Sulfonyl-Stabilized Oxiranyllithium-Based Approach to Polycyclic Ethers. Convergent Synthesis of the ABCDEF-Ring System of Yessotoxin and Adriatoxin

Article abstract of DOI:10.1021/jo035145d

Convergent synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin, marine polycyclic ether toxins causative of diarrheic shellfish poisoning, has been accomplished. The A-ring fragment was constructed by coupling of an appropriately functionalized sulfonyl-stabilized oxiranyl anion and a triflate prepared from an erythritol derivative. An iterative protocol of the oxiranyl anion strategy was also applied for the construction of the DEF-ring fragment. The triflate derivatives of the A-ring and the DEF-ring fragments were connected with lithium acetylide. The resulting acetylene derivative was further transformed into the hexacyclic ABCDEF fragment via oxidation of the acetylene unit to 1,2-diketone, double methyl acetal formation, and reductive etherification.

Full text of DOI:10.1021/jo035145d

Su lfon yl-Sta bilized Oxir a n yllith iu m -Ba sed Ap p r oa ch to P olycyclic
Eth er s. Con ver gen t Syn th esis of th e ABCDEF -Rin g System of
Yessotoxin a n d Ad r ia toxin
Yuji Mori,*,† Kouichi Nogami,† Hiasafumi Hayashi,† and Ryoji Noyori‡,§
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, J apan, and
Department of Chemisrty, Graduate School of Science, Nagoya University, Chikusa-ku,
Nagoya 464-8602, J apan
mori@ccmfs.meijo-u.ac.jp
Received August 4, 2003
Convergent synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin, marine polycyclic
ether toxins causative of diarrheic shellfish poisoning, has been accomplished. The A-ring fragment
was constructed by coupling of an appropriately functionalized sulfonyl-stabilized oxiranyl anion
and a triflate prepared from an erythritol derivative. An iterative protocol of the oxiranyl anion
strategy was also applied for the construction of the DEF-ring fragment. The triflate derivatives of
the A-ring and the DEF-ring fragments were connected with lithium acetylide. The resulting
acetylene derivative was further transformed into the hexacyclic ABCDEF fragment via oxidation
of the acetylene unit to 1,2-diketone, double methyl acetal formation, and reductive etherification.
In tr od u ction
sulfoYTX,9 and carboxyYTX,10 has also been confirmed
from scallops and mussels. As these toxins showed potent
mouse lethality,11 contamination of bivalves by YTXs and
ATX poses a problem worldwide to human health,12 as
well as to the shellfish industry.
Yessotoxin (1, YTX) is a unique polycyclic ether isolated
as one of the causative toxins of diarrheic shellfish
poisoning from the digestive glands of scallops, Pati-
nopecten yessoensis, infested by toxic dinoflagellates in
J apan,1 and Protoceratium reticulatum was identified as
the biogenetic origin of YTX.2 The relative stereochem-
istry was assigned by extensive NOE studies3 and the
absolute configuration was determined by an NMR
method, using a chiral anisotropic reagent.4 Recently,
adriatoxin (2, ATX), a new analogue of YTX, was isolated
from the mussels, Mytilus galloprovincialis, which caused
diarrheic shellfish poisoning in Italy.5 Structurally, YTX
bears a triene side chain and two sulfate ester groups
on a trans-fused undecacyclic ether ring system. The
polycyclic skeleton of ATX is identical with that of the
A-J ring system of YTX but lacks the K-ring with a side
chain containing three olefinic bonds. The occurrence of
a wide variety of yessotoxin analogues, such as 45-
hydroxy-YTX,6 45,46,47-trinorYTX,7 homoYTX,8 1-de-
Their impressive molecular architectures and biological
activities have made them challenging synthetic targets,
and efforts toward the synthesis of polycyclic ether
frameworks of YTX and ATX have been reported by us13
and by Nakata.14 Recently, we have demonstrated an
iterative linear synthesis of the ABCDEF-ring system by
repeated coupling of sulfonyl-substituted oxiranes as
building blocks.15 Although the synthesis is conceptually
very simple and efficient, the lengthy approach prompted
us to pursue an alternative convergent approach to the
ABCDEF-ring system. In this paper, we describe full
details of a convergent synthesis of the ABCDEF frag-
ment 3 of YTX and ATX, taking advantage of the rapid
assembly of two stereochemically advanced fragments.
(8) Satake, M.; Tubaro, A.; Lee, J . S.; Yasumoto, T. Nat. Toxins 1997,
5, 107-110.
† Meijo University.
(9) Daiguji, M.; Satake, M.; Ramstad, H.; Aune, T.; Naoki, H.;
Yasumoto T. Nat. Toxins 1998, 6, 235-239.
‡ Nagoya University.
§ Visiting Professor of Meijo University.
(10) Ciminiello, P.; Fattorusso, E.; Forino, M.; Poletti, R.; Viviani,
R. J . Org. Chem. 2000, 64, 1761-1763.
(1) (a) Murata, M.; Kumagai, M.; Lee, J . S.; Yasumoto, T. Tetrahe-
dron Lett. 1987, 28, 5869-5872. (b) Naoki, H.; Murata, M.; Yasumoto,
T. Rapid Commun. Mass Spectrum. 1993, 7, 179-182.
(2) Satake, M.; MacKenzie, L.; Yasumoto, T. Nat. Toxins 1997, 5,
164-167.
(3) Satake, M.; Terasawa, K.; Kadowaki, Y.; Yasumoto, T. Tetrahe-
dron Lett. 1996, 37, 5955-5958.
(4) Takahashi, H.; Kusumi, T.; Kan, Y.; Satake, M.; Yasumoto, T.
Tetrahedron Lett. 1996, 37, 7087-7090.
(5) Ciminiello, P.; Fattorusso, E.; Forino, M.; Magno, S.; Poletti, R.;
Viviani, R. Tetrahedron Lett. 1998, 39, 8897-8900.
(6) Morohashi, A.; Satake, M.; Oshima, Y.; Yasumoto, T. Biosci.
Biotechnol. Biochem. 2000, 64, 1761-1763.
(7) Satake, M.; Ichimura, T.; Sekiguchi, K.; Oshima, Y. Nat. Toxins
1999, 7, 147-150.
(11) (a) Aune, T.; Sorby, R.; Yasumoto, T.; Ramstad, H.; Landsverk,
T. Toxicon 2002, 40, 77-82. (b) Ogino, H.; Kumagai, M.; Yasumoto, T.
Nat. Toxins 1997, 5, 255-259. (c) Terao, K.; Ito, E.; Oarada, M.;
Murata, M.; Yasumoto, T. Toxicon 1990, 28, 1095-1104.
(12) (a) Ramstad, H.; Hovgaard, P.; Yasumoto, T.; Larsen, S.; Aune,
T. Toxicon 2001, 39, 1035-1043. (b) Draisci, R.; Ferretti, E.; Palleschi,
L.; Marchiafava, C.; Poletti, R.; Milandri, A.; Ceredi, A.; Pompei, M.
Toxicon 1999, 37, 1187-1193. (c) Ciminiello, P.; Fattorusso, E.; Forino,
M.; Magno, S.; Poletti, R.; Satake, M.; Viviani, R.; Yasumoto, T. Toxicon
1997, 35, 177-183.
(13) Mori, Y.; Hayashi, H. Tetrahedron 2002, 58, 1789-1797.
(14) Suzuki, K.; Nakata, T. Org. Lett. 2002, 4, 3943-3946.
(15) Mori, Y.; Takase, T.; Noyori, R. Tetrahedron Lett. 2003, 44,
2319-2322.
10.1021/jo035145d CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/22/2003
9050
J . Org. Chem. 2003, 68, 9050-9060

Convergent Synthesis of Polycyclic Ethers
F IGURE 1. Structures of yessotoxin and adriatoxin.
F IGURE 2. Retrosynthetic analysis of the ABCDEF-ring fragment of yessotoxin and adriatoxin.
The strategy for the synthesis of 3 is shown in Figure 2,
which involves the assembling of the A-ring fragment 5
and the DEF-ring fragment 6 with acetylene to alkyne
4. The conversion of 4 to 3 requires (i) oxidation of a triple
bond to a 1,2-diketone, (ii) double acetal-ring formation,
and (iii) reductive etherification of the acetal rings. This
idea of a convergent approach has been reported inde-
pendently by three groups, including our laboratory, at
almost the same time.16-18 In turn, fragments 5 and 6
could be prepared by an oxirany anion strategy developed
in our laboratory19 with use of appropriately functional-
ized epoxy sulfones 7, 9, 10, and 11 and triflate 8, in
which alkylation of a sulfonyl-stabilized oxiranyl anion
and the subsequent 6-endo cyclization of a hydroxy
epoxide are employed as key reactions.
Resu lts a n d Discu ssion
Syn th esis of th e A-Rin g F r a gm en t. Synthesis of the
A-ring started from the coupling reaction of the oxiranyl
anion generated from epoxy sulfone 7 and triflate 8
(Scheme 1). The chiral trisubstituted epoxy sulfone 7 was
synthesized from (R)-(-)-1-chloromethyl p-tolyl sulfoxide
and 4-benzyloxybutan-2-one according to the reported
procedure,20 and triflate 8 was prepared from the 1,3-O-
di-tert-butylsilylene-D-erythritol derivative.21 Alkylation
of the oxiranyl anion generated from 7 with 8 was carried
out by an internal quenching method to prevent decom-
position of the unstable oxiranyl anion.22 Thus, treatment
of a mixture of 7 and 8 with n-BuLi in THF in the
presence of HMPA at -100 °C gave epoxy sulfone 12 in
81% yield. Cyclization proceeded smoothly when 12 was
(16) Mori, Y.; Mitsuoka, S.; Furukawa, H. Tetrahedron Lett. 2000,
41, 4161-4164.
(20) (a) Satoh, T.; Oohara, T.; Ueda, Y.; Yamakawa, K. J . Org. Chem.
1989, 54, 3130-3136. (b) Mori, Y.; Yaegashi, K.; Furukawa, H. J . Org.
Chem. 1998, 63, 6200-6209.
(21) Mori, Y.; Hayashi, H. J . Org. Chem. 2001, 66, 8666-8668.
(22) (a) Ashwell, M.; Clegg, W.; J ackson, R. F. W. J . Chem. Soc.,
Perkin Trans. 1 1991, 897-908. (b) Mori, Y.; Yaegashi, K.; Iwase, K.;
Yamamori, Y.; Furukawa, H. Tetrahedron Lett. 1996, 37, 2605-2608.
(17) Fujiwara, K.; Morishita, H.; Saka, K.; Murai, A. Tetrahedron
Lett. 2000, 41, 507-508.
(18) Matsuo, G.; Hinou, H.; Koshino, H.; Suenaga, T.; Nakata, T.
Tetrahedron Lett. 2000, 41, 903-906.
(19) Mori, Y.; Yaegashi, K.; Furukawa, H. J . Am. Chem. Soc. 1996,
118, 8158-8159.
J . Org. Chem, Vol. 68, No. 23, 2003 9051

Mori et al.
SCHEME 1a
F IGURE 3. NOE correlation of 13.
was critical because elevated temperatures induced a 1,2-
sulfonyl shift of the epoxy sulfone moiety,23 rather than
6-endo cyclization, to give the corresponding R-sulfonyl
ketone as a byproduct. The stereochemistry of 13 was
established by NOE experiments as shown in Figure 3.
Stereoselective reduction with NaBH4 at -78 °C gave an
equatorial alcohol as the sole product, and the subsequent
O-benzylation with benzyl bromide and KHMDS in THF
and deprotection of the silylene group with TBAF gave
the A-ring diol 14. A one-pot double protection of 14 was
effected by selective triflation of the primary alcohol with
1 equiv of triflic anhydride followed by silylation of the
secondary alcohol with TBSOTf, affording 5 in 88% yield.
Reaction of triflate 5 with lithium trimethylsilylacetylide
in THF at -78 °C in the presence of HMPA and removal
of the TMS group with K2CO3 in MeOH provided the
A-ring acetylene 15 in 91% overall yield.
a
Conditions: (a) n-BuLi, THF, HMPA, -100 °C, 81%; (b)
Syn th esis of th e DEF -Rin g F r a gm en t. Synthesis
of the other coupling partner 6 started from the readily
available diol 1621 as shown in Scheme 2. Diol 16 was
transformed into triflate 17 by regioselective O-triflation
and O-silylation by a one-pot procedure. The coupling
reaction of triflate 17 and the oxiranyllithium generated
from 1024 in THF-HMPA at -100 °C by an in situ
quenching method afforded epoxy sulfone 18 in 89% yield.
