, 1200, 1440, 2341, 2867, 2941 cm .
+
GC-MS (EI ): m/z = 208.9833.
1
H NMR (400 MHz, CDCl ): d = 1.5–1.92 (m, 6 H), 2.28 (s, 6 H),
3
3.53–3.60 (m, 1 H), 3.85–3.93 (m, 1 H), 4.47 (dd, J = 24, 16 Hz, 2
H), 4.90 (t, J = 3.2 Hz, 1 H), 6.95 (s, 1 H), 7.08 (s, 2 H).
2
(
-[3-(3-Methoxyphenyl)prop-2-ynyloxy]tetrahydro-2H-pyran
7j)
Light yellow liquid; R = 0.55 (5% EtOAc–hexane).
1
3
C NMR (100 MHz, CDCl ): d = 19.2, 21.2, 25.5, 30.4, 54.9, 62.5,
3
f
8
4.5, 86.3, 96.9, 122.5, 129.6, 130.4, 138.0.
–
1
IR: 1022, 1118, 1200, 1463, 2219, 2851, 2924 cm .
+
HRMS: m/z [M + Na] calcd for C H NaO : 267.1361; found:
2
1
16 20
2
H NMR (400 MHz, CDCl ): d = 1.50–1.93 (m, 6 H), 3.53–3.60 (m,
3
H), 3.79 (s, 3 H), 3.85–3.93 (m, 1 H), 4.49 (dd, J = 27.6, 15.6 Hz,
H), 4.90 (t, J = 3.6 Hz, 1 H), 6.85–6.90 (m, 1 H), 6.98 (q, J = 1.2
67.1358.
1
2
15
1-Methoxy-2-(phenylethynyl)benzene (7p)
Light yellow liquid; R = 0.60 (hexane).
Hz, 1 H), 7.05 (d, J = 7.6 Hz, 1 H), 7.20 (t, J = 8 Hz, 1 H).
f
1
3
C NMR (100 MHz, CDCl ): d = 19.2, 25.5, 30.4, 54.9, 55.4, 62.2,
3
5.1, 85.8, 97.0, 115.2, 116.8, 123.8, 124.5, 129.4, 159.4.
–1
IR: 1105, 1243, 2216, 2834, 2938, 3060 cm .
8
1
H NMR (400 MHz, CDCl ): d = 3.87 (s, 3 H), 6.84–6.94 (m, 2 H),
3
+
HRMS: m/z [M + Na] calcd for C H NaO : 269.1154; found:
1
5
18
3
7
.24–7.36 (m, 4 H), 7.46–7.51 (m, 1 H), 7.52–7.58 (m, 2 H).
2
69.1158.
1
3
C NMR (100 MHz, CDCl ): d = 55.9, 85.9, 93.5, 110.8, 112.6,
3
7
120.5, 123.7, 128.1, 128.3, 129.8, 131.7, 133.6, 160.0.
1-Methyl-2-(phenylethynyl)benzene (7k)
Light yellow liquid; R = 0.78 (hexane).
+
HRMS: m/z [M + H] calcd for C H O: 209.0966; found:
209.0962.
f
1
5
13
–
IR: 2214, 2920, 3059 cm .
1
1
H NMR (400 MHz, CDCl ): d = 2.51 (s, 3 H), 7.12–7.20 (m, 1 H),
3
1-Methoxy-2-(4-tolylethynyl)benzene (7q)
Light yellow liquid; R = 0.36 (hexane).
7
.23 (d, J = 2 Hz, 2 H), 7.29–7.39 (m, 3 H), 7.47–7.57 (m, 3 H).
f
Synthesis 2009, No. 16, 2785–2789 © Thieme Stuttgart · New York

PAPER
Copper(I)-Catalyzed Caryl–Calkynyl Bond Formation
2789
–
IR: 1120, 1222, 2158, 2833, 2937, 2999 cm .
1
References
1
H NMR (400 MHz, CDCl ): d = 2.34 (s, 3 H), 3.88 (s, 3 H), 6.85–
3
(
1) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
6
(
.95 (m, 2 H), 7.13 (d, J = 8 Hz, 2 H), 7.24–7.30 (m, 1 H), 7.42–7.51
m, 3 H).
