Rhodium(I)-catalyzed cycloisomerization of 1,3-dienes with alkenes in a tether

Article abstract of DOI:10.1055/s-0028-1087973

A rhodium(I)-catalyzed cycloisomerization of 1,3-dienes with alkenes in a tether proceeded smoothly, giving cyclopentene or cyclohexene derivatives in good yields. The existence of a hetero atom between the 1,3-diene moiety and the olefin in the tether af

Full text of DOI:10.1055/s-0028-1087973

PAPER
969
Rhodium(I)-Catalyzed Cycloisomerization of 1,3-Dienes with Alkenes in a
Tether
R
hodium(I)-Cataly
o
zed
C
yclois
s
omerizatio
h
nof 1,3-Die
i
nes hiro Oonishi,a Akira Saito,a Miwako Mori,b Yoshihiro Sato*a
a
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Fax +81(11)7064982; E-mail: biyo@pharm.hokudai.ac.jp
b
Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Received 25 September 2008; revised 11 November 2008
Abstract: A rhodium(I)-catalyzed cycloisomerization of 1,3-
dienes with alkenes in a tether proceeded smoothly, giving cyclo-
pentene or cyclohexene derivatives in good yields. The existence of
a hetero atom between the 1,3-diene moiety and the olefin in the
tether affected the reaction course. In the case of the substrate hav-
ing no hetero atom between the 1,3-diene moiety and olefin in the
tether, cycloisomerization reaction proceeded, giving the corre-
sponding cyclic product. On the other hand, in the case of the sub-
strate having a hetero atom between the 1,3-diene moiety and olefin
in the tether, the reaction course was completely changed to give a
[4+2] cycloaddition product.
[Rh(dppe)]ClO4
(10 mol%)
R
R
R
R
CHO
DCE
65 °C, 4 h
77%
CHO
3
3a
4a
R = CH2OBn
Scheme 2
Various transition-metal-catalyzed cycloisomerizations
accompanying a C–C bond formation between multiple
bonds have been reported in the literature.3 However, for
cycloisomerization between 1,3-diene and alkene, only an
iron-catalyzed cycloisomerization has been reported by
Takacs, in which 1,5-diene products were formed.4 Thus,
there has been no report on cycloisomerization of 1,3-
dienes with alkenes giving 1,3-diene products. For rhodi-
um(I)-catalyzed reactions of the substrate having a 1,3-di-
ene moiety and a tethered alkene, [4+2] cycloadditions
have been reported.5 Livinghouse reported [4+2] cycload-
ditions in 3b and 3c catalyzed by [(CF3)2CHO)P]2RhCl,
giving 5b and 5c, respectively, in good yields at 55 °C
(Scheme 3, Equation 1).5a–e Gilbertson reported that the
[4+2] cycloaddition in 3b proceeded even at room temper-
Key words: cyclizations, dienes, alkenes, rhodium, transition met-
als
The development of efficient, clean, and fast methods to
synthesize polycyclic complex molecules from simple
starting materials is one of the most important challenges
in modern synthetic organic chemistry. In this context,
transition-metal-catalyzed reactions offer many attractive
possibilities for constructing various cyclic structures not
easily made by conventional methods.1 We have recently
reported a rhodium(I)-catalyzed intramolecular hydroacy-
lation of 4,6-dienals by which various cycloheptenones
were obtained in good yields (Scheme 1).2
ature
with
a
cationic
rhodium(I)
catalyst,
[Rh(dppe)]SbF6,5f,g a catalyst similar to that used in our
reaction shown in Scheme 2 (Scheme 3, Equation 2).
During our ongoing investigation of this hydroacylation,
it was found that the reaction of 4,6-dienal 3a, having an
olefin in the tether, gave cyclopentene 4a in 77% yield via
cycloisomerization of the 1,3-diene moiety and the teth-
ered olefin (Scheme 2).
Thus, we were interested in the novel cycloisomerization
reaction and report herein the results of further investiga-
tions of this reaction.6 Initially, the reaction of (2E,4E)-
3d, having no aldehyde moiety, was carried out in order to
investigate the effect of an aldehyde group in the substrate
O
[Rh(dppe)]ClO4
(10 mol%)
O
R
Livinghouse
H
[(CF3)2CHO)3P]2RhCl
R
H
DCE
65 °C
(2.5 mol%)
1
X
X
(1)
2: 60–70%
THF, 55 °C
O
H
O
H
O
R
H
R
Rh
3b (X = O, R = H)
3c (X = CH2, R = OTBS)
R
Rh
5b (98%)
5c (61%)
Rh
R
R
Gilbertson
O
ii
i
iii
H
[Rh(dppe)]SbF6
(6 mol%)
Scheme 1
O
(2)
CH2Cl2, 25 °C
H
SYNTHESIS 2009, No. 6, pp 0969–0979
Advanced online publication: 24.02.2009
x
x
.
x
x
.2
0
0
9
3b
5b (42%)
DOI: 10.1055/s-0028-1087973; Art ID: F20708SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 3

970
Y. Oonishi et al.
PAPER
OTHP
Br
[Rh(dppe)]ClO4
(10 mol%)
E
E
R
R
E
E
7
R
R
olefinic
+
isomers
NaH, DMF
72%
DCE
r.t., 24 h
OTHP
6
8
(2E,4E)-3d
4d' (27%)
(51%)
E = CO2Et
R = CH2OBn
HO
BnBr, NaH
LiAlH4
[Rh(dppe)]ClO4
(cat.)
DCE
65 °C, 90%
DMF
93%
Et2O
quant
HO
OTHP
[Rh(dppe)]SbF6
(10 mol%)
9
R
R
R
R
TsOH
DCE
65 °C, 2 h
88%
MeOH
84%
R
R
OH
4d
OTHP
10
11
Scheme 6
R = CH2OBn
R
R
1) MnO2, CH2Cl2
[Rh(dppe)]SbF6 as a catalyst and that a [4+2] cycloaddi-
tion does not occur under our conditions.
2) Ph3PEtBr, PhLi
Et2O–THF
2 steps 78%
4
2
(2E,4E)-3d
Further investigations of the reaction of (2E,4E)-3d using
various rhodium(I) complexes were carried out, and the
results are summarized in Table 1. The reaction of
Scheme 4
(2E,4E)-3d
with
[Rh(dppp)]ClO4
instead
of
3 on this reaction. The substrates (2E,4E)-3d was synthe-
[Rh(dppe)]ClO4 decreased the yield of 4d to 34% and also
afforded the [4+2] cycloaddition product 5d¢ in 41% yield
(entry 2). The use of [Rh(dppb)]ClO4 did not promote the
cycloisomerization as much as it promoted the [4+2] cy-
cloaddition, and 5d¢ was obtained in 70% yield (entry 3).
On the other hand, a neutral catalyst, [Rh(dppe)]Cl, which
was generated in situ from [Rh(coe)2Cl]2 (5 mol%) and
dppe (10 mol%), did not promote the reaction, and the
starting material (2E,4E)-3d was recovered in 78% yield
(entry 4). By the use of other neutral catalysts such as
[Rh(dppb)]Cl and RhCl(PPh3)3, the [4+2] cycloaddition
product 5d was obtained as the main product in 42 and
81% yield, respectively (entries 5 and 6). These results
sized in a stereoselective manner, as shown in Scheme 4.
Treatment of (2E,4E)-3d with 10 mol% of
[Rh(dppe)]ClO4 in dichloroethane at 65 °C for two hours
gave cycloisomerization product 4d in 85% yield as the
sole product (Scheme 5).
[Rh(dppe)]ClO4
R
R
R
(10 mol%)
DCE
65 °C, 2 h
85%
R
4d
(2E,4E)-3d
R = CH2OBn
Scheme 5
Table 1 Effect of Catalyst on Cycloisomerization of (2E,4E)-3d
This result indicates that an aldehyde group in the sub-
strate is not necessary for this cycloisomerization. As
mentioned above, [4+2] cycloadditions of 1,3-dienes with
Rh catalyst
R
R
(10 mol%)
R
R
DCE
65 °C
alkenes
under
similar
conditions
(catalytic
(2E,4E)-3d
R = CH2OBn
4d
+
[Rh(dppe)]SbF6, CH2Cl2, 25 °C) have already been re-
ported by Gilbertson.5f,g Thus, in order to confirm the ef-
fect of the reaction temperature, the reaction of (2E,4E)-
3d was carried out at room temperature using
H
R
R
R
R
+
H
5d
5d'
[Rh(dppe)]ClO4 as
a
catalyst in dichloroethane
(Scheme 6). As a result, 4d¢ was obtained in 27% yield
along with an inseparable mixture of the products (51%
yield). When the mixture of inseparable products was
treated again with a catalytic amount of [Rh(dppe)]ClO4
in dichloroethane at 65 °C, 4d was obtained as a single
isomer in 90% yield, indicating that the mixture did not
contain [4+2] cycloaddition products and should be tran-
sient isomers of 4d. Additionally, it was found that only
cycloisomerization proceeded at 65 °C even with the use
of [Rh(dppe)]SbF6 as a catalyst, giving the cyclized prod-
uct 4d in 88% yield (Scheme 6).
Entry Catalyst
Time (h) 4d
5d
–
5d¢
–
1
[Rh(dppe)]ClO4
2
6
85%
34%
2
[Rh(dppp)]ClO4
[Rh(dppb)]ClO4
[Rh(dppe)]Clb
[Rh(dppb)]Clc
RhCl(PPh3)3
–
41%
70%
–
3
12
24
36
30
trace
–
4a
5a
6
–
–
–
–
42%
81%
–
–
a (2E,4E)-3d was recovered in 78% (entry 4) and 56% yield (entry 5).
b [Rh(coe)2Cl]2 + dppe.
These results indicate that this cycloisomerization pro-
ceeds even at room temperature and also by using
c [Rh(coe)2Cl]2 + dppb.
Synthesis 2009, No. 6, 969–979 © Thieme Stuttgart · New York

PAPER
Rhodium(I)-Catalyzed Cycloisomerization of 1,3-Dienes
971
suggested that the reaction course of this cycloisomeriza-
tion is strongly affected by the nature of ligands and that
[Rh(dppe)]ClO4 is the best catalyst for this cycloisomer-
ization.
R
R
1) MnO2, CH2Cl2
2
2) Ph3PEtBr
t-BuOK, THF
2 steps 79%
4
(2Z,4E)-3d
Next, solvent effects were investigated in the reaction of
(2E,4E)-3d using 10 mol% of [Rh(dppe)]ClO4 (Table 2).