Deprotection of the triethylsilyl group of 18 and 6-endo
cyclization of the resulting epoxy alcohol were carried out
by heating 18 with TsOH‚H2O in CHCl3 at 55 °C to give
ketone 19 in 82% yield. In contrast to the case of 12,
heating was necessary to induce 6-endo cyclization
because the oxirane ring of 18 is less reactive than that
of 12, which is activated by the presence of a methyl
group.25 Fortunately, the 1,2-migration of the sulfonyl
group was not observed in this case. The oxepane
formation was accomplished by one-carbon homologation
of a keto tetrahydropyran. Thus, 19 was treated with
trimethylsilyldiazomethane24,26 in the presence of BF3‚
OEt2 at -78 °C and the resulting â-keto silane was
subjected to protonolysis with PPTS in MeOH, affording
the seven-membered ketone 20 in 60% yield along with
its regioisomeric ketone 21 in 3% yield and epoxide 22
in 18% yield. The stereochemistry of the spiro-epoxide
22 was established by NOE experiments (Figure 4).
To construct a tertiary alcohol on the E-ring, direct
methylation of 20 with MeMgBr, MeLi, and Me3Al was
first examined. However, the major product was a
TsOH‚H2O, CHCl3, 0 °C, 93%; (c) (i) NaBH4, MeOH-CH2Cl2, -78
°C, 99%; (ii) KHMDS, BnBr, THF, rt, 100%; (iii) TBAF, THF, rt,
100%; (d) Tf2O, 2,6-lutidine, CH2Cl2, -78 °C, 30 min, then TBSOTf,
88%; (e) (i) TMS-acetylene, n-BuLi, THF, HMPA, -78 °C, 95%,
(ii) K2CO3, MeOH, rt, 96%.
SCHEME 2a
a
Conditions: (a) Tf2O, 2,6-lutidine, THF, -78 °C, 30 min, then
TESOTf, 82%; (b) n-BuLi, THF, HMPA, -100 °C, 89%; (c)
TsOH‚H2O, CHCl3, 55 °C, 82%; (d) (i) Me3SiCHN2, BF3‚OEt2,
CH2Cl2, -78 °C; (ii) PPTS, MeOH, rt, 60% for 20, 3% for 21, 18%
for 22.
(23) (a) Durst, T.; Tin, K.-C. Tetrahedron Lett. 1970, 2369-2372.
(b) Tavares, D. F.; Estep, R. E.; Blezard, M. Tetrahedron Lett. 1970,
2373-2376. (c) Durst, T.; Tin, K.-C.; De Reinach-Hirtzbach, F.;
Decesare, J . M. Can. J . Chem. 1979, 57, 258-266.
(24) Mori, Y.; Yaegashi, K.; Furukawa, H. Tetrahedron 1997, 53,
12917-12932. Epoxy sulfone 10 was prepared from (R)-O-isopropy-
lideneglyceraldehyde.
(25) Mori, Y.; Furuta, H.; Takase, T.; Mitsuoka, S.; Furukawa, H.
Tetrahedron Lett. 1999, 40, 8019-8022.
(26) (a) Hashimoto, N.; Aoyama, T.; Shioiri, T. Tetrahedron Lett.
1980, 21, 4619-4622.
exposed to TsOH‚H2O in CHCl3 at 0 °C. Under these
conditions, detriethylsilylation and the subsequent ste-
reospecific 6-endo cyclization of the resulting 4,5-epoxy
alcohol led to the formation of ketone 13 in 93% yield.
The reaction temperature of the 6-endo cyclization of 12
9052 J . Org. Chem., Vol. 68, No. 23, 2003

Convergent Synthesis of Polycyclic Ethers
SCHEME 3a
F IGURE 4. NOE correlation of 22.
compound methylated undesirably from the less-hindered
R-side. Then, stereocontrolled installation of a methyl
group in this seven-membered ketone was accomplished
via a spiro-epoxide intermediate in a stepwise manner
(Scheme 3). Olefination of 20 with methylenetriphen-
ylphosphorane in THF gave olefin 23. Epoxidation with
m-CPBA in toluene resulted in the formation of a 3:1
mixture of diastereomers and the desired R-epoxide 24
was obtained as a major product in 65% yield. To improve
the diastereoselectivity, epoxidation with dioxiranes27
was then examined. The dioxirane-mediated epoxidation
is known to proceed through a spiro transition state28
and, therefore, is more sensitive to the steric environment
than other epoxidizing reagents such as m-CPBA. In the
event, substantial improvement of the diastereomeric
ratio was observed when the epoxidation was carried out
with the phenyl(trifluoromethyl)dioxirane generated in
situ from trifluoroacetophenone-Oxone29 in MeCN-CH2-
Cl2-H2O. This procedure gave a 9:1 mixture of products,
but the desired R-epoxide 24 was isolated only in 52%
yield. The moderate yield was due to an unexpected
partial cleavage of the benzyl group of the primary or
secondary alcohol (35% combined yield). Subsequent
reduction of the epoxide with lithium triethylborohydride
gave a tertiary alcohol 25 with the correct stereochem-
istry. Removal of the TBDPS group with TBAF produced
diol 26, which was converted into triflate 27 by O-
triflation and O-silylation in one pot.
a
Conditions: (a) Ph3P+CH3Br-, KHMDS, THF, -78 to 0 °C,
91%; (b) m-CPBA, NaHCO3, toluene, 65%; (c) LiBHEt3, THF, 0
°C, 96%; (d) TBAF, THF, rt, 100%; (e) Tf2O, 2,6-lutidine, THF,
-78 °C, 30 min, then TMSOTf, 99%.
of 30 was confirmed at this stage by NOE experiments,
in which 6% of NOE was observed between the two
methyl groups. The TBDPS ether in 30 was cleaved with
TBAF and the resulting diol was protected with 2,2-
dimethoxypropane to form acetonide 31. For the synthe-
sis of key fragment 6, the two benzyl groups were
removed by hydrogenolysis with Pd(OH)2/C in THF to
give diol 32, which was then converted into the TBS-
protected triflate 6 by regioselective O-triflation of the
primary alcohol and O-tert-butyldimethylsilylation of the
secondary alcohol with TBSOTf in one pot.
Construction of the F-ring is a challenging synthetic
issue because it contains sterically congested 1,3-diaxial
methyl groups adjacent to the ring oxygen, and requires
the assembly of 27 and the methyl-substituted epoxy
sulfone 11 (Scheme 4). This chiral epoxy sulfone was
prepared from 1-tert-butyldiphenylsilyloxy-propan-2-one
and (S)-(+)-1-chloromethyl p-tolyl sulfoxide according to
the reported procedure.20 The coupling reaction was
performed by adding n-BuLi to a solution of triflate 27
and epoxy sulfone 11 in THF-HMPA at -100 °C, pro-
viding 28 in 90% yield. Stereocontrolled 6-endo cycliza-
tion was successfully achieved with the method previ-
ously reported from our laboratory.25 Treatment of 28
with BF3‚OEt2 at room temperature effected the F-ring
formation to afford the tricyclic ketone 29 in 90% yield
as a single isomer. Reduction of the ketone with NaBH4
in methanol-dichloromethane gave alcohol 30 as the sole
product. The stereochemistry of the diaxial methyl groups
Syn th esis of th e ABCDEF -Rin g. Convergent syn-
thesis of the target molecule 3 is shown in Scheme 5.
Treatment of a mixture of triflate 6 and acetylene 15 in
THF at -78 °C with n-BuLi afforded the disubstituted
acetylene 4 in 80% yield. Direct oxidation of the acetylene
to the corresponding 1,2-diketone was achieved according
to the reported procedure.30 Thus, treatment of 4 with
RuO2-NaIO4 provided a yellow diketone 33 in 80% yield.
Heating of the diketone with CSA in methanol and
trimethyl orthoformate at 80 °C led to desilylation,
intramolecular double acetalization, and removal of the
acetonide group, giving the hexacyclic diol 34 as a major
product along with two other stereoisomers of the meth-
oxy groups in 87% yield (8:1:1 ratio). Finally, reduction
of the acetal mixture with Et3SiH in the presence of
TMSOTf at 0 °C completed the synthesis of the ABCDEF
fragment 3 in 70% yield, which was identical with the
1
sample synthesized by the iterative linear route15 by H
NMR, 13C NMR, and IR analysis.
(27) Adam, W.; Saha-Moller, C. R.; Ganeshpure, P. A. Chem. Rev.
2001, 101, 3499-3548.
(28) (a) Baumstark, A. L.; McCloskey, C. J . Tetrahedron Lett. 1987,
28, 3311-3314. (b) Baumstark, A. L.; Vasquez, P. C. J . Org. Chem.
1988, 53, 3437-3439. (c) Houk, K. N.; Liu, J .; DeMello, N. C.;
Condroski, K. R. J . Am. Chem. Soc. 1997, 119, 10147-10152. (d)
J enson, C.; Liu, J .; Houk, K. N.; J orgensen, W. L. J . Am. Chem. Soc.
1997, 119, 12982-15983.
Con clu sion
In summary, a rapid entry to the construction of the
ABCDEF-ring of yessotoxin and adriatoxin has been
(29) Boehlow, T. R.; Buxton, C.; Grocock, E. L.; Marples, B. A.;
Waddington, V. L. Tetrahedron Lett. 1998, 39, 1839-1842.
(30) Zibuck, R.; Seebach, D. Helv. Chim. Acta 1988, 71, 237-240.
J . Org. Chem, Vol. 68, No. 23, 2003 9053

Mori et al.
SCHEME 4a
a
Conditions: (a) n-BuLi, THF, HMPA, -100 °C, 90%; (b) BF3‚OEt2, CH2Cl2, rt, 90%; (c) NaBH4, MeOH-CH2Cl2, 0 °C, 98%; (d) TBAF,
THF, rt, 100%; (e) Me2C(OMe)2, PPTS, THF, reflux, 98%; (f) H2, Pd(OH)2/C, THF, rt, 97%; (g) Tf2O, 2,6-lutidine, THF, -78 °C, 30 min,
then TBSOTf, 96%.
SCHEME 5a
a
Conditions: (a) n-BuLi, THF, HMPA, -78 °C, 80%; (b) RuO2‚H2O, NaIO4, CCl4-MeCN-H2O, rt, 80%; (c) CSA, MeOH, CH(OMe)3, 80
°C, 87% (34 + two isomers); (d) Et3SiH, TMSOTf, CH2Cl2, 0 °C, 70%.
achieved through the connection of two fragments, pre-
pared by the oxiranyl anion strategy, by an acetylene unit
and a subsequent oxidation-double acetalization proto-
col. The convergent synthesis of 3 features 21 steps of
the longest linear sequence from 16, which was prepared
from 1,3-O-di-tert-butylsilylene-L-erythritol in eight steps,
whereas the iterative linear approach of 3 from 1,3-O-
di-tert-butylsilylene-D-erythritol required 35 steps.15 The
present study constitutes an important contribution to
the development of efficient and scalable approaches to
yessotoxin and its analogues. Further studies are ongoing
in our laboratory to synthesize natural toxins.
Exp er im en ta l Section
(2S,3R)-2-(2-Ben zyloxyet h yl)-2-m et h yl-3-(t olu en e-4-
su lfon yl)-oxir a n e (7). Compound 7 was prepared from (-)-
(R)-1-chloromethyl p-tolyl sulfoxide and 4-benzyloxybutan-2-
one according to the reported procedure.20 Colorless oil: [R]25
D
+96.4 (c 1.0, CHCl3); IR (CHCl3) 1495, 1454, 1221, 1211, 1088
1
cm-1; H NMR (400 MHz, CDCl3) δ 1.44 (3H, s), 2.46 (3H, s),
2.50 (2H, t, J ) 6.3 Hz), 3.76 (1H, s), 3.78 (2H, ddd, J ) 6.3,
6.3, 2.0 Hz), 4.56 (2H, s), 7.26-7.84 (9H, Ar); 13C NMR (100
MHz, CDCl3) δ 21.7, 23.5, 31.9, 66.7, 72.9, 74.5, 127.6, 127.7,
128.3, 128.4, 130.0, 145.4; FABMS m/z 347 (MH+).
