Easy copper-, ligand- and amine-free sonogashira coupling reaction catalyzed by palladium on carbon at low catalyst loading and by exposure to air

Article abstract of DOI:10.1055/s-2005-863720

An easy copper-, ligand and amine-free Sonogashira coupling reaction catalyzed by commercially available palladium on carbon with air at low catalyst loading (0.2 mol% Pd) has been developed. Aryl iodides coupled with aromatic alkynes gave good to excelle

Full text of DOI:10.1055/s-2005-863720

LETTER
619
Easy Copper-, Ligand- and Amine-Free Sonogashira Coupling Reaction
Catalyzed by Palladium on Carbon at Low Catalyst Loading and by Exposure
to Air
E
G
asy, Copper-, Lig
u
and- and A
m
o
ine-Free Son
l
ogash
i
ira Cou
n
pling Reaction Zhang*
Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, P. R. China
Fax +86(571)87217412; E-mail: guolinzhang@zju.edu.cn
Received 27 October 2004
based phosphinimine-phosphine ligand and tetrabutyl-
Abstract: An easy copper-, ligand and amine-free Sonogashira
1
0
ammonium acetate as an activator were used. An amino-
phosphine ligand was used.11 A ligand-, copper- and
amine-free Sonogashira reaction was also reported.12
coupling reaction catalyzed by commercially available palladium
on carbon with air at low catalyst loading (0.2 mol% Pd) has been
developed. Aryl iodides coupled with aromatic alkynes gave good
to excellent yields and with aliphatic alkyne gave moderate to good
yields. The reaction system is easy to handle.
While these examples added to the improvement of the
Sonogashira reaction, those methodologies remained
based on homogeneous palladium catalysts, which made
the separation and the recovery of the catalysts tedious if
not impossible and might result in high palladium contam-
ination of the product. Moreover, these copper- and
amine-free methodologies needed high palladium catalyst
loading, palladium complexes or ligands, which were ex-
pensive and hard to be synthesized. A way to overcome
these difficulties was the use of a heterogeneous palladi-
um catalyst such as a solid-supported metal. The most
readily available form of supported catalyst is palladium
on carbon, which is widely used in heterogeneous hydro-
genation processes and also has a growing importance in
carbon-carbon bond formation reactions.13 There are
papers that report the use of palladium on carbon as a
catalyst in the Sonogashira reactions.1 However, most
of these protocols remained linked to the use of CuI as co-
catalyst, triphenylphosphine as ligand and an amine as
base.
Key words: Sonogashira coupling, palladium, catalysis, hetero-
geneous
The palladium-catalyzed coupling of terminal acetylenes
with aryl and vinyl halides (the Sonogashira reaction) is
one of the most important and widely used carbon-carbon
1
bond formation reactions in organic synthesis. This reac-
tion gives an efficient route to aryl alkynes, which are in-
teresting intermediates for preparing many target
compounds with applications ranging from natural
2
3
products and pharmaceuticals to molecular organic ma-
terials.
4
The Sonogashira reaction is generally carried out in
organic solvents such as benzene, toluene, THF, DMF or
dioxane. This reaction needs a base, which is usually an
amine such as triethylamine, diethylamine or diisopropyl-
ethylamine. The most widely used catalysts are
4,15
Pd(PPh ) Cl or Pd(PPh ) in conjunction with copper(I)
3
2
2
3 4
The potential advantages of the Pd/C catalyst system, the
ease of separation and facile recycling of the metal and the
low level (usually below 1 ppm)1 of metal contamina-
tion in the product, suggest that a copper-, ligand- and
amine-free Sonogashira coupling protocol based on the
use of Pd/C catalyst system would be of major interest for
both industrial and academic applications.
iodide. To simplify the Sonogashira reaction protocol,
several important aspects have been improved in recent
years. The most important improvement was the elimina-
tion of copper(I) iodide, which was used as the co-catalyst
since it could induce a homocoupling reaction of terminal
alkynes to diynes in the presence of oxygen (Glaser-type
3d
5
reaction). Copper-free approaches to the Sonogashira re-
Herein, I wish to report my results that commercially
available palladium on carbon catalyzes a copper-, ligand-
and amine-free Sonogashira coupling reaction at low
catalyst loading and by exposure to air.