In the reaction of (2E,4E)-3d in toluene, a trace amount of
cycloisomerization product 4d¢ was obtained, and the
[4+2] cycloaddition product 5d was obtained in 22% yield
as the major product. The use of THF or DMF as a solvent
was not effective in the reaction of (2E,4E)-3d. These re-
sults indicate that dichloroethane is most effective for the
cycloisomerization of (2E,4E)-3d.
R
R
1) MnO2, CH2Cl2
11
2) Ph3PMeBr
t-BuOK, THF
2 steps 69%
R = CH2OBn
3e
R
R
1) MnO2, CH2Cl2
2)
Ph3P+
2 OTBS
3g
2OTBS
Br–
12
PhLi, Et2O–THF
2 steps 70%
Table 2 Effects of Solvents on Cycloisomerization of (2E,4E)-3d
[Rh(dppe)]ClO4
(10 mol%)
OTHP
E'
Br
(2E,4E)-3d
4d + 4d' + 5d
7
1) LiAlH4, Et2O
65 °C, 24 h
E'
E'
NaH, DMF
73%
2) BnBr, NaH
DMF
3) TsOH, MeOH
E'
Entry
1a
Solvent
DCE
4d
4d¢
–
5d
OTHP
13
14
E' = CO2Me
85%
–
–
3 steps 65%
2b
toluene
THF
8%
3%
–
22%
trace
–
R
1) MnO2, CH2Cl2
2) Ph3PEtBr
PhLi, Et2O–THF
2 steps 78%
R
R
3b
trace
–
R
OH
4b
DMF
15
R = CH2OBn
3f
a The reaction was carried out at 65 °C for 2 h.
Scheme 7
b (2E,4E)-3d was recovered in 56% (entry 2), 50% (entry 3), and 92%
yield (entry 4).
a,b
Table 3 Reactions of Various Trienes with [Rh(dppe)]ClO4
Next, the scope and limitations of this cycloisomerization
were investigated. Substrates (2Z,4E)-3d, 3e, 3f, and 3g
were synthesized as shown in Scheme 7.
Entry Substrate
Time Product
(h)
R
R
The reaction of (2Z,4E)-3d, having an olefinic isomer of
(2E,4E)-3d with respect to C2 carbon, gave 4d in 80%
yield (Table 3, entry 1), indicating that the difference in
geometry at the 1,3-diene moiety does not affect the reac-
tion course.
1
14
R
R
4d (80%)
(2Z,4E)-3d
R
R
2
12
R
R
In the reaction of the terminal diene 3e, the corresponding
cycloisomerization product 4e was obtained in 59% yield
(entry 2). The reaction of 3f, having an internal diene and
disubstituted olefin in a tether, also proceeded smoothly to
give 4f in 77% yield (entry 3). The existence of a silyloxy
group in the side chain is tolerated in this cycloisomeriza-
tion, and cyclopentene 4g was obtained in 85% yield (en-
try 4).
4e (59%)
3e
R
R
3
18
R
R
4f (77%)
3f
R
R
4
4
R
R
2 OTBS
2 OTBS
Next, the construction of a 6-membered ring was exam-
ined. Substrates 19a and 19b were synthesized as shown
in Scheme 8.
3g
4g (85%)
a All reactions were carried out in DCE at 65 °C using 10 mol%
[Rh(dppe)]ClO4.
Treatment of 19a with 10 mol% of [Rh(dppe)]ClO4 in
dichloroethane at 65 °C for 18 hours gave the 5-mem-
bered ring product 4f in 83% yield (Scheme 9), and no de-
sired 6-membered ring product was obtained.
b R = CH2OBn.
ing 4f via rhodacycle. On the other hand, the reaction of
19b under the same conditions gave 6-membered ring
compound 26b in 60% yield along with 5-membered-ring
compound 4h in 13% yield. It was thought that the 5-
membered ring compound 4h was produced from 3h,
This result suggested that olefin isomerization of 19a oc-
curred before cycloisomerization under the conditions,
and cycloisomerization of 3f successively occurred, giv-
Synthesis 2009, No. 6, 969–979 © Thieme Stuttgart · New York

972
Y. Oonishi et al.
PAPER
respectively.7 These results are consistent with the above-
Br
E'
1) LiAlH4
Et2O, 99%
E'
E'
mentioned
reports
of
Gilbertson
(Scheme 3,
17
Equation 2)5f,g and indicate that a hetero atom in a tether
strongly affects the reaction course; that is, a [4+2] cy-
cloaddition product is obtained in the case of substrates
having a hetero atom between a 1,3-diene moiety and alk-
ene in the tether, while a cycloisomerization product is ob-
tained in the case of substrates having no hetero atom
between a 1,3-diene moiety and alkene in the tether.
2) BnBr, NaH
DMF, 83%
NaH, THF
59%
E'
16
E' = CO2Me
18
R
R
19a
R = CH2OBn
Br(CH2)3OTHP 20
H
E
E
E
E
[Rh(dppe)]ClO4
NaH, NaI
1) LiAlH4, Et2O
(10 mol%)
2) BnBr, NaH
DMF
O
DMF
72%
O
OTHP
6
DCE
r.t., 8 h
37%
E = CO2Et
21
H
2 steps 85%
3b
3i
5b
1) TsOH, MeOH
2) DMP, CH2Cl2
R
R
R
R
H
DIBAL-H
[Rh(dppe)]ClO4
(10 mol%)
3) Ph3P=CHCO2Me
CH2Cl2
OMe
toluene
86%
OTHP
TsN
TsN
DCE
r.t., 15 h
92%
22
O
R = CH2OBn
23
H
3 steps 84%
5i
R
R
R
1) MnO2, CH2Cl2
Scheme 10
2) Ph3PEtBr, PhLi
Et2O–THF
OH
R
A plausible reaction course of the cycloisomerization and
[4+2] cycloaddition is shown in Scheme 11.
19b
2 steps 57%
24
Scheme 8
A rhodacyclopentane iv was initially formed via oxidative
cycloaddition of triene 27 to a rhodium(I) complex, and
the rhodacyclopentane iv would be in equilibrium with iv-
a and iv-b. In the case of the substrate having no hetero
atom in the tether (X = CR2), cycloisomerization product
28 would be formed through syn-b-hydride elimination
from iv-a followed by an olefin isomerization reaction.
On the other hand, in the case of the substrate having a
hetero atom in the tether (X = O, NTs), the hetero atom
can transannularly coordinate to the rhodium center,
which might stabilize the intermediate iv-b and inhibit
syn-b-hydride elimination from iv-a. Thus, the rhodacy-
cloheptene intermediate vi would be formed from iv-b via
s-p-s rearrangement, and [4+2] cycloaddition product 29
would be preferentially formed via reductive elimination
from vi.
[Rh(dppe)]ClO4
(10 mol%)
R
R
DCE
65 °C, 18 h
83%
R
R
19a
R = CH2OBn
4f
R
R
Rh(I)
R
R
Rh
3f
25
R
[Rh(dppe)]ClO4
(10 mol%)
R
R
R
DCE
65 °C, 18 h
19b
26b (60%)
R = CH2OBn
In summary, we have succeeded in developing cyclo-
isomerization of 1,3-dienes with alkenes in a tether and in
the construction of 5- or 6-membered ring compounds. It
was found that the existence of a hetero atom between a
1,3-diene moiety and alkene in the tether affected the re-
action course.
+
R
R
R
R
3h
4h (13%)
Scheme 9
All manipulations were performed under argon unless otherwise
mentioned. Solvents were distilled under argon from sodium-ben-
zophenone (THF, Et2O, and toluene), CaH2 (DMF, CH2Cl2, and
DCE), or sodium (MeOH). Allylmalonic acid diethyl ester (6) was
purchased from TCI. All other solvents and reagents were purified
when necessary using standard procedures. Column chromatogra-
phy was performed on silica gel 60 (Merck, 70–230 mesh), and
flash chromatography was performed on silica gel 60 (Merck, 230–
400 mesh) with the indicated solvent as eluent. IR spectra were ob-
which would be formed through a double isomerization of
two olefins of the 1,3-diene moiety in 19b followed by cy-
cloisomerization.
Encouraged by these results, the synthesis of heterocyclic
compounds using this cycloisomerization was examined
(Scheme 10). Interestingly, we found that only a [4+2] cy-
cloaddition reaction proceeded in the case of 3b and 3i,
each having a hetero atom between a 1,3-diene moiety and
1
tained on a Perkin-Elmer FTIR 1605 spectrometer, and H NMR
alkene in the tether, to give 5b and 5i in 37 and 92% yield, and 13C NMR spectroscopy were carried out on a Jeol EX270 or a
Synthesis 2009, No. 6, 969–979 © Thieme Stuttgart · New York

PAPER
Rhodium(I)-Catalyzed Cycloisomerization of 1,3-Dienes
973
R1
X
R2
( )n
R1
H
27
olefin
isomerization
Rh
R1
H
R1
β-elimination
oxidative
cyclization
X
Rh
Rh-H
X
R2
( )n
( )n
( )n
R2
X
R1
H
iv-a
H
v
cycloisomerization
product (28)
R2
X
Rh
( )n
R1
R1
H
H
iv
R2
R1
σ−π−σ
H
reductive
elimination
H
H
R2
R2
rearrangement
Rh
H
( )n
R2
X
X
Rh
iv-b
X
( )n
H
( )n
H
vi
[4+2] cycloaddition
product (29)
Scheme 11
Jeol AL400 NMR spectrometer. Mass spectra were obtained on a
Jeol JMS-700TZ or a Jeol JMS-FAB mate mass spectrometer for
LRMS (EI) and HRMS (EI), and a Jeol JMS-HX-110 mass spec-
trometer for LRMS (FAB) and HRMS (FAB).
Hz, 2 H), 2.02 (br s, 2 H), 3.46–3.53 (m, 1 H), 3.58 (s, 4 H), 3.84–
3.90 (m, 1 H), 3.98 (dd, J = 12.3, 5.8 Hz, 1 H), 4.19 (dd, J = 12.3,
5.8 Hz, 1 H), 4.62 (dd, J = 3.2, 3.2 Hz, 1 H), 5.09 (d, J = 10.0 Hz,
1 H), 5.10 (d, J = 16.5 Hz, 1 H), 5.67 (dt, J = 15.2, 5.8 Hz, 1 H),
5.71–5.89 (m, 2 H).
