Sonogashira reaction of aryl halides with propiolaldehyde diethyl acetal catalyzed by a tetraphosphine/palladium complex

Article abstract of DOI:10.1016/j.tet.2005.06.062

All-cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C ₃H₅)]₂ efficiently catalyzes the Sonogashira reaction of propiolaldehyde diethyl acetal with a variety of aryl bromides and chlorides. A minor electronic effect of the substituents of the aryl bromide was observed. Similar reaction rates were observed in the presence of activated aryl bromides such as 4-trifluoromethylbromobenzene and deactivated aryl bromides such as bromoanisole. Turnover numbers up to 95,000 can be obtained for this reaction. Even aryl chlorides and heteroarylbromides or chlorides have been successfully alkynylated with this catalyst. Moreover, a wide variety of substituents on the aryl halide such as fluoro, trifluoromethyl, acetyl, benzoyl, formyl, nitro, dimethylamino or nitrile are tolerated.

Full text of DOI:10.1016/j.tet.2005.06.062

Tetrahedron 61 (2005) 9839–9847
Sonogashira reaction of aryl halides with propiolaldehyde diethyl
acetal catalyzed by a tetraphosphine/palladium complex
*
Mhamed Lemhadri, Henri Doucet and Maurice Santelli
*
´ `
UMR 6180 CNRS and Universite d’Aix-Marseille III: ‘Chirotechnologies:catalyze et biocatalyze, Laboratoire de Synthese Organique’,
´
´ ˆ
Faculte des Sciences de Saint Jerome, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
Received 17 February 2005; revised 13 April 2005; accepted 10 June 2005
Available online 14 July 2005
Abstract—All-cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C3H5)]2 efficiently catalyzes the Sonogashira reaction of
propiolaldehyde diethyl acetal with a variety of aryl bromides and chlorides. A minor electronic effect of the substituents of the aryl bromide
was observed. Similar reaction rates were observed in the presence of activated aryl bromides such as 4-trifluoromethylbromobenzene and
deactivated aryl bromides such as bromoanisole. Turnover numbers up to 95,000 can be obtained for this reaction. Even aryl chlorides and
heteroarylbromides or chlorides have been successfully alkynylated with this catalyst. Moreover, a wide variety of substituents on the aryl
halide such as fluoro, trifluoromethyl, acetyl, benzoyl, formyl, nitro, dimethylamino or nitrile are tolerated.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
In order to find more efficient palladium catalysts, we have
prepared the tetrapodal phosphine ligand, Tedicyp15
(Fig. 1). We have reported recently several results obtained
in allylic substitution,15 Suzuki cross-coupling,16 and Heck
reactions.17 We have also reported the Sonogashira
reaction18 using Tedicyp as ligand in the presence of
sterically congested arylbromides,18b with arylchlorides18d
or using alkynols.18c Here, in order to further establish the
requirements for a successful Sonogashira reaction, we wish
to report on the reaction of several aryl and heteroaryl
halides with propiolaldehyde diethyl acetal using Tedicyp
as ligand.
Substituted arylpropiolaldehydes bearing various substitu-
ents on the aromatic ring are of great biological interest and
are also useful reagents in organic synthesis.1 The
Sonogashira palladium-catalyzed reaction2 of aryl and
heteroaryl halides with propiolaldehyde diethyl acetal is a
very powerful method for the synthesis of these arylpro-
piolaldehydes. However, most of the results have been
obtained with very reactive but expensive aryliodides3–9 and
the procedures reported for this reaction require relatively
high catalysts loadings (1–10%).3–12 If the catalytic load of
palladium complex could be reduced to a significantly
smaller level, this reaction would be much more practical.13
2. Results and discussion
In recent years, several thermally stable palladium catalysts
have been successfully used for Sonogashira reaction.14
However, to our knowledge, only triphenylphosphine ligand
has been used for the coupling of aryl halides with
propiolaldehyde diethyl acetal.4,5 But this phosphorus
ligand can be labile under some coupling conditions
especially at elevated temperature and gave palladium
black, which is generally inactive. To our knowledge, low-
catalyst loading Sonogashira reactions with propiolalde-
hyde diethyl acetal have not been described.
For this study, based on previous results,18 DMF was chosen
as the solvent and potassium carbonate as the base. The
reactions were performed at 130 8C under argon in the
presence of a ratio 1/2 of [Pd(C3H5)Cl]2/Tedicyp as catalyst.
For the reactions performed with aryl bromides or
iodobenzene 5% of copper(I) iodide was added as co-catalyst
(Scheme 1). The reactions with aryl chlorides were
performed without CuI. We have reported recently that for
such substrates with our catalyst the presence of CuI often
Keywords: Sonogashira reaction; Aryl bromides; Palladium; Catalysis;
Tetraphosphine.
*
Corresponding authors. Tel.: C33 4 91 28 84 16; fax: C33 4 91 98 38 65
(H.D.); tel.: C33 4 91 28 88 25 (M.S.); e-mail addresses:
henri.doucet@univ.u-3mrs.fr; m.santelli@univ.u-3mrs.fr
Figure 1.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.062

9840
M. Lemhadri et al. / Tetrahedron 61 (2005) 9839–9847
Scheme 1.
led to the formation of side-products such as the
dimerization of the alkyne.18b
(Table 2), to aryl chlorides (Table 3) and also to a few
heteroaryl halides (Table 4).
First, we have investigated the Sonogashira reaction of
several para-substituted aryl bromides with propiolalde-
hyde diethyl acetal. The results presented in Table 1
disclose a minor effect of the substituents of the aryl
bromide. In most cases the reaction performed with
propiolaldehyde diethyl acetal proceeds very smoothly in
the presence of 0.01% catalyst. We observed that turnover
numbers of 6100–95,000 can be achieved with this catalyst
for activated substrates such as 4-bromoacetophenone,
4-bromobenzaldehyde, 4-bromobenzophenone, 4-bromo-
benzonitrile, and 4-fluorobromobenzene (Table 1, entries
2–16). With the deactivated aryl bromides: 4-bromotoluene,
4-tbutylbromobenzene and 4-bromoanisole slightly lower
TONs of 700–10,000 were obtained (Table 1, entries 17–21).
The least reactive aryl bromide for this reaction was
4-dimethylaminobromobenzene, but a complete conversion
for a ratio substrate/catalyst of 1000 was observed (Table 1,
entry 24). The similar TONs obtained with 4-bromo-
benzophenone and 4-tbutylbromobenzene (6100 and 9200,
respectively) seems to indicate that the oxidative addition of
aryl bromides to palladium is not the rate-limiting step of
the reaction with this catalyst.
The influence of the presence of meta and ortho substituents
on the aryl bromide on the reaction rate is reported in
Table 2. As expected very similar TONs were obtained with
meta-substituted aryl bromides than with the para-sub-
stituted substrates (Table 2, entries 1–5). ortho-Substituents
on the aryl bromides generally have a more important effect
on the reactions rates of Sonogashira reaction.18 However,
with propiolaldehyde diethyl acetal high TONs were
obtained in most cases with the ortho- and di-ortho-
substituted aryl bromides. We observed that the coupling
of 2-bromobenzaldehyde, methyl 2-bromobenzoate,
2-bromobenzonitrile, 2-trifluoromethylbromobenzene or
2-fluorobromobenzene proceeds in the presence of 0.01%
catalyst (Table 2, entries 8–15). Even the deactivated
2-bromoanisole gave good results in the presence of 0.01%
catalyst. Again this observation is also consistent with our
suggestion that the rate-limiting step does not involve
oxidative addition of the aryl bromide (Table 2, entries 19
and 20).
With 2-bromoacetophenone the formation of an unexpected
product was observed (Scheme 2, Table 2, entries 6 and 7).
