Palladium-catalyzed carbon dioxide elimination-fixation reaction of 6-methoxycarbonyloxy-2,4-hexadien-1-ols

Article abstract of DOI:10.1016/j.tet.2006.09.010

Cyclic carbonates substituted with 1,3-butadienyl moiety were synthesized by a palladium-catalyzed reaction of dienylic carbonates including a carbon dioxide elimination-fixation process. The reaction proceeded via a migration-isomerization of the resulti

Full text of DOI:10.1016/j.tet.2006.09.010

Tetrahedron 62 (2006) 11218–11226
Palladium-catalyzed carbon dioxide elimination–fixation reaction
of 6-methoxycarbonyloxy-2,4-hexadien-1-ols
b
c,
Masahiro Yoshida,a, Yusuke Ohsawa and Masataka Ihara
*
*
aGraduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan
bDepartment of Organic Chemistry, Graduate School of Pharmaceutical Sciences,
Tohoku University, Aobayama, Sendai 980-8578, Japan
cFaculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa 142-8501, Japan
Received 3 August 2006; revised 5 September 2006; accepted 5 September 2006
Available online 27 September 2006
Abstract—Cyclic carbonates substituted with 1,3-butadienyl moiety were synthesized by a palladium-catalyzed reaction of dienylic carbon-
ates including a carbon dioxide elimination–fixation process. The reaction proceeded via a migration–isomerization of the resulting p-allyl-
palladium intermediates to afford trans-1,3-dienyl-substituted cyclic carbonates in a selective manner.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
of 6-methoxycarbonyloxy-2,4-hexadien-1-ols 1 to produce
1,3-dienyl-substituted cyclic carbonates 2 via a CO2-recy-
cling process (Scheme 1).
Fixation of carbon dioxide into organic substances repre-
sents an attractive area of study in both organic and green
chemistry.1 Palladium-catalyzed reactions are one of the
common methods to fix external carbon dioxide into organic
compounds.2 Recently, we have developed a novel type of
palladium-catalyzed reaction using propargylic carbonates
with phenols, which involves a CO2-recycling process.3
The reaction proceeds via a carbon dioxide elimination–
fixation step to afford phenoxy-substituted cyclic carbo-
nates.3a–3c This process can be successfully applied to a
palladium-catalyzed reaction using allylic carbonates.3d In
these reactions, the formation of p-allylpalladium interme-
diate followed by fixation of CO2 is a key step. We sought
to determine whether a CO2-recycling process could apply
for conjugated dienylic carbonates. Although there are
many examples about the reaction of allylic compounds
by palladium catalyst,4 only a few examples have been
reported about the reactivity for conjugated dienylic
compounds.5 We report here a palladium-catalyzed reaction
2. Results and discussion
The dienylic carbonates 1 for the palladium-catalyzed reac-
tions were synthesized as follows (Scheme 2). The ketones
3a–d were subjected to the nucleophilic addition of siloxy
enyne (E)-46 in the presence of BuLi leading to the corre-
sponding acetylenic alcohols, which were desilylated with
TBAF to afford diols (E)-5a–d. trans-Selective reduction
of the alkyne moiety using LiAlH4 followed by treatment
with methyl chloroformate to produce the dienylic carbon-
ates (E,E)-1a–d. Similarly, dienylic benzoate (E,E)-6 was
prepared from 5a in two steps.
We also prepared geometric isomers of (E,E)-1a possessing
(E,Z)-, (Z,E)-, and (Z,Z)-olefinic moieties (Scheme 3). Addi-
tion of siloxy enyne (Z)-4, which was easily prepared from
O
Pd+Ln
cat. Pd(0)
HO
O
O
O
OCO2Me
R
R
R
R
R
R
1
2
CO2
Scheme 1.
* Corresponding authors. Tel./fax: +81 88 6337294 (M.Y.); e-mail: yoshida@ph.tokushima-u.ac.jp
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.010

M. Yoshida et al. / Tetrahedron 62 (2006) 11218–11226
Table 1. Initial attempts for the reaction of (E,E)-1aa
11219
1)
OTBDPS
5 mol% Pd2(dba)3⋅CHCl3
(E)-4
O
20 mol% ligand
OH
HO
nBuLi, TMEDA, THF
2) TBAF, THF, rt
HO
R
OCO2Me
O
dioxane
under argon atmosphere
in sealed tube, 4 h
Pen Pen
R
R
R
(E,E)-1a
3a: R = pentyl
(E)-5a: R = pentyl 2 steps 68%
3b: R = β-cyclohexylethyl
3c: R+R = cyclohexyl
3d: R = methyl and phenyl
(E)-5b: R = β-cyclohexylethyl 2 steps 73%
(E)-5c: R+R = cyclohexyl 2 steps 57%
(E)-5d: R = methyl and phenyl 2 steps 38%
Pen
O
Pen
O
O
+
Pen
Pen
1) LiAlH4, NaOMe
THF, reflux
2) ClCO2Me, Py
CH2Cl2, 0 °C
2a
12a
HO
R
OCO2Me
Entry
Ligand
Temp (ꢀC)
Product’s yield (%)
R
(E,E)-1a: R = pentyl 2 steps 42%
2a
12a
(E,E)-1b: R =β-cyclohexylethyl 2 steps 34%
(E,E)-1c: R+R = cyclohexyl 2 steps 24%
(E,E)-1d: R = methyl and phenyl 2 steps 35%
1
2
3
4
5b
6
7
8
dppe
dppp
dppf
dppm
PPh3
dppv
dppv
dppv
50
50
50
50
50
50
80
100
57
15
15
7
—
—
—
60
56
27
58
74
1) LiAlH4, NaOMe
THF, reflux
4
HO
R
5a
58
28
22
OBz
2) BzCl, NEt3,
DMAP, CH2Cl2
2 steps 79%
R
(E,E)-6
a
Pen¼pentyl.
Scheme 2.
b
Ligand (40 mol %) was used.
known enyne 7,7 to dipentylketone (3a) followed by desilyl-
ation yielded the diol (Z)-5. Conversion of (Z)-5 by the same
procedure described for (E)-5a gave dienylic carbonate
(E,Z)-1a in a stereoselective manner. Isomers (Z,E)-1a and
(Z,Z)-1a were prepared from (Z)-iodoalkene 10. After the
formation of propargylic alcohol 9 from 3a, 10 was prepared
by regio- and stereoselective hydroindation–iodolysis.8 The
compound 10 was then subjected to Sonogashira reaction
with propargyl alcohol followed by LiAlH4 reduction to
provide the coupled product (Z,E)-8, which was transformed
to dienylic carbonate (Z,E)-1a. The substrate (Z,Z)-1a was
obtained by Lindlar reduction of a propargylic carbonate
11, derived from 10 in two steps.
Pd2(dba)3$CHCl3 and 20 mol % 1,2-bis(diphenylphos-
phino)ethane (dppe) in dioxane at 50 ꢀC under an argon
atmosphere in a sealed tube, cyclic carbonate 2a having a
(E)-1,3-dienyl group was produced in 57% yield (entry 1).
The yield of 2a was decreased to 15% on the reaction in
the presence of 1,3-bis(diphenylphosphino)propane (dppp)
and 1,10-bis(diphenylphosphino)ferrocene (dppf) (entries 2
and 3). Interestingly, vinyl-substituted dihydrofuran 12a
was predominantly yielded when bis(diphenylphosphino)-
methane (dppm) and triphenylphosphine were used as a
ligand (entries 4 and 5). The best result was obtained by
carrying out the reaction in the presence of 1,2-bis(diphenyl-
phosphino)ethylene (dppv) (58% yield for 2a, 27% yield for
12a) (entry 6). It was also found that the ratio of 2a to 12a was
changed by altering the reaction temperature (entries 7 and
8). Accordingly, the yield of 2a decreased to 22%, and that
of 12a increased to 74% by the reaction at 100 ꢀC (entry 8).