(4R,5S)-4-[(2S,3R)-3-(2-Ben zyloxyeth yl)-3-m eth yl-2-(tolu -
en e-4-su lfon yl)-oxir a n ylm et h yl]-2,2-d i-ter t-b u t yl-5-(t r i-
9054 J . Org. Chem., Vol. 68, No. 23, 2003

Convergent Synthesis of Polycyclic Ethers
eth ylsilyloxy)-[1,3,2]d ioxa silin a n e (12). To a stirred solu-
tion of epoxy sulfone 7 (5.13 g, 14.852 mmol) and triflate 8
(5.03 g, 9.902 mmol) in HMPA (5.17 mL, 29.705 mmol) and
THF (66 mL) at -100 °C was added n-BuLi (9.52 mL of a 1.56
M solution in hexane, 14.852 mmol) dropwise. After the
solution was stirred at -100 °C for 30 min, the reaction was
quenched with saturated aqueous NH4Cl. The reaction mixture
was warmed to room temperature and extracted with EtOAc.
The extract was washed with water and brine, dried, and
concentrated in vacuo. Purification by flash chromatography
(7f10% EtOAc in hexane) gave 12 (5.63 g, 81%) as a colorless
M solution in toluene, 12.202 mmol), and the reaction mixture
was stirred for 5 min. Benzyl bromide (1.09 mL, 9.151 mmol)
was then added and the mixture was stirred at 0 °C for 30
min. The reaction was quenched with aqueous saturated NH4-
Cl and the mixture was extracted with EtOAc. The extract
was washed with water and brine, dried, and concentrated.
Purification by flash chromatography (8% Et2O in hexane)
gave a dibenzyl ether (3.20 g, 100%) as a colorless oil. [R]25
D
+29.6 (c 0.82, CHCl3); IR (CHCl3) 1473, 1365, 1090, 827 cm-1
;
1H NMR (400 MHz, CDCl3) δ 0.99 (9H, s), 1.04 (9H, s), 1.24
(3H, s), 1.60 (1H, q, J ) 11.7 Hz), 1.88 (1H, ddd, J ) 14.2, 6.8,
6.8 Hz), 2.00 (1H, ddd, J ) 14.2, 7.3, 7.3 Hz), 2.43 (1H, ddd, J
) 12.2, 4.4, 4.4 Hz), 3.39 (1H, dd, J ) 12.7, 4.9 Hz), 3.48 (1H,
ddd, J ) 9.8, 9.8, 4.9 Hz), 3.56 (2H, t, J ) 6.8 Hz), 3.64 (1H,
ddd, J ) 11.2, 9.8, 4.4 Hz), 3.71 (1H, t, J ) 9.8 Hz), 4.00 (1H,
dd, J ) 9.8, 4.4 Hz), 4.41 and 4.61 (each 1H, d, J ) 11.7 Hz),
4.43 and 4.46 (each 1H, d, J ) 12.2 Hz), 7.27-7.35 (10H, Ar);
13C NMR (100 MHz, CDCl3) δ 16.4, 19.9, 27.1 (3 × C), 27.5 (3
× C), 33.6, 39.6, 62.8, 67.7, 70.0, 70.9, 72.9, 73.2, 78.0, 127.4,
127.5, 127.6, 128.30, 138.34, 138.4; HRFABMS calcd for
oil. [R]24 +70.5 (c 0.96, CHCl3); IR (CHCl3) 1599, 1473, 1304,
D
1
1103 cm-1; H NMR (400 MHz, CDCl3) δ 0.62 (6H, q, J ) 7.8
Hz), 0.92 (9H, s), 0.95 (9H, s), 0.98 (9H, t, J ) 7.8 Hz), 1.53
(3H, s), 2.02 (1H, dd, J ) 15.6, 9.8 Hz), 2.42 (3H, s), 2.56 (1H,
ddd, J ) 14.2, 6.8, 6.8 Hz), 2.62 (1H, ddd, J ) 14.2, 6.3, 6.3
Hz), 2.74 (1H, d, J ) 15.6 Hz), 3.23 (1H, t, J ) 8.3 Hz), 3.28
(1H, ddd, J ) 9.8, 9.8, 3.9 Hz), 3.34 (1H, t, J ) 9.8 Hz), 3.74
(1H, ddd, J ) 9.8, 6.3, 6.3 Hz), 3.80 (1H, ddd, J ) 9.8, 6.3, 6.3
Hz), 3.87 (1H, dd, J ) 9.8, 3.9 Hz), 4.54 (2H, s), 7.26-7.79
(9H, Ar); 13C NMR (100 MHz, CDCl3) δ 4.9 (3 × C), 6.8 (3 ×
C), 19.7, 21.6, 22.1, 22.6, 26.9 (3 × C), 27.4 (3 × C), 31.3, 33.4,
67.7, 68.4, 69.4, 70.9, 72.8, 75.7, 80.1, 127.4, 127.6, 128.3, 129.5,
129.6, 135.9, 138.6, 144.5; HRFABMS calcd for C37H61O7SSi2
(MH+) 705.3673, found 705.3689.
C
31H47O5Si2 (MH+) 527.3190, found 527.3184.
(iii) To a stirred solution of the dibenzyl ether (3.55 g, 6.749
mmol) in THF (44 mL) was added TBAF (16.9 mL of a 1.0 M
solution in THF, 16.90 mmol), and the mixture was stirred at
room temperature for 18 h. The reaction mixture was concen-
trated in vacuo and the residue was purified by flash chro-
matography (80% EtOAc in hexane) to give diol 14 (2.61 g,
100%) as a colorless oil. [R]25D +17.7 (c 0.89, CHCl3); IR (CHCl3)
3597, 3423, 1496, 1367, 1111, 1051 cm-1; 1H NMR (400 MHz,
CDCl3) δ 1.22 (3H, s), 1.57 (1H, q, J ) 11.7 Hz), 1.59 (1H, br,
OH), 1.89 (1H, ddd, J ) 13.9, 7.1, 7.1 Hz), 2.03 (1H, ddd, J )
13.9, 6.8, 6.8 Hz), 2.04 (1H, br, OH), 2.32 (1H, ddd, J ) 12.0,
4.9, 4.9 Hz), 3.35 (1H, dd, J ) 11.7, 4.4 Hz), 3.37 (1H, ddd, J
) 10.5, 10.5, 4.4 Hz), 3.52 (1H, ddd, J ) 11.5, 10.5, 4.9 Hz),
3.56 (1H, t, J ) 6.8 Hz), 3.68 (1H, dd, J ) 11.2, 4.9 Hz), 3.73
(1H, dd, J ) 11.2, 4.2 Hz), 4.43 and 4.59 (each 1H, d, J ) 11.7
Hz), 4.45 (2H, s), 7.27-7.34 (10H, Ar); 13C NMR (100 MHz,
CDCl3) δ 16.2, 33.4, 39.5, 63.4, 65.8, 67.0, 71.0, 71.1, 77.7,
127.5, 127.6, 127.7, 128.33, 138.34, 138.4; HRFABMS calcd
for C23H31O5 (MH+) 387.2169, found 387.2166.
(4a S,6R,8a R)-6-(2-Ben zyloxyeth yl)-2,2-d i-ter t-bu tyl-6-
m et h yl-d eca h yd r o-1,3,5-t r ioxa -2-sila -n a p h t h a len -7-on e
(13). A solution of 12 (5.63 g, 7.997 mmol) and TsOH‚H2O (2.28
g, 12.00 mmol) in CHCl3 (80 mL) was stirred at 0 °C for 23 h.
The reaction mixture was diluted with EtOAc and washed
successively with saturated aqueous NaHCO3, water, and
brine. The organic layer was dried and concentrated in vacuo.
Purification by flash chromatography (12% Et2O in hexane)
gave ketone 13 (3.22 g, 93%) as a colorless oil. [R]25 -69.2 (c
D
1.0, CHCl3); IR (CHCl3) 1716, 1473, 1365, 1097, 827 cm-1; 1H
NMR (400 MHz, CDCl3) δ 0.99 (9H, s), 1.03 (9H, s), 1.32 (3H,
s), 1.71 (1H, ddd, J ) 14.2, 5.4, 3.4 Hz), 2.31 (1H, dd, J ) 18.1,
10.7 Hz), 2.43 (1H, ddd, J ) 14.2, 9.3, 6.3 Hz), 2.83 (1H, dd, J
) 18.1, 6.3 Hz), 3.44 (1H, ddd, J ) 9.3, 6.3, 3.4 Hz), 3.61 (1H,
ddd, J ) 9.3, 9.3, 5.4 Hz), 3.66 (1H, ddd, J ) 9.8, 9.8, 4.9 Hz),
3.86 (1H, t, J ) 10.3 Hz), 4.02 (1H, ddd, J ) 10.7, 9.8, 6.3 Hz),
4.16 (1H, dd, J ) 10.3, 4.9 Hz), 4.34 and 4.44 (each 1H, d, J )
11.7 Hz), 7.24-7.35 (5H, Ar); 13C NMR (100 MHz, CDCl3) δ
19.8, 22.6, 22.9, 27.0 (3 × C), 27.4 (3 × C), 38.6, 45.6, 65.2,
67.2, 70.1, 71.8, 72.7, 81.7, 127.5, 127.5, 128.3, 138.1, 209.3;
Tr iflu or om eth a n esu lfon ic Acid (2S,3R,5S,6R)-5-Ben z-
yloxy-6-(2-benzyloxyethyl)-3-(tert-butyldimethylsilyloxy)-6-
m eth yl-tetr a h yd r op yr a n -2-ylm eth yl Ester (5). To a stirred
solution of 14 (1.28 g, 3.316 mmol) in CH2Cl2 (17 mL) and 2,6-
lutidine (1.53 mL, 13.264 mmol) at -78 °C was added Tf2O
(0.57 mL, 3.382 mmol). After the solution was stirred at -78
°C for 30 min, TBSOTf (1.14 mL, 4.749 mmol) was added and
the reaction mixture was stirred for 45 min. The reaction was
quenched with saturated aqueous NaHCO3 and the mixture
was extracted with EtOAc. The extract was washed with water
and brine, dried, and concentrated in vacuo. Purification by
flash chromatography (6% EtOAc in hexane) gave triflate 5
HRFABMS calcd for
435.2582.
C
24H39O5Si (MH+) 435.2564, found
(2S,3R,5S,6R)-5-Ben zyloxy-6-(2-ben zyloxyeth yl)-2-h y-
d r oxym eth yl-6-m eth yl-tetr a h yd r op yr a n -3-ol (14). (i) To
a stirred solution of 13 (3.22 g, 7.419 mmol) in CH2Cl2 (18 mL)
and MeOH (18 mL) at -78 °C was added NaBH4 (418 mg,
11.060 mmol), and the reaction mixture was stirred at -78
°C for 1 h. The reaction mixture was poured into water and
extracted with EtOAc. The extract was washed with water and
brine, dried, and concentrated. Purification by flash chroma-
tography (14% EtOAc in hexane) gave an alcohol (3.21 g, 99%)
as a colorless oil. [R]25D -6.75 (c 1.2, CHCl3); IR (CHCl3) 3390,
1473, 1363, 1078, 824 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.99
(9H, s), 1.04 (9H, s), 1.20 (3H, s), 1.59 (1H, q, J ) 11.2 Hz),
1.78 (1H, ddd, J ) 15.1, 4.4, 4.4 Hz), 1.87 (1H, ddd, J ) 15.1,
6.3, 6.3 Hz), 2.20 (1H, ddd, J ) 12.2, 4.9, 4.9 Hz), 3.48 (1H,
ddd, J ) 9.6, 9.6, 4.9 Hz), 3.56 (1H, ddd, J ) 12.2, 4.4, 4.4
Hz), 3.59 (2H, dd, J ) 6.3, 4.4 Hz), 3.69 (1H, ddd, J ) 11.2,
9.3, 4.4 Hz), 3.73 (1H, t, J ) 10.3 Hz), 3.95 (1H, d, J ) 3.4 Hz,
OH), 4.01 (1H, dd, J ) 10.3, 4.9 Hz), 4.51 and 4.54 (each 1H,
d, J ) 11.7 Hz), 7.28-7.38 (5H, Ar); 13C NMR (100 MHz,
CDCl3) δ 14.6, 19.9, 22.6, 27.1 (3 × C), 27.5 (3 × C), 36.3, 41.8,
60.1, 67.8, 70.0, 70.8, 73.4, 73.6, 77.6, 127.9, 128.6, 137.1;
1
(1.84 g, 88%) as a pale yellow oil. H NMR (400 MHz, CDCl3)
δ 0.06 (6H, s), 0.88 (9H, s), 1.24 (3H, s), 1.56 (1H, q, J ) 11.7
Hz), 1.96 (1H, ddd, J ) 13.9, 13.9, 6.6 Hz), 2.03 (1H, ddd, J )
13.9, 7.8, 5.9 Hz), 2.13 (1H, ddd, J ) 12.1, 4.8, 4.8 Hz), 3.39
(1H, dd, J ) 11.7, 4.8 Hz), 3.44 (1H, ddd, J ) 11.0, 9.5, 4.8
Hz), 3.54 (1H, ddd, J ) 9.5, 4.8, 2.2 Hz), 3.62 (1H, ddd, J )
9.5, 7.7, 5.9 Hz), 3.66 (1H, ddd, J ) 9.5, 7.7, 6.6 Hz), 4.47 and
4.50 (each 1H, d, J ) 11.7 Hz), 4.50 (1H, t, J ) 10.6 Hz), 4.51
and 4.55 (each 1H, d, J ) 11.7 Hz), 4.63 (1H, dd, J ) 10.6, 1.8
Hz), 7.25-7.36 (10H, Ar); FABMS m/z 633 (MH+).