When a ratio substrate/catalyst of 1000 was used, the
expected alkynylation product 19a was obtained together
with an other compound, which appears to be 19b. This
Then, the reaction with propiolaldehyde diethyl acetal was
applied to several meta- and ortho-substituted aryl bromides
Table 1. Palladium–Tedicyp catalyzed Sonogashira reaction with propiolaldehyde diethyl acetal and aryl halides (Scheme 1)
Entry
Aryl halide
Ratio substrate/catalyst
Product
Yield (%)a
1
2
3
4
5
6
7
8
Iodobenzene
4-Bromoacetophenone
4-Bromoacetophenone
4-Bromobenzaldehyde
4-Bromobenzophenone
4-Bromobenzophenone
Methyl 4-bromobenzoate
Methyl 4-bromobenzoate
4-Bromonitrobenzene
10,000
10,000
100,000
10,000
1000
10,000
1000
10,000
1000
10,000
10,000
100,000
10,000
10,000
1000
1
2
2
3
4
4
5
5
6
6
7
7
8
100 (92)
100 (94)
95
100 (94)
100 (91)
61
100 (90)
92
100 (94)
78
100 (91)
92
100 (90)
100 (92)
100 (88)
76
98 (90)
70
100 (92)
82 (74)
0
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
4-Bromonitrobenzene
4-Bromobenzonitrile
4-Bromobenzonitrile
4-Trifluoromethylbromobenzene
3,5-bis(Trifluoromethyl)bromobenzene
4-Fluorobromobenzene
4-Fluorobromobenzene
4-Bromotoluene
9
10
10
11
11
12
13
13
14
14
15
10,000
1000
4-Bromotoluene
10,000
10,000
10,000
4-tButylbromobenzene
4-Bromoanisole
4-Bromoanisole
b
—
2-Bromo-6-methoxynaphthalene
2-Bromo-6-methoxynaphthalene
4-Dimethylaminobromobenzene
1000
10,000
1000
100 (94)
94
100 (89)
Conditions: Pd–Tedicyp catalyst, ArX (1 equiv), propiolaldehyde diethyl acetal (2 equiv), CuI (0.05 equiv), K2CO3 (2 equiv), DMF, 130 8C, 20 h.
a GC and NMR conversion; yields in parenthesis are isolated.
b Reaction performed with CuI and without Pd catalyst.

M. Lemhadri et al. / Tetrahedron 61 (2005) 9839–9847
9841
Table 2. Palladium–Tedicyp catalyzed Sonogashira reaction with propiolaldehyde diethyl acetal and meta- or ortho-substituted aryl bromides (Schemes 1
and 2)
Entry
Aryl halide
Ratio substrate/catalyst
Product
Yield (%)a
1
2
3
4
5
6
7
8
3-Bromoacetophenone
3-Bromoacetophenone
3-Bromonitrobenzene
3-Bromonitrobenzene
3-Bromotoluene
2-Bromoacetophenone
2-Bromoacetophenone
2-Bromobenzaldehyde
Methyl 2-bromobenzoate
Methyl 2-bromobenzoate
2-Bromobenzonitrile
10,000
100,000
1000
10,000
1000
250
1000
10,000
1000
10,000
1000
10,000
10,000
1000
10,000
1000
1000
10,000
1000
10,000
250
1000
16
16
17
17
100 (90)
50
100 (89)
90
18
100 (92)
100 (80)b
100 (45 and 42)b,c
100 (91)
100 (90)
67
19c
19aC19c
20
9
21
21
22
22
23
24
24
25
26
26
27
27
28
28
29
29
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
100 (87)
90
100 (91)
100 (93)
55
100 (90)
100 (94)
68
100 (88)
85
90 (84)
50
100 (89)
88
100 (88)
100 (90)
40
2-Bromobenzonitrile
2-Trifluoromethylbromobenzene
2-Fluorobromobenzene
2-Fluorobromobenzene
2-Bromotoluene
1-Bromonaphthalene
1-Bromonaphthalene
2-Bromoanisole
2-Bromoanisole
2,6-Difluorobromobenzene
2,6-Difluorobromobenzene
2,4,6-Trimethylbromobenzene
2,4,6-Trimethylbromobenzene
2,6-Diethyl-4-methylbromobenzene
9-Bromoanthracene
1000
10,000
1000
1000
30
31
31
9-Bromoanthracene
10,000
Conditions: Pd–tedicyp catalyst, ArBr (1 equiv), propiolaldehyde diethyl acetal (2 equiv), CuI (0.05 equiv), K2CO3 (2 equiv), DMF, 130 8C, 20 h.
a GC and NMR conversion; yields in parenthesis are isolated.
b Before filtration on silica gel 19b was observed (see Scheme 2).
c The formation of a mixture of 19a (45%) and 19c (42%) (see Scheme 2) was observed.
reaction performed with a ratio substrate/catalyst of 250 led
exclusively to 19b. Acidic treatment or filtration on silica
gel of this compound gave the corresponding aldehyde 19c.
The formation of similar cyclization products has already
been described for the palladium-catalyzed reactions of
2-iodobenzoic acid or 2-iodobenzyl alcohol and terminal
alkynes.19
Then, the reactivity of a few aryl chlorides was studied
(Table 3). These reactions were performed without CuI as
co-catalyst. With electron-poor aryl chlorides such as
4-chloroacetophenone, 4-chloronitrobenzene or 4-chloro-
benzonitrile the alkynylation products were obtained in
good yields in the presence of 1% catalyst (Table 3, entries
1–7). On the other hand the electron-rich 4-chloroanisole
led to the adduct 13 in a very low TON of 17 (Table 3, entry
8). Thus, the oxidative-addition of the aryl chlorides be the
rate-limiting step of the reaction.
Next, we tried to evaluate the difference of reaction rate
between mono- and di-ortho-substituted aryl bromides,
and we observed that even very hindered aryl bromides
could be coupled efficiently with propiolaldehyde diethyl
acetal (Table 2, entries 21–27). For example, with 2,4,6-
trimethylbromobenzene or 9-bromoanthracene the
expected adducts were obtained in 89 and 90% yields,
respectively, in the presence of 0.1% catalyst (Table 2,
entries 23–27).
Finally, we have investigated the Sonogashira reaction of
nine heteroaryl halides. The results are summarized in
Table 4. We have observed in Tables 1 and 2 that with aryl
bromides the oxidative addition to the palladium complex is
probably not the rate-limiting step of the reaction with this
catalyst. Pyridines or quinolines are p-electron deficient.
Table 3. Palladium–Tedicyp catalyzed Sonogashira reaction with propiolaldehyde diethyl acetal and aryl chlorides (Scheme 1)
Entry
Aryl halide
Ratio substrate/catalyst
Product
Yield (%)a
1
2
3
4
5
6
7
8
4-Chloroacetophenone
4-Chlorobenzaldehyde
4-Chlorobenzaldehyde
4-Chloronitrobenzene
4-Chloronitrobenzene
4-Chlorobenzonitrile
100
100
250
100
250
100
100
100
2
3
3
6
6
7
8
13
97 (87)
100 (90)
100
100 (89)
55
100 (87)
100 (87)
17
4-Trifluoromethylchlorobenzene
4-Chloroanisole
Conditions: Pd–Tedicyp catalyst, ArCl (1 equiv), propiolaldehyde diethyl acetal (2 equiv), K2CO3 (2 equiv), reactions performed without CuI, DMF, 130 8C,
20 h.
a GC and NMR conversion; yields in parenthesis are isolated.

