Synthesis of 2-substituted cyclohexene derivatives through cross-coupling reactions via π-allylmetal intermediate using N-heterocyclic carbenes (NHCs) as ligands

Article abstract of DOI:10.1055/s-2008-1067222

Palladium- or nickel-catalyzed cross-coupling reactions of 2-substituted cyclohexenes, which are generally less reactive than those having no substituent at the C2 position, with organotin reagents (Migita-Kosugi-Stille coupling) or with Grigard reagents (Kumada-Tamao-Corriu coupling) using a NHC as a ligand was investigated. It was found that NHCs are effective as ligands for these reactions, giving the corresponding cross-coupling products in good yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1067222

2830
SPECIAL TOPIC
Synthesis of 2-Substituted Cyclohexene Derivatives through Cross-Coupling
Reactions via p-Allylmetal Intermediate Using N-Heterocyclic Carbenes
(NHCs) as Ligands
S
ynthesis of 2-S
e
ubstituted
t
Cycloh
s
exene De
uivatives ro Yamazaki, Yoshihiro Sato*
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Fax +81(11)7064982; E-mail: biyo@pharm.hokudai.ac.jp
Received 8 July 2008
of 2 and an organometallic reagent (R-M). Cross-coupling
Abstract: Palladium- or nickel-catalyzed cross-coupling reactions
of 2-substituted cyclohexenes, which are generally less reactive
than those having no substituent at the C2 position, with organotin
reagents (Migita–Kosugi–Stille coupling) or with Grigard reagents
reactions are widely used to form C–C bonds in the field
of synthetic organic chemistry.3 Recently, N-heterocyclic
carbenes (NHCs) have been found to be very effective as
(Kumada–Tamao–Corriu coupling) using a NHC as a ligand was in- ligands for various cross-coupling reactions.4 Thus, we
vestigated. It was found that NHCs are effective as ligands for these
reactions, giving the corresponding cross-coupling products in good
yields.
decided to investigate the utility of NHCs for the cross-
coupling reaction between 2-substituted allylic substrate 2
and organometallic reagents.
Key words: N-heterocyclic carbene (NHC), cross-coupling,
Migita–Kosugi–Stille reaction, Kumada–Tamao–Coriiu reaction,
palladium, nickel
S
Pd(0) catalyst
NuH, base
Nu
S
Tsuji–Trost
reaction
X
1
Cyclohexene derivatives 1, having a substituent at the C2
position on the alkene, are useful synthetic intermediates
for various natural products.1 We have already reported
syntheses of natural products from cyclohexene deriva-
tives, including the synthesis of (–)-mesembrine from 1a1a
and the syntheses of (–)-tubifoline1d,f and (–)-strychine1e,f
from 1b, respectively (Figure 1).
Pd(0) catalyst
R-M
S
2
R
cross-coupling
reaction
3
Scheme 1 Synthetic route for 2-substituted cyclohexenes
S
1a: S = 3,4-(MeO)2C6H3
R
Although there have been a number of studies on transi-
tion-metal-catalyzed cross-coupling reactions using NHC
ligands between an sp2 carbon center in the substrate (e.g.,
aryl halide, vinyl halide) and various organometallic re-
agents, examples of the reactions between allylic sub-
strates and organometallic reagents are limited. In
addition, our previous studies on the palladium-catalyzed
Tsuji–Trost reaction of 2-substituted allylic substrates 2
revealed that the reactivity of 2 is relatively low due to the
bulkiness of the C2 substituent compared to those having
no substituent at C2 position. Herein we report a palladi-
um-catalyzed cross-coupling reaction of 2 with an orga-
notin reagent (Migita–Kosugi–Stille coupling)5 and a
nickel-catalyzed cross-coupling reaction of 2 with a
Grigard reagent (Kumada–Tamao–Corriu coupling)6 us-
ing an NHC as a ligand.
