Synthesis of symmetric HIJ-ring model of ciguatoxin

Article abstract of DOI:10.1016/j.tet.2007.03.012

A tricyclic model ether compound comprising 6/8/6 ether rings was synthesized via a new route including conjugate addition to form a symmetric eight-membered ether-ketone with syn/trans stereochemistry in selective manner. The corresponding vinyl triflate

Full text of DOI:10.1016/j.tet.2007.03.012

Tetrahedron 63 (2007) 5886–5894
Synthesis of symmetric HIJ-ring model of ciguatoxin
Akihito Nonoyama,a Akinari Hamajimaa and Minoru Isobea,b,
*
aLaboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
bInstitute of Advanced Research, Nagoya University, Chikusa, Nagoya 464-8601, Japan
Received 31 January 2007; revised 28 February 2007; accepted 1 March 2007
Available online 7 March 2007
Abstract—A tricyclic model ether compound comprising 6/8/6 ether rings was synthesized via a new route including conjugate addition to
form a symmetric eight-membered ether-ketone with syn/trans stereochemistry in selective manner. The corresponding vinyl triflate of this
ketone was allowed to convert to the vinyl methyl derivative via cross-coupling reaction. This endo-olefinic tetrahydro-2H-oxocin was selec-
tively reduced to afford a-methyl product. The corresponding exo-olefinic oxocane derivative, on the other hand, provided the b-methyl iso-
mer as the major diastereoisomer (2/1). Our previous report on the synthesis of this final product was revised due to some rearrangement and
the mechanisms are discussed.
Ó 2007 Elsevier Ltd. All rights reserved.
H
Me
Me
OTIPS
1. Introduction
H
H
H
H
O
J
39
I
O
M
O
L
H
O
K
In the synthetic strategies there are many methods available
for the so-called polyether marine natural products.1 The
most critical step may be the medium ring cyclization reac-
tion, which varies to be done from seven-membered to
nine-membered ring sizes for ciguatoxin,2 for example, using
acetylene–cobalt complex in our strategy.3 We have recently
reported a convergent synthesis of the HIJKLM-ring system,
compound 1, a right segment of ciguatoxin.4 In that report,
the stereocenters on the eight-membered I-ring have been
achieved with an efficient stereocontrol on the basis of (1)
conjugate addition of ether oxygen to enone to form the H-
ring in syn/trans manner, (2) cross-coupling via the corre-
sponding endo-olefinic vinyl triflate to introduce the methyl
group, and (3) selective reduction of the endo-olefin to form
the 39-a-methyl group on the basis of the conformation of
oxocin moiety. We report here the synthesis of HIJ ring as
a much simpler model compound 2 of ciguatoxin in order
to make the stereochemical question much clearer in the
construction of the eight-membered I-ring.
HO
Me
O
O
H
OTBS
H
HO
H
H
Me
Me
H
1
TBSO
Me
H
H
O
O
H
I
J
O
H
H
2
The cobalt-mediated cyclization of 6 was facilitated
through 7 for the formation of eight-membered ether ring
8 according to our protocol of the synthesis of the medium
ring cyclization. The exocyclic olefin was once oxidized to
the corresponding carbonyl compound 9 under Lemieux–
Johnson condition, namely combination of NaIO4 and cata-
lytic amount of OsO4 in a mixed solvent system to assist the
solubility of the hydrophobic substrate and hydrophilic
reagents. We further proceeded the following reductive
decomplexation reaction with tri-n-butyltin hydride or
sodium hypophosphite for such an acetylene–dicobalthexa-
carbonyl complex to the corresponding olefin as reported in
our previous papers.7,8a It was, however, different from the
isolated acetylene complex in the reactivity of 9, as well as
the olefin 8; thus, they were convertible only in low yields
via direct reduction to the corresponding olefins such as
10. We found that two-step sequential reductions including
hydrosilylation and desilylation afforded the enone 10 in
74% overall yield.8 It was further used as precursor for
the formation of tetrahydropyran ring under different
conditions.
2. Results and discussion
2.1. Synthesis of symmetric 6/8/6-ketone rings
The acetylene compound 35 was prepared from commer-
cially available D-glucal triacetate in nine steps and subjected
to iodoboration to form the vinyl iodide 4 (Scheme 1).6 This
iodide was allowed to couple with acetylene 5 under Sonoga-
shira Pd coupling condition providing the ene–yne 6.
* Corresponding author. Tel.: +81 52 789 4109; fax: +81 52 789 4111;
e-mail: isobem@arg.nagoya-u.ac.jp
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.03.012

A. Nonoyama et al. / Tetrahedron 63 (2007) 5886–5894
5887
TBDPSO
a
b
H
H
H
H
B-I-9-BBN,
O
O
O
O
5
I
OH
then AcOH
Pd(PPh3)4, CuI,
n-PrNH2, toluene
rt, 78%
CH2Cl2, 89%
OAc
OAc
OH
OAc
d
c
4
3
H
H
Co2(CO)8
K2CO3
OTBDPS
CH2Cl2
93%
MeOH
88%
OH
6
H
H
Co2(CO)6
H
BF3 • OEt2
O
I
Co2(CO)6
OTBDPS
CH2Cl2, 82%
H
O
Figure 1. Conformation of the enone 10 on the basis of the Macromodel
MM3 calculation.9
H
H
8
OTBDPS
HO
7
dihydro-oxocinone ring in 10 leading to 11 would be as illus-
trated in Figure 1, where the conjugated enone p-system
(d 6.85 ppm) should overlap with the polarized C–O bond.
Felkin–Nguyen (Ahn) model can explain the lowest mini-
mum approach of the nucleophile oxygen along the lines
a and b shown in Figure 1. In this conformation, the nucleo-
phile oxygen atom from the directions c and d would be
obviously difficult, since it should overcome the congested
concave zone; thus, it formed a single product 11.
O
1) Et3SiH
TMS
CH2ClCH2Cl, 87%
2) TBAF, THF, 85%
Co2(CO)6
H
OsO4, NaIO4
TMS
O
OTBDPS
THF / H2O / AcOH
= 20 / 5 / 1, 76%
O
H
H
9
O
H
O
H
O
H
OTBDPS
O
O
I
TBAF
When the enone 10 was treated with TsOH$H2O, on the
other hand, the protonated enone of the dihydro-oxocinone
ring might have very different conformation as in Figure 2.
The orbital interaction with the C–O polarization might
not be significant in this case due to the even repulsive inter-
action between the two electronically deficient carbon atoms
at the neighboring position. Therefore, the conjugate addi-
tion would happen from both sides of the enone to provide
the mixture of 11 and 12.