(2S,3R,5S,6R)-5-Ben zyloxy-6-(2-ben zyloxyeth yl)-3-ter t-
bu tyld im eth ylsilyloxy-6-m eth yl-2-(p r op -2-yn yl)-tetr a h y-
d r op yr a n (15). (i) To a stirred solution of trimethylsilylacet-
ylene (1.19 mL, 8.402 mmol) in THF (9 mL) at 0 °C was added
n-BuLi (5.39 mL of a 1.56 M solution in hexane, 8.402 mmol).
After being stirred at 0 °C for 30 min, the solution was cooled
to -78 °C and a solution of 5 (1.77 g, 2.801 mmol) in HMPA
(1.46 mL, 8.402 mmol) and THF (3 mL) was added. After the
solution was stirred at -78 °C for 45 min, the reaction was
quenched with saturated aqueous NH4Cl and the mixture was
HRFABMS calcd for
437.2724.
C
24H41O5Si (MH+) 437.2721, found
(ii) To a stirred solution of the alcohol (2.26 g, 6.101 mmol)
in THF (30 mL) at 0 °C was added KHMDS (18.2 mL of a 0.67
J . Org. Chem, Vol. 68, No. 23, 2003 9055

Mori et al.
extracted with EtOAc. The extract was washed with water and
brine, dried, and concentrated in vacuo. Purification by flash
chromatography (5% EtOAc in hexane) gave TMS-acetylene
(1.66 mL, 7.480 mmol), and 2,6-lutidine (2.3 mL, 19.952 mmol)
in CH2Cl2 (18 mL). Purification by flash chromatography (7%
EtOAc in hexane) gave triflate 17 (2.47 g, 82%) as a pale yellow
oil. A solution of triflate 17 (2.47 g, 4.093 mmol) and epoxy
sulfone 10 (2.77 g, 6.139 mmol) in HMPA (2.14 mL, 12.280
mmol) and THF (41 mL) was cooled to -100 °C, and n-BuLi
(3.89 mL of a 1.58 M solution in hexane, 6.146 mmol) was
added dropwise. After the solution was stirred at -100 °C for
45 min, the reaction was quenched with saturated aqueous
NH4Cl. The reaction mixture was warmed to room tempera-
ture and extracted with EtOAc. The extract was washed with
water and brine, dried, and concentrated in vacuo. Purification
by flash chromatography (20% EtOAc in hexane) gave 18 (3.29
g, 89%) as a colorless oil. [R]20D -26.5 (c 1.0, CHCl3); IR (CHCl3)
1324, 1114, 1083 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.36 (6H,
m), 0.79 (9H, t, J ) 7.8 Hz), 1.07 (9H, s), 1.34 (1H, q, J ) 11.2
Hz), 2.10 (1H, dd, J ) 15.1, 1.5 Hz), 2.21 (1H, dd, J ) 15.1,
9.8 Hz), 2.29 (1H, ddd, J ) 12.0, 4.4, 4.4 Hz), 2.83 (1H, ddd, J
) 9.8, 9.8, 1.5 Hz), 3.19 (2H, m), 3.52 (1H, ddd, J ) 11.2, 9.8,
4.4 Hz), 3.56 (1H, dd, J ) 10.2, 1.5 Hz), 3.66 (1H, dd, J ) 10.2,
3.4 Hz), 3.82 (1H, dd, J ) 5.8, 1.9 Hz), 4.41 and 4.99 (each
1H, d, J ) 11.7 Hz), 4.44 and 4.61 (each 1H, d, J ) 12.7 Hz),
7.19-7.84 (25H, Ar); 13C NMR (100 MHz, CDCl3) δ 4.9 (3 ×
C), 6.8 (3 × C), 19.3, 26.8 (3 × C), 30.4, 39.6, 61.6, 66.6, 68.5,
69.1, 71.4, 71.6, 73.4, 75.2, 76.9, 79.8, 126.0, 127.6, 127.70,
127.73, 127.79, 128.3, 129.0, 129.1, 129.7, 133.5, 133.9, 135.0,
135.1, 135.6, 137.4, 138.2; HRFABMS calcd for C52H67O8SSi2
(MH+) 907.4091, found 907.4067.
(1.546 g, 95%) as a colorless oil. [R]25 -22.4 (c 0.96, CHCl3);
D
IR (CHCl3) 2175, 1463, 1362, 1250, 1091 cm-1; H NMR (400
1
MHz, CDCl3) δ 0.05 (3H, s), 0.07 (3H, s), 0.15 (9H, s), 0.86
(9H, s), 1.21 (3H, s), 1.52 (1H, q, J ) 11.7 Hz), 1.94 (1H, ddd,
J ) 14.2, 8.3, 6.4 Hz), 2.02 (1H, ddd, J ) 14.2, 8.3, 5.9 Hz),
2.10 (1H, ddd, J ) 12.2, 4.4, 4.4 Hz), 2.38 (1H, dd, J ) 17.1,
5.9 Hz), 2.54 (1H, dd, J ) 17.1, 2.9 Hz), 3.32-3.44 (3H, m),
3.68 (2H, m), 4.46 and 4.55 (each 1H, d, J ) 11.7 Hz), 4.47
(2H, s), 7.25-7.34 (10H, Ar); 13C NMR (100 MHz, CDCl3) δ
-4.8, -4.2, 0.2 (3 × C), 16.5, 17.9, 23.4, 25.8 (3 × C), 34.5,
39.3, 66.1, 69.3, 71.3, 72.6, 72.9, 75.4, 77.9, 85.7, 104.2, 127.4,
127.50, 127.53, 127.6, 128.3, 138.6, 138.7; HRFABMS calcd
for C34H53O4Si2 (MH+) 581.3479, found 581.3487.
(ii) A mixture of the TMS-acetylene (1.53 g, 2.638 mmol)
and K2CO3 (364 mg, 2.638 mmol) in MeOH (26 mL) was stirred
at room temperature for 19 h. The reaction mixture was
extracted with EtOAc and the extract was washed with water
and brine, dried, and concentrated in vacuo. Purification by
flash chromatography (8% EtOAc in hexane) gave acetylene
15 (1.29 g, 96%) as a colorless oil. [R]25D -22.1 (c 1.04, CHCl3);
1
IR (CHCl3) 3308, 1454, 1362, 1091 cm-1; H NMR (400 MHz,
CDCl3) δ 0.05 (3H, s), 0.07 (3H, s), 0.87 (9H, s), 1.22 (3H, s),
1.52 (1H, q, J ) 11.7 Hz), 1.89 (1H, t, J ) 2.4 Hz), 1.91-2.05
(2H, m), 2.10 (1H, ddd, J ) 12.2, 4.4, 4.4 Hz), 2.34 (1H, ddd,
J ) 16.6, 5.4, 2.4 Hz), 2.51 (1H, ddd, J ) 16.6, 2.4, 2.4 Hz),
3.33-3.43 (3H, m), 3.59-3.72 (2H, m), 4.46 and 4.49 (each 1H,
d, J ) 11.7 Hz), 4.47 and 4.55 (each 1H, d, J ) 11.7 Hz), 7.24-
7.36 (10H, Ar); 13C NMR (100 MHz, CDCl3) δ -4.8, -4.1, 16.4,
17.9, 22.1, 25.7 (3 × C), 34.4, 39.7, 66.0, 69.3, 69.3, 71.3, 72.4,
72.9, 75.4, 77.8, 81.3, 127.4, 127.52, 127.55, 127.6, 127.7, 128.3,
138.7, 138.7; HREIMS calcd for C31H44O4Si (M+) 508.3006,
found 508.3028.
(2S,3R,5S,6R)-5-Ben zyloxy-6-b en zyloxym et h yl-2-h y-
d r oxym eth yl-tetr a h yd r op yr a n -3-ol (16). To a stirred solu-
tion of (1R,6S,8R,9S)-8-benzyloxymethyl-3,3-di-tert-butyl-2,4,7-
trioxa-3-silabicyclo[4.4.0]decan-9-ol,21 [R]25D +6.17 (c 1.0, CHCl3)
(1.49 g, 3.652 mmol), and benzyl bromide (0.52 mL, 4.382
mmol) in THF (18 mL) was added excess KH (suspension in
mineral oil) at 0 °C. The reaction mixture was stirred at room
temperature for 1 h. The reaction was quenched with careful
addition of MeOH, and the mixture was extracted with EtOAc.
The extract was washed with water and brine, dried, and
concentrated in vacuo. Purification by flash chromatography
(8% Et2O in hexane) gave a dibenzyl ether (1.58 g, 87%) as a
colorless oil: [R]20D +52.5 (c 0.43, CHCl3). To a stirred solution
of the dibenzyl ether obtained above in THF (16 mL) was
added TBAF (7.56 mL of a 1 M solution in THF, 7.566 mmol).
The reaction mixture was stirred at room temperature for 17
(2S,4a S,6R,7S,8a R)-7-Ben zyloxy-6-ben zyloxym eth yl-2-
(ter t-b u t yld ip h en ylsilyloxym et h yl)-oct a h yd r op yr a n o-
[3,2-b]p yr a n -3-on e (19). A solution of 18 (971 mg, 1.072
mmol) and TsOH‚H2O (245 mg, 1.286 mmol) in CHCl3 (22 mL)
was heated at 55 °C for 4 h. The reaction mixture was
extracted with EtOAc and the extract was washed with water
and brine, dried, and concentrated in vacuo. Purification by
flash chromatography (18f30% EtOAc in hexane) gave 19
(574 mg, 82%) as a colorless oil. [R]24 +24.3 (c 1.0, CHCl3);
D
IR (CHCl3) 1724, 1454, 1112 cm-1; 1H NMR (400 MHz, CDCl3)
δ 1.02 (9H, s), 1.57 (1H, q, J ) 11.2 Hz), 2.46 (1H, dd, J )
17.1, 9.1 Hz), 2.62 (1H, ddd, J ) 11.7, 4.4, 4.4 Hz), 2.99 (1H,
dd, J ) 17.1, 5.8 Hz), 3.33 (1H, ddd, J ) 11.2, 9.3, 4.4 Hz),
3.45-3.52 (2H, m), 3.61 (1H, ddd, J ) 10.7, 9.3, 4.4 Hz), 3.69
(1H, dd, J ) 10.3, 4.4 Hz), 3.76 (1H, dd, J ) 10.7, 2.0 Hz),
3.93 (1H, dd, J ) 6.4, 2.9 Hz), 3.98 (2H, m), 4.44 and 4.61 (each
1H, d, J ) 11.7 Hz), 4.55 and 4.62 (each 1H, d, J ) 12.7 Hz),
7.24-7.71 (20H, Ar); 13C NMR (100 MHz, CDCl3) δ 19.2, 26.7
(3 × C), 35.1, 44.9, 63.3, 69.0, 71.2, 72.0, 73.5, 74.0, 75.6, 79.9,
83.6, 127.6, 127.78, 127.8, 127.9, 128.3, 128.4, 129.59, 129.62,
133.3, 133.4, 135.6, 135.7, 137.9, 138.1, 205.3; HRFABMS calcd
for C40H47O6Si (MH+) 651.3139, found 651.3148.
(2R,3S,4a R,6S,9a S)-3-Ben zyloxy-2-b en zyloxym et h yl-
6-(ter t-bu tyld ip h en ylsilyloxym eth yl)-h exa h yd r o-1,5-d i-
oxa b en zocycloh ep t a n -7-on e (20), (2R,3S,4a R,6S,9a S)-
3-Ben zyloxy-2-ben zyloxym eth yl-6-(ter t-bu tyld ip h en ylsi-
lyloxym eth yl)-h exa h yd r o-1,5-d ioxa ben zocycloh ep ta n -8-
on e (21), a n d Sp ir o-Ep oxid e 22. To a stirred mixture of
ketone 19 (540 mg, 0.831 mmol) and 3A MS (2.70 g) in CH2-
Cl2 (16.6 mL) at -78 °C were added BF3‚OEt2 (0.41 mL, 3.332
mmol) and trimethylsilyldiazomethane (0.5 mL of a 2.0 M
solution in hexane, 1.00 mmol), and the reaction mixture was
stirred for 40 min. The reaction was quenched with saturated
aqueous NaHCO3 and the mixture was extracted with Et2O.