Our initial attempt at palladium-catalyzed reaction of dien-
ylic carbonate begins with (E,E)-1a (Table 1). When (E,E)-
1a was subjected to the reaction, treated with 5 mol %
1) TBDPSCl, NEt3
DMAP, CH2Cl2
TMS
OTBDPS
2) K2CO3, MeOH
2 steps 87%
OH
(Z)-4
7
1) (Z)-4, BuLi
TMEDA, THF
-78 °C
2) TBAF, THF
2 steps 59%
LiAlH4
O
ClCO2Me, Py HO
HO
HO
NaOMe
Pen
Pen
Pen
OH
Pen Pen
(E,Z)-1a
Pen Pen
CH2Cl2, 0 °C
88%
Pen Pen
THF, reflux
54%
OCO2Me
OH
3a
(Z)-5
(E,Z)-8
1)
OH
, PdCl2(PPh3)2
CuI, NEt3, 0 °C
1)
TMS
HO
HO
HInCl2, Et3B
THF, -78 °C HO
BuLi, TMEDA
THF, -78 °C, 98%
O
Pen
Pen
Pen
Pen
ClCO2Me, Py
HO
then I2
77%
Pen 2) K2CO3, MeOH
91%
Pen
CH2Cl2, 0 °C
88%
Pen
Pen Pen
2) LiAlH4, NaOMe
THF, reflux
2 steps 41%
I
OCO2Me
OH
9
3a
10
(Z,E)-1a
(Z,E)-8
1)
OH
HO
, PdCl2(PPh3)2
CuI, NEt3, 0 °C
H2, Pd-CaCO3
HO
Pen
Pen
HO
Pen
Pb(OAc)2, quinoline
Pen
Pen
Pen
AcOEt, 23%
2) ClCO2Me, Py, CH2Cl2
0 °C
2 steps 70%
OCO2Me
I
OCO2Me
11
(Z,Z)-1a
10
Scheme 3.

11220
M. Yoshida et al. / Tetrahedron 62 (2006) 11218–11226
Dienylic carbonates having various substituents were next
subjected to the palladium-catalyzed reaction conditions
described above (Table 2). Substrate (E,E)-1b with dicyclo-
hexylethyl substitution underwent the reaction to give cyclic
carbonate 2b in 50% yield along with dihydrofuran 12b in
19% yield (entry 1). Reaction of substrate (E,E)-1c contain-
ing a cyclohexanol moiety provided the corresponding prod-
uct 2c in 68% yield (entry 2). Dienylic carbonate (E,E)-1d,
which has unsymmetric substituents, was transformed to
cyclic carbonates 2d (1.8:1 mixture, 34% total yields) and
dihydrofurans 12d (1.8:1 mixture, 33% total yields) as the
diastereomeric mixture (entry 3). Although the conversion
of (E,E)-1d to 2d was unsatisfied, the yield could be
improved to 72% (3.5:1 mixture) when the process was
conducted under a CO2 atmosphere (entry 4). Substrate
(E,Z)-1a, which is a geometric isomer of (E,E)-1a, also
reacted with palladium catalyst to give cyclic carbonate 2a
in 70% yield with dihydrofuran 12a (entry 5). Similarly, re-
actions using other isomers (Z,E)-1a and (Z,Z)-1a resulted in
the production of 2a along with 12a in moderate yields, re-
spectively (entries 6 and 7). In these reactions, the olefinic
stereochemistries in the resulting cyclic carbonates 2a–d
are all E, and the results indicate that the reaction proceeds
via a thermodynamically favorable common intermediate.
A plausible mechanism for the formation of cyclic carbon-
ates 2 and dihydrofurans 12 is shown in Scheme 4. In this
process, the palladium catalyst initially promotes decarboxyl-
ation of the conjugated dienylic carbonate 1 to generate the
p-allylpalladium complex 13 and CO2. The complex 13
would be equilibrated to the intermediates 14, in which the
p-allylpalladium is migrated to the internal allylic position.
The intermediates 14 would be further transformed to the
most thermodynamically favorable syn-configurated isomer
140 via the p–s–p isomerization process.4 Finally, fixation
of CO2 followed by cyclization of the resulting intermediate
15 produces the cyclic carbonates 2. The selective formation
of (E)-1,3-dienyl-substituted cyclic carbonate 2a regardless
of the olefinic geometry of the substrate 1a supports that all
the reactions have occurred via the common intermediate
140. On the other hand, dihydrofurans 12 would be yielded
from the direct cyclization of anti-configurated p-allyl
isomer 130 or 1400. At higher reaction temperatures, it is
expected that the direct cyclization would proceed prior to
the fixation of CO2 resulting in the selective formation of di-
hydrofurans 12 (entries 7 and 8 in Table 1).9 The best yield
for 2 was observed from the substrate (E,Z)-1a (entry 5 in
Table 2). For this reason, the initially formed p-allylinter-
mediate 1300 from (E,Z)-1a would be relatively unstable
Table 2. Reactions using various substituted dienylic carbonatesa
Entry
Dienylic carbonate 1
Product’s yield
2
12
O
Cy
HO
O
O
O
O
OCO2Me
1b
2b 50%
2c 68%
12b 19%
Cy
Cy
Cy
(E,E)-1b
Cy
Cy
O
HO
OCO2Me
2b
O
(E,E)-1c
O
O
3b
4c,e
HO
Ph
Ph
O
2d 34% (1.8:1)d,
2d 72% (3.5:1)d
12d 33% (1.8:1)d,
12d trace
OCO2Me
OCO2Me
O
O
O
Ph
(E,E)-1d
HO
Pen Pen
Pen
O
5c
2a 70%
2a 53%
12a 16%
12a 31%
O
Pen
Pen
(E,Z)-1a
Pen
HO
Pen
Pen
6c
OCO2Me
OCO2Me
(Z,E)-1a
HO
Pen
7c
2a 47%
12a 26%
Pen
(Z,Z)-1a
a
All reactions were carried out with 5 mol % Pd2(dba)3$CHCl3 and 20 mol % ligand in dioxane at 50 ꢀC for 4–12 h.
dppe was used as a ligand.
dppv was used as a ligand.
The stereochemistries of each product are not determined.
The reaction was carried out under CO2 atmosphere.
b
c
d
e

M. Yoshida et al. / Tetrahedron 62 (2006) 11218–11226
11221
because of the allylic strain, which would cause the fast con-
version to the intermediate 140 resulting in the efficient pro-
duction of cyclic carbonates 2. The increased yield of 12
from the reaction of (Z,E)-1a (entry 6 in Table 2) indicates
that initially formed p-allyl intermediate 130 or 1400 from
this substrate would facilitate the direct cyclization to give
12. Although the reason for the observed specificity for the
production of 2 and 12 depending on the ligand is not clear,
it is proposed that this CO2 elimination–fixation process is
sensitive for the steric and electronic property of the phos-
phine ligand.
and (E,E)-6 with palladium catalysis in the presence of
N,O-bis(trimethylsilyl)acetamide (BSA)10 gave cyclic car-
bonate 2a in 23% yield, which was derived from (E,E)-6,
along with the formation of (E,E)-1c-derived cyclic carbon-
ate 2c and (E,E)-6-derived dihydrofuran 12a in 31% and
14% yield, respectively. It has been clear that 2a arises by re-
action of in situ generated CO2 formed by decarboxylation
of (E,E)-1c.
3. Conclusion
O
In conclusion, we have developed a methodology for the
synthesis of 1,3-dienyl-substituted cyclic carbonates by
a CO2-recycling reaction of dienylic carbonates with a palla-
dium catalyst. This reaction proceeded via a successive
migration–isomerization of the resulting p-allylpalladium
intermediate as well as CO2 elimination–fixation process.
Cyclic carbonates are attractive and important compounds
in a variety of chemical research fields, and this reaction
would provide a new protocol for the synthesis of cyclic car-
bonates having a 1,3-dienyl substituent. Synthetic applica-
tions of the obtained products and further studies about
this type of reactions are now in progress.
O
O
HO
R
OCO2Me
R
R
R
1
2
PdLn
Pd+Ln
O
O
Pd+Ln
O
O
R
R
13
R
R
CO2
15
4. Experimental
4.1. General
Pd+Ln
Pd+Ln
O
O
R
R
14'
R
R
14
All nonaqueous reactions were carried out under a positive
atmosphere of argon and nitrogen in dried glassware unless
otherwise indicated. Materials were obtained from commer-
cial suppliers and used without further purification except
when otherwise noted. Solvents were dried and distilled
according to standard protocol. The phrase ‘residue upon
workup’ refers to the residue obtained when the organic
layer was separated and dried over anhydrous MgSO4 and
the solvent was evaporated under reduced pressure.
R
R
O
O
R
R
O
Pd+Ln
or
_
Pd+Ln
PdLn
R
R
14''
13'
12
Pd+Ln
O
14'
R
R
H
H
13''
Scheme 4. Proposed reaction mechanism for the production of 2 and 12.