actions usually include the use of an amine, such as trieth-
ylamine or piperidine, as solvent or in large excess.6
Recently, some copper- and amine-free methodologies for
the Sonogashira reaction have been reported. Stoichio-
metric amounts of silver(I) oxide for aryl iodides, and
tetrabutylammonium fluoride or tetrabutylammonium hy-
As a starting point for the development of the methodolo-
gy, I chose the coupling between 4-iodoacetophenone (1)
with 2-hydroxyethylacetylene (2) as a model reaction by
7
droxide for aryl bromides as activators were used. An
use of i-PrOH–H O (v/v = 1:1) as solvent. As illustrated
oxime palladacycle ligand and tetrabutylammonium ace-
2
8
in Table 1, the coupling reaction gave a good yield in the
presence of 1.0 mol% palladium at 40 °C (entry 2). The
catalyst loading could be decreased when the reaction
temperature was increased. The catalyst loading could be
lowered to 0.2 mol% Pd without decreasing product yield
at 80 °C (entries 4, 10, 11). Air did not have a negligible
effect on the yield (entry 8 vs. entry 9, entry 10 vs. entry
tate as an additive were used. A bulky electron-rich
9
ortho-biphenylphosphane ligand was used. A ferrocene-
SYNLETT 2005, No. 4, pp 0619–0622
0
4.
0
3.
2
0
0
5
Advanced online publication: 22.02.2005
DOI: 10.1055/s-2005-863720; Art ID: U29604ST
©
Georg Thieme Verlag Stuttgart · New York

6
20
G. Zhang
LETTER
Table 1 Screening of Conditions for the Sonogashira Coupling of 4-Iodoacetophenone with 2-Hydroxyethylacetylenea
Pd/C (X mol% Pd)
H3COC
I
+
C
CCH2CH2OH
3
H COC
C
CCH2CH2OH
Na3PO4·12H2O (2 equiv)
i-PrOH, H2O
1
2
Entry
X
Y
T (°C)
30
Gas
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
3.5c
1.0c
0.5d
0.2
0.1
0
2.5
2.5
2.5
2.5
2.5
2.5
1.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Air
Air
Ar
Air
Air
Air
24
24
4
–e
40
80
79
80
67
0
80
80
5
80
24
24
24
24
24
5
80
0.1
0.1
0.1
0.2
0.2
0.4
0.6
0.8
80
–f
80
64
64
80
80
80
79
80
80
1
1
1
1
0
1
2
3
4
80
80
5
80
4
80
0.6
0.5
1
80
a
Reactions were carried out using 0.5 mmol 4-iodoacetophenone, 0.6 mmol 2-hydroxyethylacetylene, 1% Pd/C in 2 mL i-PrOH–H O (1:1).
2
The reaction mixture was placed in a pre-heated Chemistation personal organic synthesizer at the given temperature for the allotted time.
b
Isolated yields after column chromatography.
c
10% Pd/C was used.
d
e
f
5% Pd/C was used.
1
The molar ratio of 4-iodoacetophenone to the product is 14:86 determined by H NMR.
The molar ratio of 4-iodoacetophenone to the product is 13:87 determined by H NMR.
1
1
1). Different Pd/C (10%, 5% and 1% Pd/C) were effec- In conclusion, a copper-, ligand- and amine-free Sono-
tive to the Sonogashira coupling reaction. However, the gashira coupling reaction catalyzed by commercially
reaction is limited to the use of the particular Pd/C which available palladium on carbon with low loading (0.2
is characterized by a high palladium dispersion (36%), a mol% Pd) has been developed. Aryl iodides were coupled
low reduction degree [mainly Pd(II)] and a high water with aromatic alkynes to give good to excellent yields and
1
5g
content (ca. 55%) in the literature.
with aliphatic alkyne to give moderate to good yields. The
reaction system is easy to handle (stability to air and mois-
ture, no inert atmosphere and no ligands are necessary).
