A new procedure for construction of oxocane and oxonane derivatives based on alkyne-Co2(CO)6 complexes

Article abstract of DOI:10.1016/S0040-4020(99)01103-5

Treatment of 2-(3-hydroxy-5-phenylpent-4-yn-1-yl)-2- (trimethylsilylmethyl)tetrahydrofuran (18) with Co₂(CO)₈ gave the corresponding cobalt complex, which was subsequently exposed to methanesulfonyl chloride and triethylamine in methylene chloride at refluxing temperature to provide the oxocane derivative 20 in 72% yield. This method was found to be applicable for construction of the oxonane framework. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(99)01103-5

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2203±2209
A New Procedure for Construction of Oxocane and Oxonane
Derivatives Based on Alkyne±Co2(CO)6 Complexes
*
Chisato Mukai, Haruhisa Yamashita, Tetsuya Ichiryu and Miyoji Hanaoka
Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, Kanazawa 920-0934, Japan
Accepted 7 December 1999
AbstractÐTreatment of 2-(3-hydroxy-5-phenylpent-4-yn-1-yl)-2-(trimethylsilylmethyl)tetrahydrofuran (18) with Co2(CO)8 gave the corre-
sponding cobalt complex, which was subsequently exposed to methanesulfonyl chloride and triethylamine in methylene chloride at re¯uxing
temperature to provide the oxocane derivative 20 in 72% yield. This method was found to be applicable for construction of the oxonane
framework. q 2000 Elsevier Science Ltd. All rights reserved.
There are many oxygen atom-containing heterocycles such
as tetrahydrofuran, tetrahydropyran, oxepane, and oxocane
ring systems1±3 which have frequently been found to be the
major component of many biologically important natural
products.4,5 One of the most straightforward processes to
build up the substituted oxygen atom-containing hetero-
cycles like the 3-hydroxy-2-substituted derivative 1 would
be ring opening of an epoxide by a terminal hydroxy group
of the corresponding epoxy-alcohol species 2 via endo mode
ring closure (Scheme 1, route a). According to Baldwin
rules,6 however, the endo mode ring closure (route a) is
generally regarded as an unfavorable pathway and the
competing exo mode ring closure (route b) is often preferred
over route a. In order to override this disadvantage, several
elegant and intriguing methods7 (e.g. activation of epoxides
by an adjacent vinyl moiety or by palladium catalyst) have
already been devised.
by alkyne±Co2(CO)6 complexes and their application to the
total syntheses of bioactive compounds, we paid much
attention to the propynyl cation stabilizing ability of the
alkyne±Co2(CO)6 complex for regioselective endo mode
ring closure. We envisioned that the alkyne±Co2(CO)6
complex derived from the alkyne±epoxide 3 possessing a
terminal hydroxy group would, upon exposure to acidic
conditions, regioselectively generate the propynyl cation.
The cation stabilized by the cobalt complex moiety might
be immediately captured in an endo mode fashion by a
terminal primary alcohol resulting in exclusive formation
of the oxygen atom-containing heterocyclic skeleton 4
(Scheme 2). Thus tetrahydrofuran 4 (nˆ0) and tetrahydro-
pyran derivatives 4 (nˆ1)10,11 had been shown to be formed
in a highly stereoselective as well as a stereospeci®c manner
from the corresponding alkyne±epoxide 3 (nˆ0,1). The
oxepane derivatives 4 (nˆ2)12 could also be produced by
using this endo mode cyclization. However, this procedure
was found not to be useful for construction of the eight-
membered congener 4 (nˆ3).13 These results would lead
to the conclusion that the newly developed endo mode
ring closure can be successfully applied for the construction
of ®ve-, six- and seven-membered oxygen atom-containing
heterocycles, but not for that of medium-sized oxygen atom-
containing heterocycles (e.g. oxocane and oxonane species).
Alkyne±Co2(CO)6 complexes, easily derived from the reac-
tion of propynyl alcohol or ethers with dicobaltoctacarbonyl
(Co2(CO)8), have been well known to liberate, upon treat-
ment with a Lewis acid, the corresponding propynyl cation
species, which were subsequently captured by various
nucleophiles (Nicholas reaction).8 In the course of our
program9 directed toward the development of highly stereo-
selective carbon±carbon bond formation reactions mediated
In order to overcome the limitation encountered during the
transformation of 3 into 4, an alternative method for the
synthesis of eight-membered oxygen atom-containing
Scheme 1.
Keywords: oxonane; oxocane; oxepane.
* Corresponding author. E-mail: cmukai@kenroku.kanazawa-u.ac.jp
Scheme 2.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01103-5

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C. Mukai et al. / Tetrahedron 56 (2000) 2203±2209
Scheme 3.
heterocycles based on alkyne±Co2(CO)6 was developed
as in Scheme 3. We envisaged that treatment of
afford the propynyl alcohol derivative 12 in 72% yield.
The oxidation of 12 under Swern conditions furnished 13
in 99% yield, which was then hydrogenated under hydrogen
atmosphere yielding 14 in 93% yield. Adjustment of the
protecting group of 14 from TBDMS group to p-toluene-
sulfonyl (Ts) group was realized by successive exposure to
tetra-n-butylammonium ¯uoride (TBAF) and Ts chloride
producing 15. Formation of the tetrahydrofuran framework
was completed by reaction of 15 with trimethylsilylmethyl-
lithium in THF at 2788C to provide the tetrahydrofuran
derivative 16 in 39% overall yield from 14. The tetrahydro-
furan derivative 16 possessing all carbon units required for
construction of the oxocane skeleton was thus prepared,
although the chemical yield of the conversion of 14 to 16
was unsatisfactory. The next phase in this program was the
introduction of the cobalt-complexed propynyl moiety in
the tether of 16. Upon treatment with DDQ, 16 underwent
deprotection to easily give the alcohol 17 in 74% yield.
