Synthesis of multisubstituted 1,3-butadienes using the ruthenium-catalysed double addition of trimethylsilyldiazomethane to alkynylboronates

Article abstract of DOI:10.1039/b501990g

The ruthenium-catalysed double addition of trimethylsilyldiazomethane to alkynes developed by Dixneuf and co-workers was applied to the synthesis of 2-alkyl- or 2-aryl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)1,4- bis(trimethylsilyl)-1,3-butadienes

Full text of DOI:10.1039/b501990g

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A R T I C L E
Synthesis of multisubstituted 1,3-butadienes using the
ruthenium-catalysed double addition of trimethylsilyldiazomethane
to alkynylboronates
Ryotaro Morita,a Eiji Shirakawa,*b Teruhisa Tsuchimotoa and Yusuke Kawakamia
a Graduate School of Materials Science, Japan Advanced Institute of Science and Technology,
Asahidai, Nomi, Ishikawa, 923-1292, Japan
b Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto,
606-8502, Japan. E-mail: shirakawa@kuchem.kyoto-u.ac.jp; Fax: +81-75-753-3988;
Tel: +81-75-753-3985
Received 17th December 2004, Accepted 7th February 2005
First published as an Advance Article on the web 28th February 2005
The ruthenium-catalysed double addition of trimethylsilyldiazomethane to alkynes developed by Dixneuf
and co-workers was applied to the synthesis of 2-alkyl- or 2-aryl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
1,4-bis(trimethylsilyl)-1,3-butadienes by use of alkynylboronates instead of alkynes. Di- and tetrasubstituted
1,3-butadienes were prepared from a 2-boryl-1,4-disilyl-1,3-butadiene, using the Suzuki–Miyaura coupling reaction,
iodolysis of the alkenylsilane moieties with N-iodosuccinimide and hydrolysis of the carbon–silicon bonds with triflu-
oroacetic acid. The same compound was converted also to a bicyclic compound, a trisubstituted 1,3-butadiene and a
dienone through the Diels–Alder reaction, oxidation of the alkenylboronate moiety and the Mukaiyama aldol reaction.
electron-withdrawing or -donating group underwent the double
addition at lower temperature than aliphatic alkynylboronates
Introduction
Conjugated dienes are versatile synthetic precursors, which in
(entries 5–7).
particular undergo addition reactions in combination with tran-
sition metal catalysts.1 Although much effort has been devoted
to development of methods to prepare conjugated dienes,2
it is still difficult to synthesize multisubstituted ones using
readily available compounds.3,4 Mori and co-workers reported
an excellent route to 2,3-disubstituted 1,3-butadienes from
readily available internal alkynes and ethenes by ruthenium-
catalysed enyne metathesis.5 Dixneuf and co-workers expanded
the strategy that utilizes the reaction of ruthenium–carbene
complexes with alkynes by using trimethylsilyldiazomethane (1)
or ethyl diazoacetate as a carbene source, where double addition
of diazoalkanes to alkynes afforded 1,2,3,4-tetrasubsituted 1,3-
butadienes.6 We expected that introduction of a transformable
group to the alkyne moiety in addition to conversion of the
silyl group derived from 1 to organic groups would enhance
the utility of the Dixneuf excellent method. Here we report
the ruthenium-catalysed double addition of trimethylsilyldia-
zomethane to alkynylboronates to give 2-boryl-3-organo-1,4-
disilyl-1,3-butadienes, which can be converted into multisub-
stituted 1,3-butadienes including those having four different
organic groups at the 1-, 2-, 3- and 4-positions.
(1)
The double addition products can be transformed to multi-
substituted 1,3-butadienes using the Suzuki–Miyaura coupling
protocol (Scheme 1).3a–c For example, alkenylboronate 3a was
subjected to the coupling reaction with iodobenzene to give
1,4-disilyl-1,3-butadiene 4,9 which underwent selective iodolysis
of the Si–C bond on the more electron-rich alkyl-substituted
double bond by treatment with 1.0 equiv. of N-iodosuccinimide
◦
(NIS) at 0 C.10 Alkenyl iodide 5 cross-coupled with p-
tolylboronic acid again using the Suzuki–Miyaura coupling
reaction to afford monosilyldiene 6 in 81% yield.11 Iodolysis of 6
with NIS at room temperature gave alkenyl iodide 7, which was
transformed to 1,3-butadiene 8 having four different organic
groups at 1-, 2-, 3- and 4-positions.11 Alternatively, both of
the Si–C bonds in 4 were iodolysed to give diiodide 9, which
reacted with p-tolylboronic acid leading to tetrasubstituted 1,3-
butadiene 10 with three different organic groups.11 Disubstituted
diene 11 was obtained by hydrolysis of disilyldiene 4 with
trifluoroacetic acid.12
In addition to the transformation based on the Suzuki–
Miyaura coupling reaction, the double addition products
are applicable to other carbon–carbon bond forming reac-
tions (Scheme 2). For example, the reaction of 3a with N-
phenylmaleimide gave Diels–Alder product 12, where the boryl
group was unaffected.13 Oxidation of the alkenylboronate moi-
ety of 3a with hydrogen peroxide–urea complex14 followed by
treatment with trimethylsilyl triflate afforded diene 1415 having
a silyl enolate moiety through ketone 13; 14 then underwent the
boron trifluoride-catalysed Mukaiyama aldol reaction to give
dienone 15.16
Results and discussion
The Dixneuf reaction conditions can be applied to the double
addition of 1 to diisopropyl alkynylboronates (2) essentially
as they stand but hexane was found to be a better solvent
than 1,4-dioxane. Thus, treatment of 1 and diisopropyl 1-
octynylboronate (2a) with 10 mol% of Cp*Ru(cod)Cl in hex-
◦
ane at 80 C for 12 h followed by transesterification7 with
pinacol provided 4,4,5,5-tetramethyl-2-[(1E,3E)-3-hexyl-1,4-
bis(trimethylsilyl)buta-1,3-dien-2-yl]-1,3,2-dioxaborolane (3a)8
in 82% yield (eqn. (1) and entry 1 of Table 1). Various
alkynylboronates accepted the double addition of the carbene
to give 2-boryl-3-organo-1,4-disilyl-1,3-butadienes (Table 1).
