Synthetic studies on ciguatoxin - Synthesis of H-I-J ring system

Article abstract of DOI:10.1016/S0040-4020(00)00865-6

Synthesis of a tricyclic ring system corresponding to H-I-J rings of ciguatoxin was stereoselectively achieved in 13 steps from a sugar derivative as a model study directed toward the total synthesis of ciguatoxin. (C) 2000 Elsevier science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00865-6

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 10209±10219
Synthetic Studies on CiguatoxinÐSynthesis of
H±I±J Ring System
*
Tong-Zhu Liu, Jian-Min Li and Minoru Isobe
Laboratory of Organic Chemistry, School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan
Received 8 December 1999; accepted 20 May 2000
AbstractÐSynthesis of a tricyclic ring system corresponding to H±I±J rings of ciguatoxin was stereoselectively achieved in 13 steps from a
sugar derivative as a model study directed toward the total synthesis of ciguatoxin. q 2000 Elsevier Science Ltd. All rights reserved.
Ciguatoxin is a marine trans-fused polycyclic compound
causing ciguatera poisoning.1 Our approach required a
new cyclization to prepare ring systems with stereochemical
control. We have been addressing this goal by applying the
Nicholas reaction2 to acetylene biscobalthexacarbonyl
complexes3 for the formation of medium-sized ether
rings.4 These cyclization products, endo cobalt complexes
of acetylenes, are convertible into ole®ns through reductive
decomplexation methods: for example, hydrogenation with
rhodium catalyst, hydrosilylation or tin hydride reduction.3,4
The complex was designed to assist the cyclization of 7-, 8-,
9- and 10-membered ether rings by affecting the entropy
effect which otherwise leads to poor cyclization without
the biscobalt.5 These methodologies have been reviewed
in a feature article describing the complexation to bis-
cobalthexacarbonyl, cyclization to cyclic ethers and
decomplexation.5 This paper describes the synthesis of the
H±I±J ring system (2) using this methodology.
generates a precursor B, where the ole®n is derived from
acetylene biscobalthexacarbonyl precursor of C according
to our methodology.5 The stereochemistry of its methyl
group has to be introduced. Ring-I could be prepared from
a cation intermediate D stabilized by the acetylene biscobalt
complex. The requisite acetylene compound is accessible
from a palladium-mediated coupling between a vinyl halide
E (XˆBr, I) and an acetylene F, prepared from known
tosylate G.
The starting material tosylate 4 was synthesized according
to the route reported by Martin et al.6 Addition of a THF
solution of 4 to vinylmagnesium bromide7 at 08C in the
presence of catalytic amount of copper(I) iodide8 and stir-
ring at room temperature for two days gave vinylsilane 5. A
high concentration (6.2 M in THF) was required in this step.
Exposure of the corresponding acetate 5 to iodine solution
in anhydrous and degassed dichloromethane at 08C afforded
the vinyl iodide 6.9 It was noted that acetyl group was
stable under this condition, while the tert-butyldimethylsilyl
group was unstable to iodine. Sonogashira coupling10 of the
vinyl iodide 6 with a protected propargyl alcohol in the
presence of catalytic amount of palladium(0) provided
The retrosynthetic analysis for tricyclic compound (2) is
illustrated in Scheme 1. Ring-H in the target molecule A
was planned to be derived from a d-sugar, a hexopyranoside
precursor in optically active form. Opening the ring-J
Keywords: ciguatoxin; acetylene biscobalthexacarbonyl complex; cyclization.
* Corresponding author. Tel.: 181-52-789-4109; fax: 181-52-789-4111; e-mail: isobem@agr.nagoya-u.ac.jp
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00865-6

10210
T.-Z. Liu et al. / Tetrahedron 56 (2000) 10209±10219
Scheme 1. Retrosynthetic analysis.
Scheme 2. Reagents, conditions and yields: (a) CuI (cat), THF, 08C to rt, 82%. (b) TsOH, MeOH, 93%. (c) Ac2O, Py, 100%. (d) I2, CH2Cl2, 08C to rt, 71%. (e)
CuI, n-BuNH2, Pd(0), benzene, rt, 69%. (f) K2CO3, MeOH, rt. (g) Co2(CO)8, CH2Cl2, 08C to rt, 100% (2 steps). (h) BF3´OEt2, 08C, CH2Cl2, 87%.
compound 7. Deacetylation of 7 with potassium carbonate
in methanol followed by complexation of the acetylene with
biscobaltoctacarbonyl provided the key intermediate 8 in
good yield.
mediate D (Scheme 1), and the results are summarized in
Table 1. In addition, lower temperature also disfavored the
formation of 13 presumably due to slower equilibration
(entry 4). Compound 13 thus emerged as the product of a
thermodynamically controlled ring closure.4 The stereo-
1
The stage is now set for the annulation of the oxocane ring.
Upon treatment of 8 with boron tri¯uoride etherate
(degassed CH2Cl2, 08C), the desired ring closure took
place to afford the bicyclic compound 9 in 87% yield.
NOE experiments indicated that one of the C-10 protons,
C-10 Ha (d 5.11, doublet, JH10a, H10bˆ16 Hz), is spatially
proximate to the C-4 proton (Scheme 2).
chemistry of 13 was demonstrated by two-dimensional H
NOESY experiments. The observation of an noe between
H-4 (d 3.14) and H-10 was indicative of a syn relationship
between these protons (Scheme 3).
Reduction of the terminal ole®n in compound 13 with
diimide12 in methanol in the presence of triethylamine as
an acid scavenger resulted in a mixture of two diastereo-
isomers, which was separated by chromatography to
provide the desired isomer 14a in 63% and the undesired
isomer 14b in 24% yield, respectively. The con®guration of
the newly formed methyl-bearing stereocenter at position
C-7 was assigned in a later stage. It was noted that other
conditions for the reduction of the conjugated terminal
ole®n 13, such as normal-pressure catalytic hydrogenation
These results encouraged us to use a longer acetylene in the
Sonogashira coupling step, so that we could have a side
chain precursor to ring-J. Hex-5-yn-1,4-diol,11 was prepared
as its protected form 10, and was coupled with 6, to provide
compound 11. Cobalt complexation and cyclization were
achieved under similar conditions to afford bicyclic
compound 13 as a single stereoisomer in 94% yield.
At this stage, the crucial stereoselectivity of the oxocane
ring formation (12!13) was investigated. Interestingly, if
this oxocane ring forming reaction was quenched shortly
after the addition of boron tri¯uoride etherate, then a
mixture of stereoisomeric cyclization products, epimeric
at C-10 (13a) was produced. On prolonged reaction time,
however, the anti isomer 13a (H-10, d 5.00, dd, Jˆ11, 2 Hz)
equilibrated in situ and ultimately underwent conversion to
the desired stereoisomer 13 (H-10, d 4.61, dd, Jˆ10, 3 Hz),
presumably through a process involving the cation inter-
Table 1. Cobalt complex assisted thermodynamically-controlled cycliza-
tion of 12!13 (The reaction 12!13 was carried out in CH2Cl2 solvent and
4 mM BF3´OEt2. The ratios of syn/anti were determined from the H-10
signal intensity in 1H NMR spectra)
Entry
Conditions
syn/anti 13/13a
Yield (%)
1
2
3
4
08C, 1 min
3:1
20:1
.100:1
9:1
60
88
94
76
08C, 15 min
08C, 40 min
2208C, 50 min

T.-Z. Liu et al. / Tetrahedron 56 (2000) 10209±10219
10211
Scheme 3. Reagents, conditions and yields: (a) n-BuNH2, CuI, Pd(0), benzene, rt, 89%. (b) MeOH, K2CO3, rt, 96%. (c) Co2(CO)8, CH2Cl2, 08C to rt, 87%.
(d) BF3´OEt2, CH2Cl2, 08C, 94%. (e) [HNvNH], rt, [14a, 63%; 14b, 24%]. (f) n-Bu3SnH, benzene, [15a, 96%; 15b, 86%]. (g) TBAF, THF, rt, [16a, 85%; 16b,
85%].
Figure 1. Conformation of 16a and 16b (calculated by MacroModel. Dashed lines indicate NOE to explain the validity of these conformations).
(Rh, Pd/C, PtO2, Raney Ni),2 or high-pressure hydrogena-
tion4af (.110 atm) with Wilkinson catalyst, simply gave no
reactions in this particular case, presumably due to the low
reactivity of the double bond in this complex system.
Reductive decomplexation of the acetylene±biscobalthexa-
carbonyl complex 14a,b with tri-n-butyltin hydride4e
(benzene, 508C) afforded the corresponding cis-ole®ns
15a,b in 96% and 86% yields, respectively. These ole®ns
were allowed to assist the cyclization for ring-J. Thus,
removal of the tert-butyldiphenylsilyl group in compounds
15a,b with tetrabutylammonium ¯uoride in THF provided
alcohols 16a,b (85, 85%, respectively) as potential pre-
cursors for ring-J cyclization. At this stage, the con®gura-
tion of the methyl group at C-7 in compounds 16a,b was
determined by analysis of their NOESY data. Particularly
revealing was the observation of noe between H-7 and H-4;
H-7 and H-10 in the NOESY spectrum for 16b, which
strongly suggests that the methyl group in 16b is concluded
as b-orientation. This result was supported by the data from
conformational analysis studies on 16b (MM2p force ®eld in
MacroModel version 4.5), which revealed that the H-7 in
turned to the elaboration of J-ring, where the trans juncture
at C9-C10 has to be established. Our ®rst attempt for the
construction of this six-membered ether ring was an
oxymercuration reaction.13,14 After an analysis of steric
and stereo-electronic effects,15 it was found that mercury
could engage the D8,9 double bond in 16a from its less
hindered face, namely, from the bottom direction of the
double bond (Fig. 2), then the nucleophilic hydroxyl
group would attack C-9 from the back side of the mercuric
ion. Thus, the cis product would be favored. Indeed, treat-
ment of 16a with mercury(II) acetate in CH2Cl2, followed
by washing with brine, led to the isolation of chloromercury
compound 17, albeit in modest yield. As expected, cis
stereochemistry for the juncture C9-C10 was deduced
from its 1H NMR spectra (J9H,10Hˆ2 Hz). Reductive
demercuration of 17 with tri-n-butyltin hydride and catalytic
amount of AIBN (toluene, 558C)16 afforded cis tricyclic
compound 18 (JH9,H10ˆ2.0 Hz) in 86% yield (Scheme 4).