R = N(Ts)CH2CH=CH2
1b: S = CH2OTBS
R = 2-BrC6H4(Ts)N
OMe
N
OMe
N
H
H
N
H
H
O
N
O
N
O
H
Me
H
(–)-tubifoline
(–)-strychnine
(–)-mesembrine
Figure 1 Synthetic utility of 2-substituted cyclohexenes
In the previous syntheses, the desired 2-substituted cyclo-
hexene derivatives 1a and 1b were synthesized via palla-
dium-catalyzed Tsuji–Trost reaction of allylic substrate 2
and nucleophiles in the presence of a base (Scheme 1).2
Initially, we investigated the cross-coupling reaction of 2-
substituted cyclohexene derivative 2a with tributyl(phe-
nyl)stannane using various Pd–NHC complexes, generat-
ed in situ from Pd2dba3·CHCl3 (1.5 mol%) and various
imidazolium salts as precursors of the NHC in the pres-
ence of cesium carbonate (Table 1, Figure 2). A tetra-
hydrofuran solution of Pd2(dba)3·CHCl3 (1.5 mol%),
triphenylphosphine (3.0 mol%), and 1,3-dimesityl-4,5-di-
hydro-1H-imidazolium hydrochloride (IMes·HCl, 3.0
The versatility of 2-substituted cyclohexenes as a useful
synthon prompted us to develop an alternative route to
synthesize such compounds 3 via cross-coupling reaction
SYNTHESIS 2008, No. 17, pp 2830–2834
Advanced online publication: 06.08.2008
DOI: 10.1055/s-2008-1067222; Art ID: C04008SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
8

SPECIAL TOPIC
Synthesis of 2-Substituted Cyclohexene Derivatives
2831
mol%) was stirred at 50 °C for 10 minutes. To the Next, the reactions of 2a with vinylstannane were investi-
Pd(PPh3)(NHC) catalyst solution was added a tetrahydro- gated, and the results are shown in Table 2. The reaction
furan solution of 2a and tributyl(phenyl)stannane and the of 2a with tributyl(vinyl)stannane using triphenylphos-
mixture was stirred at 50 °C for 132 hours. After the usual phine gave the desired product 3b in 55% yield along with
workup, the desired coupling product 3a was obtained in b-eliminated product 4 in 20% yield (Table 2, entry 1). In
64% yield along with b-eliminated product 4 in 9% yield this reaction system, the use of NHCs gave superior re-
(Table 1, entry 1). The use of IPr and the use of SIPr under sults. Thus, the reaction using a mixed ligand complex,
similar conditions improved the yields of 3a to 86% and Pd(PPh3)(NHC), formed from Pd2(dba)3·CHCl3 (1.5
77%, respectively (Table 1, entries 2 and 3). NHCs having mol%), triphenylphosphine (3.0 mol%), and IPr·HCl (3.0
an alkyl substituent on the nitrogen in the imidazole ring mol%) in the presence of cesium carbonate, produced 3b
such as ItBu or IiPr were less effective for the coupling re- in 71% yield (Table 2, entry 2).
action (Table 1, entries 4 and 5). The cross-coupling reac-
Table 2 Cross-Coupling Reaction of 2a with Tributyl(vinyl)stan-
nane
tion using
a
Pd–IPr catalyst prepared from
Pd2(dba)3·CHCl3 (1.5 mol%), IPr·HCl (3.0 mol%), and ce-
sium carbonate in the absence of triphenylphosphine gave
the best result, providing 3a in 90% yield (Table 1, entry
6). On the other hand, the reaction of 2a with tributyl(phe-
nyl)stannane using triphenylphosphine instead of NHCs
gave 3a in 76% yield (Table 1, entry 7), indicating that the
NHC ligand is superior to the phosphorus ligand in this re-
action system.