Starting Materials 3a, 3d–g, 19a, and 19b
Diethyl 2-Allyl-2-[(E)-4-(tetrahydro-2H-pyran-2-yloxy)but-2-
enyl]malonate (8)
13C NMR (67.8 MHz, CDCl3): d = 19.5, 25.4, 30.6, 34.5, 36.1, 42.1,
62.3, 67.7, 68.0, 97.9, 118.0, 129.1, 129.8, 133.9.
LRMS (FAB): m/z = 271 [M+ +H], 187, 169, 120, 107.
HRMS (FAB): m/z [M+ + H] calcd for C15H27O4: 271.1909; found:
To a suspension of NaH (60% oil suspension, 988 mg, 24.7 mmol)
in DMF (30 mL) was added 6 (4.2 mL, 20.6 mmol) at 0 °C, and the
mixture was stirred at the same temperature for 1 h. To the mixture
was added a solution of 78 (4.84 g, 20.6 mmol) in DMF (11 mL) at
0 °C, and the mixture was stirred at r.t. for 1.5 h. To the mixture was
added sat. aq NH4Cl (50 mL), and the aqueous layer was extracted
with EtOAc (3 × 70 mL). The combined organic layers were washed
with brine (80 mL), and dried (Na2SO4). After removal of the sol-
vent, the residue was purified by column chromatography (silica
gel, hexane–EtOAc, 5:1); yield: 5.28 g (72%); colorless oil.
271.1936.
2-(E)-5,5-Bis(benzyloxymethyl)octa-2,7-dienyloxytetrahydro-
2H-pyran (10)
To a suspension of NaH (60% oil suspension, 1.70 g, 42.5 mmol) in
DMF (14 mL) was added a solution of 9 (3.90 g, 14.4 mmol) in
DMF (5 mL) at 0 °C, and the mixture was stirred at the same tem-
perature for 30 min. To the mixture was added BnBr (3.8 mL, 31
mmol) at 0 °C, and the mixture was stirred at r.t. for 11 h. To this
mixture was added sat. aq NH4Cl (30 mL), and the aqueous layer
was extracted with EtOAc (3 × 50 mL). The combined organic lay-
ers were washed with brine (60 mL), and dried (Na2SO4). After re-
moval of the solvent, the residue was purified by column
chromatography (silica gel, hexane–EtOAc, 30:1); yield: 6.0 g
(93%); colorless oil.
IR (neat): 2980, 2940, 1732, 1442, 1366, 1280, 1208, 1136, 1098,
1026 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.24 (t, J = 7.1 Hz, 6 H), 1.50–
1.60 (m, 4 H), 1.67–1.73 (m, 1 H), 1.78–1.85 (m, 1 H), 2.62 (d,
J = 6.5 Hz, 2 H), 2.64 (d, J = 6.5 Hz, 2 H), 3.47–3.51 (m, 1 H),
3.82–3.87 (m, 1 H), 3.92 (dd, J = 12.3, 7.1 Hz, 1 H), 4.13–4.20 (m,
5 H), 4.60 (dd, J = 3.4, 3.4 Hz, 1 H), 5.08 (d, J = 10.2 Hz, 1 H), 5.10
(d, J = 16.4 Hz, 1 H), 5.55 (dt, J = 15.2, 7.1 Hz, 1 H), 5.59 (m, 2 H).
IR (neat): 2940, 2856, 1200, 1116, 1078, 1024, 734, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.48–1.61 (m, 4 H), 1.67–1.73 (m,
1 H), 1.78–1.86 (m, 1 H), 2.11 (d, J = 7.5 Hz, 4 H), 3.30 (s, 4 H),
3.47–3.50 (m, 1 H), 3.84–3.94 (m, 2 H), 4.15 (dd, J = 12.5, 5.8 Hz,
1 H), 4.47 (s, 4 H), 4.6 (dd, J = 3.6, 3.6 Hz, 1 H), 5.03 (d, J = 11.1
Hz, 1 H), 5.04 (d, J = 15.0 Hz, 1 H), 5.67 (dt, J = 15.4, 5.8 Hz, 1
H), 5.67 (dt, J = 15.4, 7.5 Hz, 1 H), 5.73–5.58 (m, 1 H), 7.26–7.34
(m, 10 H).
13C NMR (67.8 MHz, CDCl3): d = 19.5, 25.5, 30.7, 35.0, 36.6, 42.2,
62.2, 67.7, 72.5, 73.2, 97.6, 117.6, 127.3, 127.3, 128.2, 129.4,
129.6, 134.3, 138.9.
13C NMR (67.8 MHz, CDCl3): d = 14.1, 19.5, 25.4, 30.6, 35.3, 36.8,
57.3, 61.2, 62.2, 67.2, 97.7, 119.1, 127.2, 131.1, 132.3, 170.7.
LRMS (EI): m/z = 354 [M+], 325, 309, 265, 253, 225, 179, 151, 105.
HRMS (EI): m/z calcd for C19H30O6: 354.2042; found: 354.2028.
2-Allyl-2-[(E)-4-(tetrahydro-2H-pyran-2-yloxy)but-2-enyl]pro-
pane-1,3-diol (9)
To a suspension of LiAlH4 (1.6 g, 42 mmol) in Et2O (40 mL) was
added a solution of 8 (5.1 g, 14 mmol) in Et2O (8 mL) at 0 °C, and
the suspension was stirred at r.t. for 2 h. To the mixture was added
H2O (5.1 mL), 15% aq NaOH (5.1 mL), and H2O (15.3 mL) at 0 °C,
and the mixture was stirred at r.t. for 1 h. The solution was filtered
and the filtrate was concentrated in vacuo. The residue was purified
by column chromatography (silica gel, hexane–EtOAc, 1:1); yield:
3.88 g (quant.); colorless oil.
IR (neat): 3420, 2942, 1442, 1118, 1024 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.52–1.62 (m, 4 H), 1.69–1.75 (m,
1 H), 1.80–1.84 (m, 1 H), 2.08 (d, J = 6.5 Hz, 2 H), 2.10 (d, J = 6.5
LRMS (EI): m/z = 450 [M+], 365, 359, 349, 275, 257, 167, 151, 91.
HRMS (EI): m/z calcd for C29H38O4: 450.2770; found: 450.2766.
(E)-5,5-Bis(benzyloxymethyl)octa-2,7-dien-1-ol (11)
To a solution of 10 (6.00 g, 13.3 mmol) in MeOH (133 mL) was
added p-TsOH·H2O (259 mg, 1.36 mmol) at 0 °C, and the mixture
was stirred at r.t. for 1.5 h. To the mixture was added sat. aq
NaHCO3 (50 mL). After removal of MeOH, the aqueous layer was
extracted with EtOAc (3 × 70 mL). The combined organic layers
Synthesis 2009, No. 6, 969–979 © Thieme Stuttgart · New York

974
Y. Oonishi et al.
PAPER
were washed with brine (80 mL), dried (Na2SO4), and concentrated.
The residue was purified by column chromatography (silica gel,
hexane–EtOAc, 5:1); yield: 4.1 g (84%); colorless oil.
IR (neat): 3382, 2978, 2858, 1454, 1364, 1098, 734, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.10–2.12 (m, 4 H), 3.29 (s, 4 H),
3.29 (br s, 1 H), 4.04 (d, J = 3.2 Hz, 2 H), 4.47 (s, 4 H), 5.02 (d,
J = 10.7 Hz, 1 H), 5.03 (d, J = 15.5 Hz, 1 H), 5.63 (d, J = 15.3 Hz,
1 H), 5.64 (d, J = 15.3 Hz, 1 H), 5.63–5.83 (m, 1 H), 7.24–7.35 (m,
10 H).
(m, 1 H), 5.97 (dd, J = 10.1, 10.1 Hz, 1 H), 6.32 (dd, J = 14.8, 10.1
Hz, 1 H), 7.26–7.35 (m, 10 H), 9.74 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 20.7, 35.8, 36.8, 42.7, 43.8, 72.5,
73.2, 117.5, 126.8, 127.1, 127.1, 127.7, 128.0, 129.8, 131.0, 134.1,
138.6, 201.4.
LRMS (EI): m/z = 327 [M+ – Bn], 309, 235, 201, 91.
Anal. Calcd for C28H34O3: C, 80.35; H, 8.19. Found: C, 80.27; H,
8.32.
13C NMR (100 MHz, CDCl3): d = 34.9, 36.6, 42.2, 63.7, 72.3, 73.1,
117.7, 127.3, 127.3, 128.2, 128.3, 132.0, 134.2, 138.7.
(2E,4E)-7,7-Bis(benzyloxymethyl)deca-2,4,9-triene [(2E,4E)-
3d]
To a solution of 11 (1.1 g, 3.0 mmol) in CH2Cl2 (12 mL) was added
MnO2 (3.2 g, 37 mmol) and the whole suspension was stirred at r.t.
for 19 h. The solution was filtered on Celite, and removal of the sol-
vent gave the crude intermediate aldehyde. To a suspension of
[Ph3PEt]+Br– (1.22 g, 3.29 mmol) in THF (9.6 mL) and Et2O (4.8
mL) was added 1.5 M PhLi in Et2O (2.2 mL, 3.3 mmol) at r.t., and
the mixture was stirred for 30 min. To the mixture was added a so-
lution of the crude aldehyde in Et2O (4.8 mL) at –78 °C. After stir-
ring the mixture at –78 °C for 5 min, a 1.5 M solution of PhLi in
Et2O (2.2 mL, 3.3 mmol) was added at the same temperature, and
the mixture was warmed to –30 °C. To the mixture was added t-
BuOK (503 mg, 4.49 mmol) and t-BuOH (0.45 mL, 4.49 mmol) at
the same temperature and stirred at r.t. for 1 h, and then sat. aq
NH4Cl (30 mL) was added. The aqueous layer was extracted with
EtOAc (3 × 50 mL) and the combined organic layers were washed
with brine (60 mL), and dried (Na2SO4). After removal of the sol-
vent, the residue was purified by column chromatography (silica
gel, hexane–EtOAc, 50:1); yield: 875 mg (78% from 11); colorless
oil.
LRMS (EI): m/z = 275 [M+ – Bn], 257, 227, 167, 137, 107, 91.
HRMS (EI): m/z [M+ – Bn] calcd for C17H23O3: 275.1647; found:
275.1640.