Ê
16b resides in spatial proximity to H-4 (2.45 A) and H-10
Ê
(2.18 A). Similarly, the calculated conformational data for
16a are also consistent with the result from NOESY experi-
ments (Fig. 1).
With the compound 16a in hands, our attention was then
Figure 2.

10212
T.-Z. Liu et al. / Tetrahedron 56 (2000) 10209±10219
Scheme 4. Reagents, conditions and yields: (a) Hg(OAc)2, CH2Cl2, then brine, 50%. (b) n-Bu3SnH, AIBN(cat), toluene, 86%. (c) I2, CH3CN, 08C to rt, 56%.
(d) n-Bu3SnH, AIBN (cat), toluene, 72%.
however, the attack of the hydroxyl group to the C-9 from
bottom direction would favor the new bond forming, for the
adjacent electron-withdrawing C±O bond (the bold one)
antiparallel to the orbital of the double bond as well as the
attack direction of the nucleophile (Fig. 3) in this case. Thus,
trans product would be favored. Reductive removal of the
iodine in 19 with n-Bu3SnH and AIBN in toluene at 558C18
Figure 3.
afforded the trans tricyclic product 20 (J9,10ˆ9.5 Hz) in 72%
yield (Scheme 4). The NMR data of 18 and 20 are very
similar to each other as listed in Table 2.
We selected to test the feasibility of oxyiodination
reaction.17 Treatment of 16a with iodine in acetonitrile18b
at 08C provided 19 as a major product (56%). Surprisingly,
it was demonstrated to be a trans isomer (JH9,H10ˆ9 Hz). To
account for this result, it was presumed that the conforma-
tional transition state such as the one in Fig. 3 predominated
in this reaction, in which case iodine might engage the D8,9
double bond in 16a from either top or bottom direction,
The tricyclic compound 20 (trans±syn±trans) has a sym-
metry plane in the center of its planar structure, so that one
expected to have 8 lines in its 13C NMR spectrum (1H
decoupled at room temperatures). It, however, afforded 14
lines rather than 8 lines. This fact suggested non-symmetric
1
conformers around the lowest energy. H NMR spectra of
Table 2. The comparison of the chemical shifts for compound 18 and 20
Position
1
Chemical shifts of 18
Chemical shifts of 20
1H
13C
1H
13C
Ha: 3.28, ddd, Jˆ11, 9, 5 Hz
Hb: 3.84, ddd, Jˆ11, 5, 2.0 Hz
1.61±1.71, m
Ha: 1.35±1.44, m
Hb: 2.00±2.09, m
3.07, td, Jˆ10, 5 Hz
3.16, td, Jˆ10, 2 Hz
Ha: 1.52, ddd, Jˆ12, 10, 4 Hz
Hb:1.82±1.88, m
2.11±2.22, m
Ha: 1.53±1.60, m
66.7
Ha: 3.40, ddd, Jˆ12, 10, 5 Hz
67.5
Hb: 3.86±3.93, m
2
3
21.2
26.3
1.66±1.73, m, total 2H
Ha: 1.36, dd, Jˆ13, 6 Hz
Hb: 2.02, ddd, Jˆ13, 9, 2 Hz
3.02, td, Jˆ9, 6 Hz
25.6
29.4
4
5
6
75.5
81.0
29.6
75.8
78.4
36.0
2.98, td, Jˆ9, 4 Hz
Ha: 1.20, ddd, Jˆ12, 9, 4 Hz
Hb: 1.96, dt, Jˆ12, 5 Hz
1.46±1.52, m
7
8
43.0
32.1
39.1
38.6
Ha: 1.26, ddd, Jˆ12, 6, 2 Hz
Hb: 1.82, ddd, Jˆ11, 5, 2 Hz
3.59, dd, Jˆ5, 2 Hz
3.62, dd, Jˆ4, 2 Hz
Ha: 1.58±1.64, m
Hb: 1.40±1.49, m
9
10
11
82.1
75.9
26.2
3.19, td, Jˆ9.5, 2 Hz
4.08, td, Jˆ9.5, 7 Hz
Ha: 1.42±1.48, m
80.6
77.8
31.9
Hb: 2.00±2.06, m
1.84±1.92, m, 2H
Ha: 3.45, td, Jˆ11, 3 Hz
Hb: 3.92, ddd, Jˆ11, 5, 2 Hz
1.01, d, Jˆ7 Hz, 3H
Hb: 1.80, ddd, Jˆ12, 7, 2 Hz
12
13
23.7
67.8
1.86±1.92, m, 2H
25.7
67.8
Ha: 3.74, dd, Jˆ13, 7 Hz
Hb: 3.84, dd Jˆ13, 6 Hz
0.89, d, Jˆ7 Hz, 3H
14
18.1
17.7

T.-Z. Liu et al. / Tetrahedron 56 (2000) 10209±10219
10213
Table 3. Calculated energy of 20 for its two conformers (Figs. 4 and 5).
the C7-Me appeared around 0.9 ppm in different intensities
at different temperatures (25, 35, 45, 558C in CDCl3) as
shown in Fig. 6, in which three sets of doublet (Jˆ7 Hz)
exist at 258C. One of the minor ones increased at higher
temperatures. Signals became broad at temperatures higher
than 458C. On the other hand, 13C NMR spectra did not
change so clearly to show different chemical shifts, indicat-
ing that no symmetric conformer appeared in these tempera-
tures. Signal difference according to these temperatures
might correspond to some other conformers which could
not be speci®ed from these experiments. As a consequence
it is likely that 20 exists as a mixture of various conformers
at ordinary temperatures. To account for this result, it is
presumed that the symmetric crown-conformer (Fig. 4) is
not the most stable one, but the non-crown unsymmetric
conformers such as the one in Fig. 5 turned out to be
20 (symmetric crown conformer)
20 (unsymmetric non-crown
conformer)
BioGraf
BioGraf
Total energy
Bonds
Angles
Torsion
van der Waals
52.916 Total energy
5.102 Bonds
15.636 Angles
4.715 Torsion
27.463 van der Waals
52.368
4.963
12.123
7.451
27.831
MacroModel
Total energy (kcal/mol)
Stretch:
MacroModel
Total energy (kcal/mol)
Stretch:
Bend:
Prop Torsion:
Electrostatic:
van der Waals:
21.74
7.61
39.61
52.60
279.51
67.14
21.52
8.05
30.01
60.25
280.42
69.14
Bend:
Prop Torsion:
Electrostatic:
van der Waals:
more stable. This presumption was supported by computer
calculated conformational studies on 20. The results of
Molecular Mechanics Calculations for 20 from Macro-
Model are consistent with that from BioGraf package,
which revealed that the minimum energy of one of the
most stable unsymmetric conformers is 0.4,0.5 kcal
(Table 3) lower than the symmetric one.
We have demonstrated a study toward the synthesis of the
H±I±J ring system of ciguatoxin. Further extension of
above methodology is now in progress and will be reported
elsewhere.
Figure 4. View of the symmetric conformation of 20 (not global mini-
mum).
Experimental
General
All melting points were recorded on a Yanaco MP-S3 hot
stage melting point apparatus and are uncorrected. Infrared
(IR) spectra were recorded on a JASCO FT/IR-8300
spectrophotometer and are reported in wave number
(cm21). Proton NMR spectra (1H NMR) were recorded on
a Varian Gemini 2000 (300 MHz) or a Bruker ARX-400
(400 MHz). All samples were dissolved in CDCl3, and
chemical shift values are reported in parts per million
(ppm) with tetramethylsilane (TMS, d 0.00) as an internal
standard. Data are reported as follows: chemical shift (inte-
grated intensity, multiplicity, coupling constants in Hertz,
assignment). NOE experiments were performed with a
Bruker ARX-400 (400 MHz). Carbon NMR spectra (13C
Figure 5. View of one of the stable conformers of 20.
NMR) were recorded on
a Varian Gemini 2000
(75.4 MHz) or a BRUKER ARX-400 (100 MHz) with
proton decoupling. Chemical shift values are reported as d
in parts per million (ppm) with CDCl3 (d 77.0) as an internal
standard.
Low-resolution mass spectra (EI) were obtained on a JEOL
DX-300 spectrometer. High-resolution mass spectra
(HRMS) and elemental analyses were performed by the
Analytical Laboratory, School of Bioagricultural Sciences,
Nagoya University. Optical rotations were measured on a
JASCO DIP-370 automatic digital polarimeter with a
sodium lamp in 100 mm cell of 2 or 10 mL capacity and
reported as follows: [a]tD (8C) l, [c (g/100 mL), solvent].
Figure 6. Change of Me signal in 1H NMR spectra of 20 at different
temperatures.