To evaluate the scope and limitation of this procedure, the
reactions of a range of aromatic iodides with aliphatic and
aromatic alkynes were examined using 1% Pd/C (0.2
mol%) as catalyst, i-PrOH–H O (1:1) as solvent and All reagents and solvents were obtained from commercial suppliers
2
Na PO ·12H O as base at 80 °C. The results are shown in and used without further purification. Pd/C was supplied by Aldrich
3
4
2
company. Thin-layer chromatography (TLC) was performed on
glass-backed silica gel 60 F254, 0.2 mm plates (Merck), and com-
pounds were visualized under UV light (254 nm). Melting points
were determined on a Yanagimoto melting point apparatus and
were uncorrected. H NMR and C NMR spectra were recorded on
a JEOL EX-400 (400 MHz). Low- and high-resolution mass spectra
Table 2. Aryl iodides bearing electron-withdrawing sub-
stituents (NO , COCH ) were reacted with aromatic
alkynes to give almost quantitative yields (entries 5, 6, 9,
0, 13, 14) and with aliphatic alkyne 2-hydroxyethylacet-
ylene to give good yields (entries 1, 2). Electron-rich 4-io-
2
3
1
1
13
doanisole and iodobenzene were reacted with aromatic were taken on a JEOL JMS-SX 102A machine.
alkynes to give good to excellent yields (entries 7, 8, 11,
General Procedure
A 15 mL glass tube was charged with the appropriate aryl iodide
1
2, 15, 16) and with 2-hydroxyethylacetylene in moderate
yields (entries 3, 4). Phenylacetylene bearing electron-
(0.5 mmol), the appropriate terminal alkyne (0.6 mmol), 1% Pd/C
withdrawing substituent (CF ) gave higher yields than
3
(
10.6 mg, 0.001 mmol), H O (1 mL) and 2-propanol (1 mL). The re-
2
that bearing electron-donating substituent (OCH ) and
3
action mixture was placed in a pre-heated Chemistation personal or-
ganic synthesizer at 80 °C and stirred for the given time. After this
time, the mixture was diluted with 12 mL H O and 12 mL Et O, and
phenylacetylene, and aromatic alkynes gave higher yields
than aliphatic alkyne.
2
2
Synlett 2005, No. 4, 619–622 © Thieme Stuttgart · New York

LETTER
Easy Copper-, Ligand- and Amine-Free Sonogashira Coupling Reaction
621
Table 2 Amine- and Copper-Free Sonogashira Coupling of Aryl Iodides with Terminal Alkynes Catalyzed by Pd/C (0.2 mol%)a
1% Pd/C (0.2 mol% Pd)
R
I
+ CH
C
R1
R
C
C
R1
Na3PO4·12H2O (2 equiv)
i-PrOH, H2O, 80 °C
3a–o
Entry
R
CH
C
R1
Time (h)
Product
Yield (%)b
1
2
3
4
NO2
CH
CCH CH OH
2
5
5
5
3a
3b
3c
3d
79
80
37
45
2
2
COCH3
OCH3
H
5
6
7
8
NO2
3
2
6
6
3e
3f
3g
3h
98
98
60
67
COCH3
OCH3
H
HC
HC
C
C
9
NO2
2
2
5
5
3i
96
94
88
96
1
1
1
0
1
2
COCH3
OCH3
H
3j
3k
3l
CF3
1
1
1
1
3
4
5
6
NO2
5
3
6
6
3m
3n
3o
3g
98
94
60
72
COCH3
OCH3
H
HC
C
OCH3
a
Reactions were carried out using 0.5 mmol aryl iodide, 0.6 mmol alkyne, 1% Pd/C (0.2 mol% Pd) in 2 mL i-PrOH–H O (1:1). The reaction
2
mixture was placed in a pre-heated Chemistation personal organic synthesizer at 80 °C for the allotted time.
b
Isolated yields after column chromatography.
filtered using a membrane filter (Advantec Dismic-13HP, 0.45 mm).