(4Z,6E)-Ethyl 9,9-Bis(benzyloxymethyl)dodeca-4,6,11-
trienoate
To a solution of 11 (1.83 g, 5.00 mmol) in CH2Cl2 (20 mL) was add-
ed MnO2 (4.4 g, 50 mmol) and the whole suspension was stirred at
r.t. for 24 h. The solution was filtered on Celite, and removal of the
solvent gave the crude intermediate aldehyde. To a suspension of
[Ph3P(CH2)3CO2Et]+Br– (3.4 g, 7.4 mmol) in THF (18 mL) was add-
ed t-BuOK (716 mg, 6.38 mmol) at –78 °C and the mixture was
stirred for 1 h. To the mixture was added a solution of the crude al-
dehyde in THF (16 mL) at –78 °C, and the mixture was stirred at the
same temperature for 1 h and then at r.t. for 1 h. To the mixture was
added sat. aq NH4Cl (20 mL), and the aqueous layer was extracted
with EtOAc (3 × 40 mL). The combined organic layers were washed
with brine (60 mL), dried (Na2SO4), and concentrated. The residue
was purified by column chromatography (silica gel, hexane–
EtOAc, 10:1); yield: 1.96 g (85% from 11); colorless oil.
IR (neat): 2915, 2854, 1453, 1363, 1100, 734, 696 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.72 (d, J = 6.1 Hz, 3 H), 2.10 (d,
J = 7.6 Hz, 4 H), 3.29 (s, 4 H), 4.47 (s, 4 H), 5.02 (d, J = 11.1 Hz,
1 H), 5.03 (d, J = 16.4 Hz, 1 H), 5.46–5.60 (m, 2 H), 5.73–5.83 (m,
1 H), 5.98 (dd, J = 11.1, 8.1 Hz, 1 H), 6.01 (dd, J = 11.8, 8.1 Hz, 1
H), 7.24–7.36 (m, 10 H).
13C NMR (67.8 MHz, CDCl3): d = 18.2, 35.3, 36.7, 42.6, 72.4, 73.1,
117.4, 126.8, 127.0, 127.1, 128.0, 128.0, 131.5, 133.1, 134.1, 138.6.
IR (neat): 2904, 2856, 1734, 1454, 1098, 736, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.24 (t, J = 7.1 Hz, 3 H), 2.12 (d,
J = 7.4 Hz, 2 H), 2.17 (d, J = 7.4 Hz, 2 H), 2.36 (dt, J = 7.4, 7.4 Hz,
2 H), 2.46 (dd, J = 7.4, 7.4 Hz, 2 H), 3.30 (s, 4 H), 4.12 (q, J = 7.1
Hz, 2 H), 4.47 (s, 4 H), 5.03 (d, J = 11.6 Hz, 1 H), 5.04 (d, J = 15.4
Hz, 1 H), 5.27 (dt, J = 10.3, 7.4 Hz, 1 H), 5.65 (dt, J = 15.0, 7.4 Hz,
1 H), 5.73–5.84 (m, 1 H), 5.96 (dd, J = 10.3, 10.3 Hz, 1 H), 6.33 (dd,
J = 15.0, 10.3 Hz, 1 H), 7.24–7.34 (m, 10 H).
LRMS (EI): m/z = 376 [M+], 285, 262, 249, 193, 177, 147, 91.
13C NMR (100 MHz, CDCl3): d = 15.0, 23.9, 35.0, 36.3, 37.4, 43.2,
61.0, 73.2, 73.8, 118.3, 127.9, 127.9, 128.0, 128.7, 128.8, 130.4,
131.4, 139.4, 134.9, 173.5.
HRMS (EI): m/z calcd for C26H32O2: 376.2402; found: 376.2390.
Anal. Calcd for C26H32O2: C, 82.94; H, 8.57. Found: C, 82.93; H,
8.62.
LRMS (EI): m/z = 371 [M+ – Bn], 342, 314, 180, 145, 129, 117,
105, 91.
(2Z,4E)-7,7-Bis(benzyloxymethyl)deca-2,4,9-triene [(2Z,4E)-
3d]
HRMS (EI): m/z [M+ – Bn] calcd for C23H31O4: 371.2222; found:
371.2218.
To a suspension of [Ph3PEt]+Br– (241 mg, 0.65 mmol) in THF (1
mL) was added t-BuOK (73 mg, 0.65 mmol) at –78 °C and the mix-
ture was stirred for 1 h. To the mixture was added a solution of the
crude aldehyde, which was prepared from 11 (184 mg, 0.50 mmol)
using a similar procedure for the synthesis of (2E,4E)-3d, in THF
(2.3 mL) at –78 °C, and the mixture was stirred at the same temper-
ature for 1 h and then at r.t. for 1 h. To the mixture was added sat.
aq NH4Cl (10 mL), and the aqueous layer was extracted with EtOAc
(3 × 10 mL). The combined organic layers were washed with brine
(10 mL), dried (Na2SO4), and concentrated The residue was purified
by column chromatography (silica gel, hexane–EtOAc, 50:1); yield:
149 mg (79% from 11); colorless oil.
(4Z,6E)-9,9-Bis(benzyloxymethyl)dodeca-4,6,11-trienal (3a)
To a solution of the above ester (290 mg, 0.63 mmol) in toluene (2.6
mL) was added 1.0 M DIBAL-H in hexane (0.82 mL, 0.82 mmol)
at –78 °C, and the solution was stirred at the same temperature for
20 min. To the solution was added MeOH (0.1 mL) and sat. aq po-
tassium sodium tartrate (10 mL). After stirring the mixture at r.t. for
1 h, the aqueous layer was extracted with Et2O (3 × 10 mL). The
combined organic layers were washed with brine (10 mL), and dried
(Na2SO4). After removal of the solvent, the residue was purified by
column chromatography (silica gel, hexane–EtOAc, 10:1); yield:
254 mg (96%); colorless oil.
IR (neat): 2916, 2856, 1453, 1364, 1099, 734, 697 cm–1.
IR (neat): 3064, 3026, 2898, 2856, 1724, 1454, 1098, 736, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.71 (d, J = 7.1 Hz, 3 H), 2.10 (d,
J = 7.5 Hz, 2 H), 2.15 (d, J = 7.5 Hz, 2 H), 3.31 (s, 4 H), 4.47 (s, 4
H), 5.03 (d, J = 10.8 Hz, 1 H), 5.04 (d, J = 17.0 Hz, 1 H), 5.38 (dq,
J = 11.0, 7.1 Hz, 1 H), 5.61 (dt, J = 14.9, 7.5 Hz, 1 H), 5.74–5.85
1H NMR (400 MHz, CDCl3): d = 2.12 (d, J = 7.2 Hz, 2 H), 2.17 (d,
J = 7.2 Hz, 2 H), 2.43–2.54 (m, 4 H), 3.31 (s, 4 H), 4.48 (s, 4 H),
5.03 (d, J = 12.4 Hz, 1 H), 5.04 (d, J = 14.7 Hz, 1 H), 5.26 (dt,
J = 10.1, 7.2 Hz, 1 H), 5.67 (dt, J = 14.8, 7.2 Hz, 1 H), 5.73–5.84
Synthesis 2009, No. 6, 969–979 © Thieme Stuttgart · New York

PAPER
Rhodium(I)-Catalyzed Cycloisomerization of 1,3-Dienes
975
(m, 1 H), 5.95 (dd, J = 11.0, 11.0 Hz, 1 H), 6.35 (dd, J = 14.9, 11.0
Hz, 1 H), 7.25–7.34 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 13.3, 35.6, 36.7, 42.6, 72.6, 73.2,
117.6, 124.2, 127.3, 127.3, 128.2, 128.4, 129.5, 129.5, 134.5, 138.9.
13C NMR (100 MHz, CDCl3): d = –4.9, 18.6, 26.1, 35.4, 36.4, 36.7,
42.7, 63.1, 72.5, 73.2, 117.4, 127.1, 127.2, 127.8, 128.0, 128.3,
132.0, 133.1, 134.2, 138.7.
LRMS (EI): m/z = 520 [M+], 429, 412, 399, 355, 321, 249, 233,
189, 159, 91.
LRMS (EI): m/z = 376 [M+], 285, 267, 249, 193, 147, 133, 107, 91.
Anal. Calcd for C33H48O3Si: C, 76.10; H, 9.29. Found: C, 76.20; H,
9.25.
HRMS (EI): m/z calcd for C26H32O2: 376.2402; found: 376.2415.
Anal. Calcd for C26H32O2: C, 82.94; H, 8.57. Found: C, 82.99; H,
8.47.
Dimethyl 2-[(E)-But-2-enyl]-2-[(E)-4-(tetrahydro-2H-pyran-2-
yloxy)but-2-enyl]malonate (14)
(1E,3E)-6,6-Bis(benzyloxymethyl)nona-1,3,8-triene (3e)
To a suspension of NaH (60% oil suspension, 3.56 g, 45.5 mmol) in
DMF (46 mL) was added a solution of 1310 (7.0 g, 38 mmol) in
DMF (10 mL) at 0 °C, and the mixture was stirred at the same tem-
perature for 30 min. To the mixture was added a solution of 78 (10.7
g, 45.5 mmol) in DMF (10 mL) at 0 °C, and stirred at r.t. for 1.5 h.
To the mixture was added sat. aq NH4Cl (60 mL), and the aqueous
layer was extracted with EtOAc (3 × 80 mL). The combined organic
layers were washed with brine (100 mL), and dried (Na2SO4). After
removal of the solvent, the residue was purified by column chroma-
tography (silica gel, hexane–EtOAc, 9:1); yield: 9.4 g (73%); color-
less oil.
To [Ph3PMe]+Br– (786 mg, 2.20 mmol) in THF (5.3 mL) was added
n-BuLi (1.62 M in hexane, 1.36 mL, 2.20 mmol) at –78 °C and the
mixture was stirred for 1 h. To the mixture was added a solution of
the crude aldehyde, which was prepared from 11 (732 mg, 2.00
mmol) using a similar procedure for the synthesis of (2E,4E)-3d, in
THF (2.3 mL) at –78 °C, and the mixture was stirred at the same
temperature for 1 h and then at r.t. for 1 h. To the mixture was added
sat. aq NH4Cl (15 mL), and the aqueous layer was extracted with
EtOAc (3 × 30 mL). The combined organic layers were washed with
brine (40 mL), dried (Na2SO4), and concentrated. The residue was
purified by column chromatography (silica gel, hexane–EtOAc,
50:1); yield: 496 mg (69% from 11); colorless oil.