OTBS
Cl
OTBS
Pd2(dba)3⋅CHCl3 (1.5 mol%)
ligand
(2.0 equiv)
SnBu3
Cs2CO3 (6.0 mol%)
THF, 50 °C
2a
3b
Entry Ligand (mol%)
Time (h)
Yield (%)
3b
4
R
1a
2
Ph3P (6.0)
84
84
90
55
71
74
20
20
4
R
R
R
N
N
N
N
IPr–PPh3 (3.0:3.0)
IPr (3.0)
SIPr: R = 2,6-(i-Pr)2C6H3
IMes: R = Mes
IPr: R = 2,6-(i-Pr)2C6H3
ItBu: R = t-Bu
IiPr: R = i-Pr
3
a Reactions were carried out in the absence of Cs2CO3.
Figure 2 NHC ligands used
In the reaction of 2a with tributyl(vinyl)stannane using a
Pd–IPr catalyst prepared from Pd2(dba)3·CHCl3, IPr·HCl,
and cesium carbonate in the absence of triphenylphos-
phine, the yield of 3b was improved to 74% (Table 2, en-
try 3).
Table 1 Cross-Coupling Reaction of 2a with Tributyl(phenyl)stan-
nane
OTBS
Cl
OTBS
Ph
OTBS
The reaction of 2a with functionalized tributyl(1-ethoxy-
vinyl)stannane (5) would provide the coupling product 3c,
which could be converted into methyl ketone derivatives
and should be a useful synthon. In the reaction of 2a with
5 using triphenylphosphine as a ligand, however, the de-
sired product 3c was not obtained, only isomerized prod-
uct 6 (Figure 3) was obtained in 25% yield (Table 3, entry
1). On the other hand, the reaction using a mixed ligand
complex, Pd(PPh3)(NHC), gave the desired product 3c in
50% yield along with b-eliminated product 4 (3%) and 6
(8%) (Table 3, entry 2). The use of Pd–IPr was less effec-
tive in this reaction system, giving 3c in 22% yield
(Table 3, entry 3). Although the yield of 3c was still mod-
est, these results suggest the superiority of NHCs to the
phosphorus ligand in the Migita–Kosugi–Stille coupling
reaction of 2-substituted cyclohexenes.
Pd2(dba)3⋅CHCl3 (1.5 mol%)
ligand (3.0 mol%)
PhSnBu3 (2.0 equiv)
Cs2CO3 (6.0 mol%)
THF, 50 °C
2a
3a
4
Entry
Ligand
Time (h)
Yield (%)
3a
4
1a
2a
3a
4a
5a
6b
7c
IMes
IPr
132
113
138
36
64
86
77
–
9
–
5
SIPr
ItBu
IiPr
12
6
129
144
75
67
90
76
IPr
7
OTBS
OEt
Ph3P
–
a Reaction conditions: Pd(PPh3)(NHC) complex generated in situ
from Pd2(dba)3·CHCl3 (1.5 mol%), imidazolium salts (3.0 mol%),
Ph3P (3.0 mol%), Cs2CO3 (6.0 mol%), THF, 50 °C, 10 min.
b Pd–IPr complex generated in situ from Pd2(dba)3·CHCl3 (1.5
mol%), IPr·HCl (3.0 mol%), Cs2CO3 (6.0 mol%).
6
Figure 3
c In the absence of Cs2CO3.
