Formal synthesis of (-)-anisomycin based on stereoselective nucleophilic substitution along with 1,2-aryl migration

Article abstract of DOI:10.1016/j.tet.2004.09.012

The stereoselective conversion of (4R)-5-hydroxy-4-(4′-methoxyphenyl) -2(E)-pentenoate 4 into the (4S)-4-hydroxy-5-(4′-methoxyphenyl)-2(E)- pentenoate 5 using the AgNO₃/MS 4 ?/MeNO₂ system was accomplished along with complete inversi

Full text of DOI:10.1016/j.tet.2004.09.012

Tetrahedron 60 (2004) 10187–10195
Formal synthesis of (K)-anisomycin based on stereoselective
nucleophilic substitution along with 1,2-aryl migration*
*
Machiko Ono, Shin Tanikawa, Keiko Suzuki and Hiroyuki Akita
School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Received 20 July 2004; accepted 2 September 2004
Abstract—The stereoselective conversion of (4R)-5-hydroxy-4-(40-methoxyphenyl)-2(E)-pentenoate 4 into the (4S)-4-hydroxy-5-(40-
˚
methoxyphenyl)-2(E)-pentenoate 5 using the AgNO3/MS 4 A/MeNO2 system was accomplished along with complete inversion at the C4-
position, and the synthesis of the intermediate (4S)-7 for the chiral synthesis of (K)-anisomycin 6 from (4S)-7 based on osmium tetroxide-
catalyzed stereoselective hydroxylation was achieved.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
pathogenic protozoa and fungi and has clinically been
used with success in the treatment of vaginitis due
to trichomonas vaginilis and of amoebic dysentery3
(Scheme 1).
We previously reported that silica gel promotes the
g-lactonization and the concomitant 1,2-aryl migration of
4-aryl-5-tosyloxy pentanoate 1 to give g-lactone 2 along
with complete inversion in high yield.2 In the case of this
reaction, an intramolecular attack of the ester carbonyl
group to the s-bridged phenonium ion A proceeded
selectively at the C4-position to provide the g-lactone. If
the 4-aryl-5-tosyloxy-2(E)-pentenoate 3 is subjected to
solvolysis in the presence of a nucleophile, 1,2-aryl
migration followed by intermolecular nucleophilic substi-
tution along with inversion at the C4-position should occur
to afford the 5-aryl-4-substituted-2(E)-pentenoate deriva-
tives B. However, this type of reaction has not been reported
so far. In this paper, we wish to report both the possibility of
the above-mentioned reaction and its stereochemical course.
After the reaction was established, we describe the
stereoselective conversion of (4R)-5-hydroxy-4-(40-
methoxyphenyl)-2(E)-pentenoate 4 into the (4S)-4-
hydroxy-5-(40-methoxyphenyl)-2(E)-pentenoate 5 and its
application to the formal total synthesis of (K)-anisomycin
6 via synthetic intermediate (4S)-7.
2. 1,2-Aryl migration under solvolysis condition
At first, 1,2-aryl migration along with the intermolecular
nucleophilic substitution at the C4-position using (G)-4 and
(G)-8 was examined. The reported substrate (G)-44 was
treated with Ts2O to give the corresponding tosylate (G)-9
(96% yield) which was subjected to solvolysis in water-
saturated MeNO2 to provide an inseparable mixture of (G)-
5 and (G)-9. This mixture was subjected to enzymatic
hydrolysis using lipase OF-360 from Candida rugosa to
afford the desired (G)-5 (51% yield) together with the
starting (G)-9 (34% recovery). The structure of (G)-5 was
determined by NMR analysis and finally confirmed by
conversion of (4R)-4 into the synthetic intermediate (4S)-7
for (K)-anisomycin 6 as described later in the text. The
second substrate (G)-84 was also converted to the tosylate
(G)-10 (80% yield) which was subjected to solvolysis
under the same conditions as for (G)-9 to afford the 1,2-
migration product (G)-12 (53% yield). The structure of
(G)-12 was confirmed by NMR analysis and the similar
spectrum of (G)-12 to that of (G)-5. In the case of these
reactions, the reaction rate was found to be sluggish at 90 8C
for 2–4 d. It was apparent that there was no difference in
reactivity between the substrates (G)-9 and (G)-10
(Scheme 2).
The antibiotic (K)-anisomycin 6, isolated from the
fermentation broth of Streptomyces sp., was reported to
possess the 2R,3S,4S absolute configuration.3 (K)-Aniso-
mycin 6 exhibits strong and selective activity against
* See Ref. 1.
Keywords: (K)-Anisomycin; 1,2-Aryl migration; Phenonium ion.
* Corresponding author. Tel.: C81-474-72-1805; fax: C81-474-76-6195;
e-mail: akita@phar.toho-u.ac.jp
Then, the leaving group in the substrate (G)-4 was
exchanged to a bromo group. Bromination of (G)-4 gave
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.09.012

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M. Ono et al. / Tetrahedron 60 (2004) 10187–10195
Scheme 1.
the corresponding bromide (G)-135 (83% yield) which was
subjected to solvolysis in the same manner as in the case of
(G)-9 to afford (G)-5 (6% yield) and an inseparable
mixture (G)-13:(G)-14Z1.5:1) of the starting (G)-13 and
an aryl migration product (G)-14 (Scheme 3).
˚
molecular sieves (MS 4 A) at room temperature for 12 h
to furnish the nitrate (G)-15 in 63% overall yield from (G)-
13. In order to check an effect on the silver salt, six kinds of
silver salts were examined in H2O–saturated MeNO2 and
the results are shown in Table 1.
The structure of (G)-14 could be determined by NMR
analysis and the formation of (G)-14 could be presumed to
be attributed to the fact that the liberated bromo ion attacked
again at the C(4)-position of the s-bridged phenonium ion C
to provide (G)-14. In order to confirm this presumption,
conversion of the bromo group in (G)-14 to an oxygen
functional group was carried out. The above-mentioned
mixture was treated with AgNO3 in the presence of
In the cases of entries 1, 2, 3, 5 and 6, the desired (G)-5 was
obtained in moderate yield. In the case of using silver
trifluoroacetate (entry 4) and silver nitrate (entry 7),
trifluoroacetate (G)-16 and nitrate (G)-15 were obtained
in addition to (G)-5, respectively. In terms of the reaction
conditions and reagent usefulness, AgNO3 was found to be a
suitable reagent to trap the generated bromo ion. This result
focuses on the direct formation of (G)-15 from (G)-13.
Scheme 2. (a) Ts2O/pyridine; (b) H2O/MeNO2, 90 8C, 2 d; (c) lipase OF-360; (d) CH2N2; (e) (1) H2O/MeNO2, 90 8C, 4 d; (2) CH2N2.

