Regioselective hydrostannation of highly hindered arylalkynes under ortho-directing effects

Article abstract of DOI:10.1016/j.tet.2010.09.010

Palladium-catalyzed hydrostannation reactions of ortho-disubstituted arylalkynes were achieved with total stereo- and regio-selectivity in THF at room temperature. The regioselectivity was found to be under the control of the ortho-substituents (ortho-dir

Full text of DOI:10.1016/j.tet.2010.09.010

Tetrahedron 66 (2010) 8698e8706
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Regioselective hydrostannation of highly hindered arylalkynes under
ortho-directing effects
*
Abdallah Hamze, Patrick Le Menez, Olivier Provot, Estelle Morvan, Jean-Daniel Brion, Mouâd Alami
Univ Paris-Sud, CNRS, BioCIS, UMR 8076, Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, rue J.-B. Clément, F-92296 Châtenay-Malabry, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 July 2010
Received in revised form 1 September 2010
Accepted 3 September 2010
Available online 15 September 2010
Palladium-catalyzed hydrostannation reactions of ortho-disubstituted arylalkynes were achieved with
total stereo- and regio-selectivity in THF at room temperature. The regioselectivity was found to be under
the control of the ortho-substituents (ortho-directing effects, ODE) and pure
duced in good yields and as single isomers regardless of the substituents’ nature. These hydrostannation
-products are precursors of choice for the preparation of stereo-defined triarylolefins.
Ó 2010 Elsevier Ltd. All rights reserved.
a-vinylstannanes are pro-
a
Keywords:
Alkynes
Palladium
ortho-Directing effects
Regioselectivity
1. Introduction
control of stereoselectivity is not a problem since the addition of
tributyltin hydride proceeds in a syn manner (cis-addition).2d,4 In
contrast, the regiochemical control of this reaction appears to be
dependent on steric,2d,4,5 electronic,2d and chelating2d,6 factors of
the alkyne substituents. We previously described the regioselective
palladium-catalyzed hydrostannation of conjugated alkynes. With
(Z)-enyne7 and (Z)-enediyne8 substrates, the regioselectivity of the
HeSn bond addition was found to be totally controlled by the ge-
ometry of the double bond (Z-Directing Effect, ZDE) rather than the
Organostannanes, and particularly vinylstannanes are of in-
creasing importance as synthetic intermediates in organic chem-
istry due to the large number of carbonecarbon bond forming
reactions available to these substrates.1 As a result of their synthetic
utility, considerable effort has been expended toward their prepa-
ration2 and the addition of tributyltin hydride to alkynes remains
the most simple and straightforward route to these vinylstannanes
intermediates.2c,d,3 The challenge in the hydrostannation of un-
symmetrical alkynes is to directly produce vinylstannanes of high
purity with a total regio- and stereo-selectivity because mixtures of
vinyl stannanes are tedious to separate (destannylation, non-polar
isomers,.). For palladium-catalyzed hydrostannation of alkynes,
nature of its substituents (Cl, alkyl, aryl,.) to give exclusively a-
vinylstannanes (Scheme 1). With ortho substituted internal9 and
terminal10 arylalkyne derivatives, we demonstrated that an ortho
substituent delivered the Bu3Sn group on the carbon atom (Ca)
whatever the electronic nature of the substituent, electron with-
R1
R1
Bu3SnH
α
β
Bu3SnH
R1
H
H
PdCl2(PPh3)2
PdCl2(PPh3)2
THF
SnBu3
R
SnBu3
THF
R
H
Sn
R
Ortho-directing effect (ODE)
α-β : 90/10 to 100/0
Z directing effect (ZDE)
exclusive α-isomer
Scheme 1.
drawing or electron donating (e.g., CO2R, COR, OR, Cl,.). This trend
in a-regioselectivity was also observed with substrates having ortho
non-chelating alkyl substituents (e.g., CH3, iPr,.), clearly indicating
* Corresponding author. E-mail address: mouad.alami@u-psud.fr (M. Alami).
that coordinating factors were not at the origin of this remarkable
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.010

A. Hamze et al. / Tetrahedron 66 (2010) 8698e8706
8699
regioselectivity (Scheme 1). The results have been rationalized in
terms of electronic polarization across the alkyne bond, induced by
the ortho substituent whatever its electronic nature.9b Although at
example depicted in entry 8 with ‘pushepull’ diarylalkyne 1h is
particularly interesting. In this case, where ODE is opposed by
a strong electronic effect (induced by the para-CN), the
lectivity was less spectacular and -vinylstannane was obtained as
minor products together with -adduct (entry 8, -2h/ -2h: 81/19).
By replacing the ortho and ortho0 electron-donating substituents
with chlorine atoms, the -regioselectivity is entirely governed by
a-regiose-
the moment, we did not succeed in correlating the
a
-selectivity
b
observed with the triple bond polarization, this ortho-directing
effect (ODE) has been successfully extended to control the regio-
chemistry of the platinum-catalyzed hydrosilylation of internal
aliphatic arylalkynes as well as diarylalkynes.11
Although it was clearly established that the regioselectivity of
the Pd-catalyzed hydrostannation of aliphatic alkynes is very sen-
sitive to the steric hindrance,2d,5a,b we showed previously in the
case of internal ortho substituted diarylalkynes9b that increasing
a
a
b
a
ODE rather than the p-CN induced polarization of the triple bond
(entry 9). For substrate 1jel, ODE and electronic factors cooperate to
give a-substituted vinylstannanes 2jel exclusively in good yields
(entries 10e12). We next tested the ortho-directing effect on the
distribution products with arylalkynol 1m. It was found that
steric hindrance of ortho substituent provides better
lectivities (anti steric effects) as depicted in Scheme 2.
a-regiose-
hydrostannation of 1m proceeded with an excellent
a-regiose-
lectivity in a nearly quantitative yield (entry 13, -2m/ -2m: 95/5).
a
b
As it was observed fordiarylalkynes 1beg,1iel, the hydrostannation
of arylalkynols 1m and 1n bearing two substituents on the ortho
position was totally regioselective and produced a-vinylstannanes
2m and 2n in good yields. The last example, described in entry 15
sums up this study. The two triple bonds of alkyne 1o were suc-
cessfully hydrostannylated with a total regioselectivity furnishing
Ph
Ph
α
β
Bu3SnH
+
Ph
SnBu3
H
PdCl2(PPh3)2
THF
H
R
SnBu3
R
R
R = OMe (94%)
R = OBn (81%)
:
:
90
10
a single compound
if ortho-substituents are at the origin of the
served for the hydrostannation of the hindered alkyne, the exclusive
a
,a
-2o in an excellent isolated yield. In this case,
100
0
a
-regioselectivity ob-
R = Me (91%)
:
:
93
7
0
a
-stannylation of the alkynol moiety is not immediately clear.
R = iPr (76%)
100
The success of this ortho/ortho0-substituent regiocontrol
prompted additional investigations with ortho-disubstituted ter-
minal arylalkynes. The results of this study are abstracted in
Scheme 3. Hydrostannation of electron-rich arylalkyne 1p as well
as electron deficient arylalkyne 1q was achieved and again, a total
R
R
Ar
α
Bu3SnH
β
Ar
This work
H
1
SnBu3
R
R
regioselectivity was observed. In these cases, exclusive
2p and 2q were produced in excellent yields (2p: 92%, 2q: 98%).
Next, to examine the synthetic utility of -vinylstannanes of
a-isomers
Scheme 2.
a
These findings clearly highlighted the role of steric hindrance of
substituent in directing the -addition of the metals to the more
type 2, we first evaluated the Stille coupling of 4-iodoanisole with
2k and 2o. However, the coupling products 4a and 4b were not
obtained in satisfactory yields. Therefore, a second synthetic ap-
proach involving an iododestannylationeNegishi sequence was
explored (Scheme 4).8b,9c Thus, stereospecific iodo-destannylation
of 2k and 2o with molecular iodine (1 equiv) in CH2Cl2 at 20 ꢀC
provided cleanly and rapidly the suitable electrophilic vinyl iodides
3a and 3b in quantitative yields. Further coupling with 4-methoxy-
arylzinc chloride in the presence of PdCl2(PPh3)2 (5 mol %) fur-
nished the triarylated ethylenic compounds 4a,b with a total
stereospecificity in good yields (Scheme 4).
a
hindered alkyne carbon atom (Ca). To the best of our knowledge
there has been no systematic study on metal-catalyzed hydro-
metallation of highly hindered arylalkynes 1 having ortho/ortho0
substituents. Herein, the results of these studies are reported using
tributyltin hydride or triethylsilane in order to determine the im-
pact of ortho/ortho0 substituents of 1 on the
a-regioselectivity.