IR (neat): 2950, 2869, 1737, 1438, 1275, 1202, 1134, 1077, 1025,
970 cm–1.
IR (neat): 2922, 2857, 1453, 1363, 1099, 734, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.52–1.85 (m, 6 H), 1.64 (d,
J = 6.4 Hz, 3 H), 2.55 (d, J = 7.4 Hz, 2 H), 2.62 (d, J = 6.4 Hz, 2 H),
3.47–3.52 (m, 1 H), 3.70 (s, 6 H), 3.82–3.94 (m, 2 H), 4.15 (dd,
J = 12.6, 5.5 Hz, 1 H), 4.59–4.61 (m, 1 H), 5.24 (dt, J = 15.2, 7.4
Hz, 1 H), 5.47–5.57 (m, 2 H), 5.65 (dt, J = 15.2, 6.4 Hz, 1 H).
13C NMR (67.8 MHz, CDCl3): d = 18.0, 19.5, 25.4, 30.6, 35.4, 35.7,
52.2, 57.9, 62.1, 67.1, 97.6, 124.4, 127.3, 129.9, 130.9, 171.2.
1H NMR (400 MHz, CDCl3): d = 2.12 (d, J = 7.3 Hz, 2 H), 2.14 (d,
J = 7.3 Hz, 2 H), 3.30 (s, 4 H), 4.47 (s, 4 H), 4.98–5.10 (m, 4 H),
5.66 (dt, J = 15.1, 7.3 Hz, 1 H), 5.74–5.84 (m, 1 H), 6.06 (dd,
J = 15.1, 10.3 Hz, 1 H), 6.30 (ddd, J = 16.6, 10.3, 10.3 Hz, 1 H),
7.22–7.32 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 35.4, 36.8, 42.7, 72.5, 73.2,
114.8, 117.5, 127.1, 127.2, 128.0, 130.5, 133.7, 134.1, 137.0, 138.6.
LRMS (EI): m/z = 340 [M+], 309, 279, 239, 207, 179, 119, 85.
LRMS (EI): m/z = 362 [M+], 271, 245, 179, 163, 133, 91.
HRMS (EI): m/z calcd for C18H28O6: 340.1886; found: 340.1888.
HRMS (EI): m/z calcd for C25H30O2: 362.2245; found: 362.2249.
(2E,7E)-5,5-Bis(benzyloxymethyl)nona-2,7-dien-1-ol (15)
To a suspension of LiAlH4 (2.27 g, 60.0 mmol) in Et2O (57 mL) was
added a solution of 14 (5.1 g, 15 mmol) in Et2O (10 mL) at 0 °C, and
the suspension was stirred at r.t. for 5 h. To the mixture was added
H2O (2.3 mL), 15% aq NaOH (2.3 mL), and H2O (6.9 mL) at 0 °C,
and stirred at r.t. for 1 h. The solution was filtered and the filtrate
was concentrated in vacuo to give a crude diol. To a suspension of
NaH (60% oil suspension, 1.68 g, 42.0 mmol) in DMF (43 mL) was
added a solution of the crude diol in DMF (25 mL) at 0 °C, and the
mixture was stirred at the same temperature for 30 min. To the mix-
ture was added BnBr (3.7 mL, 31 mmol) at 0 °C, and stirred at r.t.
for 14 h. To this mixture was added sat. aq NH4Cl (50 mL), and the
aqueous layer was extracted with EtOAc (3 × 80 mL). The com-
bined organic layers were washed with brine (100 mL), and dried
(Na2SO4). The solution was concentrated in vacuo to give the crude
intermediate benzyl ether. To a solution of the benzyl ether in
MeOH (130 mL) was added p-TsOH·H2O (269 mg, 1.41 mmol) at
0 °C, and the mixture was stirred at r.t. for 10 h. To the mixture was
added sat. aq NaHCO3 (80 mL). After the removal of MeOH, the
aqueous layer was extracted with EtOAc (3 × 120 mL). The com-
bined organic layers were washed with brine (120 mL), dried
(Na2SO4), and concentrated. The residue was purified by column
chromatography (silica gel, hexane–EtOAc, 5:1); yield: 3.71 g
(65% from 14); colorless oil.
Anal. Calcd for C25H30O2: C, 82.83; H, 8.34. Found: C, 82.81; H,
8.41.
[(3E,5E)-8,8-Bis(benzyloxymethyl)undeca-3,5,10-trienyl-
oxy](tert-butyl)dimethylsilane (3g)
To a suspension of phosphonium salt 129 (1.43 g, 2.77 mmol) in
THF (3.8 mL) and Et2O (1.9 mL) was added 1.12 M PhLi in Et2O
(2.50 mL, 2.77 mmol) at r.t., and the mixture was stirred for 30 min.
To the mixture was added a solution of the crude aldehyde, which
was prepared from 11 (846 mg, 2.31 mmol) using a similar proce-
dure for the synthesis of (2E,4E)-3d, in Et2O (1.9 mL) at –78 °C.
After stirring the mixture at –78 °C for 5 min, a 1.12 M solution of
PhLi in Et2O (2.50 mL, 2.77 mmol) was added at the same temper-
ature, and the mixture was warmed to –30 °C. To the mixture was
added t-BuOK (389 mg, 3.47 mmol) and t-BuOH (0.33 mL, 3.47
mmol) at the same temperature and stirred at r.t. for 1 h, and then
sat. aq NH4Cl (10 mL) was added. The aqueous layer was extracted
with EtOAc (3 × 20 mL) and the combined organic layers were
washed with brine (30 mL), and dried (Na2SO4). After removal of
the solvent, the residue was purified by column chromatography
(silica gel, hexane–EtOAc, 50:1); yield: 842 mg (70% from 11);
colorless oil.
IR (neat): 2927, 2856, 1099, 991 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.05 (s, 6 H), 0.90 (s, 9 H), 2.10
(d, J = 7.3 Hz, 2 H), 2.11 (d, J = 7.3 Hz, 2 H), 2.29 (dt, J = 7.3, 7.3
Hz, 2 H), 3.30 (s, 4 H), 3.64 (t, J = 7.3 Hz, 2 H), 4.47 (s, 4 H), 5.03
(d, J = 11.1 Hz, 1 H), 5.04 (d, J = 16.1 Hz, 1 H), 5.54 (dt, J = 14.4,
7.3 Hz, 2 H), 5.73–5.84 (m, 1 H), 6.00 (dd, J = 14.4, 7.9 Hz, 1 H),
6.03 (dd, J = 14.4, 7.9 Hz, 1 H), 7.24–7.35 (m, 10 H).
IR (neat): 3384, 2917, 2856, 1453, 1099, 1028, 972, 735, 697 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.12 (t, J = 6.0 Hz, 1 H), 1.63 (d,
J = 5.9 Hz, 3 H), 2.01 (d, J = 7.2 Hz, 2 H), 2.08 (d, J = 5.0 Hz, 2 H),
3.27 (s, 4 H), 4.03–4.04 (m, 2 H), 4.47 (s, 4 H), 5.36 (dt, J = 15.0,
7.2 Hz, 1 H), 5.44 (dq, J = 15.0, 5.9 Hz, 1 H), 5.62–5.64 (m, 2 H),
7.17–7.32 (m, 10 H).
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Y. Oonishi et al.
PAPER
13C NMR (100 MHz, CDCl3): d = 18.1, 34.8, 35.0, 42.3, 63.7, 72.4,
4.95 (ddd, J = 10.7, 1.2, 1.2 Hz, 1 H), 5.03 (ddd, J = 17.0, 1.3, 1.3
Hz, 1 H), 5.52 (dt, J = 14.0, 7.3 Hz, 1 H), 5.61 (dq, J = 14.1, 6.7 Hz,
1 H), 5.66–5.86 (m, 1 H), 5.99–6.10 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 18.2, 27.4, 30.3, 34.2, 42.0, 67.8,
114.1, 125.8, 127.4, 131.1, 133.2, 138.6.
73.1, 126.3, 127.3, 127.4, 128.1, 128.2, 128.6, 131.9, 138.9.
LRMS (EI): m/z = 289 [M+ – Bn], 271, 163, 151, 107, 91.
HRMS (EI): m/z [M+ – Bn] calcd for C18H25O3: 289.1804; found:
289.1818.
LRMS (EI): m/z = 210 [M+], 192, 174, 161, 145, 119, 105.
(2E,4E,9E)-7,7-Bis(benzyloxymethyl)undeca-2,4,9-triene (3f)
The crude product prepared from 15 (689 mg, 1.88 mmol) by a pro-
cedure similar to that used for the synthesis of (2E,4E)-3d, was pu-
rified by column chromatography (silica gel, hexane–EtOAc, 5:1);
yield: 575 mg (78% from 15); colorless oil.
HRMS (EI): m/z calcd for C13H22O2: 210.1620; found: 210.1604.
(7E,9E)-5,5-Bis(benzyloxymethyl)undeca-1,7,9-triene (19a)
To a suspension of NaH (60% oil suspension, 240 mg, 6.00 mmol)
in DMF (2 mL) was added a solution of the above-prepared 2-but-
3-enyl-2-[(2E,4E)-hexa-2,4-dienyl]propane-1,3-diol (421 mg, 2.00
mmol) in DMF (2 mL) at 0 °C, and the mixture was stirred at the
same temperature for 30 min. To the mixture was added BnBr (0.5
mL, 4.2 mmol) at 0 °C, and stirred at r.t. for 14 h. To this mixture
was added sat. aq NH4Cl (5 mL), and the aqueous layer was extract-
ed with EtOAc (3 × 10 mL). The combined organic layers were
washed with brine (10 mL), and dried (Na2SO4). After removal of
the solvent, the residue was purified by column chromatography
(silica gel, hexane–EtOAc, 30:1); yield: 648 mg (83%); colorless
oil.
IR (neat): 2913, 2853, 1453, 1099 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.63 (d, J = 6.3 Hz, 3 H), 1.73 (d,
J = 6.1 Hz, 3 H), 2.01 (d, J = 7.6 Hz, 2 H), 2.07 (d, J = 6.4 Hz, 2
H), 3.27 (s, 4 H), 4.47 (s, 4 H), 5.36 (dt, J = 15.8, 7.6 Hz, 1 H), 5.40–
5.44 (m, 1 H), 5.46–5.60 (m, 2 H), 5.98 (dd, J = 10.4, 5.6 Hz, 1 H),
6.01 (dd, J = 10.4, 5.6 Hz, 1 H), 7.23–7.34 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 18.0, 18.1, 35.1, 35.1, 42.7, 72.5,
73.1, 126.5, 126.8, 127.2, 127.3, 127.3, 127.9, 128.1, 131.8, 133.2,
138.9.