9842
M. Lemhadri et al. / Tetrahedron 61 (2005) 9839–9847
Table 4. Palladium–Tedicyp catalyzed Sonogashira reaction with propiolaldehyde diethyl acetal and heteroaryl halides (Scheme 1)
Entry
Aryl halide
Ratio substrate/catalyst
Product
Yield (%)a
1
2
3
4
5
6
7
8
2-Bromopyridine
2-Bromopyridine
2-Chloropyridine
2-Chloropyridine
3-Bromopyridine
2-Chloroquinoline
2-Chloroquinoline
3-Bromoquinoline
3-Bromoquinoline
4-Bromoisoquinoline
5-Bromopyrimidine
5-Bromopyrimidine
2-Bromothiophene
2-Bromothiophene
3-Bromothiophene
3-Bromothiophene
1,000
10,000
100
32
32
32
32
33
34
34
35
35
36
37
37
38
38
39
39
100 (89)
100
100b
250
65b
100 (93)
100 (90)b
66b
100 (94)
52
100 (90)
100 (90)
100
100 (88)
95
100 (90)
100
10,000
100
250
1000
10,000
10,000
1000
10,000
1000
10,000
100
9
10
11
12
13
14
15
16
1000
Conditions: Pd–Tedicyp catalyst, ArX (1 equiv), propiolaldehyde diethyl acetal (2 equiv), CuI (0.05 equiv), K2CO3 (2 equiv), DMF, 130 8C, 20 h.
a GC and NMR conversion; yields in parenthesis are isolated.
b Reactions performed without CuI.
Thiophenes or furanes are p-electron excessive. If the
oxidative-addition is rate-limiting, the reactions should be
slower with thiophenes or furanes than with pyridines or
quinolines. In the presence of 2-bromopyridine,
3-bromopyridine, 3-bromoquinoline, 4-bromoisoquinoline,
and 5-bromopyrimidine the reactions were performed
successfully with 0.1–0.01% catalyst (Table 4, entries 1,
2, 5, and 8–12). Similar reactions rates were observed with
2-bromothiophene and 3-bromothiophene (Table 4, entries
13–16). These results seem to confirm that the oxidative
addition of the aryl bromides to palladium is not the rate-
limiting step of this reaction. The two heteroaryl chlorides:
2-chloropyridine and 2-chloroquinoline were also success-
fully alkynylated, but the presence of 0.4% catalyst was
required (Table 4, entries 3, 4, 6, and 7).
The synthesis of 1,4- and 1,2-bis(3,3-diethoxyprop-1-ynyl)-
benzene 40 and 41 from 1,4- and 1,2-dibromobenzene using
4 equiv of propiolaldehyde diethyl acetal also proceeds in
good yields (Scheme 3). With 1,4-dibromobenzene, the
Scheme 2.
Scheme 3.

M. Lemhadri et al. / Tetrahedron 61 (2005) 9839–9847
9843
monoaddition product was not observed and the diaddition
3.2. General procedure
product 40 was selectively obtained in 92% yield in the
presence of 0.1% catalyst. On the other hand, with 1,2-
dibromobenzene, if the diaddition product was selectively
obtained in the presence of 0.4% catalyst, mixtures of mono
and diaddition products 41 and 42 were obtained when
ratios substrate/catalyst of 1000 and 10,000 were used. The
slower reaction rate observed with 1,2-dibromobenzene
probably comes from steric reasons.
In a typical experiment, the aryl halide (1 mmol),
propiolaldehyde diethyl acetal (0.256 g, 2 mmol or 0.
512 g 4 mmol, see Tables 1–4 and Scheme 3), K2CO3
(0.276 g, 2 mmol or 0.552 g 4 mmol, see Tables 1–4 and
Scheme 3) and CuI for the reactions performed with aryl
bromides (0.01 g, 0.05 mmol) were dissolved in DMF
(3 mL) under an argon atmosphere. The prepared Pd–
Tedicyp catalyst complex (see Tables 1–4) was then
transferred to the reaction flask via cannula. The reaction
mixture was stirred at 130 8C for 20 h. Then, the product
was extracted three times with Et2O or CH2Cl2. (For
compound 19c, the mixture was acidified with an HCl
solution (pH 6) then the product was extracted three times
with Et2O). The combined organic layer was dried over
MgSO4 and the solvent was removed in vacuo. The crude
product was purified by silica gel column chromatography.
In summary, we have established that the Tedicyp–
palladium system provides an efficient catalyst for the
coupling of aryl bromides with propiolaldehyde diethyl
acetal. The uses of this Pd–tetraphosphine catalyst allow the
use of low-catalyst loading. This reaction can be performed
with as little as 0.01% catalyst with most of the aryl
bromides. Due to the high price of palladium, the practical
advantage of such low catalyst loadings can become
increasingly important for industrial processes. A wide
range of functions such as methoxy, fluoro, acetyl, formyl,
benzoyl, carboxylate, nitro, nitrile or dimethylamino on the
aryl bromide are tolerated. The steric hindrance of the aryl
bromide has a minor effect on the reaction rates. Lower
TONs were obtained for the coupling of aryl chlorides. With
these substrates the use of 1% catalyst was necessary. Some
heteroaromatic substrates such as bromo- or chloropyr-
idines, a bromopyrimidine or bromothiophenes have also
been used successfully. Moreover, propiolaldehyde diethyl
acetal is commercially available and this is a practical
advantage of this reaction.
3.2.1. 1-Phenyl-3,3-diethoxyprop-1-yne 1. From iodoben-
zene (0.204 g, 1 mmol), product 1 was obtained in 92%
(0.187 g) yield.
1H NMR (300 MHz, CDCl3) d 7.40 (m, 2H), 7.26 (m, 3H),
5.42 (s, 1H), 3.73 (m, 2H), 3.60 (m, 2H), 1.21 (t, 6H, JZ7.
1 Hz).
3.2.2. 1-(4-Acetylphenyl)-3,3-diethoxyprop-1-yne 2.
From 4-bromoacetophenone (0.199 g, 1 mmol), product 2
was obtained in 94% (0.231 g) yield.
1H NMR (300 MHz, CDCl3) d 7.86 (d, 2H, JZ8.4 Hz), 7.52
(d, 2H, JZ8.4 Hz), 5.46 (s, 1H), 3.77 (m, 2H), 3.65 (m, 2H),
2.55 (s, 3H), 1.24 (t, 6H, JZ7.2 Hz); 13C NMR (75 MHz,
CDCl3) d 197.1, 136.7, 132.0, 128.1, 126.6, 91.6, 87.5, 84.1,
61.0, 26.5, 15.0; C15H18O3: Calcd C, 73.15; H, 7.37. Found:
C, 72.97; H, 7.43.
3. Experimental
3.1. General remarks
3.2.3. 1-(4-Formylphenyl)-3,3-diethoxyprop-1-yne 3.
From 4-bromobenzaldehyde (0.185 g, 1 mmol), product 3
was obtained in 94% (0.218 g) yield.
All reactions were run under argon in Schlenk tubes using
vacuum lines. DMF analytical grade was not distilled before
use. Potassium carbonate (99C) was used. Commercial
propiolaldehyde diethyl acetal was used without purifi-
cation. The reactions were followed by GC and NMR for
high boiling point substrates and by GC for low boiling
point substrates. 1H and 13C spectrum were recorded with a
Bruker 300 MHz spectrometer in CDCl3 solutions. Chemi-
cal shift are reported in ppm relative to CDCl3 (7.25 for 1H
NMR and 77.0 for 13C NMR). Flash chromatography were
performed on silica gel (230–400 mesh). GC and NMR
yields in Tables 1–4 are conversions of the aryl halides into
1H NMR (300 MHz, CDCl3) d 9.98 (s, 1H), 7.79 (d, 2H, JZ
7.8 Hz), 7.60 (d, 2H, JZ7.8 Hz), 5.48 (s, 1H), 3.76 (m, 2H),
3.62 (m, 2H), 1.23 (t, 6H, JZ6.2 Hz); 13C NMR (75 MHz,
CDCl3) d 191.3, 135.8, 132.4, 129.4, 128.0, 91.6, 88.2, 84.0,
61.1, 15.0; C14H16O3: Calcd C, 72.39; H, 6.94. Found: C,
72.47; H, 7.09.
3.2.4. 1-(4-Benzoylphenyl)-3,3-diethoxyprop-1-yne 4.
From 4-bromobenzophenone (0.261 g, 1 mmol), product 4
was obtained in 91% (0.280 g) yield.
1
the product calculated with GC and H NMR spectrum of
the crude mixtures.
1H NMR (300 MHz, CDCl3) d 7.80–7.70 (m, 4H), 7.60–7.52
(m, 3H), 7.45 (t, 2H, JZ7.2 Hz), 5.49 (s, 1H), 3.79 (m, 2H), 3.