Synthesis 2008, No. 17, 2830–2834 © Thieme Stuttgart · New York

2832
T. Yamazaki, Y. Sato
SPECIAL TOPIC
Table 4 Nickel-Catalyzed Cross-Coupling Reaction of 2-Substi-
tuted Cyclohexenes 2 with Phenylmagnesium Chloride
Table 3 Cross-Coupling Reaction of 2a with Tributyl(1-ethoxy-
vinyl)stannane
OTBS
OTBS
Pd2(dba)3⋅CHCl3 (1.5 mol%)
ligand
Ni complex (5 mol%)
ligand
PhMgCl (2.0 equiv)
OTBS
Cl
OTBS
X
Ph
THF
EtO
SnBu3
(2.0 equiv)
5
OEt
3a
2a: X = Cl
2b: X = OMe
Cs2CO3 (6.0 mol%)
THF, 50 °C
2a
3c
Entry Substrate Catalyst, ligand (mol%) Conditions Yield (%)
Entry
Ligand (mol%)
Time (h) Yield (%)
3a
–
9
3c
4
–
3
5
1a
2a
2b
2b
Ni(acac)2, 8 (10)
r.t., 17 h
r.t., 17 h
–
1a,b
2b
3
Ph3P (6.0)
84
84
90
–
Ni(acac)2, Ph3P (20)
–
–
IPr–PPh3 (3.0:3.0)
IPr (3.0)
50
22
3a,b 2b
Ni(cod)2, IPr–PPh3 (5:5) r.t., 48 h
Ni(cod)2, Ph3P (10) r.t., 2 h
Ni(cod)2, IPr–PPh3 (5:5) r.t., 2 h
Ni(cod)2, IPr (5)
–
–
4
2a
2a
2a
38
48
35
37
4
a Reactions were carried out in the absence of Cs2CO3.
5b
6b
b Byproduct 6 was also obtained in 25% (entry 1) or 8% yield (entry
2).
r.t., 1.5 h 82
a The starting material 2b was recovered in 84% (entry 1), 82% (entry
2), or 87% (entry 3).
Next, we turned our attention to the synthesis of 2-substi-
tuted cyclohexenes through a nickel-catalyzed Kumada–
Tamao–Corriu coupling reaction. Recently, Uemura and
co-workers have reported an asymmetric Kumada–
Tamao–Corriu coupling reaction of simple cyclohexene
derivatives 7 with Grignard reagents using nickel com-
plexes (Scheme 2).7
b The reaction was carried out in the presence of Cs2CO3 (6 mol%).
use of a mixed ligand complex, Ni(IPr)(PPh3), which was
generated in situ from Ni(cod)2 (5 mol%), IPr·HCl (5
mol%), and triphenylphosphine (5 mol%) in the presence
of cesium carbonate (6.0 mol%), was not effective in this
reaction (Table 4, entry 3). On the other hand, the sub-
strate 2a was found to be more reactive toward this reac-
tion than 2b, and the reaction of 2a with
phenylmagnesium chloride in the presence of Ni(cod)2 (5
mol%) and triphenylphosphine (20 mol%) gave the de-
sired product 3a in 38% yield along with the dimer 9
(Figure 4) in 35% yield (Table 4, entry 4). The use of a
mixed ligand complex slightly improved the yield of 3a to
48%, but a significant amount of the dimer 9 was also ob-
tained (Table 4, entry 5). On the other hand, the use of Ni–
IPr complex, generated in situ from Ni(cod)2 (5 mol%)
and IPr·HCl (5 mol%) in the presence of cesium carbonate
(6 mol%), gave the best result, giving 3a in 82% yield and
also suppressing the formation of 9 (Table 4, entry 6).
Ni(acac)2, ligand
Y
Ph
3d: ~100% yield
PhMgX
*
THF, r.t.
~88% ee
7
ex)
O
7 (Y = OMe), PhMgCl
THF, r.t., 17 h
3d: 91% yield (52% ee)
N
i-Pr
PPh2
8
Scheme 2 Asymmetric Kumada–Tamao–Corriu coupling reaction
of nonsubstituted cyclohexene derivatives reported by Uemura and
co-workers
In their study, the yield and enantiomeric excess of 3d
varied up to 100% yield and 88% ee, depending on the
reaction conditions and the properties of the ligands. For
example, the reaction of 7 (Y = OMe) with phenyl-
magnesium chloride using Ni(acac)2 (5 mol%) and chiral
ligand 8 gave the product 3d in 91% yield and 52% ee.