4.1.1. (E)-6-Hydroxy-1,1-dipentyl-4-hexen-2-yn-1-ol
[(E)-5a]. To a stirred solution of siloxy enyne (E)-4 (1.5 g,
4.7 mmol) and TMEDA (1.1 mL, 7.05 mmol) in THF
(25 mL) was added dropwise a 1.60 M solution of BuLi in
hexane (4.4 mL, 7.05 mmol) at ꢁ78 ꢀC. After stirring was
continued for 2 h at ꢁ78 ꢀC, a solution of the 6-undecanone
(3a) (1.4 mL, 7.05 mmol) in THF (5 mL) was added drop-
wise to this solution, and stirring was continued for 4 h at
the same temperature. The reaction mixture was diluted
with water and extracted with Et2O. The combined extracts
were washed with aqueous NH4Cl and saturated aqueous
NaCl. The residue upon workup was chromatographed on sil-
ica gel with hexane–AcOEt (95:5 v/v) as eluent to give the
alcohol. To a stirred solution of alcohol in THF (30 mL)
was added dropwise a 1.0 M TBAF in THF (9.6 mL,
9.6 mmol) at rt. After stirring was continued for 24 h at the
same temperature. The reaction mixture was diluted with
water and extracted with Et2O. The combined extracts
were washed with aqueous NaHCO3 and saturated NaCl.
The residue upon workup was chromatographed on silica
gel with hexane–AcOEt (80:20 v/v) as eluent to give diol
(E)-5a [814 mg, 68% from (E)-4] as a yellow oil; IR (neat)
To examine whether CO2 dissociates from the substrate in
the reaction, a crossover experiment with allylic carbonate
(E,E)-1c and allylic benzoate (E,E)-6 was next performed
(Scheme 5). Reaction of an equimolar mixture of (E,E)-1c
HO
OCO2Me
5 mol% Pd2(dba)3⋅CHCl3
(E,E)-1c (0.5 eq)
20 mol% dppv
+
BSA, dioxane,
HO
under argon atmosphere
OBz
in sealed tube, 4 h
Pen Pen
(E,E)-6 (0.5 eq)
O
O
O
O
O
O
Pen
Pen
+
+
O
Pen
Pen
2a
2c
12a
31%
14%
23%
Scheme 5. Crossover experiment using carbonate (E,E)-1c and benzoate
(E,E)-6.
3304, 2934, 2860 cmꢁ1 1H NMR (300 MHz, CDCl3)
;

11222
M. Yoshida et al. / Tetrahedron 62 (2006) 11218–11226
d 0.96 (6H, t, J¼6.6 Hz), 1.31–1.68 (17H, m), 1.90 (1H, s),
4.22 (2H, dd, J¼3.6 and 6.4 Hz), 5.78 (1H, td, J¼3.6 and
15.9 Hz), 6.23 (1H, td, J¼6.4 and 15.9 Hz); 13C NMR
(75 MHz, CDCl3) d 13.8, 22.4, 23.7, 31.8, 41.8, 62.4, 71.5,
82.0, 92.9, 109.9, 141.8; MS m/z 181 [M+ꢁ71(C5H11)];
HRMS m/z calcd for C11H17O2 [M+ꢁ71(C5H11)]:
181.1228, found 181.1221.
5.70 (1H, d, J¼15.0 Hz), 5.74 (1H, td, J¼6.6 and
14.7 Hz), 6.23 (1H, dd J¼10.2 and 15.0 Hz), 6.34 (1H, dd,
J¼14.7 Hz); 13C NMR (75 MHz, CDCl3) d 13.9, 22.5,
23.1, 32.2, 41.0, 54.7, 68.1, 75.2, 124.9, 126.7, 134.8,
142.0, 155.8; MS m/z 241 [M+ꢁ71(C5H11)]; HRMS m/z
calcd for C13H21O4 [M+ꢁ71(C5H11)]: 241.1440, found
241.1432.
4.1.2. (E)-6-Hydroxy-1,1-bis(2-cyclohexylethyl)-4-hexen-
2-yn-1-ol [(E)-5b]. Yield 73% (for two steps); colorless oil;
4.1.6. (2E,4E)-1,1-Bis(2-cyclohexylethyl)-6-methoxycar-
bonyloxy-2,4-hexadien-1-ol [(E,E)-1b]. Yield 34% (for
two steps); yellow oil; IR (neat) 3479, 2922, 2851,
IR (neat) 3329, 2920, 2851 cmꢁ1 1H NMR (300 MHz,
;
CDCl3) d 0.84–0.96 (4H, m), 1.11–1.24 (10H, m), 1.33–
1.41 (4H, m), 1.63–1.74 (14H, m), 4.18–4.26 (2H, m),
5.78 (1H, d, J¼15.1 Hz), 6.23 (1H, td, J¼5.1 and
15.1 Hz); 13C NMR (75 MHz, CDCl3) d 26.2, 26.5, 31.6,
33.2, 37.8, 39.2, 62.6, 71.7, 82.0, 93.1, 110.0, 141.7; MS
m/z 301 [M+ꢁ31(CH2OH)]; HRMS m/z calcd for C21H33O
[M+ꢁ31(CH2OH)]: 301.2531, found 301.2525.
1747 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.85–0.87
;
(4H, m), 1.11–1.24 (10H, m), 1.45–1.50 (4H, m), 1.51–
1.69 (13H, m), 3.79 (3H, s), 4.66 (2H, d, J¼6.6 Hz), 5.71
(1H, d, J¼15.1 Hz), 5.78 (1H, dd, J¼6.6 and 14.9 Hz),
6.20 (1H, dd, J¼10.5 and 15.1 Hz), 6.32 (1H, dd, J¼10.5
and 14.9 Hz); 13C NMR (75 MHz, CDCl3) d 26.2, 26.5,
30.8, 33.2, 33.3, 38.0, 38.3, 54.6, 68.1, 75.1, 124.8, 126.8,
134.8, 142.0, 155.7; MS m/z 374 [M+ꢁ18(H2O)]; HRMS
m/z calcd for C24H38O2 [M+ꢁ18(H2O)]: 374.2821, found
374.2818.
4.1.3. 1-{(E)-(5-Hydroxy-3-hexen-1-yl)}-cyclohexanol
[(E)-5c]. Yield 57% (for two steps); yellow oil; IR (neat)
3461, 2931, 2856 cmꢁ1 1H NMR (300 MHz, CDCl3)
;
d 1.19–1.94 (10H, m), 2.51 (1H, br s), 2.68 (1H, s), 4.20
(2H, dd, J¼1.5 and 4.8 Hz), 5.79 (1H, dt, J¼1.5 and
15.9 Hz), 6.24 (1H, dt, J¼4.8 and 15.9 Hz); 13C NMR
(75 MHz, CDCl3) d 23.1, 25.0, 39.8, 62.3, 62.6, 69.0, 82.1,
93.5, 109.9, 141.9; MS m/z 180 (M+); HRMS m/z calcd for
C11H16O2 (M+): 180.1151, found 180.1150.
4.1.7. 1-{(1E,3E)-(5-Methoxycarbonyloxy-1,3-hexa-
dienyl)}-cyclohexanol [(E,E)-1c]. Yield 24% (for two
steps); yellow oil; IR (neat) 3400, 2932, 2856, 1732 cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 1.25–1.32 (2H, m), 1.49–
1.68 (9H, m), 3.78 (3H, s), 4.65 (2H, dd, J¼0.96 and
6.6 Hz), 5.76 (1H, td, J¼6.6 and 14.6 Hz), 5.87 (1H, d,
J¼14.6 Hz), 6.24–6.35 (2H, m); 13C NMR (75 MHz,
CDCl3) d 21.7, 25.2, 37.5, 54.6, 67.9, 71.2, 125.2, 125.9,
134.8, 143.3, 155.6; MS m/z 240 (M+); HRMS m/z calcd
for C13H20O4 (M+): 240.1361, found 240.1347.
