Stereoselective access to functionalized β-γ unsaturated acids

Article abstract of DOI:10.1016/S0040-4020(03)00616-1

Stereoselective synthesis of vinylstannanes bearing a carboxylic acid function was achieved from β-γ alkynoic acids via hydrostannation, stannylcupration or silastannation reactions. Regioselectivity is highly dependent on the nature of the stannylanions used and on protection of the carboxylic acid function.

Full text of DOI:10.1016/S0040-4020(03)00616-1

Tetrahedron 59 (2003) 4433–4441
Stereoselective access to functionalized b-g unsaturated acids
a,b
Jerome Thibonnet, Mohamed Abarbri, Jean-Luc Parrain and Alain Duchene
a
b
a
,
*
´ ˆ
ˆ
a
´ ´
Laboratoire de Physicochimie des Interfaces et des Milieux Reactionnels, EA 2098-LRC-MO2, Faculte des Sciences et Techniques de Tours,
Parc de Grandmont, 37200 Tours, France
b
` ´ ´ ´ ˆ
Laboratoire de Synthese Organique associe au CNRS, UMR 6009, Faculte des Sciences et Techniques de Saint Jerome,
Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
Received 13 December 2002; revised 21 March 2003; accepted 7 April 2003
Abstract—Stereoselective synthesis of vinylstannanes bearing a carboxylic acid function was achieved from b-g alkynoic acids via
hydrostannation, stannylcupration or silastannation reactions. Regioselectivity is highly dependent on the nature of the stannylanions used
and on protection of the carboxylic acid function. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
which is a formal equivalent of C. Nevertheless, the main
formation of conjugated enal during the acidic deprotection
of acetal function prompted us to investigate another
acylfunction equivalent. We report here the synthesis and
the reactivity of tributylstannyl 4-tributylstannylbut-3-
enoate.6
Vinyltin reagents have proved to be efficient tools for the
transfer of a vinyl unit, with a high tolerance of numerous
functions both on the substrate and on the reagent.1 In this
context, we have proposed numerous vinylstannanes and
dienylstannanes bearing a conjugated non-protected car-
boxylic acid function, which is certainly one of the most
often used functions in organic synthesis.2 The most
significant studies to date have focused on reagents able to
transfer an ‘umpolung’ unit of d3 type (vinyltins bearing
acetal3 or ester4 functions) although some new vinyltin
reagents such as those bearing an homoallylic acetal
function have been described.5 The most effective studies
to date have focused on reagents able to transfer an acrylic
or pentadienoic unit (A and B). To the best of our
knowledge, the transfer of deconjugated butenoic acid has
not been examined, although the synthon C is found in
numerous natural products.
2. Results and discussions
The synthesis of vinyltin reagents was historically obtained
through radical hydrostannation of alkynes.7 However, this
method was found to be limited because of its low
selectivity, and numerous methods such as transition
metal catalysed hydrostannation8 have been proposed to
resolve this problem. Among these, the stannylcupration
reaction of alkynes generally offers good regio- and
stereoselectivity.9,10 Moreover, the intermediate vinyl
copper can be alkylated, yielding trisubstituted vinyl-
stannanes with fixed configuration.11 Interestingly, the
stannylcopper reagents were found to be inert towards
hydroxy or NH amide functions at low temperature.12
Another possibility is the addition of a bimetallic Si–Sn
system13 on alkynes,14 although these reactions have been
mostly achieved by the catalysis of palladium phosphine
complexes.15
It would be valuable to offer new organotin reagents for the
transfer of a four carbon chain bearing such a carboxylic
acid function. We have previously described the synthesis
and the reactivity of vinyltin bearing on homoallylic acetal
Keywords: hydrostannation; regioselectivity; iododestannylation.
*
Corresponding author. Tel.: þ33-2-47-36-69-59; fax: þ33-2-47-36-69-
60; e-mail: duchene@delphi.phys.univ-tours.fr
Scheme 1.
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00616-1

4434
J. Thibonnet et al. / Tetrahedron 59 (2003) 4433–4441
Table 1. Stannylmetallation of alk-3-ynoic acids
Entry
R
S
E
M
Tin reagent
2a/3
No.
Yield (%)b
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
Et
H
H
H
H
H
H
SnBu3
SnBu3
H
H
D
H
H
H
H
H
H
Me
Cu(Bu)Li, LiCNc
Cu(Bu)Li, LiCNc
AlEt2, 15% CuCNf
MgMe, 15% CuCNg
ZnSnBu3, [Pd]h 5%
Cu(Bu)Li, LiCNc
MgMe, 15% CuCNg
Cu(Bu)Li, LiCNc
Cu(Bu)Li, LiCNc
D
D
A
B
C
D
B
D
D
95/5
95/5
20/80
70/30
67/33
5/95
30/70
90/10
98/2
2a/3a
2b/3b
2a/3a
2a/3a
2a/3a
2a/3a
2a/3a
2c/3c
2d/3d
55 d
53 e
28
35
40
47
53
40
55
H
a
Only the E isomer is obtained.
b
c
d
e
f
1
Yield ratio 2/3 determined by H NMR.
Isolated yield.
The reaction was quenched with D2O at 2788C.
THF, 2788C, 1 h.
THF, 2308C, 3 h.
THF, 08C, 2 h.
[Pd]¼Pd(PPh3)4.
g
h
2.1. Hydrostannation of but-3-ynoic acid 1a
The required organotin precursor 2a was easily obtained
with 83% yield as a thermodynamic mixture (E)-2a/(Z)-
2a¼85/15 (Scheme 1) by radical hydrostannation of but-3-
ynoic acid 1a which was prepared via carbonatation of the
corresponding allenylmagnesium bromide.16
Scheme 2.
2.3. Silastannation of but-3-ynoic acid 1a
The best results for stereospecific addition of (tributyl-
stannyl)trimethylsilane on the tributylstannyl ester of but-3-
ynoic acid derivatives was obtained using tetrakis(tri-
phenylphosphine)palladium as catalyst, THF as the solvent,
a small amount of galvinoxyl18 and protection of the acidic
function with a tributylstannyl group19 (using acid 1a, the
reaction failed leaving the starting material unchanged).
Under these experimental conditions, (Z)-tributylstannyl-3-
tributylstannyl-4-trimethylsilylbut-3-enoate (Z)-4 was
isolated (80% yield) (Scheme 3).
2.2. Stannylmetallation of alk-3-ynoic acids
To improve the selectivity of this reaction, we studied the
stannylmetallation of 1a (results are consigned in Table 1).
Numerous tin anion systems known to add to the triple bond
were tested. When using Bu3SnAlEt2/CuCN A,17 Bu3-
SnMgMe/CuCN B,9b (Bu3Sn)2Zn/Pd(PPh3)4 C,9b only low
conversion rates into (E)-tributylstannyl 4-tributylstannyl-
but-3-enoate 2a were obtained. The best results were
obtained with high order Bu3Sn(Bu)Cu(CN)Li2 cyano-
cuprate D (2.3 equiv.),12d which afford fair yields of the
same isomer. As already observed,12d a clean cis-addition of
stannylcuprate occurred and no Bu ligand was transferred to
the triple bond.
Scheme 3.
In order to acquire information regarding the influence of
protection of the carboxylic acid function, tributylstannyl
ester of but-3-ynoic acid 1b (entry 6) was used in place of 1a
and was found to react with D with complete reverse
regioselectivity in comparison to entry 1. Similarly,
stannylanion B gave a 30/70 mixture in favour of internal
vinylstannane 3a (entry 7). Stannylcupration of hex-3-ynoic
acid (entry 8) with D confirmed the regioselectivity of the
addition. Finally, treatment of intermediate vinylcopper
(entry 9) with methyl iodide led to trisubstituted vinyl-
stannanes in fair yield but with an excellent regioselectivity.