LRMS (EI): m/z = 390 [M+], 299, 282, 191, 173, 161, 133, 91.
IR (neat): 2925, 2855, 1451, 1362, 1098, 990, 733 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.37–1.43 (m, 2 H), 1.73 (d,
J = 6.1 Hz, 3 H), 1.96 (m, 2 H), 2.12 (d, J = 7.7 Hz, 2 H), 3.24 (s, 4
H), 4.47 (s, 4 H), 4.90 (dd, J = 10.2, 1.1 Hz, 1 H), 4.97 (dd, J = 17.2,
1.8 Hz, 1 H), 5.43–5.60 (m, 2 H), 5.73–5.84 (m, 1 H), 5.97 (dd,
J = 11.0, 8.3 Hz, 1 H), 6.01 (dd, J = 11.0, 8.3 Hz, 1 H), 7.25–7.37
(m, 10 H).
HRMS (EI): m/z calcd for C27H34O2: 390.2559; found: 390.2573.
Anal. Calcd for C27H34O2: C, 83.03; H, 8.77. Found: C, 83.19; H,
8.77.
Dimethyl 2-(But-3-enyl)-2-[(2E,4E)-hexa-2,4-dienyl]malonate
(18)
13C NMR (100 MHz, CDCl3): d = 18.3, 27.7, 31.5, 35.3, 42.2, 72.6
73.1, 113.8, 126.8, 126.9, 127.1, 127.2, 128.0, 131.5, 133.0, 138.7,
139.2.
To a suspension of NaH (60% oil suspension, 296 mg, 7.40 mmol)
in THF (12 mL) was added a solution of 1611 (1.25 g, 6.71 mmol)
in THF (5 mL) at 0 °C, and the mixture was stirred at the same tem-
perature for 30 min. To the mixture was added a solution of 1712 (1.2
g, 7.4 mmol) in THF (5 mL) at 0 °C, and stirred at r.t. for 1 h. To the
mixture was added sat. aq NH4Cl (10 mL), and the aqueous layer
was extracted with EtOAc (3 × 15 mL). The combined organic lay-
ers were washed with brine (20 mL), and dried (Na2SO4). After re-
moval of the solvent, the residue was purified by column
chromatography (silica gel, hexane–EtOAc, 5:1); yield: 1.05 g
(59%); colorless oil.
LRMS (EI): m/z = 390 [M+], 299, 282, 191, 173, 131, 91.
HRMS (EI): m/z calcd for C27H34O4: 390.2559, found: 390.2556.
Anal. Calcd for C27H34O2: C, 83.03; H, 8.77. Found: C, 83.11; H,
8.59.
Diethyl 2-Allyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]ma-
lonate (21)
IR (neat): 2954, 2924, 1723, 1271, 1240, 1205, 1156, 991cm–1.
To a suspension of NaH (60% oil suspension, 840 mg, 21.0 mmol)
in DMF (25 mL) was added a solution of 6 (3.60 mL, 17.5 mmol)
in DMF (10 mL) at 0 °C, and the mixture was stirred at the same
temperature for 30 min. To the mixture was added a solution of 2013
(4.3 g, 19.3 mmol) in DMF (5 mL) and NaI (2.89 g, 19.3 mmol) at
0 °C, and stirred at 50 °C for 24 h. To the mixture was added sat. aq
NH4Cl (40 mL), and the aqueous layer was extracted with EtOAc (3
× 60 mL). The combined organic layers were washed with brine (80
mL), and dried (Na2SO4). After removal of the solvent, the residue
was purified by column chromatography (silica gel, hexane–
EtOAc, 5:1); yield: 4.3 g (72%); colorless oil.
1H NMR (400 MHz, CDCl3): d = 1.72 (d, J = 6.9 Hz, 3 H), 1.75–
1.97 (m, 4 H), 2.65 (d, J = 7.5 Hz, 2 H), 3.71 (s, 6 H), 4.96 (d,
J = 10.0 Hz, 1 H), 5.02 (d, J = 15.8 Hz, 1 H), 5.33 (dt, J = 13.1, 7.5
Hz, 1 H), 5.61 (dq, J = 13.1, 6.9 Hz, 1 H), 5.71–5.81 (m, 1 H), 5.95
(dd, J = 13.1, 10.6 Hz, 1 H), 6.35 (dd, J = 13.1, 10.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 18.8, 28.4, 31.8, 36.1, 52.3, 57.7,
115.0, 124.2, 128.7, 131.1, 134.4, 137.5, 171.6.
LRMS (EI): m/z = 266 [M+], 234, 212, 206, 147, 133, 105, 81.
HRMS (EI): m/z calcd for C15H22O4: 266.1518; found: 266.1518.
IR (neat): 2942, 2871, 1732, 1444, 1201, 1034 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.25 (t, J = 7.1 Hz, 6 H), 1.47–
1.82 (m, 8 H), 1.91–1.98 (m, 2 H), 2.66 (d, J = 7.6 Hz, 2 H), 3.37
(dd, J = 9.8, 7.6 Hz, 1 H), 3.47–3.51 (m, 1 H), 3.72 (dd, J = 9.8, 7.6
Hz, 1 H), 3.81–3.89 (m, 1 H), 4.18 (q, J = 7.1 Hz, 4 H), 4.57 (dd,
J = 2.4, 2.4 Hz, 1 H), 5.08 (d, J = 9.9 Hz, 1 H), 5.10 (d, J = 17.6 Hz,
1 H), 5.66 (ddd, J = 17.6, 9.9, 7.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 13.9, 19.3, 24.1, 25.3, 28.6, 30.5,
36.6, 56.9, 61.0, 62.0, 67.0, 98.4, 118.7, 132.2, 171.0.
LRMS (FAB): m/z = 343 [M+ + H], 259, 241, 213, 154, 136, 121.
HRMS (FAB): m/z [M+ + H] calcd for C18H30O6: 343.2134; found:
2-(But-3-enyl)-2-[(2E,4E)-hexa-2,4-dienyl]propane-1,3-diol
To a suspension of LiAlH4 (342 mg, 9.01 mmol) in Et2O (8 mL) was
added a solution of 18 (799 mg, 3.00 mmol) in Et2O (2 mL) at 0 °C,
and the suspension was stirred at r.t. for 5 h. To the mixture was
added H2O (0.34 mL), 15% aq NaOH (0.34 mL), and H2O (1.02
mL) at 0 °C, and the mixture was stirred at r.t. for 1 h. The mixture
was filtered and the filtrate was concentrated in vacuo. The residue
was purified by column chromatography (silica gel, hexane–
EtOAc, 1:1); yield: 624 mg (99%); colorless oil.
IR (neat): 3374, 2925, 2857, 1052, 1024, 990, 910 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.36–1.42 (m, 2 H), 1.73 (d,
J = 6.7 Hz, 3 H), 2.02–2.11 (m, 6 H), 3.58 (s, 2 H), 3.60 (s, 2 H),
343.2121.
Synthesis 2009, No. 6, 969–979 © Thieme Stuttgart · New York

PAPER
Rhodium(I)-Catalyzed Cycloisomerization of 1,3-Dienes
977
2-[4,4-Bis(benzyloxymethyl)hept-6-enyloxy]tetrahydro-2H-py-
ran (22)
(E)-6,6-Bis(benzyloxymethyl)nona-2,8-dien-1-ol (24)
To a solution of 23 (1.45 g, 3.56 mmol) in toluene (12 mL) was add-
ed 0.95 M DIBAL-H in hexane (8.20 mL, 7.83 mmol) at –78 °C,
and the solution was stirred at the same temperature for 1.5 h. To the
solution was added MeOH (0.5 mL) and sat. aq potassium sodium
tartrate (20 mL). After stirring the mixture at r.t. for 1 h, the aqueous
layer was extracted with Et2O (3 × 30 mL). The combined organic
layers were washed with brine (40 mL), and dried (Na2SO4). After
removal of the solvent, the residue was purified by column chroma-
tography (silica gel, hexane–EtOAc, 3:1); yield: 1.16 g (86%); col-
orless oil.
To a suspension of LiAlH4 (569 mg, 15.0 mmol) in Et2O (10 mL)
was added a solution of 21 (1.7 g, 5.0 mmol) in Et2O (7 mL) at 0 °C,
and the suspension was stirred at r.t. for 5 h. To the mixture was
added H2O (0.57 mL), 15% aq NaOH (0.57 mL), and H2O (1.7 mL)
at 0 °C, and the mixture was stirred at r.t. for 1 h. The solution was
filtered and the filtrate was concentrated in vacuo to give a crude di-
ol. To a suspension of NaH (60% oil suspension, 540 mg, 13.5
mmol) in DMF (4.5 mL) was added a solution of the diol in DMF
(4.5 mL) at 0 °C, and the mixture was stirred at the same tempera-
ture for 30 min. To the mixture was added BnBr (1.3 mL, 10.4
mmol) at 0 °C, and stirred at r.t. for 17 h. To this mixture was added
sat. aq NH4Cl (10 mL), and the aqueous layer was extracted with
EtOAc (3 × 15 mL). The combined organic layers were washed with
brine (20 mL), and dried (Na2SO4). After removal of the solvent, the
residue was purified by column chromatography (silica gel, hex-
ane–EtOAc, 50:1); yield: 1.87 g (85% from 21); colorless oil.
IR (neat): 3382, 2920, 2857, 1098, 735, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.20 (dt, J = 5.7 Hz, 1 H), 1.38–
1.42 (m, 2 H), 2.00 (dt, J = 10.4, 4.5 Hz, 2 H), 2.12 (d, J = 7.7 Hz,
2 H), 3.30 (s, 4 H), 4.06 (dd, J = 5.7 Hz, 2 H), 4.47 (s, 4 H), 5.02 (d,
J = 10.8 Hz, 1 H), 5.03 (d, J = 16.9 Hz, 1 H), 5.52–5.70 (m, 2 H),
5.72–5.81 (m, 1 H), 7.26–7.34 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 26.1, 31.6, 36.7, 41.7, 63.4, 72.6,
73.2, 117.3, 127.1, 127.1, 128.0, 128.4, 133.5, 138.4, 138.6.