66 (m, 2H), 1.25 (t, 6H, JZ6.2 Hz); 13C NMR (75 MHz,
CDCl3) d 195.7, 137.3, 137.1, 132.5, 131.7, 129.9, 129.8,
128.3, 125.9, 91.6, 87.2, 84.2, 61.0, 15.0; C20H20O3: Calcd
C, 77.90; H, 6.54. Found: C, 77.67; H, 6.74.
3.1.1. Preparation of the Pd–tedicyp catalyst. An oven-
dried 40-mL Schlenk tube equipped with a magnetic stirring
bar under argon atmosphere, was charged with [Pd(h3-
C3H5)Cl]2 (30 mg, 81 mmol) and Tedicyp (140 mg,
162 mmol). Anhydrous DMF (10 mL) were added, then
the solution was stirred at room temperature for 10 min. The
appropriate catalyst concentration was obtained by succes-
sive dilutions. 31P NMR (162 MHz, CDCl3) d 25 (wZ
80 Hz), 19.4 (wZ110 Hz).
3.2.5. 1-(4-Methoxycarbonylphenyl)-3,3-diethoxyprop-
1-yne 5. From methyl 4-bromobenzoate (0.215 g,
1 mmol), product 5 was obtained in 90% (0.236 g) yield.

9844
M. Lemhadri et al. / Tetrahedron 61 (2005) 9839–9847
1H NMR (300 MHz, CDCl3) d 7.97 (d, 2H, JZ8.3 Hz), 7.52
(d, 2H, JZ8.3 Hz), 5.48 (s, 1H), 3.89 (s, 3H), 3.77 (m, 2H),
3.65 (m, 2H), 1.27 (t, 6H, JZ7.2 Hz).
12. From 4-tbutylbromobenzene (0.213 g, 1 mmol), product
12 was obtained in 92% (0.239 g) yield.
1H NMR (300 MHz, CDCl3) d 7.43 (d, 2H, JZ8.4 Hz), 7.34
(d, 2H, JZ8.4 Hz), 5.50 (s, 1H), 3.83 (m, 2H), 3.68 (m, 2H),
1.32 (s, 9H), 1.27 (t, 6H, JZ7.2 Hz); 13C NMR (75 MHz,
CDCl3) d 152.1, 131.6, 125.2, 118.3, 91.5, 85.4, 83.7, 60.9,
34.8, 31.2, 15.1. This compound was characterized by
deprotection into the corresponding aldehyde.20
3.2.6. 1-(4-Nitrophenyl)-3,3-diethoxyprop-1-yne 6. From
4-bromonitrobenzene (0.202 g, 1 mmol), product 6 was
obtained in 94% (0.234 g) yield.
1H NMR (300 MHz, CDCl3) d 8.16 (d, 2H, JZ8.5 Hz), 7.59
(d, 2H, JZ8.5 Hz), 5.48 (s, 1H), 3.77 (m, 2H), 3.65 (m, 2H),
1.26 (t, 6H, JZ7.2 Hz).
3.2.13. 1-(4-Anisyl)-3,3-diethoxyprop-1-yne 13. From
4-bromoanisole (0.187 g, 1 mmol), product 13 was obtained
in 74% (0.173 g) yield.
3.2.7. 1-(4-Cyanophenyl)-3,3-diethoxyprop-1-yne 7.
From 4-bromobenzonitrile (0.182 g, 1 mmol), product 7
was obtained in 91% (0.209 g) yield.
1H NMR (300 MHz, CDCl3) d 7.40 (d, 2H, JZ8.4 Hz), 6.81
(d, 2H, JZ8.4 Hz), 5.46 (s, 1H), 3.80 (m, 2H), 3.79 (s, 3H),
3.64 (m, 2H), 1.26 (t, 6H, JZ7.2 Hz).
1H NMR (300 MHz, CDCl3) d 7.59 (d, 2H, JZ8.5 Hz), 7.53
(d, 2H, JZ8.5 Hz), 5.47 (s, 1H), 3.77 (m, 2H), 3.65 (m, 2H),
1.26 (t, 6H, JZ7.2 Hz); 13C NMR (75 MHz, CDCl3) d 132.4,
131.9, 126.7, 118.2, 112.2, 91.5, 88.7, 83.2, 61.1, 15.0;
C14H15NO2: Calcd C, 73.34; H, 6.59. Found: C, 73.21; H, 6.47.
3.2.14.
2-(3,3-Diethoxy-prop-1-ynyl)-6-methoxy-
naphthalene 14. From 2-bromo-6-methoxynaphthalene
(0.237 g, 1 mmol), product 14 was obtained in 94%
(0.267 g) yield.
3.2.8. 1-(4-Trifluoromethylphenyl)-3,3-diethoxyprop-1-
yne 8. From 4-trifluoromethylbromobenzene (0.225 g,
1 mmol), product 8 was obtained in 90% (0.245 g) yield.
1H NMR (300 MHz, CDCl3) d 7.92 (s, 1H), 7.65 (m, 2H), 7.
45 (dd, 1H, JZ8.5, 1.5 Hz), 7.13 (dd, 1H, JZ8.7, 2.4 Hz),
7.06 (d, 1H, JZ2.4 Hz), 5.53 (s, 1H), 3.85 (s, 3H), 3.83 (m,
2H), 3.68 (m, 2H), 1.29 (t, 6H, JZ7.2 Hz); 13C NMR
(75 MHz, CDCl3) d 158.4, 134.3, 131.8, 129.2, 128.8, 128.
2, 126.6, 119.3, 116.6, 105.6, 91.8, 85.6, 83.9, 60.8, 55.1,
15.0; C18H20O3: Calcd C, 76.03; H, 7.09. Found: C, 75.81;
H, 7.31.
1H NMR (300 MHz, CDCl3) d 7.59 (m, 4H), 5.51 (s, 1H), 3.83
(m, 2H), 3.68 (m, 2H), 1.29 (t, 6H, JZ7.2 Hz); 13C NMR
(75 MHz, CDCl3)d 132.2,130.5(q, JZ32.4 Hz), 125.6, 125.2
(q, JZ3.8 Hz), 123.8 (q, JZ274.2 Hz), 91.6, 86.8, 83.6, 61.1,
15.0; C14H15F3O2: Calcd C, 61.76; H, 5.55. Found: C, 61.66;
H, 5.34.
3.2.15. 1-(4-Dimethylaminophenyl)-3,3-diethoxyprop-1-
yne 15. From 4-dimethylaminobromobenzene (0.200 g,
1 mmol), product 15 was obtained in 89% (0.220 g) yield.
3.2.9. 1-[3,5-Bis(trifluoromethyl)phenyl]-3,3-diethoxy-
prop-1-yne 9. From 3,5-bis(trifluoromethyl)bromobenzene
(0.293 g, 1 mmol), product 9 was obtained in 92% (0.313 g)
yield.
1H NMR (300 MHz, CDCl3) d 7.32 (d, 1H, JZ8.9 Hz), 6.59
(d, 1H, JZ8.9 Hz), 5.47 (s, 1H), 3.81 (m, 2H), 3.64 (m, 2H),
2.94 (s, 6H), 1.26 (t, 6H, JZ7.2 Hz); 13C NMR (75 MHz,
CDCl3) d 150.3, 132.9, 111.5, 108.4, 92.0, 86.4, 82.1, 60.7,
40.0, 15.1. This compound was characterized by deprotec-
tion into the corresponding aldehyde.21
1H NMR (300 MHz, CDCl3) d 7.89 (s, 2H), 7.81 (s, 1H), 5.48
(s, 1H), 3.83 (m, 2H), 3.68 (m, 2H), 1.27 (t, 6H, JZ7.2 Hz);
13C NMR (75 MHz, CDCl3) d 132.0 (q, JZ34.5 Hz), 131.8,
124.5, 122.8 (q, JZ272.3 Hz), 122.2 (m), 91.5, 88.0, 81.9,
61.2, 15.0; C15H14F6O2: Calcd C, 52.95; H, 4.15. Found: C,
52.80; H, 4.39.