2. Results and discussion
At the beginning of this work, hindered ortho/ortho0-diaryl-
alkynes 1 were prepared according to SonogashiraeLinstrumelle
(SL) couplings12 using PdCl2(PPh3)2 (5 mol %), CuI (10 mol %), pi-
peridine as the base in THF, in good to excellent yields. The hydro-
stannation of diarylalkynes 1 was conducted under standard
conditions using PdCl2(PPh3)2 (5 mol %) and Bu3SnH (1.3 equiv) in
THF. The results of this study are summarized in Table 1. In order to
establish a baseline regioselectivity control, 1-(2-methoxyphenyl)-
2-phenylacetylene 1a bearing a single ortho MeO substituent was
evaluated. Under the above conditions, 1a was hydrostannylated to
Finally, we wanted to examine if this total a-selectivity could be
successfully extended to the hydrosilylation of various ortho-di-
substituted alkynes. Preliminary results are presented in Table 2.
Reaction of ortho-disubstituted diarylalkyne 1b with triethylsilane
in THF in the presence of PtO2 (5 mol %) at 70 ꢀC for 1 h afforded
regioselectively an inseparable 90/10 mixture of the vinylsilanes
3a and -3b in 90% yield (entry 1, Table 2). For comparison, the
hydrosilylation of alkyne 1a bearing a single MeO substituent on
the ortho position (baseline control) afforded a mixture of - and
-vinylsilanes but with a lower -selectivity ( : 80/20).
A similar -preference was also observed with alkyne 1e bearing
a-
a
a
b
a
a/b
give a diastereomeric mixture of non-separable
stannanes with an excellent but not total -preference (entry 1,
1a/ -2a: 90/10). For comparison, by switching the MeO substituent
from the ortho to the para position on the aromatic, an equimolar
isomeric -2/ -2 product distribution was obtained (data not
a
and
b
vinyl-
a
a
a
-
two MeO-substituents on the ortho and ortho0 position (97%, entry
2). As previously observed for the hydrostannation of 1j (entry 10,
Table 1), the hydrosilylation of 1j bearing two chlorine atoms on the
ortho positions was totally regioselective. Again, electronic factors,
generated by the chlorine atoms, and ODE cooperate and the re-
b
a
b
shown). More interestingly, hydrostannation of ortho-disubstituted
arylalkyne 1b,1c, and 1d bearing on the same aromatic nucleus two
ortho electron-donating substituents was totally regioselective13
action produced a single a-vinylsilane 3c in a nearly quantitative
yield (98%, entry 3, Table 2).
furnishing a-vinylstannanes 2bed in good yields (entries 2e4). As
expected for electronic considerations, hydrostannation of ortho/
ortho0 disubstituted diarylalkynes 1eeg, bearing a para MeO sub-
stituent on the second aromatic nucleus, furnished vinylstannanes
3. Conclusion
In summary, we demonstrated that hydrostannation of hindered
2eeg, again with a total
a-regioselectivity (entries 5e7). The
arylalkynes bearing on the same aromatic nucleus two ortho-

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A. Hamze et al. / Tetrahedron 66 (2010) 8698e8706
Table 1
Hydrostannation of highly hindered arylalkynes 1 under palladium catalysis
Entry
Alkyne 1
a
/b
ratioa
Vinyl stannane 2
Yieldb (%)
1
1a
1b
1c
1d
1e
1f
90/10
100/0
100/0
100/0
100/0
100/0
100/0
2a
2b
2c
2d
2e
2f
94
MeO
Bu3Sn
OMe
OMe
H
OMe
2
3
4
5
6
7
86
90
65
71
55
70
MeO
Bu3Sn
OMe
OBn
H
OBn
BnO
Bu3Sn
OBn
OAc
H
OAc
AcO
Bu3Sn
OAc
H
OMe
OMe
OMe
OMe
OMe
OMe
MeO
Bu3Sn
OMe
OBn
H
H
H
OMe
OMe
OBn
OAc
BnO
Bu3Sn
OBn
OAc
1g
2g
AcO
Bu3Sn
OAc
CN
OMe
OMe
8
9
1h
81/19
100/0
2h
86
88
CN
CN
MeO
Bu3Sn
OMe
Cl
H
CN
Cl
1i
2i
Cl
Bu3Sn
Cl
Cl
H
Cl
10
11
1j
100/0
100/0
2j
98
98
Cl
Bu3Sn
Cl
Cl
H
OMe
Cl
1k
2k
OMe
Cl
Bu3Sn
Cl
H

A. Hamze et al. / Tetrahedron 66 (2010) 8698e8706
8701
Table 1 (continued)
Entry
Alkyne 1
a
/b
ratioa
Vinyl stannane 2
Yieldb (%)
F
Br
Br
Br
12
1l
100/0
2l
48
F
Br
Bu3Sn
H
OH
OH
13
14
1m
1n
95/5
2m
2n
97
81
OH
Me
Me
SnBu3
H
Me
Me
Me
100/0
Me
OH
Me
Me
Bu3Sn
H
Bu3Sn
H
MeO
OMe
OMe
CO2Me
OH
4
OH
100/0
100/0
4
15
1o
2o
91c
MeO
MeO
OMe
MeO2C
Bu3Sn
H
a
b
c
Ratio was determined by 1H NMR analysis.
Yields were given for isolated products.
Bu3SnH (3.0 equiv) was used.
Table 2
Hydrosilylation of ortho-disubstituted arylalkynes 1
R
Cl
OMe
SnBu3
SnBu3
(i)
(i)
α
β
R1
R1
R1
Et3SiH (1.6 equiv)
PtO2 (5 mol%)
Ar
Ar
Ar
R1
R1
R
Cl
OMe
70° C, 1h
Et3Si
H
H
SiEt3
R1
Exclusive α-isomer
2p (92%)
1p: R = OMe
1q: R = Cl
Exclusive α-isomer
2q (98%)
α-3
β-3
1
Scheme 3. Hydrostannation of terminal ortho/ortho0 disubstituted arylalkynes 1p and
1q. Reagents and conditions. (i) Bu3SnH (1.3 equiv), PdCl2(PPh3)2 (5 mol %), 20 ꢀC, THF,
0.5 h.
Entry Alkyne 1 Selectivity
a
/
ba
Vinylsilane
a
-3
Yieldb (%)
OMe
1
2
1b
1e
90/10
92/8
a
a
-3a 90
-3b 97
MeO
Et3Si
H
OMe
OMe
OMe
Cl
Cl
OMe
Cl
(i)
(ii)
2k
Cl
Cl
I
H
H
MeO
Et3Si
3a (100%)
4a (73%)
H
MeO
MeO
3
1j
100/0
a
-3c 98
I
H
Cl
H
Et3Si
MeOOC
MeO
H
(i)
(ii)
MeOOC
MeO
Ratio was determined by 1H NMR analysis.
Yields were given for isolated products.
2o
OH
( )4
a
OMe
OMe
OH
( )4
b
OMe
OMe
I
H
H
substituents give exclusively the a-vinylstannanes in good yields
whatever the electronic nature and steric hindrance of substituents.
Moreover, preliminary results indicate that the PtO2-catalyzed
hydrosilylation of these hindered alkynes was also highly regiose-
4b (61%)
3b (100%)
MeO
Scheme 4. Iodo-destannylation of 2k and 2o followed by Negishi Cross-coupling re-
actions under palladium catalysis. Reagents and conditions. (i) I2, CH2Cl2. (ii) 4-
MeOC6H4ZnCl, PdCl2(PPh3)2 5 mol %, THF.
lective. The factors governing this total
a-selectivity would be close to
those observed in the hydrostannation or hydrosilylation of

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A. Hamze et al. / Tetrahedron 66 (2010) 8698e8706
arylalkynes bearing on the ortho position a single substituent (ODE).
This study shows that it is possible to predict the exclusive -isomers
(cmꢁ1, neat): 1761, 1494, 1457, 1371, 1182, 1026, 882, 758, 690. Anal.
Calcd for C18H14O4 (294.30): C 73.46, H 4.79, found C 73.74, H 4.65.
a
formation even if the exact origin of this regioselectivity remains
unclear.9b,14 Interestingly, the products of the hydrostannation re-
action can be efficiently used as versatile substrates in iododes-
tannylationeNegishisequencestoafford stereo-definedtriarylolefins
of therapeutic interest.15
4.2.4. 1,3-Dimethoxy-2-((4-methoxyphenyl)ethynyl)benzene
(1e). Brown solid, mp: 142e144 ꢀC. Yield (71%). Rf¼0.15 (Et2O/cy-
clohexane, 10/90, SiO2). 1H NMR (CDCl3, 300 MHz):
d 3.82 (3H, s),
3.91 (6H, s), 6.56 (2H, d, J¼8.4 Hz), 6.86 (2H, d, J¼8.4 Hz), 7.24 (1H, t,
J¼8.4 Hz), 7.53 (2H, d, J¼8.4 Hz). 13C NMR (75 MHz, CDCl3):
d 55.3
4. Experimental
(CH3), 56.2 (2CH3), 80.4 (C), 97.9 (C), 102.0 (C), 103.6 (2CH), 113.9
(2CH), 116.2 (C), 129.5 (CH), 133.2 (2CH), 159.4 (C), 161.3 (2C). IR
(cmꢁ1, neat): 1579, 1513, 1472, 1252, 1103, 826, 778, 726. Anal. Calcd
for C17H16O3 (268.31): C 76.10, H 6.01, found C 76.25, H 5.84.