10214
T.-Z. Liu et al. / Tetrahedron 56 (2000) 10209±10219
Analytical thin-layer chromatography (TLC) was conducted
on 0.25 mm E. Merk silica gel 60F-254 plates. Column
chromatography was performed on Merk Silica gel 60
(70±230 mesh). Flash chromatography was performed
using the forced ¯ow of indicated solvent system on
Merck Silica Gel 60 (230±400 mesh).
alcohol intermediate (5a) (4.51 g, 93%) as a colorless oil.
t
1H NMR (300 MHz, CDCl3) d 0.11 (9H, s, BuSi), 1.33±
1.47 (1H, m, H-3a), 1.58±1.73 (2H, m, H-2£2), 2.06±2.14
(1H, m, H-3b), 2.29 (1H, ddt, Jˆ15.0, 9.0, 1.0 Hz, H-6a),
2.72 (1H, ddt, Jˆ15.0, 4.5, 1.0 Hz, H-6b), 3.18 (1H, td
Jˆ9.0, 4.0 Hz, H-5), 3.24±3.40 (2H, m, H-1a, H-4), 3.87
(1H, br d Jˆ11.0 Hz, H-1b), 5.43 (1H, dt Jˆ3.0, 1.0 Hz,
CvCH2), 5.71 (1H, dt, Jˆ3.0, 1.5 Hz, CvCH2). 13C NMR
(75 MHz, CDCl3) d 21.3, 25.4, 32.7, 40.0, 67.4, 70.9, 81.2,
126.6, 149.9. IR (KBr): 3412, 2954, 2855, 1248, 1096,
Unless otherwise noted, all non-aqueous reactions were
carried out under an atmosphere of nitrogen or argon in
glassware which had been either ¯ame-dried or oven-dried
(1208C). Operations of degassed solvent were performed on
dualbank vacuum manifold through a three-way stopcock
and repeated twice before used. THF was distilled from
potassium metal/benzophenone ketyl. CH2Cl2 and DMF
1034, 838 cm21
.
Acetoxyvinylsilane (5b). A mixture of 5a (4.43 g,
20.21 mmol), acetic anhydride (5.97 mL, 63.30 mmol),
pyridine (33.78 mL, 422 mmol) and 4-dimethylaminopyri-
dine (710 mg, 6.3 mmol) in dichloromethane (100 mL) was
stirred at room temperature for 1 h. The resulting solution
was diluted with CH2Cl2 (300 mL), washed sequentially
with cold 1N aqueous HCl solution, saturated aqueous
NaHCO3 solution (£2), brine, dried over Na2SO4 and
concentrated. The residue was puri®ed by column chroma-
tography on silica gel (20% diethyl ether in hexane) to
afford the vinylsilane 5b (5.32 g, 100%) as a colorless oil.
[a]2D5ˆ134.5 (c 1.00, CHCl3). 1H NMR (300 MHz, CDCl3)
Ê
were dried over activated molecular sieves 4 A (2508C,
several hours). Pyridine was dried over KOH. All other
commercially available reagents were used as received.
Trimethylsilylethenylmagnesium bromide
To a dry three-necked ¯ask equipped with a mechanical
stirrer, a water condenser, and a constant-pressure dropping
funnel were placed THF (30 mL) and magnesium turnings
(1.56 g, 64.91 mmol). To this mixture was added 0.10 mL
of 1,2-dibromoethane to initiate the reaction (heat the
solution if necessary), followed by dropwise addition of
(1-bromovinyl)trimethylsilane (9.68 mL, 63.64 mmol)
under nitrogen atmosphere. After addition, the mixture
was heated at 708C for 1 h. The resulting mixture was
cooled to room temperature and used directly in the next
step.
t
d 0.10 (9H, s, BuSi), 1.37±1.41 (1H, m, H-3a), 1.62±1.83
(2H, m, H-2£2), 2.04 (3H, s, CH3CO), 2.15±2.24 (2H, m,
H-3b, H-6a), 2.47 (1H, dd, Jˆ15.0 Hz, 1.0 Hz, H-6b), 3.39
(1H, td, Jˆ12.0, 3.0 Hz, H-1a), 3.34 (1H, td, Jˆ10.0,
3.0 Hz, H-5), 3.89 (1H, ddd, Jˆ12.0, 4.0, 2.0 Hz, H-1b),
4.50 (1H, td Jˆ10.0, 4.5 Hz, H-4), 5.39 (1H, dd, Jˆ3.0,
1.0 Hz, CvCH2), 5.62 (1H, dd, Jˆ2.0, 1.0 Hz, CvCH2).
13C NMR (75 MHz, CDCl3) d 21.4, 21.1, 25.0, 29.3, 39.3,
67.4, 72.1, 78.7, 126.6, 148.7, 170.3. IR (KBr): 2954, 2853,
1745, 1375, 1240, 1099, 1037, 839 cm21. Anal. Calcd for
C13H24O3Si: C, 60.89; H, 9.43. Found: C, 60.89; H, 9.63.
Protected vinylsilane (5). To the above Grignard reagent
were added CuI (592 mg, 3.11 mmol) and a solution of the
tosylate 4 (12.46 g, 31.15 mmol) in THF (5 mL) at 08C
under nitrogen atmosphere. After stirring at 08C for 3 h
and then at room temperature for 2 days, the reaction was
quenched with saturated aqueous NH4Cl solution (250 mL),
the mixture was extracted with CH2Cl2 (£3), the organic
phase was dried over Na2SO4, ®ltered and concentrated.
The residue was puri®ed by chromatography on silica gel
(2.5!40% diethyl ether in hexane) to afford the vinylsilane
5 (7.61 g, 82%,) as a colorless oil. Small amount (9%) of
SM was recovered. [a]2D5ˆ133.7 (c 0.70, CHCl3). 1H NMR
(300 MHz, CDCl3) d 0.07 (6H, s, Me2Si), 0.10 (9H, s,
Vinyliodide (6). To a solution of iodine (12.50 g,
49.2 mmol) in degassed CH2Cl2 (130 mL) was added drop-
wise a solution of the silane 5b (4.13 g, 16.40 mmol) in
CH2Cl2 (40 mL). After stirring at room temperature for
30 min, the reaction was quenched with cold saturated
aqueous Na2SO3 solution. The mixture was stirred until
the yellow color of the solution disappeared, and extracted
with CH2Cl2 (£3). The combined organic extracts were
washed with brine, dried over Na2SO4 and concentrated.
The residue was puri®ed by chromatography on silica gel
(14!20% diethyl ether in hexane) to afford 6 (3.61 g, 71%)
as a pale yellow oil. Rfˆ0.33 (silica gel, 1:3, ether±hexane).
[a]2D4ˆ111.4 (c 1.03, CHCl3). 1H NMR (300 MHz, CDCl3)
d 1.43±1.57 (1H, m, H-3a), 1.65±1.84 (2H, m, H-2£2), 2.06
(3H, s, CH3CO), 2.14±2.24 (1H, m, H-3b), 2.43 (1H, ddd,
Jˆ15.0, 9.0, 1.0 Hz, H-6a), 2.63 (1H, ddt, Jˆ15.0, 3.0,
1.5 Hz, H-6b), 3.39 (1H, td, Jˆ11.0, 3.0 Hz, H-1a), 3.53
(1H, td, Jˆ9.0, 3.0 Hz, H-5), 3.94 (1H, ddt, Jˆ11.0, 4.0,
2.0 Hz, H-1b), 4.59 (1H, ddd, Jˆ10.5, 9.0, 5.0 Hz, H-4),
5.80 (1H, dd, Jˆ2.0, 1.0 Hz, CvCH2), 6.12 (1H, dd
Jˆ2.5, 1.0 Hz, CvCH2). 13C NMR (75 MHz, CDCl3) d
21.1, 24.9, 29.3, 47.6, 67.8, 71.2, 77.9, 106.9, 128.0,
170.3. IR (KBr): 2946, 2855, 1741, 1619, 1434, 1375,
1239, 1102, 893 cm21. Anal. Calcd for C10H15O3Si: C,
38.73; H, 4.88. Found: C, 38.73; H, 5.03.
t
Me3Si), 0.88 (9H, s, BuSi), 1.36±1.50 (1H, m, H-3),
1.58±1.71 (2H, m, H-2£2), 1.99±2.07 (2H, m, H-6, H-3),
2.83 (1H, dd, Jˆ15.0, 1.5 Hz, H-6), 3.15 (1H, td Jˆ10.0,
2.0 Hz, H-5), 3.2-3.31 (2H, m, H-1, H-4), 3.86 (1H, dt,
Jˆ11.0, 2.0 Hz, H-1), 5.39 (1H, dd, Jˆ3.0, 1.5 Hz,
CvCH2), 5.65 (1H, dd,2.0, 1.0 Hz, CvCH2). 13C NMR
(75 MHz, CDCl3) d 24.8, 24.1, 21.4, 17.8, 25.6, 25.7,
33.6, 39.6, 67.6, 71.5, 81.7 125.9, 149.6. IR (KBr): 2956,
2939, 2859, 1249, 1128, 1099, 837 cm21. Anal. Calcd for
C17H36O2Si: C, 62.13; H, 11.04. Found: C, 62.26; H, 11.21.
Hydroxyvinylsilane (5a).