3.2.16. 1-(3-Acetylphenyl)-3,3-diethoxyprop-1-yne 16.
From 3-bromoacetophenone (0.199 g, 1 mmol), product
16 was obtained in 90% (0.222 g) yield.
3.2.10. 1-(4-Fluorophenyl)-3,3-diethoxyprop-1-yne 10.
From 4-fluorobromobenzene (0.175 g, 1 mmol), product
10 was obtained in 88% (0.196 g) yield.
1H NMR (300 MHz, CDCl3) d 8.01 (s, 1H), 7.87 (d, 1H, JZ
8.0 Hz), 7.62 (d, 1H, JZ8.0 Hz), 7.38 (t, 1H, JZ8.0 Hz), 5.
46 (s, 1H), 3.79 (m, 2H), 3.63 (m, 2H), 2.56 (s, 3H), 1.23 (t,
6H, JZ7.2 Hz); 13C NMR (75 MHz, CDCl3) d 197.3, 137.0,
136.0, 131.8, 128.6, 128.3, 122.4, 91.6, 85.4, 84.0, 61.0, 26.
5, 15.0; C15H18O3: Calcd C, 73.15; H, 7.37. Found: C, 73.
41; H, 7.18.
1H NMR (300 MHz, CDCl3) d 7.44 (dd, 2H, JZ5.5, 8.5 Hz),
6.97 (t, 2H, JZ8.5 Hz), 5.44 (s, 1H), 3.78 (m, 2H), 3.62 (m,
2H), 1.24 (t, 6H, JZ7.2 Hz).
3.2.11. 1-(4-Tolyl)-3,3-diethoxyprop-1-yne 11. From
4-bromotoluene (0.171 g, 1 mmol), product 11 was obtained
in 90% (0.196 g) yield.
3.2.17. 1-(3-Nitrophenyl)-3,3-diethoxyprop-1-yne 17.
From 3-bromonitrobenzene (0.202 g, 1 mmol), product 17
was obtained in 89% (0.222 g) yield.
1H NMR (300 MHz, CDCl3) d 7.34 (d, 2H, JZ8.2 Hz), 7.09
(d, 2H, JZ8.2 Hz), 5.47 (s, 1H), 3.80 (m, 2H), 3.64 (m, 2H),
2.32 (s, 3H), 1.25 (t, 6H, JZ7.2 Hz).
1H NMR (300 MHz, CDCl3) d 8.28 (s, 1H), 8.15 (d, 1H, JZ
8.3 Hz), 7.73 (d, 1H, JZ8.3 Hz), 7.48 (t, 1H, JZ8.3 Hz), 5.
46 (s, 1H), 3.79 (m, 2H), 3.63 (m, 2H), 1.24 (t, 6H, JZ7.
2 Hz); 13C NMR (75 MHz, CDCl3) d 147.9, 137.4, 129.3,
3.2.12. 1-(4-tert-Butylphenyl)-3,3-diethoxyprop-1-yne

M. Lemhadri et al. / Tetrahedron 61 (2005) 9839–9847
9845
126.5, 123.6, 123.4, 91.5, 87.0, 82.4, 61.0, 15.0;
C13H15NO4: Calcd C, 62.64; H, 6.07. Found: C, 62.47; H,
5.84.
3.64 (m, 2H), 1.25 (t, 6H, JZ7.2 Hz); 13C NMR (75 MHz,
CDCl3) d 132.7, 132.6, 132.3, 128.9, 125.7, 117.1, 115.4,
91.5, 90.7, 80.9, 61.2, 15.0; C14H15NO2: Calcd C, 73.34; H,
6.59. Found: C, 73.60; H, 6.71.
3.2.18. 1-(3-Tolyl)-3,3-diethoxyprop-1-yne 18. From
3-bromotoluene (0.171 g, 1 mmol), product 18 was obtained
in 92% (0.201 g) yield.
3.2.23. 1-(2-Trifluoromethylphenyl)-3,3-diethoxyprop-1-
yne 23. From 2-trifluoromethylbromobenzene (0.225 g,
1 mmol), product 23 was obtained in 91% (0.248 g) yield.
1H NMR (300 MHz, CDCl3) d 7.27 (m, 2H), 7.17 (t, 1H, JZ
7.8 Hz), 7.11 (d, 1H, JZ7.8 Hz), 5.46 (s, 1H), 3.81 (m, 2H),
3.64 (m, 2H), 2.30 (s, 3H), 1.25 (t, 6H, JZ7.2 Hz).
1H NMR (300 MHz, CDCl3) d 7.62 (m, 2H), 7.44 (t, 1H, JZ
7.6 Hz), 7.40 (t, 1H, JZ7.4 Hz), 5.49 (s, 1H), 3.81 (m, 2H),
3.66 (m, 2H), 1.26 (t, 6H, JZ7.2 Hz); 13C NMR (75 MHz,
CDCl3) d 134.6, 131.8 (q, JZ30.7 Hz), 131.3, 128.5, 125.7
(q, JZ4.9 Hz), 123.3 (q, JZ274.0 Hz), 120.2 (q, JZ2.
1 Hz), 91.7, 90.1, 80.8, 61.0, 15.0; C14H15F3O2: Calcd C,
61.76; H, 5.55. Found: C, 61.50; H, 5.72.
3.2.19. 1-(2-Benzoylphenyl)-3,3-diethoxyprop-1-yne 19a.
From 2-bromoacetophenone (0.199 g, 1 mmol), product
19a was obtained in 45% (0.111 g) yield.
1H NMR (300 MHz, CDCl3) d 7.93 (dd, 1H, JZ1.1, 7.5 Hz), 7.
57 (dd, 1H, JZ1.2, 7.6 Hz), 7.44 (dt, 1H, JZ1.1, 7.5 Hz), 7.36
(dt, 1H, JZ1.2, 7.6 Hz), 5.52 (s, 1H), 3.84 (s, 3H), 3.80 (m,
2H), 3.69 (m, 2H), 1.25 (t, 6H, JZ7.2 Hz); 13C NMR
(75 MHz, CDCl3) d 166.3, 134.4, 132.3, 131.6, 130.3, 128.4,
122.3, 91.8, 89.3, 83.6, 60.9, 52.1, 15.1; C15H18O3: Calcd C,
73.15; H, 7.37. Found: C, 73.44; H, 7.58. The formation of
19b was also observed: 1H NMR (300 MHz, CDCl3) d
7.55–7.45 (m, 2H), 7.40–7.30 (m, 2H), 5.61 (d, 1H, JZ
7.6 Hz), 5.27 (d, 1H, JZ7.6 Hz), 4.77 (d, 1H, JZ2.6 Hz),
4.47 (d, 1H, JZ2.6 Hz), 3.75 (m, 2H), 3.60 (m, 2H), 1.23 (t,
6H, JZ7.2 Hz); 13C NMR (75 MHz, CDCl3) d 157.6, 153.3,
133.4, 133.3, 130.1 (CH), 129.9 (CH), 120.8 (2CH), 97.2
(CH), 96.1 (CH), 82.5 (]CH2), 61.3 (CH2), 15.2 (Me).
3.2.24. 1-(2-Fluorophenyl)-3,3-diethoxyprop-1-yne 24.
From 2-fluorobromobenzene (0.175 g, 1 mmol), product
24 was obtained in 93% (0.207 g) yield.
1H NMR (300 MHz, CDCl3) d 7.43 (t, 1H, JZ7.3 Hz), 7.30
(m, 1H), 7.06 (m, 2H), 5.49 (s, 1H), 3.82 (m, 2H), 3.65 (m,
2H), 1.26 (t, 6H, JZ7.2 Hz); 13C NMR (75 MHz, CDCl3) d
162.8 (d, JZ252.4 Hz), 133.6, 130.5 (d, JZ7.7 Hz), 123.8
(d, JZ3.3 Hz), 115.4 (d, JZ21.7 Hz), 110.5 (d, JZ15.4 Hz),
91.7, 89.5, 78.6, 61.0, 15.0; C13H15FO2: Calcd C, 70.25; H,
6.80. Found: C, 70.01; H, 6.69.
3.2.25. 1-(2-Tolyl)-3,3-diethoxyprop-1-yne 25. From
2-bromotoluene (0.171 g, 1 mmol), product 25 was obtained
in 90% (0.197 g) yield.