Swern oxidation of 17 was followed by the addition of
phenylacetylide to afford the adduct 18 as a mixture of
diastereoisomers in 64% yield. Cobalt complexation was
performed by the reaction of 18 with Co2(CO)8 in Et2O at
room temperature affording the compound 19 in 97% yield.
the 2-trimethylsilylmethyltetrahydrofuran derivative
5
possessing a propynyl ether portion with Co2(CO)8 would
afford the corresponding cobalt complex 6 as usual. Upon
exposure to a Lewis acid, this complex 6 would produce the
propynyl cation 7 which might be subsequently captured by
an oxygen atom on the tetrahydrofuran ring resulting in the
formation of the oxonium intermediate 8. The b-effect14 of
the trimethylsilylmethyl moiety of 8 would help to generate
the eight-membered cation species 9 which is then collapsed
to the desired oxocane derivative 10.15 On the basis of this
consideration, we tried to convert the tetrahydrofuran
derivative 5 into the oxocane derivative 10. This paper
describes a new procedure for the preparation of eight-
membered and nine-membered oxygen atom-containing
heterocycles by taking advantage of the inherent property
of the alkyne±Co2(CO)6 complex.
The required tetrahydrofuran derivative for construction of
the oxocane derivative was prepared by conventional means
(Scheme 4). Swern oxidation of 4-(tert-butyldimethyl-
siloxy)butan-1-ol (11) gave the corresponding aldehyde,
which was subsequently treated with the acetylide, derived
from 3-(p-methoxy-benzyloxy)propyne, at 2788C to
With the required tetrahydrofuran derivative 19 having
Scheme 4. Reactions and conditions: (a) Swern oxid.; (b) LiCuCCH2OPMB, THF, 2788C; (c) H2, Pd±C, AcOEt, r.t.; (d) TBAF, THF, r.t.; (e) TsCl, Et3N,
CH2Cl2, r.t.; (f) TMSCH2Li, THF, 2788C; (g) DDQ, CH2Cl2, H2O, r.t.; (h) THF, LiCuCPh, 2788C; (i) Co2(CO)8, Et2O, r.t.

C. Mukai et al. / Tetrahedron 56 (2000) 2203±2209
2205
Scheme 5.
the cobalt-complexed propynyl moiety in hand, we next
investigated the transformation of 19 into the oxocane
derivative 20 (Scheme 5) according to our scenario
described in Scheme 3. Treatment of 19 with BF3´OEt2 in
methylene chloride, however, only gave an intractable
mixture. No desired oxocane derivatives could be obtained
when the other Lewis acids16 were employed. Finally,
methanesulfonyl chloride (MsCl) was found to be effective
for our purpose. Thus, the cobalt complex 19 was treated
with MsCl in methylene chloride in the presence of triethyl-
amine at room temperature to afford the eight-membered
exo-methylene product 20 in 54% yield along with the
endo-ole®n product 2117 in 23% yield. When the reaction
was carried out at re¯uxing temperature in methylene
chloride, 20 could be isolated as the sole product in 72%
yield. The formation of these two oxocanes, 20 and 21, can
be tentatively rationalized in terms of the intermediacy of
the carbocation 22, stabilized by the b-trimethylsilyl (TMS)
group,14 leading to 20 and 21 through elimination of the
b-TMS group18 and the b-hydrogen (Ha), respectively.
Decomplexation of 20 and 21 under standard conditions
with cerium ammonium nitrate (CAN) furnished 23 and
24 in 91 and 80% yields, respectively.
involved the application of these conditions to prepare
other medium sized oxygen atom containing heterocycles.
Thus, we chose the oxanone derivative (oxygen atom-
containing nine-membered heterocycle) as the second target
molecule in this program. The starting d-valerolactone was
successively exposed to the following conditions: addition of
the acetylide of 3-(tert-butyldimethylsiloxy)propyne, hydro-
genation, protection of the resulting hydroxy group with a
pivaloyl group, and acid hydrolysis leading to 25 in 61%
overall yield. The formation of the tetrahydrofuran frame-
work was realized by the consecutive reaction of 25 with Ts
chloride and trimethylsilylmethyllithium to furnish 26, the
pivaloyl protecting group of which was then removed by
diisobutylaluminum hydride (DIBAL-H) producing 27 in
26% yield from 25. Next, the propynyl alcohol derivative
28 was obtained in 54% yield from 27 according to the
procedure described for the conversion of 17 to 18. Treat-
ment of 28 with Co2(CO)8 provided the corresponding
cobalt-complex, which was exposed to the conditions,
developed for the conversion of 19 to the oxocane derivative
20 (MsCl, Et3N, CH2Cl2, room temperature), to afford only
one product with cobalt complexation. The cobalt
complexed 29 was then exposed to CAN in methanol at
room temperature to provide the desired oxonane derivative
29 in 52% yield (Scheme 6).
A new procedure for construction of the oxocane skeleton
was developed based on the chemistry of the alkyne±
Co2(CO)6 complex. The next phase of our study now
We have developed a new method for the preparation of the
Scheme 6. Reagents and conditions: (a) LiCuCCH2OTBDMS, THF, 2788C; (b) H2, Pd±C, AcOEt, r.t.; (c) PivCl, Et3N, CH2Cl2, r.t.; (d) 10% HCl aq., THF,
rt; (e) TsCl, DMAP, Et3N, CH2Cl2, rt; (f) TMSCH2Li, THF, 2788C; (g) DIBAL±H, CH2Cl2, 2788C (26% from 25); (h) Swern oxid.; (i) LiCuCPh, THF,
2788C; (j) Co2(CO)8, Et2O, rt; (k) MsCl, Et3N, CH2Cl2, rt; (l) CAN, MeOH, rt.