4.1. General comments
All glasswares were oven-dried at 140 ꢀC and all reactions were
conducted under a nitrogen atmosphere. Solvents: cyclohexane,
ethyl acetate (EtOAc), for chromatography were technical grade.
Diethylether (Et2O) and tetrahydrofuran (THF) were distilled under
argon from sodium-benzophenone ketyl, piperidine, triethylamine
from potassium hydroxide. PdCl2(PPh3)2 and Bu3SnH16 were pre-
pared following literature procedure. All new compounds were
characterized by 1H NMR, 13C NMR, IR spectroscopy and elemental
analysis. 1H and 13C NMR spectra were measured in CDCl3 with
a Bruker ARX 400 or Bruker Avance 300. 1H chemical shifts are
reported in ppm from an internal standard TMS or of residual
chloroform (7.27 ppm). The following abbreviations are used: m
(multiplet), s (singlet), br s (broad singlet), d (doublet), t (triplet) dd
(doublet of doublet), q (quadruplet), sextet (sextuplet). 13C chemical
shifts are reported in parts per million from the central peak of
deuteriochloroform (77.14). IR spectra were measured on a Bruker
Vector 22 spectrophotometer (neat, cmꢁ1). Elemental analyses were
performed with a PerkineElmer 240 analyzer. Analytical TLC was
performed on Merck precoated silica gel 60 F-254 plates. Merck
silica gel 60 (230e400 mesh) was used for column chromatography.
The plates were visualized by either UV light (254 nm), or by a so-
lution of phosphomolybdic acid in ethanol. Melting points (mp)
were recorded on a Büchi B-450 apparatus and were uncorrected.
4.2.5. (2-((4-Methoxyphenyl)ethynyl)-1,3-phenylene) bis(oxy)bis (meth-
ylene)dibenzene (1f). Brown solid, mp: 89e91ꢀC. Yield (55%). Rf¼0.20
(Et2O/cyclohexane, 5/95, SiO2). 1H NMR (CDCl3, 300 MHz):
d 3.84 (3H,
s), 5.21 (4H, s), 6.61 (2H, d, J¼8.3 Hz), 6.87 (2H, d, J¼8.8 Hz), 7.17 (1H, t,
J¼8.3 Hz), 7.66e7.25 (12H, m). 13C NMR (75 MHz, CDCl3):
d 55.4 (CH3),
70.7 (2CH2), 81.1 (C), 98.4 (C), 104.1 (C), 106.1 (2CH), 114.0 (2CH), 116.6
(C), 127.0 (4CH), 127.8 (2CH),128.5 (4CH),129.2 (CH),133.0 (2CH), 137.3
(2C), 159.4 (C), 160.4 (2C). IR (cmꢁ1, neat): 1574,1509,1449,1378, 1247,
1087, 1028, 830, 780, 727, 692. Anal. Calcd for C29H24O3 (420.50): C
82.83, H 5.75, found C 82.72, H 5.64.
4.2.6. 2-((4-Methoxyphenyl)ethynyl)-1,3-phenylene diacetate (1g)
(in this case TEA was used as base instead piperidine). Brown solid,
mp: 117e119 ꢀC. Yield (85%). Rf¼0.45 (Et2O/cyclohexane, 30/70,
SiO2). 1H NMR (CDCl3, 300 MHz):
d 2.36 (6H, s), 3.83 (3H, s), 6.88
(2H, d, J¼8.8 Hz), 7.04 (2H, d, J¼8.0 Hz), 7.35 (1H, t, J¼8.0 Hz), 7.40
(2H, d, J¼8.8 Hz). 13C NMR (75 MHz, CDCl3):
d 20.9 (2CH3), 55.4
(CH3), 78.4 (C), 99.0 (C), 112.8 (C), 114.2 (2CH), 114.8 (C), 119.9 (2CH),
128.8 (CH), 133.1 (2CH), 152.2 (2C), 160.2 (C), 168.6 (2C). IR (cmꢁ1
,
neat): 1756, 1515, 1458, 1374, 1190, 1029, 882, 836, 734. Anal. Calcd
for C19H16O5 (324.33): C 70.36, H 4.97, found C 70.01, H 4.75.
4.2.7. 4-((2,6-Dimethoxyphenyl)ethynyl)benzonitrile
(1h). White
4.2. General procedure for the synthesis of diarylalkynes 1
solid, White solid, mp: 120e122 ꢀC. Yield (88%). Rf¼0.20 (Et2O/cy-
clohexane, 5/95, SiO2). 1H NMR (CDCl3, 300 MHz):
d 3.92 (6H, s),
4.2.1. Procedure for the synthesis of diarylalkynes (A). To a flame-
dried flask under a nitrogen atmosphere were added PdCl2(PPh3)2
(120 mg, 0.17 mmol), CuI (76 mg, 0.4 mmol), aryliodide (4.0 mmol),
and piperidine (1.2 mL, 12.0 mmol) in THF (12 mL). To this solution
was added dropwise 1-alkyne (6.0 mmol). After stirring at room
temperature for 12 h, the mixture was diluted in Et2O (25 mL), and
then washed with a saturated NH4Cl solution (20 mL). After ex-
traction with Et2O (25 mL) the combined organic layers were dried
over MgSO4. After concentration under reduced pressure, the res-
idue was purified by column chromatography over silica gel, to
yield the desired ortho-disubstituted alkyne 1.
6.57 (2H, d, J¼8.4 Hz), 7.27 (1H, t, J¼8.4 Hz), 7.60 (2H, d, J¼8.6 Hz),
7.65 (2H, d, J¼8.6 Hz). 13C NMR (75 MHz, CDCl3):
d 56.2 (2CH3), 87.0
(C), 96.2 (C), 100.7 (C), 103.6 (2CH), 111.0 (C), 118.8 (C), 129.1 (C),
130.9 (CH), 131.9 (2CH), 132.2 (2CH), 161.7 (2C). IR (cmꢁ1, neat):
2215, 1585, 1475, 1257, 1110, 834, 774, 725. Anal. Calcd for
C17H13NO2 (263.29): C 77.55, H 4.98, found C 77.13, H 4.70.
4.2.8. 4-((2,6-Dichlorophenyl)ethynyl)benzonitrile (1i). White solid,
mp: 144e146 ꢀC. Yield (90%). Rf¼0.32 (Et2O/cyclohexane, 5/95,
SiO2). 1H NMR (CDCl3, 300 MHz):
d
7.22 (1H, t, J¼8.8 Hz), 7.38 (2H, d,
J¼8.8 Hz), 7.66 (2H, d, J¼8.7 Hz), 7.69 (2H, d, J¼8.7 Hz). 13C NMR
(75 MHz, CDCl3):
d 87.5 (C), 97.7 (C), 112.3 (C), 118.5 (C), 122.5 (C),
4.2.2. 1,3-Bis(benzyloxy)-2-(phenylethynyl)benzene
(1c). White
127.5 (C),127.8 (2CH),130.0(CH),132.2(2CH),132.4 (2CH),137.6(2C).
IR (cmꢁ1, neat): 2229, 1550, 1504, 1425, 1192, 834, 778, 718. Anal.