J
H
THF, 85%
O
O
H
H
H
H
H
10
trans
11
O
H
O
H
O
TsOH • H2O
I
11
+
H
J
CH3NO2, 86%
O
11 : 12 = 47 : 53
H
trans
cis
12
Scheme 1. Synthesis of the symmetric trans/syn/trans ketone of 6/8/6 ring
system and its trans/syn/cis isomer.
The a and b protons of the unsaturated carbonyl compound
10 appeared at d 5.66 and 5.92 ppm in its 1H NMR spectrum.
This implied that the olefin and carbonyl groups are not
strongly conjugated at the ground state, but seem to be at
the transition state since it ends up with the conjugate addi-
tion with stereoselectively under basic condition, but non-
selectively under acidic conditions.
The enone 10 having O-TBDPS group was first subjected to
the same acidic condition for a cyclization of tetrahydro-
pyran H-ring as our previous case in the HIJKLM-ring syn-
thesis; thus, p-toluenesulfonic acid in nitromethane solvent.
Surprisingly, this acidic condition allowed the reaction pro-
viding a mixture of trans/cis isomers of 11 and 12 in almost
1/1 ratio. Alternative basic condition was applied for this
conjugate addition cyclization; thus, treatment with TBAF
first provided a penta-coordinated fluoro silane, which might
enhance the nucleophilicity of the neighboring oxygen atom
under a possible milder condition rather than a corresponding
alkoxide nucleophile. In fact, TBAF/THF condition afforded
exclusively trans isomer 11 in 85% yield. Interestingly, this
product showed only seven lines in its 13C NMR to prove this
molecule being symmetric.
This seems contradictory in comparison with our previous
case in a stereoselective synthesis of 1 (giving only trans
product by treatment with TsOH$H2O). The difference
from the current system (from 10 to 11) might be attributed
to the fact that there is a presence of an additional stereogenic
carbon atom, which might help the preferable conformation
as shown in Figure 1. In fact, the protected secondary hydro-
xyl group did situate in an equatorial position of the trans
product (tetrahydropyran ring). In the cis isomer, this hydr-
oxylgroupislocatedinacongestedconcaveposition, instead.
These results demonstrated a striking difference in the selec-
tivity for 10 to undergo the conjugate addition cyclization
under different conditions and to provide a mixture of
trans-11 and cis-12 products. The conformation of the
2.2. Synthesis of the symmetric HIJ ring
The trans/syn/trans tricyclic ketone 11 was further con-
verted into racemic vinyl triflate 13, which was allowed to

5888
A. Nonoyama et al. / Tetrahedron 63 (2007) 5886–5894
Figure 2. 13C NMR spectrum of symmetric ketone 11 showing only seven lines.
do cross-coupling with methylmagnesium bromide in the
presence of Fe(acac)3 catalyst to afford the endo-olefin 14
in good yield.10 This endo-olefin product was hydrogenated
stereoselectively using Crabtree’s catalyst to give a single
diastereoisomer HIJ-ring model 2.11
once again. We then confirmed the previous route and com-
pounds of our previous HIJ-ring model.
2.3. Reduction of exo-olefin
The stereochemistry of the methyl group is of interesting
outcome depending on the olefin precursor. As shown in
Scheme 2, the endo-olefin (14) afforded the a-methyl prod-
uct (2) with high stereoselectivity. The corresponding exo-
olefin precursor 15 was prepared via Wittig methylenation
from the ketone 11, and reduction with PtO2 in EtOH solvent
afforded a mixture of the stereoisomer in 2/1 ratio; thus, ma-
jor b-methyl derivative 16 and minor a-methyl derivative 2
in total 86% yield (Scheme 3). The products were insepara-
ble from each other, so this ratio was estimated from the
NMR data; 1.06 (d, 7.5 Hz) and 1.05 (d, 7.5 Hz), respec-
tively. Although the data are not shown, the platinum or
We summarized the 1H and 13C NMR data of HIJ-ring model
2 in Table 1. Figure 3 shows 13C NMR spectrum, which has
only eight lines corresponding to the symmetry of 2. Previ-
ously we had reported about the same compound, which we
synthesized in a different route. It showed all the 14 lines in
the 13C NMR spectrum.12 There was difference between this
result and previous result. In 2004, Tachibana’s group
(Tokyo University) reported the synthesis of the same
HIJ-ring model via an alternative route and they also re-
ported that the compound was observed with only eight lines
in 13C NMR.13 Their report prompted us to repeat this model
Table 1. Comparison of 1H and 13C spectra of 2 with previous work (now assigned as 21)12 and Tachibana’s work13
H4,H10
H5,H9
81
83
88
Me
C5,C9
H
7
I
H
5
9
O
O
1
10
J
4
H
O
H
H
2
C4,C10
3.15
3.10
3.05
3.00
(ppm)
Position
1H (ppm)
13C (ppm)
Previous work
3.74
Tachibana’s work
This work
Previous work
Tachibana’s work
This work
1,13
2,12
3,11
3.40
3.25
3.80
1.60
1.60
1.41
2.02
3.13
3.05
1.56
1.79
1.88
1.02
3.25
3.80
1.61
1.61
1.41
2.02
3.13
3.05
1.56
1.79
1.88
1.02
67.5
—
67.8
—
67.4
—
25.9
—
33.0
—
81.7
84.3
46.4
—
67.4
—
25.9
—
33.0
—
84.4
81.7
46.4
—
3.86–3.93
1.66–1.73
1.66–1.73
1.36
3.84
1.86–1.92
1.86–1.92
1.42–1.48
1.80
25.6
—
25.7
—
29.4
—
31.9
—
2.02
3.02
2.98
1.20
4,10
5,9
6,8
4.08
3.19
75.8
78.4
36.0
—
77.8
80.6
38.6
—
1.26
1.40–1.49
1.96
1.46–1.52
0.89
7
7-Me
39.1
17.1
27.9
28.1
28.0
28.1
The 13C signals of C-4(10) and C-5(9) of this work was correctly assigned on the basis of HMBC.

A. Nonoyama et al. / Tetrahedron 63 (2007) 5886–5894
5889
Figure 3. 13C NMR spectrum of symmetric HIJ-ring model 2 showing only eight lines.
OTf
palladium catalysts seem to isomerize the double bond
between 14 and 15 under the reduction condition and the ste-
reochemistry of the product may be depended on the relative
reduction rate versus isomerization.