The extract was washed with water and brine, dried, and
concentrated in vacuo. The residue was dissolved in CH2Cl2
(3.0 mL) and MeOH (3.0 mL), and PPTS (42 mg) was added
to the solution. After the mixture was stirred at room tem-
perature for 3 h, the reaction was quenched with triethylamine
(0.2 mL) and the mixture was concentrated in vacuo. Purifica-
tion by flash chromatography (14f20% EtOAc in hexane) gave
epoxide 22 (112 mg, 18%), ketone 20 (333 mg, 60%), and ketone
h
and then concentrated in vacuo. Purification by flash
chromatography (EtOAc) gave diol 16 (993 mg, 88%) as a
crystalline solid, mp 43-45 °C. [R]25 +42.5 (c 0.28, CHCl3);
D
IR (CHCl3) 3586, 3438, 1454, 1211, 1036 cm-1; H NMR (400
1
MHz, CDCl3) δ 1.48 (1H, q, J ) 11.9 Hz), 2.56 (1H, ddd, J )
11.9, 4.4, 4.4 Hz), 3.23 (1H, ddd, J ) 14.0, 4.9, 3.9 Hz), 3.43
(1H, ddd, J ) 9.3, 4.4, 1.9 Hz), 3.47 (1H, ddd, J ) 11.2, 9.3,
4.4 Hz), 3.63 (1H, ddd, J ) 14.0, 11.9, 4.4 Hz), 3.66 (1H, dd, J
) 13.2, 4.4 Hz), 3.76 (1H, dd, J ) 13.2, 1.9 Hz), 3.79 (1H, dd,
J ) 11.7, 4.9 Hz), 3.86 (1H, dd, J ) 11.7, 3.9 Hz), 4.41 and
4.59 (each 1H, d, J ) 11.2 Hz), 4.52 and 4.58 (each 1H, d, J )
11.7 Hz), 7.22-7.33 (10H, Ar); 13C NMR (100 MHz, CDCl3) δ
38.2, 63.0, 66.3, 69.3, 71.1, 72.1, 73.5, 79.8, 81.2, 127.72, 127.76,
127.79, 127.9, 128.37, 128.42, 138.15, 138.18; FABMS m/z 359
(MH+). Anal. Calcd for C21H26O5: C, 70.37; H, 7.31. Found:
C, 70.11; H, 7.45.
(2S,3R,5S,6R)-2-[(2S,3R)2-Ben zen esu lfon yl-3-(ter t-bu -
tyldiph en ylsilyloxym eth yl)-oxir an ylm eth yl]-5-ben zyloxy-
6-b en zyloxym et h yl-3-t r iet h ylsilyloxy-t et r a h yd r op yr a n
(18). The procedure for compound 5 was employed with diol
16 (1.79 g, 4.988 mmol), Tf2O (0.86 mL, 5.088 mmol), TESOTf
21 (17 mg, 3%) in this order. Ketone 20: [R]25 -26.7 (c 1.0,
D
CHCl3); IR (CHCl3) 1715, 1454, 1428, 1112 cm-1; 1H NMR (400
9056 J . Org. Chem., Vol. 68, No. 23, 2003

Convergent Synthesis of Polycyclic Ethers
MHz, CDCl3) δ 1.02 (9H, s), 1.57 (1H, m), 1.64 (1H, q, J )
11.7 Hz), 2.23 (1H, m), 2.45 (1H, ddd, J ) 12.2, 7.3, 1.5 Hz),
2.57 (1H, ddd, J ) 12.2, 12.2, 4.4 Hz), 2.98 (1H, ddd, J ) 12.2,
12.2, 2.0 Hz), 3.06 (1H, ddd, J ) 12.2, 9.3, 4.4 Hz), 3.39 (1H,
ddd, J ) 10.7, 8.8, 4.4 Hz), 3.46 (1H, m), 3.65 (1H, dd, J )
10.7, 4.4 Hz), 3.76 (1H, dd, J ) 10.7, 1.5 Hz), 3.86-3.90 (2H,
m), 3.94 (1H, dd, J ) 10.7, 4.4 Hz), 4.41 and 4.58 (each 1H, d,
J ) 11.7 Hz), 4.54 and 4.61 (each 1H, d, J ) 12.2 Hz), 7.22-
7.73 (20H, Ar); 13C NMR (100 MHz, CDCl3) δ 19.3, 26.7 (3 ×
C), 29.1, 37.0, 38.2, 66.1, 69.2, 71.1, 72.3, 73.5, 80.0, 80.2, 80.8,
87.8, 127.6, 127.66, 127.73, 127.76, 127.8, 128.3, 128.4, 129.7,
133.7, 135.6, 135.7, 138.0, 138.2, 214.9; HRFABMS calcd for
127.8, 128.3, 128.4, 129.5, 133.7, 133.8, 135.7, 138.2, 138.4,
150.3; HRFABMS calcd for C42H51O5Si (MH+) 663.3503, found
663.3538.
(2R,3S,4aR,6S,7S,9aS)-3-Ben zyloxy-2-ben zyloxym eth yl-
6-(ter t-bu tyld ip h en ylsilyloxym eth yl)-h exa h yd r o-1,5-d i-
oxa ben zocycloh ep ta n e-7-sip r o-2′-oxir a n e (24). A solution
of 23 (460 mg, 0.695 mmol), m-CPBA (600 mg, 3.474 mmol),
and NaHCO3 (292 mg, 3.474 mmol) in toluene (14 mL) was
stirred at room temperature for 3 h. The reaction quenched
with saturated aqueous Na2S2O3, the mixture was extracted
with EtOAc, and the extract was washed with saturated
aqueous NaHCO3, water, and brine, dried, and concentrated
in vacuo. Purification by flash chromatography (15% EtOAc
in hexane) gave epoxide 24 (306 mg, 65%) as a colorless oil.
C
41H49O6Si (MH+) 665.3296, found 665.3273.
Ketone 21: [R]25 +50.6 (c 1.0, CHCl3); IR (CHCl3) 1708,
D
[R]24D -0.72 (c 1.0, CHCl3); IR (CHCl3) 1601, 1453, 1112 cm-1
;
1428, 1113 cm-1; H NMR (400 MHz, CDCl3) δ 1.05 (9H, s),
1.47 (1H, q, J ) 11.2 Hz), 2.46 (1H, dd, J ) 18.1, 11.2 Hz),
2.50 (1H, m), 2.70 (1H, dd, J ) 18.1, 2.4 Hz), 2.84 (1H, dd, J
) 12.7, 2.4 Hz), 3.02 (1H, t, J ) 12.7 Hz), 3.19 (1H, ddd, J )
12.7, 8.8, 2.4 Hz), 3.35 (2H, m), 3.52 (1H, dd, J ) 10.3, 5.4
Hz), 3.54 (1H, m), 3.63-3.74 (3H, m), 4.38 and 4.53 (each 1H,
d, J ) 11.7 Hz), 4.52 and 4.63 (each 1H, d, J ) 12.2 Hz), 4.53
(1H, m), 7.19-7.71 (20H, Ar); 13C NMR (100 MHz, CDCl3) δ
19.2, 26.8 (3 × C), 36.4, 47.8, 50.1, 66.4, 68.9, 71.1, 71.9, 73.5,
77.9, 80.3, 81.4, 91.3, 127.6, 127.70, 127.73, 127.76, 127.8,
128.3, 128.4, 129.77, 129.82, 133.4, 135.56, 135.63, 207.1;
1
1H NMR (400 MHz, CDCl3) δ 1.05 (9H, s), 1.23 (1H, ddd, J )
13.6, 5.9, 3.4 Hz), 1.45 (1H, q, J ) 11.2 Hz), 1.77 (1H, m), 1.97
(1H, m), 2.08 (1H, ddd, J ) 13.6, 13.6, 2.4 Hz), 2.49 (1H, ddd,
J ) 12.2, 4.4, 4.4 Hz), 2.67 and 2.82 (each 1H, d, J ) 4.9 Hz),
3.16 (1H, ddd, J ) 10.7, 9.3, 5.4 Hz), 3.31 (1H, t, J ) 5.4 Hz),
3.39 (1H, m), 3.42 (1H, ddd, J ) 9.8, 9.8, 4.4 Hz), 3.47 (1H,
ddd, J ) 11.2, 8.8, 4.9 Hz), 3.61 (1H, dd, J ) 10.7, 4.8 Hz),
3.64 (1H, dd, J ) 10.7, 5.4 Hz), 3.66 (1H, dd, J ) 10.7, 5.4
Hz), 3.76 (1H, dd, J ) 10.7, 1.5 Hz), 4.39 and 4.56 (each 1H,
d, J ) 11.2 Hz), 4.55 and 4.61 (each 1H, d, J ) 12.2 Hz), 7.22-
7.65 (20H, Ar); 13C NMR (100 MHz, CDCl3) δ 19.2, 25.5, 26.8
(3 × C), 29.1, 37.0, 52.1, 60.3, 65.2, 69.5, 71.0, 72.4, 73.4, 74.9,
79.7, 80.4, 83.6, 127.5, 127.66, 127.76, 127.8, 128.3, 128.4,
129.8, 133.2. 135.6, 138.1, 138.4; HRFABMS calcd for C42H51O6-
Si (MH+) 679.3452, found 679.3486.
HRFABMS calcd for
665.3259.
C
41H49O6Si (MH+) 665.3296, found
Spiro-epoxide 22: [R]25 +14.5 (c 0.5, CHCl3); IR (CHCl3)
D
1605, 1454, 1428, 1112 cm-1; 1H NMR (400 MHz, acetone-d6)
δ 0.13 (9H, s), 1.04 (9H, s), 1.42 (1H, q, J ) 11.7 Hz), 1.83
(1H, dd, J ) 12.2, 4.4 Hz), 1.97 (1H, ddd, J ) 12.2, 12.2, 1.5
Hz), 2.41 (1H, d, J ) 1.0 Hz), 2.51 (1H, ddd, J ) 11.2, 11.2,
4.4 Hz), 3.14 (1H, ddd, J ) 11.7, 8.8, 4.4 Hz), 3.24 (1H, ddd, J
) 11.2, 8.8, 4.4 Hz), 3.45 (1H, ddd, J ) 9.8, 4.9, 2.0 Hz), 3.60
(1H, ddd, J ) 10.7, 8.3, 4.4 Hz), 3.63 (1H, dd, J ) 11.2, 5.9
Hz), 3.67 (1H, dd, J ) 11.2, 2.4 Hz), 3.69 (1H, dd, J ) 10.7,
4.9 Hz), 3.78 (1H, dd, J ) 10.7, 1.5 Hz), 3.82 (1H, dd, J ) 5.9,
2.4 Hz), 4.52 and 4.57 (each 1H, d, J ) 12.2 Hz), 4.53 and
4.68 (each 1H, d, J ) 11.7 Hz), 7.27-7.76 (20H, Ar); 13C NMR
(100 MHz, CDCl3) δ -1.7 (3 × C), 19.3, 26.8 (3 × C), 35.1,
36.8, 55.3, 59.7, 61.9, 69.1, 71.2, 72.3, 73.5, 75.7, 77.2, 80.3,
81.7, 127.5, 127.6, 127.7, 127.9, 128.32, 128.39, 129.46, 129.54,
133.6, 133.9, 135.7, 135.8, 138.1, 138.2; HRFABMS calcd for
(2R,3S,4aR,6S,7R,9aS)-3-Ben zyloxy-2-ben zyloxym eth yl-
6-(ter t-b u t yld ip h en ylsilyloxym et h yl)-7-m et h yl-h exa h y-
d r o-1,5-d ioxa -ben zocycloh ep ta n -7-ol (25). To a stirred
solution of 24 (680 mg, 1.003 mmol) in dry THF (10 mL) at 0
°C was added lithium triethylborohydride (3.0 mL of a 1.0 M
solution in THF, 3.00 mmol), and the reaction mixture was
stirred at 0 °C for 40 min. The reaction was quenched with
water and the mixture was extracted with EtOAc. The extract
was washed with water and brine, dried, and concentrated.