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C. Mukai et al. / Tetrahedron 56 (2000) 2203±2209
oxocane as well as the oxonane skeletons by taking advan-
tage of the inherent property of the alkyne±Co2(CO)6
complex. In combination with the previously reported
endo mode cyclization procedure of cobalt-complexed
epoxy derivatives for construction of tetrahydrofuran and
tetrahydropyran frameworks, this method could provide a
powerful tool for the preparation of ®ve-membered through
medium-sized oxygen atom-containing heterocycles.
Further studies in line with this strategy as well as its appli-
cation to the total synthesis of natural products are now in
progress.
Jˆ1.5 Hz, C1±H), 3.81 (3H, s, OMe), 3.73±3.64 (2H, m,
C7±H), 1.90±1.66 (4H, m, CH2), 0.90 (9H, s, t-Bu±Si), 0.07
(6H, s, Me±Si); 13C NMR d 59.33, 129.73, 129.47, 113.78,
87.54, 80.48, 71.12, 63.16, 62.10, 57.05, 55.25, 35.34,
28.51, 25.87, 18.27. Anal. Calcd for C21H34O4Si: C,
66.62; H, 9.05. Found: C, 66.24; H, 9.20.
7-(tert-Butyldimethylsiloxy)-1-[(p-methoxybenzyl)oxy]-
2-heptyn-4-one (13). According to the procedure described
for Swern oxidation of 11, 12 (1.50 g, 3.96 mmol) was
oxidized with DMSO (0.67 mL, 9.51 mmol), oxalyl
chloride (0.42 mL, 4.75 mmol), and Et3N (2.76 mL,
19.8 mmol) to afford, after chromatography with hexane±
AcOEt (10:1), 13 (1.48 g, 99%) as a pale yellow oil: MS m/z
(%) 376 (M1, 0.3), 319 (13), 289 (90), 121 (100), 75 (37);
IR 1675 (CO) cm21; 1H NMR d 7.29±7.27 (2H, m, aromatic
H), 6.9±6.88 (2H, m, aromatic H), 4.55 (2H, s, benzylic H),
4.29 (2H, s, C1±H), 3.81 (3H, s, OMe), 3.64 (2H, t,
Jˆ6.4 Hz, C7±H), 2.67 (2H, t, Jˆ7.3 Hz, C5±H), 1.99
(2H, tt, Jˆ7.3, 6.4 Hz, C6±H), 0.89 (9H, s, t-Bu±Si), 0.05
(6H, s, Me±Si); 13C NMR d 186.48, 158.83, 129.12, 128.01,
113.19, 86.86, 84.66, 76.76, 76.30, 75.81, 70.92, 61.04,
55.80, 54.54, 41.26, 26.17, 25.16, 17.54, 26.12. Anal.
Calcd for C21H32O4Si: C, 66.98; H, 8.57. Found: C, 66.66;
H, 8.73.
Experimental
Infrared spectra were measured with a Shimazu IR-460
spectrometer in CHCl3, mass spectra with a Hitachi M-80
mass spectrometer, 1H NMR spectra with JEOL JNM-
EX270 and JNM-GSX500 spectrometers for samples in
CDCl3, using either tetramethylsilane as an internal stan-
dard for compounds that have no silyl group or CHCl3
(7.26 ppm) for compounds possessing the silyl group, and
13C NMR spectra with JEOL JNM-EX270 and JNM-
GSX500 spectrometers in CDCl3 with CDCl3 (77.00 ppm)
as an internal reference. CH2Cl2 was freshly distilled from
P2O5, and THF from sodium diphenylketyl prior to use.
Silica gel (Silica gel 60, 230±400 mesh, Merck) was used
for chromatography. Organic extracts were dried over
anhydrous Na2SO4. All reactions were carried out under
nitrogen atmosphere. Reactions involving the complexation
with Co2(CO)8 and decomplexation of the alkyne±
Co2(CO)6 complexes should be carried out under well
ventilated conditions since carbon monoxide is produced.
7-(tert-Butyldimethylsiloxy)-1-[(p-methoxybenzyl)oxy]-
heptan-4-one (14). A solution of 13 (387 mg, 1.03 mmol)
in AcOEt (10 mL) was hydrogenated in the presence of 5%
Pd±C (39.0 mg) under hydrogen atmosphere for 3 h at room
temperature. The catalyst was removed by passing through a
short pad of Celite and the ®ltrate was concentrated to
dryness. Chromatography of the residue with hexane±
AcOEt (10:1) afforded 14 (361 mg, 93%) as a colorless
oil: MS m/z (%) 380 (M1, 1.7), 323 (4), 185 (38), 121
(^)-7-(tert-Butyldimethylsiloxy)-1-[(p-methoxybenzyl)-
oxy]-2-heptyn-4-ol (12). A solution of DMSO (1.70 mL,
24.0 mmol) in CH2Cl2 (10 mL) was added to a solution of
oxalyl chloride (1.05 mL, 12.0 mmol) in CH2Cl2 (80 mL) at
2788C over a period of 5 min. After the mixture was stirred
for 30 min, a solution of 11 (2.04 g, 10.0 mmol) in CH2Cl2
(10 mL) was added to the CH2Cl2 solution, and the reaction
mixture was stirred at the same temperature for 90 min.
Et3N (6.97 mL, 50.0 mmol) was then added to the reaction
mixture, which was gradually warmed to room temperature
and diluted with CH2Cl2. The CH2Cl2 solution was washed
with water and brine, dried, and concentrated to dryness.
The residue was passed through a short pad of silica gel
with hexane±AcOEt (10:1) to leave the crude aldehyde.