4-Phenyl-3-butyn-1-ol (3d)
1
The organic phase was separated, and the aqueous layer was ex-
Colorless oil. H NMR (CDCl ): d = 1.99 (br s, 1 H, disappeared af-
3
tracted with Et O (2 × 12 mL). The combined organic layers were
ter being exchanged with D O), 2.69 (t, J = 6.4 Hz, 2 H), 3.80 (br s,
2
2
washed with brine (12 mL), H O (12 mL) and dried over anhyd
exchanged with D O, t, J = 6.4 Hz, 2 H), 7.28 (m, 3 H), 7.41 (m, 2
2
2
1
3
MgSO . After filtration the solvent was removed by evaporation in
H). C NMR (CDCl ): d = 24.6, 62.0, 81.3, 87.2, 124.2, 128.8,
129.1, 132.5. HRMS (EI): m/z calcd for C H O [M ]: 146.0732;
4
3
+
vacuo. The residue was chromatographed on a silica gel column, us-
1
0
10
ing hexane–Et O as eluent.
found: 146.0735. MS (EI): m/z = 146, 115 (base peak).
2
4
-(4¢-Nitrophenyl)-3-butyn-1-ol (3a)
4-(Phenylethynyl) Nitrobenzene (3e)
Yellow solid, mp 118–120 °C (lit. mp 114–116 °C). H NMR
1
16
1
Yellow solid, mp 65–66 °C. H NMR (CDCl ): d = 1.96 (br s, 1 H,
disappeared after being exchanged with D O), 2.74 (t, J = 6.4 Hz, 2
H), 3.86 (br s, exchanged with D O, t, J = 6.4 Hz, 2 H), 7.54 (d,
3
(CDCl ): d = 7.40 (m, 3 H), 7.56 (m, 2 H), 7.65 (d, J = 8.8 Hz, 2 H),
2
3
1
3
8.21 (d, J = 8.8 Hz, 2 H). C NMR (CDCl ): d = 87.5, 94.7, 122.1,
123.4, 123.6, 128.5, 129.3, 130.3, 131.8, 132.3. MS (EI): m/z = 223
2
3
1
3
J = 8.8 Hz, 2 H), 8.16 (dd, J = 2.0 Hz, J = 8.8 Hz, 2 H). C NMR
CDCl ): d = 23.9, 60.8, 80.7, 92.6, 123.5, 130.4, 132.4, 146.8.
(
(base peak), 193, 176.
3
+
HRMS (EI): m/z calcd for C H NO [M ]: 191.0583; found:
1
0
9
3
1
91.0589. MS (EI): m/z = 191, 161 (base peak), 115.
4-(Phenylethynyl) Acetophenone (3f)
Pale yellow solid, mp 100–102 °C (lit. mp 96–98 °C). H NMR
1
6
1
4
-(4¢-Acetylphenyl)-3-butyn-1-ol (3b)
(CDCl ): d = 2.61 (s, 3 H), 7.35–7.38 (m, 3 H), 7.54–7.56 (m, 2 H),
3
1
White solid, mp 74–76 °C. H NMR (CDCl ): d = 2.05 (br s, 1 H,
disappeared after being exchanged with D O), 2.60 (s, 3 H), 2.72 (t,
J = 6.0 Hz, 2 H), 3.84 (q, exchanged with D O, t, J = 6.0 Hz, 2 H),
7
7.60 (dd, J = 1.6 Hz, J = 6.8 Hz, 2 H), 7.94 (dd, J = 1.6 Hz, J = 6.8
3
1
3
Hz, 2 H). C NMR (CDCl ): d = 26.4 88.4, 92.5, 122.5, 128.0,
2
3
128.1, 128.2, 128.6, 131.5, 131.6, 136.1, 197.1. MS (EI): m/z = 220,
2
1
3
.48 (d, J = 8.4 Hz, 2 H), 7.88 (d, J = 8.4 Hz, 2 H). C NMR
205 (base peak), 176.
(
1
CDCl ): d = 23.9, 26.6, 61.0, 81.7, 90.3, 128.2, 128.4, 131.8,
3
+
36.0, 197.4. HRMS (EI): m/z calcd for C H O [M ]: 188.0837;
4-(Phenylethynyl) Anisole (3g)
Pale yellow solid, mp 63–64 °C (lit. mp 60–62 °C). H NMR
1
2
12
2
1
6
1
found: 188.0834. MS (EI): m/z = 188, 173 (base peak).