Lett. 1975, 16, 4467. (b) Sonogashira, K. In Comprehensive
Organic Synthesis, Vol. 3; Trost, B. M.; Fleming, I., Eds.;
Pergamon Press: Oxford, 1999, 521. (c) Kawanami, H.;
Matsushima, K.; Sato, M.; Ikushima, Y. Angew. Chem. Int.
Ed. 2007, 46, 5129. (d) Yi, W. B.; Chi, C.; Wang, X. Eur. J.
Org. Chem. 2007, 3445. (e) Li, J. H.; Liang, Y.; Xie, Y. X.
J. Org. Chem. 2005, 70, 4393.
1
3
C NMR (100 MHz, CDCl ): d = 21.6, 55.9, 85.2, 93.7, 110.8,
3
12.8, 120.56, 120.59, 129.1, 129.7, 131.6, 133.6, 138.3, 159.9.
1
+
GC-MS (EI ): m/z = 222.68.
2
-[3-(2-Methoxyphenyl)prop-2-ynyloxy]tetrahydro-2H-pyran
7r)
Light yellow liquid; R = 0.39 (5% EtOAc–hexane).
(
(
(
2) Theil, F. Angew. Chem. Int. Ed. 1999, 38, 2345.
3) Stephens, R. D.; Castro, C. E. J. Org. Chem. 1963, 28, 3313.
4) (a) Okuro, K.; Furuune, M.; Miura, M.; Nomura, M.
Tetrahedron Lett. 1992, 33, 5363. (b) Okuro, K.; Furuune,
M.; Enna, M.; Miura, M.; Nomura, M. J. Org. Chem. 1993,
(
f
–
1
IR: 1022, 1118, 1237, 1447, 2341, 2833, 2939 cm .
1
H NMR (400 MHz, CDCl ): d = 1.46–1.93 (m, 6 H), 3.53–3.60 (m,
3
58, 4716. (c) Saejueng, P.; Bates, C. G.; Venkataraman, D.
1
H), 3.85–3.94 (m, 4 H), 4.54 (dd, J = 24.4, 15.6 Hz, 2 H), 4.94 (t,
Synthesis 2005, 1706. (d) Tang, B. X.; Wang, F.; Li, J. H.;
Xie, Y. X.; Zhang, M. B. J. Org. Chem. 2007, 72, 6294.
J = 3.6 Hz, 1 H), 6.84–6.92 (m, 2 H), 7.26–7.32 (m, 1 H), 7.42 (dd,
J = 7.6, 1.6 Hz, 1 H).
(
e) Gujadhar, R. K.; Bates, C. G.; Venkataraman, D. Org.
Lett. 2001, 3, 4315. (f) Ma, D.; Liu, F. Chem. Commun.
004, 1934. (g) He, H.; Wu, Y. J. Tetrahedron Lett. 2004,
1
3
C NMR (100 MHz, CDCl ): d = 19.2, 25.5, 30.4, 55.2, 55.9, 62.1,
3
8
2.2, 89.3, 96.9, 110.8, 112.0, 120.5, 130.0, 134.0, 160.2.
2
+
HRMS: m/z [M + Na] calcd for C H NaO : 269.1154; found:
45, 3237. (h) Colacino, E.; Daich, L.; Martinez, J.; Lamaty,
F. Synlett 2007, 1279. (i) Chinchilla, R.; Nájera, C. Chem.
Rev. 2007, 107, 874. (j) Li, J.-H.; Li, J.-L.; Wang, D.-P.; Pi,
S.-F.; Xie, Y.-X.; Zhang, M.-B.; Hu, X.-C. J. Org. Chem.
2007, 72, 2053. (k) Monnier, F.; Turtaut, F.; Doroure, L.;
Taillefer, M. Org. Lett. 2008, 10, 3203. (l) Guan, J. T.; Yu,
G.-A.; Chen, L.; Weng, T. Q.; Yuan, J. J.; Liu, S. H. Appl.
Organomet. Chem. 2009, 23, 75.
1
5
18
3
2
69.1150.
7
1-(Phenylethynyl)naphthalene (7s)
Light yellow liquid; R = 0.63 (hexane).
f
–
IR: 2341, 2923, 3056 cm .