Concerning the factors governing the regioselectivity of the
addition reaction, it is difficult to predict the trend of the
addition which can be reversed by a slight change in
the nature of both alkyne and stannyl reagents. Other tin
anion reagents gave poor regioselectivity but with a reverse
trend (entries 3–5) (Scheme 2). The results are recorded in
Table 1.
2.4. Reactivity of 2a and 4
The reactivity of 2a and (Z)-4 was examined in the case of
cross-coupling with organic halides under catalysis with
palladium complexes.20 In order to find optimal experimen-
tal conditions, various catalysts were tested and we found
that tetrakis(triphenylphosphine)palladium was the most
efficient for 2a (entries 1–13). The substitution reaction of 4
appears to have a general character only if the aryl halide
used exhibits an electron withdrawing group in its structure
(entries 14–19). The results are reported in Table 2,
(Scheme 4).
As seen in the results reported in Table 2, good yields were
obtained with aryl or heteroaryl halides (entries 1–12). We
observed that (E)-adduct reacted under our experimental

J. Thibonnet et al. / Tetrahedron 59 (2003) 4433–4441
Table 2. Reactivity of 2a and 4 with organic halides
4435
iodotributylstannylester 7a,b,d and (Z)-tributylstannyl-3-
iodo-4-trimethylsilylbut-3-enoate 8 in nearly quantitative
amounts without isomerisation of the double bond. It is
interesting to note that iodine treatment did not affect the
tributyltincarboxylate function. Iodo vinylic acids 9a,b,d
were obtained by acidic hydrolysis (Scheme 5).
Entry
Substrate
Organic halide
Catalyst
Yield (%)
No.
1
2
3
4
5
6
7
8
2a
2a
2a
2a
2a
2a
2a
2a
Ph-I
p-F-Ph-Br
A
A
A
A
A
A
A
A
72
66
55
65
65
73
75
88
5a
5b
5c
5d
5e
5f
p-MeO-Ph-Br
p-Acetyl-Ph-Br
p-CHO-Ph-Br
p-CF3-Ph-Br
p-Br-Ph-Br
5g
5h
9
2a
A
55
5i
10
11
12
2a
2a
2a
m-CF3-Ph-Br
m-Br-Ph-Br
A
A
A
74
78
85
5j
5ka
5lb
Scheme 5.
13
14
15
16
17
18
2a
4
4
4
4
p-tol-SO2-Cl
o-NO2-Ph-I
p-CHO-Ph-Br
m-CF3-Ph-Br
p-F-Ph-Br
B
A
A
A
A
C
83
68
50
57
59
63
5m
6a
6b
6c
6d
6e
Using a similar procedure, 7a, 9a and 8 were cross-coupled
with vinyltin reagents or organozinc reagents affording fair
to good yields of 10a–h and 11a–c (Scheme 6, Table 3).
4
19
4
Ph-I
A
0
–
A¼toluene, Pd(PPh3)4, 1008C, 12 h; B¼THF, Pd(PPh3)4, 558C, 12 h;
C¼DMF, PdCl2(MeCN)2, 508C, 8 h.
a
Only monosubstitution adduct is recovered.
Isolated as a stannylester.
b
Scheme 6.
Table 3. Reactivity of 7a, 8 and 9a with vinyltin or organozinc reagents
Entry Substrate
RM
Catalyst Yield (%) No.
1
2
9a
9a
B
B
72
61
10a
10b
Scheme 4.
3
4
9a
7a
B
B
80
75
10c
10d
conditions (1.2 equiv. of vinyltin), thus revealing the great
difference in reactivity between the two isomers. When the
thermodynamic mixture of (E)-2a/(Z)-2a¼85/15 was used
for cross-coupling with organic halides, the crude mixture
was found to contain a small amount of (Z)-5 (,5%) which
was eliminated during the crystallization purification
process. In the particular case of 2-bromopyridine (entry
12, Table 1) the ratio E/Z of 5 L was 85/15. The temporary
protection of the carboxylic acid function was removed by
simple hydrolysis at room temperature with HCl/water 1 M
or by stirring on silica gel. These results demonstrate the
efficiency of 2a to obtain the homocinnamyl skeleton
cleanly and more generally to transfer the d4 but-3-enoic
acid synthon onto miscellaneous substrates.
5
6
8
8
A
A
71
56
11a
11b
7
8
A
65
11c
9
9a
9a
9a
9a
MeZnBr
EtZnBr
BnZnBr
B
B
B
B
90
92
75
79
10e
10f
10g
10h
10
11
12
A¼toluene, Pd(PPh3)4, 12 h; B¼DMF, PdCl2(MeCN)2, 12 h.
The experimental conditions applied here are derived from
the systematic study carried out on 3-iodobut-3-enoic acid2a,d
and 3 equiv. of organozinc reagent were required to achieve
complete conversion (entries 9–12). No isomerisation of
the double bond was observed and no cyclisation, affording
butenolides, occurred.
2.5. Iododestannylation and reactivity of 7, 8 and 9
In order to extend the potential of compounds 2a,b,d and 4,
reverse cross-coupling reactions were investigated.21 Iodo-
destannylation of 2a,b,d and 4 yielded the corresponding

4436
J. Thibonnet et al. / Tetrahedron 59 (2003) 4433–4441
3. Conclusion
homogeneous solution was obtained). The mixture was
allowed to react for 15 min and then Bu3SnH (10.9 mL,
40 mmol) was added dropwise (yellow coloration was
obtained) at 2808C. After stirring for 15 min at 2808C, but-
3-ynoic acid 1a (0.68 g, 8 mmol) in THF (5 mL) was added
slowly and allowed to react for 2 h at 2808C.
In summary, we investigated the hydrostannation, the
stannylcupration and the silastannation reaction of homo-
propargylic acids, stereoselective synthesis of vinyl-
stannanes bearing a carboxylic acid function was
achieved. We, also, demonstrated that the regioselectivity
is highly dependent on the nature of the stannylanions used
and on protection of the carboxylic acid function.
(a) The reaction mixture was then quenched with a saturated
NH4Cl or D2O solution at 2808C and Et2O was added. After
filtration over Celite, the organic layer was separated,
extracted with Et2O, washed with brine and dried over
MgSO4. After evaporation of solvents, the crude products
were used without further purification (entry 1).
4. Experimental
General Methods. 1H NMR spectra were recorded at 200 or
at 300 MHz using CDCl3 as solvent. Results, reported using
the residual proton resonance of CDCl3 (dH¼7.25 ppm) as
the internal reference, were as follows (in order): chemical
shift (d in ppm relative to Me4Si), multiplicity (s, d, t, m, b
for singlet, doublet, triplet, multiplet, broad), coupling
constants (J in Hz). 13C NMR spectra were recorded at 50 or
75 MHz using CDCl3 solvent peak at dC¼77.0 ppm as the
reference. Electron impact mass spectra were measured at
70 ev by GC-MS or direct introduction mode. The isotopic
patterns are given for 120Sn (isotopic values 33%) in
organotin fragments; this means that the reported values
(values in brackets) for organotin fragments were only
roughly one third of the correct value, taking into account
the 10 isotopes of tin compared with those of organic
fragment. Raman spectra were recorded on a Bruker RFS
100, excitation with a laser Nd: YAG (1064 nm, 130 mW).
Melting points were uncorrected. Standard column
(b) The vinylcopper intermediate was trapped by an excess
of methyl iodide (30 mL) in the presence of HMPA (4 mL)
at 2808C. The mixture was allowed to react at room
temperature for 24 h. The reaction mixture was then
quenched with a saturated NH4Cl solution at 08C and
Et2O was added. After filtration over Celite, the organic
layer was separated, extracted with Et2O, washed with brine
and dried over MgSO4. After evaporation of solvents, the
crude product was used without further purification.
A similar procedure for the stannylmetallation of 1b (the
preparation of tributylstannylbut-3-ynoate (1b) was
described19) was employed.