Chloroalkane and ether moieties were compatible with the
addition (entries 2 and 3). An ethynylboronate having an
electron-withdrawing group participated in the reaction (entry
4). A phenylethynylboronate, and related compounds having an
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 6 3 – 1 2 6 8
1 2 6 3
©

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Table 1 Ruthenium-catalysed double addition of trimethylsilyldiazomethane to alkynylboronatesa
Entry
1
R
T/◦C
t/h
Product
Yield (%)b
82
Hex
80
12
2
Cl(CH2)3
MeOCH2
EtOCO
Ph
80
80
80
0
12
12
12
48
24
73
83
64
77
81
3
4
5
6c
4-CF3-C6H4
0
7c
4-MeO-C6H4
0
7
72
a The reaction was carried out in hexane (0.2 mL) using trimethylsilyldiazomethane (1: 0.4 mL of a 2.0 M solution in hexane, 0.80 mmol), an
alkynylboronate (2: 0.20 mmol) and Cp*Ru(cod)Cl (20 lmol), which was followed by transesterification with pinacol. b Isolated yield based on the
alkynylboronate. c Transesterification was done in the presence of a catalytic amount of acetic acid.
recycling gel permeation chromatography was performed with a
Conclusion
JAI LC-908 equipped with JAIGEL-1H and -2H using chloro-
We have disclosed a convenient method to prepare multisubsti-
form as an eluent. High-resolution mass spectra were obtained
tuted 1,3-butadienes, utilizing the ruthenium-catalysed double
addition of trimethylsilyldiazomethane to alkynylboronates.
The combination of the ruthenium-catalysed reaction with the
palladium-catalysed Suzuki–Miyaura coupling reaction enables
with a Bruker Bio APEX 70e (EI) or JEOL JMS-HX110A
(FAB+) spectrometer. Unless otherwise noted, reagents were
commercially available and used without further purification.
Hexane, diethyl ether, THF and toluene were distilled from
us to prepare highly conjugated systems based on the 1,3-
sodium/benzophenone ketyl. Cp*Ru(cod)Cl was prepared ac-
butadiene framework.
cording to the literature procedure.17
Experimental
Preparation of alkynylboronates. A general procedure18
General remarks
To a solution of an alkyne (10 mmol) in diethyl ether (20 mL)
was added BuLi (1.56 M in hexane, 6.4 mL, 10 mmol) at −78 ◦C
and the reaction mixture was stirred for 3 h at −78 ◦C. The
resulting mixture was added to a solution of triisopropyl borate
(1.88 g, 10 mmol) in diethyl ether (20 mL) and slowly warmed to
room temperature over 3 h. The solvent was removed in vacuo for
All manipulations of oxygen- and moisture-sensitive materials
were conducted with standard Schlenk techniques under a
nitrogen atmosphere. Nuclear magnetic resonance spectra were
taken on a Varian Gemini 2000 (1H, 300 MHz) or a Varian
UNITY 500 plus (13C, 126 MHz) spectrometer. Preparative
1 2 6 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 6 3 – 1 2 6 8

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Scheme 1 Transformation of double addition product 3a to di- and tetrasubstituted 1,3-butadienes.
Scheme 2 Transformation of double addition product 3a to a bicyclic compound and a dienone.
24 h. Diethyl ether (10 mL) and anhydrous hydrogen chloride
(1.5 M diethyl ether solution, 6.6 mL, 10 mmol) were added
(d, J = 6.0 Hz, 12 H), 4.65 (sept, J = 6.0 Hz, 2 H), 7.28–7.38
(m, 3 H), 7.47–7.55 (m, 2 H).
◦
to the resulting powder at −78 C and the mixture was slowly
Diisopropyl 4-(trifluoromethyl)phenylethynylboronate (2f).
warmed to room temperature over 3 h. Filtration of the resulting
◦
1
suspension followed by distillation gave alkynylboronates 2.18
Bp 70 C/0.2 mmHg, a pale yellow oil. H NMR (300 MHz,
CDCl3): d 1.25 (d, J = 6.3 Hz, 12 H), 4.64 (sept, J = 6.3 Hz,
2 H), 7.57–7.61 (m, 4 H).
Diisopropyl oct-1-ynylboronate (2a). Bp 70 ◦C/0.3 mmHg, a
colorless oil. 1H NMR (300 MHz, CDCl3): d 0.89 (t, J = 6.9 Hz,
3 H), 1.19 (d, J = 6.0 Hz, 12 H), 1.24–1.60 (m, 8 H), 2.27 (t, J =
6.9 Hz, 2 H), 4.55 (sept, J = 6.0 Hz, 2 H).
Diisopropyl 4-methoxyphenylethynylboronate (2g). Bp 75 ◦C/
1
0.2 mmHg, a pale yellow oil. H NMR (300 MHz, CDCl3): d
Diisopropyl 5-chloropent-1-ynylboronate (2b). Bp 60 ◦C/0.2
mmHg, a colorless oil. 1H NMR (300 MHz, CDCl3): d 1.19 (d,
J = 6.0 Hz, 12 H), 2.00 (quint, J = 6.6 Hz, 2 H), 2.48 (t, J =
6.6 Hz, 2 H), 3.66 (t, J = 6.6 Hz, 2 H), 4.54 (sept, J = 6.0 Hz,
2 H).
1.24 (d, J = 6.3 Hz, 12 H), 3.81 (s, 3 H), 4.64 (sept, J = 6.3 Hz,
2 H), 6.81–6.87 (m, 2 H), 7.42–7.48 (m, 2 H).
Ruthenium-catalysed double addition of
trimethylsilyldiazomethane to alkynylborates.