O
KHMDS,
PhNTf2
Fe(acac)3
MeMgBr,
H
H
H
H
O
O
O
O
O
I
THF 86%
NMP
H
J
O
H
O
THF, 90%
H
H
H
H
11
13
2.4. Revision of previous structure and rearrangement
mechanism
Me
Me
H
H2
H
H
H
[(cod)Py(Cy3P)Ir]PF6
CH2Cl2, 99%
O
O
O
I
J
We have re-examined our synthesis from compound 8
according to our previous route, which is indicated in
Scheme 4. Diimide reduction afforded 17 having a-methyl
group, which was decomplexed with tri-n-butyltin hydride
to olefin 18. After removal of the silyl protecting group,
the alcohol 19 was subjected to the critical condition with
iodine in acetonitrile solvent. It afforded a condensed cyclic
compound 20 carrying an iodine atom, which was identical
with the previous HIJ-ring model compound on the basis of
1H and 13C NMR spectra. Then reductive de-iodination from
20 with tri-n-butyltin hydride in the presence of AIBN gave
21, which was also identical with the previous reduction
product. Here we have to revise the structure, which was
reported to be as 2 in the previous paper, to be 21.
H
O
O
H
H
H
2
14
Scheme 2. Synthesis of the symmetric 6/8/6-oxocane, as a model of
HIJ-ring of ciguatoxin.
O
H
H
H
H
O
O
Ph3P=CH2
80%
I
O
O
I
H
J
H
J
O
11
O
H
H
H
H
15
Me
Me
H2, PtO2
When we compared the possible reaction mechanism lead-
ing to compound 20 (Scheme 5), we have later observed
a transannular mechanism with a nine-membered ring com-
pound, which will be discussed later (Scheme 6).14
H
H
H
H
(0.1 equiv.)
O
O
O
O
I
+
H
J
EtOH
O
O
1 hr 86%
H
H
H
H
16
2
Scheme 3. Stereochemistryof7-methylgroupfromtheexo-olefinicprecursor.
The iodoetherification in the tetrahydrooxocin 19 might not
allow to include a strained 6/4-bicyclic intermediate (A0),
but might allow to undergo transetherification from opening
the eight-membered allylic ether (A) into closing the five-
membered intermediate B. Iodoetherification between the
secondary alcohol and olefin C would provide the 6/6-bicy-
clic iodide 20. On the other hand, acidic ether transformation
would occur through D to E. Iodoetherification might occur
with interaction of the five-membered ring formation as F to
form 20.
i
Me
Pr
i
Co2(CO)6
n-Bu3SnH
Pr
SO2NHNH2
Pr
H
i
O
8
Et3N
MeOH, 2 days
44%
toluene, 65 °C
70%
OTBDPS
O
H
H
17
H
Me
H
H
H
H
O
Me
R1
H
I2
Scheme 6 illustrates a mechanism of a similar case in a tetra-
hydrooxonin G. In this case, bromonium ion coordinates
with one of the two olefins as in H, which allow a transannu-
lar interaction with an allylic carbon to form 6/6/5-tricyclic
intermediate I. A transetherification to the new tetrahydro-
pyran ring, in fact, afforded the tetracyclic vinyl silane J.
An alternative mechanism may be possible through an open-
ing of the nine-membered ring with assistance of the free
O
O
CH3CN, 75%
OR1
O
O
H
H
n-Bu3SnH
AIBN
TBAF
THF
20 R1 = I
18 R1 = TBDPS
19 R1 = H
84%
toluene
94%
21 R1 = H
Scheme 4. Previous synthetic route, which led us 21.

5890
A. Nonoyama et al. / Tetrahedron 63 (2007) 5886–5894
Me
Me
O
Me
Me
H
H
H
H
H+
O
O
H+
O
O
OH
HO
H
OH
O
H
O
OH
H
H
OH
H
H
H
19
B
D
A
I2
Me
Me
O
I+
H
H
I+
H
H
O
O
Me
O
O
OH
OH
OH
O
O
H
OH
H
H
H
E
C
A'
or
Me
H
H
H
H
O
I
O
Me
Me
O+
H
O
H
OH
H
O
O
H
F
I+
H
H
I
A"
20
Scheme 5. Proposed rearrangement mechanism of the iodoetherification.
OBn
H
OBn
OBn
OBn
H
H
H
O
O
H
H
H
H
TBCO
CH2Cl2
0 °C
O
O
O
H
O
H
HO
HO
H
H
SiEt3
SiEt3
Br
G
H
OBn
H
H
Et3Si
H
OBn
H
O
H
H
H
H
H
O
H
O
H
100%
HO
O
OBn
H
O
Br
O
H
O
H
H
SiEt3
OBn
J
Br
I
TBCO = 2,4,4,6-tetrabromo-2,5-cyclohexadienone
Scheme 6. Proposed transannular mechanism of the bromoetherification.
hydroxyl group, which could follow the bromoetherification.
These acidic transformation is potentially the problem of
medium size unsaturated ring system.
spectra were recorded on
a
BRUKER ARX-400
(400 MHz) or a BRUKER AVANCE-400 (400 MHz).
Chemical shifts are reported in parts per million from tetra-
methylsilane and are assigned using tetramethylsilane
(d 0.00 ppm) as an internal standard. Data are reported as
follows: chemical shift, integration, multiplicity (s¼singlet,
3. Conclusion
d¼doublet,
t¼triplet,
q¼quartet,
br¼broadened,
We have synthesized HIJ-ring model 2 via a new route.
Its NMR spectra showed symmetric nature, which disagreed
with our previous report. Thus, we confirmed the previous
route again and concluded that the structure of final product
in previous paper had to be revised as rearranged 21.
m¼multiplet), coupling constant(s), and assignment. Car-
bon nuclear magnetic resonance (13C NMR) spectra were re-
corded on a BRUKER ARX-400 (100 MHz) or a BRUKER
AVANCE-400 (100 MHz). Chemical shifts are reported in
parts per million from tetramethylsilane using the solvent
resonance as an internal standard (CDCl3: d 77.00 ppm). Op-
tical rotations were measured on a JASCO DIP-370 digital
polarimeter. Elemental analyses were performed by Analyt-
ical Laboratory at School of Bioagricultural Sciences, Na-
goya University. Reactions were monitored by thin-layer
chromatography carried out on 0.25 mm silica gel 60F254
coated glass plates (Merck, Art 1.05715) using UV light as
visualizing agent and 7% ethanolic phosphomolybdic acid
or p-anisaldehyde solution and heated as developing agents.
4. Experimental
4.1. General
Infrared spectra (IR) were recorded on a JASCO FTIR-
7000S spectrophotometer and are reported in wave number
(cmꢀ1). Proton nuclear magnetic resonance (1H NMR)

A. Nonoyama et al. / Tetrahedron 63 (2007) 5886–5894
5891
Silica gel 60 (particle size 63–200 mm, 70–230 mesh,
ASTM, purchased from Kanto Chemical Co., Inc) was
used for open-column chromatography. Silica gel 60 (spher-
ical, particle size 40–50 mm, purchased from Kanto Chemi-
cal Co., Inc) was used for flash column chromatography.