4.1.1. 3-Tributylstannylbut-3-enoic acid (3a0). (By puri-
fication of crude product 3a on silica gel using PE/Et2O¼95/
5, 0we only observed deprotection of stannyl ester into acid
3a .) IR: 3020, 1710, 1645, 1230. 1H NMR (d ppm): 0.85 (t,
J¼7.2 Hz, 9H), 0.88–1.05 (m, 6H), 1.20–1.60 (m, 12H),
3.24 (s, JSn–H¼43 Hz, 2H), 5.24 (bs, JSn–H¼56.7 Hz, 1H),
5.76 (bs, JSn–H¼127 Hz, 1H), 11.60 (bs, 1H). 13C NMR (d
ppm): 10.7 (JSn–C¼344–328 Hz, 3C), 14.2 (3C), 27.9
(JSn–C¼56 Hz, 3C), 29.6 (JSn–C¼18.6 Hz, 3C), 44.5
˚
chromatography was performed on Merck silica gel (60 A,
230–400 mesh silica gel) by flash column chromatography
techniques. Analytical thin-layer chromatography (TLC)
was conducted on Merck precoated silica gel 60 F254 Plate.
All reactions were performed in oven-dried glassware under
positive argon pressure, unless otherwise noted. Reaction
mixtures were stirred magnetically. Ether was dried and
freshly distilled from sodium/benzophenone. DMF was
dried by distillation over calcium hydride prior to use.
Tributyltin methoxide and tributyltin hydride were com-
mercialy available (or prepared according to Refs. 22,23).
Acid 1a was prepared by a previously reported procedure.16
Vinyltributylstannane was prepared from vinylmagnesium
bromide and bistributyltin oxide.24 (E)-1-Trimethylsilyl-2-
n-tributylstannylethylene was prepared by hydrostannation
of trimethylsilylacetylene.25 (E)-b-Styryltributyltin was
prepared by hydrostannation of phenylacetylene.26 (E)-1-
Tributylstannyl-4,4-diethoxybut-1-ene was obtained by
stannylmetallation of the homopropargylic acetal using
tributylstannylmethyl magnesium in the presence of
cuprous cyanide.27 Tributyltinacetylide was prepared from
lithium acetylide, ethylenediamine complex and tributyltin
chloride.28 The preparation of tributylstannyl 4-tributyl-
stannylbut-3-enoate (2a) was already described.29
(JSn–C¼33.3 Hz),
129.6
(JSn–C¼42.4 Hz),
147.9
(JSn–C¼320 Hz), 179.2 (JSn–C¼58 Hz). MS (70 eV, EI)
m/z: 319 (Mþ257, 100), 291 (22), 275 (18), 235 (12), 205
(11), 179 (26), 177 (76), 121 (15), 57 (9), 41 (25), 39 (14).
4.1.2. (E)-Tributylstannyl 3-2H-4-tributylstannylbut-3-
1
enoate (2b). H NMR (d ppm): 0.80–1.70 (54H, m), 3.18
(2H, s), 5.72 (1H, s, JSn–H¼65.5 Hz).
4.1.3. (E)-Tributylstannyl 3-methyl-4-tributylstannyl-
but-3-enoate (2d). 1H NMR (d ppm): 0.80–1.70 (m,
54H), 1.89 (s, 3H), 3.20 (s, 2H), 5.66 (s, JSn–H¼65.5 Hz,
1H).
4.2. Silastannation of but-3-ynoic acid (1a)
A solution of (trimethylsilyl)tributylstannane (0.98 g,
2.7 mmol) in THF (1 mL) was added dropwise by syringe
to a solution of 1b tributylstannylbut-3-ynoate (1 g,
2.7 mmol), tetrakis(triphenylphosphine)palladium (62 mg,
2 mol%), and galvinoxyl (10 mg) in THF (50 mL) at room
temperature. After stirring at 708C for 6 h, the reaction
mixture was filtered through a Celite pad and concentrated
under vacuum. Silylstannane 4Z (1.58 g, 2.14 mmol, 80%)
was purified by crystallization from Et2O/hexane (5/95) to
provide white needles (mp: 458C).
4.1. Stannylmetallation of but-3-ynoic acid 1a
Tributylstannylcuprate was prepared according to the route
described by Lipshutz et al.12d CuCN (1.8 g, 20 mmol) was
suspended in freshly distilled THF (80 mL), cooled at
2808C and 25 mL of n-BuLi 1.6 M in hexane (40 mmol)
were added dropwise at 2808C (green coloration until a

J. Thibonnet et al. / Tetrahedron 59 (2003) 4433–4441
4437
4.2.1. (Z)-Tributylstannyl 3-tributylstannyl-4-trimethyl-
silyl-but-3-enoate (4). 1H NMR (d ppm): 0.14 (s, 9H), 0.93
(t, J¼7.3 Hz, 18H), 1.22–1.65 (m, 36H), 3.32 (s, JSn–H¼42
Hz, 2H), 6.44 (s, JSn–H¼168 Hz, 1H). 13C NMR (d ppm):
20.7, 11.6 (JSn–C¼318–330 Hz, 3C), 13.5 (6C), 16.3
(JSn–C¼344–360 Hz, 3C), 26.9 (JSn–C¼80 Hz, 3C), 27.5
(JSn–C¼116 Hz, 3C), 27.7 (JSn–C¼21 Hz, 3C), 29.1
(JSn–C¼19 Hz, 3C), 52.4 (JSn–C¼51 Hz), 146.2 (JSn–C¼60
Hz), 158.6 (JSn–C¼435 Hz), 171.4. MS (70 eV, EI) m/z: 681
(Mþ257, 62), 679 (74), 291 (15), 235 (58), 179 (94), 177
(100), 73 (41), 57 (57), 41 (80), 39 (25). 119Sn (d ppm): 107,
54.
38.0, 55.3, 114.0 (2C), 118.5, 127.5 (2C), 129.5, 133.4,
159.3, 178.2. MS (70 eV, EI) m/z: 192 (Mþ, 100), 148 (10),
147 (96), 115 (14), 103 (10), 91 (16), 45 (13). Anal. calcd
for C11H12O3: C, 68.74; H, 6.29. Found: C, 68.77; H, 6.34.
4.3.4. (E)-4-(p-Acetophenyl)but-3-enoic acid (5d). Mp:
1328C. IR (KBr): 3441, 3069, 2930, 2878, 1724, 1643,
1601, 1406, 1269, 1194, 969, 793. RAMAN: 3069, 2926,
1
1654, 1595, 1272, 1179, 1081. H NMR (d ppm): 2.63 (s,
3H), 3.37 (d, J¼6.2 Hz, 2H), 6.46 (dt, J¼16.0, 6.2 Hz, 1H),
6.61 (d, J¼16.0 Hz, 1H), 7.48 (d, J¼8.0 Hz, 2H), 7.94 (d,
J¼8.0 Hz, 2H), 8.80 (bs, 1H). 13C NMR (d ppm): 26.6, 38,
124, 133, 126.4 (2C), 128.8, (2C), 136, 141.3, 177, 198. MS
(70 eV, EI) m/z: 204 (Mþ, 38), 190 (12), 189 (100), 115
(33), 45 (10), 43 (46). Anal. calcd for C12H12O3: C, 70.57;
H, 5.92. Found: C, 70.50; H, 5.95.
4.3. Cross-coupling of 2a and 4 with organic halides:
preparation of compounds 5 and 6
In a 50 mL flask are introduced toluene (20 mL), 2a
(7 mmol) or 7 (7 mmol), aryl bromide (5.8 mmol) and
tetrakis(triphenylphosphine)palladium (3 mol%). The mix-
ture is degased under vacuum and stirred overnight at
1008C. After cooling, the stannyl ester is hydrolysed with
10 mL of 1N HCl solution. After extraction with diethyl
ether, the organic layer was treated with 1N NaOH solution.