To a solution of 3-[(p-methoxybenzyl)oxy]prop-1-yne
(1.94 g, 11.0 mmol) in THF (90 mL) was added n-BuLi in
hexane (1.47 M 7.48 mL, 11.0 mmol) at 2788C. After the
mixture was stirred for 30 min, a solution of the crude alde-
hyde in THF (10 mL) was added to the THF solution, and
the reaction mixture was stirred at the same temperature for
30 min. The reaction mixture was quenched by addition of
saturated aqueous NH4Cl and extracted with AcOEt which
was washed with water and brine, dried, and concentrated to
dryness. Chromatography of the residue with hexane±
AcOEt (6:1) afforded 12 (2.72 g, 72%) as a colorless oil:
MS m/z (%) 378 (M1, 0.2), 360 (0.3), 291 (32), 199 (30),
1
(100), 75 (73); IR 1710 (CO) cm21; H NMR d 7.25±7.22
(2H, m, aromatic H), 6.89±6.86 (2H, m, aromatic H), 4.41
(2H, s, benzylic H), 3.80 (3H, s, OMe), 3.59 (2H, t,
Jˆ6.3 Hz, CH2), 3.44 (2H, t, Jˆ6.3 Hz, CH2), 2.52 (2H, t,
Jˆ7.3 Hz, CH2), 2.47 (2H, t, Jˆ7.3 Hz, CH2), 1.90±1.84
(2H, m, CH2), 1.79±1.74 (2H, m, CH2), 0.88 (9H, s,
t-Bu±Si), 0.03 (6H, Me±Si); 13C NMR d 210.64, 159.12,
130.48, 129.22, 113.73, 72.47, 69.04, 62.16, 55.22, 39.39,
39.12, 26.79, 25.89, 23.85, 18.27, 25.39; HRMS calcd
for C21H36O4Si 380.2383, found 380.2386. Anal. Calcd
for C21H36O4Si: C, 66.27; H, 9.53. Found: C, 65.86; H,
9.61.
(^)-2-[30-((p-Methoxybenzyl)oxy)prop-10-yl]-2-(trimethyl-
silylmethyl)tetrahydrofuran (16). To a solution of 14
(2.00 g, 5.25 mmol) in THF (53 mL) was added TBAF in
THF (1.0 M, 7.88 mL, 7.88 mmol) at room temperature and
the mixture was stirred for 30 min. The reaction mixture
was diluted with water and extracted with AcOEt, which
was washed with water and brine, dried, and concentrated
to dryness. The crude alcohol was dissolved in CH2Cl2
(53 mL), to which TsCl (2.00 g, 10.5 mmol) and Et3N
(2.93 mL, 21.0 mmol) was added at room temperature.
The reaction mixture was stirred for 10 h at room tempera-
ture and washed with water and brine, dried, and concen-
trated to dryness. Trimethylsilylmethyllithium in pentane
(1.0 M 7.88 mL, 7.88 mmol) was added to a solution of
the crude tosylate 15 in THF (53 mL) at 2788C. The reaction
1
121 (100), 91 (15); IR 3339 (OH) cm21; H NMR d 7.28±
7.27 (2H, m, aromatic H), 6.89±6.86 (2H, m, aromatic H),
4.52 (2H, s, benzylic H), 4.50 (1H, m, C4±H), 4.17 (2H, d,

C. Mukai et al. / Tetrahedron 56 (2000) 2203±2209
2207
mixture was stirred for 30 min, quenched by addition of
water, and extracted with AcOEt. The extract was washed
with water and brine, dried, and concentrated to dryness.
Chromatography of the residue with hexane±AcOEt
(10:1) afforded 16 (689 mg, 39% from 14) as a pale yellow
oil: MS m/z (%) 336 (M1, 4), 318 (9), 215 (6), 157 (12), 137
(20), 121 (100), 73 (56); H NMR d 7.23±7.20 (2H, m,
aromatic H), 6.85±6.82 (2H, m, aromatic H), 4.43 (2H, s,
benzylic H), 3.82±3.72 (2H, m, C5±H), 3.80 (3H, s, OMe),
for C19H28O2Si: C, 72.10; H, 8.92. Found: C, 71.85; H,
8.98.
Hexacarbonyl-m-[h4-(2Rp,30Rp) and (2Rp,30Sp)-2-(30-
hydroxy-50-phenylpent-40-yn-10-yl)-2-(trimethylsilyl-
methyl)tetrahydrofuran]dicobalt](Co±Co) (19). Co2(CO)8
(189 mg, 0.55 mmol) was added to a solution of 18 (159 mg,
0.50 mmol) in Et2O (5.0 mL) at room temperature. After
being stirred for 30 min, the Et2O solution was concentrated
to leave the residue, which was chromatographed with
hexane±AcOEt (10:1) to afford 19 (294 mg, 97%) as a
mixture of two diastereoisomers in a ratio of ca. 50±50.
Compound 19 was obtained as a deep brown oil; MS m/z
(%) 602 (M1, 0.1), 546 (15), 490 (38), 434 (47), 157 (100),
127 (13), 73 (60); IR 3330 (OH), 2091 (CO), 2054 (CO),
1
0
3.44 (2H, d, Jˆ6.8 Hz C3 ±H), 1.95±1.46 (8H, m, CH2),
1.08, 0.98 (2H, AB-q, Jˆ14.7 Hz, TMSCH2), 0.04 (9H, s,
TMS); 13C NMR d 159.03, 130.76, 129.13, 113.69, 85.05,
72.42, 70.59, 66.54, 55.24, 37.68, 37.38, 28.88, 26.08,
25.00, 0.22; HRMS calcd for C19H32O3Si 336.2121, found
336.2118.
1
2027 (CO) cm21; H NMR d 7.65±7.25 (5H, m, aromatic
(^)-2-(30-Hydroxyprop-10-yl)-2-(trimethylsilylmethyl)-
tetrahydrofuran (17). DDQ (506 mg, 2.23 mmol) was
added to a solution of 16 (500 mg, 1.49 mmol) in CH2Cl2
and H2O (15 mL, 20:1). The reaction mixture was stirred at
room temperature for 20 min, quenched by addition of
saturated aqueous NaHCO3, and extracted with AcOEt.