1
After HCl hydrolysis of 19b, 19c was obtained: H NMR
(300 MHz, CDCl3) d 10.25 (d, 1H, JZ8.3 Hz), 7.67 (m,
2H), 7.59 (t, 1H, JZ7.6 Hz), 7.51 (t, 1H, JZ7.6 Hz), 5.75
(d, 1H, JZ8.1 Hz), 5.15 (d, 1H, JZ3.2 Hz), 5.09 (d, 1H,
JZ3.2 Hz); 13C NMR (75 MHz, CDCl3) d 188.8, 166.3,
157.2, 133.8, 132.5, 132.4, 130.3, 122.1, 120.8, 99.5, 88.0.
1H NMR (300 MHz, CDCl3) d 7.43 (d, 1H, JZ7.4 Hz), 7.20
(m, 2H), 7.12 (t, 1H, JZ7.1 Hz), 5.53 (s, 1H), 3.83 (m, 2H),
3.66 (m, 2H), 2.44 (s, 3H), 1.26 (t, 6H, JZ7.2 Hz).
3.2.20. 1-(2-Formylphenyl)-3,3-diethoxyprop-1-yne 20.
From 2-bromobenzaldehyde (0.185 g, 1 mmol), product 20
was obtained in 91% (0.211 g) yield.
3.2.26. 1-(3,3-Diethoxyprop-1-ynyl)-naphthalene 26.
From 1-bromonaphthalene (0.207 g, 1 mmol), product 26
was obtained in 94% (0.239 g) yield.
1H NMR (300 MHz, CDCl3) d 10.49 (s, 1H), 7.89 (d, 1H,
JZ7.4 Hz), 7.55 (m, 2H), 7.44 (t, 1H, JZ7.4 Hz), 5.52 (s,
1H), 3.80 (m, 2H), 3.66 (m, 2H), 1.23 (t, 6H, JZ7.2 Hz);
13C NMR (75 MHz, CDCl3) d 191.5, 136.1, 133.6, 133.5,
129.1, 127.1, 125.2, 91.6, 91.4, 80.6, 61.2, 15.0; C14H16O3:
Calcd C, 72.39; H, 6.94. Found: C, 72.17; H, 6.70.
1H NMR (300 MHz, CDCl3) d 8.31 (d, 1H, JZ8.1 Hz), 7.84
(m, 2H), 7.72 (d, 1H, JZ7.3 Hz), 7.57 (t, 1H, JZ7.5 Hz), 7.51
(t, 1H, JZ7.5 Hz), 7.41 (t, 1H, JZ7.5 Hz), 5.64 (s, 1H), 3.90
(m, 2H), 3.73 (m, 2H), 1.29 (t, 6H, JZ7.2 Hz).
3.2.27. 1-(2-Anisyl)-3,3-diethoxyprop-1-yne 27. From
2-bromoanisole (0.187 g, 1 mmol), product 27 was obtained
in 88% (0.206 g) yield.
3.2.21. 1-(2-Methoxycarbonylphenyl)-3,3-diethoxyprop-
1-yne 21. From methyl 2-bromobenzoate (0.215 g,
1 mmol), product 21 was obtained in 90% (0.236 g) yield.
1H NMR (300 MHz, CDCl3) d 7.39 (dd, 1H, JZ1.7, 7.5 Hz),
7.25 (dt, 1H, JZ1.7, 8.3 Hz), 6.85 (t, 1H, JZ8.3 Hz), 6.82 (d,
1H, JZ8.3 Hz), 5.49 (s, 1H), 3.81 (s, 3H), 3.79 (m, 2H), 3.64
(m, 2H), 1.24 (t, 6H, JZ7.2 Hz).
1H NMR (300 MHz, CDCl3) d 7.90 (dd, 1H, JZ1.5, 7.7 Hz),
7.56 (dd, 1H, JZ1.5, 7.5 Hz), 7.43 (dt, 1H, JZ1.5, 7.7 Hz),
7.34 (dt, 1H, JZ1.5, 7.5 Hz), 5.50 (s, 1H), 3.87 (s, 3H), 3.82
(m, 2H), 3.66 (m, 2H), 1.23 (t, 6H, JZ7.2 Hz).
3.2.28. 1-(2,6-Difluorophenyl)-3,3-diethoxyprop-1-yne
28. From 2,6-difluorobromobenzene (0.193 g, 1 mmol),
product 28 was obtained in 84% (0.202 g) yield.
3.2.22. 1-(2-Cyanophenyl)-3,3-diethoxyprop-1-yne 22.
From 2-bromobenzonitrile (0.182 g, 1 mmol), product 22
was obtained in 87% (0.200 g) yield.
1H NMR (300 MHz, CDCl3) d 7.27 (m, 1H), 6.87 (m, 2H),
5.50(s,1H),3.83(m,2H),3.65(m,2H),1.24(t,6H,JZ7.2 Hz);
13C NMR (75 MHz, CDCl3) d 163.2 (dd, JZ5.2, 254.7 Hz),
130.5 (t, JZ10.2 Hz), 111.2 (d, JZ24.7 Hz), 101.1 (t, JZ19.
1H NMR (300 MHz, CDCl3) d 7.11 (d, 1H, JZ7.8 Hz), 7.50
(m, 2H), 7.41 (t, 1H, JZ7.8 Hz), 5.49 (s, 1H), 3.81 (m, 2H),

9846
M. Lemhadri et al. / Tetrahedron 61 (2005) 9839–9847
5 Hz), 94.4, 91.6, 91.3, 61.2, 15.1; C13H14F2O2: Calcd C, 64.99;
H, 5.87. Found: C, 65.13; H, 5.70.
3.2.35. 1-(3-Quinolyl)-3,3-diethoxyprop-1-yne 35. From
3-bromoquinoline (0.208 g, 1 mmol), product 35 was
obtained in 94% (0.240 g) yield.
3.2.29. 1-(2,4,6-Trimethylphenyl)-3,3-diethoxyprop-1-
yne 29. From 2,4,6-trimethylbromobenzene (0.199 g,
1 mmol), product 29 was obtained in 89% (0.219 g) yield.
1H NMR (300 MHz, CDCl3) d 8.95 (m, 1H), 8.24 (s, 1H), 8.12
(d, 1H, JZ8.2 Hz), 7.74 (d, 1H, JZ8.4 Hz), 7.69 (t, 1H, JZ
7.5 Hz), 7.52 (t, 1H, JZ7.5 Hz), 5.52 (s, 1H), 3.82 (m, 2H),
3.67 (m, 2H), 1.27 (t, 6H, JZ7.2 Hz); 13C NMR (75 MHz,
CDCl3) d 151.8, 146.9, 138.9, 130.2, 129.3, 127.5, 127.2,
126.9, 115.9, 91.6, 87.6, 82.2, 61.0, 15.0; C16H17NO2: Calcd
C, 75.27; H, 6.71. Found: C, 75.28; H, 6.57.
1H NMR (300 MHz, CDCl3) d 6.83 (s, 2H), 5.55 (s, 1H), 3.83
(m, 2H), 3.67 (m, 2H), 2.38 (s, 6H), 2.26 (s, 3H), 1.25 (t, 6H,
JZ7.2 Hz).
3.2.30. 1-(2,6-Diethyl-4-methylphenyl)-3,3-diethoxy-
prop-1-yne 30. From 2,6-diethyl-4-methylbromobenzene
(0.227 g, 1 mmol), product 30 was obtained in 88%
(0.242 g) yield.