Calcd for C15H7Cl2N (272.13): C 66.20, H 2.59, found C 65.91, H 2.50.
solid, mp: 106e108 ꢀC. Yield (90%). Rf¼0.23 (Et2O/cyclohexane, 5/
95, SiO2). 1H NMR (CDCl3, 300 MHz):
d 5.14 (4H, s), 6.54 (2H, d,
J¼8.4 Hz), 7.11 (1H, t, J¼8.4 Hz), 7.15e7.54 (15H, m). 13C NMR
(75 MHz, CDCl3): dC 70.6 (2CH2), 82.6 (C), 98.4 (C), 103.7 (C), 106.0
(2CH), 124.3 (C), 126.9 (4CH), 127.8 (2CH), 127.9 (CH), 128.3 (2CH),
4.2.9. 1,3-Dichloro-2-(phenylethynyl)benzene (1j). White solid, mp:
56e58 ꢀC. Yield (75%). Rf¼0.60 (Et2O/cyclohexane, 2/98, SiO2). 1H
128.5 (4CH), 129.6 (CH), 131.6 (2CH), 137.2 (2C), 160.6 (2C). IR (cmꢁ1
,
NMR (CDCl3, 300 MHz):
d
6.95 (1H, dd, J¼7.5, 1.2 Hz), 7.10e7.23 (5H,
neat): 1582, 1474, 1446, 1375, 1261, 1116, 771, 732, 690. Anal. Calcd
for C28H22O2 (390.47): C 86.13, H 5.68, found C 85.91, H 5.70.
m), 7.35e7.45 (2H, m).13C NMR (75 MHz, CDCl3):
d 83.6 (C),100.0 (C),
122.7 (C), 123.5 (C), 127.6 (2CH), 128.5 (2CH), 129.0 (CH), 129.1 (CH),
132.0 (2CH),137.3 (2C). IR (cmꢁ1, neat): 2220,1553,1493,1443,1428,
1189, 1101, 788, 766, 749, 716. Anal. Calcd for C14H8Cl2 (247.12): C
68.04, H 3.26, found C 67.84, H 3.31.
4.2.3. 2-(Phenylethynyl)-1,3-phenylene diacetate (1d). Brown solid,
mp: 106e108 ꢀC. Yield (65%). Rf¼0.40 (Et2O/cyclohexane, 30/70,
SiO2).1H NMR (CDCl3, 300 MHz):
d
2.37 (6H, s), 7.06 (2H, d, J¼8.2 Hz),
7.40e7.32 (4H, m), 7.51e7.43 (2H, m). 13C NMR (75 MHz, CDCl3):
20.9 (2CH3), 79.7 (C), 98.8 (C),112.5 (C),119.9 (2CH), 122.7 (C),128.5
(2CH), 128.9 (CH), 129.2 (CH), 131.5 (2CH), 152.3 (2C), 168.5 (2C). IR
4.2.10. 1,3-Dichloro-2-((4-methoxyphenyl)ethynyl)benzene
d
(1k). White solid, mp: 71e73 ꢀC. Yield (53%). Rf¼0.34 (Et2O/cyclo-
hexane, 5/95, SiO2). 1H NMR (CDCl3, 300 MHz):
d 3.77 (3H, s), 6.83

A. Hamze et al. / Tetrahedron 66 (2010) 8698e8706
8703
(2H, d, J¼8.8 Hz), 7.10 (1H, t, J¼8.1 Hz), 7.26 (2H, d, J¼8.1 Hz), 7.50
(2CH), 128.0 (2CH), 128.2 (2CH), 128.3 (4CH), 137.7 (2C), 139.3 (C),
139.5 (1CH), 142.0 (C), 154.5 (2C). IR (cmꢁ1, neat): 2954, 2921, 2870,
2852, 1580, 1496, 1449, 1418, 1377, 1246, 1229, 1201, 1177, 1155,
1096, 1074, 1029, 961, 922, 864, 843, 733, 693. Anal. Calcd for
C40H50O2Sn (681.53): C 70.49, H 7.39, found C 70.10, H 7.50.
(2H, d, J¼8.8 Hz). 13C NMR (75 MHz, CDCl3):
d 55.4 (CH3), 82.6 (C),
100.3 (C), 114.2 (2CH), 114.8 (C), 123.7 (C), 127.6 (2CH), 128.6 (CH),
133.5 (2CH), 137.0 (2C), 160.3 (C). IR (cmꢁ1, neat): 2195, 1604, 1509,
1429, 1248, 1024, 830, 716. Anal. Calcd for C15H10Cl2O (277.15): C
65.01, H 3.64, found C 64.88, H 3.54.
4.3.3. Hydrostannation of 1d.
4.2.11. 1,3-Dibromo-5-fluoro-2-(phenylethynyl)benzene (1l). Brown
oil. (55%). Rf¼0.60 (Et2O/cyclohexane, 5/95, SiO2). 1H NMR (CDCl3,
4.3.3.1. (E)-2-(2-phenyl-1-(tributylstannyl)vinyl)-1,3-phenylene
300 MHz):
d
7.20e7.33 (3H, m), 7.42e7.48 (4H, m). 13C NMR
diacetate (2d). Colorless oil (65%). Rf¼0.60 (Et2O/cyclohexane, 3/7
(75 MHz, CDCl3): dC 73.9 (C), 81.5 (C), 103.7 (d, JCeF¼3.7 Hz, C), 119.1
(d, JCeF¼24.0 Hz, 2CH), 121.7 (C), 129.2 (2CH), 131.3 (d, JCeF¼10.0 Hz,
2C,), 131.6 (CH), 132.5 (2CH), 161.9 (d, JCeF¼255.0 Hz, C). Anal. Calcd
for C14H7Br2F (354.01): C 47.50, H 1.99, found C 47.02, H 1.98.
TEA 1%, SiO2). 1H NMR (CDCl3, 300 MHz):
d 0.63e1.10 (15H, m), 1.23
(6H, sextet, J¼7.4 Hz), 1.33e1.58 (6H, m), 2.02 (6H, s), 6.66 (1H, s,
JSneH¼61.4 Hz), 6.87 (2H, d, J¼8.0 Hz), 6.98e7.21 (6H, m). 13C NMR
(75 MHz, CDCl3): d 11.3 (3CH2),13.8 (3CH3), 21.0 (2CH3), 27.6 (3CH2),
29.0 (3CH2), 120.3(2CH), 126.2 (CH), 127.4 (CH), 128.2 (2CH), 128.3
(2CH), 131.8 (C), 137.6 (C), 139.3 (C), 142.0 (1CH), 146.9 (2C), 168.8
(2CO). IR (cmꢁ1, neat): 2956, 2921, 2851, 1767, 1493, 1455, 1366,
1184, 1156, 1074, 1025, 985, 962, 926, 881, 867. Anal. Calcd for
C30H42O4Sn (585.36): C 61.56, H 7.23, found C 61.74, H 7.48.
4.2.12. Methyl 2-((4-(6-hydroxyhex-1-ynyl)phenyl)ethynyl)-3,4,5-
tri-methoxybenzoate (1o). Compound 1o was prepared from
methyl-2-iodo-3,4,5-tri-methoxybenzoate and 6-(4-ethynyl phe-
nyl)hex-5-yn-1-ol (in this case heating to 80 ꢀC was necessary).
Yellow solid, mp: 118e120 ꢀC. Yield (77%). Rf¼0.43 (Et2O/cyclo-
hexane, 50/50, SiO2). 1H NMR (CDCl3, 300 MHz):
d
1.63 (4H, m), 2.37
4.3.4. Hydrostannation of 1e.
(2H, t, J¼6.4 Hz), 3.59 (2H, t, J¼6.5 Hz), 3.79 (3H, s), 3.83 (3H, s), 3.86
(3H, s), 3.92 (3H, s), 7,24 (1H, s), 7.35 (4H, m). 13C NMR (75 MHz,
CDCl3): dC 19.3 (CH2), 25.0 (CH2), 31.8 (CH2), 52.2 (CH3), 56.1 (CH3),
61.1 (CH3), 61.3 (CH3), 62.1 (CH2), 80.7 (C), 85.2 (C), 92.1 (C), 97.1 (C),
109.8 (C), 112.1 (C), 122.8 (C), 123.9 (C), 127.6 (C), 131.2 (2CH), 131.4
(2CH), 145.7 (C), 153.0 (C), 155.2 (C), 166.1 (CO). IR (cmꢁ1, neat):
3058, 2937, 1728, 1338, 1115. Anal. Calcd for C25H26O6 (422.47): C
71.07, H 6.20, found C 69.95, H 6.32.
4.3.4.1. (E)-Tributyl(1-(2,6-dimethoxyphenyl)-2-(4-methox-
yphenyl) vinyl)stannane (2e). Colorless oil (71%). Rf¼0.14 (Et2O/cy-
clohexane, 2/98 TEA 1%, SiO2). 1H NMR (CDCl3, 300 MHz):
d
0.66e0.92 (15H, m), 1.20 (6H, sextet, J¼7.3 Hz), 1.30e1.44 (6H, m),
3.57 (6H, s), 3.65 (3H, s), 6.44 (2H, d, J¼8.3 Hz), 6.52e6.67 (3H, m),
6.93 (2H, d, J¼8.8 Hz), 7.05 (1H, t, J¼8.3 Hz). 13C NMR (75 MHz,
CDCl3):
d 10.6 (3CH2), 13.9 (3CH3), 27.5 (3CH2), 29.1 (3CH2), 55.3
(CH3), 55.7 (2CH3),104.1 (2CH),113.3 (2CH),126.4 (CH),129.4 (2CH),
132.3 (C), 138.6 (CH), 138.8 (C), 155.5 (2C), 158.2 (C), 177.1 (C). IR
(cmꢁ1, neat): 2994, 2954, 2927, 2870, 2835, 1604, 1582, 1508, 1466,
1431, 1375, 1292, 1244, 1175 1109, 1036, 960, 896, 874, 823, 805, 781,
760, 732. Anal. Calcd for C29H44O3Sn (559.37): C 62.27, H 7.93, found
C 62.00, H 8.18.