The extract was washed with water and brine, dried, and
concentrated to dryness. Chromatography of the residue
with hexane±AcOEt (10:1) afforded 17 (236 mg, 74%) as
a pale yellow oil; MS m/z (%) 199 (M1-OH, 4), 157 (100),
137 (21), 129 (22), 73 (76); IR 3367 (OH) cm21; 1H NMR d
H), 5.10±4.89 (1H, m, C3 ±H), 4.53 (1H£50/100, d,
0
Jˆ3.0 Hz, OH), 4.01 (1H£50/100, d, Jˆ4.3 Hz, OH),
3.90±3.82 (2H, m, C5±H), 2.16±1.64 (8H, m, CH2), 1.23,
1.06 (2H£50/100, AB-q, Jˆ14.5 Hz, TMSCH2), 1.12, 1.03
(2H£50/100, AB-q, Jˆ14.9 Hz, TMSCH2), 0.07 (9H£50/
100, s, TMS), 0.04 (9H£50/100, s, TMS). Anal. Calcd for
C25H28Co2O8Si: C, 49.84; H, 4.68. Found: C, 49.99; H, 4.73.
Hexacarbonyl-m-[h4-5-methylene-2-(20-phenylethynyl)-
oxocane]dicobalt(Co±Co) (20) and hexacarbonyl-m-[h4-
5-(trimethylsilylmethyl)-2-(20-phenylethynyl)-5-oxo-
cene]dicobalt-(Co±Co) (21). MsCl (0.03 mL, 0.35 mmol)
was added to a solution of 19 (21.2 mg, 3.5£1022 mmol) in
CH2Cl2 (0.2 mL) at re¯uxing temperature. The reaction
mixture was stirred for 10 min at the same temperature
and diluted with CH2Cl2, which was washed with water
and brine, dried, and concentrated to dryness. Chromato-
graphy of the residue with hexane-AcOEt (100:1) afforded
20 (9.80 mg, 54%) and 21 (4.80 mg, 23%). Compound
20 was obtained as a reddish brown oil; MS m/z (%)
512 (M1, 1.4), 456 (55), 400 (100), 344 (75), 226 (53),
187 (23), 91 (17); IR 2089 (CO), 2053 (CO), 2027
0
3.81±3.73 (2H, m, C5±H), 3.63±3.53 (2H, m, C3 ±H), 2.74
(1H, t, Jˆ4.9 Hz, OH), 1.92±1.86 (4H, m, CH2), 1.72±1.53
(4H, m, CH2), 1.12, 0.97 (2H, AB-q, Jˆ14.2 Hz, TMSCH2),
0.04 (9H, s, TMS); 13C d 85.18, 66.53, 63.49, 38.10, 37.99,
28.57, 27.91, 26.00, 0.20. Anal. Calcd for C11H24O2Si: C,
61.06; H, 11.18. Found: C, 60.76; H, 11.02.
(2Rp,30Rp) and (2Rp,30Sp)-2-(30-Hydroxy-50-phenylpent-
40-yn-10-yl)-2-(trimethylsilylmethyl)tetrahydrofuran
(18). According to the procedure described for Swern oxida-
tion of 11, 17 (212 mg, 0.98 mmol) was oxidized with
DMSO (0.17 mL, 2.36 mmol), oxalyl chloride (0.10 mL,
1.18 mmol), and Et3N (0.68 mL, 4.91 mmol) to afford the
crude aldehyde after chromatography with hexane±AcOEt
(10:1). To a solution of phenylacetylene (0.18 mL,
1.47 mmol) in THF (5.0 mL) was added n-BuLi in hexane
(1.51 M 0.97 mL, 1.47 mmol) at 2788C. After the mixture
was stirred for 30 min, a solution of the crude aldehyde in
THF (5.0 mL) was added to the THF solution, and the reac-
tion mixture was stirred at the same temperature for 30 min.
The reaction mixture was quenched by addition of water and
extracted with AcOEt, which was washed with water and
brine, dried, and concentrated to dryness. Chromatography
of the residue with hexane±AcOEt (15:1) afforded 18
(199 mg, 64%) as a mixture of two diastereoisomers in a
ratio of ca. 50±50. Compound 18 was obtained as a pale
yellow oil; MS m/z (%) 316 (M1, 1), 298 (1), 229 (7), 185
(4), 157 (100), 127 (19), 102 (35), 73 (79); IR 3218
(CO) cm21 1H NMR d 7.56±7.29 (5H, m, aromatic
;
H), 4.90 (1H, s, ole®nic H), 4.83 (1H, s, ole®nic H),
4.78 (1H, dd, Jˆ10.6, 3.0 Hz, C2±H), 3.96 (1H, ddd,
Jˆ12.5, 6.3, 3.3 Hz, C8±H), 3.72 (1H, dt, Jˆ12.5,
4.3 Hz, C8±H), 2.58±1.66 (8H, m, CH2); 13C NMR d
190.66, 150.64, 137.90, 129.70, 128.77, 111.36, 79.95,
70.68, 39.30, 34.59, 32.62, 28.97; HRMS calcd for
C22H18Co2O7 511.9716, found 511.9718. Compound 21
was obtained as a reddish brown oil; MS m/z (%) 584
(M1, 0.9), 528 (47), 472 (38), 416 (73), 386 (20), 298
(37), 115 (22), 73 (100); IR 2090 (CO), 2052 (CO),
2027 (CO) cm21
; d 7.56±7.28 (5H, m,
1H NMR
aromatic H), 5.41 (1H, t, Jˆ7.3 Hz, C6±H), 4.75 (1H,
dd, Jˆ11.2, 3.3 Hz, C2±H), 4.06 (1H, dt, Jˆ11.9,
3.6 Hz, C8±H), 3.56±3.43 (1H, m, C8±H), 2.89±2.75
(1H, m, C7±H), 2.57 (1H, dddd, Jˆ14.5, 10.9, 7.3,
3.6 Hz, C7±H), 2.11±1.79 (4H, m, CH2), 1.60, 1.52
(2H, AB-q, Jˆ13.5 Hz, TMSCH2), 0.04 (9H, s, TMS);
13C NMR d 199.59, 139.86, 138.01, 129.70, 128.75,
127.60, 120.68, 99.98, 90.60, 80.34, 73.16, 36.39,
30.46, 29.42, 27.03, 21.27; HRMS calcd for
C25H26Co2O7Si 584.0112, found 584.0106. When MsCl
(0.02 mL, 0.21 mmol) was added to a re¯uxing solution of
19 (12.5 mg, 2.1£1022 mmol) and Et3N (0.06 mL,
0.42 mmol) in CH2Cl2 (0.1 mL) and the reaction mixture
1
(OH) cm21; H NMR d 7.47±7.25 (5H, m, aromatic H),
0
4.69±4.58 (1H, m, C3 ±H), 4.18 (1H£50/100, d,
Jˆ7.6 Hz, OH), 3.96±3.79 (2H, m, C5±H), 3.39 (1H£50/
100, d, Jˆ5.0 Hz, OH), 2.11±1.58 (8H, m, CH2), 1.27, 1.05
(2H£50/100, AB-q, Jˆ14.8 Hz, TMSCH2), 1.18, 1.02
(2H£50/100, AB-q, Jˆ14.5 Hz, TMSCH2), 0.06 (9H£50/
100, s, TMS), 0.05 (9H£50/100, s, TMS). Anal. Calcd

2208
C. Mukai et al. / Tetrahedron 56 (2000) 2203±2209
was stirred at the same temperature for 5 min, compound 20
(7.60 mg, 72%) was obtained as a sole product.