4.1.4. 6-Hydroxy-1-methyl-1-phenyl-4-hexen-2-yn-1-ol
[(E)-5d]. Yield 38% (for two steps); yellow oil; IR (neat)
3287, 2984, 2927, 2862 cmꢁ1
;
1H NMR (300 MHz,
CDCl3) d 1.43 (3H, s), 1.43 (1H, s), 2.33 (1H, s), 4.23
(2H, dd, J¼1.8 and 5.1 Hz), 5.84 (1H, td, J¼1.8 and
15.9 Hz), 6.31 (1H, td, J¼5.1 and 15.9 Hz), 7.27–7.40
(3H, m), 7.64–7.67 (2H, m); 13C NMR (75 MHz, CDCl3)
d 33.2, 62.8, 70.3, 82.7, 93.2, 109.7, 124.9, 127.7, 128.3,
142.3, 145.5; MS m/z 187 [M+ꢁ15(CH3)]; HRMS m/z calcd
for C12H11O2 [M+ꢁ15(CH3)]: 187.0759, found 187.0747.
4.1.8. (2E,4E)-6-Methoxycarbonyloxy-1-methyl-1-phe-
nyl-2,4-hexadien-1-ol [(E,E)-1d]. Yield 35% (for two
steps); yellow oil; IR (neat) 3443, 2976, 2956, 1747 cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 1.68 (3H, s), 1.90 (1H, s),
3.78 (3H, s), 4.69 (2H, dd, J¼1.0 and 6.8 Hz), 5.79 (1H,
dt, J¼6.8 and 14.9 Hz), 6.04 (1H, d, J¼14.7 Hz), 6.27
(1H, dd, J¼10.4 and 14.7 Hz), 6.34 (1H, t, J¼10.4 Hz),
7.23–7.27 (1H, m), 7.32–7.36 (2H, m), 7.42–7.46 (2H, m);
13C NMR (75 MHz, CDCl3) d 29.5, 54.7, 67.9, 74.3,
125.2, 126.3, 126.7, 127.2, 128.4, 134.3, 142.0, 146.4,
155.7; MS m/z 247 [M+ꢁ15(CH3)]; HRMS m/z calcd for
C14H15O4 [M+ꢁ15(CH3)]: 247.0970, found 247.0953.
4.1.5. (2E,4E)-1,1-Dipentyl-6-methoxycarbonyloxy-2,4-
hexadien-1-ol [(E,E)-1a]. To a stirred suspension of LAH
(30.4 mg, 0.8 mmol) and NaOMe (86.4 mg, 1.6 mmol) in
THF (20 mL) was added dropwise the solution of diol (E)-
5a (100.0 mg, 0.4 mmol) in THF (5 mL) at 0 ꢀC. After
refluxing for 3 h, the reaction mixture was treated with the
minimum amount of cold water, and extracted with AcOEt.
The combined extracts were washed with aqueous NaHCO3
and saturated NaCl. The residue upon workup was chroma-
tographed on silica gel with hexane–AcOEt (95:5 v/v) as
eluent to give the dienylic alcohol. To a stirred solution of
this dienylic alcohol and pyridine (97.1 mL, 1.2 mmol) in
CH2Cl2 (20 mL) was added dropwise methyl chloroformate
(34.0 mL, 0.44 mmol) at 0 ꢀC, and stirring was continued for
1 h at the same temperature. The reaction mixture was
diluted with water and extracted with AcOEt. The combined
extracts were washed with aqueous NH4Cl and saturated
NaCl. The residue upon workup was chromatographed on
silica gel with hexane–AcOEt (70:30 v/v) as eluent to give
dienylic carbonate (E,E)-1a [52.6 mg, 42% from (E)-5a]
4.1.9. (2E,4E)-1,1-Dipentyl-6-benzoyloxy-2,4-hexadien-
1-ol [(E,E)-6]. To a stirred suspension of LAH (96.4 mg,
2.54 mmol) and NaOMe (274 mg, 5.08 mmol) in THF
(25 mL) was added dropwise the solution of diol (E)-5a
(257 mg, 1.27 mmol) in THF (5 mL) at 0 ꢀC. After refluxing
for 3 h, the reaction mixture was treated with the minimum
amount of cold water, and extracted with AcOEt. The com-
bined extracts were washed with aqueous NaHCO3 and
saturated NaCl. The residue upon workup was chromato-
graphed on silica gel with hexane–AcOEt (95:5 v/v) as
eluent to give the dienylic alcohol. To a stirred solution of
the resulting dienylic alcohol, triethylamine (0.35 mL,
2.54 mmol) and a catalytic amount of DMAP in CH2Cl2
(20 mL) was added dropwise benzoyl chloride (0.15 mL,
1.27 mmol) at 0 ꢀC, and stirring was continued for 1 h at
the same temperature. The reaction mixture was diluted
with water and extracted with AcOEt. The combined
as a colorless oil; IR (neat) 3477, 2932, 2858, 1732 cmꢁ1
;
1H NMR (300 MHz, CDCl3) d 0.88 (6H, t, J¼6.9 Hz),
1.25–1.51 (17H, m), 3.79 (3H, s), 4.66 (2H, d, J¼6.6 Hz),

M. Yoshida et al. / Tetrahedron 62 (2006) 11218–11226
11223
extracts were washed with aqueous NH4Cl and saturated
NaCl. The residue upon workup was chromatographed on
silica gel with hexane–AcOEt (80:20 v/v) as eluent to give
dienyl allylic benzoate (E,E)-6 [358 mg, 79% from (E)-5a]
chromatographed on silica gel with AcOEt–hexane (20:80
v/v) as eluent to give diol (Z)-5 (162 mg, 59% from (Z)-4)
as a yellow oil; IR (neat) 3333, 2934, 2860 cmꢁ1 1H
;
NMR (300 MHz, CDCl3) d 0.91 (6H, t, J¼6.9 Hz), 1.26–
1.69 (16H, m), 1.94 (1H, s), 2.05 (1H, s), 4.40 (2H, dd,
J¼1.5 and 5.7 Hz), 5.64 (1H, td, J¼1.5 and 10.8 Hz), 6.08
(1H, td, J¼5.7 and 10.8 Hz); 13C NMR (75 MHz, CDCl3)
d 13.9, 22.5, 23.8, 31.8, 41.8, 60.8, 71.7, 79.8, 98.6, 110.4,
141.4; MS m/z 181 [M+ꢁ71(C5H11)]; HRMS m/z calcd for
C11H17O2 [M+ꢁ71(C5H11)]: 181.1229, found 181.1229.
as a colorless oil; IR (neat) 3416, 2932, 2860, 1715 cmꢁ1
;
1H NMR (300 MHz, CDCl3) d 0.88 (6H, t, J¼6.6 Hz),
1.27–1.63 (16H, m), 4.86 (2H, d, J¼6.3 Hz), 5.75 (2H, d,
J¼15.3 Hz), 5.87 (1H, td, J¼6.6 and 14.7 Hz), 6.26
(1H, dd, J¼10.5 and 14.7 Hz), 6.39 (1H, dd, J¼10.5
and 15.3 Hz), 7.41–7.47 (2H, m), 7.53–7.59 (1H, m),
8.05–8.08 (2H, m); 13C NMR (75 MHz, CDCl3) d 13.9,
22.5, 23.1, 32.2, 41.1, 65.2, 75.2, 125.8, 126.9, 128.4,
129.7, 130.3, 133.0, 134.1, 141.6, 166.5; MS m/z
340 [M+ꢁ18(H2O)]; HRMS m/z calcd for C23H32O2
[M+ꢁ18(H2O)]: 340.2402, found 340.2383.
4.1.12. (2E,4Z)-6-Hydroxy-1,1-dipropyl-2,4-hexadien-1-
ol [(E,Z)-8]. To a stirred suspension of LAH (22.8 mg,
0.60 mmol) and NaOMe (64.8 mg, 1.20 mmol) in THF
(15 mL) was added dropwise the solution of diol (Z)-5
(75.7 mg, 0.30 mmol) in THF (5 mL) at 0 ꢀC. After reflux-
ing for 3 h, the reaction mixture was treated with the mini-
mum amount of cold water, and extracted with AcOEt.
The combined extracts were washed with aqueous NaHCO3
and saturated NaCl. The residue upon workup was chroma-
tographed on silica gel with hexane–AcOEt (95:5 v/v) as
eluent to give dienylic alcohol (E,Z)-8 (41.5 mg, 54%) as
a colorless oil; IR (neat) 3360, 2955, 2860 cmꢁ1; 1H NMR
(300 MHz, CDCl3) d 0.88 (6H, t, J¼6.6 Hz), 1.26–1.33
(12H, m), 1.49–1.55 (4H, m), 1.78 (1H, s), 2.08 (1H, s),
4.33 (2H, d, J¼6.9 Hz), 5.35 (1H, td, J¼6.9 and 11.1 Hz),
5.73 (1H, d, J¼15.0 Hz), 6.10 (1H, t, J¼11.1 Hz), 6.51
(1H, dd, J¼11.1 and 15.0 Hz); 13C NMR (75 MHz,
CDCl3) d 13.9, 22.5, 23.1, 32.2, 41.0, 58.6, 75.3, 122.5,
128.8, 130.4, 142.1; MS m/z 183 [M+ꢁ71(C5H11)]; HRMS
m/z calcd for C11H19O2 [M+ꢁ71(C5H11)]: 183.1385, found
183.1366.