A solution of 5 (7.27 g,
23.15 mmol) in methanol (200 mL) was treated with
p-toluenesulfonic acid monohydrate (421 mg, 2.2 mmol)
at room temperature for 10 h. The reaction was quenched
with trimethylamine (0.6 mL, 4.5 mmol). The solvent was
evaporated and the residue was puri®ed by chromatography
on silica gel (33% diethyl ether in hexane) to afford the
En-yne compound (7). A slurry of palladium(II) acetate

T.-Z. Liu et al. / Tetrahedron 56 (2000) 10209±10219
10215
(22 mg, 0.1 mmol) and copper(I) iodide (15 mg,
0.08 mmol) in benzene (5 mL) was treated with triphenyl-
phosphine (51 mg, 0.2 mmol) at 258C for 15 min. A solution
of 6 (300 mg, 0.97 mmol) and protected propargyl alcohol
(330 mg, 0.2 mmol) in benzene (5 mL) was added to above
solution, the resulting mixture was degassed twice with an
argon line, and then treated with n-butylamine (0.14 mL,
0.15 mmol). After stirring at room temperature over night
under argon atmosphere, the color of the solution changed
from brown to orange. The reaction mixture was poured into
saturated NH4Cl solution (15 mL), and extracted with
diethyl ether (£3). The combined organic extracts were
washed with brine, dried over Na2SO4, ®ltered and concen-
trated. The residue was puri®ed by chromatography on
silica gel (20% diethyl ether in hexane) to afford compound
(2H, m, H-11£2), 2.14 (1H, br d, Jˆ11.0 Hz, H-3b), 2.43
(1H, dd, Jˆ14.5, 8.5 Hz, H-6a), 2.91 (1H, dd, Jˆ14.5,
2.5 Hz, H-6b), 3.24±3.44 (3H, m, H-1a, H-4, H-5), 3.88
(1H, br d, Jˆ11.0 Hz, H-1b), 4.87 (2H, s, H-10£2), 5.48
(1H, s, CvCH2), 5.56 (1H, d, Jˆ1.0 Hz, CvCH2). 13C
NMR (125 MHz, CDCl3) d 25.7, 22.6, 25.5, 25.8, 33.2,
39.6, 64.2, 67.4, 70.5, 81.6, 119.6, 143.1. MS-EI (m/z):
596 (M1), 568 (M12CO), 540 (M122CO), 512
(M123CO), 484 (M124CO), 456 (M125CO), 428
(M126CO). HRMS-EI (m/z): [M22CO]1 calcd for
C21H30Co2O7Si, 540.0424; found, 540.0426.
Bicyclic acetylene±biscobalthexacarbonyl complex (9).
A solution of 8 (96 mg, 0.16 mmol) in degassed CH2Cl2
(40 mL) was cooled to 08C, and treated with a solution of
boron tri¯uoride etherate (0.03 mL, 0.16 mmol) in degassed
CH2Cl2 (40 mL) for 20 min under argon atmosphere. The
resulting mixture was washed with cold saturated aqueous
NaHCO3 solution and brine, dried over Na2SO4 and concen-
trated. The residue was puri®ed by column chromatography
on silica gel (11% diethyl ether in hexane, Rfˆ0.22) to
afford 9 (65.0 mg, 87%) as a dark-red oil. [a]2D7ˆ271.3 (c
1
7 (234 mg, 69%) as a colorless oil. H NMR (400 MHz,
CDCl3) d 0.15 (6H, s, Me2Si), 0.94 (9H, s, BuSi), 1.40±
t
1.54 (1H, m, H-3a), 1.65±1.83 (2H, m, H-2£2), 2.04 (3H, s,
CH3CO), 2.13±2.22 (1H, m, H-3b), 2.24 (1H, dd, Jˆ14.0,
9.0 Hz, H-6a), 2.44 (1H, dt, Jˆ14.0, 2.0 Hz, H-6b), 3.31
(1H, td, Jˆ11.0, 3.5 Hz, H-1a), 3.58 (1H, td, Jˆ9.0,
3.0 Hz, H-5), 3.93 (1H, ddd, Jˆ11.0, 3.5, 2.0 Hz, H-1b),
4.46 (2H, s, H-10£2), 4.54 (1H, ddd, Jˆ10.0, 9.0, 4.5 Hz,
H-4), 5.30 (1H, s, CvCH2) 5.40 (1H, s, CvCH2). 13C NMR
(100 MHz, CDCl3) d 25.2, 18.2, 21.1, 25.0, 25.8, 29.4,
40.0, 52.1, 67.8, 71.9, 77.2, 84.5, 88.0, 123.5, 127.6,
170.3. MS-EI (m/z): 337 (M12Me), 295 (M12tBu).
1
0.05, CHCl3). H NMR (400 MHz, CDCl3) d 1.45±1.54
(1H, m, H-3a), 1.58±1.70 (2H, m, H-2£2), 2.10±2.13
(1H, m, H-3b), 2.64 (1H, dd, Jˆ14.0, 2.0 Hz, H-6a), 2.79
(1H, dd, Jˆ14.0, 4.0 Hz, H-6b), 3.11 (1H, td, Jˆ10.0,
4.5 Hz, H-4), 3.31±3.38 (2H, m, H-1a, H-5), 3.90 (1H, dd,
Jˆ12.0, 4.0 Hz, H-1b), 4.88 (1H, d, Jˆ16.0 Hz, H-10a),
5.11 (1H, d, Jˆ16.0 Hz, H-10b), 5.46 (1H, s, CvCH2),
5.56 (1H, s, CvCH2). 13C NMR (100 MHz, CDCl3) d
26.1, 30.5, 40.5, 68.1, 74.0, 77.4, 80.7, 122.1, 141.0. MS-
EI (m/z): 464 (M1), 436 (M12CO), 408 (M122CO), 380
(M123CO), 352 (M124CO), 324 (M125CO), 296
(M126CO). HRMS-EI (m/z): M1 calcd for C17H14O8Co2,
463.9352; found, 463.9325.
En-yne compound (7a). A solution of 7 (195 mg,
0.55 mmol) in MeOH (6 mL) was treated with Potassium
carbonate (76 mg, 0.55 mmol) at room temperature for 2 h.
The solvent was evaporated and the residue was taken up
with a mixture of 14% diethyl ether in hexane, ®ltered to
remove precipitate, the ®ltrate was concentrated. Puri®ca-
tion of the residue by column chromatography on silica gel
(14% diethyl ether in hexane) afforded 8 (171 mg, 100%) as
1
a colorless oil. [a]D25ˆ112.1 (c 0.55, CHCl3). H NMR
Protected 1,4-butanediol (10a). A solution of 1,4-butane-
diol (3.28 g, 36.4 mmol) in anhydrous THF (60 mL) was
cooled to 08C, and treated with Sodium hydride (60%
dispersion in mineral oil, 1.46 g, 36.4 mmol) for 40 min
under nitrogen atmosphere, white precipitate formed during
this period. A solution of tert-butylchlorodiphenylsilane
(10.0 g, 36.4 mmol) in THF (40 mL) was added to the
above solution over 1 h, the resulting mixture was stirred
at room temperature for 1 h. The reaction mixture was
poured into saturated aqueous NH4Cl (100 mL), extracted
with diethyl ether (£3), dried over Na2SO4 and concen-
trated. Puri®cation the residue by column chromatography
silica gel (50% diethyl ether in hexane, Rfˆ0.32) afforded
(400 MHz, CDCl3) d 0.11 (6H, s, Me2Si), 0.90 (9H, s,
Me3CSi), 1.35±1.45 (1H, m, H-3a), 1.63±1.70 (2H, m,
H-2£2), 1.77 (1H, s, OH), 2.09 (1H, dd, Jˆ12.0, 3.0 Hz,
H-3b), 2.26 (1H, dd, Jˆ14.0, 8.0 Hz, H-6a), 2.69 (1H, dd,
Jˆ14.0, 1.0 Hz, H-6b), 3.28±3.40 (3H, m, H-1a, H-4, H-5),
3.87 (1H, dt, Jˆ11.0, 2.0 Hz, H-1b), 4.41 (2H, s, H-10£2),
5.32 (1H, s, CvCH2), 5.40 (1H, s, CvCH2). 13C NMR
(125 MHz, CDCl3) d 25.1, 18.3, 25.6, 25.9, 33.0, 40.0,
52.2, 67.7, 70.2, 80.5, 85.2, 88.0, 123.6, 127.9. MS-EI
(m/z): 253 (M12tBu). IR (KBr): 3422, 2932, 2858,
1734, 1718, 1473, 1363, 1258, 1097, 837 cm21. Anal.
Calcd for C17H30O3Si: C, 65.76; H, 9.74. Found: C, 65.64;
H, 9.96.
1
alcohol 10a (10.72 g, 90%) as a colorless oil. H NMR
(300 MHz, CDCl3) d 1.05 (9H, s, SiBut), 1.60±1.74 (4H,
m, CH2£2), 1.99 (1H, t, Jˆ5.0 Hz, OH), 3.64±3.72 (4H, m,
OCH2£2), 7.34±7.69 (10H, m, Ph£2).
Acetylene±biscobalthexacarbonyl complex (8). To a
solution of 7a (70 mg, 89 mmol) in degassed CH2Cl2
(1 mL) was added dropwise a solution of biscobaltocta-
carbonyl (160 mg, 0.18 mmol) in degassed CH2Cl2 (2 mL)
at 08C under argon atmosphere, the mixture was stirred at
room temperature for 2 h. The solvent was evaporated and
the residue was directly subjected to column chromato-
graphy on silica gel (20% diethyl ether in hexane) to afford
the cobalt complex 8 (53 mg, 100%) as a dark-red oil.