(
CDCl ): d = 3.81 (s, 3 H), 6.87 (dd, J = 2.0 Hz, J = 8.8 Hz, 2 H),
3
4
-(4¢-Methoxyphenyl)-3-butyn-1-ol (3c)
7.33 (m, 3 H), 7.45–7.52 (m, 4 H). MS (EI): m/z = 208, 164 (base
1
White solid, mp 65–66 °C. H NMR (CDCl ): d = 1.88 (br s, 1 H,
disappeared after being exchanged with D O), 2.67 (t, J = 6.0 Hz, 2
peak).
3
2
1
7
H), 3.79 (m, 5 H), 6.82 (dd, J = 2.0 Hz, J = 8.8 Hz, 2 H), 7.34 (dd,
Diphenylacetylene (3h)
1
3
1
J = 2.0 Hz, J = 8.8 Hz, 2 H). C NMR (CDCl ): d = 23.9, 55.3,
Colorless oil. H NMR (CDCl ): d = 7.31–7.36 (m, 6 H), 7.52–7.54
(m, 4 H). MS (EI): m/z = 178 (base peak), 152.
3
3
6
1.3, 82.3, 84.7, 113.9, 115.5, 133.0, 159.4. HRMS (EI): m/z calcd
+
for C H O [M ]: 176.0837; found: 176.0830. MS (EI): m/z = 176,
11
12
2
1
45 (base peak).
4-(2-Trifluoromethylphenylethynyl)nitrobenzene (3i)
1
Light orange solid, mp 94–96 °C. H NMR (CDCl ): d = 7.49 (t,
3
J = 8.0 Hz, 1 H), 7.57 (t, J = 8.0 Hz, 1 H), 7.68–7.74 (m, 4 H), 8.23
Synlett 2005, No. 4, 619–622 © Thieme Stuttgart · New York

6
22
G. Zhang
LETTER
(
1
d, J = 8.8 Hz, 2 H). 13C NMR (CDCl ): d = 90.2, 92.6, 120.4,
1999, 40, 4211. (d) Yoshimura, F.; Kawata, S.; Hirama, M.
Tetrahedron Lett. 1999, 40, 8281. (e) Toyota, M.; Komori,
C.; Ihara, M. J. Org. Chem. 2000, 65, 7110. (f) Paterson, I.;
Davies, R. D.; Marquez, R. Angew. Chem. Int. Ed. 2001, 40,
3
22.1, 123.7, 126.1, 126.2, 129.0, 129.6, 131.6, 132.4, 134.0, 147.4.
+
HRMS (EI): m/z calcd for C H NO F [M ]: 291.0507; found:
2
1
5
8
2 3
91.0499. MS (EI): m/z = 291 (base peak), 261, 245, 225.
603.
4
-(2-Trifluoromethylphenylethynyl)acetophenone (3j)
(3) (a) Nicolaou, K. C.; Dai, W. M. Angew. Chem., Int. Ed. Engl.
1991, 30, 1387. (b) Grissom, J. W.; Gunawardena, G. U.;
Klingberg, D.; Huang, D. Tetrahedron 1996, 52, 6453.
(4) (a) Wu, R.; Schumm, J. S.; Pearson, D. L.; Tour, J. M. J.
Org. Chem. 1996, 61, 6906. (b) Tour, J. M. Acc. Chem. Res.
2002, 33, 791. (c) Bunz, U. H. F. Chem. Rev. 2000, 100,
1605.
1
White solid, mp 83–85 °C. H NMR (CDCl ): d = 2.62(s, 3 H), 7.46
3
(
t, J = 7.2 Hz, 1 H), 7.52 (t, J = 7.2 Hz, 1 H), 7.62–7.64 (m, 2 H),
1
3
7
.70 (t, J = 7.6 Hz, 2 H), 7.96 (d, J = 7.2 Hz, 2 H). C NMR
(
1
CDCl ): d = 26.1, 88.0, 93.4, 120.5, 124.4, 125.5, 125.6, 127.1,
3
27.8, 128.0, 131.0, 131.3, 133.4, 136.3, 196.7. HRMS (EI): m/z
+
calcd for C H OF [M ]: 288.0762; found: 288.0767. MS (EI): m/
17
11
3
z = 288, 273 (base peak), 245, 225.