M. Ono et al. / Tetrahedron 60 (2004) 10187–10195
10189
˚
˚
Scheme 3. (a) CBr4/Ph3P/CH3CN; (b) H2O/MeNO2, 80 8C, 1 d; (c) AgNO3/MeNO2, MS 4 A, rt, 12 h; (d) AgNO3/MeNO2, MS 4 A, rt, 4 h; (e)
Zn/NH4OAc/MeOH, 0 8C, 1 h.
˚
(Scheme 3) The reaction of (G)-13 and AgNO3, MS 4 A in
MeNO2 at room temperature for 4 h yielded (G)-15 (91%
yield) which was treated with Zn and NH4OAc in MeOH to
give the desired (G)-5 in 88% yield from (G)-13. This
reaction was explained as follows. When substrates
possessing a methoxyl group at least at the ortho and/or
para positions of the phenyl group are applied, this type
reaction should occur because electrophilicity of the
presumed phenonium ion is adequately high. This presump-
tion should be supported by the fact that tosylate 1
possessing a methoxyl group at least at the 20, 40 and 60
positions of the phenyl ring afforded g-lactone 2 in good
yield.2 From the above-mentioned experiment of this type
reaction, MeNO2 was regarded as the best reaction solvent
and the presence of AgC was essential. Oxygen nucleo-
philes such as the hydroxyl, trifluoroacetoxyl and nitrate
groups were considered to be active, while nitrogen
nucleophiles such as the azide ion, primary or secondary
amines and phthalimide, and AgCN were inactive, to afford
the starting (G)-13.
3. Confirmation of the stereochemical course and formal
synthesis of (K)-anisomycin 6
In order to clarify the stereochemical course of the above-
mentioned reaction, the synthesis of (4R)-4 from (4R)-4,5-
epoxy-2(E)-pentenoate 17 is required because the reaction
of (G)-17 and anisole in the presence of BF3$Et2O was
reported to afford (G)-4 as a main product.4 (Scheme 4) The
synthesis of (4R)-17 was carried out by way of the following
process from the commercially available (E)-unsaturated
ester (4S)-18. By applying the reported procedure,6
subsequent treatment of (4S)-18 with 80% aqueous AcOH
at 80 8C afforded the diol (4S)-19 in quantitative yield.
Bromination of (4S)-19 with CBr4 and triphenylphosphine
in CH2Cl2 at reflux provided a mixture of bromohydrins
(4S)-20 and (4R)-21. This mixture was subjected to
silylation followed by chromatographic separation to give
the desired (4S)-20 (32% overall yield from (4S)-18) and
(4R)-22 (15% overall yield from (4S)-18). The bromohydrin
(4S)-20 was treated with K2CO3 in MeOH to afford the
Table 1.
Entry
Ag salt (equiv)
Temperature
Time (h)
Products (%)
1
2
3
4
5
6
7
Ag(CF3SO3) (2.0)
AgClO4 (2.0)
AgClO4 (0.8)
Ag(CF3COO) (2.0)
Ag2CO3 (2.0)
Ag2SO4 (2.0)
K20 to 0 8C
08C–rt
08C–rt
rt
80 8C
80 8C
rt
1
1
1
(G)-5 (42%)
(G)-5 (38%)
(G)-5 (61%)
1
(G)-5C(G)-16 (59%)a
(G)-5 (49%)
(G)-5 (32%)
15
15
21
AgNO3 (2.0)
(G)-5 (28%)C(G)-15 (47%)
a
Yield after conversion of a mixture of (G)-5 and (G)-16 into (G)-5.

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M. Ono et al. / Tetrahedron 60 (2004) 10187–10195
t
Scheme 4. (a) 80% AcOH aq.; (b) CBr4/Ph3P/CH2Cl2; (c) BuMe2SiCl/imidazole/DMF; (d) K2CO3/MeOH; (e) PhCH2OH/BF3$Et2O/CH2Cl2; (f) AlCl3/m-
˚
xylene/CH2Cl2; (g) anisole/BF3$Et2O/CH2Cl2; (h) AgNO3/MS 4 A/MeNO2; (i) Zn/NH4OAc/MeOH; (j) (1) OsO4/N-methylmorpholine N-oxide/acetone–H2O,
(2) recrystallization; (k) MOM-Cl/diisoproethylpylamine/MeCN; (l) Dibal-H/benzene.
desired (4S)-4,5-epoxy-2(E)-pentenoate 17 in 85% yield.
Optical purity of the present (4S)-17 was estimated to be
93% ee by means of HPLC analysis. Conversion of (4S)-17
into (4R)-17 without loss of optical purity was carried out by
modification of the reported procedure.7 The reaction of
(4S)-17 with benzyl alcohol in the presence of BF3$Et2O
gave (4R)-23 ([a]DZK57.0 (cZ0.52, CHCl3) correspond-
ing to 93% ee) in 55% yield. Bromination of (4R)-23
provided (4R)-24 ([a]DZK40.2 (cZ0.52, CHCl3) corre-
sponding to 93% ee; 95% yield)) followed by deprotection
of the benzyl group using the AlCl3/m-xylene system7
afforded bromohydrin (4R)-20 ([a]D K2.50 (cZ0.52,
CHCl3) in 87% yield. An alkaline treatment of (4R)-20
yielded the desired (4R)-17 ([a]DZK29.1 (cZ0.51,
CHCl3) corresponding to 93% ee) in 85% yield. The
reaction of (4R)-17 and anisole in the presence of BF3$Et2O
followed by enzymatic separation gave (4R)-4 ([a]DZ
C2.00 (cZ0.51, CHCl3) corresponding to 93% ee; 47%
yield) and (4R)-8 ([a]DZC17.7 (cZ0.50, CHCl3) corre-
sponding to 93% ee; 14% yield). The former (4R)-4 was
converted into the bromide (4R)-13 ([a]DZC3.00 (cZ0.5,
CHCl3) in 92% yield in the same way as (G)-13. Treatment
˚
of (4R)-13 with AgNO3 and MS 4 A in MeNO2 furnished
the nitrate (4S)-15 ([a]DZC15.9 (cZ0.51, CHCl3); 91%
yield) which was converted to the desired (4S)-5 ([a]DZ
C1.00 (cZ0.5, CHCl3) corresponding to 93% ee) in 87%
yield in the same way as in the case of (G)-15. Osmium
tetroxide-catalyzed dihydroxylation followed by treatment
with N-methylmorpholine N-oxide gave the 3,4-anti-g-
lactone (4S)-25 ([a]DZK72.2 (cZ0.41, MeOH)
corresponding to 93% ee; 78% yield) and the 3,4-syn-
diastereomer ([a]DZK86.0 (cZ0.11, MeOH); 2% yield).