IR (neat): 2941, 2860, 1453, 1364, 1117, 1030, 735, 697 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.33–1.37 (m, 2 H), 1.53–1.57 (m,
6 H), 1.66–1.72 (m, 1 H), 1.81–1.86 (m, 1 H), 2.12 (d, J = 7.6 Hz,
2 H), 3.32–3.37 (m, 5 H), 3.45–3.50 (m, 1 H), 3.67 (dd, J = 9.4 Hz,
1 H), 3.82–3.88 (m, 1 H), 4.47 (s, 4 H), 4.56 (dd, J = 3.6, 3.6 Hz, 1
H), 5.01 (d, J = 10.0 Hz, 1 H), 5.04 (d, J = 17.8 Hz, 1 H), 5.77 (ddd,
J = 17.8, 10.0, 7.6 Hz, 1 H), 7.26–7.33 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 19.6, 23.3, 25.4, 28.0, 30.7, 36.3,
41.3, 62.2, 68.1, 72.5, 73.0, 98.6, 117.4, 127.2, 127.2, 128.1, 134.3,
138.8.
LRMS (FAB): m/z = 381 [M+ + H], 181, 154, 136, 107.
HRMS (FAB): m/z [M+ + H] calcd for C25H33O3: 381.2451; found:
381.2430.
(7E,9E)-4,4-Bis(benzyloxymethyl)undeca-1,7,9-triene (19b)
The crude product prepared from 24 (381 mg, 1.00 mmol) by a pro-
cedure similar to that used for the synthesis of (2E,4E)-3d, was pu-
rified by column chromatography (silica gel, hexane–EtOAc, 5:1);
yield: 221 mg (57% from 25); colorless oil.
LRMS (FAB): m/z = 439 [M+ + H], 355, 245, 181, 154.
HRMS (FAB): m/z [M+ + H] calcd for C28H39O4: 439.2874; found:
IR (neat): 2914, 2856, 1451, 1099, 989, 909, 734, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.37–1.41 (m, 2 H), 1.72 (d,
J = 6.4 Hz, 3 H), 1.97–2.03 (m, 2 H), 2.11 (d, J = 7.3 Hz, 2 H), 3.30
(s, 4 H), 4.47 (s, 4 H), 5.02 (d, J = 10.3 Hz, 1 H), 5.03 (d, J = 16.7
Hz, 1 H), 5.47–5.59 (m, 2 H), 5.76 (ddd, J = 16.7, 10.3, 7.3 Hz, 1
H), 5.96 (dd, J = 14.0, 10.3 Hz, 1 H), 5.99 (dd, J = 14.0, 10.3 Hz, 1
H), 7.24–7.34 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 18.3, 26.5, 31.9, 36.7, 41.8, 72.7,
73.2, 117.4, 126.6, 127.2, 127.2, 128.1, 129.8, 131.5, 132.2, 134.2,
138.7.
439.2848.
(E)-Methyl 6,6-Bis(benzyloxymethyl)nona-2,8-dienoate (23)
To a solution of 22 (1.87 g, 4.27 mmol) in MeOH (43 mL) was add-
ed p-TsOH·H2O (41 mg, 0.22 mmol) at 0 °C, and the mixture was
stirred at r.t. for 36 h. To the mixture was added sat. aq NaHCO3 (40
mL). After removal of MeOH, and the aqueous layer was extracted
with EtOAc (3 × 60 mL). The combined organic layers were washed
with brine (80 mL), dried (Na2SO4), and concentrated to give a
crude alcohol. To a suspension of the Dess–Martin periodinane
(DMP, 2.1 g, 5.0 mmol) in CH2Cl2 (30 mL) was added a solution of
the crude alcohol in CH2Cl2 (10 mL) at 0 °C, and the mixture was
stirred at r.t. for 1 h. To the mixture was added sat. aq NaHCO3 (20
mL) and 10% aq Na2S2O3 (20 mL), and the aqueous layer was ex-
tracted with EtOAc (3 × 60 mL). The combined organic layers were
washed with brine (80 mL), dried (Na2SO4), and concentrated to
give the crude intermediate aldehyde. To a solution of the crude al-
dehyde in CH2Cl2 (14 mL) was added Ph3P=CHCO2Me (1.62 g,
4.85 mmol) at r.t., and the mixture was stirred at the same tempera-
ture for 12 h. After removal of the solvent, the residue was purified
by column chromatography (silica gel, hexane–EtOAc, 50:1); yield:
1.47 g (84% from 22); colorless oil.
LRMS (FAB): m/z = 391 [M+ + H], 181, 154, 136, 107, 91.
Anal. Calcd for C27H34O2: C, 83.03; H, 8.77. Found: C, 82.91; H,
8.66.
Cycloisomerization of Trienes; (E)-4,4-Bis(benzyloxymethyl)-1-
(but-1-enyl)-2-methylcyclopentene (4d); Typical Procedure
A solution of [Rh(dppe)(nbd)]ClO4 (11.1 mg, 0.016 mmol) in de-
gassed DCE (0.62 mL) was stirred under H2 atmosphere at r.t. for 1
h. Then the reaction vessel was flushed with argon, and a solution
of triene (2E,4E)-3d (60.2 mg, 0.16 mmol) in degassed DCE (0.98
mL) was added to the mixture. The reaction mixture was stirred at
65 °C for 2 h. After removal of the solvent, the residue was purified
by column chromatography (silica gel) to afford 4d (51.1 mg, 85%)
as a colorless oil. All cyclization reactions were carried out by this
procedure.
IR (neat): 2920, 2858, 1724, 1655, 1098 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.44–1.48 (m, 2 H), 2.11–2.17 (m,
2 H), 2.12 (d, J = 7.4 Hz, 2 H), 3.30 (s, 4 H), 3.71 (s, 3 H), 4.46 (s,
4 H), 5.03 (d, J = 12.0 Hz, 1 H), 5.04 (d, J = 14.0 Hz, 1 H), 5.68–
5.80 (m, 2 H), 6.94 (dt, J = 15.5, 7.0 Hz, 1 H), 7.26–7.35 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 26.3, 30.6, 36.7, 41.6, 51.4, 72.4,
73.2, 117.6, 120.3, 127.2, 127.2, 128.1, 133.7, 138.4, 149.8, 166.8.
LRMS (FAB): m/z = 409 [M+ + H], 181, 154, 136, 107.
HRMS (FAB): m/z [M+ + H] calcd for C26H33O4: 409.2407; found:
IR (neat): 2925, 2850, 1453, 1361, 1102, 733, 697 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.01 (d, J = 7.1 Hz, 3 H), 1.69 (s,
3 H), 2.13 (dq, J = 7.1, 7.1 Hz, 2 H), 2.28 (s, 2 H), 2.35 (s, 2 H), 3.43
(s, 4 H), 4.52 (s, 4 H), 5.52 (dt, J = 15.6, 7.1 Hz, 1 H), 6.26 (d,
J = 15.6 Hz, 1 H), 7.25–7.34 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 14.1, 14.2, 26.3, 40.0, 44.8, 45.7,
73.2, 74.2, 123.3, 127.1, 127.2, 128.0, 131.3, 131.6, 133.0 138.7.
409.2379.
LRMS: m/z = 376 [M+], 268, 177, 162, 147, 91.
Synthesis 2009, No. 6, 969–979 © Thieme Stuttgart · New York

978
Y. Oonishi et al.
PAPER
(E)-[5-4,4-Bis(benzyloxymethyl)-2-methylcyclopent-1-enyl-
Anal. Calcd for C26H32O2: C, 82.94; H, 8.57. Found: C, 82.99; H,
8.69.
pent-4-enyloxy]-tert-butyldimethylsilane (4g)
IR (neat): 2927, 2854, 1100 cm–1.
(E)-6-[4,4-Bis(benzyloxymethyl)-2-methylcyclopent-1-
enyl]hex-5-enal (4a)
1H NMR (400 MHz, CDCl3): d = 0.01 (s, 6 H), 0.86 (s, 9 H), 1.57
(tt, J = 7.1, 7.1 Hz, 2 H), 1.65 (s, 3 H), 2.11 (dt, J = 7.1, 7.1 Hz, 2
H), 2.24 (s, 2 H), 2.30 (s, 2 H), 3.39 (s, 4 H), 3.57 (t, J = 7.1 Hz, 2
H), 4.46 (s, 4 H), 5.43 (dt, J = 15.6, 7.1 Hz, 1 H), 6.24 (d, J = 15.6
Hz, 1 H), 7.19–7.30 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = –5.0, 14.1, 18.6, 26.2, 29.6, 32.9,
40.0, 44.7, 45.7, 62.6, 73.2, 74.1, 124.6, 127.1, 127.2, 128.0, 129.3,
131.3, 133.2, 138.7.
IR (neat): 3028, 2850, 1724, 1454, 1100, 736, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.69 (s, 3 H), 1.73 (tt, J = 7.3, 7.3
Hz, 2 H), 2.15 (dt, J = 7.3, 7.3 Hz, 2 H), 2.29 (s, 2 H), 2.33 (s, 2 H),
2.42 (td, J = 7.3, 1.4 Hz, 2 H), 3.43 (s, 4 H), 4.52 (s, 4 H), 5.40 (dt,
J = 15.5, 7.3 Hz, 1 H), 6.27 (d, J = 15.5 Hz, 1 H), 7.25–7.34 (m, 10
H), 9.76 (t, J = 1.4 Hz, 1 H).
13C NMR (67.8 MHz, CDCl3): d = 14.0, 22.0, 32.4, 39.8, 43.2, 44.7,
45.6, 73.2, 74.1, 125.6, 127.3, 127.3, 128.2, 128.3, 131.3, 134.1,
138.8, 202.5.
LRMS (EI): m/z = 520 [M+], 505, 429, 412, 355, 321, 249, 181, 91.
HRMS (EI): m/z calcd for C33H48O3Si: 520.3373; found: 520.3374.
LRMS (EI): m/z = 400 [M+ – H2O], 310, 279, 105, 91.
(E)-4,4-Bis(benzyloxymethyl)-1-methyl-2-pent-1-enylcyclopen-
tene (4h)
Anal. Calcd for C28H34O3: C, 80.35; H, 8.19. Found: C, 80.24; H,
8.23.