Protected butanaldehyde (10b). To a slurry of the alcohol
10a (10.70 g, 32.6 mmol) in CH2Cl2 (250 mL) containing
potassium acetate (0.96 g, 9.78 mmol) was added pyridi-
nium chlorochromate (10.55 g, 48.9 mmol) in one portion,
the mixture was stirred at room temperature for 2 h. The
resulting mixture was diluted with diethyl ether, ®ltered
through a pad of silica gel, washed thoroughly with diethyl
ether. The ®ltrate was concentrated, and the residue was
puri®ed by column chromatography on silica gel (20%
1
[a]2D5ˆ28.0 (c 0.03, CHCl3). H NMR (400 MHz, CDCl3)
d 0.13 (6H, s, Me2Si), 0.94 (9H, s, Me3CSi) 1.35±1.49 (1H,
m, H-3a), 1.61±1.74 (4H, m, H-2£2, H-12£2), 1.80±1.98

10216
T.-Z. Liu et al. / Tetrahedron 56 (2000) 10209±10219
diethyl ether in hexane, Rfˆ0.30) to afford the aldehyde 10b
(8.55 g, 80%) as a colorless oil. Rfˆ0.59 (silica gel, 1:1,
s, SiBut), 1.89 (2H, m, CH2), 2.55 (2H, td, Jˆ7.0, 2.0 Hz,
CH2CHO), 3.69 (2H, t, Jˆ6.0 Hz, OCH2, 7.34±7.69 (10H,
m, Ph£2), 9.79 (1H, t, Jˆ2.0 Hz, CHO).
CDCl3) d 1.04 (9H, s, SiBut), 1.37±1.50 (1H, m, H-3a),
1.64±1.84 (4H, m, H-2£2, H-12£2), 1.87±1.97 (2H, m,
H-11£2), 2.02 (3H, s, CH3CO), 2.15 (1H, br d, Jˆ12 Hz,
H-3b), 2.26 (1H, dd, Jˆ14.0, 9.0 Hz, H-6a), 2.48 (1H, dt,
Jˆ14.0, 2.0 Hz, H-6b), 3.33 (1H, dt, Jˆ12.0, 3.0 Hz, H-1a),
3.59 (1H, td, Jˆ9.5, 3.2 Hz, H-5), 3.69 (1H, t, Jˆ6.5 Hz,
H-13£2), 3.92 (1H, ddd, Jˆ12.0, 4.0, 1.5 Hz, H-1b), 4.26
(1H, t, Jˆ6.5 Hz, H-10), 4.53±4.60 (1H, td, Jˆ9.5, 5.0 Hz,
H-4), 4.51 (1H, dd, Jˆ12.0, 2.0 Hz, OCH2Ph), 4.81 (1H, d,
Jˆ12.0 Hz, CH2Ph), 5.30 (1H, s, CvCH2), 5.43 (1H, s,
CvCH2), 7.28±7.68 (10H, m, Ph£2). 13C NMR (75 MHz,
CDCl3) d 19.1, 21.1, 25.0, 26.8, 28.4, 29.4, 32.2, 40.1, 63.5,
67.8, 68.9, 70.4, 71.9, 85.7, 88.5, 123.5, 127.5, 127.7, 128.0,
128.4, 129.6, 134.0, 138.1. IR (KBr): 2931, 2858, 1739,
1239, 1101, 702 cm21. HRMS-EI (m/z): M1 calcd for
C39H48O5Si, 624.3271; found, 624.3257. Anal. Calcd for
C39H48O5Si: C, 74.96; H, 7.74. Found, C, 74.97; H, 7.80.
1
ether±hexane). H NMR (300 MHz, CDCl3) d 1.04 (9H,
Propargyl alcohol (10c). A solution of trimethylsilylacetyl-
ene (5.2 mL, 36.7 mmol) in THF (150 mL) was treated
dropwise with n-butyllithium (1.6 M in hexane, 24.6 mL,
39.4 mmol) at 2788C under nitrogen atmosphere, the
mixture was stirred at 08C for 30 min. A solution of 10b
(8.55 g, 26.2 mmol) in THF (50 mL) was added to the above
solution, and the resulting mixture was stirred at 08C for
15 min. The reaction mixture was poured into saturated
aqueous NH4Cl solution, extracted with diethyl ether (£3),
dried over Na2SO4 and concentrated. The residue was puri-
®ed by column chromatography on silica gel (14% diethyl
ether in hexane, Rfˆ0.21) to afford 10c (10.98 g, 92%) as a
Alcohol (12a). A solution of 11 (5.67 g, 9.07 mmol) in
MeOH (50 mL) was treated with potassium carbonate
(750 mg, 5.43 mmol) at room temperature for 2 h. The
resulting mixture was evaporated to dryness, the residue
was taken up with CH2Cl2 (400 mL), washed with saturated
aqueous NH4Cl, brine, and water, dried over Na2SO4 and
concentrated. The residue was puri®ed by column chroma-
tography silica gel (50% diethyl ether in hexane, Rfˆ0.20)
1
colorless oil. Rfˆ0.25 (silica gel, 1:4, ether±hexane). H
NMR (300 MHz, CDCl3) d 0.20 (9H, s, Me3Si), 0.90 (9H,
s, SiBut), 1.68±1.92 (4H, m, CH2£2), 2.78 (total 1H, two d,
Jˆ2.0 Hz, OH), 3.68±3.78 (2H, m, OCH2), 4.45 (total 1H,
two t, Jˆ6.0 Hz, CHOH), 7.38±7.76 (10H, m, Ph£2).
Hex-5-yn-1,4-diol (10). A solution of 10c (10.96 g,
25.8 mmol) in DMF (200 mL) was treated with sodium
hydride (60% dispersion in mineral oil, 1.24 g,
31.0 mmol) at 08C for 30 min. Benzyl bromide (4.0 mL,
33.6 mmol) was added to the above solution, and the result-
ing mixture was stirred at room temperature for 2 h. The
reaction solution was poured into cold saturated aqueous
NH4Cl solution, extracted with diethyl ether (£3). The
combined organic extracts were dried over Na2SO4 and
concentrated. The residue was puri®ed by column chroma-
tography on silica gel (3% diethyl ether in hexane, Rfˆ0.18)
to afford 10 (9.71 g, 85%) as a colorless oil. Rfˆ0.66 (silica
gel, 1:4, ether±hexane). 1H NMR (300 MHz, CDCl3) d 1.03
(9H, s, SiBut), 1.70±1.94 (4H, m, CH2£2), 2.46 (1H, s,
CuCH), 3.67 (2H, t, Jˆ6.0 Hz, OCH2), 4.11 (total 1H,
two t, Jˆ6.0 Hz, OCHCuC), 4.48 (1H, d, Jˆ11.0 Hz,
OCH2Ph), 4.79 (1H, d, Jˆ11.0 Hz, OCH2Ph), 7.33±7.69
(10H, m, Ph£2). 13C NMR (75 MHz, CDCl3) d 19.1, 26.8,
28.2, 32.1, 63.4, 68.3, 70.4, 73.9, 82.8, 127.7, 128.0, 128.4,
129.6, 134.0, 135.6, 137.9.
1
to afford 12a (5.08 g, 96%) as a colorless oil. H NMR
(300 MHz, CDCl3) d 1.05 (9H, s, SiBut), 1.23±1.45 (1H,
m,H-3a), 1.43±1.78 (4H, m, H-2£2, H-12£2), 1.86±1.93
(2H, m, H-11£2), 2.00±2.10 (1H, m, H-3b), 2.36 (1H, dd,
Jˆ15.0, 8.2 Hz, H-6a), 2.93 (1H, br d, Jˆ15.0 Hz, H-6b),
3.20±3.32 (3H, m, H-1a, H-4, H-5), 3.60±3.72 (2H, m,
H-13£2), 3.86 (1H, br d, Jˆ11.0 Hz, H-1b), 4.68 (total
1H, two t, Jˆ3.0 Hz, H-10), 4.52 (1H, d, Jˆ11.0 Hz,
OCH2Ph), 4.81 (1H, dd, Jˆ11.0 Hz, OCH2Ph), 5.48 (1H,
s, CvCH2), 5.50 (1H, s, CvCH2), 7.26±7.70 (15H, m,
Ph£3). 13C NMR (75 MHz, CDCl3) d 14.0, 19.1, 25.5, 26.8,
28.4, 32.2, 32.9, 40.1, 63.5, 67.8, 70.2, 70.4, 80.6, 86.2, 88.5,
123.7, 127.7, 128.0, 128.4, 129.6, 134.0, 135.6, 138.2.
Cobalt complex (12).
5.40 mmol) in degassed CH2Cl2 (140 mL) was treated
with solution of biscobaltoctacarbonyl (3.32 g,
A solution of 12a (3.14 g,
a
9.72 mmol) in degassed CH2Cl2 (60 mL) at 08C under
argon atmosphere, the mixture was stirred at room tempera-
ture for 2 h. The solvent was evaporated, and the residue
was puri®ed by column chromatography on silica gel (33%
diethyl ether in hexane, Rfˆ0.25) to afford cobalt complex
12 (4.37 g, 87%) as a dark-red oil. Rfˆ0.36 (silica gel, 1:1,
En-yne compound (11). A slurry of palladium(II) acetate
(232 mg, 1.0 mmol) and copper(I) iodide (185 mg,
0.1 mmol) in benzene (50 mL) was treated with triphenyl-
phosphine (535 mg, 2.0 mmol), and the mixture was stirred
at room temperature for 20 min. To the resulting solution
was added a solution of 10 (4.90 g, 11.1 mmol) and 6
(3.17 g, 10.2 mmol) in benzene (20 mL), the mixture was
degassed twice with argon line, and then treated with
n-butylamine (0.10 mL, 1.1 mmol), stirred over night
under argon atmosphere. The color of the solution changed
from brown to orange during this period. The reaction
mixture was poured into saturated aqueous NH4Cl solution,
extracted with diethyl ether (£3). The combined organic
extracts were dried over Na2SO4 and concentrated. The
residue was puri®ed by column chromatography on silica
gel (25% diethyl ether in hexane, Rfˆ0.24) to afford 11
(4.44 g, 89%) as a colorless oil. 1H NMR (300 MHz,
1
ether±hexane). H NMR (300 MHz, CDCl3) d 1.03 (9H, s,
tBu), 1.22±1.42 (1H, m, H-3a), 1.54±1.80 (4H, m, H-11a,
H-12a, H-2£2), 1.80±2.07 (3H, m, H-11b, H-12b, H-3b),
2.36 (1H, dd, Jˆ15.0, 8.0 Hz, H-6a), 2.93 (1H, d,
Jˆ15.0 Hz, H-6b), 3.20±3.30 (3H, m, H-1a, H-4, H-5),
3.68 (2H, m, H-13£2), 3.85 (1H, m, H-1b), 4.28 (2H, t,
Jˆ3.0 Hz, H-13£2), 4.57 (1H, d, Jˆ11.5 Hz, PhCH2O),
4.67 (1H, two dt, Jˆ4.0, 3.0 Hz, H-10), 4.82 (1H, dd,
Jˆ11.5, 2.0 Hz, PhCH2), 5.48 (1H, d, Jˆ1.0 Hz,
CvCH2), 5.51 (1H, d, Jˆ1.0 Hz, CvCH2), 7.28±7.67
(15H, m, Ph£3). 13C NMR (75 MHz, CDCl3) d 19.2, 25.6,
26.9, 29.5, 33.2, 35.0, 35.1, 39.6, 63.6, 67.3, 70.4, 72.6,
79.9, 81.8, 118.3, 127.5, 127.6, 127.9, 128.3, 129.5, 134.0,
135.6, 135.9, 136.1, 138.2, 199.9.