Preparative thin-layer chromatography separations were car-
ried out on 0.5 mm silica gel 60F254 coated glass plates
(Merck, Art 1.05744). Unless otherwise noted, non-aqueous
reactions were conducted in oven-dried (120 ꢁC) or flame-
dried glassware under inert atmosphere of dry nitrogen or ar-
gon. Dry THF was purchased from Kanto Chemical Co., Inc.
in a bottle as tetrahydrofran, dehydrated. Anhydrous toluene
was purchased from Kanto Chemical Co., Inc. in a bottle.
Dry CH2Cl2 was purchased from Kanto Chemical Co., Inc.
in a bottle as dichloromethane, dehydrated. BF3$OEt2 was
distilled from CaH2. All other commercially available re-
agents were used as received.
stirring for 17 h 40 min, the reaction mixture was poured
into H2O and extracted with Et2O (ꢂ2). The combined
organic extract was washed with H2O, brine, dried over
Na2SO4, and concentrated under reduced pressure. The
residue was purified by silica gel column chromatography
(SiO2: 1 g, hexane/AcOEt¼8/1) to give cyclic ketone cobalt
complex 9 (22.7 mg, 2%) as a dark brown oil. Total yield
was 76%.
[a]2D4 +130.0 (c 0.07, CHCl3). 1H NMR (400 MHz, CDCl3):
d 1.07 (9H, s, –SitBu), 1.41–1.52 (1H, m, H-3a), 1.55–1.85
(4H, m, H-2 ꢂ2, H-11a, H-12a), 1.87–1.97 (1H, m, H-
12b), 2.00–2.07 (1H, m, H-3b), 2.09–2.17 (1H, m, H-11b),
2.75 (1H, dd, J¼12.0, 3.5 Hz, H-6a), 3.19 (1H, td, J¼10.0,
4.5 Hz, H-4), 3.27–3.35 (1H, m, H-1a), 3.32 (1H, dd,
J¼12.0, 5.0 Hz, H-6b), 3.50 (1H, ddd, J¼10.0, 5.0, 3.5 Hz,
H-5), 3.70–3.82 (2H, m, H-13 ꢂ2), 3.95 (1H, ddt, J¼11.5,
4.5, 2.0 Hz, H-1b), 4.62 (1H, dd, J¼9.5, 3.5 Hz, H-10),
7.35–7.46 (6H, m, aromatic), 7.65–7.70 (4H, m, aromatic).
13C NMR (100 MHz): d 19.2, 25.8, 26.7, 29.5, 30.8, 34.8,
47.3, 63.3, 68.2, 79.4, 80.3, 82.9, 87.9, 100.9, 127.6,
129.6, 133.7, 133.8, 135.51, 135.54, 198.1, 200.3. IR (KBr):
nmax 2937, 2859, 2101, 2062, 2031, 1672, 1553, 1428, 1306,
1214, 1138, 1088, 1037, 1006, 824 cmꢀ1. Anal. Calcd for
C37H42Co2O10Si: C, 56.06; H, 5.34. Found: C, 56.07; H,
5.11.
4.1.1. Vinyl iodide 4. To a solution of B-I-9-BBN (1.0 M
hexane solution, 3.5 mL, 3.52 mmol) in dry CH2Cl2 (24 mL)
was added dropwise acetylene 3 (610 mg, 3.35 mmol) dis-
solved in dry CH2Cl2 (10 mL) over 10 min at ꢀ20 ꢁC under
nitrogen atmosphere. After stirring for 2 h 30 min at the same
temperature, AcOH (574 mL) was added dropwise to the re-
action mixture over 5 min. The reaction mixture was stirred
further for 30 min at 0 ꢁC, then poured into H2O. NaOH so-
lution (3 M) was added to the mixture and the mixture was
extracted with CH2Cl2 (ꢂ2). The combined organic extract
was washed with saturated NH4Cl solution, H2O, brine, dried
over anhydrous Na2SO4, and concentrated under reduced
pressure. The residue was purified by silica gel column chro-
matography (SiO2: 30 g, hexane/AcOEt¼4/1) to give vinyl
iodide 4 (924 mg, 89%) as a yellow oil.
4.1.3. Enone 10. A solution of cyclic ketone cobalt complex
9 (530 mg, 729 mmol) in dichloroethane (24 mL) was heated
with bis(trimethylsilyl)acetylene (330 mL, 1.46 mmol) and
Et3SiH (1.2 mL, 7.29 mmol) at 60 ꢁC for 5 h. The mixture
was concentrated under reduced pressure and the residue
was purified by silica gel column chromatography (SiO2:
30 g, hexane/AcOEt¼4/1) to give the vinyl silane (structure
not shown 377 mg, 87%) as a dark brown oil.
1H NMR (400 MHz, CDCl3): d 1.43–1.57 (1H, m, H-3a),
1.65–1.77 (2H, m, H-2 ꢂ2), 2.04 (3H, s, –COCH3), 2.13–
2.21 (1H, m, H-3b), 2.42 (1H, ddd, J¼15.0, 9.0, 1.0 Hz,
H-6a), 2.64 (1H, ddt, J¼15.0, 3.0, 1.5 Hz, H-6b), 3.37
(1H, td, J¼11.0, 3.5 Hz, H-1a), 3.52 (1H, td, J¼9.0,
3.0 Hz, H-5), 3.92 (1H, ddt, J¼11.0, 4.0, 1.5 Hz, H-1b),
4.58 (1H, ddd, J¼11.5, 9.0, 4.0 Hz, H-4), 5.78 (1H, t,
J¼1.5 Hz, –C¼CH2), 6.10 (1H, q, J¼1.0 Hz, –C¼CH2).
13C NMR (100 MHz): d 21.2, 25.1, 29.5, 47.7, 67.9, 71.3,
77.9, 106.8, 127.9, 170.2.