However, the reaction of the corresponding 2-substituted
cyclohexene derivative 2b with phenylmagnesium chlo-
ride under the same conditions did not give the coupling
product 3a, indicating the low reactivity of 2-substituted
cyclohexene substrates toward this cross-coupling reac-
tion (Table 4, entry 1).
TBSO
OTBS
9
Figure 4
In summary, a palladium- or nickel-catalyzed cross-cou-
pling of 2-substituted cyclohexene derivatives 2 with or-
ganotin reagent (Migita–Kosugi–Stille coupling) or with
Grigard reagent (Kumada–Tamao–Corriu coupling) was
investigated using NHC as a ligand. Although 2-substitut-
ed cyclohexenes 2 are generally less reactive as substrates
toward these types of cross-coupling reactions due to the
bulkiness of the C2 substituent, compared to those having
Thus, combinations of catalyst and ligand were screened
in the reaction of 2a or 2b with phenylmagnesium chlo-
ride, and the results are summarized in Table 4. The reac-
tion of 2b with phenylmagnesium chloride in the presence
of Ni(acac)2 (5 mol%) and triphenylphosphine (20 mol%)
also gave no desired product 3a (Table 4, entry 2). The
Synthesis 2008, No. 17, 2830–2834 © Thieme Stuttgart · New York

SPECIAL TOPIC
Synthesis of 2-Substituted Cyclohexene Derivatives
2833
through a pad of Celite and the filtrate was concentrated. The resi-
due was purified by column chromatography (KF/SiO2,8 hexane) to
give 3a (85 mg, 90%) as a colorless oil.
IR (neat): 3060, 2929, 1601 cm–1.
1H NMR (270 MHz, CDCl3): d = 7.15–7.27 (m, 5 H), 5.97 (m, 1 H),
3.86 (m, 2 H), 3.44 (m, 1 H), 1.45–2.14 (m, 6 H), 0.84 (s, 9 H),
–0.07 (s, 3 H), –0.08 (s, 3 H).
no substituent at the C2 position, it was found that NHCs
are effective as ligands for these reactions and can sup-
press the formation of byproducts such as a b-eliminated
product for Migita–Kosugi–Stille coupling and a dimeric
product for Kumada–Tamao–Corriu coupling.
All manipulations were performed under an argon atmosphere. THF
was purified using a Glass Contour Solvent Purification System,
and all other solvents and reagents were purified when necessary by
standard procedures. Column chromatography was performed on
silica gel 60 (Merck, 70–230 mesh), and flash chromatography on
silica gel (Merck, 230–400 mesh) with the indicated solvent as elu-
ent. IR spectra were obtained on a Jasco FT/IR-460 plus, and 1H and
13C NMR spectroscopy were carried out on a Jeol EX270 or a Jeol
AL400 NMR spectrometer. Mass spectra were obtained on a Jeol
JMS-700TZ for LRMS (EI) and HRMS (EI), and a Shimadzu
GCMS-QP5050A for LCMS (EI).
13C NMR (100 MHz, CDCl3): d = 145.7, 138.6, 129.2, 128.8, 126.6,
124.8, 66.5, 41.7, 32.9, 26.5, 25.6, 19.2, 19.0, –4.9.
LR-MS (EI): m/z = 302 [M]+, 287 [M – Me]+, 245 [M – t-Bu]+.
HRMS (EI): m/z [M]+ calcd for C19H30OSi: 302.2066; found:
302.2054.
1-[(tert-Butyldimethylsiloxy)methyl]-6-vinylcyclohex-1-ene
(3b)
IR (neat): 2930, 1634, 913, 836 cm–1.
1H NMR (270 MHz, CDCl3): d = 5.69–5.82 (m, 2 H), 5.02 (br s, 1
H), 4.96 (m, 1 H), 3.99 (m, 2 H), 2.78 (m, 1 H), 2.03 (m, 2 H), 1.53–
1.76 (m, 4 H), 0.90 (s, 9 H), 0.05 (s, 3 H), 0.04 (s, 3 H).