washed with saturated aqueous NaHCO3, water, and brine,
dried, and concentrated to dryness. Chromatography of the
residue with hexane±AcOEt (1:1) afforded 25 (4.47 g, 61%)
as a colorless oil FABMS m/z (%) (M11Na, 12), 227 (100),
154 (20), 125 (32), 97 (29), 57 (90); IR 3467 (OH), 1718
(CO) cm21; 1H NMR d 4.06 (2H, t, Jˆ6.9 Hz, C8±H), 3.65
(2H, t, Jˆ6.4 Hz, C1±H), 2.56 (2H, t, Jˆ7.4 Hz, CH2), 2.48
(2H, t, Jˆ6.8 Hz, CH2), 1.87±1.82 (2H, m, CH2), 1.70±1.62
(4H, m, CH2), 1.20 (9H, s, t-Bu); 13C NMR d 211.03,
178.60, 63.81, 61.98, 42.07, 39.37, 38.65, 28.00, 27.08,
26.38, 20.02; HRFABMS calcd for C13H24O4Na (M11Na)
267.1572, found 267.1575.
5-Methylene-2-(20-phenylethynyl)oxocane (23). CAN
(210 mg, 0.38 mmol) was added to a solution of 20
(49.0 mg, 0.10 mmol) in MeOH (1.0 mL) at 08C. After
being stirred for 30 min, the reaction mixture was concen-
trated, diluted with water, and extracted with AcOEt. The
extract was washed with water and brine, dried, and con-
centrated to dryness. Chromatography of the residue with
hexane±AcOEt (40:1) afforded 23 (19.8 mg, 91%) as a
colorless oil; MS m/z (%) 226 (M1, 27), 181 (36), 167
1
(100), 141 (82), 128 (85), 115 (68), 102 (50), 84 (31); H
NMR d 7.47±7.27 (5H, m, aromatic H), 4.82 (1H, s, ole®nic
H), 4.80 (1H, s, ole®nic H), 4.52 (1H, dd, Jˆ8.9, 4.3 Hz,
C2±H), 3.89 (1H, ddd, Jˆ12.5, 9.2, 3.6 Hz, C8±H), 3.70
(1H, dt Jˆ12.5, 4.6 Hz, C8±H), 2.57±1.69 (8H, m, CH2);
13C NMR d 150.66, 131.70, 128.18, 122.86, 110.82, 88.75,
84.44, 69.15, 67.17, 34.29, 32.90, 32.78, 31.13; HRMS
calcd for C16H18O 226.1358, found 226.1355.
(^)-2-(40-Hydroxybut-10-yl)-2-(trimethylsilylmethyl)-
tetrahydrofuran (27). According to the procedure
described for conversion of 14 into 16, a solution of 25
(2.00 g, 8.19 mmol) in CH2Cl2 (82 mL) was treated with
TsCl (2.34 g, 12.3 mmol), 4(-N,N-dimethylamino)pyridine
(100 mg, 8.19£1021 mmol), and Et3N (3.40 mL, 24.6
mmol) at room temperature for 6 h to provide the crude
tosylate. Trimethylsilylmethyllithium in pentane (1.0 M,
16.4 mL, 16.4 mmol) was then added to a solution of the
crude tosylate in THF (82 mL) at 2788C. The reaction
mixture was stirred for 1 h at the same temperature and
work-up gave the crude 26. To a solution of 26 in CH2Cl2
(82 mL) was added DIBAL-H in hexane (0.95 M, 12.9 mL,
12.9 mmol) at 2788C and the reaction mixture was stirred
for 30 min at the same temperature and quenched by
addition of water. The organic layer was washed with
water and brine, dried, and concentrated to dryness.