The aqueous layer was washed with ether then was acidified
with 1N HCl solution and extracted with ether. After
removal of the solvents under reduced pressure, compounds
5 or 6 were recovered from the crudes by crystallization
from PE/Et2O (95/5) or by column chromatography on
silica gel with first EP/Et2O 99/1 as eluent, then elution: PE/
Et2O 80/20.
4.3.5. (E)-4-(p-Formylphenyl)but-3-enoic acid (5e). IR
(KBr): 3437, 2978, 2845, 1722, 1678, 1653, 1601, 1398,
1313, 1180, 974, 852. RAMAN: 3069, 2916, 1653, 1601,
1219, 1170. 1H NMR (d ppm): 3.40 (d, J¼6.0 Hz, 2H), 6.50
(dt, J¼16.0, 6.0 Hz, 1H), 6.64 (d, J¼16.0 Hz, 1H), 7.55–
7.68 (m, 2H), 7.86–8.00 (m, 2H), 10 (s, 1H), 10.40 (s, 1H).
13C NMR (d ppm): 38, 124.8, 126.8 (2C), 130.2 (2C), 131.7,
131.9, 133, 177, 191.8. MS (70 eV, EI) m/z: 190 (Mþ, 63),
148 (19), 145 (16), 118 (12), 117 (100), 116 (22), 115 (89),
91 (36), 89 (13), 77 (15), 65 (16), 63 (17), 51 (21), 45 (10),
39 (14). Anal. calcd for C11H10O3: C, 69.46; H, 5.30. Found:
C, 69.51; H, 5.28.
4.3.6. (E)-4-(p-Trifluoromethylphenyl)but-3-enoic acid
(5f). Mp: 58–608C. IR (KBr): 3400–2500, 3047, 1708,
1598, 1428, 1325, 1284, 1232, 1122, 1066, 857, 808.
RAMAN: 3067, 3022, 2934, 1662, 1610, 1279, 1213, 1183,
4.3.1. (E)-4-Phenylbut-3-enoic acid (5a). Mp: 78–808C.
IR (KBr): 3433, 3059, 2955, 1701, 1655, 1493, 1417, 1300,
1223, 976, 746. RAMAN: 3062, 3028, 2952, 2890, 1661 (s),
1
1
1597 (s), 1279, 1210, 1000. H NMR (d ppm): 3.35 (dd,
765. H NMR (d ppm): 3.38 (d, J¼6.5 Hz, 2H), 6.43 (dt,
J¼6.9, 1.2 Hz, 2H), 6.33 (dt, J¼15.9, 6.9 Hz, 1H), 6.57 (dt,
J¼15.9, 1.2 Hz, 1H), 7.32–7.47 (m, 5H), 11.26 (bs, 1H).
13C NMR (d ppm): 38.1, 120.8, 126.4 (2C), 127.7, 128.4
(2C), 134.0, 136.6, 178.4. MS (70 eV, EI) m/z: 162 (Mþ,
49), 118 (10), 117 (100), 116 (17), 115 (60), 91 (27), 45
(10), 39 (10). Anal. calcd for C10H10O2: C, 74.06; H, 6.21.
Found: C, 74.11; H, 6.28.
J¼16.0, 6.5 Hz, 1H), 6.60 (d, J¼16.0 Hz, 1H), 7.47–7.64
(m, 4H), 8.34 (s, 1H). 13C NMR (d ppm): 38.3, 124, 124.6
(JC–F¼270 Hz), 126 (JC–F¼3.2 Hz, 2C), 126.9 (2C), 129.9
(JC–F¼32.2 Hz), 133.1, 140.5, 177.2. MS (70 eV, EI) m/z:
230 (Mþ, 80), 211 (21), 188 (32), 186 (12), 185 (100), 165
(71), 164 (19), 145 (15), 133 (10), 117 (17), 116 (29), 115
50), 45 (17). Anal. calcd for C11H9F3O2: C, 57.40; H, 3.94.
Found: C, 57.47; H, 3.98.
4.3.2. (E)-4-(p-Fluorophenyl)but-3-enoic acid (5b). Mp:
1018C. IR (KBr): 3410, 3036, 2893, 1703, 1657, 1594,
1508, 1226, 976, 807. RAMAN: 3075, 2894, 1659, 1599,
1275, 1206, 999. 1H NMR (d ppm): 3.33 (dd, J¼7.0, 1.1 Hz,
2H), 6.24 (dt, J¼15.9, 7.0 Hz, 1H), 6.52 (dt, J¼15.9, 1.1 Hz,
1H), 7.0–7.10 (m, 2H), 7.35–7.42 (m, 2H), 10.3 (bs, 1H).
13C NMR (d ppm): 37.9, 115.4 (JC–F¼21.6 Hz), 120.5,
127.8 (JC–F¼8 Hz), 130.0 (JC–F¼21.6 Hz), 132.8, 162.4
(JC–F¼247 Hz), 178.2. MS (70 eV, EI) m/z: 180 (Mþ, 46),
136 (12), 135 (100), 134 (12), 133 (38), 115 (32), 109 (27),
83 (11), 57 (12), 45 (10). Anal. calcd for C10H9FO2: C,
66.66; H, 5.03. Found: C, 66.71; H, 4.98.
4.3.7. (E)-4-(p-Bromophenyl)but-3-enoic acid (5g). Mp:
1108C. IR (KBr): 3300–2400, 3048, 1718, 1602, 1487,
1423, 1302, 1219, 1072, 972, 790. RAMAN: 3059, 3022,
2926, 2889, 1661, 1603, 1583, 1272, 1208, 1073. 1H NMR
(d ppm): 3.30 (d, J¼6.5 Hz, 2H), 6.30 (dt, J¼15.9, 6.5 Hz,
1H), 6.50 (d, J¼15.9 Hz, 1H), 7.27 (d, J¼8.4 Hz, 2H), 7.47
(d, J¼8.5 Hz, 2H), 8.79 (s, 1H). 13C NMR (d ppm): 37.8,
121.5, 127.7 (2C), 131.5 (2C), 132.3, 132.7, 135.4, 177.5.
MS (70 eV, EI) m/z: 242 (Mþ, 36), 240 (35), 197 (19), 195
(20), 117 (13), 116 (100), 115 (54), 89 (10), 45 (10). Anal.
calcd for C10H9BrO2: C, 49.82; H, 3.76. Found: C, 49.77; H,
3.74.
4.3.3. (E)-4-(p-Methoxyphenyl)but-3-enoic acid (5c). Mp:
1028C. IR (KBr): 3443, 3036, 3016, 2951, 2835, 1709,
1655, 1606, 1512, 1290, 1242, 1176, 1032, 802. RAMAN:
4.3.8. (E)-4-[(8,9-Methylenedioxy)phenyl]but-3-enoic
acid (5h). Mp: 1158C. IR (KBr): 3400–2500, 3018, 2903,
1689, 1604, 1498, 1430, 1257, 1230, 1179, 1100, 927, 782.
RAMAN: 3073, 2897, 1654, 1617, 1603, 1448, 1284, 1198,
816. 1H NMR (d ppm): 3.30 (d, J¼7.0 Hz, 2H), 6.00 (s, 2H),
6.14 (dt, J¼15.8, 7.0 Hz, 1H), 6.46 (d, J¼15.8 Hz, 1H),
1
1656, 1607, 1285, 1179, 756. H NMR (d ppm): 3.26 (dd,
J¼6.9, 1.1 Hz, 2H), 3.79 (s, 3H), 6.12 (dt, J¼15.9, 6.9 Hz,
1H), 6.45 (dt, J¼15.9, 1.1 Hz, 1H), 6.84 (d, J¼8.5 Hz, 2H),
7.30 (d, J¼8.5 Hz, 2H), 9.98 (bs, 1H). 13C NMR (d ppm):

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J. Thibonnet et al. / Tetrahedron 59 (2003) 4433–4441
1
6.76–6.86 (m, 2H), 6.96–7.00 (m, 1H), 8.55 (bs, 1H). 13C
NMR (d ppm): 38.3, 101.5, 106, 108.7, 119.4, 121.4, 131.5,
133.9, 147.7, 148.4, 178.4. MS (70 eV, EI) m/z: 206 (Mþ,
91), 161 (32), 132 (11), 131 (100), 104 (10), 103 (85), 102
(15), 77 (32), 51 (15), 45 (12). Anal. calcd for C11H10O4: C,
64.07; H, 4.89. Found: C, 64.07; H, 4.91.