4.3. General procedure for the hydrostannation of alkynes (B)
Tributyltin hydride (11 mmol) was added dropwise at room
temperature to a solution of PdCl2(PPh3)2 (0.1 mmol) and alkyne 1
(10 mmol) in THF (15 mL). The dark brown reaction mixture was
stirred for 30 min and tributyltin hydride (2 mmol) was added
more on the crude mixture to complete the hydrostannation re-
action. After stirring for 30 additional minutes, the solution was
concentrated in vacuo. Purification by flash chromatography on
silica gel gave the desired products.
4.3.5. Hydrostannation of 1f.
4.3.5.1. (E)-(1-(2,6-Bis(benzyloxy)phenyl)-2-(4-methoxyphenyl)-
vinyl)tributyl-stannane (2f). Colorless oil (55%). Rf¼0.37 (Et2O/cy-
clohexane, 5/95 TEA 1%, SiO2). 1H NMR (CDCl3, 300 MHz):
4.3.1. Hydrostannation of 1b.
d
0.70e0.92 (15H, m), 1.18 (6H, sextet, J¼7.3 Hz), 1.29e1.49 (6H, m),
3.75 (3H, s), 4.94 (2H, d, J¼12.7 Hz), 4.98 (2H, d, J¼12.7 Hz), 6.53
(2H, d, J¼8.3 Hz), 6.67 (2H, d, J¼8.6 Hz), 6.73 (1H, s, JSneH¼67.0 Hz),
6.97e7.10 (3H, m), 7.17e7.38 (10H, m). 13C NMR (75 MHz, CDCl3): dC
10.6 (3CH2), 13.8 (3CH3), 27.5 (3CH2), 29.0 (3CH2), 55.2 (CH3), 70.1
(2CH2), 105.8 (2CH), 113.4 (2CH), 123.8 (C), 126.2 (CH), 127.0 (4CH),
127.4 (2CH), 128.3 (4CH), 129.4 (2CH), 132.5 (C), 137.8 (2C), 138.8
(CH), 139.3 (C), 154.7 (2C), 158.2 (C). IR (cmꢁ1, neat): 2953, 2929,
2869, 2852, 2836, 1604, 1582, 1508, 1464, 1449, 1417, 1377, 1291,
1245, 1226, 1201, 1175, 1110, 1095, 1072, 1031, 959, 935, 901, 877,
862, 823, 784, 766. Anal. Calcd for C41H52O3Sn (711.56): C 69.21, H
7.37, found C 69.36, H 7.20.
4.3.1.1. (E)-Tributyl(1-(2,6-dimethoxyphenyl)-2-phenylvinyl)
stannane (2b). Colorless oil (86%). Rf¼0.75 (Et2O/cyclohexane, 1/9
TEA 1%, SiO2). 1H NMR (CDCl3, 300 MHz):
d 0.73e0.83 (15H, m), 1.20
(6H, sextet, J¼7.2 Hz), 1.32e1.44 (6H, m), 3.57 (6H, s), 6.43 (2H, d,
J¼8.3 Hz,), 6.64 (1H, s, JSneH¼67.0 Hz), 6.91e7.11 (6H, m). 13C NMR
(75 MHz, CDCl3):
d 10.6 (3CH2), 13.9 (3CH3), 27.5 (3CH2), 29.1
(3CH2), 55.7 (2CH3), 104.0 (2CH), 122.4 (C), 126.4 (CH), 126.5 (CH),
127.9 (2CH), 128.1 (2CH), 139.2 (C), 139.4 (CH), 141.6 (C), 155.4 (2C).
IR (cmꢁ1, neat): 2954, 2925, 2870, 2852, 1579, 1494, 1467, 1431,
1375, 1282, 1245, 1171, 1110, 1074, 961, 921, 865, 778, 756, 713. Anal.
Calcd for C28H42O2Sn (529.34): C 63.53, H 8.00, found C 63.41, H
8.05.
4.3.6. Hydrostannation of 1g.
4.3.2. Hydrostannation of 1c.
4.3.6.1. (E)-2-(2-(4-Methoxyphenyl)-1-(tributylstannyl)vinyl)-
1,3-phenylene diacetate (2g). Colorless oil (70%). Rf¼0.52 (Et2O/cy-
clohexane, 30/70 TEA 1%, SiO2). 1H NMR (CDCl3, 300 MHz):
4.3.2.1. (E)-(1-(2,6-Bis(benzyloxy)phenyl)-2-phenylvinyl)tributyl-
stannane (2c). Colorless oil (90%). Rf¼0.56 (Et2O/cyclohexane, 5/95
d
0.64e1.00 (15H, m), 1.22 (6H, sextet, J¼7.3 Hz), 1.34e1.49 (6H, m),
TEA 1%, SiO2). 1H NMR (CDCl3, 300 MHz):
d
0.54e0.91 (15H, m), 1.10
2.02 (6H, s), 3.65 (3H, s), 6.58 (1H, s, JSneH¼62.0 Hz), 6.61 (2H, d,
J¼8.8 Hz), 6.88 (2H, d, J¼8.1 Hz), 6.96 (2H, d, J¼8.8 Hz), 7.13 (1H, t,
(6H, sextet, J¼7.4 Hz), 1.21e1.41 (6H, m), 4.82 (2H, d, J¼12.4 Hz),
4.86 (2H, d, J¼12.4 Hz), 6.43 (2H, d, J¼8.3 Hz), 6.70 (1H, s,
JSneH¼68.0 Hz), 6.85e7.25 (16H, m). 13C NMR (75 MHz, CDCl3):
J¼8.1 Hz). 13C NMR (75 MHz, CDCl3):
d 11.3 (3CH2), 13.8 (3CH3), 21.0
(2CH3), 27.6 (3CH2), 29.0 (3CH2), 55.2 (CH3), 113.5 (2CH), 120.3
(2CH), 126.0 (CH), 129.7 (2CH), 130.6 (C), 132.1 (C), 136.2 (C), 141.3
(CH), 147.2 (2C), 158.9 (C), 168.9 (2CO). IR (cmꢁ1, neat): 2955, 2929,
d
10.7 (3CH2), 13.8 (3CH3), 27.5 (3CH2), 29.0 (3CH2), 70.1 (2CH2),
105.6 (2CH), 123.5 (C), 126.3 (CH), 126.4 (CH), 127.0 (4CH), 127.5

8704
A. Hamze et al. / Tetrahedron 66 (2010) 8698e8706
1767, 1604, 1509, 1454, 1419, 1367, 1293, 1250, 1191, 1177, 1157, 1113,
1074, 1026, 985, 959, 908, 878, 825, 802, 781. Anal. Calcd for
C31H44O5Sn (615.39): C 60.50, H 7.21, found C 60.24, H 7.18.
4.3.11. Hydrostannation of 1l. 4.3.11.1. (E)-Tributyl(1-(2,6-dibromo-
4-fluorophenyl)-2-phenylvin yl) stannane (2l). Colorless oil (48%).