4.1.10. (Z)-5-tert-Butyldiphenylsilyloxy-3-penten-1-yne
[(Z)-4]. To a stirred solution of (Z)-allylic alcohol 7
(308 mg, 2.0 mmol), triethylamine (0.56 mL, 4.0 mmol)
and a catalytic amount of DMAP in CH2Cl2 (20 mL) was
added TBDPSCl (0.627 mL, 2.4 mmol) at 0 ꢀC, and stirring
was continued for 1 h at rt. The reaction mixture was diluted
with water and extracted with AcOEt. The combined ex-
tracts were washed with aqueous NH4Cl and saturated aque-
ous NaCl. The residue upon workup was chromatographed
on silica gel with hexane–AcOEt (95:5 v/v) as eluent to
give TBDPS ether. To a stirred solution of the formed
TBDPS ether in methanol (20 mL) was added K2CO3
(332 mg, 2.4 mmol) at rt. After stirring was continued for
5 h at rt, the reaction mixture was diluted with water and ex-
tracted with Et2O. The combined extracts were washed with
saturated NaCl. The residue upon workup was chromato-
graphed on silica gel with hexane–AcOEt (90:10 v/v) as
eluent to give silyl ether (Z)-4 (559.7 mg, 87% from 7) as
a colorless oil; IR (neat) 3294, 2932, 2856 cmꢁ1; 1H NMR
(400 MHz, CDCl3) d 1.05 (9H, s), 3.00 (1H, s), 4.49 (2H,
dd, J¼1.6 and 6.0 Hz), 5.45 (1H, ddd, J¼1.6, 3.6 and
10.8 Hz), 6.17 (1H, dt, J¼6.0 and 10.8 Hz), 7.53–7.44
(6H, m), 7.64–17.69 (4H, m); 13C NMR (100 MHz,
CDCl3) d 19.2, 26.9, 62.4, 79.3, 82.8, 108.0, 127.6, 129.6,
133.5, 135.5, 144.4; MS m/z 320 (M+); HRMS m/z calcd
for C21H24OSi (M+): 320.1596, found 320.1578.
4.1.13. (2E,4Z)-1,1-Dipentyl-6-methoxycarbonyloxy-2,4-
hexadien-1-ol [(E,Z)-1a]. To a stirred solution of dienylic
alcohol (E,Z)-8 (40.7 mg, 0.16 mmol) and pyridine
(38.8 mL, 0.48 mmol) in CH2Cl2 (5 mL) was added drop-
wise methyl chloroformate (13.6 mL, 0.18 mmol) at 0 ꢀC,
and stirring was continued for 1 h at the same temperature.
The reaction mixture was diluted with water and extracted
with AcOEt. The combined extracts were washed with aque-
ous NH4Cl and saturated NaCl. The residue upon workup
was chromatographed on silica gel with hexane–AcOEt
(80:20 v/v) as eluent to give dienylic carbonate (E,Z)-1a
(44.0 mg, 88%) as a colorless oil; IR (neat) 3485, 2931,
4.1.11. (Z)-6-Hydroxy-1,1-dipentyl-4-hexen-2-yn-1-ol
[(Z)-5]. To a stirred solution of silyl ether (Z)-4 (352 mg,
1.1 mmol) and TMEDA (0.25 mL, 1.65 mmol) in THF
(20 mL) was added dropwise a 1.60 M solution of BuLi in
hexane (1.0 mL, 1.65 mmol) at ꢁ78 ꢀC. After stirring was
continued for 2 h at ꢁ78 ꢀC, a solution of the 6-undecanone
(3a) (0.34 mL, 1.65 mmol) in THF (5 mL) was added drop-
wise to this solution, and stirring was continued for 4 h at the
same temperature. The reaction mixture was diluted with
water and extracted with Et2O. The combined extracts
were washed with aqueous NH4Cl and saturated aqueous
NaCl. The residue upon workup was chromatographed on
silica gel with hexane–AcOEt (90:10 v/v) as eluent to give
propargylic alcohol. To a stirred solution of the formed prop-
argylic alcohol in THF (30 mL) was added dropwise a 1.0 M
TBAF in THF (2.2 mL, 2.2 mmol) at rt. After stirring was
continued for 24 h at the same temperature. The reaction
mixture was diluted with water and extracted with Et2O.
The combined extracts were washed with aqueous NaHCO3
and saturated NaCl. The residue upon workup was
2860, 1730 cmꢁ1 1H NMR (300 MHz, CDCl3) d 0.88
;
(6H, t, J¼7.2 Hz), 1.27–1.34 (11H, m), 1.45–1.54 (6H, m),
3.79 (3H, s), 4.83 (2H, d, J¼7.2 Hz), 5.52 (1H, td, J¼7.2
and 10.2 Hz), 5.78 (1H, d, J¼15.0 Hz), 6.21 (1H, dd,
J¼10.2 and 11.2 Hz), 6.51 (1H, dd, J¼11.2 and 15.0 Hz);
13C NMR (75 MHz, CDCl3) d 13.9, 22.5, 23.1, 32.2, 41.0,
54.7, 63.8, 75.3, 122.1, 122.7, 133.0, 143.5, 155.9; MS m/z
237 [M+ꢁ75(OCO2CH3)]; HRMS m/z calcd for C16H29O
[M+ꢁ75(OCO2CH3)]: 237.2218, found 237.2208.
4.1.14. 3-Pentyl-1-octyn-3-ol (9). To a stirred solution of tri-
methylsilyl acetylene (7.1 mL, 50.0 mmol) and TMEDA
(7.5 mL, 50.0 mmol) in THF (225 mL) was added dropwise
a 1.60 M BuLi in hexane (31.3 mL, 50.0 mmol) at ꢁ78 ꢀC.
After stirring was continued for 2 h at ꢁ78 ꢀC, a solution
of the 6-undecanone (3a) (5.1 mL, 25.0 mmol) in THF
(25.0 mL) was added dropwise to this solution, and stirring
was continued for 4 h at the same temperature. The reaction

11224
M. Yoshida et al. / Tetrahedron 62 (2006) 11218–11226
mixture was diluted with water and extracted with AcOEt.
The combined extracts were washed with aqueous NH4Cl
and saturated NaCl. The residue upon workup was chroma-
tographed on silica gel with hexane–AcOEt (90:10 v/v) as
eluent to give propargylic alcohol (6.58 g, 98%) as a color-
less oil. To a stirred solution of the above propargylic alcohol
(3.30 g, 12.3 mmol) in methanol (120 mL) was added
K2CO3 (2.04 g, 14.8 mmol) at rt. After stirring was contin-
ued for 5 h at rt, the reaction mixture was diluted with water
and extracted with Et2O. The combined extracts were
washed with saturated NaCl. The residue upon workup
was chromatographed on silica gel with hexane–AcOEt
(90:10 v/v) as eluent to give alkyne 9 (2.20 g, 91%) as a col-
orless oil; IR (neat) 3400, 3310, 2935, 3862 cmꢁ1; 1H NMR
(400 MHz, CDCl3) d 0.93 (6H, t, J¼6.8 Hz), 1.26–1.39 (8H,
m), 1.46–1.54 (4H, m), 1.61–1.69 (4H, m), 1.88 (1H, s), 2.43
(1H, s); 13C NMR (150 MHz, CDCl3) d 13.9, 22.5, 23.7,
31.9, 41.7, 71.0, 72.0, 87.0; MS m/z 125 [M+ꢁ71(C5H11)];
HRMS calcd for C8H13O [M+ꢁ71(C5H11)]: 125.1004,
found 125.0985.
reaction mixture was treated with the minimum amount of
cold water, and extracted with AcOEt. The combined
extracts were washed with aqueous NaHCO3 and saturated
NaCl. The residue upon workup was chromatographed on
silica gel with toluene–AcOEt (90:10 v/v) as eluent to give
dienylic alcohol (Z,E)-8 (165.9 mg, 41% from 10) as a
yellow oil; IR (neat) 3360, 2955, 2860 cmꢁ1 1H NMR
;
(400 MHz, CDCl3) d 0.88 (6H, t, J¼7.1 Hz), 1.22–1.30
(10H, m), 1.43–1.57 (8H, m), 4.20 (2H, d, J¼6.1 Hz), 5.30
(1H, d, J¼11.7 Hz), 5.77 (1H, td, J¼6.1 and 15.2 Hz),
6.01 (1H, t, J¼11.7 Hz), 7.14 (1H, dd, J¼11.5 and
15.2 Hz); 13C NMR (100 MHz, CDCl3) d 14.1, 22.7, 23.5,
32.4, 42.4, 63.6, 77.5, 128.3, 128.7, 133.4, 136.3; MS m/z
183 [M+ꢁ71(C5H11)]; HRMS m/z calcd for C11H19O2
[M+ꢁ71(C5H11)]: 183.1385, found 183.1373.