3073, 3041, 2985, 2926, 1661, 1588, 1252, 1147, 757. H
NMR (d ppm): 2.49 (s, 3H), 3.99 (dd, J¼7.7, 0.9 Hz, 2H),
5.89 (dt, J¼15.6, 0.9 Hz, 1H), 6.92 (dt, J¼15.6, 7.7 Hz, 1H),
7.40 (d, J¼8.0 Hz, 2H), 7.78 (d, J¼8.0 Hz, 2H), 8.76 (bs,
1H). 13C NMR (d ppm): 21.7, 59.2, 128.3 (2C), 128.5, 130.1
(2C), 135.1, 135.9, 145.5, 169.8. MS (70 eV, EI) m/z: 240
(Mþ, 1), 223 (13), 155 (21), 139 (10), 92 (10), 91 (100), 68
(91), 65 (33), 39 (20). Anal. calcd for C11H12O4S: C, 54.99;
H, 5.03. Found: C, 55.05; H, 5.08.
4.3.9. (E)-4-[(6,7-Methylenedioxy)phenyl]but-3-enoic
acid (5i). IR (KBr): 3018, 2960, 2920, 2714, 2609, 2553,
1711, 1655, 1547, 1452, 1288, 1250, 1221, 1060, 970, 939,
788, 761. 1H NMR (d ppm): 3.35 (d, J¼4.8 Hz, 2H), 6.03 (s,
2H), 6.48–6.55 (m, 2H), 6.75–6.85 (m, 3H), 11.52 (bs, 1H).
13C NMR (d ppm): 38.4, 100.8, 107.4, 119, 120.6, 121.5
(3C), 123.8, 128.3, 144.5, 147.6 (2C), 177.9. MS (70 eV, EI)
m/z: 206 (100), 161 (40), 132 (14), 131 (91), 104 (14), 103
(94), 102 (17), 78 (10), 77 (42), 76 (12), 75 (11), 63 (14), 51
(21), 50 (10), 45 (18). Anal. calcd for C11H10O4: C, 64.07;
H, 4.89. Found: C, 64.11; H, 4.86.
4.3.14. (Z)-4-Trimethylsilyl-3-(o-nitrophenyl)but-3-
enoic acid (6a). IR: 3500–2800, 1710, 1615, 1600. 1H
NMR (d ppm): 20.29 (s, 9H), 3.51 (s, 2H), 5.89 (s, 1H),
7.34–7.51 (m, 4H), 10.55 (bs, 1H). 13C NMR (d ppm): 20.9
(3C), 46.8, 124.4, 128.6, 129.1, 132.5, 132.9, 134.6, 137.4,
145.8, 177.4. MS (70 eV, EI) m/z: 206 (Mþ273, 10), 75
(17), 73 (100), 45 (27), 43 (11). Anal. calcd for
C13H17NO4Si: C, 55.89; H, 6.13; N, 5.01. Found: C,
55.95; H, 6.18; N, 5.12.
4.3.10. (E)-4-(m-Trifluoromethylphenyl)but-3-enoic acid
(5j). IR (KBr): 3038, 2926, 2854, 2737, 1709, 1593, 1419,
1402, 1332, 1228, 1167, 1120, 1070, 966, 792, 700. H
4.3.15. (Z)-4-Trimethylsilyl-3-(p-formylphenyl)but-3-
enoic acid (6b). IR: 3400–2860, 1700, 1672, 1595, 1284,
1225. 1H NMR (d ppm): 20.25 (s, 9H), 3.45 (s, 2H), 5.86 (s,
1H), 7.34–7.38 (2H), 7.79–7.83 (2H), 9.98 (s, 1H), 10.3
(bs, 1H). 13C NMR (d ppm): 20.22 (3C), 47.6, 114.8, 129.3
(2C), 130 (2C), 136, 148.9, 149.2, 176.3, 192.4. MS (70 eV,
EI) m/z: 218 (Mþ244, 18), 117 (10), 116 (100), 66 (22), 64
(11), 45 (22), 43 (11). Anal. calcd for C14H18O3Si: C, 64.09;
H, 6.91. Found: C, 64.15; H, 6.95.
1
NMR (d ppm): 3.37 (d, J¼6.6 Hz, 2H), 6.40 (dt, J¼16.0,
6.6 Hz, 1H), 6.60 (d, J¼16.0 Hz, 1H), 7.42–7.60 (m, 3H),
7.66 (s, 1H), 9.57 (bs, 1H). 13C NMR (d ppm): 37.7, 122.8,
122.9, 123.9 (JC–F¼270 Hz), 124.2, 128.9, 129.3, 131.2
(JC–F¼32.2 Hz), 132.6, 137, 177.4. MS (70 eV, EI) m/z:
230 (Mþ, 78), 211 (16), 188 (43), 186 (12), 185 (100), 165
(89), 145 (30), 117 (41), 116 (51), 115 (64), 39 (13). Anal.
calcd for C11H9F3O2: C, 57.40; H, 3.94. Found: C, 57.43; H,
3.97.
4.3.16. (Z)-4-Trimethylsilyl-3-(m-trifluoromethyl-
phenyl)but-3-enoic acid (6c). Mp: 1348C. IR (KBr):
1
4.3.11. (E)-4-(m-Bromophenyl)but-3-enoic acid (5k). IR:
3038, 2978, 2928, 2555, 1712, 1657, 1593, 1562, 1473,
3300–2800, 1710, 1603, 1438, 1400, 1333, 1214, 845. H
NMR (d ppm): 20.17 (s, 9H), 2.87 (s, 2H) 5.89 (s, 1H),
7.40–7.54 (m, 4H), 11.2 (bs, 1H). 13C NMR (d ppm): 0.2,
47.9, 124.8 (q, JC–F¼4 Hz), 125.8 (q, JC–F¼4 Hz), 129.1,
131.1, 132.0, (q, JC–F¼32 Hz), 132.8 (q, JC–F¼272 Hz),
136.1, 143.7, 148.9, 177.9. MS (70 eV, EI) m/z: 302 (Mþ,
62), 288 (13), 287 (88), 283 (11), 243 (35), 166 (100), 165
(18), 117 (10), 115 (18), 75 (15), 73 (99). Anal. calcd for
C14H17F3O2Si: C, 55.61; H, 5.67. Found: C, 55.69; H, 5.62.
1
1420, 1292, 1221, 1074, 964. H NMR (d ppm): 3.34 (d,
J¼6.5 Hz, 2H), 6.33 (dt, J¼15.9, 6.5 Hz), 6.43 (d,
J¼15.9 Hz), 7.16–7.47 (m, 3H), 7.57 (s, 1H), 11.83 (bs,
1H). 13C NMR (d ppm): 37.8, 122.7, 122.4, 124.9, 129.2,
130, 130.5, 132.5, 138.7, 178.1. MS (70 eV, EI) m/z: 242
(Mþ, 28), 240 (27), 198 (10), 197 (14), 195 (14), 117 (22),
116 (100), 115 (61), 89 (12), 63 (12), 45 (10), 39 (11). Anal.
calcd for C10H9BrO2: C, 49.82; H, 3.76. Found: C, 49.84; H,
3.81.