T.-Z. Liu et al. / Tetrahedron 56 (2000) 10209±10219
10217
Bicyclic cobalt complex (13). A solution of 12 (4.37 g,
4.73 mmol) in degassed CH2Cl2 (1120 mL) was cooled to
08C. To this solution was added dropwise a solution of
boron tri¯uoride etherate (0.59 mL, 4.73 mmol) in degassed
CH2Cl2 (118 mL), the mixture was stirred at 08C for 40 min
under argon atmosphere. The reaction mixture was washed
with cold saturated aqueous NaHCO3 (400 mL), brine and
water, dried over Na2SO4 and concentrated. The residue was
puri®ed by column chromatography on silica gel (20%
diethyl ether in hexane, Rfˆ0.31) to afford 13 (3.62 g,
94%) as a dark-red oil. Rfˆ0.59 (silica gel, 1:1, ether±
hexane). [a]2D7ˆ223.6 (c 0.03, CHCl3). 1H NMR
(400 MHz, CDCl3) d 1.03 (9H, s, But), 1.40±1.51 (1H, m,
H-3a), 1.50±1.62 (H, m, H-2£2), 1.65±1.78 (2H, m, H-11a,
H-12a), 1.89±94 (1H, m, H-12b), 2.00±2.04 (1H, m, H-3b),
2.07±2.16 (1H, m, H-11b), 2.63 (1H, dd, Jˆ14.0, 2.0 Hz,
H-6a), 2.75 (1H, dd, Jˆ14.0, 4.0 Hz, H-6b), 3.14 (1H, td,
Jˆ10.0, 4.0 Hz, H-4), 3.30±3.36 (2H, m, H-1a, H-5), 3.69±
3.80 (2H, m, H-13£2), 3.90 (1H, dd, Jˆ12.0, 4.0 Hz, H-1b),
4.61 (1H, dd, Jˆ10.0, 3.0 Hz, H-10), 5.42 (1H, s, CvCH2),
5.55 (1H, s, CvCH2), 7.34±7.68 (10H, m, Ph£2). 13C NMR
(75 MHz, CDCl3) d 19.1, 26.0, 26.7, 29.6, 30.4, 40.4, 63.4,
68.0, 77.3, 80.7, 82.5, 96.6, 102.4, 121.3, 127.7, 129.6,
133.9, 134.0, 135.6, 141.4, 199.6. EIMS (m/z): 760 (M1),
676 (M123CO), 592 (M126CO). HRMS-EI (m/z):
[M23CO]1 calcd for C33H38Co2O6Si, 676.1101; found,
676.1084.
SiBut), 1.38 (3H, d, Jˆ7.0 Hz, CH3), 1.42±1.50 (1H, m,
H-3a), 1.57±1.66 (3H, m, H-2£2, H-11a), 1.75±1.90 (3H,
m, H-6a, H-12£2), 1.98 (1H, br d, Jˆ14.0 Hz, H-6b), 2.00±
2.10 (2H, m, H-11b, H-3b), 3.04±3.14 (2H, m, H-7, H-4),
3.17 (1H, dt, Jˆ8.5, 2.0 Hz, H-5), 3.26 (1H, td, Jˆ11.0,
3.0 Hz, H-1a), 3.68±3.79 (2H, m, H-13£2), 3.85 (1H, dt,
Jˆ11.0, 2.0 Hz, H-1b), 4.52 (1H, dd, Jˆ10.5, 2.8 Hz,
H-10), 7.33±7.70 (10H, m, Ph£2). 13C NMR (75 MHz,
CDCl3) d 19.1, 25.1, 25.7, 26.7, 29.5, 31.7, 35.3, 36.8,
45.1, 63.5, 67.6, 83.1, 83.2, 84.3, 100.0, 107.9, 127.7,
129.6, 134.0, 135.6, 200.0. EIMS (m/z): 678 (M123CO),
594 (M126CO). HRMS-EI (m/z): calcd for C33H40Co2O6Si
[M23CO]1, 678.1258; found, 678.1238. 14b (the minor
product): Rfˆ0.43 (silica gel, 1:10, ether±hexane, repeated
three times). [a]D25ˆ281.0 (c 0.03, CHCl3). 1H NMR
(400 MHz, CDCl3) d 1.03 (9H, s, SiBut), 1.35 (3H, d,
Jˆ7.0 Hz, CH3), 1.42±1.49 (1H, m, H-3a), 1.55±1.72
(3H, m, H-2£2, H-11a), 1.69±1.71 (1H, m, H-12a), 1.96±
2.09 (3H, m, H-3b, H-6a, H-11b), 3.17 (1H, m, H-7), 3.32±
3.36 (3H, m, H-1a, H-4, H-5), 3.75 (2H, m, H-13£2), 3.88
(1H, dd Jˆ11.0, 4.0 Hz, H-1b), 4.64 (1H, dd, Jˆ10.0,
2.5 Hz, H-10), 7.34±7.67 (10H, m, Ph£2). 13C NMR
(75 MHz, CDCl3) d 19.1, 24.7, 26.1, 26.7, 29.6, 30.4,
31.8, 34.7, 40.7, 63.4, 68.0, 76.9, 80.1, 82.6, 101.1, 108.9,
127.7, 129.6, 133.9, 134.0, 135.6, 200.2. EIMS (m/z): 678
(M123CO), 594 (M126CO). HRMS-EI (m/z): [M23CO]1
calcd for C33H40Co2O6Si, 678.1258; found, 678.1235.
Bicyclic cobalt complex (13a). A solution of 12 (29 mg,
31 mmol) in degassed CH2Cl2 (25 mL) was cooled to 08C.
To this solution was added dropwise a solution of boron
tri¯uoride etherate (4 mL, 1 mM) in degassed CH2Cl2
(5 mL). After stirring 1 min, the reaction was quenched
with cold saturated aqueous NaHCO3 (10 mL), the mixture
was extracted with dichloromethane (£2), washed with
brine and water, dried over Na2SO4 and concentrated. The
residue was puri®ed by column chromatography on silica
gel (20% diethyl ether in hexane, Rfˆ0.31) to afford a
mixture of 13a and 13 (15 mg, 60%, calcd 13a:13ˆ1:3 on
a-Methyl bicyclic ole®n (15a). A solution of 14a (840 mg,
1.03 mmol) and n-butyltin hydride (1.41 mL, 5.15 mmol) in
benzene (20 mL) was heated at 508C for 5 h. The color of
the solution changed from dark-red to yellow during this
period. The solvent was evaporated in vacuo, and the resi-
due was directly subjected to column chromatography (11%
diethyl ether in hexane) to afford ole®n 15a (813 mg, 96%)
as a colorless oil. Rfˆ0.58 (silica gel, 1:3, ether±hexane).
[a]2D5ˆ238.4 (c 0.40, CHCl3). 1H NMR (300 MHz, CDCl3)
d 1.04 (9H, s, SiBut), 1.40±1.5 (1H, m, H-3a), 1.50±1.65
(4H, m, H-12a, H-11a, H-2£2), 1.65±1.80 (3H, H-6, H-11b,
H-12b), 1.99 (1H, br d, Jˆ12 Hz, H-3b), 3.05 (1H, br quart,
Jˆ7.0 Hz, H-7), 3.16±3.26 (2H, m, H-4, H-5), 2.29 (1H, dd,
Jˆ11.0, 3.0, H-1a), 3.68 (2H, t, Jˆ5.5 Hz, H-13£2), 3.82
(1H, dt, Jˆ11.0, 3.0 Hz, H-1b), 3.94 (1H, m, H-10), 5.18
(1H, ddd, Jˆ11.0, 3.5, 1.0 Hz, H-9), 5.31 (1H, ddd, Jˆ11.0,
7.0, 1.0 Hz, H-8), 7.75±7.33 (10H, m, Ph£2). 13C NMR
(100 MHz, CDCl3) d 19.1, 24.5, 25.5, 26.8, 27.1, 28.8,
30.7, 32.0, 43.0, 63.7, 67.3, 76.6, 79.4, 79.6, 127.6, 128.9,
129.5, 134.1, 135.6, 137.9.