Purification by flash chromatography (30% EtOAc in hexane)
gave 25 (657 mg, 96%) as a colorless oil. [R]24 -38.5 (c 1.0,
D
CHCl3); IR (CHCl3) 3505, 1455, 1114 cm-1; 1H NMR (400 MHz,
CDCl3) δ 1.06 (9H, s), 1.22 (3H, s), 1.41 (1H, q, J ) 11.7 Hz),
1.64 (1H, m), 1.91 (2H, m), 1.96 (1H, m), 2.45 (1H, ddd, J )
11.7, 4.4, 4.4 Hz), 2.98 (1H, ddd, J ) 9.8, 9.8, 2.9 Hz), 3.04
(1H, s, OH), 3.14 (1H, ddd, J ) 11.7, 9.3, 3.9 Hz), 3.35 (1H,
ddd, J ) 9.3, 4.9, 2.0 Hz), 3.46 (1H, ddd, J ) 9.8, 9.8, 4.9 Hz),
3.63 (2H, m), 3.37 (3H, m), 4.32 and 4.50 (each 1H, d, J )
11.2 Hz), 4.54 and 4.61 (each 1H, d, J ) 12.7 Hz), 7.22-7.70
(20H, Ar); 13C NMR (100 MHz, CDCl3) δ 19.1, 24.3, 26.8 (3 ×
C), 27.1, 36.8, 38.6, 64.1, 69.3, 70.9, 72.6, 73.4, 80.3, 82.0, 83.9,
84.7, 127.6, 127.7, 127.9, 128.3, 130.1, 132.4, 135.58, 135.6,
138.0; HRFABMS calcd for C42H53O6Si (MH+) 681.3608, found
681.3587.
C
44H57O6Si2 (MH+) 737.3690, found 737.3673.
(2R,3S,4a R,6R,9a S)-3-Ben zyloxy-2-ben zyloxym eth yl-6-
(ter t-bu tyld ip h en ylsilyloxym eth yl)-7-m eth ylen e-h exa h y-
d r o-1,5-d ioxa ben zocycloh ep ta n e (23). To a stirred suspen-
sion of methyltriphenylphosphonium bromide (717 mg, 2.006
mmol) in THF (5.0 mL) was added KHMDS (2.24 mL of a 0.67
M solution in toluene, 1.501 mmol) at 0 °C, and the reaction
mixture was stirred for 30 min. The mixture was then cooled
to -78 °C and a solution of the ketone 20 (333 mg, 0.502 mmol)
in THF (5.0 mL) was added. After the solution was stiired at
-78 °C for 0.5 h, the reaction mixture was warmed to 0 °C
and stirred for another 30 min. The reaction was quenched
with saturated aqueous NH4Cl and the mixture was extracted
with EtOAc. The extract was washed with water and brine,
dried, and concentrated in vacuo. Purification by flash chro-
matography (14% EtOAc in hexane) gave 23 (303 mg, 91%)
as a colorless oil. [R]24D -9.08 (c 0.5, CHCl3); IR (CHCl3) 1498,
(2R,3S,4aR,6S,7R,9aS)-3-Ben zyloxy-2-ben zyloxym eth yl-
6-h yd r oxym et h yl-7-m et h yl-oct a h yd r o-1,5-d ioxa -b en zo-
cycloh ep ten -7-ol (26). To a solution of 25 (657 mg, 0.967
mmol) in THF (10 mL) was added TBAF (1.45 mL of a 1.0 M
solution in THF, 1.45 mmol), and the reaction mixture was
stirred at room temperature for 1.5 h. The reaction mixture
was concentrated in vacuo. Purification of the residue by flash
chromatography (EtOAc) gave diol 26 (426 mg, 100%) as a
1
1453, 1112 cm-1; H NMR (400 MHz, CDCl3) δ 1.05 (9H, s),
colorless oil. [R]24 +25.3 (c 0.72, CHCl3); IR (CHCl3) 3599,
1.34 (1H, m), 1.49 (1H, q, J ) 11.2 Hz), 2.12 (2H, m), 2.18
(1H, m), 2.49 (1H, ddd, J ) 12.2, 4.4, 4.4 Hz), 3.14 (2H, m),
3.35 (1H, ddd, J ) 9.3, 4.9, 2.0 Hz), 3.40 (1H, ddd, J ) 9.3,
9.3, 4.4 Hz), 3.52 (1H, dd, J ) 10.7, 5.4 Hz), 3.61 (1H, dd, J )
10.7, 4.9 Hz), 3.69 (1H, dd, J ) 10.7, 6.4 Hz), 3.73 (1H, dd, J
) 10.7, 1.5 Hz), 4.16 (1H, t, J ) 5.8 Hz), 4.38 and 4.57 (each
1H, d, J ) 11.7 Hz), 4.54 and 4.60 (each 1H, d, J ) 12.2 Hz),
4.75 (1H, s), 4.97 (1H, s), 7.20-7.72 (20H, Ar); 13C NMR (100
MHz, CDCl3) δ 19.3, 26.8 (3 × C), 27.6, 35.8, 37.0, 66.9, 69.3,
70.9, 72.4, 73.4, 75.6, 79.6, 80.6, 83.9, 113.2, 127.5, 127.6, 127.7,
D
3477, 1501, 1454, 1074 cm-1
;
1H NMR (400 MHz, CDCl3) δ
1.17 (3H, s), 1.51 (1H, q, J ) 11.2 Hz), 1.75 (1H, m), 1.85 (2H,
m, including OH), 1.92 (1H, m), 2.05 (1H, br s, OH), 2.56 (1H,
ddd, J ) 11.2, 4.4, 4.4 Hz), 3.05 (1H, m), 3.24 (1H, ddd, J )
11.2, 9.3, 3.9 Hz), 3.39 (1H, ddd, J ) 9.3, 4.9, 2.0 Hz), 3.50
(1H, ddd, J ) 10.7, 10.7, 4.4 Hz), 3.53 (1H, dd, J ) 7.8, 5.4
Hz), 3.62 (1H, dd, J ) 10.7, 5.4 Hz), 3.65 (1H, m), 3.74 (1H,
dd, J ) 10.7, 2.0 Hz), 3.75 (1H, m), 4.38 and 4.57 (each 1H, d,
J ) 11.2 Hz), 4.54 and 4.61 (each 1H, d, J ) 12.2 Hz), 7.19-
J . Org. Chem, Vol. 68, No. 23, 2003 9057

Mori et al.
7.35 (10H, Ar); 13C NMR (100 MHz, CDCl3) δ 20.4, 27.1, 36.9,
39.2, 62.4, 69.3, 71.0, 72.7, 73.4, 74.4, 80.3, 81.8, 83.3, 86.9,
127.6, 127.7, 127.9, 128.3, 128.4, 138.0, 138.2; HRFABMS calcd
for C26H35O6 (MH+) 443.2431, found 443.2436.
Hz), 3.74 (1H, dd, J ) 10.7, 1.5 Hz), 4.19 (1H, dd, J ) 10.7,
6.8 Hz), 4.39 and 4.58 (each 1H, d, J ) 11.2 Hz), 4.54 and
4.59 (each 1H, d, J ) 12.2 Hz), 7.20-7.70 (20H, Ar); 13C NMR
(100 MHz, CDCl3) δ 19.3, 20.5, 23.4, 26.9 (3 × C), 28.2, 36.9,
38.4, 42.1, 69.4, 70.9, 72.5, 73.4, 78.3, 79.3, 80.2, 82.7, 83.4,
127.7, 127.8, 127.8, 128.3, 128.4, 129.9, 132.5, 133.1, 135.5,
135.6, 138.0, 138.3, 213.0; HRFABMS calcd for C46H57O7Si
(MH+) 749.3870, found 749.3887.
Tr iflu or om et h a n esu lfon ic Acid (2R,3S,4a R,6S,7R,-
9aS)-3-Benzyloxy-2-benzyloxymethyl-7-methyl-7-(trimethyl-
silyloxy)-oct a h yd r o-1,5-d ioxa -b e n zocycloh e p t e n -6-yl-
m eth yl Ester (27). The procedure for compound 5 was
employed with diol 26 (916 mg, 2.071 mmol), Tf2O (0.358 mL,
2.113 mmol), TMSOTf (0.496 mL, 2.279 mmol), and 2,6-
lutidine (0.720 mL, 6.214 mmol) in CH2Cl2 (10 mL). Purifica-
tion by flash chromatography (12% EtOAc in hexane) gave
triflate 27 (1.32 g, 99%) as a pale yellow oil. 1H NMR (400
MHz, CDCl3) δ 0.12 (9H, s), 1.13 (3H, s), 1.49 (1H, q, J ) 11.2
Hz), 1.68 (1H, m), 1.88 (2H, m), 1.92 (1H, m), 1.97 (1H, m),
2.64 (1H, ddd, J ) 11.2, 4.4, 4.4 Hz), 3.04 (1H, ddd, J ) 8.8,
8.8, 4.4 Hz), 3.17 (1H, ddd, J ) 11.7, 9.3, 3.9 Hz), 3.39 (1H,
ddd, J ) 9.8, 5.4, 2.0 Hz), 3.49 (1H, ddd, J ) 10.7, 10.7, 4.9
Hz), 3.60 (1H, dd, J ) 10.7, 4.9 Hz), 3.68 (1H, dd, J ) 9.3, 1.9
Hz), 3.74 (1H, dd, J ) 10.7, 1.9 Hz), 4.37 and 4.59 (each 1H,
d, J ) 11.2 Hz), 4.45 (1H, t, J ) 9.8 Hz), 4.53 and 4.60 (each
1H, d, J ) 12.2 Hz), 4.63 (1H, dd, J ) 9.8, 2.0 Hz), 7.19-7.35
(10H, Ar); 13C NMR (100 MHz, CDCl3) δ 2.3 (3 × C), 24.6, 27.1,
36.3, 38.2, 69.4, 71.0, 72.7, 73.5, 76.5, 77.2, 80.4, 82.5, 83.2,
86.1, 127.6, 127.7, 127.8, 127.9, 128.3, 128.4, 137.9, 138.2;
FABMS m/z 647 (MH+).
(2S,3R,4a S,5a R,7S,8R,9a S,11a R)-7-Ben zyloxy-8-ben zyl-
oxym et h yl-2-(ter t-b u t yld ip h en ylsilyloxym et h yl)-2,11a -
d im et h yl-d od eca h yd r o-1,5,9-t r ioxa -d ib en zo[a ,d ]cyclo-
h ep ten -3-ol (30). To a stirred solution of 29 (1.236 g, 1.652
mmol) in CH2Cl2 (6.5 mL) and MeOH (6.5 mL) at 0 °C was
added NaBH4 (94 mg, 2.478 mmol), and the reaction mixture
was stirred at 0 °C for 30 min. The reaction mixture was
poured into water and extracted with EtOAc. The extract was
washed with water and brine, dried, and concentrated. Puri-
fication by flash chromatography (14% EtOAc in hexane) gave
alcohol 30 (1.21 g, 98%) as a colorless oil. [R]20 +1.75 (c 1.0,
D
CHCl3); IR (CHCl3) 3521, 1475, 1457, 1067 cm-1; 1H NMR (400
MHz, CDCl3) δ 1.06 (9H, s), 1.25 (3H, s), 1.32 (3H, s), 1.46
(1H, q, J ) 11.2 Hz), 1.68-1.78 (2H, m), 1.81 (1H, q, J ) 11.7
Hz), 1.83 (1H, m), 1.99 (2H, m), 2.58 (1H, ddd, J ) 11.7, 4.4,
4.4 Hz), 3.13-3.26 (3H, m), 3.32 (1H, ddd, J ) 9.3, 4.9, 1.5
Hz), 3.37 (1H, dd, J ) 11.7, 3.9 Hz), 3.46 (3H, m), 3.59 (1H,
dd, J ) 10.7, 3.4 Hz), 3.72 (1H, dd, J ) 10.7, 2.0 Hz), 3.86
(1H, ddd, J ) 11.7, 4.4, 1.5 Hz), 4.37 and 4.57 (each 1H, d, J
) 11.2 Hz), 4.53 and 4.60 (each 1H, d, J ) 12.2 Hz), 7.20-
7.66 (20H, Ar); 13C NMR (100 MHz, CDCl3) δ 18.5, 19.1, 23.2,
26.9 (3 × C), 29.2, 31.5, 37.0, 39.6, 69.3, 70.8, 72.3, 73.4, 73.5,
73.7, 75.2, 77.5, 79.3, 79.9, 80.4, 80.7, 127.5, 127.66, 127.71,
127.8, 128.29, 128.34, 129.9, 130.0, 132.2, 135.5, 135.7, 138.1,
138.3; HRFABMS calcd for C46H59O7Si (MH+) 751.4027, found
751.4059.