1-[(tert-Butyldimethylsiloxy)methyl]-6-chlorocyclohex-1-ene
(2a)
To a soln of 2-[(tert-butyldimethylsiloxy)methyl]cyclohex-2-enol1d
(410 mg, 1.7 mmol) in CH2Cl2 (3.5 mL) was added i-Pr2NEt (0.4
mL, 2.5 mmol) and MsCl (0.2 mL, 2.5 mmol) and the mixture was
stirred at 0 °C for 2 h then at r.t. for 3 h. To the mixture was added
sat. aq NH4Cl soln at 0 °C, and the soln was extracted with CH2Cl2.
The combined organic layers were washed with sat. NaCl and dried
(Na2SO4). After removal of the solvent, the residue was purified by
column chromatography (silica gel, hexane–EtOAc, 19:1) to give
2a (400 mg, 90%) as a colorless oil.
13C NMR (100 MHz, CDCl3): d = 141.0, 137.4, 122.6, 114.6, 65.6,
39.4, 29.1, 26.2, 25.2, 19.1, 18.6, –4.9.
LR-MS (EI): m/z = 252 [M]+, 237, 219, 195, 75.
HRMS (EI): m/z [M]+ calcd for C15H28OSi: 252.1909; found:
252.1897.
1-[(tert-Butyldimethylsiloxy)methyl]-6-(1-ethoxyvinyl)cyclo-
hex-1-ene (3c)
IR (neat): 2931, 1649, 1068 cm–1.
IR (neat): 2953, 1742, 838, 777 cm–1.
1H NMR (270 MHz, CDCl3): d = 5.82 (m, 1 H), 4.05 (m, 2 H), 3.93
(d, J = 1.6 Hz, 1 H), 3.80 (d, J = 1.6 Hz, 1 H), 3.69 (m, 2 H), 2.82
(m, 1 H), 1.47–2.04 (m, 6 H), 1.28 (t, J = 7.1 Hz, 3 H), 0.90 (s, 9 H),
0.04 (s, 6 H).
13C NMR (100 MHz, CDCl3): d = 163.9, 136.4, 123.7, 82.2, 65.7,
62.7, 40.6, 27.4, 26.2, 25.0, 18.9, 18.7, 14.7, –5.08.
LR-MS (EI): m/z = 296 [M]+, 267, 239, 75.
HRMS (EI): m/z [M]+ calcd for C17H32O2Si: 296.2172; found:
1H NMR (270 MHz, CDCl3): d = 5.85 (m, 1 H), 4.68 (m, 1 H), 4.22–
4.29 (m, 1 H), 4.05–4.12 (m, 1 H), 1.54–2.19 (m, 6 H), 0.92 (s, 9 H),
0.09 (s, 3 H), 0.08 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 136.8, 127.1, 64.7, 55.2, 32.3,
26.1, 24.9, 18.6, 17.4, –5.0.
LR-MS (EI): m/z = 259 [M – 1]+, 225 [M – Cl]+, 203 [M – t-Bu]+.
HRMS (EI): m/z [M – t-Bu]+ calcd for C9H16ClOSi: 203.0659;
found: 203.0649.
296.2174.
1-[(tert-Butyldimethylsiloxy)methyl]-6-methoxycyclohex-1-ene
(2b)
1-[(tert-Butyldimethylsiloxy)methyl]-6-phenylcyclohex-1-ene
(3a) by Kumada–Tamao–Corriu Coupling (Table 4, Entry 6);
Typical Procedure
To a suspension of NaH (60% dispersion in mineral oil, 160 mg, 4.0
mmol) in THF (2.5 mL) were successively added a soln of 2-[(tert-
butyldimethylsiloxy)methyl]cyclohex-2-enol (485 mg, 2.0 mmol)
in THF (2.5 mL) and MeI (1.3 mL, 20 mmol) at 0 °C, and the mix-
ture was stirred at r.t. for 2 h. To the mixture was added sat. aq
NH4Cl soln and the soln was extracted with Et2O. The combined or-
ganic layers were washed with sat. NaCl and dried (Na2SO4). After
removal of the solvent, the residue was purified by column chroma-
tography (silica gel, hexane–Et2O, 40:1) to give 2b (497 mg, 97%)
as a colorless oil.