A general procedure
◦
Diisopropyl 3-methoxyprop-1-ynylboronate (2c). Bp 60 C/
1.0 mmHg, a colorless oil. 1H NMR (300 MHz, CDCl3): d 1.20
(d, J = 6.3 Hz, 12 H), 3.40 (s, 3 H), 4.16 (s, 2 H) 4.57 (sept, J =
6.3 Hz, 2 H).
A solution (0.2 mL) of an alkynylboronate (0.20 mmol) and
Cp*Ru(cod)Cl (7.6 mg, 20 lmol) in hexane (0.2 mL) was
degassed by three freeze–thaw cycles. To the solution was added
trimethylsilyldiazomethane (2.0 M◦ hexane solution, 0.4 mL,
0.80 mmol), and stirred at 80 or 0 C. After the time specified
in Table 1, the solvent was evaporated, and benzene (1.0 mL)
and pinacol (11.8 mg, 1.00 mmol) was added to the resulting
mixture [for entries 6 and 7 in Table 1, acetic acid (0.6 mg.
0.01 mmol) also was added]. After stirring at room temperature
for 12–48 h, evaporation of the solvent followed by purification
Diisopropyl (ethoxycarbonyl)ethynylboronate (2d). Bp 60 ◦C/
1
0.1 mmHg, a pale yellow oil. H NMR (300 MHz, CDCl3): d
1.21 (d, J = 6.3 Hz, 12 H), 1.31 (t, J = 7.2 Hz, 3 H), 4.25 (q, J =
7.2 Hz, 2 H), 4.56 (sept, J = 6.3 Hz, 2 H).
Diisopropyl phenylethynylboronate (2e). Bp 80 ◦C/0.3
mmHg, a pale yellow oil. 1H NMR (300 MHz, CDCl3): d 1.25
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 6 3 – 1 2 6 8
1 2 6 5

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by gel permeation chromatography gave the corresponding 1,3-
butadiene. Yields are listed in Table 1.
Determination of configuration of the double addition products
with NOESY NMR spectra
Double addition products 3a and 3e as the representatives
were subjected to NOESY NMR measurement. The cross-peak
between the methyl protons of one of the trimethylsilyl groups
and R (3a: the methylene protons of the allylic position of
the hexyl group; 3e: the ortho-protons of the phenyl group)
in addition to that between the methyl protons of the other
trimethylsilyl group and the methyl protons of the pinacol ester
were observed. These results in conjunction with other observed
cross-peaks shown below should show that the silyl groups are
located cis to R or the boronate group.
4,4,5,5-Tetramethyl-2-[(1E,3E)-3-hexyl-1,4-bis(trimethylsilyl)-
buta-1,3-dien-2-yl]-1,3,2-dioxaborolane (3a). A pale yellow oil.
1H NMR (300 MHz, CDCl3): d 0.11 (s, 9 H), 0.15 (s, 9 H), 0.88
(t, J = 6.9 Hz, 3 H), 1.22–1.38 (m, 8 H), 1.31 (s, 12 H), 2.28–2.37
(m, 2 H), 5.45 (s, 1 H), 6.35 (s, 1 H). 13C NMR (126 MHz,
CDCl3): d 0.2, 0.3, 14.0, 22.6, 25.3, 29.5, 29.6, 31.7, 34.0, 83.6,
127.1, 142.7, 163.1; the resonance of C–B was not detected due
to the low intensity. HRMS (EI): Calcd for C22H45BO2Si2 [M]+,
408.30486; found, 408.30689.
4,4,5,5-Tetramethyl-2-[(1E,3E)-3-(3-chloropropyl)-1,4-bis(tri-
methylsilyl)buta-1,3-dien-2-yl]-1,3,2-dioxaborolane
pale yellow oil. H NMR (300 MHz, CDCl3): d 0.13 (s, 9 H),
(3b).
A
1
0.15 (s, 9 H), 1.31 (s, 12 H), 1.75–1.87 (m, 2 H), 2.47–2.55 (m,
2 H), 3.52 (t, J = 6.6 Hz, 2 H), 5.51 (s, 1 H), 6.37 (s, 1 H). 13
C
NMR (126 MHz, CDCl3): d 0.2, 0.3, 25.3, 31.3, 32.4, 45.1, 83.7,
128.5, 143.8, 161.1; the resonance of C–B was not detected due
to the low intensity. HRMS (EI): Calcd for C19H38BClO2Si2
[M]+, 400.21897; found, 400.22044.
4,4,5,5-Tetramethyl-2-[(1E,3Z)-3-methoxymethyl-1,4-bis(tri-
methylsilyl)buta-1,3-dien-2-yl]-1,3,2-dioxaborolane
(3c).
A
1
pale yellow oil. H NMR (300 MHz, CDCl3): d 0.12 (s, 9 H),
0.15 (s, 9 H), 1.30 (s, 12 H), 3.24 (s, 3 H), 4.19 (s, 2 H), 5.74 (s, 1 H),
6.57 (s, 1 H). 13C NMR (126 MHz, CDCl3): d 0.3, 0.4, 25.2,
57.3, 73.2, 83.5, 129.2, 145.8, 159.3; the resonance of C–B was
not detected due to the low intensity. HRMS (EI): Calcd for
C18H37BO3Si2 [M–Me]+, 353.21375; found, 353.21404.
4,4,5,5-Tetramethyl-2-[(1E,3Z)-3-ethoxycarbonyl-1,4-bis(tri-
methylsilyl)buta-1,3-dien-2-yl]-1,3,2-dioxaborolane
(3d).