1
1
the base of H NMR) as a dark-red oil. 13a: H NMR
(300 MHz, CDCl3) d 1.03 (9H, s, But), 1.40±1.51 (1H, m,
H-3a), 1.50±1.62 (H, m, H-2£2), 1.65±1.78 (2H, m, H-11a,
H-12a), 1.89±94 (1H, m, H-12b), 2.00±2.04 (1H, m, H-3b),
2.07±2.16 (1H, m, H-11b), 2.63 (1H, dd, Jˆ14.0, 2.0 Hz,
H-6a), 2.76 (1H, dd, Jˆ14.0, 4.0 Hz, H-6b), 3.14 (1H, td,
Jˆ10.0, 4.0 Hz, H-4), 3.30±3.36 (2H, m, H-1a, H-5), 3.69±
3.80 (2H, m, H-13£2), 3.90 (1H, dd, Jˆ12.0, 4.0 Hz, H-1b),
5.00 (1H, dd, Jˆ11.0, 2.0 Hz, H-10), 5.49 (1H, s, CvCH2),
5.59 (1H, s, CvCH2), 7.34±7.68 (10H, m, Ph£2).
Alcohol (16a). A solution of 15a (450 mg, 0.94 mmol) in
THF (12 mL) was treated with tetrabutylammonium
¯uoride (1.0 M in THF, 0.94 mL, 0.94 mmol) at room
temperature for 3 h. The resulting mixture was diluted
with diethyl ether (100 mL), washed with brine, dried
over Na2SO4 and concentrated. The residue was puri®ed
by column chromatography on silica gel (67% diethyl
ether in hexane, Rfˆ0.25) to afford alcohol 16a (193 mg,
Bicyclic acetylene±biscobalthexacarbonyl complex (14a,
14b). A solution of 13 (1.79 g, 2.36 mmol) and 2,4,6-tri-
isopropylbenzenesulfonylhydrazide (10 g, 33.5 mmol) in
MeOH (15 mL) was treated with triethylamine (1.23 mL,
16.8 mmol). After stirring at room temperature for 2 days,
the mixture was ®ltered through a pad of silica gel, washed
thoroughly with diethyl ether. The ®ltrate was concentrated
to give a dark-red residue, which was separated with ¯ash
chromatography on silica gel (2% diethyl ether in hexane) to
afford the major product 14a (1.12 g, 63%), and the minor
product 14b (433 mg, 24%). 14a: Rfˆ0.44 (silica gel, 1:10,
ether±hexane, repeat three time). [a]2D6ˆ129.3 (c 0.05,
CHCl3). 1H NMR (400 MHz, CDCl3) d 1.03 (9H, s,
1
85%) as a colorless oil. [a]2D5ˆ246.5 (c 1.00, CHCl3). H
NMR (400 MHz, CDCl3) d 0.99 (3H, d, Jˆ7.0 Hz, CH3),
1.34±1.46 (2H, m, H-3a, H-6a), 1.46±1.60 (2H, m,
H-11£2), 1.62±1.71 (4H, m, H-2£2, H-12£2), 1.74 (1H,
dd, Jˆ14.0, 5.6 Hz, H-6b), 2.08 (1H, br d, Jˆ12.0 Hz,
H-3), 2.20 (1H, br s, OH), 3.07 (1H, m, H-7), 3.18±3.35

10218
T.-Z. Liu et al. / Tetrahedron 56 (2000) 10209±10219
(3H, m, H-1a, H-4, H-5), 3.63 (2H, d, Jˆ2.5 Hz, H-13£2),
3.80 (1H, dt, Jˆ11.0, 2.0 Hz, H-1b), 3.98 (1H, m, H-10),
5.17 (1H, ddd, Jˆ11.5, 4.0, 1.5 Hz, H-9), 5.31 (1H, ddd,
Jˆ11.5, 7.5, 1.0 Hz, H-8). 13C NMR (75 MHz, CDCl3) d
24.4, 25.4, 27.1, 29.3, 30.7, 32.3, 42.9, 62.8, 67.3, 76.8,
79.4, 79.6, 128.4, 138.2. IR (KBr): 342, 2932, 2857,
1457.4, 1338, 1097, 952, 730.2 cm21. Anal. Calcd for
C14H24O3: C, 69.96; H, 10.06. Found: C, 69.94; H, 10.30.
3.02±3.11 (1H, td, Jˆ9.5, 4.0 Hz, H-4), 3.17 (1H, br t,
Jˆ9.5 Hz, H-5), 3.24±3.32 (1H, m, H-1a), 3.43 (1H, dd,
Jˆ11.0, 3.0 Hz, H-13a), 3.50 (1H, dd, Jˆ10.5, 3.5 Hz,
H-8), 3.67 (1H, dd, Jˆ5.0, 2.0 Hz, H-10), 3.77 (1H, dd,
Jˆ10.5, 2.0 Hz, H-9), 3.81±3.94 (2H, m, H-13b, H-1b).
13C NMR (125 MHz, CDCl3) d 14.0, 21.1, 22.6, 24.9,
26.0, 28.9, 31.6, 32.5, 62.6, 67.1, 68.0, 75.3, 80.6, 81.5.
9,10-cis-Tricyclic compound (18). To a solution of 17
(14 mg, 0.03 mmol) in toluene (1.0 mL) was added n-butyl-
tin hydride (0.09 mL, 0.09 mmol) and AIBN (1 mg), the
mixture was heated at 558C for 2 h. The solvent was evapo-
rated and the residue was puri®ed by column chromato-
graphy on silica gel (hexane!20% diethyl ether in
hexane) to afford 18 (6.1 mg, 85%) as a colorless oil.
Rfˆ0.47 (silica gel, 1:1, ether±hexane). [a]2D5ˆ156.3 (c
b-Methyl bicyclic ole®n (15b). A solution of 14b (100 mg,
0.12 mmol) and n-butyltin hydride (0.40 mL, 1.44 mmol) in
benzene (6 mL) was heated at 508C for 3 h. The color of
solution change from dark-red to yellow during this period.
The solvent was evaporated in vacuo, and the residue was
puri®ed by column chromatography on silica gel
(hexane!11% diethyl ether in hexane, Rfˆ0.24) to afford
15b (50 mg, 86%) as a colorless oil. Rfˆ0.58 (silica gel, 1:3,
SiBut), 1.16 (3H, d, Jˆ7.0 Hz, CH3), 1.20±1.50 (2H, m,
H-6a, H-3a), 1.51±1.68 (4H, m, H-12£2, H-2£2), 1.69±
1.82 (2H, m, H-11£2), 1.93 (1H, dd, Jˆ8.5, 3.5 Hz,
H-6b), 2.01 (1H, m, H-3b), 2.63 (1H, br quart, Jˆ7.0 Hz,
H-7), 3.18±3.31 (2H, m, H-4, H-5), 3.34 (1H, dd, Jˆ10.5,
3.5 Hz, H-1a), 3.64±3.70 (2H, m, H-13£2), 3.84 (1H, m,
H-1b), 4.06 (1H, m, H-10), 5.24 (1H, ddd, Jˆ12.0, 4.5,
2.0 Hz, CHvCH), 5.57 (1H, ddd, Jˆ12.0, 8.0, 2.0 Hz,
CHvCH), 7.68 (10H, m, Ph£2). 13C NMR (75 MHz,
CDCl3) d 19.1, 22.1, 25.1, 26.8, 28.8, 29.6, 30.5, 32.9,
40.1, 63.7, 67.3, 77.4, 77.6, 79.0, 127.6, 129.6, 131.1,
134.1, 135.6, 136.4.
1
0.11, CHCl3). H NMR (300 MHz, CDCl3) d 1.01 (3H, d,
1
ether±hexane). H NMR (300 MHz, CDCl3) d 1.04 (9H, s,
Jˆ7 Hz, CH3), 1.35±1.44 (1H, m, H-3a), 1.52 (1H, ddd,
Jˆ12, 10, 4 Hz, H-6a), 1.58±1.64 (1H, m, H-11a), 1.61±
1.71 (2H, m, H-2£2), 1.84±1.92 (2H, m, H-12£2), 2.00±
2.09 (2H, m, H-3b, H-11b), 2.11±2.22 (1H, m, H-7), 3.07
(1H, td, Jˆ10, 5 Hz, H-4), 3.16 (1H, td, Jˆ10, 2 Hz, H-5),
3.28 (1H, ddd, Jˆ11, 9, 5 Hz, H-1a), 3.45 (1H, td, Jˆ11,
3 Hz, H-13a), 3.59 (H, dd, Jˆ5, 2 Hz, H-9), 3.62 (1H, dd,
Jˆ4, 2 Hz, H-10), 3.84 (1H, ddd, Jˆ11, 5, 2 Hz, H-1b), 3.92
(1H, ddd, Jˆ11, 5, 2 Hz, H-13b). 13C NMR (125 MHz) d
18.1, 21.2, 23.7, 26.2, 26.3, 29.6, 32.1, 43.0, 66.7, 67.8,
75.5, 75.9, 81.0, 82.1. Anal. Calcd for C14H24O3: C, 69.96;
H, 10.06. Found: C, 69.85; H, 10.18. HRMS-EI (m/z): M1
calcd for C14H24O3, 240.1725; found, 240.1718.