This high diastereoselectivity (3,4-anti: 3,4-synZ39:1) was
understood by the reported explanation.8 A transition state
D in which the carbon–oxygen bond is near the plane of the
conjugated double bond is compatible with the observed
stereochemical course of the hydroxylation reaction. Pre-
sumably, this conformation results from a favorable
interaction between the p-orbital of the double bond and
an unshared pair on the g-oxygen. Consequently, osmium
tetroxide attacks from the less stereochemically hindered
b-side. Recrystallization of the 93% ee of (4S)-25 afforded

M. Ono et al. / Tetrahedron 60 (2004) 10187–10195
10191
the enantiomerically pure (4S)-25. Treatment of (4S)-25
with chloromethyl methyl ether (MOM-Cl) furnished the di-
MOM ether (4S)-26 ([a]DZK19.7 (cZ0.49, CHCl3); 78%
yield). Reduction of (4S)-26 with Dibal-H gave the (4S)-diol
7 ([a]DZK39.3 (cZ0.51, MeOH)) in 81% yield, whose
spectral data were identical with those ([a]DZK22.7 (cZ
4.1.2. (G) Methyl 4-(20-methoxyphenyl)-5-tosyloxy-2(E)-
pentenoate 10. A mixture of (G)-8 (1.042 g, 4.41 mmol),
p-toluenesulfonic anhydride (Ts2O, 1.73 g, 5.3 mmol),
pyridine (2 mL) in benzene (15 mL) was stirred for 3 d at
50 8C. The reaction mixture was worked up in the same way
for (G)-9 to afford (G)-10 (1.38 g, 80%) as a colorless oil.
(G)-9: IR (neat): 1722 cmK1; 1H NMR: d 2.44 (3H, s), 3.71
(3H, s), 3.73 (3H, s), 4.16 (1H, q, JZ10 Hz), 4.26 (1H, dd,
JZ6, 10 Hz), 4.30 (1H, dd, JZ7, 10 Hz), 5.80 (1H, dd, JZ
2, 16 Hz), 6.81 (1H, d, JZ8 Hz), 6.87 (1H, t, JZ8 Hz), 7.00
(1H, dd, JZ2, 8 Hz), 7.02 (1H, dd, JZ8, 16 Hz), 7.23 (1H,
dt, JZ2, 8 Hz), 7.295 (2H, d, JZ8 Hz), 7.69 (2H, d, JZ
9 Hz). Anal. Calcd for C20H22SO6: C, 61.52; H, 5.68.
Found: C, 61.09; H, 5.87. MS (FAB) m/z: 391 (MCC1).
1
16.21, MeOH) and H NMR) of the reported (4S)-7.9 The
synthesis of (K)-anisomycin 6 from (4S)-7 is already
achieved.9 From these experiments, conversion of the
bromide (4R)-13 into the nitrate (4S)-15 from a stereo-
chemical point of view was found to occur along with
complete inversion at the C4-position. In conclusion, the
stereoselective conversion of (4R)-5-hydroxy-4-(40-
methoxypheny)-2(E)-pentenoate
4 into the (4S)-4-
hydroxy-5-(40-methoxyphenyl)-2(E)-pentenoate 5 using
˚
the AgNO3/MS 4 A/MeNO2 system was accomplished
4.1.3. Solvolysis of (G)-9. A solution of (G)-9 (0.500 g,
1.28 mmol) in water-saturated nitromethane (50 mL) was
stirred for 2 d at 90 8C. The reaction mixture was diluted
with water and extracted with ether. The organic layer was
dried over MgSO4 and evaporated to give a residue. A
suspension of the above-mentioned residue and lipase OF-
360 from Candida rugosa (0.20 g) in phosphate buffer (pH
7.4, 150 mL) was stirred for 3 d at 33 8C. The reaction
mixture was extracted with ether and the organic layer was
dried over MgSO4. Evaporation of the organic solvent
gave a residue, which was chromatographed on silica gel
(20 g, n-hexane/AcOEtZ5:1) to afford (G)-9 (0.170 g,
34% recovery). On the other hand, the water layer was
acidified with 1 M aqueous HCl and extracted with ether.
Evaporation of the organic solvent gave a residue (G)-11,
which was treated with CH2N2–ether solution to afford an
oil. It was chromatographed on silica gel (20 g, n-hexane/
AcOEtZ5:1) to afford (G)-5 (0.153 g, 51%) as a colorless
along with complete inversion at the C4-position, and the
synthesis of the intermediate (4S)-7 for the chiral synthesis
of (K)-anisomycin 6 from (4S)-5 based on osmium
tetroxide-catalyzed stereoselective hydroxylation was
achieved.
4. Experimental
4.1. General
All melting points were measured on a Yanaco MP-3S
micro melting point apparatus and are uncorrected. 1H NMR
spectra were recorded by a JEOL EX 400 spectrometer
(Tokyo, Japan). Spectra were taken with 5–10% (w/v)
solution in CDCl3 with Me4Si as an internal reference.
High-resolution mass spectra (HRMS) and the fast atom
bombardment mass spectra (FAB MS) were obtained with a
JEOL JMS-DX 303 (matrix; glycerol, m-nitrobenzyl
alcohol) spectrometer. IR spectra were recorded on a
JASCO FT/IR-300 spectrometer. The HPLC system was
composed of a detector (UV detector SSC-5200, Senshu),
pump (SSC-3210, Senshu) and integrator (chromatocorder
SIC 21). HPLC analysis conditions were as follows;
column: CHIRALCEL AS, eluent: n-hexane/EtOHZ
100:1, Detection: UV at 254 nm, Flow rate; 1 mL/min. All
evaporations were performed under reduced pressure. For
column chromatography, silica gel (Kieselgel 60) was
employed.
1
oil. (G)-5: IR (neat): 3456, 1722 cmK1; H NMR: d 2.12
(1H, br.s), 2.73 (1H, dd, JZ8, 14 Hz), 2.88 (1H, dd, JZ5,
14 Hz), 3.73 (3H, s), 3.78 (3H, s), 4.47 (1H, dq, JZ2, 5 Hz),
6.05 (1H, dd, JZ2, 16 Hz), 6.85 (2H, d, JZ8 Hz), 6.99 (1H,
dd, JZ5, 16 Hz), 7.13 (2H, d, JZ8 Hz). Anal. Calcd for
C13H16O4: C, 66.09; H, 6.83. Found: C, 65.95; H, 6.85. MS
(FAB) m/z: 237 (MCC1).