4.3.17. (Z)-4-Trimethylsilyl-3-(p-fluorophenyl)but-3-
enoic acid (6d). IR: 3400–2800, 1675, 1602, 1214. 1H
NMR (d ppm): 20.13 (s, 9H), 2.84 (s, 2H), 5.87 (s, 1H),
7.03–7.40 (m, 4H), 11.43 (bs, 1H). 13C NMR (d ppm):
20.64 (3C), 26.4, 112.9, 115.7, 116.1, 128.9, 129.1, 139.4,
163.6, 166.2, 172.9. MS (70 eV, EI) m/z: 252 (Mþ, 4), 193
(17), 115 (100), 70 (12), 45 (12). Anal. calcd for
C13H17FO2Si: C, 61.87; H, 6.79. Found: C, 61.91; H, 6.85.
4.3.12. (E)-Tributylstannyl-4-[(20-pyridynyl)]but-3-eno-
ate (5l). IR: 2049, 2960–2850, 1655, 1587, 1469, 1375,
1
1286, 1153, 1078, 972, 910, 787–734. H NMR (d ppm):
E-isomer: 0.76 (t, J¼7.1 Hz, 9H), 0.98–1.58 (m, 18H), 3.26
(dd, J¼7.0, 1.0 Hz, 2H), 6.54 (d, J¼15.9 Hz, 1H), 6.77 (dt,
J¼15.9, 7.0 Hz, 1H), 7.06 (m, 1H), 7.29 (m, 1H), 7.55 (m,
1H), 8.48 (m, 1H); Z-isomer: 3.66 (dd, J¼6.8, 1.3 Hz, 2H),
5.88 (dt, J¼15.4, 1.3 Hz, 1H). 13C NMR (d ppm): E-isomer:
13.5 (3C), 16.4 (JSn–C¼341–357 Hz, 3C), 26.9
(JSn–C¼65.3 Hz, 3C), 27.7 (JSn–C¼27 Hz, 3C), 38.7,
120.9, 121.9, 128.7, 132, 136.5, 149, 155.3, 175.8.
Z-isomer: 40.6, 121, 124.6, 135.8, 144.2, 149.1. MS
(70 eV, EI) m/z: 396 (Mþ257, 10), 352 (43), 238 (26),
177 (23), 121 (22), 120 (17), 119 (26), 118 (100), 117 (54),
65 (10), 57 (25), 52 (10), 51 (21), 45 (10), 41 (100), 39 (42).
4.3.18. (Z)-5-Chloro-3-(20-trimethylsilylethenyl)pent-4-
enoic acid (6e). IR: 2970, 2930, 1720, 1635, 1590, 1260.
1H NMR (d ppm): 0.15 (s, 9H), 3.24 (s, 2H), 5.70 (s, 1H),
6.30 (d, J¼13.5 Hz, 1H), 6.68 (d, J¼13.5 Hz, 1H), 9.0 (bs,
1H). 13C NMR (d ppm): 0.7 (3C), 43.6, 121.6, 134.2, 138.5,
143.2, 177.5. MS (70 eV, EI) m/z: 205 (Mþ215, 36), 203
(100), 183 (19), 97 (14), 95 (50), 75 (53), 73 (14), 65 (13).
4.4. Iododestannylation
4.3.13. (E)-4-(p-Toluenesulfonyl)but-3-enoic acid (5m).
Mp: 1648C. IR (KBr): 3489, 2993, 2930, 1695, 1646, 1595,
1421, 1318, 1246, 1216, 1145, 1055, 982, 810. RAMAN:
At 08C, to vinylstannane 2a (12 mmol) in freshly distilled
Et2O (30 mL) was added iodine (3.5 g, 14 mmol) in Et2O

J. Thibonnet et al. / Tetrahedron 59 (2003) 4433–4441
4439
(35 mL). The mixture was stirred for 2 h at room
temperature. Excess I2 was eliminated by washing with a
0.5 M solution of sodium thiosulfate. The solution was then
hydrolysed with 25 mL of a saturated solution of potassium
fluoride and 25 mL of acetone in order to remove all the
tributyltin salts formed. After vigourous stirring for 3 h, the
reaction mixture was filtered and washed with water,
the aqueous layer was acidified with 1 M HCl solution,
extracted with Et2O and washed with brine. After usual
treatments, the crude acid 9a (1.40 g, 6.6 mmol, 55%) was
purified by crystallisation with PE/Et2O (90/10).
77.2, 139.4, 172.6. MS (70 eV, EI) m/z: 445 (Mþ257, 30),
361 (15), 305 (14), 291 (15), 247 (32), 177 (28), 121 (26), 97
(18), 85 (15), 57 (33), 55 (93), 41 (100), 40 (16), 39 (69).
4.5.2. (Z)-Tributylstannyl 3-iodo-4-trimethylsilylbut-3-
1
enoate (8). Mp: 1058C. IR: 1591, 1566, 1241. H NMR (d
ppm): 0.24 (s, 9H), 0.95 (t, J¼7.1 Hz, 9H), 1.28–1.85 (m,
18H), 3.71 (d, J¼1.0 Hz, 2H), 6.53 (t, J¼1.0 Hz, 1H). 13C
NMR (d ppm): 20.7, 14.2 (3C), 17.2 (JSn–C¼339–357 Hz;
3C), 27.6 (JSn–C¼65.3 Hz, 3C), 28.4 (JSn–C¼20 Hz, 3C),
57.6, 111.2, 141, 177. MS (70 eV, EI) m/z: 517 (Mþ257, 8),
361 (100), 305 (45), 247 (31), 245 (23), 179 (15), 177 (27),
97 (17), 75 (18), 73 (67), 67 (15), 57 (31), 55 (10), 45 (27),
44 (13), 43 (20), 41 (59), 39 (23). 119Sn (d ppm): 121.
4.4.1. (E)-4-Iodobut-3-enoic acid (9a). Mp: 56–588C. IR
(KBr): 3450, 3065, 3010, 2910, 1701, 1614, 1421, 1398,
1290, 1213, 952. RAMAN: 3042, 3024, 2912, 1614, 1421,
1398, 1290, 1213, 952. 1H NMR (d ppm): 3.14 (dd, J¼7.1,
1.3 Hz, 2H), 6.30 (dt, J¼14.6, 1.3 Hz, 1H), 6.60 (dt, J¼14.6,
7.1 Hz, 1H), 10.36 (bs, 1H). 13C NMR (d ppm): 40.5, 79.7,
136.4, 176.3. MS (70 eV, EI) m/z: 212 (Mþ, 11), 167 (24),
127 (15), 85 (100), 57 (13), 45 (11), 39 (44), 29 (21). Anal.
calcd for C4H5IO2: C, 22.66; H, 2.38. Found: C, 22.72; H,
2.45.
4.6. Stille coupling of 7a, 8 or 9a with vinyltin reagents
7a (5 mmol) diluted in DMF (5 mL) was added to a DMF
soln of vinyltin reagent (5.5 mmol). At the end of the
addition, dichlorobis(acetonitrile)palladium (II) (65 mg,
5 mol%) was added. The mixture was stirred for 6 h at
508C then hydrolysed with a saturated solution of NH4Cl.
The organic layer was then treated with 1N NaOH solution
at 08C until the pH was .8. After washing with Et2O, the
aqueous layer was acidified with 1N HCl solution and
extracted with Et2O. The etheral solution was dried over
MgSO4. The solvent was removed and the crude products 10
or 11 were purified by column chromatography on silica gel
first with PE/Et2O 95/5 as eluent, then with EP/Et2O 70/30.
4.4.2. (E)-4-Iodo-3-2H-but-3-enoic acid (9b). Mp: 558C.