A
pale yellow solid. 1H NMR (300 MHz, CDCl3): d 0.14 (s, 9 H),
0.16 (s, 9 H), 1.28 (s, 12 H), 1.31 (t, J = 7.2 Hz, 3 H), 4.20
(q, J = 7.2 Hz, 2 H), 6.27 (s, 1 H), 6.53 (s, 1 H). 13C NMR
(126 MHz, CDCl3): d −0.3, 0.2, 14.2, 25.1, 60.6, 83.7, 139.6,
149.2, 153.7, 168.5; the resonance of C–B was not detected due
to the low intensity. HRMS (EI): Calcd for C19H37BO4Si2 [M]+,
396.23212; found, 396.23377.
The coupling reaction of 4,4,5,5-tetramethyl-2-[(1E,3E)-3-hexyl-
1,4-bis-(trimethylsilyl)buta-1,3-dien-2-yl]-1,3,2-dioxaborolane
(3a) with iodobenzene9
A solution of 3a (40.9 mg, 0.100 mmol), iodobenzene (30.6 mg,
0.150 mmol), Pd(PPh3)4 (57.8 mg, 0.050 mmol) and NaOEt
(0.5 M ethanol solution, 0.3 mL, 0.150 mmol) in ethanol
(1.0 mL) was degassed by three freeze–thaw cycles. After the
solution was stirred at 80 ◦C for 72 h, water (10 mL) was
added and the resulting mixture was extracted with diethyl
ether (20 mL × 3). The combined organic layer was washed
with brine (10 mL) and dried over anhydrous magnesium
sulfate. Evaporation of the solvent followed by purification by
gel permeation chromatography gave (1E,3E)-3-hexyl-2-phenyl-
1,4-bis(trimethylsilyl)buta-1,3-diene (4: 25.3 mg, 71%) as a pale
yellow oil. 1H NMR (300 MHz, CDCl3): d −0.21 (s, 9 H), 0.07
(s, 9 H), 0.89 (t, J = 7.2 Hz, 3 H), 1.20–1.51 (m, 8 H), 2.30–2.39
(m, 2 H), 5.24 (s, 1 H), 5.89 (s, 1H), 7.05–7.10 (m, 2 H), 7.23–7.31
(m, 3 H). 13C NMR (126 MHz, CDCl3): d −0.1, 0.2, 14.0, 22.6,
29.5, 29.8, 31.7, 33.6, 126.8, 127.5, 128.2, 129.5, 130.5, 142.8,
159.9, 160.2. HRMS (EI): Calcd for C22H38Si2 [M]+, 358.25100;
found, 358.25029.
4,4,5,5-Tetramethyl-2-[(1E,3Z)-3-phenyl-1,4-bis(trimethyl-
silyl)buta-1,3-dien-2-yl]-1,3,2-dioxaborolane (3e). A pale yellow
solid. 1H NMR (300 MHz, CDCl3): d −0.22 (s, 9 H), 0.09 (s, 9 H),
1.31 (s, 12 H), 5.95 (s, 1 H), 6.01 (s, 1 H), 7.08–7.14 (m, 2 H),
7.21–7.31 (m, 3 H). 13C NMR (126 MHz, CDCl3): d −0.4, 0.1,
25.4, 83.9, 126.9, 127.5, 130.0, 131.7, 141.9, 145.2, 161.9; the
resonance of C–B was not detected due to the low intensity.
HRMS (EI): Calcd for C22H37BO2Si2 [M]+, 400.24230; found,
400.24404.
4,4,5,5-Tetramethyl-2-[(1E,3Z)-3-{4-(trifluoromethyl)phe-
nyl}-1,4-bis(trimethylsilyl)buta-1,3-dien-2-yl]-1,3,2-dioxaboro-
1
lane (3f). A pale yellow solid. H NMR (300 MHz, CDCl3):
d −0.21 (s, 9 H), 0.10 (s, 9 H), 1.30 (s, 12 H), 5.95 (s, 1 H),
6.03 (s, 1 H), 7.23–7.25 (m, 2 H), 7.54–7.57 (m, 2 H). 13C NMR
1
(126 MHz, CDCl3): d −0.2, 0.0, 25.4, 84.0, 124.4 (q, JC
=
–F
Partial iodolysis of (1E,3E)-3-hexyl-2-phenyl-1,4-bis(tri-
272 Hz), 124.5 (q, 3JC = 3.8 Hz), 129.3 (q, 2JC = 32.7 Hz),
methylsilyl)buta-1,3-diene (4)10
–F
–F
130.2, 132.5, 146.0, 146.4, 160.4; the resonance of C–B was
not detected due to the low intensity. HRMS (EI): Calcd for
C23H36BF3O2Si2 [M]+, 468.22968; found, 468.22868.
N-Iodosuccinimide (9.0 mg, 0.040 mmol) was added to a
solution of 4 (14.3 mg, 0.040 mmol) in propionitrile (0.5 mL)
◦
◦
at −50 C. The reaction was slowly warmed to 0 C over 6 h,
at which time a saturated sodium thiosulfate aqueous solution
(5.0 mL) was added. The mixture was extracted with diethyl
ether (10 mL × 3), then the combined organic layers were
washed with brine (10 mL) and dried over anhydrous magnesium
sulfate. Evaporation of the solvent followed by purification by
gel permeation chromatography gave (1E,3E)-2-hexyl-1-iodo-
3-phenyl-4-(trimethylsilyl)buta-1,3-diene (5: 12.9 mg, 78%) as
4,4,5,5-Tetramethyl-2-[(1E,3Z)-3-(4-methoxyphenyl)-1,4-bis-
(trimethylsilyl)buta-1,3-dien-2-yl]-1,3,2-dioxaborolane (3g).
A
pale yellow solid. 1H NMR (300 MHz, CDCl3): d −0.20 (s, 9 H),
0.09 (s, 9 H), 1.31 (s, 12 H), 3.82 (s, 3 H), 5.91 (s, 1 H), 6.02
(s, 1 H), 7.00–7.03 (m, 2 H), 7.03–7.06 (m, 2 H). 13C NMR
(126 MHz, CDCl3): d −0.1, 0.0, 25.5, 55.2, 83.8, 112.9, 131.0,
131.3, 134.4, 144.9, 158.8, 161.6; the resonance of C–B was
not detected due to the low intensity. HRMS (EI): Calcd for
C23H39BO3Si2 [M]+, 430.25285; found, 430.25077.