Alcohol (16b). A solution of 15b (60 mg, 0.13 mmol) in
THF (1.5 mL) was treated with tetrabutylammonium
¯uoride (1.0 M in THF, 0.13 mL, 0.13 mmol). After stirring
at room temperature for 3 h, the reaction mixture was
diluted with diethyl ether (10 mL), washed with brine,
dried over Na2SO4 and concentrated. The residue was puri-
®ed by column chromatography on silica gel (67% diethyl
ether in hexane, Rfˆ0.25) to afford alcohol 16b (28 mg,
8-Iodo-9,10-trans-tricyclic compound (19). A solution of
16a (16 mg, 0.067 mmol) in CH3CN (0.5 mL) was treated
with iodine (88 mg, 0.23 mmol) at 08C. After stirring at
room temperature for 1 h, the reaction was quenched with
cold saturated aqueous Na2SO3 (1 mL), the mixture was
stirred until the yellow color disappeared, extracted with
diethyl ether (£3), dried over Na2SO4, concentrated. The
residue was puri®ed by column chromatography on silica
gel (25% diethyl ether in hexane, Rfˆ0.22) to afford 19
(13.7 mg, 56%) as a colorless oil. Rfˆ0.45 (silica gel, 1:1,
ether±hexane). 1H NMR (400 MHz, CDCl3) d 0.82 (3H, d,
Jˆ6.5 Hz, CH3), 1.29±1.41 (1H, m, H-6a), 1.50 (1H, m,
H-3a), 1.62±1.74 (2H, m, H-2£2), 1.72±1.93 (4H, m,
H-7, H-12£2, H-11a), 1.93±2.04 (2H, m, H-6b, H-3b),
2.29 (1H, td, Jˆ6.5, 2.0 Hz, H-11b), 2.51 (1H, dd, Jˆ9.0,
1.5 Hz, H-8), 3.03 (1H, ddd, Jˆ10.5, 8.5, 4.0 Hz, H-5), 3.16
(1H, ddd, Jˆ10.5, 8.5, 4.0 Hz, H-4), 3.36±3.49 (1H, m,
H-1a), 3.84±3.93 (3H, m, H-1b, H-13£2), 4.04 (1H, dd,
Jˆ9.0, 1.5 Hz, H-9), 4.24 (1H, dt, Jˆ9.0, 6.5 Hz, H-10).
13C NMR (75 MHz, CDCl3) d 16.6, 25.6, 25.8, 29.2, 33.9,
36.3, 37.7, 42.6, 67.8, 68.9, 77.8, 78.0, 79.6, 80.4. HRMS-EI
(m/z): [M2I]1 calcd for C14H23O3, 239.1637; found,
239.1645.
1
85%) as a colorless oil. H NMR (400 MHz, CDCl3) d
1.14 (3H, d, Jˆ7.0 Hz, CH3), 1.35±1.46 (2H, m, H-3a,
H-6a), 1.53±1.46 (6H, m, H-2£2, H-11£2, H-12£2), 1.73
(1H, ddd, Jˆ14.0, 6.0, 2.0 Hz, H-6b), 1.94 (1H, ddd,
Jˆ12.0, 9.0, 4.0 Hz, H-3b), 2.04 (1H, m, OH), 2.61 (1H,
br quart, Jˆ7.0 Hz, H-7), 3.20±3.36 (3H, m, H-1a, H-4,
H-5), 3.63 (2H, m, H-13£2), 3.81 (1H, dt, Jˆ10.0, 4.0 Hz,
H-1b), 4.12 (1H, m, H-10), 5.22 (1H, ddd, Jˆ13.0, 4.0,
1.5 Hz, H-9), 5.56 (1H, ddd, Jˆ13.0, 6.0, 1.5 Hz, H-8).
13C NMR (100 MHz, CDCl3) d 22.4, 25.1, 29.3, 29.6,
30.4, 33.2, 40.0, 62.8, 67.3, 77.5, 77.8, 79.0, 130.5, 136.6.
8-Chloromercurric-9,10-cis-tricyclic compound (17). A
solution of 16a (15 mg, 0.063 mmol) and mercury(II)
acetate (96 mg, 0.32 mmol) in CH2Cl2 (0.8 mL) was stirred
at room temperature for 20 h. The reaction mixture was
diluted with CH2Cl2, washed with brine. The organic
phase was dried over Na2SO4 and concentrated. The residue
was puri®ed by column chromatography on silica gel (50%
diethyl ether in hexane) to afford 17 as a white foam (15 mg,
50%). 1H NMR (300 MHz, CDCl3) d 1.22 (3H, d,
Jˆ7.0 Hz, CH3), 1.36±1.46 (1H, m, H-12), 1.58±1.73
(2H, m, H-6a, H-3a), 1.73±1.96 (3H, m, H-6b, H-11,
H-12), 2.05 (1H, br d, Jˆ12 Hz, H-3), 2.54 (1H, m, H-7),
9,10-trans-Tricyclic compound (20). A solution of 19
(10.0 mg, 0.027 mmol), n-butyltin hydride (0.14 mL,
0.14 mmol) and AIBN (1 mg) in toluene (0.5 mL) was
heated at 558C for 2 h. The solvent was evaporated and
the residue was puri®ed by column chromatography on
silica gel (hexane!33% diethyl ether in hexane) to afford
20 (4.7 mg, 72%) as a colorless oil. Rfˆ0.38 (silica gel, 1:1,
1
ether±hexane). [a]D25ˆ135.8 (c 0.17, CHCl3). H NMR

T.-Z. Liu et al. / Tetrahedron 56 (2000) 10209±10219
10219
8. (a) Nunomoto, S. J. Org. Chem. 1983, 48, 1912±1914.
(b) Derguini-Boumechal, F.; Linstrumelle, G. Tetrohedron Lett.
1976, 36, 3225±3226. (c) Huynh, C.; Linstrumelle, G. Tetrahedron
Lett. 1979, 12, 1073±1075. (d) Fouquet, G.; Schlosser, M. Angew.
Chem., Int. Ed. Engl. 1974, 13, 82. (e) Shea, K. J.; Pham, P. Q.
Tetrahedron Lett. 1983, 24, 1463.
(300 MHz, CDCl3) d 0.89 (3H, d, Jˆ7 Hz, CH3), 1.20 (1H,
ddd, Jˆ12, 9. 4 Hz, H-6a), 1.26 (1H, ddd, Jˆ12, 6, 2 Hz, H-
8a), 1.36 (1H, dd, Jˆ13, 6 Hz, H-3a), 1.40±1.49 (2H, m, H-
8b, H-11a), 1.46±1.52 (1H, m, H-7), 1.66±1.73 (2H, m, H-
2£2), 1.80 (1H, ddd, Jˆ12, 7, 2 Hz, H-11b), 1.86±1.92 (2H,
m, H-12£2), 1.96 (1H, dt, Jˆ12, 5 Hz, H-6b), 2.02 (1H,
ddd, Jˆ13, 9, 2 Hz, H-3b), 2.98 (1H, td, Jˆ9, 4 Hz, H-5),
3.02 (1H, td, Jˆ9, 6 Hz, H-4), 3.19 (1H, td, Jˆ9.5, 2 Hz, H-
9), 3.40 (1H, ddd, Jˆ12, 10, 5 Hz, H-1a), 3.74 (1H, dd,
Jˆ13, 7 Hz, H-13a), 3.84 (1H, dd, Jˆ13, 7 Hz, H-13b),
3.86±3.93 (1H, m, H-1b), 4.08 (1H, td, Jˆ9.5, 7 Hz, H-
10). 13C NMR (75 MHz, CDCl3) d 17.7, 25.6, 25.7,
29.4,31.9, 36.0, 38.6, 39.1, 67.5, 67.8, 75.8, 77.8, 78.4,
80.6. HRMS-EI (m/z): M1 calcd for C14H24O3, 240.1725;
found, 240.1719. Anal. Calcd for C14H24O3: C, 69.96; H,
10.06. Found: C, 69.91; H, 10.15.
9. (a) Chan, T. H.; Lau, P. W. K.; Mychajlowskij, W. Tetrahedron
Lett. 1977, 38, 3317±3320. (b) Barluenga, J.; Alvarez-Garcia, J.;
Gonzalez, J. M. Tetrahedron Lett. 1995, 36, 2153±2156. (c) Chan,
T. H.; Koumaglo, K. Tetrahedron Lett. 1986, 27, 883±886. Miller,
R. B.; Reichenbach, T. Tetrahedron Lett. 1974, 6, 543±546.
10. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 4467±4470. (b) Cassar, L. J. Organomet. Chem.
1975, 93, 253. (c) Ratovelomanana, V.; Hammoud, A.;
Linstrumelle, G. Tetrahedron Lett. 1987, 28, 1649.
11. Preparation of the protected form of Hex-5-yn-1,4-diol (10).
Acknowledgements
This research was ®nancially supported by a Grant-In-Aids
for Scienti®c Research from the Ministry of Education,
Science, Sports and Culture and by JSPS-RFTF. T.-Z. Liu
and J.-M. Li are both leave from Nankai University, Tianjin,
China. Special thanks are due to Mr K. Koga and Mr S.
Kitamura of this school for assistance of spectroscopic
analyses and for execution of elemental analyses, T.-Z.
Liu is grateful to Meitetsu International Scholarship for
their ®nancial support during his graduate studies for PhD.
12. (a) Nicholas, K. M.; Pettit, R. Tetrahedron Lett. 1971, 37,
3475±3478. (b) Cusack, N. J.; Reese, C. B.; Roozpeikar, B.
J. Chem. Soc. Chem. Commun. 1972, 1132±1133. (c) Cusack,
N. J.; Reese, C. B.; Roozpeikar, B. Tetrahedron 1976, 32, 2157±2162.
13. (a) Chamblin, A. R.; Mulholand, Jr. R. L. Tetrahedron 1984,
40, 2297±2302. (b) Danishefsky, S. J.; Larson, E.; Springer, J. P.
J. Am. Chem. Soc. 1985, 107, 1274±1280. (c) Giese, B.; Bartman,
D. Tetrahedron Lett. 1985, 26, 1197±1200. (d) Chamblin, A. R.;
Dezube, M.; Dussault, P.; McMills, M. J. Am. Chem. Soc. 1983,
105, 5819±5825. (e) Still, W. C.; Barirish, J. J. Am. Chem. Soc.
1983, 105, 2487±2489. (f) Midland, M. M.; Halterman, R. L.
J. Org. Chem. 1981, 46, 1227±1229.
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