Chromatography of the residue with hexane±AcOEt (3:1)
afforded 27 (488 mg, 26%) as a colorless oil; MS m/z (%)
230 (M1, 2.7), 157 (44), 143 (11), 95 (13), 81 (60), 73 (100);
IR 3421 (OH) cm21; 1H NMR d 3.87±3.73 (2H, m, C5±H),
5-(Trimethylsilylmethyl)-2-(20-phenylethynyl)-5-oxo-
cene (24). According to the procedure described for
preparation of 23 from 20, 24 (6.80 mg, 80%) was obtained
from 21 (16.7 mg, 0.03 mmol) and CAN (62.7 mg,
1.14£1021 mmol). Compound 24 was a colorless oil; MS
m/z (%) 298 (M1, 12), 270 (32), 255 (9), 211 (914), 167
1
(15), 115 (21), 73 (100); H NMR d 7.43±7.21 (5H, m,
aromatic H), 5.30 (1H, t, Jˆ7.6 Hz, C6±H), 4.38 (1H, dd,
Jˆ10.9, 3.6 Hz, C2±H), 3.98 (1H, dt, Jˆ11.9, 3.6 Hz,
C8±H) 3.49 (1H, td, Jˆ11.9, 1.6 Hz, C8±H), 2.64 (1H, m,
C7±H), 2.43 (1H, dddd, Jˆ14.5, 11.9, 7.6, 3.6 Hz, C7±H),
2.52±1.80 (4H, m, CH2), 1.51, 1.45 (2H, AB-q, Jˆ17.5 Hz,
TMSCH2), 20.01 (9H, s, TMS); 13C NMR d 139.46,
131.64, 128.14, 123.04, 120.38, 89.45, 85.00, 72.74,
69.79, 35.74, 30.28, 29.69, 28.63, 27.14, 21.31; HRMS
calcd for C19H26OSi 298.1753, found 298.1758.
0
3.65 (2H, dt, Jˆ6.4, 5.6 Hz, C4 ±H), 1.76±1.33 (10H, m,
CH2), 1.09, 0.98 (2H, AB-q, Jˆ14.7 Hz, TMSCH2), 0.04
(9H, s, TMS); 13C NMR d 85.34, 66.49, 62.70, 40.67,
37.67, 33.12, 28.79, 26.08, 20.63, 0.18; HRMS calcd for
C12H26O2Si 230.1702, found 230.1706.
1-Hydroxy-8-[(pivaloyl)oxy]octan-4-one (25). To a solu-
tion of 3-(tert-butyldimethylsiloxy). prop-1-yne (5.62 g,
33.0 mmol) in THF (100 mL) was added n-BuLi in hexane
(1.46 M, 22.6 mL, 33.0 mmol) at 2788C. After the mixture
was stirred for 30 min, a solution of d-valerolactone (3.00 g,
30.0 mmol) in THF (50 mL) was added to the THF solution,
and the reaction mixture was stirred at the same temperature
for 30 min. The reaction mixture was quenched by addition
of saturated aqueous NH4Cl and extracted with AcOEt,
which was washed with water and brine, dried, and concen-
trated to dryness. A solution of the residue in AcOEt
(150 mL) was hydrogenated in the presence of 5% Pd±C
(300 mg) under hydrogen atmosphere for 30 min at room
temperature. The catalyst was removed by passing through a
short pad of Celite and the ®ltrate was concentrated to leave
the residual oil, which was then dissolved in CH2Cl2
(150 mL). Et3N (9.20 mL, 66.0 mmol) and pivaloyl chloride
(4.10 mL, 33.0 mmol) were successively added to the
CH2Cl2 solution and the mixture was allowed to stand at
room temperature for 4 h. The reaction mixture was washed
with water and brine, dried, and concentrated to dryness.
10% aqueous HCl solution (10.0 mL) was added to a solu-
tion of the residue in THF (150 mL) and the reaction
mixture was stirred at room temperature for 1 h, diluted
with water, and extracted with AcOEt. The extract was
(2Rp,40Rp) and (2Rp, 40Sp)-2-(40-Hydroxy-60-phenylhex-
50-yn-10-yl)-2-(trimethylsilylmethyl)tetrahydrofuran
(28). According to the procedure described for conversion
of 17 into 18, 27 (215 mg, 0.93 mmol) was oxidized under
Swern conditions oxalyl chloride (0.10 mL, 1.12 mmol),
DMSO (0.16 mL, 2.24 mmol), and Et3N (0.65 mL,
4.67 mmol)] to afford, after chromatography with hexane±
AcOEt (10:1), the crude aldehyde. A solution of the crude
aldehyde in THF (9.5 mL) was subsequently exposed to
lithium phenylacetylide, prepared from phenylacetylene
(0.15 mL, 1.40 mmol) and n-BuLi in hexane (1.23 M,
1.52 mL, 1.40 mmol) to afford, after chromatography with
hexane±AcOEt (10:1), 28 (167 mg, 54%) as a colorless oil
MS m/z (%) 330 (M1, 1.2), 271 (5), 243 (7), 157 (100), 141
1
(10), 115 (9), 73 (35); IR 3389 (OH) cm21; H NMR d
7.43±7.30 (5H, m, aromatic H), 4.61 91H, t, Jˆ5.9 Hz,
C40 ±H), 3.84±3.75 (2H, m, C5±H), 2.05±1.48 (10H, m,
CH2), 1.11, 1.10 (2H, AB-q, Jˆ14.7 Hz, TMSCH2), 0.04
(9H, s, TMS); HRMS calcd for C20H30O2Si 330.2015, found
330.2013.