1
a pale yellow oil. H NMR (300 MHz, CDCl3): d −0.20 (s,
9 H), 0.91 (t, J = 6.6 Hz, 3 H), 1.24–1.50 (m, 8 H), 2.42–2.52
1 2 6 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 6 3 – 1 2 6 8

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(m, 2 H), 5.95 (s, 1 H), 6.05 (s, 1 H), 7.04–7.12 (m, 2 H), 7.26–7.33
(m, 3 H). 13C NMR (126 MHz, CDCl3): d −0.3, 14.0, 22.6, 27.8,
29.1, 31.6, 35.2, 85.1, 127.4, 127.8, 129.4, 130.2, 141.4, 154.1,
155.5. HRMS (EI): Calcd for C19H29ISi [M]+, 412.10817; found,
412.10655.
130.3, 130.8, 135.6, 136.0, 140.3, 143.2, 145.3, 158.2. HRMS
(FAB+): Calcd for C30H34O [M]+, 410.26079; found, 410.2613.
Iodolysis of (1E,3E)-3-hexyl-2-phenyl-1,4-bis(trimethylsilyl)-
buta-1,3-diene (4)10
N-Iodosuccinimide (90.0 mg, 0.400 mmol) was added to a
solution of 4 (35.9 mg, 0.100 mmol) in propionitrile (1 mL)
at room temperature and the solution was stirred at the
temperature for 24 h. The resulting mixture was treated with
a saturated sodium thiosulfate aqueous solution (1.0 mL) and
extracted with diethyl ether (10 mL × 3). The combined organic
layer was washed with brine (10 mL) and dried over anhydrous
magnesium sulfate. Evaporation of the solvent followed by
purification by gel permeation chromatography gave (1E,3E)-
3-hexyl-1,4-diiodo-2-phenylbuta-1,3-diene (9: 33.6 mg, 72%) as
The coupling reaction of (1E,3E)-2-hexyl-1-iodo-3-phenyl-4-
(trimethylsilyl)buta-1,3-diene (5) with p-tolylboronic acid11
A mixture of 5 (24.7 mg, 0.060 mmol), p-tolylboronic acid
(16.3 mg, 0.120 mmol), Pd(PPh3)4 (3.5 mg, 0.003 mmol), Na2CO3
(15.3 mg, 0.144 mmol), toluene (0.5 mL) and methanol (0.1 mL)
was degassed by three freeze–thaw cycles. After the solution
was stirred at 120 ◦C for 6 h, water (10 mL) was added
and the resulting mixture was extracted with diethyl ether
(20 mL × 3). The combined organic layer was washed with
brine (10 mL) and dried over anhydrous magnesium sulfate.
Evaporation of the solvent followed by purification by gel
permeation chromatography gave (1Z,3E)-3-hexyl-2-phenyl-4-
(p-tolyl)-1-(trimethylsilyl)buta-1,3-diene (6: 18.4 mg, 81%) as a
pale yellow oil. 1H NMR (300 MHz, CDCl3): d −0.19 (s, 9 H),
0.89 (t, J = 6.6 Hz, 3 H), 1.24–1.60 (m, 8 H), 2.32 (s, 3 H), 2.41–
2.50 (m, 2 H), 5.95 (s, 1 H), 6.05 (s, 1 H) 7.03–7.12 (m, 4 H),
7.14–7.19 (m, 2 H), 7.26–7.34 (m, 3 H). 13C NMR (126 MHz,
CDCl3): d −0.1, 14.0, 21.1, 22.6, 28.2, 29.1, 29.4, 31.5, 126.9,
127.6, 128.4, 128.7, 128.8, 129.7, 131.1, 135.6, 136.1, 142.8,
145.4, 159.0. HRMS (EI): Calcd for C26H36Si [M]+, 376.25844;
found, 376.25921.
1
a pale yellow oil. H NMR (300 MHz, CDCl3): d 0.90 (t, J =
6.6 Hz, 3 H), 1.20–1.48 (m, 8 H), 2.30–2.38 (m, 2 H), 6.28 (s,
1 H), 6.79 (s, 1 H), 7.12–7.18 (m, 2 H), 7.36–7.43 (m, 3 H). 13
C
NMR (126 MHz, CDCl3): d 14.0, 22.5, 27.5, 29.0, 31.5, 35.4,
81.0, 84.6, 128.2, 128.4, 128.9, 140.2, 151.9, 152.1. HRMS (EI):
Calcd for C16H20I2 [M]+, 465.96534; found, 465.96717.
The coupling reaction of (1E,3E)-3-hexyl-1,4-diiodo-2-phenyl-
buta-1,3-diene (9) with p-tolylboronic acid11
A mixture of 9 (23.3 mg, 0.050 mmol), p-tolylboronic acid
(27.2 mg, 0.200 mmol), Pd(PPh3)4 (5.8 mg, 0.005 mmol), Na2CO3
(23.3 mg, 0.220 mmol), toluene (1.0 mL) and methanol (0.2 mL)
was degassed by three freeze–thaw cycles. After the solution was
stirred at 50 ◦C for 15 h, water (10 mL) was added and the
resulting mixture was extracted with diethyl ether (20 mL × 3).