[a]2D2 ꢀ74.3 (c 0.48, CHCl3). 1H NMR (400 MHz, CDCl3):
d 0.59–0.67 (6H, m, –Si(CH2CH3)3), 0.95 (9H, t, J¼7.5,
–Si(CH2CH3)3), 1.04 (9H, s, –SitBu), 1.35–1.48 (2H, m,
H-3a, H-11a), 1.52–1.74 (5H, m, H-2 ꢂ2, H-11b, H-12
ꢂ2), 1.94–2.04 (1H, m, H-3b), 2.62–2.67 (2H, m, H-6
ꢂ2), 3.01 (1H, ddd, J¼10.0, 9.5, 4.5 Hz, H-4), 3.34 (1H,
td, J¼11.5, 2.5 Hz, H-1a), 3.49 (1H, ddd, J¼9.5, 9.0,
7.0 Hz, H-5), 3.60–3.69 (2H, m, H-13 ꢂ2), 3.85 (1H, ddt,
J¼11.5, 4.5, 2.0 Hz, H-1b), 3.92 (1H, dt, J¼8.5, 2.5 Hz,
H-10), 5.56 (1H, d, J¼2.5 Hz, C-9), 7.34–7.45 (6H, m, aro-
matic), 7.62–7.67 (4H, m, aromatic). 13C NMR (100 MHz):
d 2.9, 7.1, 19.2, 25.3, 26.9, 28.8, 30.2, 32.2, 49.0, 63.5, 67.6,
79.5, 80.4, 81.6, 127.6, 127.6, 129.7, 129.6, 133.97, 134.03,
134.8, 135.6, 140.0, 144.5, 208.3. IR (KBr): nmax 3072,
2955, 2857, 2100, 2062, 2032, 1677, 1590, 1463, 1428,
1390, 1336, 1284, 1237, 1209, 1196, 1181, 1006, 966,
824 cmꢀ1. Anal. Calcd for C35H52O4Si2: C, 70.89; H,
8.84. Found: C, 70.91; H, 8.92.
4.1.2. Cyclic ketone cobalt complex 9. A solution of cyclic
exo-olefin cobalt complex 8 (1.62 g, 2.13 mmol) in dry THF
(107 mL) and H2O (21 mL) was stirred with OsO4 (4% H2O
solution, 1.35 mL, 213 mmol), NaIO4 (2.27 g, 10.6 mmol),
and acetic acid (5.4 mL) at room temperature. Additional
NaIO4 (2.27 g, 10.6 mmol) was added to the reaction mix-
ture in portion wise three times until the starting material
was consumed completely for 12 h 20 min. The reaction
mixture was poured into H2O and extracted with Et2O
(ꢂ2). The combined organic extract was washed with
H2O, brine, dried over Na2SO4, and concentrated under re-
duced pressure. The residue was purified by flash silica gel
column chromatography (SiO2: 55 g, hexane/AcOEt¼6/1)
to give cyclic ketone cobalt complex 9 (1.21 g, 74%) as
a dark brown oil and a mixture containing diol.
This vinyl silane (780 mg, 1.32 mmol) was dissolved in
dry THF (132 mL), and mixed with TBAF (1.0 M THF
solution, 1.45 mL, 1.45 mmol) at 0 ꢁC. After stirring for
5 min at the same temperature, the reaction mixture was
poured into NH4Cl solution and extracted with AcOEt
(ꢂ3). The combined organic extract was washed with
H2O, brine, dried over anhydrous Na2SO4, and concentrated
under reduced pressure. The residue was purified by silica
The mixture was dissolved in dry THF (10.7 mL), H2O
(2.1 mL), to which NaIO4 (450 mg) was added. After

5892
A. Nonoyama et al. / Tetrahedron 63 (2007) 5886–5894
gel column chromatography (SiO2: 20 g, hexane/
AcOEt¼20/1–1/1) to give enone 10 (540 mg, 85%) as a
brown oil.
trans/syn/cis-Fused tricyclic ketone 12. [a]2D5 +91.7 (c 0.53,
CHCl3). 1H NMR (400 MHz, CDCl3): d 1.42–1.81 (7H, m,
H-2 ꢂ2, H-3a, H-11 ꢂ2, H-12 ꢂ2), 2.03–2.11 (1H, m, H-
3b), 2.53 (1H, dd, J¼14.0, 4.5 Hz, H-8a), 2.63 (1H, dd,
J¼11.0, 4.0 Hz, H-6a), 2.72 (1H, t, J¼11.0 Hz, H-6b),
3.01 (1H, dd, J¼14.0, 11.0 Hz, H-8b), 3.13 (1H, ddd,
J¼11.0, 9.0, 5.0 Hz, H-4), 3.33 (1H, td, J¼11.0, 4.0 Hz,
H-1a), 3.40 (1H, ddd, J¼11.0, 9.0, 4.0 Hz, H-5), 3.52–3.59
(1H, m, H-13a), 3.63 (1H, dt, J¼12.0, 2.0 Hz, H-13b),
3.67 (1H, dt, J¼9.0, 4.5 Hz, H-10), 3.86 (1H, ddt, J¼11.0,
4.0, 2.0 Hz, H-1b), 4.48 (1H, dt, J¼10.0, 4.5 Hz, H-9). 13C
NMR (100 MHz): d 23.7, 25.5, 26.3, 31.1, 43.9, 46.8,
62.6, 67.7, 73.6, 76.4, 80.3, 81.0, 203.9. IR (KBr): nmax
2939, 2864, 2731, 1701, 1445, 1374, 1290, 1187, 1078, 961,
922, 844 cmꢀ1. Anal. Calcd for C13H20O4: C, 64.98; H, 8.39.
Found: C, 64.98; H, 8.52.
[a]2D5 ꢀ41.0 (c 0.42, CHCl3). 1H NMR (400 MHz, CDCl3):
d 1.06 (9H, s, –SitBu), 1.40–1.54 (2H, m, H-3a, H-11a),
1.60–1.74 (5H, m, H-2 ꢂ2, H-11b, H-12 ꢂ2), 2.03–2.09
(1H, m, H-3b), 2.76 (1H, dd, J¼10.0, 5.5 Hz, H-6a), 2.82
(1H, t, J¼10.0 Hz, H-6b), 3.12 (1H, ddd, J¼10.0, 9.5,
4.5 Hz, H-4), 3.37 (1H, ddd, J¼12.0, 11.5, 3.0 Hz, H-1a),
3.47 (1H, ddd, J¼10.0, 9.5, 5.5 Hz, H-5), 3.66–3.71 (2H,
m, H-13 ꢂ2), 3.86–3.92 (1H, m, H-1b), 3.98 (1H, dq,
J¼8.5, 2.5 Hz, H-10), 5.66 (1H, dd, J¼12.0, 2.5 Hz, H-9),
5.92 (1H, dd, J¼12.0, 2.5 Hz, H-8), 7.37–7.47 (6H, m, aro-
matic), 7.65–7.70 (4H, m, aromatic). 13C NMR (100 MHz):
d 19.2, 25.3, 26.9, 28.7, 30.3, 32.3, 49.1, 63.4, 67.7, 79.4,
80.3, 80.8, 127.6, 127.7, 129.6, 130.1, 133.9, 134.77,
134.79, 135.6, 204.7. IR (KBr): nmax 2931, 2858, 2092,
2052, 2029, 1694, 1428, 1390, 1334, 1289, 1183, 1096,
824 cmꢀ1. Anal. Calcd for C29H38O4Si: C, 72.76; H, 8.00.