4.1.17. (2Z,4E)-1,1-Dipentyl-6-methoxycarbonyloxy-2,4-
hexadien-1-ol [(Z,E)-1a]. To a stirred solution of dienylic
alcohol (Z,E)-8 (166 mg, 0.65 mmol) and pyridine
(0.16 mL, 1.95 mmol) in CH2Cl2 (10 mL) was added drop-
wise methyl chloroformate (60.2 mL, 0.78 mmol) at 0 ꢀC,
and stirring was continued for 1 h at the same temperature.
The reaction mixture was diluted with water and extracted
with AcOEt. The combined extracts were washed with aque-
ous NH4Cl and saturated NaCl. The residue upon workup
was chromatographed on silica gel with hexane–AcOEt
(95:5 v/v) as eluent to give dienylic carbonate (Z,E)-1a
(178 mg, 88%) as a yellow oil; IR (neat) 3520, 2932,
4.1.15. (Z)-1,1-Dipentyl-3-iode-2-propen-1-ol (10). To
a stirred suspension of anhydrous indium trichloride
(747 mg, 3.4 mmol) in THF (25 mL) was added dropwise
DIBAL (1.0 M hexane solution, 3.3 mL, 3.3 mmol) at
ꢁ78 ꢀC. After stirring was continued for 30 min at
ꢁ78 ꢀC, a solution of alkyne 9 (491 mg, 2.5 mmol) in
THF (5 mL) and triethylborane (1.0 M hexane solution
0.5 mL, 0.5 mmol) were added to this suspension, and stir-
ring was continued for 2.5 h at the same temperature. Iodine
(1.9 g, 7.5 mmol) was then added to the reaction mixture,
and the mixture was continuously stirred for 30 min at
ꢁ78 ꢀC. The reaction mixture was poured into saturated
NaHCO3 solution and sodium thiosulfate solution was
added. The product was extracted with Et2O, and the com-
bined extracts were washed with saturated NaCl. The residue
upon workup was chromatographed on silica gel with
hexane–AcOEt (90:10 v/v) as eluent to give alkenyl iodide
10 (577 mg, 77%) as a colorless oil; IR (neat) 3467, 2930,
1
2860, 1747 cmꢁ1; H NMR (400 MHz, C6D6) d 0.43 (6H,
t, J¼6.8 Hz), 0.71–0.95 (17H, m), 2.86 (3H, s), 4.08 (2H,
dd, J¼1.2 and 6.6 Hz), 4.66 (1H, d, J¼12.0 Hz), 5.13
(1H, dt, J¼6.6 and 15.4 Hz), 5.45 (1H, t, J¼11.7 Hz), 7.07
(1H, ddd, J¼1.2, 11.7 and 15.4 Hz); 13C NMR (75 MHz,
CDCl3) d 13.9, 22.5, 23.2, 32.2, 42.3, 54.7, 68.4, 77.6,
127.1, 128.4, 132.1, 137.9, 155.8; MS m/z 237
[M+ꢁ75(OCO2CH3)]; HRMS m/z calcd for C16H29OI
[M+ꢁ75(OCO2CH3)]: 237.2219, found 237.2231.
4.1.18. (Z)-1,1-Dipentyl-6-methoxycarbonyloxy-2-hexen-
4-yn-1-ol (11). To a suspension of CuI (13.8 mg, 72.5 mmol)
and PdCl2(PPh3)4 (50.9 mg, 72.5 mmol) in triethyl-
amine (10 mL) was added propargyl alcohol (0.12 mL,
1.45 mmol) at 0 ꢀC. After stirring was continued for
30 min at 0 ꢀC, a solution of alkenyl iodide 10 (471 mg,
1.45 mmol) in triethylamine (5 mL) was added to this solu-
tion, and stirring was continued for 1 h at the same temper-
ature. The reaction mixture was poured into saturated NH4Cl
solution and extracted with AcOEt. The combined extracts
were washed with saturated NaCl. The residue upon workup
was chromatographed on silica gel with hexane–AcOEt
(70:30 v/v) as eluent to give enyne. To a stirred solution of
the formed enyne and pyridine (0.35 mL, 4.35 mmol) in
CH2Cl2 (20 mL) was added dropwise methyl chloroformate
(0.11 mL, 1.45 mmol) at 0 ꢀC, and stirring was continued for
1 h at the same temperature. The reaction mixture was di-
luted with water and extracted with AcOEt. The combined
extracts were washed with aqueous NH4Cl and saturated
NaCl. The residue upon workup was chromatographed on
silica gel with hexane–AcOEt (85:15 v/v) as eluent to give
propargylic carbonate 11 (315 mg, 70% from 10) as a yellow
1
2954 cmꢁ1; H NMR (400 MHz, CDCl3) d 0.89 (6H, t,
J¼6.8 Hz), 1.24–1.43 (12H, m), 1.54–1.71 (4H, m), 2.12
(1H, s), 6.25 (1H, d, J¼8.5 Hz), 6.49 (1H, d, J¼8.5 Hz);
13C NMR (100 MHz, CDCl3) d 14.1, 22.7, 23.2, 32.3,
40.6, 75.5, 77.3, 144.4; MS m/z 253 [M+ꢁ71(C5H11)];
HRMS m/z calcd for C8H14OI [M+ꢁ71(C5H11)]: 253.0089,
found 253.0074.
4.1.16. (2Z,4E)-6-Hydroxy-1,1-dipropyl-2,4-hexadien-1-
ol [(Z,E)-8]. To a suspension of CuI (16.2 mg, 85.0 mmol),
PdCl2(PPh3)2 (59.7 mg, 85.0 mmol) in triethylamine
(20 mL) was added propargyl alcohol (0.14 mL, 1.7 mmol)
at 0 ꢀC. After stirring was continued for 30 min at 0 ꢀC, a so-
lution of alkenyl iodide 10 (551 mg, 1.7 mmol) in triethyl-
amine (5 mL) was added to this solution, and stirring was
continued for 1 h at the same temperature. The reaction mix-
ture was poured into saturated NH4Cl solution and extracted
with AcOEt. The combined extracts were washed with satu-
rated NaCl. The residue upon workup was chromatographed
on silica gel with hexane–AcOEt (70:30 v/v) as eluent to
give enyne. To a stirred suspension of LAH (129 mg,
3.4 mmol) and NaOMe (367 mg, 6.8 mmol) in THF
(20 mL) was added dropwise the solution of the produced
enyne in THF (5 mL) at 0 ꢀC. After refluxing for 3 h, the
oil; IR (neat) 3562, 2932, 2860, 1747 cmꢁ1 1H NMR
;
(300 MHz, CDCl3) d 0.88 (6H, t, J¼6.9 Hz), 1.24–1.41
(12H, m), 1.43–1.56 (4H, m), 2.82 (1H, s), 3.81 (3H, s),

M. Yoshida et al. / Tetrahedron 62 (2006) 11218–11226
11225
4.86 (2H, d, J¼2.4 Hz), 5.56 (1H, td, J¼2.4 and 12.0 Hz),
5.93 (1H, d, J¼12.0 Hz); 13C NMR (75 MHz, CDCl3)
d 13.8, 22.4, 23.0, 32.1, 41.0, 54.9, 55.9, 76.4, 83.5, 88.8,
105.8, 150.6, 155.0; MS m/z 310 (M+); HRMS m/z calcd
for C18H30O4 (M+): 310.2144, found 310.02115.