4.1.4. Solvolysis of (G)-10. A solution of (G)-10 (0.251 g,
0.64 mmol) in water-saturated nitromethane (40 mL) was
stirred for 4 d at 90 8C. The reaction mixture was diluted
with water and extracted with ether. The organic layer was
dried over MgSO4 and evaporated to give a residue, which
was treated with CH2N2–ether solution to afford an oil. It
was chromatographed on silica gel (20 g, n-hexane/
AcOEtZ5:1) to afford (G)-12 (0.081 g, 53%) as a colorless
4.1.1. (G) Methyl 4-(40-methoxyphenyl)-5-tosyloxy-2(E)-
pentenoate 9. A mixture of (G)-4 (2.774 g, 11.7 mmol),
p-toluenesulfonic anhydride (Ts2O, 4.60 g, 14.1 mmol),
pyridine (1.40 g, 17.7 mmol) in benzene (25 mL) was
stirred for 2 d at 50 8C. The generated precipitate was
filtered off with the aid of celite and the filtrate was washed
with 1 M aqueous HCl and 7% aqueous NaHCO3. The
organic layer was dried over MgSO4 and evaporated to give
a residue, which was chromatographed on silica gel (80 g,
n-hexane/AcOEtZ5:1) to afford (G)-9 (4.393 g, 96%) as a
colorless oil. (G)-9: IR (neat): 1722 cmK1; 1H NMR: d 2.44
(3H, s), 3.71 (3H, s), 3.76 (1H, br.q, JZ8 Hz), 3.79 (3H, s),
4.20 (2H, d, JZ7 Hz), 5.79 (1H, dd, JZ2, 16 Hz), 6.81 (2H,
d, JZ8 Hz), 6.97 (1H, dd, JZ8, 16 Hz), 7.00 (2H, d, JZ
8 Hz), 7.30 (2H, d, JZ8 Hz), 7.70 (2H, d, JZ8 Hz). Anal.
Calcd for C20H22SO6: C, 61.52; H, 5.68. Found: C, 61.32;
H, 5.56. MS (FAB) m/z: 391 (MCC1).
1
oil. (G)-12: IR (neat): 3451, 1717 cmK1; H NMR: d 2.49
(1H, br.s), 2.82 (1H, dd, JZ8, 14 Hz), 3.01 (1H, dd, JZ5,
14 Hz), 3.73 (3H, s), 3.84 (3H, s), 4.56 (1H, ddt, JZ2, 5,
5 Hz), 6.06 (1H, dd, JZ2, 16 Hz), 6.88 (1H, br.d, JZ9 Hz),
6.92 (1H, t, JZ8 Hz), 7.02 (1H, dd, JZ5, 16 Hz), 7.13 (1H,
dd, JZ2, 8 Hz), 7.24 (1H, t, JZ8 Hz). Anal. Calcd for
C13H16O4: C, 66.09; H, 6.83. Found: C, 65.67; H, 6.80. MS
(FAB) m/z: 237 (MCC1).
4.1.5. (G) Methyl-5-bromo-4-(40-methoxyphenyl)-2(E)-
pentenoate 13. To a solution of (G)-4 (2.012 g, 8.52 mmol)
in MeCN (40 mL) were added triphenyl phosphine (Ph3P;
10.06 g, 38.4 mmol) and N-bromosuccinimide (NBS;
6.83 g, 38.3 mmol) at 0 8C and the reaction mixture was

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M. Ono et al. / Tetrahedron 60 (2004) 10187–10195
stirred for 2 h at room temperature. The reaction mixture
was diluted with water and extracted with ether. The organic
layer was dried over MgSO4 and evaporated to give a
residue, which was chromatographed on silica gel (80 g,
n-hexane/AcOEtZ5:1) to afford (G)-13 (2.104 g, 83%) as
4) To a solution of (G)-13 (0.401 g, 1.34 mmol) in water-
saturated nitromethane (10 mL) was added silver
trifluoroacetate (Ag(CF3COO); 0.592 g, 2.68 mmol)
and the whole mixture was stirred for 1 h at room
temperature. The reaction mixture was worked up in the
same way as 1) to afford a mixture (0.42 g) of (G)-5 and
(G)-16. To a solution of the above mixture in MeOH
(8 mL) was added K2CO3 (90 mg) and the whole
mixture was stirred for 1.5 h at room temperature. The
reaction mixture was diluted with water and extracted
with ether. The organic layer was washed with brine and
dried over MgSO4. Evaporation of the organic solvent
gave a residue, which was chromatographed on silica
gel (10 g, n-hexane/AcOEtZ15:1) to afford (G)-5
(0.188 g, 59%).
5) To a solution of (G)-13 (0.401 g, 1.34 mmol) in water-
saturated nitromethane (10 mL) was added silver
carbonate (Ag2CO3; 0.739 g, 2.68 mmol) and the
whole mixture was stirred for 15 h at 80 8C. The reaction
mixture was worked up in the same way as 1) to afford
(G)-5 (0.155 g, 49%).
6) To a solution of (G)-13 (0.401 g, 1.34 mmol) in water-
saturated nitromethane (10 mL) was added silver sulfate
(Ag2SO4; 0.835 g, 2.68 mmol) and the whole mixture
was stirred for 15 h at 80 8C. The reaction mixture was
worked up in the same way as 1) to afford (G)-5
(0.100 g, 32%).
1
a colorless oil. (G)-13: IR (neat): 1723 cmK1; H NMR: d
3.60 (2H, dd, JZ2, 7 Hz), 3.73 (3H, s), 3.79 (3H, s), 3.80
(1H, br.q, JZ7 Hz), 5.88 (1H, dd, JZ2, 16 Hz), 6.88
(2H, d, JZ9 Hz), 7.09 (1H, dd, JZ8, 16 Hz), 7.11 (2H, d,
JZ9 Hz). Anal. Calcd for C13H15BrO3: C, 52.19; H,
5.05. Found: C, 52.48; H, 4.64. MS (FAB) m/z: 299, 301
(MCC1).
4.1.6. Solvolysis of (G)-13. A solution of (G)-13 (0.500 g,
1.67 mmol) in water-saturated nitromethane (20 mL) was
stirred for 12 h at 80 8C. The reaction mixture was diluted
with water and extracted with ether. The organic layer was
dried over MgSO4 and evaporated to give a residue, which
was chromatographed on silica gel (20 g) to afford a mixture
(0.382 g) of (G)-13 and (G)-14 from n-hexane/AcOEtZ
10:1eluent and (G)-5 (0.024 g, 6%) from n-hexane/
AcOEtZ5:1eluent. To a solution of this mixture (0.382 g)
˚
in MeNO2 (10 mL) were added molecular sieves (4 A;
0.5 g) and silver nitrate (AgNO3; 0.43 g, 2.53 mmol) and the
whole mixture was stirred for 12 h at room temperature. The
generated precipitate was filtered off with the aid of celite
and the filtrate was diluted with water and ether. The organic
layer was washed with brine and dried over MgSO4.