6-Methylene-2-(20-phenylethynyl)oxonane (29). Accord-
ing to the procedure described for preparation of 19 from

C. Mukai et al. / Tetrahedron 56 (2000) 2203±2209
2209
18, 28 (23.8 mg, 0.72£1021 mmol) was treated with
Co2(CO)8 (27.1 mg, 0.79£1021 mmol) to give the cobalt
complex. To a solution of the cobalt complex in CH2Cl2
(0.7 mL) was added MsCl (0.06 mL, 0.72 mmol) and Et3N
(0.20 mL, 1.44 mmol). The reaction mixture was stirred at
room temperature for 10 min, washed with water and brine,
dried, and concentrated to dryness. Chromatography of the
residue with hexane±AcOEt (80:1) afforded 29 (9.0 mg,
52%) as a colorless oil; MS m/z (%) 240 (M1, 100), 197
(83), 181 (64), 141 (70), 128 (94), 115 (72), 97 (87), 91 (26);
1H NMR d 7.43±7.27 (5H, m, aromatic H), 4.99 (1H, d,
Jˆ1.5 Hz, ole®nic H), 4.87 (1H, d, Jˆ1.5 Hz, ole®nic H),
4.45 (1H, t, Jˆ5.8 Hz, C2±H), 3.81 (1H, ddd, Jˆ10.8, 7.3,
5.4 Hz, C9±H), 3.57 (1H, dt, Jˆ10.8, 5.4 Hz, C9±H), 2.29±
2.18 (4H, m, CH2), 1.97±1.71 (6H, m, CH2); 13C NMR d
149.22, 131.72, 128.18, 122.93, 112.74, 88.97, 84.30, 68.77,
63.87, 37.76, 31.52, 29.69, 28.83, 21.55; HRMS calcd for
C17H20O 240.1514, found 240.1518.
10. (a) Mukai, C.; Ikeda, Y.; Sugimoto, Y.; Hanaoka, M. Tetrahedron
Lett. 1994, 35, 2179. (b) Mukai, C.; Sugimoto, Y.; Ikeda, Y.;
Hanaoka, M. Tetrahedron Lett. 1994, 35, 2183. (c) Mukai, C.;
Sugimoto, Y.; Ikeda, Y.; Hanaoka, M. J. Chem. Soc., Chem. Commun.
1994, 1161. (d) Mukai, C.; Sugimoto, Y.; Ikeda, Y.; Hanaoka, M.
Tetrahedron 1998, 54, 823.
11. Mukai, C.; Sugimoto, Y.; Miyazawa, K.; Yamaguchi, S.;
Hanaoka, M. (This endo cyclization could be used for the stereo-
selective construction of the 3-hydroxy-2-substituted-piperidine
framework). J. Org. Chem. 1998, 63, 6281.
12. Mukai, C.; Yamaguchi, S.; Miyakoshi, N.; Sugimoto, Y.;
Kasamatsu, E.; Hanaoka, M. In preparation.
13. Mukai, C.; Yamaguchi, S.; Hanaoka, M. Unpublished data.
14. Colvin, E. W. Silicon in Organic Synthesis, Butterworths:
London, 1981.
15. Chakraborty, R.; Simpkins, N. S. Tetrahedron 1991, 47, 7689.
16. Mineral acids and organic acids were also used instead of a
Lewis acid. However, the formation of oxocanes could not be
detected in the reaction mixture.
17. The structure of 21 was determined by NMR spectral analyses.
The decoupling experiments between the C6-ole®nic proton and
C7-methylene protons as well as between C7- and C8-protons
enabled us to con®rm the depicted structure of 21.
References
1. (a) Rao, A. S.; Paknikar, S. K.; Kirtane, J. G. Tetrahedron 1983,
39, 2323. (b) Bovin, T. L. B. Tetrahedron 1987, 43, 3309. (c)
 Â
Alvarez, E.; Candenas, M.-L.; Perez, R.; Ravelo, J. L.; Martõn,
18. When the methyl and benzyl congeners 30 and 31 were
independently submitted to the reaction conditions described for
the transformation of 19 into 20, the corresponding oxocane
derivatives, 20 and 32, could not be detected in the reaction
mixture. These results can tentatively be interpreted in terms of
the lack of a cationic intermediate like 22. Therefore, it might be
concluded that the b-trimethylsilylmethyl group at the C-2 position
of the tetrahydrofuran ring is mandatory for conversion of 19 to 20.
The details of these results will be reported in the near future.
J. D. Chem. Rev. 1995, 95, 1953.
2. Hoberg, J. O. Tetrahedron 1998, 54, 12631 (and references
cited therein).
3. Rousseau, G.; Hosmi, F. Chem. Soc. Rev. 1997, 26, 453 (and
references cited therein).
4. (a) Moore, R. E. Marine Natural Products: Chemical and
Biological Perspectives; Scheuer, P. J., Ed.; Academic Press:
New York, 1978, Vol. 2. (b) Polyether Antibiotics: Naturally
Occurring Acid Ionophores; Westley, J. W., Ed.; Marcel Dekker:
New York, 1982. (c) Faulkner, D. J. Nat. Prod. Rep. 1986, 3, 1.
5. Faulker, D. J. Nat. Prod. Rep. 1996, 13, 75 (and references cited
therein).
6. Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734.
7. (a) Trost, B. M.; Tenaglia, A. Tetrahedron Lett. 1988, 29, 2927.
(b) Nicolaou, K. C.; Prasad, C. V. C.; Soners, P. K.; Hwang, C.-K.
J. Am. Chem. Soc. 1989, 111, 5330. (c) Nicolaou, K. C.; Prasad, C.
V. C.; Soners, P. K.; Hwang, C.-K. J. Am. Chem. Soc. 1989, 111,
5335. (d) Suzuki, T.; Sato, O.; Hirama, M. Tetrahedron Lett. 1990,
31, 4747. (e) Janda, K. D.; Shevlin, C. G.; Lerner, R. A. Science,
1993, 259, 490. (f) Na, J.; Houk, K. N.; Shevlin, C. G.; Janda, K.
D.; Lerner, R. A. J. Am. Chem. Soc. 1993, 115, 8453. (g) Fujiwara,
K.; Tokiwano, T.; Murai, A. Tetrahedron Lett. 1995, 36, 8063. (h)
Matsukura, H.; Morimoto, M.; Koshino, H.; Nakata, T. Tetrahedron
Lett. 1997, 38, 5545.
8. Nicholas, K. M. Acc. Chem. Res. 1987, 20, 207.
9. Mukai, C.; Hanaoka, M. Synlett 1996, 11 (and references cited
therein).