Found: C, 72.74; H, 8.00.
4.1.6. Vinyl triflate 13. The trans/syn/trans-fused tricyclic
ketone 11 (39.6 mg, 165 mmol) in dry THF (4.2 mL) was
cooled to ꢀ78 ꢁC and treated dropwise with KHMDS
(0.5 M toluene solution, 494 mL, 247 mmol) under argon at-
mosphere. After stirring for 30 min at the same temperature,
PhNTf2 dissolved in dry THF (4 mL) was added dropwise to
the reaction mixture for over 5 min. The reaction mixture
was stirred further for 30 min, then poured into NH4Cl solu-
tion, and extracted with Et2O (ꢂ2). The combined organic
extract was washed with H2O, brine, dried over anhydrous
Na2SO4, and concentrated under reduced pressure. The res-
idue was purified by flash silica gel column chromatography
(SiO2: 4 g, hexane/AcOEt¼6/1) to give vinyl triflate 13
(54.8 mg, 86%) as a yellow oil.
4.1.4. trans/syn/trans-Fused tricyclic ketone 11. To a solu-
tion of enone 10 (17.8 mg, 37.2 mmol) in dry THF (1.9 mL)
was added TBAF (1.0 M THF solution, 37.2 mL, 37.2 mmol)
at room temperature. After stirring for 2 h, additional TBAF
(1.0 M THF solution, 37.2 mL, 37.2 mmol) was added to the
reaction mixture. The reaction mixture was stirred further
for 13 h 15 min at the same temperature, then poured into
NH4Cl solution and extracted with AcOEt (ꢂ2). The com-
bined organic extract was washed with H2O, brine, dried
over anhydrous Na2SO4, and concentrated under reduced
pressure. The residue was purified by silica gel column chro-
matography (SiO2: 1 g, hexane/AcOEt¼10/1–1/1) to give
trans/syn/trans-fused tricyclic ketone 11 (7.6 mg, 85%) as
a white solid.
1
[a]2D3 +1.6 (c 0.64, CHCl3). H NMR (400 MHz, CDCl3):
d 1.40–1.54 (2H, m, H-3a, H-11a), 1.62–1.71 (4H, m, H-2
ꢂ2, H-12 ꢂ2), 1.99–2.07 (1H, m, H-11b), 2.08–2.15 (1H,
m, H-13b), 2.51 (1H, dt, J¼15.0, 2.0 Hz, H-8a), 3.04 (1H,
dd, J¼15.0, 4.5 Hz, H-8b), 3.24–3.31 (2H, m, H-1a, H-13a),
3.28 (1H, ddd, J¼11.0, 9.0, 5.0 Hz, H-4), 3.32 (1H, ddd,
J¼9.5, 4.5, 2.0 Hz, H-9), 3.43 (1H, ddd, J¼11.0, 9.0,
4.5 Hz, H-10), 3.72 (1H, dd, J¼9.0, 5.5 Hz, H-5), 3.89 (2H,
ddt, J¼11.5, 4.5, 2.0 Hz, H-1b, H-13b), 5.75 (1H, dd, J¼5.5,
2.0 Hz, H-6). 13C NMR (100 MHz): d 25.2, 25.9, 31.1, 31.4,
34.6, 67.3, 68.4, 77.3, 78.4, 79.5, 81.2, 118.4 (q, J¼320 Hz),
124.8, 147.1. IR (KBr): nmax 2948, 2857, 1684, 1417, 1209,
1148, 1090, 1014, 956, 903, 866 cmꢀ1. Anal. Calcd for
C14H19F3O6S: C, 45.16; H, 5.14. Found: C, 45.16; H, 5.34.
1
[a]2D4 +1.6 (c 1.18, CHCl3). H NMR (400 MHz, CDCl3):
d 1.46–1.60 (2H, m, H-3a, H-11a), 1.64–1.72 (4H, m, H-2
ꢂ2, H-12 ꢂ2), 2.06–2.13 (2H, m, H-3b, H-11b), 2.72 (2H,
ddd, J¼11.0, 4.5, 2.0 Hz, H-6a, H-8a), 2.81 (2H, t, J¼
11.0 Hz, H-6b, H-8b), 3.24 (2H, ddd, J¼11.0, 9.0, 5.0 Hz,
H-4, H-10), 3.29–3.37 (2H, m, H-1a, 13a), 3.44 (2H, ddd,
J¼11.0, 9.0, 4.5 Hz, H-5, H-9), 3.87 (2H, ddt, J¼11.0, 4.0,
2.0 Hz, H-1b, H-13b). 13C NMR (100 MHz): d 25.5, 32.3,
50.1, 67.6, 82.0, 85.0, 205.1. IR (KBr): nmax 3005, 2938,
2851, 2724, 1701, 1450, 1376, 1340, 1289, 1179, 1092,
1048, 1016, 991, 966, 896, 874, 848 cmꢀ1. Anal. Calcd for
C13H20O3: C, 64.98; H, 8.39. Found: C, 64.97; H, 8.22.
4.1.7. endo-Olefin 14. Vinyl triflate 13 (49.6 mg, 128 mmol)
in dry THF (6.4 mL) was cooled to ꢀ40 ꢁC and Fe(acac)3
(4.5 mg, 12.8 mmol) and NMP (25 mL) were added to the
solution under argon atmosphere. MeMgBr (0.82 M THF
solution, 313 mL, 257 mmol) was added dropwise to the mix-
ture at the same temperature. After stirring for 1 h 50 min at
the same temperature, additional Fe(acac)3 (4.5 mg,
12.8 mmol) and MeMgBr (0.82 M THF solution, 160 mL,
131 mmol) were added to the reaction mixture. The reaction
mixture was stirred further for 1 h, then poured into NH4Cl
solution, and extracted with Et2O (ꢂ2). The combined
organic extract was washed with H2O, brine, dried over
anhydrous Na2SO4, and concentrated under reduced pres-
sure. The residue was purified by flash silica gel column
chromatography (SiO2: 4 g, hexane/AcOEt¼8/1) to give
endo-olefin 14 (27.4 mg, 90%) as a yellow oil.
4.1.5. trans/syn/trans-Fused tricyclic ketone 11 and trans/
syn/cis-fused tricyclic ketone 12. A solution of enone 10
(190 mg, 397 mmol) in CH3NO2 (40 mL) containing
TsOH$H2O (411 mg, 2.3 mmol) was stirred at room temper-
ature for 12 h 30 min. The reaction mixture was poured into
NaHCO3 solution and extracted with CH2Cl2 (ꢂ3). The
combined organic extract was washed with H2O, brine, dried
over anhydrous Na2SO4, and concentrated under reduced
pressure. The residue was purified by flash silica gel column
chromatography (SiO2: 20 g, hexane/AcOEt¼1/1) to give
trans/syn/trans-fused tricyclic ketone 11 (38.6 mg, 40%)
as a white solid and trans/syn/cis-fused tricyclic ketone 12
(43.8 mg, 46%) as a yellow oil.