Rf¼0.50 (Et2O/cyclohexane, 2/98 TEA 1%, SiO2). 1H NMR (CDCl3,
300 MHz):
d 0.54e0.86 (15H, m), 1.08e1.42 (12H, m), 6.29 (1H, s,
4.3.7. Hydrostannation of 1h.
JSneH¼66.0 Hz), 7.05e7.10 (1H, m), 7.18 (2H, t, J¼6.9 Hz), 7.29 (2H, d,
J¼7.6 Hz), 7.37 (2H, m). 13C NMR (75 MHz, CDCl3):
d 11.0 (3CH2), 13.7
4.3.7.1. (E)-4-(2-(2,6-Dimethoxyphenyl)-2-(tributylstannyl)vinyl)
(3CH3), 27.5 (3CH2), 29.0 (3CH2), 103.7 (d, JCeF¼5.0 Hz, C), 119.1 (d,
JCeF¼24.0 Hz, 2CH), 126.4 (C), 128.1 (2CH), 128.2 (2CH), 131.3 (d,
JCeF¼10.0 Hz, 2C), 131.6 (CH), 140.1 (1C), 154.2 (CH), 161.9 (d,
1JCeF¼255.0 Hz, C). Anal. Calcd for C26H35Br2FSn (645.07): C 48.41, H
5.47, found C 48.60, H 5.33.
benzonitrile (2l) (major
a
-isomer). Colorless oil (86%). Rf¼0.59
(Et2O/cyclohexane, 30/70 TEA 1%, SiO2). 1H NMR (CDCl3, 300 MHz):
d
0.73e1.01 (15H, m), 1.27 (6H, sextet, J¼7.4 Hz), 1.37e1.53 (6H, m),
3
3.61 (6H, s), 6.50 (2H, d, J¼8.4 Hz), 6.72 (1H, s, JSneH¼66.0 Hz),
7.05e7.20 (3H, m), 7.37 (2H, d, J¼8.4 Hz). 13C NMR (75 MHz, CDCl3):
d
10.7 (3CH2), 13.9 (3CH3), 27.5 (3CH2), 29.0 (3CH2), 55.6 (2CH3),
4.3.12. Hydrostannation of 1n.
103.9 (2CH), 109.4 (C), 119.5 (CN), 121.2 (C), 127.3 (CH), 128.4 (2CH),
131.8 (2CH), 137.6 (CH), 143.5 (C), 147.8 (C), 155.0 (2C). IR (cmꢁ1
,
4.3.12.1. (E)-3-Mesityl-3-(tributylstannyl)prop-2-en-1-ol
neat): 2957, 2925, 2893, 2870, 2853, 2836, 2226, 1730, 1714, 1600,
1582, 1494, 1468, 1431, 1376, 1290, 1246,1208, 1173,1155, 1111, 1075,
1039, 960, 901, 879, 862, 840, 820, 781, 757. Anal. Calcd for
C29H41NO2Sn (554.35): C 62.83, H 7.45, found C 62.75, H 7.27.
(2n). Colorless oil (81%). Rf¼0.41 (AcOEt/cyclohexane, 5/95 TEA 1%,
SiO2). 1H NMR (CDCl3, 300 MHz):
d 0.78e0.86 (9H, m), 1.16e1.44
(19H, m), 2.05 (6H, s), 2.23 (3H, s), 3.87 (2H, s), 5.98 (1H, t, J¼5.6 Hz,
JSneH¼63.0 Hz), 6.78 (2H, s). 13C NMR (75 MHz, CDCl3):
d 10.9 (3CH2),
14.1 (3CH3), 20.9 (2CH3), 21.3 (CH3), 27.8 (3CH2), 29.2 (3CH2), 61.8
(CH2), 128.4 (2CH), 132.8 (C), 134.8 (C), 139.7 (C), 139.8 (2C), 148.4
(CH). IR (cmꢁ1, neat): 3340, 2950, 2930, 2840,1460, 1370,1010. Anal.
Calcd for C24H42OSn (465.30): C 61.95, H 9.10, found C 62.21, H 8.98.
4.3.8. Hydrostannation of 1i.
4.3.8.1. (E)-4-(2-(2,6-Dichlorophenyl)-2-(tributylstannyl)vinyl)
benzonitrile (2i). Colorless oil (88%). Rf¼0.50 (Et2O/cyclohexane, 5/
95 TEA 1%, SiO2). 1H NMR (CDCl3, 300 MHz):
d
0.79 (9H, t, J¼7.3 Hz),
4.3.13. Hydrostannation of 1o.
0.86e1.00 (6H, m), 1.21 (6H, sextet, J¼7.3 Hz), 1.33e1.48 (6H, m),
6.73 (1H, s, JSneH¼57.0 Hz), 6.92e7.08 (3H, m), 7.21 (2H, d,
4.3.13.1. Methyl-2-((E)-2-(4-((E)-6-hydroxy-1-(tributyl
hex-1-enyl)phenyl)-1-(tributylstannyl)vinyl)-3,4,5trimetho-xybenzoate
stannyl)
J¼8.0 Hz), 7.36 (2H, d, J¼8.4 Hz). 13C NMR (75 MHz, CDCl3):
d
11.5
(3CH2), 13.7 (3CH3), 27.4 (3CH2), 28.8 (3CH2), 110.5 (C), 119.1 (CN),
127.3 (CH), 128.2 (2CH), 128.4 (2CH), 131.4 (2C), 132.2 (2CH), 138.5
(CH), 141.8 (C), 142.2 (C), 150.5 (C). IR (cmꢁ1, neat): 2955, 2930,
2871, 2851, 2227, 1602, 1553, 1502, 1462, 1426, 1405, 1377, 1339,
1253, 1187, 1148, 1088, 1071, 1017, 961, 903, 876, 824, 777, 729. Anal.
Calcd for C27H35Cl2NSn (563.19): C 57.58, H 6.26, found C 57.41, H
6.03.
(2o). Yellow oil (91%). Rf¼0.28 (AcOEt/cyclohexane, 30/70 TEA 1%,
SiO2). 1H NMR (CDCl3, 300 MHz):
d 0.35 (30H, m),1.23 (14H, m),1.43
(14H, m), 1.97 (2H, q, J¼7.0 Hz), 3.48 (2H, dd, J¼5.5 Hz), 3.57 (3H, s),
3.65 (3H, s), 3.89 (3H, s), 3.90 (3H, s), 5.66 (1H, t, J¼7.0 Hz,
3JSneH¼62.0 Hz), 6.61 (1H, s, JSneH¼66.0 Hz), 6.64 (2H, d, J¼8.2 Hz),
6.81 (2H, d, J¼8.2 Hz), 7.23 (1H, s). 13C NMR (75 MHz, CDCl3):
d 10.9
(6CH2), 13.6 (6CH3), 25.7 (CH2), 26.9 (CH2), 27.2 (6CH2), 28.9 (6
CH2’), 31.9 (CH2), 51.7 (CH3), 55.9 (CH3), 60.6 (CH3), 60.7 (CH3), 62.4
(CH2),109.7 (CH),122.5 (C),126.7 (2CH),127.9 (2CH),134.7 (C),135.4
(C), 137.2 (CH), 141.6 (CH), 143.4 (C), 144.8 (C), 145.3 (C), 146.1 (C),
148.9 (C),150.8 (C),167.7 (C). IR (cmꢁ1, neat): 2961, 2849, 1721,1589,
1291, 1061. Anal. Calcd for C49H82O6Sn2 (1004.59): C 58.58, H 8.23,
found C 58.39, H 8.50.
4.3.9. Hydrostannation of 1j.
4.3.9.1. (E)-Tributyl (1- (2,6-dichlorophenyl)-2-phenylvinyl) stan-
nane (2j). Colorless oil (98%). Rf¼0.64 (Et2O/cyclohexane, 2/98 TEA
1%, SiO2). 1H NMR (CDCl3, 300 MHz):
d
0.79 (9H, t, J¼7.3 Hz),
0.85e1.01 (6H, m), 1.21 (6H, sextet, J¼7.3 Hz), 1.32e1.47 (6H, m),
6.70 (1H, s, JSneH¼60.8 Hz), 6.88e7.14 (6H, m), 7.21 (2H, d, J¼7.9 Hz).
4.3.14. Hydrostannation of 1p.
13C NMR (75 MHz, CDCl3):
d 11.3 (3CH2), 13.8 (3CH3), 27.5 (3CH2),
28.9 (3CH2), 126.8 (CH), 127.3 (CH), 127.9 (2CH), 128.0 (2CH), 128.3
(2CH), 131.8 (2C), 138.0 (C), 140.3 (1CH), 142.8 (C), 144.8 (C). IR
(cmꢁ1, neat): 2955, 2923, 2870, 2851, 1553, 1493, 1463, 1425, 1376,
1254, 1191, 1148, 1088, 1073, 1047, 1028, 1001, 960, 921, 893, 874,
774. Anal. Calcd for C26H36Cl2Sn (538.18): C 58.02, H 6.74, found C
58.37, H 6.77.
4.3.14.1. Tributyl(1-(2,6-dimethoxyphenyl)vinyl)stannane
(2p). Colorless oil (92%). Rf¼0.70 (AcOEt/cyclohexane, 5/95 TEA 1%,
SiO2). 1H NMR (300 MHz, CDCl3)
d 0.93e0.74 (15H, m), 1.62e1.09
(12H, m), 3.75 (6H, s), 5.63 (1H, d, J¼3.3 Hz, JHeSn¼64.3 Hz), 5.89
(1H, d, J¼3.3 Hz, JHeSn¼137.0 Hz), 6.52 (2H, t, J¼8.5 Hz), 7.08 (1H, t,
J¼8.5 Hz). 13C NMR (75 MHz, CDCl3)
d 10.6 (3CH2), 13.9 (3CH3), 27.5
(3CH2), 29.1 (3CH2), 55.80 (2CH3), 103.9 (2CH), 124.2 (C), 126.4 (CH),
129.0 (2C), 147.4 (C), 156.0 (C). IR (cmꢁ1, neat): 2957, 2928, 2870,
1585, 1468, 1433, 1247, 1115. Anal. Calcd for C22H38O2Sn (453.25): C
58.30, H 8.45, found C 58.34, H 8.42.