The combined organic layer was washed with brine (10 mL)
and dried over anhydrous magnesium sulfate. Evaporation of
the solvent followed by purification by column chromatography
on silica gel (hexane) gave (1Z,3E)-3-hexyl-2-phenyl-1,4-di(p-
tolyl)buta-1,3-diene (10: 15.5 mg, 79%) as a pale yellow solid. 1H
NMR (300 MHz, CDCl3): d 0.87 (t, J = 6.9 Hz, 3 H), 1.20–1.38
(m, 6 H), 1.52–1.65 (m, 2 H), 2.25 (s, 3 H), 2.34 (s, 3 H), 2.42–2.48
(m, 2 H), 6.37 (s, 1 H), 6.75 (s, 1 H), 6.78–6.82 (m, 2 H), 6.89–6.93
Iodolysis of (1Z,3E)-3-hexyl-2-phenyl-4-(p-tolyl)-1-(trimethyl-
silyl)buta-1,3-diene (6)10
N-Iodosuccinimide (45.0 mg, 0.200 mmol) was added to a
solution of 6 (37.6 mg, 0.100 mmol) in propionitrile (1 mL)
at room temperature and the solution was stirred at the
temperature for 24 h. The resulting mixture was treated with
a saturated sodium thiosulfate aqueous solution (1.0 mL) and
extracted with diethyl ether (10 mL × 3). The combined organic
layer was washed with brine (10 mL) and dried over anhydrous
magnesium sulfate. Evaporation of the solvent followed by
purification by gel permeation chromatography gave (1Z,3E)-
3-hexyl-1-iodo-2-phenyl-4-(p-tolyl)buta-1,3-diene (7: 34.0 mg,
79%) as a pale yellow oil. 1H NMR (300 MHz, CDCl3): d 0.86
(t, J = 6.6 Hz, 3 H), 1.18–1.54 (m, 8 H), 2.28–2.35 (m, 2 H),
2.33 (s, 3 H), 6.39 (s, 1 H), 6.72 (s, 1 H), 7.12 (s, 4 H), 7.21–7.27
(m, 2 H), 7.30–7.44 (m, 3 H). 13C NMR (126 MHz, CDCl3): d
14.0, 21.2, 22.6, 28.8, 28.9, 29.2, 31.5, 78.9, 127.8, 128.2, 128.7,
128.9, 129.2, 131.4, 134.6, 136.7, 141.4, 143.5, 155.3. HRMS
(EI): Calcd for C23H27I [M]+, 430.11561; found, 430.11462.
(m, 2 H), 7.13 (s, 4 H), 7.18–7.22 (m, 2 H), 7.28–7.34 (m, 3 H). 13
C
NMR (126 MHz, CDCl3): d 14.0, 21.08, 21.14, 22.6, 28.6, 29.0,
29.3, 31.6, 126.9, 127.0, 128.5, 128.6, 128.7, 128.8, 129.5, 130.0,
130.1, 134.8, 135.6, 136.1, 136.2, 140.2, 144.2, 145.3. HRMS
(FAB+): Calcd for C30H34 [M]+, 394.26588; found, 394.2657.
Hydrolysis of (1E,3E)-3-hexyl-2-phenyl-1,4-bis(trimethylsilyl)-
buta-1,3-diene (4)12
A solution of 4 (35.8 mg, 0.100 mmol) and trifluoroacetic acid
(45.6 mg, 0.400 mmol) in hexane (2.5 mL) was stirred at room
temperature for 24 h. The resulting mixture was treated with
a saturated NaHCO3 aqueous solution (5 mL) and extracted
with diethyl ether (10 mL × 3). The combined organic layer was
washed with brine (10 mL) and dried over anhydrous magnesium
sulfate. Evaporation of the solvent followed by purification by
gel permeation chromatography gave 3-hexyl-2-phenylbuta-1,3-
diene (11: 17.6 mg, 82%) as a pale yellow oil. 1H NMR (300 MHz,
CDCl3): d 0.88 (t, J = 6.9 Hz, 3 H), 1.20–1.51 (m, 8 H), 2.24
(t, J = 7.5 Hz, 2 H), 4.94 (d, J = 1.1 Hz, 1 H), 5.06 (d, J = 1.1 Hz,
1 H), 5.17 (d, J = 2.1 Hz, 1 H), 5.27 (d, J = 2.1 Hz, 1 H), 7.26–
7.35 (m, 5 H). 13C NMR (126 MHz, CDCl3): d 14.0, 22.6, 28.2,
29.0, 31.7, 34.5, 115.1, 113.3, 127.2, 128.0, 128.1, 141.4, 149.4,
150.9. MS (EI) m/z (rel. intensity): 214 (10), 199 (2), 185 (1), 171
(5), 157 (16), 143 (33), 129 (100), 115 (23), 91 (16), 77(13).
The coupling reaction of (1Z,3E)-3-hexyl-1-iodo-2-phenyl-4-(p-
tolyl)buta-1,3-diene (7) with p-methoxyphenylboronic acid11
A mixture of 7 (17.2 mg, 0.040 mmol), p-methoxyphenylboronic
acid (12.2 mg, 0.080 mmol), Pd(PPh3)4 (2.3 mg, 0.002 mmol),
Na2CO3 (9.3 mg, 0.088 mmol), toluene (1.0 mL) and methanol
(0.2 mL) was degassed by three freeze–thaw cycles. After the
solution was stirred at 50 ◦C for 8 h, water (10 mL) was added and
the resulting mixture was extracted with diethyl ether (20 mL ×
3). The combined organic layer was washed with brine (10 mL)
and dried over anhydrous magnesium sulfate. Evaporation of
the solvent followed by purification by column chromatography
on silica gel (hexane–ethyl acetate = 100 : 1) gave (1Z,3E)-3-
hexyl-1-(p-methoxyphenyl)-2-phenyl-4-(p-tolyl)buta-1,3-diene
1
(8: 14.1 mg, 86%) as a pale yellow oil. H NMR (300 MHz,
CDCl3): d 0.87 (t, J = 6.8 Hz, 3 H), 1.20–1.38 (m, 6 H),
1.56–1.65 (m, 2 H), 2.34 (s, 3 H), 2.41–2.47 (m, 2 H), 3.74 (s, 3
H), 6.35 (s, 1 H), 6.61–6.67 (m, 2 H), 6.73 (s, 1 H), 6.81–6.86 (m,
The Diels–Alder reaction of 4,4,5,5-tetramethyl-2-[(1E,3E)-3-
hexyl-1,4-bis(trimethylsilyl)buta-1,3-dien-2-yl]-1,3,2-dioxa-
borolane (3a) with N-phenylmaleimide13
2 H), 7.13 (s, 4 H), 7.18–7.22 (m, 2 H), 7.28–7.34 (m, 3 H). 13
C
NMR (126 MHz, CDCl3): d 14.0, 21.1, 22.6, 28.6, 29.1, 29.4,
31.6, 55.2, 113.4, 126.4, 127.0, 128.6, 128.7, 128.8, 129.7, 130.2,
A solution of 3a (40.9 mg, 0.100 mmol) and N-phenylmaleimide
(26.0 mg, 0.15 mmol) in toluene (0.4 mL) was stirred at 120 ◦C
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 6 3 – 1 2 6 8
1 2 6 7

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for 24 h. Evaporation of the solvent followed by purification by
gel permeation chromatography gave ( )-(3aR,4S,7R,7aS)-5-
hexyl-2-phenyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
4,7-bis(trimethylsilyl)-3a,4,7,7a-tetrahydroisoindole-1,3-dione
6.51 (s, 1 H), 7.26 (d, J = 15.9 Hz, 1 H), 7.33–7.44 (m, 3 H),
7.52–7.64 (m, 3 H). 13C NMR (126 MHz, CDCl3): d −0.1, 14.0,
22.6, 29.6, 29.7, 31.7, 31.9, 123.0, 128.3, 128.9, 130.2, 135.2,
138.2, 143.6, 158.1, 193.2. HRMS (EI): Calcd for C20H30OSi
[M]+, 304.20643; found, 304.20659.