A. Nonoyama et al. / Tetrahedron 63 (2007) 5886–5894
5893
1
[a]2D6 +10.7 (c 0.22, CHCl3). H NMR (400 MHz, CDCl3):
1H NMR (400 MHz, CDCl3): d 0.85 (3H, d, J¼6.5 Hz,
–Me), 1.38 (1H, td, J¼12.0, 11.0 Hz, H-6a), 1.45–1.57
(1H, m, H-3a), 1.68–1.74 (2H, m, H-2 ꢂ2), 1.77–1.96
(4H, m, H-11a, H-7, H-12 ꢂ2), 2.00 (1H, dt, J¼12.0,
4.0 Hz, H-6b), 2.05 (1H, m, H-3b), 2.24–2.32 (1H, m, H-
11b), 2.53 (1H, dd, J¼9.0, 1.5 Hz, H-8), 3.05 (1H, ddd,
J¼11.0, 9.0, 4.0 Hz, H-5), 3.17 (1H, ddd, J¼11.0, 9.0,
4.0 Hz, H-4), 3.38–3.46 (1H, m, H-1a), 3.87–3.94 (3H, m,
H-1b, H-13 ꢂ2), 4.06 (1H, dd, J¼9.0, 1.5 Hz, H-9), 4.26
(1H, dt, J¼9.0, 6.5 Hz, H-10). 13C NMR (100 MHz):
d 16.6, 25.6, 25.9, 29.3, 33.9, 36.4, 37.8, 42.7, 67.9, 68.9,
77.9, 78.0, 79.6, 80.4.
d 1.36–1.50 (4H, m, H-2a, H-3a, H-11a, H-12a), 1.51–1.70
(2H, m, H-2b, H-12b), 1.82 (3H, s, –Me), 1.95–2.02 (1H,
m, H-11b), 2.03–2.11 (1H, m, H-3b), 2.08 (1H, dd,
J¼13.5, 2.0 Hz, H-8a), 2.83 (1H, dd, J¼13.5, 4.5 Hz, H-
8b), 3.13 (1H, ddd, J¼11.0, 9.0, 4.5 Hz, H-4), 3.22–3.36
(4H, m, H-1a, H-9, H-10, H-13a), 3.71 (1H, dd, J¼9.0,
5.0 Hz, H-5), 3.82–3.91 (2H, m, H-1b, H-13b), 5.36 (1H,
d, J¼5.0 Hz, H-6). 13C NMR (100 MHz): d 25.6, 26.0,
26.3, 31.4, 31.6, 35.6, 67.2, 68.3, 76.4, 78.4, 80.9, 82.7,
127.8, 135.2. IR (KBr): nmax 2937, 2855, 1439, 1272,
1214, 1148, 1090, 1027, 966, 855 cmꢀ1. Anal. Calcd for
C14H22O3: C, 70.56; H, 9.30. Found: C, 70.65; H, 9.29.
4.1.11. Reduction product 21. To a solution of 20 (14.4 mg,
39.3 mmol) in toluene (780 mL) were added tri-n-butyltin hy-
dride (53 mL, 197 mmol) and AIBN (1.4 mg, 8.5 mmol) at
room temperature. The reaction mixture was warmed to
55 ꢁC and stirred for 1 h 35 min. The reaction mixture was
concentrated under reduced pressure and the residue was
purified by silica gel column chromatography (SiO2: 0.7 g,
hexane/AcOEt¼4/1) to give reduction product 21 (8.8 mg,
94%) as a yellow oil.
4.1.8. HIJ-ring model 2. To a solution of endo-olefin 14
(27.4 mg, 115 mmol) in dry CH2Cl2 (5.6 mL) was added
[(cod)py(Cy3P)Ir]PF6 (9.3 mg, 11.5 mmol) at 0 ꢁC under hy-
drogen atmosphere. After stirring for 1 h 10 min, the reac-
tion mixture was concentrated under reduced pressure and
purified by silica gel column chromatography (SiO2: 0.8 g,
hexane/AcOEt¼4/1) to give HIJ-ring model 2 (27.6 mg,
99%) as a white solid.
1
[a]2D9 0.29 (c 1.07, CHCl3). H NMR (400 MHz, CDCl3):
1H NMR (400 MHz, CDCl3): d 0.91 (3H, d, J¼6.5 Hz,
–Me), 1.23 (1H, td, J¼12.5, 10.5 Hz, H-6a), 1.40–1.57 (4H,
m, H-3a, H-7, H-9a, H-11a), 1.66–1.77 (2H, m, H-2 ꢂ2),
1.82 (1H, ddd, J¼14.0, 9.0, 2.0 Hz, H-9b), 1.83–1.93 (2H,
m, H-12 ꢂ2), 1.96 (1H, dt, J¼12.0, 4.0 Hz, H-6b), 1.99–
2.08 (2H, m, H-3b, H-11b), 3.40 (1H, td, J¼11.5, 4.0 Hz,
H-1a), 3.75 (1H, td, J¼7.5, 6.5 Hz, H-13a), 3.87 (1H, dt,
J¼8.5, 6.5 Hz, H-13b), 3.90 (1H, ddt, J¼11.5, 4.5, 2.0 Hz,
H-1b), 4.11 (1H, dddd, J¼9.0, 8.0, 6.0, 3.5 Hz, H-10). 13C
NMR (100 MHz): d 17.7, 25.7, 25.8, 29.5, 32.0, 36.1,
38.7, 39.2, 67.8, 67.9, 75.8, 77.8, 78.4, 80.6.
d 1.02 (3H, d, J¼7.5 Hz, –Me), 1.41 (2H, m, H-3a, H-11a),
1.56 (2H, ddd, J¼13.5, 10.5, 9.0 Hz, H-6a, H-8a), 1.61
(4H, m, H-2 ꢂ2, H-12 ꢂ2), 1.79 (2H, ddd, J¼13.5, 3.5,
1.5 Hz, H-6b, H-8b), 1.88 (1H, m, H-7), 2.02 (2H, m, H-3b,
H-11b), 3.05 (2H, ddd, J¼10.0, 9.0, 3.5 Hz, H-5, H-9),
3.13 (2H, ddd, J¼10.5, 9.0, 4.5 Hz, H-4, H-10), 3.25 (2H,
m, H-1a, H-13a), 3.80 (2H, ddt, J¼11.5, 4.0, 2.0 Hz, H-1b,
H-13b). 13C NMR (100 MHz): d 25.9 (C2, C12), 28.0 (C7),
28.1 (Me), 33.0 (C3, C11), 46.4 (C6, C8), 67.4 (C1, C13),
81.7 (C5, C9), 84.4 (C4, C10). IR (KBr): nmax 2936, 2846,
2713, 1450, 1376, 1345, 1326, 1294, 1265, 1224, 1180,
1147, 1098, 1026, 969, 947, 895 cmꢀ1. Anal. Calcd for
C14H24O3: C, 69.96; H, 10.07. Found: C, 69.97; H, 10.01.