IR (neat): 2923, 2852, 1452, 1100, 734, 697 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.90 (t, J = 7.5 Hz, 3 H), 1.40 (tq,
J = 7.5, 7.5 Hz, 2 H), 1.69 (s, 3 H), 2.09 (dt, J = 7.5, 7.5 Hz, 2 H),
2.28 (s, 2 H), 2.35 (s, 2 H), 3.43 (s, 4 H), 4.52 (s, 4 H), 5.47 (dt,
J = 15.4, 7.5 Hz, 1 H), 6.26 (d, J = 15.4 Hz, 1 H), 7.24–7.31 (m, 10
H).
13C NMR (100 MHz, CDCl3): d = 14.0, 14.1, 23.1, 34.5, 40.0, 44.7,
45.7, 73.2, 74.2, 124.4, 127.1, 127.2, 128.0, 129.9, 131.4, 133.0,
138.7.
(E)-1,1-Bis(benzyloxymethyl)-3-(but-2-enyl)-4-methylenecyclo-
pentane (4d¢)
IR (neat): 2923, 2856, 1116, 1100 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.16–1.25 (m, 1 H), 1.64 (d,
J = 5.1 Hz, 3 H), 1.87–1.95 (m, 2 H), 2.26–2.39 (m, 3 H), 2.42–2.51
(m, 1 H), 3.31–3.43 (m, 4 H), 4.52 (s, 4 H), 4.77 (s, 1 H), 4.84 (s, 1
H), 5.38 (dt, J = 15.3, 5.2 Hz, 1 H), 5.44 (dq, J = 15.3, 5.1 Hz, 1 H),
7.24–7.34 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 17.9, 37.6, 37.8, 40.2, 41.8, 45.8,
72.8, 73.2, 74.7, 105.2, 125.9, 127.3, 127.4, 128.2, 129.7, 138.9,
154.9.
LRMS (EI): m/z = 390 [M+], 299, 282, 191, 176, 161, 149, 131, 91.
HRMS (EI): m/z calcd for C27H34O2: 390.2559, found: 390.2558.
2,2-Bis(benzyloxymethyl)-5-methyl-cis-2,3,3a,4,5,7a-hexahy-
dro-1H-indene (5d)
LRMS (EI): m/z = 376 [M+ – Bn], 268, 207, 177, 147, 105, 91.
Anal. Calcd for C26H32O2: C, 82.94; H, 8.57. Found: C, 82.95; H,
8.63.
IR (neat): 2924, 2854, 2453, 1362, 1098, 733, 696 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.92–0.95 (m, 1 H), 0.93 (d,
J = 7.0 Hz, 3 H), 1.20–1.32 (m, 2 H), 1.50–1.55 (m, 1 H), 1.79–1.90
(m, 2 H), 2.09–2.10 (m, 2 H), 2.41–2.43 (m, 1 H), 3.35–3.46 (m, 4
H), 4.51 (s, 4 H), 5.46 (d, J = 10.1 Hz, 1 H), 5.67 (ddd, J = 10.1,
3.3, 3.3 Hz, 1 H), 7.24–7.30 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 21.9, 31.1, 37.1, 37.3, 38.7, 38.9,
39.2, 47.6, 73.1, 74.1, 76.1, 127.0, 127.1, 128.0, 128.8, 133.1,
138.7.
(E)-4,4-Bis(benzyloxymethyl)-1-methyl-2-(propen-1-yl)cyclo-
pentene (4e)
IR (neat): 2911, 2850, 1452, 1361, 1100 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.69 (s, 3 H), 1.78 (d, J = 6.8 Hz,
3 H), 2.27 (s, 2 H), 2.34 (s, 2 H), 3.43 (s, 4 H), 4.52 (s, 4 H), 5.48
(dq, J = 15.3, 6.8 Hz, 1 H), 6.28 (d, J = 15.3 Hz, 1 H), 7.23–7.33 (m,
10 H).
13C NMR (100 MHz, CDCl3): d = 14.1, 18.8, 40.0, 44.8, 45.7, 73.2,
74.2, 124.4, 125.7, 127.1, 127.2, 128.1, 131.4, 132.8, 138.7.
LRMS (EI): m/z = 376 [M+], 285, 267, 267, 177, 159, 147, 131, 91.
Anal. Calcd for C26H32O2: C, 82.94; H, 8.57. Found: C, 82.89; H,
8.53.
LRMS (EI): m/z = 362 [M+], 271, 254, 165, 148, 133, 91.
Anal. Calcd for C25H30O2: C, 82.83; H, 8.34. Found: C, 82.64; H,
8.52.
2,2-Bis(benzyloxymethyl)-5-methyl-2,3,4,5,6,7-hexahydro-1H-
indene (5d¢)
IR (neat): 2920, 2846, 1453, 1361, 1099, 734, 697 cm–1.
(E)-4,4-Bis(benzyloxymethyl)-1-(but-1-enyl)-2-ethylcyclopen-
tene (4f)
1H NMR (400 MHz, CDCl3): d = 0.94 (d, J = 6.5 Hz, 3 H), 1.16–
1.25 (m, 1 H), 1.43–1.54 (m, 1 H), 1.63–1.68 (m, 2 H), 1.90–1.94
(m, 3 H), 2.06–2.17 (m, 4 H), 3.42 (s, 2 H), 3.43 (s, 2 H), 4.52 (s, 4
H), 7.23–7.34 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 21.8, 25.6, 29.2, 31.4, 34.3, 42.6,
42.8, 45.9, 73.2, 74.4, 127.2, 127.4, 128.2, 131.9, 132.0, 139.1.
IR (neat): 2922, 2850, 1453, 1362, 1101 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.96 (t, J = 7.4 Hz, 3 H), 1.01 (t,
J = 7.5 Hz, 3 H), 2.08–2.18 (m, 4 H), 2.31 (s, 2 H), 2.36 (s, 2 H),
3.44 (s, 4 H), 4.52 (s, 2 H), 4.53 (s, 2 H), 5.52 (dt, J = 15.6, 6.8 Hz,
1 H), 6.27 (d, J = 15.6 Hz, 1 H), 7.26–7.37 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 13.0, 14.2, 21.5, 26.4, 40.1, 42.7,
44.6, 73.2, 74.1, 123.1, 127.1, 127.2, 128.0, 130.5, 131.6, 138.7,
138.9.
LRMS (EI): m/z = 376 [M+], 268, 177, 162, 147, 91.
HRMS (EI): m/z calcd for C26H32O2: 376.2402; found: 376.2399.
(E)-4,4-Bis(benzyloxymethyl)-1-(but-1-enyl)-2-methylcyclohex-
ene (26b)
LRMS (EI): m/z = 390 [M+], 298, 282, 191, 161, 131, 91.
Anal. Calcd for C27H34O2: C, 83.03; H, 8.77. Found: C, 82.97; H,
9.06.
IR (neat): 2921, 2852, 1453, 1099, 734, 697 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.02 (t, J = 7.3 Hz, 3 H), 1.60 (dd,
J = 6.5, 6.5 Hz, 2 H), 1.73 (s, 3 H), 1.99 (s, 2 H), 2.11–2.17 (m, 4
H), 3.34 (d, J = 8.8 Hz, 2 H), 3.40 (d, J = 8.8 Hz, 2 H), 4.48 (s, 4
Synthesis 2009, No. 6, 969–979 © Thieme Stuttgart · New York

PAPER
Rhodium(I)-Catalyzed Cycloisomerization of 1,3-Dienes
979
H), 5.59 (dt, J = 15.7, 7.2 Hz, 1 H), 6.45 (d, J = 15.7 Hz, 1 H), 7.23–
7.33 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 14.2, 19.2, 22.1, 26.4, 26.4, 37.9,
38.1, 73.3, 73.5, 126.5, 127.1, 127.3, 127.3, 128.2, 128.6, 129.2,
139.1.
see: (m) Brummond, K. M.; Chen, H.; Sill, P.; You, L. J. Am.
Chem. Soc. 2002, 124, 15186. (n) Shibata, T.; Takesue, Y.;
Kadowaki, S.; Takagi, K. Synlett 2003, 268.
(o) Brummond, K. M.; Mitasev, B. Org. Lett. 2004, 6, 2245.
(p) Mukai, C.; Inagaki, F.; Yoshida, T.; Kitagaki, S.
Tetrahedron Lett. 2004, 45, 4117. (q) Mukai, C.; Inagaki,
F.; Yoshida, T.; Yoshitani, K.; Hara, Y.; Kitagaki, S. J. Org.
Chem. 2005, 70, 7159.
LRMS (EI): m/z = 390 [M+], 282, 191, 176, 161, 149, 133, 91.
HRMS (EI): m/z calcd for C27H34O2: 390.2559; found: 390.2564.
(4) For cycloisomerizations of 1,3-dienes with alkenes, only
iron-catalyzed reactions have so far been reported by
Takacs, see: (a) Takacs, J. M.; Anderson, L. G. J. Am. Chem.
Soc. 1987, 109, 2200. (b) Takacs, J. M.; Anderson, L. G.;
Creswell, M. W.; Takacs, B. E. Tetrahedron Lett. 1987, 28,
5627. (c) Takacs, J. M.; Newsome, P. W.; Kuehn, C.
Tetrahedron 1990, 46, 5507. (d) Takacs, B. E.; Takacs, J.
M. Tetrahedron Lett. 1990, 31, 2865. (e) Takacs, J. M.;
Myoung, Y. C. Tetrahedron Lett. 1992, 33, 317. For other
related Rh(I)-catalyzed cycloadditions of 1,3-dienes with
alkenes, see: [2+2+1] cycloaddition: (f) Wender, P. A.;
Croatt, M. P.; Deschamps, N. M. J. Am. Chem. Soc. 2004,
126, 5948. [2+2+2] cycloaddition: (g) Wender, P. A.;
Christy, J. P. J. Am. Chem. Soc. 2006, 128, 5354.
(5) (a) Jolly, R. S.; Luedtke, G.; Sheehan, D.; Livinghouse, T.
J. Am. Chem. Soc. 1990, 112, 4965. (b) McKinstry, L.;
Livinghouse, T. Tetrahedron 1994, 50, 6145.
Acknowledgment
This work was financially supported by a Grant-in-Aid for Scienti-
fic Research on Priority Areas (No. 18032003, ‘Creation of Biolo-
gically Functional Molecules’) from the Ministry of Education,
Culture, Sports, Science and Technology, Japan, and also by Grant-
in-Aid for Young Scientist (B) (No. 20790003) and for Scientific
Research (B) (No. 19390001) from JSPS.
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Synthesis 2009, No. 6, 969–979 © Thieme Stuttgart · New York