(2R,3S,4a R,6S,7R,9a S)-3-Ben zyloxy-2-ben zyloxym eth -
yl-6-[(2S,3R)-3-(ter t-bu tyldiph en ylsilyloxym eth yl)-3-m eth -
yl-2-(tolu en e-4-su lfon yl)-oxir a n ylm eth yl]-7-m eth yl-7-(tr i-
m eth ylsilyloxy)-octa h yd r o-1,5-d ioxa -ben zocycloh ep ten e
(28). The procedure for compound 12 was employed with
triflate 27 (1.32 g, 2.049 mmol), epoxy sulfone 11 (1.47 g, 3.074
mmol), n-BuLi (1.97 mL of a 1.56 M solution in hexane, 3.074
mmol), and HMPA (1.06 mL, 6.149 mmol) in THF (13 mL).
Purification by flash chromatography (20% EtOAc in hexane)
(2R,3S,4a R,5a S,6a R,10a S,11a R,13a S)-3-Ben zyloxy-2-
ben zyloxym eth yl-8,8,10a ,11a -tetr a m eth yl-d od eca h yd r o-
1,5,7,9,11-p en ta oxa -ben zo[4,5]cycloh ep ta [1,2-b]n a p h th a -
len e (31). (i) To a solution of 30 (1.21 g, 1.613 mmol) in THF
(13 mL) was added TBAF (1.93 mL of a 1 M solution in THF,
1.930 mmol), and the reaction mixture was stirred at room
temperature for 70 min. The reaction mixture was concen-
trated in vacuo. Purification of the residue by flash chroma-
tography (90% EtOAc in hexane) gave a diol (827 mg, 100%)
as a colorless oil. [R]20D +22.6 (c 1.0, CHCl3); IR (CHCl3) 3599,
gave 28 (1.80 g, 90%) as a colorless oil. [R]20 -17.8 (c 1.0,
D
CHCl3); IR (CHCl3) 1597, 1453, 1319, 1154 cm-1; 1H NMR (400
MHz, CDCl3) δ 0.12 (9H, s), 1.05 (3H, s), 1.10 (9H, s), 1.33
(1H, q, J ) 11.2 Hz), 1.56 (3H, s), 1.58 (1H, m), 1.70 (1H, m),
1.77 (1H, m), 1.92 (1H, dd, J ) 14.4, 7.8 Hz), 2.08 (1H, dd, J
) 15.6, 10.3 Hz), 2.35 (1H, d, J ) 15.6 Hz), 2.38 (3H, s), 2.78
(1H, ddd, J ) 11.2, 3.9, 3.9 Hz), 2.92 (1H, ddd, J ) 9.3, 9.3,
3.4 Hz), 3.02 (1H, ddd, J ) 11.7, 11.7, 3.9 Hz), 3.37 (2H, m),
3.45 (1H, ddd, J ) 10.7, 10.7, 4.9 Hz), 3.59 (1H, dd, J ) 10.7,
5.4 Hz), 3.73 (1H, dd, J ) 10.7, 1.5 Hz), 4.30 and 4.34 (each
1H, d, J ) 11.2 Hz), 4.32 and 4.58 (each 1H, d, J ) 9.8 Hz),
4.54 and 4.60 (each 1H, d, J ) 12.2 Hz), 7.15-7.76 (25H, Ar);
13C NMR (100 MHz, CDCl3) δ 2.5 (3 × C), 17.2, 19.4, 21.7,
24.4, 26.8, 26.9 (3xC), 28.7, 36.1, 38.2, 64.8, 69.6, 70.0, 70.9,
73.1, 73.4, 77.8, 80.4, 81.1, 81.9, 83.9, 84.8, 127.5, 127.68,
127.73, 127.9, 128.27, 128.30, 129.2, 129.5, 129.7, 129.8, 133.2,
133.3, 135.7, 138.2, 138.3, 144.5; HRFABMS calcd for C56H73O9-
SSi2 (MH+) 977.4483, found 977.4451.
3442, 1497, 1454, 1065 cm-1 1H NMR (400 MHz, CDCl3) δ
;
1.15 (3H, s), 1.28 (3H, s), 1.46 (1H, q, J ) 11.2 Hz), 1.79-1.89
(4H, m), 1.96-2.15 (4H, m), 2.57 (1H, ddd, J ) 11.7, 4.4, 4.4
Hz), 3.21 (2H, m), 3.35 (2H, m), 3.36 and 3.43 (each 1H, d, J
) 10.7 Hz), 3.46 (1H, ddd, J ) 10.7, 9.3, 4.4 Hz), 3.60 (1H, dd,
J ) 10.7, 5.4 Hz), 3.73 (1H, dd, J ) 10.7, 1.5 Hz), 3.91 (1H,
dd, J ) 12.2, 4.4 Hz), 4.38 and 4.57 (each 1H, d, J ) 11.7 Hz),
4.54 and 4.60 (each 1H, d, J ) 12.2 Hz), 7.19-7.34 (10H, Ar);
13C NMR (100 MHz, CDCl3) δ 19.4, 22.9, 29.1, 32.2, 37.0, 39.6,
68.1, 68.2, 69.3, 70.9, 72.3, 73.4, 76.5, 77.7, 79.3, 79.9, 80.6,
80.8, 127.5, 127.68, 127.71, 127.8, 128.3, 128.4, 138.0, 138.2;
HRFABMS calcd for C30H41O7 (MH+) 512.2772, found 512.2758.
(2S,4a S,5a R,7S,8R,9a S,11a R)-7-Ben zyloxy-8-b en zyl-
oxym eth yl-2-(ter t-bu tyldiph en ylsilyloxym eth yl)-2,11a-di-
methyl-decahydro-1,5,9-trioxa-dibenzo[a ,d]cyclohepten-3-one
(29). To a solution of 28 (1.80 g, 1.844 mmol) in CH2Cl2 (37
mL) was added BF3‚OEt2 (1.13 mL, 9.221 mmol) at 0 °C, and
the reaction mixture was stirred at room temperature for 1.5
h. The reaction was quenched with saturated aqueous NaH-
CO3 and the mixture was extracted with CH2Cl2. The extract
was washed with water and brine, dried, and concentrated in
vacuo. Purification by flash chromatography (20% EtOAc in
(ii) A solution of the diol (827 mg, 1.616 mmol), PPTS (20
mg, 0.081 mol), and 2,2-dimethoxypropane (4 mL) in THF (16
mL) was refluxed for 45 min. After the solution was cooled to
room temperature, the reaction was quenched with triethyl-
amine (0.2 mL) and the mixture was concentrated in vacuo.
Purification of the residue by flash chromatography (25%
EtOAc in hexane) gave acetonide 31 (875 mg, 98%) as a
colorless oil. [R]20D +7.93 (c 1.0, CHCl3); IR (CHCl3) 1455, 1383,
1073 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.32 (3H, s), 1.37 (3H,
s), 1.41 (3H, s), 1.48 (3H, s), 1.47 (1H, q, J ) 11.2 Hz), 1.84
(1H, q, J ) 11.2 Hz), 1.86 (2H, m), 2.02 (1H, m), 2.57 (1H,
ddd, J ) 11.7, 3.9, 3.9 Hz), 3.21 (2H, m), 3.33 (1H, ddd, J )
9.8, 5.4, 2.0 Hz), 3.43 and 3.50 (each 1H, d, J ) 10.3 Hz), 3.47
(1H, m), 3.55 (1H, dd, J ) 10.7, 4.9 Hz), 3.57-3.63 (2H, m),
3.73 (1H, dd, J ) 10.7, 2.0 Hz), 4.38 and 4.58 (each 1H, d, J )
11.7 Hz), 4.54 and 4.60 (each 1H, d, J ) 12.2 Hz), 7.20-7.34
hexane) gave ketone 29 (1.24 g, 90%) as a colorless oil. [R]20
D
+2.75 (c 1.0, CHCl3); IR (CHCl3) 1716, 1455, 1114, 1089 cm-1
;
1H NMR (400 MHz, CDCl3) δ 1.04 (9H, s), 1.14 (6H, s), 1,43
(1H, q, J ) 11.2 Hz), 1.80 (1H, ddd, J ) 15.1, 9.3, 3.4 Hz),
1.98 (2H, m), 2.22 (1H, ddd, J ) 15.1, 8.3, 3.4 Hz), 2.39 (1H,
dd, J ) 19.0, 10.7 Hz), 2.48 (1H, ddd, J ) 11.7, 3.9, 3.9 Hz),
2.83 (1H, dd, J ) 19.0, 6.9 Hz), 2.98 (1H, ddd, J ) 11.2, 9.3,
3.9 Hz), 3.07 (1H, ddd, J ) 8.3, 8.3, 4.9 Hz), 3.36 (2H, m), 3.56
and 3.65 (each 1H, d, J ) 9.8 Hz), 3.60 (1H, dd, J ) 10.7, 4.9
9058 J . Org. Chem., Vol. 68, No. 23, 2003

Convergent Synthesis of Polycyclic Ethers
(10H, Ar); 13C NMR (100 MHz, CDCl3) δ 18.4, 19.3, 25.5, 29.2,
29.5, 29.5, 36.9, 39.8, 69.3, 69.8, 70.8, 71.1, 72.3, 73.0, 73.4,
79.0, 79.9, 79.9, 80.0, 81.0, 99.9, 127.5, 127.66, 127.70, 127.8,
128.29, 128.34, 138.1, 138.3; HRFABMS calcd for C33H45O7
(MH+) 553.3163, found 553.3177.
7.34 (10H, Ar); 13C NMR (100 MHz, CDCl3) δ -4.7 (2 × C),
-4.2, -4.1, 16.5, 17.9, 18.4, 19.3, 22.2, 22.6, 25.6, 25.7 (3 ×
C), 25.8 (3 × C), 29.2, 29.5, 29.6, 34.5, 39.7, 39.8, 40.7, 66.1,
69.1, 69.4, 69.8, 71.1, 71.3, 72.9, 72.9, 73.1, 75.3, 77.5, 77.9,
78.1, 79.0, 80.0, 80.1, 80.4, 80.9, 99.9, 127.4, 127.5, 127.7, 128.3,
138.7, 138.7; HRFABMS calcd for C56H89O10Si2 (MH+) 977.1408,
found 977.1452.
(2R,3S,4aR,5aS,6aR,10aS,11aR,13aS)-2-Hydr oxym eth yl-
8,8,10a,11a-tetr am eth yl-dodecah ydr o-1,5,7,9,11-pen taoxa-
ben zo[4,5]cycloh ep ta [1,2-b]n a p h th a len -3-ol (32). A sus-
pension of dibenzyl ether 31 (775 mg, 1.404 mmol) and 10%
Pd(OH)2-C (232 mg) in THF (9.4 mL) was stirred under
hydrogen at room temperature for 1 h. The reaction mixture
was filtered through a short pad of Celite, and the filtrate was
concentrated in vacuo to give diol 32 (506 mg, 97%) as a white
solid, mp 209-210 °C. [R]23D -23.3 (c 0.27, CHCl3); IR (CHCl3)
3599, 3451, 1462, 1383, 1118, 1072 cm-1; 1H NMR (400 MHz,
CDCl3) δ 1.33 (3H, s), 1.38 (3H, s), 1.41 (3H, s), 1.48 (3H, s),
1.50 (1H, q, J ) 11.7 Hz), 1.60 (1H, br s, OH), 1.79-1.91 (5H,
m), 1.92-2.03 (2H, m, including OH), 2.41 (1H, ddd, J ) 11.7,
4.4, 4.4 Hz), 3.14 (1H, ddd, J ) 9.3, 4.9, 4.9 Hz), 3.23 (2H, m),
3.44 and 3.50 (each 1H, d, J ) 10.3 Hz), 3.55 (1H, dd, J )
10.7, 4.9 Hz), 3.60 (1H, dd, J ) 11.2, 4.4 Hz), 3.64 (1H, ddd, J
) 11.2, 9.3, 4.9 Hz), 3.75 (1H, dd, J ) 11.2, 4.9 Hz), 3.84 (1H,
dd, J ) 11.2, 4.4 Hz); 13C NMR (100 MHz, CDCl3) δ 18.4, 19.3,
25.4, 29.2, 29.5 (2 × C), 39.7, 40.1, 36.2, 66.9, 69.8, 71.1, 73.1,
78.9, 79.8, 79.9, 80.8, 81.3, 100.0; HRFABMS calcd for C197H33O7
(MH+) 373.2224, found 373.2238.