1
(12: 55.1 mg, 95%) as a pale yellow oil. H NMR (300 MHz,
CDCl3): d 0.25 (s, 9 H), 0.27 (s, 9 H), 0.79 (t, J = 6.6 Hz, 3 H),
1.06–1.36 (m, 8 H), 1.30 (s, 12 H), 1.41–1.49 (m, 1 H), 1.73–1.78
(m, 1 H), 1.90–2.60 (m, 1 H), 2.46–2.60 (m, 1 H), 3.28 (dd, J =
8.5, 3.8 Hz, 1 H), 3.36 (dd, J = 5.1, 3.8 Hz, 1 H), 7.17–7.24
(m, 2 H), 7.29–7.43 (m, 3 H). 13C NMR (126 MHz, CDCl3):
d 0.4, 0.5, 14.0, 22.4, 25.4, 25.5, 29.7, 31.6, 31.8, 33.4, 37.2,
44.0, 44.5, 83.3, 126.8, 128.1, 128.8, 132.5, 158.1, 178.4, 178.8.
HRMS (EI): Calcd for C32H52NO4Si2 [M]+, 581.35246; found,
581.35615.
References
1 J. Tsuji, Transition Metal Reagents and Catalysts: Innovations in
Organic Synthesis, Wiley, Chichester, 2000, pp. 169–197.
2 R. C. Larock, Comprehensive Organic Transformations, 2nd edn.,
Wiley-VCH, New York, 1999, pp. 463–522.
3 The cross-coupling reaction of alkenylmetals with alkenyl halides,
i.e., the Suzuki–Miyaura and the Kosugi–Migita–Stille coupling
reactions, should be one of the most effective methods leading to
conjugated dienes in a stereospecific way. However, the coupling
reaction sometimes can be cumbersome since both substrates,
multisubstituted alkenylmetals and alkenyl halides, must be prepared
stereoselectively prior to the coupling. For the Suzuki–Miyaura
coupling reaction, see: (a) N. Miyaura, H. Suginome and A. Suzuki,
Tetrahedron Lett., 1981, 22, 127–130; (b) N. Miyaura and A. Suzuki,
Chem. Rev., 1995, 95, 2457–2483; (c) N. Miyaura, Top. Curr. Chem.,
2002, 219, 11–59; (d) For the Kosugi–Migita–Stille coupling reaction,
see: M. Kosugi, K. Sasazawa, Y. Shimizu and T. Migita, Chem. Lett.,
1977, 301–302; (e) V. Farina, V. Krishnamurthy and W. J. Scott, Org.
React., 1997, 50, 1–652.
4 Although the Mizoroki–Heck reaction may be an alternative for the
cross-coupling reaction, low reactivity of multisubstituted alkenes
upon the reaction with alkenyl halides may be a major drawback.
For recent reviews of the Mizoroki–Heck reaction, see: S. Bro¨se
and A. de Meijere, in Metal-catalyzed Cross-coupling Reactions, ed.
F. Diederich and P. J. Stang, Wiley-VCH, Weinheim, 1998, ch. 3,
pp. 99–166; G. T. Crisp, Chem. Soc. Rev., 1998, 27, 427–436; I. P.
Beletskaya and A. V. Cheprakov, Chem. Rev., 2000, 100, 3009–3066.
5 A. Kinoshita, N. Sakakibara and M. Mori, J. Am. Chem. Soc., 1997,
119, 12388–12389.
Oxidation of 4,4,5,5-tetramethyl-2-[(1E,3E)-3-hexyl-1,4-bis(tri-
methylsilyl)-buta-1,3-dien-2-yl]-1,3,2-dioxaborolane (3a)14
A solution of 3a (81.7 mg, 0.200 mmol), hydrogen peroxide–
urea complex (18.8 mg, 0.200 mmol) and NaOAc (16.4 mg,
0.200 mmol) in THF (1.0 mL) was stirred at 0 ◦C for 24 h.