Evaporation of the organic solvent gave a residue, which
was chromatographed on silica gel (20 g, n-hexane/
AcOEtZ30:1) to afford (G)-15 (0.298 g, 63% overall
yield) as a colorless oil. (G)-15: IR (neat): 1726 cmK1; 1H
NMR: 2.93 (1H, dd, JZ6, 14 Hz), 3.03 (1H, dd, JZ7,
15 Hz), 3.75 (3H, s), 3.79 (3H, s), 5.58 (1H, dq, JZ2, 6 Hz),
6.01 (1H, dd, JZ2, 16 Hz), 6.84 (1H, dd, JZ6, 16 Hz), 6.85
(2H, d, JZ8 Hz), 7.12 (2H, d, JZ8 Hz). Anal. Calcd for
C13H15NO6: C, 55.51; H, 5.38; N, 4.98. Found: C, 55.77; H,
5.32; N, 5.02. MS (FAB) m/z: 281 (MC).
7) To a solution of (G)-13 (0.400 g, 1.33 mmol) in water-
saturated nitromethane (10 mL) was added silver nitrate
(AgNO3; 0.451 g, 2.66 mmol) and the whole mixture
was stirred for 21 h at room temperature. The reaction
mixture was worked up in the same way as 1) to afford
(G)-15 (0.175 g, 47%) and (G)-5 (0.087 g, 28%).
4.1.8. Synthesis of (G) methyl-4-hydroxy-5-(40-methoxy-
phenyl)-2(E)-pentenoate 5 from (G)-13 via (G)-15. To a
solution of (G)-13 (1.43 g, 4.78 mmol) in nitromethane
˚
(20 mL) were added molecular sieves (4 A; 2.0 g) and silver
4.1.7. Solvolysis of (G)-13 (Table 1).
nitrate (AgNO3; 1.62 g, 9.54 mmol) and the whole mixture
covered with aluminum foil was stirred for 4 h at room
temperature. The reaction mixture was worked up in the
same way as the previous (G)-15 to give (G)-15 (1.222 g,
91%). To a mixture of Zn-dust (0.7 g) and CH3COONH4
(0.5 g) in MeOH (5 mL) was added a solution of (G)-15
(0.501 g, 1.78 mmol) in MeOH (5 mL) and the whole
mixture was stirred for 1 h at 0 8C. After the generated
precipitate was filtered off with the aid of celite, the filtrate
was diluted with water and ether. The organic layer was
dried over MgSO4 and evaporated to give a residue, which
was chromatographed on silica gel (20 g, n-hexane/
AcOEtZ5:1) to afford (G)-5 (0.371 g, 88%) as a colorless
oil. The NMR data of the present (G)-5 were identical with
those of the previous (G)-5.
1) To a solution of (G)-13 (0.400 g, 1.33 mmol) in water-
saturated nitromethane (10 mL) was added silver trifrate
(Ag(CF3SO3); 0.683 g, 2.66 mmol) and the whole
mixture was stirred for 1 h at 0 8C. The generated
precipitate was filtered off with the aid of celite and the
filtrate was diluted with water and ether. The organic
layer was washed with brine and dried over MgSO4.
Evaporation of the organic solvent gave a residue, which
was chromatographed on silica gel (10 g, n-hexane/
AcOEtZ15:1) to afford (G)-5 (0.132 g, 42%).
2) To a solution of (G)-13 (0.403 g, 1.34 mmol) in water-
saturated nitromethane (10 mL) was added silver
perchlorate (AgClO4; 0.555 g, 2.68 mmol) and the
whole mixture was stirred for 1 h at 0 8C. The reaction
mixture was worked up in the same way as 1) to afford
(G)-5 (0.119 g, 38%).
4.1.9. Methyl (4S)-(4,5)-epoxy-2(E)-pentenoate 17. (1) A
solution of commercially available (4S)-18 (31.19 g,
0.17 mol) in 80% aqueous AcOH (200 mL) was stirred for
30 min at 80 8C. The reaction mixture was diluted with
toluene and condensed under reduced pressure to give a
crude diol (4S)-19 (25.21 g, quantitative yield). (2) To a
solution of (4S)-19 (25.21 g) in CH2Cl2 (120 mL) were
added Ph3P (16.92 g, 0.0645 mol) and carbon tetrabromide
3) To a solution of (G)-13 (0.400 g, 1.33 mmol) in water-
saturated nitromethane (10 mL) was added silver
perchlorate (AgClO4; 0.220 g, 1.06 mmol) and the
whole mixture was stirred for 1 h at 0 8C. The reaction
mixture was worked up in the same way as 1) to afford
(G)-5 (0.193 g, 61%).