4.2.3. (3E)-1,2-Carbonyldioxy-bis(2-cyclohexylethyl)-
hexadiene (2b). Yield 50%; yellow oil; IR (neat) 2922,
2851, 1801 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.87–
;
0.94 (4H, m), 1.11–1.33 (12H, m), 1.62–1.78 (14H, m),
4.77 (1H, d, J¼7.6 Hz), 5.28 (1H, d, J¼9.5 Hz), 5.36 (1H,
d, J¼14.9 Hz), 5.64 (1H, dd, J¼7.6 and 14.9 Hz), 6.32–
6.42 (2H, m); 13C NMR (75 MHz, CDCl3) d 26.1, 26.4,
30.2, 30.2, 30.6, 33.0, 33.0, 33.1, 33.2, 33.8, 37.7, 37.8,
84.5, 88.5, 120.8, 124.4, 135.1, 136.7, 154.2; MS m/z 360
(M+); HRMS m/z calcd for C23H36O3 (M+): 360.2655, found
360.2642.
4.1.19. (2Z,4E)-1,1-Dipentyl-6-methoxycarbonyloxy-2,4-
hexadien-1-ol [(Z,Z)-1a]. To a stirred solution of propar-
gylic carbonate 11 (79.1 mg, 0.23 mmol) in AcOEt
(2.6 mL) was added to Pd/CaCO3 (14.0 mg) poisoned with
lead and quinoline (5.6 mL) at rt. The reaction flask was
purged with H2. After stirring was continued for 4 h at
same temperature. The reaction mixture was filtered through
a short pad of Celite. The residue upon workup was chroma-
tographed on silica gel with hexane–AcOEt (95:5 v/v) as
eluent to give dienylic carbonate (Z,Z)-3a (16.0 mg, 23%)
4.2.4. 2,2-Bis-(2-cyclohexyl-ethyl)-5-vinyl-2,5-dihydro-
furan (12b). Yield 19%; colorless oil; IR (neat) 2922,
2851, 1448 cmꢁ1 1H NMR (400 MHz, CDCl3) d 0.78–
;
0.81 (4H, m), 1.07–1.22 (12H, m), 1.41–1.63 (14H, m),
5.02 (1H, dd, J¼1.2 and 10.2 Hz), 5.07 (1H, dd, J¼1.0
and 7.3 Hz), 5.17 (1H, dd, J¼1.2 and 17.4 Hz), 5.58 (1H,
dd, J¼2.0 and 6.1 Hz), 5.61 (1H, d, J¼6.1 Hz), 5.72 (1H,
ddd, J¼7.3, 10.2, and 17.4 Hz); 13C NMR (100 MHz,
CDCl3) d 26.4, 26.4, 26.7, 31.5, 32.0, 33.4, 33.4, 33.5,
37.1, 37.6, 38.2, 38.2, 87.1, 93.5, 115.5, 128.3, 133.4,
139.0; MS m/z 316 (M+); HRMS m/z calcd for C22H36O
(M+): 316.2767, found 316.2758.
as a yellow oil; IR (neat) 3498, 2955, 2860, 1747 cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 0.88 (6H, t, J¼6.8 Hz),
1.21–1.34 (11H, m), 1.54–1.58 (6H, m), 3.79 (3H, s), 4.81
(2H, dd, J¼1.5 and 7.1 Hz), 5.44 (1H, d, J¼12.0 Hz), 5.58
(1H, td, J¼7.1 and 12.0 Hz), 6.27 (1H, t, J¼12.0 Hz), 7.13
(1H, tt, J¼1.5 and 12.0 Hz); 13C NMR (100 MHz, CDCl3)
d 14.1, 22.7, 23.4, 32.3, 42.4, 54.8, 63.2, 77.6, 123.1,
124.0, 129.3, 138.9, 155.6; MS m/z 294 [M+ꢁ18(H2O)];
HRMS m/z calcd for C18H30O3 [M+ꢁ18(H2O)]: 294.2195,
found 294.2179.
4.2.5. (3E)-1,2-Carbonyldioxy-(1-spirocyclohexyl)-3,5-
hexadiene (2c). Yield 68%; yellow oil; IR (neat) 3026,
4.2. General procedure for the palladium-catalyzed
reaction of dienylic carbonate 1. Reaction of (E,E)-1a
(entry 6 in Table 1)
2928, 1800 cmꢁ1 1H NMR (400 MHz, CDCl3) d 1.21–
;
1.30 (1H, m), 1.39–1.46 (1H, m), 1.55–1.58 (6H, m),
1.60–1.92 (2H, m), 4.64 (1H, d, J¼7.8 Hz), 5.27 (1H, d,
J¼5.6 and 9.3 Hz), 5.35 (1H, d, J¼5.6 and 15.6 Hz), 5.65
(1H, dd, J¼7.8 and 14.2 Hz), 6.31–6.42 (2H, m); 13C
NMR (75 MHz, CDCl3) d 21.5, 22.1, 24.7, 31.5, 35.4,
85.7, 85.7, 120.1, 123.9, 134.9, 136.6, 153.9; MS m/z 208
(M+); HRMS m/z calcd for C12H16O3 (M+): 208.1100, found
208.1061.
To a stirred solution of dienylic carbonate [(E,E)-1a]
(34.3 mg, 0.11 mmol) in dioxane (1.1 mL) were added
Pd2(dba)3$CHCl3 (5.7 mg, 5.5 mmol) and dppv (8.7 mg,
22.0 mmol) in a sealed tube at rt. After stirring was continued
for 4 h at 50 ꢀC, the reaction mixture was concentrated
and the residue was chromatographed on silica gel with
hexane–AcOEt (90:10 v/v) as eluent to give cyclic carbonate
2a (17.8 mg, 58%) and dihydrofuran 12a (7.0 mg, 27%) as
a colorless oil, respectively.
4.2.6. Carbonyldioxy-1-methyl-1-phenyl-(3E)-hexadiene
(2d). Yield 34% (1.8:1 diastereomeric mixture); major prod-
uct: yellow oil; IR (neat) 2983, 2930, 1798 cmꢁ1; 1H NMR
(400 MHz, CDCl3) d 1.68 (3H, s), 4.96 (1H, d, J¼7.8 Hz),
5.33 (1H, d, J¼9.5 Hz), 5.39 (1H, d, J¼15.8 Hz), 5.80
(1H, dd, J¼8.0 and 14.4 Hz), 6.37–6.48 (2H, m), 7.32–
7.44 (5H, m); 13C NMR (100 MHz, CDCl3) d 23.1, 86.4,
86.7, 121.5, 122.8, 123.8, 128.9, 129.0, 134.8, 137.9,
140.9, 153.4; MS m/z 230 (M+); HRMS m/z calcd for
C14H14O3 (M+): 230.0943, found 230.0936. Minor product:
yield 12%; yellow oil; IR (neat) 2982, 2927, 1798 cmꢁ1; 1H
NMR (400 MHz, CDCl3) d 1.88 (3H, s), 4.93 (1H, dd, J¼8.5
and 18.1 Hz), 4.96 (1H, d, J¼8.5 Hz), 5.16 (1H, dd, J¼1.2
and 10.4 Hz), 5.28 (1H, dd, J¼1.2 and 17.1 Hz), 6.08 (1H,
td, J¼10.4 and 17.1 Hz), 6.29 (1H, dd, J¼10.4 and
18.1 Hz), 7.20–7.24 (2H, m), 7.32–7.41 (3H, m); 13C
NMR (100 MHz, CDCl3) d 26.7, 86.7, 87.2, 120.9, 124.9,
125.1, 128.4, 128.5, 134.7, 136.9, 137.6, 153.9; MS m/z
230 (M+); HRMS m/z calcd for C14H14O3 (M+): 230.0943,
found 230.0936.
4.2.1. (3E)-1,2-Carbonyldioxy-1,1-dipentyl-hexadiene
(2a). Yield 58%; colorless oil; IR (neat) 2931, 2870,
1
1790 cmꢁ1; H NMR (400 MHz, CDCl3) d 0.89 (6H, t,
J¼6.8 Hz), 1.26–1.75 (16H, m), 4.80 (1H, d, J¼7.6 Hz),
5.27 (1H, d, J¼9.2 Hz), 5.35 (1H, d, J¼14.7 Hz), 5.67
(1H, dd, J¼7.6 and 14.4 Hz), 6.33–6.41 (2H, m); 13C
NMR (75 MHz, CDCl3) d 13.8, 22.3, 22.5, 22.5, 31.8,
31.8, 33.2, 36.3, 84.5, 88.3, 120.9, 124.3, 135.1, 136.8,
154.2; MS m/z 236 [M+ꢁ44(CO2)]; HRMS m/z calcd for
C16H28O [M+ꢁ44(CO2)]: 236.2140, found 236.2134.