Filtration of the resulting mixture and evaporation followed
by purification by gel permeation chromatography gave (E)-3-
hexyl-1,4-bis(trimethylsilyl)but-3-en-2-one (13: 54.6 mg, 92%) as
a pale yellow oil. 1H NMR (300 MHz, CDCl3): d 0.07 (s, 9 H),
0.18 (s, 9 H), 0.87 (t, J = 7.2 Hz, 3 H), 1.20–1.36 (m, 8 H), 2.27–
2.37 (m, 2 H), 2.48 (s, 2 H), 6.43 (s, 1 H). 13C NMR (126 MHz,
CDCl3): d −1.1, −0.4, 13.9, 22.5, 29.7, 30.3, 31.3, 31.6, 32.5,
139.6, 157.7, 201.9. HRMS (EI): Calcd for C16H34OSi2 [M]+,
298.21463; found, 298.21314.
Preparation of (E)-2-hexyl-3-trimethylsiloxy-1-(trimethylsilyl)-
buta-1,3-diene (14)15
¨
6 J. Le Paih, S. De´rien, I. Ozdemir and P. H. Dixneuf, J. Am. Chem.
Soc., 2000, 122, 7400–7401.
To a solution of 13 (35.8 mg, 0.120 mmol) in hexane (1.0 mL)
was added TMSOTf (1.7 mg, 0.012 mmol) and the mixture was
stirred at room temperature for 30 min. Triethylamine (1.0 mL)
and water (10 mL) were added and the resulting mixture was
extracted with diethyl ether (20 mL × 3). The combined organic
layers were washed with brine (10 mL) and dried over anhydrous
magnesium sulfate. Evaporation of the solvent followed by pu-
rification by gel permeation chromatography gave (E)-2-hexyl-
3-trimethylsiloxy-1-(trimethylsilyl)buta-1,3-diene (14: 35.7 mg,
99%) as a colorless oil. 1H NMR (300 MHz, CDCl3): d 0.13 (s,
9 H), 0.20 (s, 9 H), 0.89 (t, J = 6.6 Hz, 3 H), 1.20–1.52 (m, 8 H),
2.24–2.32 (m, 2 H), 4.35–4.37 (m, 1 H), 4.56–4.58 (m, 1 H), 5.95
(s, 1 H). 13C NMR (126 MHz, CDCl3): d 0.0, 0.1, 14.0, 22.6, 29.8,
30.7, 31.7, 33.0, 93.0, 126.5, 152.5, 156.5. HRMS (EI): Calcd for
C16H34OSi2 [M]+, 298.21463; found, 298.21305.
7 Since diisopropyl dienylboronates were found to be unstable to mois-
ture, we transesterified them to pinacol esters. Transesterification was
carried out in benzene (1.0 mL) at rt for 12–48 h using 5.0 equiv. of
pinacol after evaporation of the reaction mixture of the ruthenium-
catalysed reaction. For details, see the Experimental section.
8 Configuration of 3a and 3e (R = Ph) was determined by NOESY
NMR spectra. For details, see the Experimental section. Although
we have not elucidated the stereochemistry of the other products 3,
formation as the single isomer should show that they also have the
same configuration.
9 L. Deloux, E. S. Jankun, B. V. Cheesman and M. Srebnik, J. Am.
Chem. Soc., 1994, 116, 10302–10303.
10 N. A. Yakelis and W. R. Roush, J. Org. Chem., 2003, 68, 3838–3843;
D. P. Stamos, A. G. Taulor and Y. Kishi, Tetrahedron Lett., 1996, 37,
8647–8650.
11 S. Ma, J. Zhang, Y. Cai and L. Lu, J. Am. Chem. Soc., 2003, 125,
13954–13955.
12 C. Dehnhardt, M. McDonald, S. Lee, H. G. Floss and J. Mulzer,
J. Am. Chem. Soc., 1999, 121, 10848–10849; Z. Xi, X. Liu, J. Lu,
F. Bao, H. Fan, Z. Li and T. Takahashi, J. Org. Chem., 2004, 69,
8547–8549.
13 For the Diels–Alder reaction of 1,3-butadienes having one or two
boryl groups, see: A. Kamabuchi, N. Miyaura and A. Suzuki,
Tetrahedron Lett., 1993, 34, 4827–4828; M. Shimizu, T. Kurahashi
and T. Hiyama, Synlett, 2001, 34, 1006–1008.
14 N. G. Bhat, A. Tamm and A. Gorena, Synlett, 2004, 297–298.
15 Y. Yamamoto, K. Ohdoi, M. Nakatani and K.-Y. Akiba, Chem. Lett.,
1984, 1967–1968.
16 For a review, see: T.-H. Chan, in Comprehensive Organic Synthesis,
ed. B. M. Trost, Pergamon Press, New York, 1991, vol. 2, pp. 595–628.
17 N. Oshima, H. Suzuki and Y. Moro-oka, Chem. Lett., 1984, 1161–
1164.
Aldol reaction of (E)-2-hexyl-3-trimethylsiloxy-1-(trimethyl-
silyl)buta-1,3-diene (14) with benzaldehyde
A solution of 14 (29.8 mg, 0.100 mmol), benzaldehyde (10.6 mg,
0.100 mmol) and boron trifluoride–diethyl ether complex
(2.1 mg, 0.015 mmol) in toluene (1.0 mL) was stirred at 50 C
◦
for 60 h. Triethylamine (1.0 mL) and water (10 mL) was added
and the resulting mixture was extracted with diethyl ether
(20 mL × 3). The combined organic layers were washed with
brine (10 mL) and dried over anhydrous magnesium sulfate.
Evaporation of the solvent followed by purification by gel
permeation chromatography gave (1E,4E)-2-hexyl-5-phenyl-1-
(trimethylsilyl)penta-1,4-dien-3-one (15: 21.9 mg, 70%) as a pale
yellow oil. 1H NMR (300 MHz, CDCl3): d 0.22 (s, 9H), 0.87 (t,
J = 6.9 Hz, 3 H), 1.20–1.43 (m, 8 H), 2.48 (t, J = 7.5 Hz, 2 H),
18 H. C. Brown, N. G. Bhat and M. Srebnik, Tetrahedron Lett., 1988,
29, 2631–2634.
1 2 6 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 6 3 – 1 2 6 8