(5) Siemsen, P.; Livingston, R. C.; Diederich, F. Angew. Chem.
Int. Ed. 2000, 39, 2632.
4
-(2-Trifluoromethylphenylethynyl)anisole (3k)
(6) (a) Alami, M.; Ferri, F.; Linstrumelle, G. Tetrahedron Lett.
1993, 34, 6403. (b) Bohm, V. P. W.; Herrmann, W. A. Eur.
J. Org. Chem. 2000, 3679. (c) Fu, X.; Zhang, S.; Yin, J.;
Schumacher, D. P. Tetrahedron Lett. 2002, 43, 6673.
(d) Pal, M.; Parasuraman, K.; Gupta, S.; Yeleswarapu, K. R.
Synlett 2002, 1976. (e) Mery, D.; Heuze, K.; Astruc, D.
Chem. Commun. 2003, 1934.
1
White solid, mp 66–68 °C. H NMR (CDCl ): d = 3.82 (s, 3 H), 6.87
3
(
(
9
1
dd, J = 2.0 Hz, J = 6.8 Hz, 2 H), 7.37 (t, J = 7.6 Hz, 1 H), 7.46–7.51
m, 3 H), 7.62–7.67 (m, 2 H). C NMR (CDCl ): d = 55.3, 84.3,
1
3
3
5.2, 114.1, 114.3, 114.9, 126.0, 126.8, 127.5, 128.2, 131.4, 133.3,
+
33.5, 160.2. HRMS (EI): m/z calcd for C H OF [M ]: 276.0762;
1
6
11
3
found: 276.0756. MS (EI): m/z = 276 (base peak), 261, 233.
(
7) Mori, A.; Kawashima, J.; Shimada, T.; Suguro, M.;
(
2-Trifluoromethylphenylethynyl)benzene (3l)
Hirabayashi, K.; Nishihara, Y. Org. Lett. 2000, 2, 2935.
(8) Alonso, D. A.; Najera, C.; Pacheco, M. C. Tetrahedron Lett.
2002, 43, 9365.
(9) Gelman, D.; Buchwald, S. L. Angew. Chem. Int. Ed. 2003,
42, 5993.
1
Light yellow oil. H NMR (CDCl ): d = 7.35–7.41 (m, 4 H), 7.48–
3
1
3
7
9
1
.56 (m, 3 H), 7.66 (t, J = 7.6 Hz, 2 H). C NMR (CDCl ): d = 85.4,
3
5.0, 122.8, 125.9, 125.9, 126.9, 127.9, 128.3, 128.8, 128.8, 131.4,
+
31.7, 133.7. HRMS (EI): m/z calcd for C H F [M ]: 246.0656;
1
5
9 3
found: 246.0662. MS (EI): m/z = 246 (base peak), 225.
(10) Arques, A.; Aunon, D.; Molina, P. Tetrahedron Lett. 2004,
45, 4337.
4
-(4-Nitrophenylethynyl)anisole (3m)
(11) Cheng, J.; Sun, Y.; Wang, F.; Guo, M.; Xu, J.; Pan, Y.;
Zhang, Z. J. Org. Chem. 2004, 69, 5428.
1
Yellow solid, mp 122–124 °C. H NMR (CDCl ): d = 3.84 (s, 3 H),
6
Hz, 2 H), 8.19 (d, J = 8.8 Hz, 2 H). C NMR (CDCl ): d = 55.4,
8
HRMS (EI): m/z calcd for C H NO [M ]: 253.0739; found:
2
3
.90 (d, J = 8.8 Hz, 2 H), 7.49 (d, J = 8.8 Hz, 2 H), 7.63 (d, J = 8.8
(12) Urgaonkar, S.; Verkade, J. G. J. Org. Chem. 2004, 69, 5752.