1
1
H NMR (400 MHz, CDCl ): d = 7.38–7.59 (m, 4 H), 7.62 (t, J = 6.8
3
Hz, 1 H), 7.69–7.74 (m, 1 H), 7.76 (dd, J = 6, 1.6 Hz, 2 H), 7.85–
8
(
(
5) (a) Mannam, S.; Kumar, S. A.; Sekar, G. Adv. Synth. Catal.
2007, 349, 2253. (b) Mannam, S.; Sekar, G. Tetrahedron
Lett. 2008, 49, 1083. (c) Mannam, S.; Sekar, G.
.10 (m, 3 H), 8.58 (t, J = 6.8 Hz, 1 H).
1
3
C NMR (100 MHz, CDCl ): d = 87.7, 94.5, 121.0, 123.5, 125.4,
3
Tetrahedron Lett. 2008, 49, 2457. (d) Alamsetti, S. K.;
Sreedevi, M.; Muthupandi, P.; Sekar, G. Chem. Eur. J. 2009,
1
1
26.3, 126.5, 126.9, 128.4, 128.5, 128.6, 128.9, 130.5, 131.8, 133.3,
33.4.
15, 1086.
+
GC-MS (EI ): m/z = 229.0405.
6) (a) Naidu, A. B.; Raghunath, O. R.; Prasad, D. J. C.; Sekar,
G. Tetrahedron Lett. 2008, 49, 1057. (b) Naidu, A. B.;
Sekar, G. Tetrahedron Lett. 2008, 49, 3147. (c) Prasad, D.
J. C.; Naidu, A. B.; Sekar, G. Tetrahedron Lett. 2009, 50,
1411.
7
1-(Phenylethynyl)-4-(trifluoromethyl)benzene (7t)
White solid; mp 100 °C; R = 0.83 (hexane).
f
–1
IR: 2221 cm .
1
(7) Mino, T.; Shirae, Y.; Saito, T.; Sakamoto, M.; Fujita, T.
J. Org. Chem. 2006, 71, 9499.
H NMR (400 MHz, CDCl ): d = 7.34 (t, J = 2 Hz, 3 H), 7.51–7.57
3
m, 2 H), 7.57–7.63 (m, 4 H).
(
(
(
8) Okuro, K.; Furuune, M.; Enna, M.; Miura, M.; Nomura, M.
J. Org. Chem. 1993, 58, 4716.
9) Arcadi, A.; Cacchi, S.; Marinelli, F.; Pace, P.; Sanzi, G.
Synlett 1995, 823.
1
3
C NMR (100 MHz, CDCl ): d = 88.1, 92.0, 122.7, 125.3, 125.38,
3
1
25.42, 125.5, 128.6, 129.0, 131.89, 131.94.
+
GC-MS (EI ): m/z = 245.0619.
(
(
10) Jincan, Y.; Zhiyuan, W.; Lei, W. J. Chem. Res. 2004, 71.
11) Tang, B. X.; Wang, F.; Li, J. H.; Xie, Y. X.; Zhang, M. B.
J. Org. Chem. 2007, 72, 6294.
Acknowledgment
(
12) Soler, R.; Cacchi, S.; Fabrizi, G.; Forte, G.; Martin, L.;
Martinez, S.; Molins, E.; Manas, M. M.; Petrucci, F.; Roig,
A.; Sebastian, R. R.; Vallribera, A. Synthesis 2007, 3068.
13) Moon, J.; Jeong, M.; Nam, H.; Ju, J.; Moon, J. H.; Jung, H.
M.; Lee, S. Org. Lett. 2008, 10, 945.
We thank DST (Project No.: SR/S1/OC-06/2008), New Delhi for
the financial support. K.G.T. thanks CSIR for a senior research
fellowship. We thank DST, New Delhi, for the funding towards
the 400 MHz NMR machine to the Department of Chemistry,
IIT-Madras under the IRPHA scheme and ESI-MS facility under
the FIST programme.
(
(
(
14) Liang, Y.; Xie, Y. X.; Li, J. H. J. Org. Chem. 2006, 71, 379.
15) Urgaonkar, S.; Verkade, J. G. J. Org. Chem. 2004, 69, 5752.
Synthesis 2009, No. 16, 2785–2789 © Thieme Stuttgart · New York