4.3.10. Hydrostannation of 1k.
4.3.10.1. (E)-Tributyl(1-(2,6-dichlorophenyl)-2-(4-methox-
yphenyl)-vinyl)stannane (2k). Colorless oil (98%). Rf¼0.43 (Et2O/
cyclohexane, 5/95 TEA 1%, SiO2). 1H NMR (CDCl3, 300 MHz):
d
0.80
4.3.15. Hydrostannation of 1q.
(9H, t, J¼7.3 Hz), 0.84e0.95 (6H, m), 1.20 (6H, sextet, J¼7.3 Hz),
1.33e1.53 (6H, m), 6.60 (2H, d, J¼8.8 Hz), 3.66 (3H, s), 6.62 (1H, s,
JSneH¼62.1.0 Hz), 6.84 (2H, d, J¼8.8 Hz), 6.95 (1H, t, J¼8.3 Hz), 7.21
4.3.15.1. Tributyl(1-(2,6-dichlorophenyl)vinyl)stannane
(2q). Colorless oil (98%). Rf¼0.8 (cyclohexane, TEA 1%, SiO2). 1H
(2H, d, J¼8.0 Hz). 13C NMR (75 MHz, CDCl3):
d
11.3 (3CH2), 13.8
NMR (300 MHz, CDCl3) d 1.03e0.74 (15H, m), 1.52e1.15 (12H, m),
(3CH3), 27.5 (3CH2), 28.9 (3CH2), 55.3 (1CH3), 113.8 (2CH), 126.7
(CH), 128.0 (2CH), 129.4 (2CH), 131.0 (C), 132.1 (2C), 139.7 (CH),
142.0 (C), 142.9 (C), 158.8 (C). IR (cmꢁ1, neat): 2955, 2925, 2870,
2852, 1603, 1552, 1508, 1462, 1426, 1376, 1340, 1292, 1249, 1176,
1148, 1112, 1088, 1072, 1036, 960, 879, 823. Anal. Calcd for
C27H38Cl2OSn (568.21): C 57.07, H 6.74, found C 57.22, H 6.38.
5.69 (1H, d, J¼2.5 Hz), 5.79 (1H, d, J¼2.5 Hz), 7.01 (1H, t, J¼8.0 Hz),
7.39e7.17 (2H, m). 13C NMR (75 MHz, CDCl3)
d
11.3 (3CH2), 13.8
(3CH3), 27.4 (3CH2), 28.9 (3CH2), 126.8 (CH), 127.8 (2CH), 130.1 (2C),
132.2 (C), 152.2 (C). IR (cmꢁ1, neat): 2955, 2922, 1555, 1425, 1192,
1075, 930, 774, 743, 688. Anal. Calcd for C20H32Cl2Sn (462.08): C
51.98, H 6.98, found C 51.95, H 6.94.

A. Hamze et al. / Tetrahedron 66 (2010) 8698e8706
8705
4.4. Typical procedure for iodination of ortho-ortho0
vinylstannes (C)
1462, 1441, 1427, 1366, 1302, 1288, 1256, 1241, 1175, 1153, 1113, 1090,
1031, 908, 850, 827, 783, 767, 754, 681. Anal. Calcd for C22H18Cl2O2
(385.28): C 68.58, H 4.71, found C 68.62, H 4.54.
To a flame-dried flask under a nitrogen atmosphere were added
at 0ꢀC vinyl stannane 2k (1 equiv), dry CH2Cl2 (2 mL per mmol of
substrate), sublimed finely divided I2 (1.05 equiv), and the dark
wine solution was vigorously stirred at room temperature until all
of the substrate had been consumed (TLC). Saturated aqueous
Na2S2O3 was added to remove the excess of iodine followed by
addition of a potassium fluoride aqueous solution. After stirring at
room temperature for 1 h, the resulting white precipitate of trib-
utyltin fluoride was removed by filtration and the filtrate was
extracted with ether. The combined organic layers were washed
with brine, dried over MgSO4, and concentrated (the crude vinyl
iodide could be used in the further step without purification).
4.5.2. Methyl 2-((Z)-2-(4-((E)-6-hydroxy-1-(4-methoxyphenyl) hex-
1-enyl)phenyl)-1-(4-methoxyphenyl)vinyl)-3,4,5-tri-methox-
ybenzoate (4b). Following the above General procedure (D), using
bromo (4-methoxyphenyl)zinc (6 equiv) in THF, PdCl2(PPh3)2 (5%)
and 3l (1 equiv). The reaction was stirred at room temperature for
2 h in the dark.
Yellow oil (yield¼61%). Rf¼0.10 (AcOEt/cyclohexane, 30/70,
SiO2). 1H NMR (400 MHz, CDCl3):
d 1.44 (4H, m), 1.62 (2H, m), 2.01
(1H, br s, OH), 3.71 (2H, m), 3.76 (6H, s), 3.81 (3H, s), 3.91 (3H, s),
3.94 (3H, s), 3.97 (3H, s), 6.08 (1H, t, J¼7.8 Hz), 6.87e6.91 (12H, m),
7.12 (1H, s), 7.23 (1H, s). 13C NMR (100 MHz, CDCl3):
d 25.9 (CH2),
29.1 (CH2), 31.9 (CH2), 51.1 (CH3), 59.9 (CH3), 60.5 (CH3), 60.7 (CH3),
62.3 (CH2), 109.4 (CH), 113.3 (2CH), 113.5 (2CH), 127.8 (2 CH), 127.5
(2 CH), 128.1 (2C), 129.4 (C), 135.3 (2CH), 135.5 (2CH), 135.8 (C),
136.4 (2C), 136.7 (C), 138.5 (C), 139.0 (CH), 140.9 (CH), 152.6 (C),
158.6 (2C), 158.8 (2C), 167.3 (C]O). IR (cmꢁ1, neat): 2940, 2250,
1726, 1510, 1335, 1115, 910, 730. Anal. Calcd for C39H42O8 (638.75): C
73.33, H 6.63, found C 73.42, H 6.32.
4.4.1. (E)-1,3-Dichloro-2-(1-iodo-2-(4-methoxyphenyl)vinyl)
ben-
zene (3a). Colorless oil (yield¼98% after filtration through silica
gel). Rf¼0.50 (Et2O/cyclohexane, 5/95 TEA 1%, SiO2). 1H NMR
(300 MHz, CDCl3):
d
3.65 (3H, s), 6.61 (2H, d, J¼8.8 Hz), 6.75 (2H, d,
J¼8.8 Hz), 7.15 (1H, t, J¼8.8 Hz), 7.28 (2H, d, J¼8.5 Hz,), 7.39 (s, 1H).
13C NMR (75 MHz, CDCl3)
d
55.3 (CH3), 86.5 (C), 114.0 (2CH), 128.7
(2CH), 129.1 (C), 129.6 (2CH), 130.0 (CH), 134.2 (2C), 139.6 (C), 143.9
(CH), 159.5 (C). IR (cmꢁ1, neat): 3077, 2955, 2837, 1602, 1574, 1554,
1509,1459, 1428,1355, 1308, 1294,1260,1179,1169, 1151,1114,1092,
1034, 951, 935, 891, 878, 816, 780, 739, 679.
4.6. General procedure for the hydrosilylation of alkynes (E)
In a sealed tube, PtO2 (11.35 mg, 0.05 mmol) and alkyne
(1 mmol) were placed under nitrogen atmosphere. Triethylsilane
(0.24 mL, 1.5 mmol) was introduced via syringe and the mixture
was stirred at 60 ꢀC in an oil bath for 1 h in the absence of solvent.
The residue was then purified by column chromatography over
4.4.2. Methyl
2-((E)-2-(4-((E)-6-hydroxy-1-iodohex-1-enyl)phe-
nyl)-1-iodovinyl)-3,4,5-tri-methoxybenzoate (3b). Following the
above General procedure (C), using vinylstannane 2o (1.3 g,
1.29 mmol), DCM (40 mL) as solvent, I2 solution (2.2 equiv 723 mg,
2.85 mmol) in DCM (40 mL). The reaction was stirred at ꢁ40 ꢀC for
4 h in the dark.
silica gel to yield the title adducts either as a single
a mixture of inseparables 5 and 5 -isomers.
a-isomer 5 or as
a
b
Yellow oil (yield¼98% after filtration through silica gel). Rf¼0.37
(AcOEt/cyclohexane, 20/80 TEA 1%, SiO2). 1H NMR (300 MHz,
4.6.1. (E)-(1-(2,6-Dimethoxyphenyl)-2-phenylvinyl)triethylsilane (
5a). Colorless oil (yield¼90% after filtration through silica gel).