IR (KBr): 3065, 2832, 2235, 1715, 1687, 1211, 952, 843. 1H
NMR (d ppm): 3.17 (d, J¼1.4 Hz, 2H), 6.35 (t, J¼1.4 Hz,
1H), 10.5 (1H, bs). 13C NMR (d ppm): 40.1, 79.4 (t,
JC–D¼28 Hz), 110.3, 175.5. MS (70 eV, EI) m/z: 213 (Mþ,
8), 168 (12), 127 (13), 87 (10), 86 (100), 85 (24), 58 (13), 45
(22), 41 (20), 40 (68), 39 (49), 38 (13). Anal. calcd for
C4H4DIO2 C, 22.56; H, 2.84. Found: C, 22.59; H, 2.82.
4.6.1. (3E)-Hex-3,5-dienoic acid (10a). IR: 3088, 3022,
2966, 1713, 1653, 1604, 1417, 1292, 1221, 1005. 1H NMR
(d ppm): 3.21 (d, J¼7.1 Hz, 2H), 5.13 (dd, J¼10.0, 1.5 Hz,
1H), 5.23 (dd, J¼16.9, 1.5 Hz, 1H), 5.80 (dt, J¼15.0,
7.1 Hz, 1H), 6.14–6.48 (m, 2H), 10.22 (bs, 1H). 13C NMR
(d ppm): 37.6, 117.4, 124.6, 134.9, 136.2, 178.1. MS
(70 eV, EI) m/z: 112 (Mþ, 100), 83 (27), 67 (23), 66 (17), 65
(14), 55 (22), 53 (28), 45 (18), 39 (67). Anal. calcd for
C6H8O2: C, 64.27; H, 7.19. Found: C, 64.31; H, 7.23.
4.4.3. 4-Iodo-3-methylbut-3-enoic acid (9d). IR: 3400,
3057, 2957, 2927, 1705, 1616, 1443, 1373, 1288. 1H NMR
(d ppm): 1.99 (d, J¼1.1 Hz, 3H), 3.28 (d, J¼1.1 Hz, 2H),
6.25 (q, J¼1.1 Hz, 1H), 8.05 (bs, 1H). 13C NMR (d ppm):
23.9, 43.7, 80.3, 139.5, 176.5. MS (70 eV, EI) m/z: 226 (Mþ,
10), 99 (100), 81 (10), 71 (28), 54 (19), 53 (55), 45 (13), 43
(85), 41 (23), 39 (47). Anal. calcd for C5H7IO2: C, 26.57; H,
3.12. Found: C, 26.62; H, 3.15.
4.6.2. (3E, 5E)-8,8-Diethoxyoct-3,5-dienoic acid (10b).
IR: 3409, 3030, 2978, 2924, 1712, 1376, 1124, 1059, 985,
4.5. Iododestannylation: preparation of stannyl
iodobutenoate
1
730. H NMR (d ppm): 1.16 (t, J¼7.0 Hz, 6H), 2.39 (bt,
J¼6.3 Hz, 2H), 3.11 (d, J¼6.7 Hz, 2H), 3.45–3.68 (qd,
J¼7.0, 29.4 Hz, 4H), 4.50 (t, J¼5.6 Hz, 1H), 5.54–5.70
(m, 2H), 6.0–6.16 (m, 2H), 9.25 (bs, 1H). 13C NMR (d
ppm): 15.2 (2C), 37.1, 37.6, 61.2 (2C), 102.3, 122.8, 128.6,
132, 134, 177. MS (70 eV, EI) m/z: 183 (Mþ245, 75), 125
(100), 117 (13), 111 (85), 83 (25), 45 (20), 39 (50). Anal.
calcd for C12H20O4: C, 63.14; H, 8.83. Found: C, 63.18; H,
8.87.
At 08C, to vinylstannane 2a (12 mmol) in freshly distilled
Et2O (30 mL) was added iodine (3.5 g, 14 mmol) in Et2O
(35 mL). The mixture was stirred for 2 h at room
temperature. Excess I2 was eliminated by washing with a
0.5 M solution of sodium thiosulfate. The solution was then
hydrolysed with 25 mL of a saturated solution of potassium
fluoride and 25 mL of acetone in order to remove all the
tributyltin salts formed. After vigourous stirring for 3 h, the
reaction mixture was filtered over Celite, extracted with
Et2O and washed with brine. After usual treatments, the
crude stannyl ester 7a was purified by crystallisation with
PE/Et2O (90/10).
4.6.3. (3E, 5E)-6-Phenylhex-3,5-dienoic acid (10c). IR:
3088, 3019, 2910, 1699, 1641, 1413, 1293, 994. 1H NMR (d
ppm): 3.29 (d, J¼7.1 Hz, 2H), 5.92 (dt, J¼15.2, 7.1 Hz,
1H), 6.37 (dd, J¼15.2, 10.2 Hz, 1H), 6.56 (d, J¼15.6 Hz,
1H), 6.83 (dd, J¼15.6, 10.2 Hz, 1H), 7.26–7.45 (m, 5H),
10.20 (bs, 1H). 13C NMR (d ppm): 37.7, 124.4, 126.3 (2C),
127.5, 128, 128.5 (2C), 132.4, 134.4, 159, 177. MS (70 eV,
EI) m/z: 188 (Mþ, 15), 143 (10), 129 (22), 128 (100), 115
(21), 91 (11), 65 (12), 51 (11), 45 (23), 39 (20).
4.5.1. (E)-Tributylstannyl 4-iodobut-3-enoate (7a). Mp:
708C. IR: 3028, 1583, 1216, 1151. 1H NMR (d ppm): 0.94 (t,
J¼7.2 Hz, 9H), 1.16–1.7 (m, 18H), 3.08 (d, J¼7.3 Hz, 2H),
6.18 (d, J¼14.5 Hz, 1H), 6.69 (dt, J¼14.5, 7.3 Hz, 2H). 13C
NMR (d ppm): 13.5 (3C), 16.4 (JSn–C¼339–359 Hz, 3C),
26.9 (JSn–C¼66.7 Hz, 3C), 27.6 (JSn–C¼20.5 Hz, 3C), 41.4,
4.6.4. (E)-Hex-3-en-5-ynoic acid (10d). IR: 3303, 3043,

4440
J. Thibonnet et al. / Tetrahedron 59 (2003) 4433–4441
2253, 2106, 1712, 1649, 1419, 1293, 1229, 1073, 1020, 748.
1H NMR (d ppm): 2.93 (s, 1H), 3.24 (d, J¼7.0 Hz, 2H), 5.64
(d, J¼16.0 Hz, 1H), 6.32 (dt, J¼16.0, 7.0 Hz, 1H), 11.36
(bs, 1H). 13C NMR (d ppm): 37.6, 77.7, 81.1, 112.9, 136,
177. MS (70 eV, EI) m/z: 110 (Mþ, 34), 71 (100), 68 (30),
66 (24), 65 (59), 63 (19), 62 (11), 60 (11), 57 (11), 45 (22),
44 (10), 43 (81), 42 (51), 41 (43), 40 (37), 39 (100), 38 (19),
37 (10). Anal. calcd for C6H6O2: C, 65.45; H, 5.49. Found:
C, 65.49; H, 5.53.
solution obtained is acidified and extracted with diethyl
ether. The solvent is removed and crude 10 g is purified
using column chromatography on silica gel (PE/Et2O: 70/30
as an eluent).
4.7.1. (3E)-Pent-3-enoic acid (10e). IR: 3038, 1714, 1294,
1223, 970, 912. 1H NMR (d ppm): 1.72 (bd, J¼4.8 Hz, 3H),
3.08 (bd, J¼5.7 Hz, 2H), 5.60 (m, 2H), 10.9 (bs, 1H). 13C
NMR (d ppm): 17.7, 37.6, 121.8, 129.9, 178.6. MS (70 eV,
EI) m/z: 100 (Mþ, 53), 58 (13), 57 (10), 56 (15), 55 (100), 54
(22), 53 (17), 45 (16), 43 (16), 41 (30), 39 (39). Anal. calcd
for C5H8O2: C, 59.98; H, 8.05. Found: C, 60.05; H, 8.12.