M. Ono et al. / Tetrahedron 60 (2004) 10187–10195
10193
(CBr4; 21.39 g, 0.0645 mol) and the whole mixture was
refluxed for 1 h with stirring. The reaction mixture was
evaporated to afford a residue, which was chromatographed
on silica gel (150 g, n-hexane/AcOEtZ10:1) to provide an
inseparable mixture (18.81 g) of (4S)-20 and (4R)-21. (3) To
a solution of the above-mentioned mixture (18.81 g) in
DMF (120 mL) were added imidazole (18.38 g, 0.270 mol)
and tert-butyldimethylsilyl chloride (TBDMSCl; 5.42 g,
0.034 mol) at 0 8C and the whole mixture was stirred for 2 h
at 0 8C. The reaction mixture was diluted with brine and
extracted with ether. The organic layer was dried over
MgSO4 and evaporated to provide a residue, which was
chromatographed on silica gel (200 g) to afford an oily (4R)-
22 (8.25 g, 15% overall yield from (4S)-18) from n-hexane/
AcOEtZ20:1 elute and an oily (4S)-20 (11.11 g, 32%
overall yield from (4S)-18) from n-hexane/AcOEtZ5:1
elute, respectively. (4S)-20: IR (neat): 3451, 1716 cmK1; 1H
NMR: d 2.72 (1H, d, JZ7 Hz), 3.42 (1H, dd, JZ7, 11 Hz),
3.57 (1H, dd, JZ4, 11 Hz), 3.76 (3H, s), 4.51–4.58 (1H, m),
6.16 (1H, dd, JZ2, 16 Hz), 6.88 (1H, dd, JZ5, 16 Hz). MS
(FAB) m/z: 209.211 (MCC1). (4R)-22: IR (neat):
(3.596 g, 95%) as a colorless oil. (4R)-24: [a]2D4ZK40.2
(cZ0.52, CHCl3) corresponding to 93% ee); IR (neat):
1
1722 cmK1; H NMR: d 3.41 (1H, dd, JZ7, 12 Hz), 3.46
(1H, dd, JZ7, 12 Hz), 3.77 (3H, s), 4.21 (1H, dq, JZ2,
7 Hz), 4.50 (1H, d, JZ12 Hz), 4.63 (1H, d, JZ12 Hz), 6.13
(1H, dd, JZ2, 15 Hz), 6.86 (1H, dd, JZ7, 15 Hz), 7.28–
7.40 (5H, m). Anal. Calcd for C13H15BrO3: C, 52.19; H,
5.05. Found: C, 51.65; H, 4.88. MS (FAB) m/z: 299.301
(MCC1). (3) To a suspension of AlCl3 (8.92 g, 66.9 mmol)
in CH2Cl2 (120 mL) was added a solution of (4R)-24
(10.167 g, 34 mmol) in m-xylene (25 mL) at K20 8C and
the whole mixture was stirred for 30 min at the same
temperature. The reaction mixture was poured into ice-
water and extracted with CH2Cl2. The organic layer was
dried over MgSO4 and evaporated to provide a residue,
which was chromatographed on silica gel (200 g, n-hexane/
AcOEtZ5:1) to afford (4R)-20 (6.170 g, 87%) as a colorless
oil. (4R)-20: [a]2D3ZK2.50 (cZ0.52, CHCl3) correspond-
ing to 93% ee. The spectral data (IR and NMR) of (4R)-20
were identical with those of (4S)-20. (4) A mixture of
˚
molecular sieves (3 A; 3.0 g) and K2CO3 (8.98 g, 65 mmol)
1
1725 cmK1; H NMR: d 0.06 (3H, s), 0.07 (3H, s), 0.88
in MeOH (350 mL) was stirred for 30 min at 0 8C, and (4R)-
20 (13.59 g, 65 mmol) in MeOH (50 mL) was slowly added
to the above-mentioned mixture. The reaction mixture was
stirred for 30 min at 0 8C and filtered with the aid of filter
paper. The MeOH was distilled under ordinary pressure
and the residue was chromatographed on silica gel (200 g,
n-hexane/AcOEtZ20:1) to afford (4R)-17 (7.101 g, 85%) as
a colorless oil. (4R)-17: [a]2D4ZK29.1 (cZ0.51, CHCl3)
corresponding to 93% ee by means of HPLC analysis),
HPLC analysis conditions were the same as for (4S)-17. The
NMR data of (4R)-17 were identical with those of the
reported (G)-17.4b
(9H, s), 3.75 (3H, s), 3.83 (1H, dd, JZ7, 11 Hz), 3.93 (1H,
dd, JZ5, 11 Hz),4.47–4.53 (1H, m), 6.02 (1H, dd, JZ1,
15 Hz), 6.93 (1H, dd, JZ9, 15 Hz). MS (FAB) m/z: 323.325
C
˚
(M C1). (4) A mixture of molecular sieves (3 A; 7.5 g)
and K2CO3 (17.1 g, 0.124 mol) in MeOH (450 mL) was
stirred for 30 min at 0 8C, and (4S)-20 (14.42 g, 0.069 mol)
in MeOH (50 mL) was slowly added to the above-
mentioned mixture. The reaction mixture was stirred for
2.5 h at 0 8C and filtered with the aid of filter paper. The
MeOH was distilled under ordinary pressure and the
residue was chromatographed on silica gel (200 g,
n-hexane/AcOEtZ20:1) to afford (4S)-17 (7.51 g, 85%) as
a colorless oil. (4S)-17: [a]2D4ZC22.3 (cZ0.51, CHCl3)
corresponding to 93% ee by means of HPLC analysis).
(4R)-17: tRZ17.1 min, (4S)-17: tRZ20.0 min. The
NMR data of (4S)-17 were identical with those of the
reported (G)-17.4b
4.1.11. Methyl (4R)-5-hydroxy-4-(40-methoxyphenyl)-
2(E)-pentenoate 4. (1) To a solution of (4R)-17 (3.71 g,
28.9 mmol) in CH2Cl2 (50 mL) were added anisole
(PhOMe; 9.39 g, 86.8 mmol) and BF3$Et2O (7 mL,
56 mmol) at K20 8C and the whole mixture was stirred
for 1 h at K20 8C. The reaction mixture was diluted with
brine and extracted with CH2Cl2. The organic layer was
dried over MgSO4 and evaporated to provide a residue,
which was chromatographed on silica gel (100 g) to afford
(4R)-8 (0.375 g, 5% yield) from n-hexane/AcOEtZ3:1
elute, and 1:3 mixture (2.620 g) of (4R)-8 and (4R)-4 from
n-hexane/AcOEtZ3:1 elute, and (4R)-4 (1.504 g, 22%
yield) from n-hexane/AcOEtZ2:1 elute, respectively. (2)
To a solution of a 1:3 mixture (2.620 g) of (4R)-8 and (4R)-4
in pyridine (5 mL) was added Ac2O (2.26 g, 22.1 mmol) and
the whole mixture was stirred for 24 h at room temperature.
The reaction mixture was diluted with brine and extracted
with ether. The organic layer was washed with 2 M aqueous
HCl, and 7% aqueous NaHCO3 and dried over MgSO4.
Evaporation of the organic solvent gave a residue, which
was chromatographed on silica gel (60 g, n-hexane/
AcOEtZ10:1) to afford a mixture of the corresponding
acetates (2.81 g). (3) A suspension of the above-mentioned
mixture (2.81 g) and lipase Amano P from Pseudomonas sp.
(0.50 g) in phosphate buffer (pH 7.4; 300 mL) was stirred at
33 8C for 12 h. The reaction mixture was filtered, and the
precipitate was washed with ether. The combined organic
layer was dried over MgSO4 and evaporated. The residue
was chromatographed on silica gel (60 g) to give an acetate
4.1.10. Methyl (4R)-(4,5)-epoxy-2(E)-pentenoate 17. (1)
To a solution of (4S)-17 (7.62 g, 0.0595 mol) in CH2Cl2
(80 mL) were added benzyl alcohol (PhCH2OH; 32.12 g,
0.298 mol) and BF3$Et2O (8 mL, 0.064 mol) at K20 8C and
the whole mixture was stirred for 1.5 h at 0 8C. The reaction
mixture was diluted with brine and extracted with CH2Cl2.