A soln of Ni(cod)2 (4.3 mg, 0.016 mmol), IPr·HCl (6.7 mg, 0.016
mmol), and Cs2CO3 (11.0 mg, 0.032 mmol) in degassed THF (3
mL) was stirred at r.t. for 1 h to generate, in situ, Ni–IPr complex.
To the catalyst soln was added a soln of 2a (81 mg, 0.31 mmol) in
THF (3 mL) and 1.7 M PhMgCl in THF (0.36 mL, 0.62 mmol) and
the mixture was stirred at r.t. for 1.5 h. To the mixture was added
sat. aq NH4Cl soln at 0 °C and the soln was extracted with EtOAc.
The combined organic layers were washed with sat. NaCl and dried
(Na2SO4). After removal of the solvent, the residue was purified by
column chromatography (silica gel, hexane) to give 3a (77 mg,
82%) as a colorless oil along with the dimer 9 (2.6 mg, 4%).
1H NMR (270 MHz, CDCl3): d = 5.83 (m, 1 H), 4.21–4.27 (m, 1 H),
4.03–4.09 (m, 1 H), 3.76 (m, 1 H), 3.35 (s, 3 H), 1.54–2.19 (m, 6 H),
0.91 (s, 9 H), 0.08 (s, 3 H), 0.07 (s, 3 H).
2,2¢-Bis[(tert-butyldimethylsiloxy)methyl]-1,1¢-bi(cyclohex-2-
ene) (9)
1-[(tert-Butyldimethylsiloxy)methyl]-6-phenylcyclohex-1-ene
(3a) by Migita–Kosugi–Stille Coupling (Table 1, Entry 6);
Typical Procedure
A soln of Pd2(dba)3·CHCl3 (4.8 mg, 0.0047 mmol), IPr·HCl (3.9
mg, 0.0094 mmol), and Cs2CO3 (6.0 mg, 0.019 mmol) in degassed
THF (3 mL) was stirred at 50 °C for 10 min to generate, in situ, Pd–
IPr complex. To the catalyst soln was added a soln of 2a (81 mg,
0.31 mmol) in THF (3 mL) and PhSnBu3 (0.2 mL, 0.62 mmol) and
the mixture was stirred at 50 °C for 144 h. The mixture was filtered
1H NMR (270 MHz, CDCl3): d = 5.78–5.84 (m, 2 H), 4.04–4.14 (m,
4 H), 2.46–2.53 (m, 2 H), 1.23–1.78 (m, 12 H), 0.91 (s, 9 H), 0.89
(m, 9 H), 0.03 (s, 6 H), 0.01 (s, 6 H).
13C NMR (100 MHz, CDCl3): d = 139.8, 138.1, 123.9, 122.9, 65.7,
38.3, 36.1, 27.7, 26.2, 25.4, 25.3, 24.2, 22.5, 22.2, 18.6, –4.99.
LR-MS (EI): m/z = 450 [M]+, 393 [M – t-Bu]+, 318 [M –
OTBDMS]+.
Synthesis 2008, No. 17, 2830–2834 © Thieme Stuttgart · New York

2834
T. Yamazaki, Y. Sato
SPECIAL TOPIC
(4) (a) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew.
Chem. Int. Ed. 2007, 46, 2768. (b) Glorius, F. N-Hetero-
cyclic Carbenes in Transition Metal Catalysis; Springer
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Acknowledgment
This work was financially supported by a Grant-in-Aid for Scienti-
fic Research (B) (No. 19390001) from the Japan Society for the Pro-
motion of Science (JSPS) and by the Akiyama Foundation, which
are gratefully acknowledged.
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