4.2.2. 2,2-Dipentyl-5-vinyl-2,5-dihydrofuran (12a). Yield
27%; yellow oil; IR (neat) 2930, 2860, 1468 cmꢁ1 1H
;
NMR (300 MHz, CDCl3) d 0.88 (6H, t, J¼6.9 Hz), 1.26–
1.37 (12H, m), 1.50–1.61 (4H, m), 5.09 (1H, dd, J¼1.2
and 10.2 Hz), 5.16 (1H, dd, J¼1.8 and 7.2 Hz), 5.25 (1H,
dd, J¼1.2 and 17.1 Hz), 5.60 (1H, dd, J¼1.8 and 6.0 Hz),
5.61 (1H, d, J¼6.0 Hz), 5.80 (1H, ddd, J¼7.2, 10.2 and
17.1 Hz); 13C NMR (75 MHz, CDCl3) d 13.9, 22.5, 22.6,
23.6, 24.0, 32.3, 32.3, 39.8, 40.1, 87.1, 93.5, 115.7, 128.4,
133.4, 139.1; MS m/z 236 (M+); HRMS m/z calcd for
C16H28O (M+): 236.2140, found 236.2133.
4.2.7. 2-Methyl-2-phenyl-5-vinyl-2,5-dihydrofuran
(12d). Yield 33% (1.8:1 diastereomeric mixture); colorless
oil; IR (neat) 2923, 2852, 1462 cmꢁ1; 1H NMR (400 MHz,
CDCl3) d 1.65 (1.92H, s), 1.69 (1.08H, s), 5.10 (0.64H, dt,
J¼1.2 and 10.2 Hz), 5.17 (0.36H, dt, J¼1.2 and 10.2 Hz),

11226
M. Yoshida et al. / Tetrahedron 62 (2006) 11218–11226
M.; Fukuzawa, S.; Sakai, S. Chem. Lett. 1985, 199; (b)
Trost, B. M.; Angle, S. R. J. Am. Chem. Soc. 1985, 107,
6123; (c) Trost, B. M.; Lynch, J. K.; Angle, S. R.
Tetrahedron Lett. 1987, 28, 375; (d) Wershofen, S.; Scharf,
H. D. Synthesis 1988, 854; (e) Suzuki, S.; Fujita, Y.;
Kobayashi, Y.; Sato, F. Tetrahedron Lett. 1989, 30, 3487;
Uemura, K.; Shiraishi, D.; Noziri, M.; Inoue, Y. Bull. Chem.
Soc. 1999, 72, 1063.
5.26 (1H, m), 5.31–5.37 (1H, m), 5.72 (1H, m), 5.80 (0.64H,
ddd, J¼7.3, 10.0 and 17.3 Hz), 5.90 (0.36H, ddd, J¼7.0, 9.5
and 17.3 Hz), 6.04 (1H, m), 7.23 (1H, m), 7.30–7.34 (2H,
m), 7.40–7.45 (2H, m); MS m/z 186 (M+); HRMS m/z calcd
for C13H14O (M+): 186.1044, found 186.1040.
4.3. Crossover experiment of (E,E)-1a and (E,E)-6
3. (a) Yoshida, M.; Ihara, M. Angew. Chem., Int. Ed. 2001, 40,
616; (b) Yoshida, M.; Fujita, M.; Ishii, T.; Ihara, M. J. Am.
Chem. Soc. 2003, 125, 4874; (c) Yoshida, M.; Fujita, M.;
Ihara, M. Org. Lett. 2003, 5, 3325; (d) Yoshida, M.; Ohsawa,
Y.; Ihara, M. J. Org. Chem. 2004, 69, 1590; (e) Yoshida, M.;
Ihara, M. Chem.—Eur. J. 2004, 2886.
4. For reviews about palladium-catalyzed reactions of allylic
compounds: (a) Tsuji, J. Acc. Chem. Res. 1969, 2, 144; (b)
Tsuji, J. Pure Appl. Chem. 1982, 54, 197; (c) Tsuji, J.
J. Organomet. Chem. 1986, 300, 281; (d) Tsuji, J.
Tetrahedron 1986, 42, 4261; (e) Tsuji, J.; Minami, I. Acc.
Chem. Res. 1987, 20, 140; (f) Trost, B. M.; Van Vranken,
D. L. Chem. Rev. 1996, 96, 395.
To a stirred solution of dienylic carbonate (E,E)-1c
(35.4 mg, 0.15 mmol) and dienylic benzoate (E,E)-6
(53.7 mg, 0.15 mmol) in dioxane (3.0 mL) were added
Pd2(dba)3$CHCl3 (15.5 mg, 15.0 mmol), dppv (23.8 mg,
0.06 mmol), and BSA (55.6 mL, 0.23 mmol) in a sealed
tube at rt. After stirring was continued for 4 h at 50 ꢀC, the
reaction mixture was concentrated and the residue was chro-
matographed on silica gel with hexane–AcOEt (95:5 v/v) as
eluent to give 2a (9.5 mg, 23%), 2c (9.6 mg, 31%), and dihy-
drofuran 12a (5.0 mg, 14%) as a colorless oil, respectively.
Acknowledgements
5. (a) Trost, B. M.; Lautens, M.; Hung, M.-H.; Carmichael, C. S.
J. Am. Chem. Soc. 1984, 106, 7641; (b) Ishii, Y.; Gao, C.; Xu,
W.-X.; Iwasaki, M.; Hidai, M. J. Org. Chem. 1993, 58, 6818;
(c) Kang, S.-K.; Park, D.-C.; Jeon, J.-H.; Rho, H.-S.; Yu,
C.-M. Tetrahedron Lett. 1994, 35, 2357; (d) Kang, S.-K.;
Park, D.-C.; Rho, H.-S.; Yu, C.-M.; Hong, J.-H. Synth.
Commun. 1995, 25, 203.
We are grateful to the referee for the suggestion about a part
of reaction mechanism in Scheme 4. This study was sup-
ported in part by a Grant-in-Aid for the Encouragement
for Young Scientists (B) from the Japan Society for the
Promotion of Science (JSPS) and Mitsubishi Chemical
Corporation Fund (for M.Y.).
6. Pearson, W. H.; Hines, J. V. J. Org. Chem. 2000, 65,
5785.
References and notes
€
7. Hartung, I. V.; Eggert, U.; Haustedt, L. O.; Niess, B.; Schafer,
P. M.; Hoffmann, H. M. R. Synthesis 2003, 1844.
8. Takami, K.; Mikami, S.; Yorimitsu, H.; Shinokubo, H.;
Oshima, K. J. Org. Chem. 2003, 68, 6627.
9. As another possibility for the production of 12, reversible ring
opening of 2 by palladium followed by the direct cyclization
from the p-allyl complex 130 or 1400 would be occurred (see
Refs. 5c and 5d). However, no reaction has occurred from a
reaction of the isolated cyclic carbonate 2a with palladium
catalyst. The result implies that cyclic carbonate 2 is produced
irreversibly.
1. Arakawa, H.; Aresta, M.; Armor, J. N.; Barteau, M. A.;
Beckman, E. J.; Bell, A. T.; Bercaw, J. E.; Creutz, C.; Dinjus,
E.; Dixon, D. A.; Domen, K.; DuBois, D. L.; Eckert, J.;
Fujita, E.; Gibson, D. H.; Goddard, W. A.; Goodman, D. W.;
Keller, J.; Kubas, G. J.; Kung, H. H.; Lyons, J. E.; Manzer,
L. E.; Marks, T. J.; Morokuma, K.; Nicholas, K. M.; Periana,
R.; Que, L.; Rostrup-Nielson, J.; Sachtler, W. M. H.;
Schmidt, L. D.; Sen, A.; Somorjai, G. A.; Stair, P. C.; Stults,
B. R. Chem. Rev. 2001, 101, 953.
2. Examples about palladium-catalyzed CO2 fixation reactions to
give cyclic carbonates: (a) Fujinami, T.; Suzuki, T.; Kamiya,
10. For a review on BSA: El Gihani, M. T.; Heaney, H. Synthesis
1998, 357.