The organic layer was dried over MgSO4 and evaporated to
provide a residue, which was chromatographed on silica gel
(200 g, n-hexane/AcOEtZ5:1) to afford (4R)-23 (7.794 g,
56%) as a colorless oil. (4R)-23: [a]2D3ZK57.0 (cZ0.52,
CHCl3) corresponding to 93% ee): IR (neat): 3433,
1
1721 cmK1; H NMR: d 3.65 (1H, dd, JZ8, 12 Hz), 3.73
(1H, br.dd, JZ5, 12 Hz), 3.81 (3H, s), 4.16–4.21 (1H, m),
4.49 (1H, d, JZ12 Hz), 4.71 (1H, d, JZ12 Hz), 6.18 (1H,
dd, JZ2, 16 Hz), 6.92 (1H, dd, JZ6, 16 Hz), 7.32–7.44
(5H, m). MS (FAB) Calcd For C13H16O4 m/z: 237.1127
(MCC1). Found m/z: 237.1154. (2) To a solution of (4R)-
23 (3.00 g, 12.7 mmol) in CH2Cl2 (50 mL) were added Ph3P
(6.66 g, 25.4 mmol) and carbon tetrabromide (CBr4; 8.42 g,
25.4 mmol) at 0 8C and the whole mixture was stirred for 1 h
at room temperature. The reaction mixture was evaporated
to afford a residue, which was chromatographed on silica gel
(150 g, n-hexane/AcOEtZ20:1) to provide (4R)-24

10194
M. Ono et al. / Tetrahedron 60 (2004) 10187–10195
(0.707 g, 9% yield from (4R)-17)) of (4R)-8 from n-hexane/
AcOEtZ7:1 elute and (4R)-4 (1.737 g, total; 3.241 g
(47% overall yield from (4R)-17)) as a homogeneous oil
from n-hexane/AcOEtZ2:1 elute, respectively. (4R)-4:
[a]2D4ZC2.00 (cZ0.51, CHCl3) corresponding to 93% ee
by means of HPLC analysis), The NMR data of (4R)-4 were
identical with those of the reported (G)-4.5 Acetate of (4R)-
8: [a]2D6ZC8.98 (cZ0.50, CHCl3) corresponding to 93%
ee by means of HPLC analysis): IR (neat): 1740 cmK1; 1H
NMR: d 2.02 (3H, s), 3.72 (3H, s), 3.82 (3H, s), 4.23 (1H, br,
q, JZ7.0 Hz), 4.33 (1H, dd, JZ11.0, 5.0 Hz), 4.40 (1H, dd,
JZ11.0, 9.0 Hz), 5.87 (1H, dd, JZ16.0, 2.0 Hz), 6.88 (1H,
dd, JZ8.0, 2.0 Hz), 6.92 (1H, dt, JZ8.0, 2.0 Hz), 7.11 (1H,
dd, JZ8.0, 2.0 Hz), 7.16 (1H, dd, JZ16.0, 7.0 Hz), 7.25
(1H, dt, JZ8.0, 2.0 Hz). FAB MS m/z: 279 (MC1)C; Anal.
Found: C, 64.60; H, 6.50. Calcd for C15H18O5: C, 64.74; H,
6.52%.
stirred for 30 min. The generated precipitate was filtered
with the aid of celite and the filtrate was condensed. The
residue was diluted with ether and treated with 10% aqueous
HCl. The organic layer was dried over MgSO4 and
evaporated to give a residue, which was chromatographed
on silica gel (30 g, n-hexane/AcOEtZ1:1) to afford
diastereomeric lactone (2S,3R,4S)-25 (0.010 g, 2%) and
the desired (2R,3S,4S)-25 (0.463 g, 78%) in elution order.
Crystallization of (2R,3S,4S)-25 from CHCl3 gave a color-
less crystal. (2R,3S,4S)-25: mp 81–82 8C, [a]2D4ZK72.2
(cZ0.41, MeOH) corresponding to O99% ee by means of
1
HPLC analysis): IR (KBr): 3298, 1756 cmK1; H NMR: d
2.82 (1H, dd, JZ8, 15 Hz), 3.13 (1H, dd, JZ3, 15 Hz), 3.74
(3H, s), 3.88 (1H, t, JZ9 Hz), 4.25 (1H, dt, JZ3, 8 Hz),
4.30 (1H, d, JZ9 Hz), 6.84 (2H, d, JZ9 Hz), 7.17 (2H, d,
JZ9 Hz). Anal. Calcd for C12H14O5: C, 60.50; H, 5.92.
Found: C, 50.90; H, 5.90. MS (FAB) m/z: 239 (MCC1).
(2S,3R,4S)-25: [a]2D2ZK86.0 (cZ0.11, MeOH) corre-
sponding to 93% ee by means of HPLC analysis): IR
4.1.12. Methyl (4S)-4-hydroxy-5-(40-methoxyphenyl)-
2(E)-pentenoate 5. (1) To a solution of (4R)-4 (2.01 g,
8.51 mmol) in CH2Cl2 (40 mL) were added triphenyl
phosphine (Ph3P; 4.46 g, 17 mmol) and carbon tetrabromide
(CBr4; 8.46 g, 25.5 mmol) at 0 8C and the whole mixture
was stirred for 1.5 h at room temperature. The reaction
mixture was evaporated to afford a residue, which was
chromatographed on silica gel (80 g, n-hexane/AcOEtZ
30:1) to provide (4R)-13 (2.342 g, 92%) as a colorless oil.
(4R)-13: [a]2D7ZC3.00 (cZ0.50, CHCl3) corresponding to
93% ee by means of HPLC analysis), The NMR data of
(4R)-13 were identical with those of the reported (G)-13.