3.2.36. 1-(4-Isoquinolyl)-3,3-diethoxyprop-1-yne 36.
From 4-bromoisoquinoline (0.208 g, 1 mmol), product 36
was obtained in 90% (0.230 g) yield.
1H NMR (300 MHz, CDCl3) d 6.86 (s, 2H), 5.55 (s, 1H), 3.81
(m, 2H), 3.68 (m, 2H), 2.74 (q, 4H, JZ7.6 Hz), 2.30 (s, 3H),
1.24 (m, 12H); 13C NMR (75 MHz, CDCl3) d 146.8, 138.6,
126.1, 117.3, 92.1, 91.3, 82.5, 60.8, 27.8, 21.5, 15.1, 15.0;
C18H26O2: Calcd C, 78.79; H, 9.55. Found: C, 78.99; H, 9.56.
1H NMR (300 MHz, CDCl3) d 9.19 (m, 1H), 8.71 (m, 1H),
8.16 (d, 1H, JZ8.5 Hz), 7.93 (d, 1H, JZ8.2 Hz), 7.74 (t,
1H, JZ7.5 Hz), 7.60 (t, 1H, JZ7.5 Hz), 5.60 (s, 1H), 3.85
(m, 2H), 3.70 (m, 2H), 1.28 (t, 6H, JZ7.2 Hz); 13C NMR
(75 MHz, CDCl3) d 151.0, 146.7, 135.3, 131.1, 127.8, 127.7,
124.8, 91.7, 80.3, 61.0, 15.1; C16H17NO2: Calcd C, 75.27;
H, 6.71. Found: C, 75.47; H, 6.60.
3.2.31. 9-(3,3-Diethoxy-prop-1-ynyl)-anthracene 31.
From 9-bromoanthracene (0.257 g, 1 mmol), product 31
was obtained in 90% (0.274 g) yield.
3.2.37. 1-(5-Pyrimidolyl)-3,3-diethoxyprop-1-yne 37.
From 5-bromopyrimidine (0.158 g, 1 mmol), product 37
was obtained in 90% (0.186 g) yield.
1H NMR (300 MHz, CDCl3) d 8.56 (d, 2H, JZ8.7 Hz), 8.41
(s, 1H), 7.99 (d, 2H, JZ8.5 Hz), 7.59 (t, 2H, JZ7.8 Hz), 7.50
(t, 2H, JZ7.8 Hz), 5.86 (s, 1H), 4.03 (m, 2H), 3.86 (m, 2H),
1.35 (t, 6H, JZ7.2 Hz); 13C NMR (75 MHz, CDCl3) d 132.8,
130.9, 128.6, 128.3, 126.7, 126.5, 125.6, 115.7, 95.7, 92.3,
81.9, 61.2, 15.2. This compound was characterized by
deprotection into the corresponding aldehyde.22
1H NMR (300 MHz, CDCl3) d 9.14 (s, 1H), 8.78 (s, 2H), 5.47
(s, 1H), 3.77 (m, 2H), 3.63 (m, 2H), 1.24 (t, 6H, JZ7.2 Hz);
13C NMR (75 MHz, CDCl3) d 158.9, 157.2, 118.5, 91.5, 91.4,
78.2, 61.2, 15.0; C11H14N2O2: Calcd C, 64.06; H, 6.84.
Found: C, 64.00; H, 6.71.
3.2.32. 1-(2-Pyridyl)-3,3-diethoxyprop-1-yne 32. From
2-bromopyridine (0.158 g, 1 mmol), product 32 was
obtained in 89% (0.183 g) yield.
3.2.38. 1-(2-Thienyl)-3,3-diethoxyprop-1-yne 38. From
2-bromothiophene (0.163 g, 1 mmol), product 38 was
obtained in 88% (0.185 g) yield.
1H NMR (300 MHz, CDCl3) d 8.55 (d, 1H, JZ4.8 Hz), 7.60
(t, 1H, JZ7.7 Hz), 7.43 (d, 1H, JZ7.9 Hz), 7.20 (dd, 1H,
JZ4.8, 7.0 Hz), 5.44 (s, 1H), 3.77 (m, 2H), 3.62 (m, 2H), 1.21
(t, 6H, JZ7.2 Hz).
1H NMR (300 MHz, CDCl3) d 7.25 (m, 2H), 6.95 (dd, 1H,
JZ3.8, 4.9 Hz), 5.48 (s, 1H), 3.80 (m, 2H), 3.64 (m, 2H),
1.26 (t, 6H, JZ7.2 Hz).
3.2.39. 1-(3-Thienyl)-3,3-diethoxyprop-1-yne 39. From
3-bromothiophene (0.163 g, 1 mmol), product 39 was
obtained in 90% (0.189 g) yield.
3.2.33. 1-(3-Pyridyl)-3,3-diethoxyprop-1-yne 33. From
3-bromopyridine (0.158 g, 1 mmol), product 33 was
obtained in 93% (0.191 g) yield.
1H NMR (300 MHz, CDCl3) d 7.48 (d, 1H, JZ3.0 Hz), 7.23
(dd, 1H, JZ3.0, 5.1 Hz), 7.12 (d, 1H, JZ5.1 Hz), 5.45 (s,
1H), 3.79 (m, 2H), 3.64 (m, 2H), 1.24 (t, 6H, JZ7.2 Hz);
13C NMR (75 MHz, CDCl3) d 129.8, 129.7, 125.6, 120.8,
91.7, 84.0, 80.4, 60.9, 15.0; C11H14O2S: Calcd C, 62.83; H,
6.71. Found: C, 62.95; H, 6.84.
1H NMR (300 MHz, CDCl3) d 8.74 (m, 1H), 8.60 (m, 1H),
7.77 (d, 1H, JZ8.0 Hz), 7.26 (m, 1H), 5.50 (s, 1H), 3.82 (m,
2H), 3.67 (m, 2H), 1.28 (t, 6H, JZ7.2 Hz).
3.2.34. 1-(2-Quinolyl)-3,3-diethoxyprop-1-yne 34. From
2-chloroquinoline (0.164 g, 1 mmol), product 34 was
obtained in 90% (0.230 g) yield.
3.2.40. 1,4-Bis(3,3-diethoxy-prop-1-ynyl)benzene 40.
From 1,4-dibromobenzene (0.236 g, 1 mmol), product 40
was obtained in 92% (0.304 g) yield.
1H NMR (300 MHz, CDCl3) d 8.09 (d, 1H, JZ8.1 Hz), 8.07
(d, 1H, JZ8.1 Hz), 7.76 (d, 1H, JZ8.1 Hz), 7.69 (t, 1H, JZ
7.7 Hz), 7.53 (t, 1H, JZ7.7 Hz), 7.52 (d, 1H, JZ8.1 Hz), 5.54
(s, 1H), 3.84 (m, 2H), 3.69 (m, 2H), 1.26 (t, 6H, JZ7.2 Hz);
13C NMR (75 MHz, CDCl3) d 148.0, 142.3, 136.1, 130.0,
129.4, 127.4, 127.3, 127.2, 124.2, 91.7, 84.7, 84.6, 61.2, 15.0;
C16H17NO2: Calcd C, 75.27; H, 6.71. Found: C, 75.46; H,
6.97.
1H NMR (300 MHz, CDCl3) d 7.39 (s, 4H), 5.45 (s, 2H),
3.79 (m, 4H), 3.64 (m, 4H), 1.24 (t, 12H, JZ7.2 Hz); 13C
NMR (75 MHz, CDCl3) d 131.7, 122.5, 91.7, 86.3, 84.5,
60.9, 15.0; C20H26O4: Calcd C, 72.70; H, 7.93. Found: C,
72.89; H, 7.81.

M. Lemhadri et al. / Tetrahedron 61 (2005) 9839–9847
9847
9. Roesch, K. R.; Larock, R. C. J. Org. Chem. 2002, 67, 86.
3.2.41. 1,2-Bis(3,3-diethoxy-prop-1-ynyl)benzene 41.