4.6.5. (Z)-Tributylstannyl-4-trimethylsilyl-3-vinylbut-3-
enoate (11a). Mp: 848C. IR: 3092, 1581, 1556, 1392, 1250,
869, 837. 1H NMR (d ppm): 0.19 (s, 9H), 0.94 (t, J¼7.2 Hz,
9H), 1.23–1.83 (m, 18H), 3.32 (d, J¼0.8 Hz, 2H), 5.18 (d,
J¼10.9 Hz, 1H), 5.33 (d, J¼17.3 Hz, 1H), 5.72 (d,
J¼0.8 Hz, 1H), 6.65 (dd, J¼17.3, 10.9 Hz, 1H). 13C NMR
(d ppm): 20.7 (3C), 13.5 (3C), 16.3 (JSn–C¼342–358 Hz,
3C), 26.9 (JSn–C¼65 Hz, 3C), 27.7 (JSn–C¼20 Hz, 3C),
42.8, 115, 134.8, 137, 147.6, 176.8. MS (70 eV, EI) m/z: 417
(Mþ257, 31), 373 (27), 291 (39), 249 (68), 235 (22), 193
(26), 179 (38), 177 (45), 135 (25), 133 (19), 123 (14), 121
(22), 79 (13), 75 (56), 73 (59), 61 (14), 59 (27), 57 (35), 56
(10), 55 (19), 45 (41), 44 (22), 43 (42), 41 (100), 39 (40).
4.7.2. (3E)-Hex-3-enoic acid (10f). IR: 3350, 3042, 2968,
2935, 1714, 1410, 1290, 1223, 968. 1H NMR (d ppm): 1.01
(t, J¼7.4 Hz, 3H), 2.08 (m, J¼7.4 Hz, 2H), 3.09 (dd, J¼6.4,
0.8 Hz, 2H), 5.44–5.73 (m, 2H), 10.5 (bs, 1H). 13C NMR (d
ppm): 13.8, 26, 38.3, 120.5, 137.4, 179.2. MS (70 eV, EI)
m/z: 114 (Mþ, 28), 73 (14), 69 (31), 68 (43), 67 (14), 60
(34), 57 (17), 55 (68), 54 (11), 53 (18), 45 (22), 43 (17), 42
(22), 41 (100), 40 (10), 39 (55). Anal. calcd for C6H10O2: C,
63.14; H, 8.83. Found: C, 63.18; H, 8.89.
4.7.3. (3E)-5-Phenylpent-3-enoic acid (10g). IR: 3450,
3088, 3063, 3028, 2880, 1709, 1664, 1600, 1580, 1207,
4.6.6. (Z)-3-(20-Trimethylsilylethenyl)-5-trimethylsilyl-
pent-4-enoic acid (11b). Mp: 708C. IR: 2956–2855,
1714, 1701, 1574, 1550, 1250, 850, 800. 1H NMR (d
ppm): 0.07 (s, 9H), 0.14 (s, 9H), 3.29 (s, 2H), 5.72 (s, 1H),
5.96 (d, J¼19.0 Hz, 1H), 6.80 (d, J¼19.0 Hz, 1H), 9.50 (bs,
1H). 13C NMR (d ppm): 21.64 (3C), 0.22 (3C), 41.8, 131.1,
136.2, 136.7, 143.7, 178.2. MS (70 eV, EI) m/z: 256 (Mþ,
4), 75 (17), 73 (100), 45 (12). Anal. calcd for C12H24O2Si2:
C, 56.19; H, 9.43. Found: C, 56.25; H, 9.51.
1
1022. H NMR (d ppm): 3.15 (d, J¼6.2 Hz, 2H), 3.44 (d,
J¼6.4 Hz, 2H), 5.68 (dt, J¼15.3, 6.4 Hz, 1H), 5.80 (dt,
J¼15.3, 6.2 Hz, 1H), 7.22–7.44 (m, 5H), 9.70 (bs, 1H). 13C
NMR (d ppm): 37.5, 41.2, 123.8, 126.9, 129 (2C), 129.7
(2C), 137.4, 139.6, 177.1. MS (70 eV, EI) m/z: 176 (Mþ,
73), 131 (82), 130 (25), 129 (32), 128 (14), 117 (37), 116
(57), 115 (66), 91 (100), 89 (13), 77 (10), 65 (35), 63 (15),
51 (17), 45 (26), 39 (24). Anal. calcd for C11H12O2: C,
74.98; H, 6.86. Found: C, 74.90; H, 6.89.
4.6.7. (Z)-7,7-Diethoxy-3-(20-trimethylsilylethenyl)hept-
4-enoic acid (11c). IR: 2990, 2970, 2950, 1730, 1650,
4.7.4. (3E)-7-Methoxyhept-2-en-3-ynoic acid (10h). IR:
3460, 2939, 2832, 2204, 1712, 1619, 1313, 1150. 1H NMR
(d ppm): 3.21 (dd, J¼7.2, 1.4 Hz, 2H), 3.42 (s, 3H), 4.26 (d,
J¼1.7 Hz, 2H), 5.68 (dd, J¼15.9, 1.7 Hz, 1H), 6.25 (dd,
J¼15.9, 7.2 Hz, 1H), 10.5 (bs, 1H). 13C NMR (d ppm): 38.2,
57.8, 60.5, 83.1, 96.8, 124.5, 138.6, 176.8. MS (70 eV, EI)
m/z: 154 (Mþ, 18), 139 (100), 123 (21), 111 (83), 109 (20),
99 (15), 95 (20), 93 (33), 83 (52), 69 (18), 68 (22), 67 (43),
55 (12), 45 (30), 42 (22), 41 (39), 40 (10), 39 (55). Anal.
calcd for C8H10O3: C, 62.33; H, 6.54. Found: C, 62.36; H,
6.58.
1
1580. H NMR (d ppm): 0.18 (s, 9H), 0.93 (t, J¼7.1 Hz,
6H), 2.48 (dd, J¼5.9, 5.7 Hz, 2H), 3.30 (s, 2H), 3.57–3.68
(m, 4H), 4.54 (t, J¼5.7 Hz, 1H), 5.61 (s, 1H), 5.80 (dt,
J¼15.7, 5.9 Hz, 1H), 6.46 (d, J¼15.7 Hz, 1H), 9.0 (bs, 1H).
13C NMR (d ppm): 0.66 (3C), 15.7 (2C), 38.2, 43.0, 61.7
(2C), 96.3, 102.7, 127.2, 133.4, 177.5. MS (70 eV, EI) m/z:
255 (Mþ245, 18), 211 (14), 197 (35), 167 (10), 103 (100),
93 (20), 75 (97), 73 (50), 45 (23). Anal. calcd for
C15H28O4Si: C, 59.96; H, 9.39. Found: C, 59.91; H, 9.43.
4.7. Procedure for the substitution with organozinc
reagents
Acknowledgements
Zinc bromide (7 g, 31 mmol) is added to an etheral solution
of benzylmagnesium bromide, made from magnesium
(0.729 g, 30 mmol) and benzylbromide (5.13 g, 32 mmol)
in anhydrous ether (30 mL). The solution is stirred
overnight at room temperature. THF (15 mL) and DMF
(15 mL) are then added to the newly prepared organozinc
until a homogeneous solution is obtained. Next, 9a
(10 mmol) diluted in DMF (5 mL) is added dropwise. At
the end of the addition, dichlorobis(acetonitrile)palladium(II)
(0.52 mg, 0.2 mmol) is added. The mixture is stirred for
12 h at 258C then hydrolysed with a cold solution of
hydrochloric acid (1N) and washed with a saturated solution
of ammonium chloride. The organic phase is treated at 08C
with a solution of sodium hydroxide (1N). The aqueous
We thank the CNRS and MESR for financial support, the
‘Service d’analyse du vivant de Tours’ for recording NMR
´
and mass spectra and the ‘Conseil Regional de la Region
Centre’ for the fellowship granted to J. T.
´
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