(2) To a solution of (4R)-13 (1.43 g, 4.8 mmol) in
1
(KBr): 3429, 1758 cmK1; H NMR: d 2.90 (1H, dd, JZ8,
15 Hz), 3.08 (1H, dd, JZ5, 15 Hz), 3.76 (3H, s), 4.03 (1H,
d, JZ5 Hz), 4.19 (1H, t, JZ5 Hz), 4.72 (1H, dt, JZ5,
8 Hz), 6.84 (2H, d, JZ9 Hz), 7.20 (2H, d, JZ9 Hz). Anal.
Calcd for C12H14O5: C, 60.50; H, 5.92. Found: C, 60.37; H,
5.91. MS (FAB) m/z: 239 (MCC1). (2) To a solution of
(2R,3S,4S)-25 (0.101 g, 0.42 mmol) and N,N-diisopropyl-
ethylamine (1.32 g, 9.29 mmol) in MeCN (1 mL) was added
chloromethylmethyl ether (CH3OCH2Cl; 0.68 g,
8.45 mmol) at 0 8C and the whole mixture was stirred for
24 h at room temperature. The reaction mixture was diluted
with brine and ether at 0 8C, the organic layer was dried over
MgSO4. Evaporation of the organic solvent gave a residue,
which was chromatographed on silica gel (10 g, n-hexane/
AcOEtZ8:1) to afford (2R,3S,4S)-26 (0.107 g, 78%) as a
colorless oil. (2R,3S,4S)-26: [a]2D4ZK18.7 (cZ0.49,
CHCl3) corresponding to O99% ee by means of HPLC
analysis): IR (neat): 1790 cmK1; 1H NMR: d 2.94 (1H, dd,
JZ7, 14 Hz), 3.15 (1H, dd, JZ4, 14 Hz), 3.40 (3H, s), 3.44
(3H, s), 3.79 (3H, s), 4.07 (1H, t, JZ7 Hz), 4.42 (1H, dt, JZ
4, 7 Hz), 4.47 (1H, d, JZ7 Hz), 4.65 (1H, d, JZ7 Hz), 4.73
(1H, d, JZ7 Hz), 4.79 (1H, d, JZ7 Hz), 5.02 (1H, d, JZ
7 Hz), 6.85 (2H, d, JZ8 Hz), 7.18 (2H, d, JZ8 Hz). Anal.
Calcd for C16H22O7: C, 58.89; H, 6.80. Found: C, 58.96; H,
6.97. MS (FAB) m/z: 326 (MC). (3) To a solution of
(2R,3S,4S)-26 (0.076 g, 0.23 mmol) in benzene (5 mL) was
added 1 M diisobutylaluminum hydride (Dibal-H) in
toluene solution (1.41 mL, 1.41 mmol) at 0 8C and the
whole mixture was stirred for 1 h at 0 8C. The reaction
mixture was diluted with brine and extracted with ether. The
organic layer was dried over MgSO4 and evaporated to
give a residue, which was chromatographed on silica gel
(10 g, n-hexane/AcOEtZ1:1) to afford (4S)-7 (0.062 g,
81%) as a colorless oil. (4S)-7: [a]2D4ZK39.3 (cZ0.51,
MeOH) corresponding to O99% ee by means of HPLC
analysis): IR (neat): 3439 cmK1; 1H NMR: d 2.62 (1H, dd,
JZ10, 14 Hz), 2.92 (1H, d, JZ5 Hz), 3.00 (1H, dd, JZ3,
14 Hz), 3.21 (1H, t, JZ6 Hz), 3.41 (3H, s), 3.46 (3H, s),
3.65 (1H, dd, JZ4, 7 Hz), 3.74–3.78 (2H, m), 3.79 (3H, s),
3.91–3.97 (2H, m), 4.71–4.77 (4H, m), 6.85 (2H, d, JZ
9 Hz), 7.18 (2H, d, JZ9 Hz). Anal. Calcd for C16H26O7: C,
58.17; H, 7.93. Found: C, 57.75; H, 8.06. MS (FAB) m/z:
369 (MCCK).
˚
nitromethane (20 mL) were added molecular sieves (4 A;
2.0 g) and silver nitrate (AgNO3; 1.62 g, 9.54 mmol) and the
whole mixture covered with aluminum foil was stirred for
24 h at room temperature. The reaction mixture was worked
up in the same way as the previous (G)-15 to give (4S)-15
(1.22 g, 91%). (4S)-15: [a]2D7ZC15.9 (cZ0.51, CHCl3)
corresponding to 93% ee by means of HPLC analysis), The
NMR data of (4S)-15 were identical with those of the
reported (G)-15. (3) To a mixture of Zn-dust (1.14 g) and
CH3COONH4 (1.14 g) in MeOH (5 mL) was added a
solution of (4S)-15 (1.140 g, 4.06 mmol) in MeOH (7 mL)
and the whole mixture was stirred for 1 h at 0 8C. The
generated precipitate was filtered off with the aid of celite
and the filtrate was diluted with water and ether. The organic
layer was dried over MgSO4 and evaporated to give a
residue, which was chromatographed on silica gel (40 g,
n-hexane/AcOEtZ5:1) to afford (4S)-5 (0.833 g, 87%) as a
colorless oil. (4S)-5: [a]2D6ZC1.00 (cZ0.50, CHCl3)
corresponding to 93% ee by means of HPLC analysis),
The NMR data of (4S)-5 were identical with those of the
previous (G)-5.
4.1.13. (2S,3S,4S)-4-Hydroxy-2,3-dimethoxymethyl-5-
(40-methoxyphenyl)-pentanol 7. (1) To a solution of 50%
aqueous N-methylmorpholine N-oxide (0.58 mL,
2.49 mmol) and 2% aqueous osmium tetraoxide (OsO4;
3.16 mL, 10 mol%) in acetone (5 mL) was added a solution
of (4S)-5 (0.588 g, 2.49 mmol) in acetone (5 mL) at 0 8C
and the whole mixture was stirred for 2 h at the same
temperature. The reaction mixture was diluted with 10%
aqueous Na2SO3 (5 mL) at 0 8C and the whole mixture was

M. Ono et al. / Tetrahedron 60 (2004) 10187–10195
10195
Todoriki, R.; Akita, H. Chem. Pharm. Bull. 1994, 42,
1590–1595. (c) Ono, M.; Yamamoto, Y.; Akita, H. Chem.
Pharm. Bull. 1995, 43, 553–558.
References and notes
1. This work was published as a preliminary communication: Ono,
M.; Suzuki, K.; Akita, H. Tetrahedron Lett. 1999, 40, 8223–8226.
2. (a) Nagumo, S.; Furukawa, T.; Ono, M.; Akita, H. Tetrahedron
Lett. 1997, 38, 2849–2852. (b) Nagumo, S.; Ono, M.; Kakimoto,
Y.; Furukawa, T.; Hisano, T.; Mizukami, M.; Kawahara, N.;
Akita, H. J. Org. Chem. 2002, 67, 6618–6622.
5. Under this condition, an aryl migration product was not
obtained because a catalytic reduction of (G)-13 gave 4-(40-
methoxyphenyl)-pentanoate.
6. Miyazawa, M.; Ishibashi, N.; Ohnuma, S.; Miyashita, M.
Tetrahedron Lett. 1997, 38, 3419–3422.
7. Ono, M.; Saotome, C.; Akita, H. Tetrahedron:Asymmetry 1996,
7, 2595–2602.
3. Recent references concerning the structure determination and
syntheses of (K)-anisomycin Delair, P.; Brot, E.; Kanazawa,
A.; Greene, A. E. J. Org. Chem. 1999, 64, 1383–1386.
8. Stork, G.; Kahn, M. Tetrahedron Lett. 1983, 24, 3951–3954.
9. Iida, H.; Yamazaki, N.; Kibayashi, C. J. Org. Chem. 1986, 51,
1069–1073.
4. (a) Ono, M.; Yamamoto, Y.; Todoriki, R.; Akita, H. Hetero-
cycles 1994, 37, 181–185. (b) Ono, M.; Yamamoto, Y.;