From 1,2-dibromobenzene (0.236 g, 1 mmol), product 41
was obtained in 94% (0.310 g) yield.
10. Toussaint, D.; Suffert, J.; Wermuth, C. G. Heterocycles 1994,
38, 1273.
11. Kelly, T. R.; Lee, Y.-J.; Mears, R. J. J. Org. Chem. 1997, 62,
2774.
1H NMR (300 MHz, CDCl3) d 7.45 (m, 2H), 7.25 (m, 2H),
5.48 (s, 2H), 3.82 (m, 4H), 3.66 (m, 4H), 1.24 (t, 12H, JZ
7.2 Hz); 13C NMR (75 MHz, CDCl3) d 132.3, 128.4, 124.7,
91.7, 88.3, 83.5, 60.9, 15.1; C20H26O4: Calcd C, 72.70; H,
7.93. Found: C, 72.67; H, 7.98. The monoaddition product
42 was also isolated 1H NMR (300 MHz, CDCl3) d 7.56 (d,
1H, JZ7.8 Hz), 7.48 (d, 1H, JZ7.8 Hz), 7.28–7.10 (m, 2H),
5.52 (s, 1H), 3.86 (m, 2H), 3.66 (m, 2H), 1.27 (t, 6H, JZ
7.2 Hz); 13C NMR (75 MHz, CDCl3) d 133.8, 132.4, 129.9,
126.9, 125.6, 124.2, 91.7, 88.9, 83.5, 61.1, 15.1.
12. Armengol, M.; Joule, J. A. J. Chem. Soc., Perkin Trans. 1
2001, 978.
13. Farina, V. Adv. Synth. Catal. 2004, 346, 1553.
14. For examples of Sonogashira reactions catalysed efficient
palladium catalysts, see: (a) Herrmann, W. A.; Reisinger, C.-P.;
Spiegler, M. J. Organomet. Chem. 1998, 557, 93. (b) Nakamura,
K.; Okubo, H.; Yamaguchi, M. Synlett 1999, 549. (c) Herrmann,
¨
W. A.; Bohm, V.; Reisinger, C.-P. J. Organomet. Chem. 1999,
576, 23. (d) McGuinness, D.; Cavell, K. Organometallics 2000,
¨
19, 741. (e)Bohm, V. P.W.;Herrmann, W.A. Eur. J.Org. Chem.
3.3. Registry No.: 1
2000, 3679. (f) Hundertmark, T.; Littke, A.; Buchwald, S.; Fu, G.
Org. Lett. 2000, 2, 1729. (g) Buchmeiser, M.; Schareina, T.;
Kempe, R.; Wurst, K. J. Organomet. Chem. 2001, 634, 39.
(h) Batey, R. A.; Shen, M.; Lough, A. J. Org. Lett. 2002, 4, 1411.
(i) Alonso, D.; Najera, C.; Pacheco, C. Tetrahedron Lett. 2002,
43, 9365. (j) Choudary, B. M.; Madhi, S.; Chowdari, N. S.;
Kantam, M. L.;Sreedhar, B. J.Am. Chem. Soc. 2002, 124, 14127.
(k) Dai, W.-W.; Sun, L.-P.; Guo, D.-S. Tetrahedron Lett. 2002,
43, 7699. (l) Hillier, A.; Grasa, G.; Viciu, M.; Lee, H.; Yang, C.;
Nolan, S. J. Organomet. Chem. 2002, 653, 69. (m) Yang, C.;
Nolan, S. Organometallics 2002, 21, 1020. (n) Eberhard, M. R.;
Wang, Z.; Jensen, C. M. Chem. Commun. 2002, 818. (o) Gelman,
D.; Buchwald, S. L. Angew. Chem., Int. Ed. 2003, 42, 5993.
6142-95-6; 5, 181419-95-4; 6, 83758-93-4; 10, 74929-22-9;
11, 62358-86-5; 13, 62358-88-7; 18, 62358-87-6; 21,
181419-89-6; 25, 181419-85-2; 26, 2375725 (Beilstein
Registry Number); 27, 202391-28-4; 29, 73057-39-3; 32,
49836-19-3; 33, 143952-62-9; 38, 13781-32-3.
Acknowledgements
´ ´
We thank CNRS and the ‘Conseil General des Bouches-du-
ˆ
Rhone, Fr’ for financial support.
¨
(p) Kollhofer, A.; Plenio, H. Chem. Eur. J. 2003, 9, 1416.
¨
(q) Kollhofer, A.; Pullmann, T.; Plenio, H. Angew. Chem., Int.
´ ´
Ed. 2003, 42, 1056. (r) Mery, D.; Heuze, K.; Astruc, D. Chem.
References and notes
Commun. 2003, 1934.
15. Laurenti, D.; Feuerstein, M.; Pepe, G.; Doucet, H.; Santelli, M.
`
1. Lee, K. Y.; Lee, M. J.; Gowrisankar, S.; Kim, J. N.
Tetrahedron Lett. 2004, 45, 5043 and references herein.
2. (a) Sonogashira, K. In Diederich, F., Stang, P. J., Eds. Metal-
Catalyzed Cross-Coupling Reactions; Wiley: New York, 1998.
(b) Brandsma, L.; Vasilevsky, S. F.; Verkruijsse, H. D.
Application of Transition Metal Catalysts in Organic Synthesis;
Springer: Berlin, 1998. (c) Sonogashira, K. J. Organomet. Chem.
2002, 653, 46.
J. Org. Chem. 2001, 66, 1633.
16. Feuerstein, M.; Laurenti, D.; Bougeant, C.; Doucet, H.;
Santelli, M. Chem. Commun. 2001, 325.
17. Feuerstein, M.; Doucet, H.; Santelli, M. J. Org. Chem. 2001,
66, 5923.
18. (a) Feuerstein, M.; Berthiol, F.; Doucet, H.; Santelli, M. Org.
Biomol. Chem. 2003, 2235. (b) Feuerstein, M.; Berthiol, F.;
Doucet, H.; Santelli, M. Synthesis 2004, 1281. (c) Feuerstein,
M.; Doucet, H.; Santelli, M. Tetrahedron Lett. 2004, 45, 1603.
(d) Feuerstein, M.; Doucet, H.; Santelli, M. Tetrahedron Lett.
2004, 45, 8443. (e) Feuerstein, M.; Doucet, H.; Santelli, M.
Tetrahedron Lett. 2005, 46, 1717.
3. Sakamoto, T.; Kondo, Y.; Iwashita, S.; Nagano, T.;
Yamanaka, H. Chem. Pharm. Bull. 1988, 36, 1305.
4. Sakamoto, T.; Shiga, F.; Yasuhara, A.; Uchiyama, D.; Kondo,
Y.; Yamanaka, H. Synthesis 1992, 746.
5. Cacchi, S.; Fabrizi, G.; Marinelli, F.; Moro, L.; Pace, P.
Tetrahedron 1996, 52, 10225.
19. (a) Kundu, N. G.; Pal, M.; Nandi, B. J. Chem. Soc., Perkin
Trans. 1 1998, 561. (b) Khan, M. W.; Kundu, N. G. Synlett
1999, 456.
6. Cacchi, S.; Fabrizi, G.; Moro, L.; Pace, P. Synlett 1997, 1367.
7. Jiang, J.-L.;vanRhee, A.M.;Chang,L.;Patchornik, A.;Ji, X-D.;
Evans, P.; Melman, N.; Jacobson, K. A. J. Med. Chem. 1997,
40, 2596.
20. Denmark, S. E.; Almstead, N. G. J. Am. Chem. Soc. 1993, 115,
3133.
21. Clair, J. J. L. J. Am. Chem. Soc. 1997, 119, 7676.
22. Kelly, T. R.; Sestelo, J. P.; Tellitu, I. J. Org. Chem. 1998, 63,
3655.
8. Gryko, D. T.; Clausen, C.; Roth, K. M.; Dontha, N.; Bocian,
D. F.; Kuhr, W. G.; Lindsey, J. S. J. Org. Chem. 2000, 65,
7345.