Rf¼0.70 (AcOEt/cyclohexane, 20/80, SiO2). Major
isomer: 1H NMR
(300 MHz, CDCl3)
0.61 (6H, q, J¼6.1 Hz), 0.93 (9H, t, J¼6.2 Hz), 3.63
a-
CDCl3):
d
1.21 (4H, m), 1.76 (2H, q, J¼7.4 Hz), 3.35 (2H, t, J¼5.7 Hz),
3.61 (3H, s), 3.67 (3H, s), 3.69 (3H, s), 3.78 (3H, s), 6.21 (1H, t,
a
J¼7.4 Hz), 6.62 (2H, d, J¼8.6 Hz), 6.85 (2H, d, J¼8.7 Hz), 7.14 (1H, s),
d
7.29 (1H, s). 13C NMR (75 MHz, CDCl3):
d
18.9 (CH2), 32.6 (2CH2),
(6H, s), 6.52 (2H, d, J¼8.3 Hz), 6.85 (1H, s), 7.12e6.99 (5H, m), 7.16
46.1 (CH2), 51.3 (CH3), 55.6 (CH3), 59.9 (CH3), 60.1 (CH3), 60.2 (CH2),
91.6 (C), 94.3 (C), 108.7 (CH), 123.9 (2 CH), 127.4 (C), 128.5 (C), 131.2
(2 CH), 136.8 (CH), 140.5 (CH), 145.9 (C), 150.1 (C), 153.2 (2C), 170.9
(C]O). IR (cmꢁ1, neat): 3406, 2937, 2857, 1725, 1585, 1489, 1451,
1431, 1393, 1333, 1255, 1223, 1194, 1171, 1116, 1052, 755.
(1H, t, J¼8.3 Hz). 13C NMR (75 MHz, CDCl3)
d 3.7 (3CH2), 7.4 (3CH3),
55.6 (2 CH3), 104.0 (2 CH), 120.2 (C), 126.8 (CH), 127.1 (CH), 127.9 (2
CH), 128.5 (2 CH), 136.2 (C), 138.9 (C), 139.6 (CH), 156.5 (2C). IR
(cmꢁ1, neat): 2950, 2875, 1583, 1468, 1431, 1246, 1110, 1006, 907,
781, 762, 649. Anal. Calcd for C22H30O2Si (354.56): C 74.53, H 8.53,
found C 74.41, H 8.44.
4.5. Typical procedure for Negishi coupling between ortho-
ortho0 vinyl iodide and organozinc compounds (D)
4.6.2. (E)-(1-(2,6-Dimethoxyphenyl)-2-(4-methoxyphenyl)vinyl)
triethylsilane
through silica gel). Rf¼0.65 (AcOEt/cyclohexane, 20/80, SiO2). Major
isomer: 1H NMR (300 MHz, CDCl3)
(
a
-5b). Colorless oil (yield¼97% after filtration
To a solution of vinyl iodide 2, PdCl2(PPh3)2 (5 mol %) in THF was
added at room temperature ArZnCl (2 equiv) prepared by trans-
metallation from the corresponding Grignard reagent (2 equiv) and
anhydrous ZnCl2 (2.1 equiv). The reaction was stirred at room
temperature and monitored by TLC until complete consumption of
starting materials (2e4 h). The reaction was hydrolyzed at 0ꢀC with
aqueous HCl (1 N), extracted with Et2O, the organic extract was
dried over MgSO4, and the solvent was removed in vacuo.
a
d
0.58 (6H, q, J¼7.8 Hz), 0.93
(9H, t, J¼7.8 Hz), 3.65 (6H, s), 3.72 (3H, s), 6.54 (2H, d, J¼8.3 Hz), 6.64
(2H, d, J¼8.8 Hz), 6.78 (1H, s), 6.99 (2H, d, J¼8.8 Hz), 7.16 (1H, t,
J¼8.3 Hz). 13C NMR (75 MHz, CDCl3)
d 3.7 (3CH2), 7.4 (3CH3), 55.2
(CH3), 55.6 (2 CH3), 104.1 (2CH), 113.4 (2CH), 120.4 (C), 127.0 (CH),
129.8 (2CH), 131.9 (C), 133.5 (C), 138.8 (CH), 156.6 (2C), 158.5 (C). IR
(cmꢁ1, neat): 2950, 1508, 1468, 1432, 1246, 1176, 1111, 1036, 1007,
905, 762, 727,696, 650. Anal. Calcd for C23H32O3Si (384.58): C 71.83,
H 8.39, found C 71.49, H 8.32.
4.5.1. (Z)-4,40-(1-(2,6-Dichlorophenyl)ethene-1,2-diyl)bis(methox-
ybenzene) (4a). Colorless oil (yield¼73%). Rf¼0.29 (Et2O/cyclohex-
ane, 5/95, SiO2). 1H NMR (300 MHz, CDCl3):
d
3.66 (3H, s), 3.73 (3H,
4.6.3. (E)-(1-(2,6-Dichlorophenyl)-2-phenylvinyl)triethylsilane
(a-
s), 6.63 (2H, d, J¼8.9 Hz), 6.79 (2H, d, J¼8.9 Hz), 6.84 (2H, d,
5c). Colorless oil (yield¼98% after filtration through silica gel).
J¼8.9 Hz), 6.99 (1H, s), 7.22e7.11 (3H, m), 7.31 (2H, d, J¼7.7 Hz). 13C
Rf¼0.40 (cyclohexane, SiO2). 1H NMR (300 MHz, CDCl3)
d 0.72 (6H,
NMR (75 MHz, CDCl3):
d
55.3 (CH3), 55.4 (CH3), 113.8 (2CH), 114.1
q, J¼6.1 Hz), 0.96 (9H, t, J¼6.1 Hz), 7.18e6.88 (6H, m), 7.30e7.26 (3H,
(2CH), 127.2 (2CH), 128.6 (2CH), 128.6 (CH), 129.4 (CH), 129.7 (2CH),
129.8 (C), 132.8 (C), 133.9 (C), 135.7 (2C), 138.4 (C), 158.8 (C), 159.2
(C). IR (cmꢁ1, neat): 3001, 2955, 2932, 2900, 1606, 1573, 1555, 1511,
m). 13C NMR (75 MHz, CDCl3)
d 4.4 (3CH2), 7.4 (3CH3), 127.6 (CH),
127.7 (CH), 128.2 (CH), 128.3 (2CH), 133.4 (2C), 137.7 (C), 140.7 (C),
141.5 (2CH), 148.2 (C). IR (cmꢁ1, neat): 2954, 2875, 1426, 1009, 965,

8706
A. Hamze et al. / Tetrahedron 66 (2010) 8698e8706
2417; (f) Paley, R. S.; Weers, H. L.; Fernandez, P. Tetrahedron Lett. 1995, 36,
3605.
7. (a) Alami, M.; Ferri, F. Synlett 1996, 755; (b) Hamze, A.; Provot, O.; Brion, J.-D.;
Alami, M. J. Org. Chem. 2007, 72, 3868.
937, 777, 765, 749, 730, 717, 688. Anal. Calcd for C20H24Cl2Si
(363.40): C 66.10, H 6.66, found C 66.05, H 6.45.
8. (a) Ferri, F.; Alami, M. Tetrahedron Lett. 1996, 37, 7971; (b) Bujard, M.; Ferri, F.;
Alami, M. Tetrahedron Lett. 1998, 39, 4243.
Acknowledgements
9. (a) Liron, F.; Le Garrec, P.; Alami, M. Synlett 1999, 246; (b) Alami, M.; Liron, F.;
Gervais, M.; Peyrat, J.-F.; Brion, J.-D. Angew. Chem., Int. Ed. 2002, 41, 1578; (c)
Liron, F.; Gervais, M.; Peyrat, J.-F.; Alami, M.; Brion, J.-D. Tetrahedron Lett. 2003,
44, 2789.
We thank the CNRS for supporting this research.
10. Hamze, A.; Veau, D.; Provot, O.; Brion, J.-D.; Alami, M. J. Org. Chem. 2009, 74,
1337.
11. Hamze, A.; Provot, O.; Brion, J.-D.; Alami, M. Org. Lett. 2005, 7, 5625.
12. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467; (b)
Alami, M.; Ferri, F.; Linstrumelle, G. Tetrahedron Lett. 1993, 34, 6403; (c) Alami,
M.; Ferri, F.; Gaslain, Y. Tetrahedron Lett. 1996, 37, 57.
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