Acknowledgements
4.1.9. Reduction product 2 and 16. exo-Olefin 15 (3.3 mg,
13.8 mmol) was dissolved in EtOH (1.4 mL) and PtO2 was
added (0.3 mg, 1.3 mmol) at room temperature under hydro-
gen atmosphere. After stirring for 1 h, the reaction mixture
was filtered through a Celite column by washing with
MeOH. The filtrate was concentrated under reduced pres-
sure, then the residue was purified by silica gel column chro-
matography (hexane/AcOEt¼5/1) to give reduction product
2 and 16 (2.8 mg, 86%) as a pale yellow oil.
This work was supported in parts by a Grand-in-Aid for
Specially Promoted Research (16002007) and a Grand of
the 21st Century COE program from the Ministry of Educa-
tion, Culture, Sports, Science and Technology (MEXT),
Japan. We are grateful to Mr. Kitamura (analytical labora-
tory in this school) for elemental analysis.
References and notes
4.1.10. Rearrangement product 20. Iodine (31.0 mg,
122 mmol) was placed in a small vessel and dissolved with
CH3CN (2.5 mL), and cooled to 0 ꢁC. To this mixture was
added dropwise a solution of alcohol 19 (8.4 mg, 35 mmol)
dissolved in CH3CN (1.0 mL). After stirring for 5 min at
the same temperature, the reaction mixture was warmed to
room temperature and stirred further for 1 h 40 min. The
reaction mixture was quenched with saturated Na2SO3
solution and the mixture was stirred until the yellow color
disappeared. The mixture was extracted with AcOEt (ꢂ2).
The combined organic extract was washed with H2O, brine,
dried over anhydrous Na2SO4, and concentrated under
reduced pressure. The residue was purified by silica gel col-
umn chromatography (SiO2: 1.5 g, hexane/AcOEt¼2/1) to
give rearrange product 20 (9.6 mg, 75%) as a yellow oil.
1. Nakata, T. Chem. Rev. 2005, 105, 4314–4347.
2. Isolation: Scheuer, P. J.; Takahashi, W.; Tsutumi, J.; Yoshida, T.
Science 1967, 155, 1267–1268; Structure: (a) Murata, M.;
Legurand, A. M.; Ishibashi, Y.; Fukui, M.; Yasumoto, T.
J. Am. Chem. Soc. 1990, 112, 4380–4386; (b) Satake, M.;
Morohashi, A.; Oguri, H.; Oishi, T.; Hirama, M.; Harada, N.;
Yasumoto, T. J. Am. Chem. Soc. 1997, 119, 11325–11326; (c)
Yasumoto, T. Chem. Rec. 2001, 1, 228–242; Total synthesis:
(d) Hirama, M.; Oishi, T.; Uehara, H.; Inoue, M.; Maruyama,
M.; Oguri, H.; Satake, M. Science 2001, 294, 1904–1907; (e)
Inoue, M.; Miyazaki, K.; Ishihara, Y.; Tatami, A.; Ohuma, Y.;
Komano, K.; Yamashita, S.; Lee, N.; Hirama, M. J. Am.
Chem. Soc. 2006, 128, 9352–9354.
3. (a) Isobe, M.; Yenjai, C.; Tanaka, S. Synlett 1994, 916–918;
(b) Yenjai, C.; Isobe, M. Tetrahedron 1998, 54, 2509–2520;

5894
A. Nonoyama et al. / Tetrahedron 63 (2007) 5886–5894
(c) Isobe, M.; Hosokawa, S.; Kira, K. Chem. Lett. 1996,
8. (a) Hosokawa, S.; Isobe, M. Tetrahedron Lett. 1998, 39, 2609–
2612; (b) Kira, K.; Tanda, H.; Hamajima, A.; Baba, T.; Takai,
S.; Isobe, M. Tetrahedron 2002, 58, 6485–6492.
9. It was calculated which dihedral angle of C]O and C]C was
fixed on the same plane as transition state.
473–474; (d) Hosokawa, S.; Isobe, M. J. Org. Chem. 1999,
64, 37–48; (e) Saeeng, R.; Isobe, M. Tetrahedron Lett.
1999, 40, 1911–1914. For a review, see Ref. 7a.
4. Hamajima, A.; Isobe, M. Org. Lett. 2006, 8, 1205–1208.
5. (a) Nicolaou, K. C.; Hwang, C.-K.; Marron, B. E.; De Frees,
S. A.; Couladouros, E. A.; Abe, Y.; Caroll, P. J. J. Am. Chem.
Soc. 1990, 112, 3040–3054; (b) Fujiwara, K.; Morishita, H.;
Saka, K.; Murai, A. Tetrahedron Lett. 2000, 41, 507–508.
6. Hara, S.; Dojo, H.; Takinami, S.; Suzuki, A. Tetrahedron Lett.
1983, 24, 731–734.
7. (a) Isobe, M.; Nishizawa, R.; Hosokawa, S.; Nishikawa, T.
Chem. Commun. 1998, 2665–2676; (b) Shibuya, S.; Isobe,
M. Tetrahedron 1998, 54, 6677–6698; (c) Takai, S.;
Ploypradith, P.; Hamajima, A.; Kira, K.; Isobe, M. Synlett
2002, 588–592.
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10. Scheiper, B.; Bonnekessel, M.; Krause, H.; Furstner, A. J. Org.
Chem. 2004, 69, 3943–3949.
11. (a)Crabtree, R. H.;Morris, G. E. J. Chem. Soc., Chem. Commun.
1976, 716–717; (b) Domon, D.; Fujiwara, K.; Murai, A.; Kawai,
H.; Suzuki, T. Tetrahedron Lett. 2005, 46, 8285–8288.
12. Liu, T.-Z.; Li, J.-M.; Isobe, M. Tetrahedron 2000, 56, 10209–
10219.
13. Shida, T.; Tachibana, K. 46th Symposium on The Chemistry of
Natural Products, Hiroshima, 2004; pp 227–231.
14. Takai, S.; Sawada, N.; Isobe, M. J. Org. Chem. 2003, 68, 3225–
3231.