Tr iflu or om eth a n esu lfon ic Acid (2R,3S,4a R,5a S,6a R,-
10a S,11a R,13a S)-3-(ter t-Bu tyld im eth ylsilyloxy)-8,8,10a ,-
11a -tetr a m eth yl-d od eca h yd r o-1,5,7,9,11-p en ta oxa -ben zo-
[4,5]cycloh ep t a [1,2-b]n a p h t h a len -2-ylm et h yl E st er (6).
The procedure for compound 5 was employed with diol 32 (506
mg, 1.360 mmol), Tf2O (0.235 mL, 1.387 mmol), TBSOTf (0.468
mL, 2.040 mmol), and 2,6-lutidine (0.730 mL, 6.800 mmol) in
THF (13.6 mL). Purification by flash chromatography (5%
acetone in hexane) gave triflate 6 (805 mg, 96%) as a pale
yellow oil. 1H NMR (400 MHz, CDCl3) δ 0.07 (3H, s), 0.10 (3H,
s), 0.87 (9H, s), 1.32 (3H, s), 1.38 (3H, s), 1.41 (3H, s), 1.48
(3H, s), 1.53 (1H, q, J ) 12.2 Hz), 1.78-1.90 (5H, m), 2.01 (1H,
m), 2.35 (1H, ddd, J ) 12.2, 4.4, 4.4 Hz), 3.18-3.27 (2H, m),
3.33 (1H, ddd, J ) 9.3, 5.4, 2.0 Hz), 3.44 and 3.50 (each 1H, d,
J ) 10.3 Hz), 3.53 (1H, dd, J ) 9.8, 4.7 Hz), 3.56 (1H, m), 3.60
(1H, dd, J ) 11.7, 3.9 Hz), 4.49 (1H, dd, J ) 10.7, 5.4 Hz),
4.69 (1H, dd, J ) 10.7, 2.0 Hz); 13C NMR (100 MHz, CDCl3) δ
-5.1, -4.0, 17.8, 18.4, 19.3, 25.4, 25.6 (3 × C), 29.1, 29.2, 29.5,
39.6, 40.5, 65.9, 69.8, 71.1, 73.0, 75.3, 78.8, 78.9, 79.4, 80.0,
81.3, 100.0; FABMS m/z 619 (MH+).
1-[(2S,3R,5S,6R)-5-Ben zyloxy-6-(2-b en zyloxyet h yl)-3-
(t er t -b u t yld im e t h ylsilyloxy)-6-m e t h yl-t e t r a h yd r op y-
r an -2-yl]-4-[(2R,3S,4aR,5aS,6aR,10aS,11aR,13aS)-3-(ter t-bu -
tyldim eth ylsilyloxy)-8,8,10a,11a-tetr am ethyl-dodecah ydr o-
1,5,7,9,11-p en ta oxa ben zo[4,5]cycloh ep ta [1,2-b]n a p h th a -
len -2-yl]-bu ta n e-2,3-d ion e (33). To a suspension of 4 (85 mg,
0.0871 mmol) in CCl4 (0.4 mL), MeCN (0.4 mL), and water
(0.6 mL) were added NaIO4 (46.5 mg, 0.2177 mmol) and RuO2‚
H2O (0.6 mg), and the reaction mixture was stirred vigorously
at room temperature for 1 h. The reaction mixture was
extracted with EtOAc and the extract was washed with water
and brine, dried, and concentrated in vacuo. Purification by
flash chromatography (8% acetone in hexane) gave 33 (70.3
mg, 80%) as a yellow oil. [R]24 -7.32 (c 0.43, CHCl3); IR
D
(CHCl3) 1716, 1463, 1383, 1074 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 0.03 (6H, s), 0.07 (3H, s), 0.08 (3H, s), 0.85 (9H, s),
0.86 (9H, s), 1.19 (3H, s), 1.30 (3H, s), 1.36 (3H, s), 1.41 (3H,
s), 1.47 (3H, s), 1.46-1.58 (2H, m), 1.75-1.95 (8H, m), 2.10
(1H, ddd, J ) 12.2, 4.4, 4.4 Hz), 2.27 (1H, ddd, J ) 12.2, 4.4,
4.4 Hz), 2.68 (1H, dd, J ) 16.1, 9.3 Hz), 2.82 (1H, dd, J ) 16.1,
9.3 Hz), 2.98 (2H, dd, J ) 16.1, 2.9 Hz), 3.12 (1H, ddd, J )
11.7, 11.7, 4.4 Hz), 3.17 (1H, m), 3.23 (1H, ddd, J ) 11.2, 9.3,
4.9 Hz), 3.31 (1H, dd, J ) 11.7, 4.4 Hz), 3.39 (1H, ddd, J )
10.7, 9.3, 4.9 Hz), 3.43 (1H, d, J ) 10.2 Hz), 3.47-3.53 (5H,
m), 3.57 (1H, dd, J ) 11.7, 3.9 Hz), 3.83 (1H, ddd, J ) 9.3, 9.3,
2.9 Hz), 4.41 and 4.44 (each 1H, d, J ) 13.2 Hz), 4.45 and
4.54 (each 1H, d, J ) 11.7 Hz), 7.24-7.35 (10H, Ar); 13C NMR
(100 MHz, CDCl3) δ -4.7, -4.1, -4.0 (2 × C), 16.2, 17.9, 18.4,
19.3, 25.6, 25.6 (3 × C), 25.7 (3 × C), 29.2, 29.3, 29.4, 29.5,
29.7, 34.7, 38.6, 39.55, 39.65, 40.7, 65.9, 69.8, 70.2, 70.78, 70.80,
71.1, 71.3, 72.9, 73.0, 75.7, 77.7, 77.9, 79.0, 79.9, 80.0, 80.9,
99.9, 127.4, 127.6, 128.3, 128.4, 129.6, 138.5, 138.7, 197.7,
197.9; HRFABMS calcd for C56H89O12Si2 (MH+) 1009.5887,
found 1009.5851.
ABCDEF -Rin g F r a gm en t (3). To a solution of diketone
33 (338 mg, 0.3350 mmol) in MeOH (3.4 mL) and trimethyl
orthoformate (3.4 mL) was added CSA (156 mg, 0.670 mmol).
The reaction mixture was stirred at room temperature for 1.5
h and then heated at 80 °C for 12 h. After the solution was
cooled to room temperature, reaction was quenched with
triethylamine (0.5 mL) and the mixture was concentrated in
vacuo. Purification by flash chromatography (8% acetone in
hexane) gave a mixture of 34 and its isomers (223 mg, 87%).
To a solution of the mixture (223 mg, 0.290 mmol) and
triethylsilane (0.465 mL, 2.909 mmol) in CH2Cl2 (2.9 mL) was
added TMSOTf (0.116 mL, 0.640 mmol) at 0 °C, and the
reaction mixture was stirred at 0 °C for 90 min. The reaction
was quenched with saturated aqueous NaHCO3 and the
mixture was extracted with EtOAc. The extract was washed
with water and brine, dried, and concentrated in vacuo.
Purification by flash chromatography (20f30% EtOAc in Et2O)
gave the ABCDEF fragment 3 (144 mg, 70%) as a crystalline
(2R,3S,4a R,5a S,6a R,10a S,11a R,13a S)-2-{4-[(2S,3R,5S,-
6R )-5-Be n zyloxy-6-(2-b e n zyloxye t h yl)-3-(t er t -b u t yld i-
methylsilyloxy)-6-methyl-tetrahydropyran-2-yl]-but-2-ynyl}-
3-(ter t-bu tyldim eth ylsilyloxy)-8,8,10a,11a-tetr am eth yl-do-
decah ydr o-1,5,7,9,11-pen taoxa-ben zo[4,5]cycloh epta[1,2-b]-
n a p h th a len e (4). To a stirred solution of acetylene 15 (347
mg, 0.683 mmol) and triflate 6 (141 mg, 0.227 mmol) in THF
(2.3 mL) and HMPA (0.2 mL, 1.138 mmol) was added n-BuLi
(0.390 mL of a 1.58 M solution in hexane) at -78 °C, and the
reaction mixture was stirred for 30 min. The reaction was
quenched with saturated aqueous NH4Cl and the mixture was
extracted with EtOAc. The extract was washed with water and
brine, dried, and concentrated in vacuo. Purification by flash
chromatography (10f25% Et2O in hexane) gave 4 (178 mg,
80%) as a colorless oil. [R]24D -3.91 (c 0.65, CHCl3); IR (CHCl3)
solid, mp 159-160 °C. [R]25 +0.95 (c 1.0, CHCl3); IR (CHCl3)
D
3674, 3462, 1455, 1066 cm-1; 1H NMR (400 MHz, acetone-d6)
δ 1.11 (3H, s), 1.21 (3H, s), 1.26 (3H, s), 1.31 (1H, q, J ) 11.7
Hz), 1.36 (1H, q, J ) 11.7 Hz), 1.40 (1H, q, J ) 11.7 Hz), 1.48
(1H, q, J ) 11.7 Hz), 1.73-1.82 (2H, m), 1.80 (1H, q, J ) 11.7
Hz), 1.87-1.96 (5H, m), 2.10 (1H, ddd, J ) 11.7, 3.7, 3.7 Hz),
2.20 (1H, ddd, J ) 11.7, 3.7, 3.7 Hz), 2.33 (1H, ddd, J ) 11.7,
4.4, 4.4 Hz), 2.93 (1H, ddd, J ) 11.7, 9.5, 4.4 Hz), 3.00 (1H,
ddd, J ) 11.7, 8.8, 3.7 Hz), 3.02 (1H, ddd, J ) 11.7, 11.0, 3.7
Hz), 3.07 (1H, ddd, J ) 11.7, 9.5, 4.4 Hz), 3.11 (1H, ddd, J )
11.7, 8.8, 4.4 Hz), 3.17-3.22 (2H, m), 3.24-3.36 (4H, m), 3.42
(1H, dd, J ) 11.7, 3.7 Hz), 3.52 (1H, dd, J ) 11.7, 4.4 Hz),
3.56-3.63 (2H, m), 3.87 (1H, m), 3.90 (1H, br d, J ) 4.4 Hz,
1463, 1383, 1259, 1074 cm-1 1H NMR (400 MHz, CDCl3) δ
;
0.04 (3H, s), 0.07 (3H, s), 0.08 (6H, s), 0.87 (18H, s), 1.21 (3H,
s), 1.31 (3H, s), 1.37 (3H, s), 1.41 (3H, s), 1.47 (3H, s), 1.48
(1H, q, J ) 11.2 Hz), 1.52 (1H, q, J ) 12.2 Hz), 1.78-1.91 (4H,
m), 1.92-2.04 (4H, m), 2.10 (1H, ddd, J ) 12.2, 4.4, 4.4 Hz),
2.24-2.32 (3H, m), 2.50 (1H, dd, J ) 17.0, 2.4 Hz), 2.58 (1H,
dd, J ) 17.1, 2.4 Hz), 3.08 (1H, ddd, J ) 8.8, 6.8, 2.9 Hz), 3.15-
3.24 (2H, m), 3.30-3.41 (3H, m), 3.43 (1H, d, J ) 10.3 Hz),
3.48 (1H, m), 3.50 (1H, d, J ) 10.3 Hz), 3.54 (1H, dd, J ) 11.2,
4.9 Hz), 3.59 (1H, dd, J ) 11.7, 3.9 Hz), 3.61-3.73 (2H, m),
4.45 and 4.55 (each 1H, d, J ) 11.7 Hz), 4.46 (2H, s), 7.25-
J . Org. Chem, Vol. 68, No. 23, 2003 9059

Mori et al.
OH), 4.44 and 4.46 (each 1H, d, J ) 12.5 Hz), 4.49 and 4.65
(each 1H, d, J ) 11.7 Hz), 7.25-7.34 (10H, Ar); 13C NMR (100
MHz, CDCl3) δ 17.1, 19.0, 23.5, 31.2, 33.2, 33.3, 36.1, 36.5,
37.9, 40.3, 40.6, 66.4, 68.8, 69.3, 70.1, 71.4, 73.2, 76.6, 77.1,
77.6, 77.7, 77.80, 77.81, 78.0, 78.2, 79.0, 80.5, 81.67, 81.71,
128.0, 128.2, 128.3, 128.5, 128.9, 129.0, 139.9, 140.0; HR-
FABMS calcd for C41H57O10 (MH+) 709.3948, found 709.3932.
Culture, Sports, Science and Technology, J apan, and a
Grant-in-Aid for Creative Scientific Research (No.
14GS0214) from J apan Society for the Promotion of
Sciences.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
compounds 3-6, 12-15, and 18-34. This material is available
free of charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research and the High-Tech
Research Center Project from the Ministry of Education,
J O035145D
9060 J . Org. Chem., Vol. 68, No. 23, 2003