(13) (a) Whitcombe, N. J.; Hii, K. K.; Gibson, S. E. Tetrahedron
2001, 57, 7449. (b) Hagiwara, H.; Shimizu, Y.; Hoshi, T.;
Suzuki, T.; Ando, M.; Ohkubo, K.; Yokoyama, C.
Tetrahedron Lett. 2001, 42, 4349. (c) Djakovitch, L.;
Koehler, K. J. Am. Chem. Soc. 2001, 123, 5990.
1
3
3
6.7, 95.2, 114.2, 114.3, 123.6, 130.7, 132.0, 133.5, 146.7, 160.5.
+
1
5
11
3
53.0736. MS (EI): m/z = 253 (base peak), 223, 207, 163.
4
-(4-Methoxyphenylethynyl)acetophenone (3n)
(d) LeBlond, C. R.; Andrews, A. T.; Sun, Y.; Sowa, J. R.
Org. Lett. 2001, 3, 1555. (e) Sakurai, H.; Tsukuda, T.;
Hirao, T. J. Org. Chem. 2002, 67, 2721.
1
Pale yellow solid, mp 126–127 °C. H NMR (CDCl ): d = 2.61 (s, 3
H), 3.84 (s, 3 H), 6.90 (dd, J = 2.0 Hz, J = 6.8 Hz, 2 H), 7.48 (dd,
J = 2.0 Hz, J = 6.8 Hz, 2 H), 7.58 (dd, J = 2.0 Hz, J = 6.8 Hz, 2 H),
7
5
1
3
(14) (a) De la Rosa, M. A.; Velarde, E.; Guzman, A. Synth.
Commun. 1990, 20, 2059. (b) Novak, Z.; Szabo, A.; Repasi,
J.; Kotschy, A. J. Org. Chem. 2003, 68, 3327.
1
3
.92 (dd, J = 2.0 Hz, J = 6.8 Hz, 2 H). C NMR (CDCl ): d = 26.6,
3
5.3, 87.5, 93.0, 114.2, 114.8, 128.3, 128.6, 131.5, 133.3, 136.0,
+
60.1, 197.3. HRMS (EI): m/z calcd for C H O [M ]: 250.0994;
(15) Examples of singular Pd/C-catalyzed Sonogashira reactions
1
7
14
2
1
4a
found: 250.0992. MS (EI): m/z = 250 (base peak), 235, 207, 163.
from ref. are: (a) Potts, K. T.; Horwitz, C. P.; Fessak, A.;
Keshavarz, K. M.; Nash, K. E.; Toscano, P. J. J. Am. Chem.
Soc. 1993, 115, 10444. (b) Bleicher, L.; Cosford, N. D. P.
Synlett 1995, 1115. (c) Cosford, N. D. P.; Bleicher, L.;
Herbaut, A.; McCallum, J. S.; Vernier, J.; Dawson, H.;
Whitten, J. P.; Adams, P.; Chavez-Noriega, L.; Correa, L.
D.; Crona, J. H.; Mahaffy, L. S.; Menzaghi, F.; Rao, T. R.;
Reid, R.; Sacaan, A. I.; Santori, E.; Stauderman, K. A.;
Whelan, K.; Lloyd, G. K.; McDonald, I. A. J. Med. Chem.
(
4,4¢-Dimethoxy)diphenylacetylene (3o)
1
Light yellow solid, mp 144–146 °C. H NMR (CDCl ): d = 3.82 (s,
3
6
H), 6.85 (dd, J = 1.2 Hz, J = 7.2 Hz, 4 H), 7.44 (dd, J = 1.2 Hz,
1
3
J = 7.2 Hz, 4 H). C NMR (CDCl ): d = 55.3, 88.0, 114.0, 115.8,
1
found: 238.1000. MS (EI): m/z = 238 (base peak), 223.
3
+
32.9, 159.4. HRMS (EI): m/z calcd for C H O [M ]: 238.0994;
16 14 2
1
996, 39, 3235. (d) Bleicher, L. S.; Cosford, N. D. P.;
References
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(
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Synlett 2005, No. 4, 619–622 © Thieme Stuttgart · New York