Stereoselective synthesis of microcarpalide

Article abstract of DOI:10.1016/j.tet.2005.05.057

Microcarpalide is a strong microfilament disrupting agent. The convergent and stereoselective synthesis of microcarpalide was succeeded via Julia olefination and macrolactonization.

Full text of DOI:10.1016/j.tet.2005.05.057

Tetrahedron 61 (2005) 7546–7553
Stereoselective synthesis of microcarpalide
*
Ken Ishigami, Hidenori Watanabe and Takeshi Kitahara
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi,
Bunkyo-ku, Tokyo 113-8657, Japan
Received 21 April 2005; revised 13 May 2005; accepted 16 May 2005
Available online 14 June 2005
Abstract—Microcarpalide is a strong microfilament disrupting agent. The convergent and stereoselective synthesis of microcarpalide was
succeeded via Julia olefination and macrolactonization.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
to give diol 4 (95% ee) as colorless crystals. Purification of
the desired enantiomer could be realized by two times of
recrystallization, affording 4 with O99% ee (determined by
chiral HPLC). This diol was converted to p-methoxybenzyl-
ideneacetal 5 and the residual secondary alcohol was
protected by MOM group. After removal of p-methoxy-
benzylidene group, the primary hydroxyl group of 7 was
converted to corresponding 1-phenyl-1H-tetrazol-5-yl sul-
fone13 8 by Mitsunobu reaction and subsequent Mo(VI)
catalyzed oxidation.14 Preparation of the sulfone unit 9 was
achieved by protection of the secondary alcohol.
Microcarpalide, a 10-membered lactone, was isolated from
the fermentation broth of an unidentified endophytic fungus
by Hemscheidt and co-workers in 2001.1 This compound
acts as a strong microfilament disrupting agent and shows
weak cytotoxicity to mammalian cells. Because of the large
difference between the effective concentration for the
antimicrofilament activity and the cytotoxicity, it is thought
that this compound will be an effective tool for the studies of
cell motility and metastasis. Then, we started the synthesis
of microcarpalide. We have already published a rapid
communication,2 and here, we wish to report a full account
of our work (Fig. 1).
On the other hand, synthesis of the aldehyde unit 16 is
shown in Scheme 3. Starting from diol 10,15 olefinic ester 11
was prepared by Claisen rearrangement.16,17 In our previous
report,2 ester 11 was temporarily hydrolyzed into carboxylic
acid 12, which was subjected to Sharpless asymmetric
dihydroxylation4 to afford the desired diol. This unstable
diol was protected immediately together with re-esterifica-
tion of the carboxyl group to give 13. But the enantiomeric
purity of this compound was determined to be only 60% ee.
Therefore, we revised the synthetic route to intermediate 13
for the better enantiomeric purity. Direct dihydroxylation of
11 gave exclusively g-lactone 14, instead of the desired diol,
as colorless crystals (95% ee). Purification of the desired
enantiomer could be achieved by recrystallization, affording
14 with O99% ee (determined by chiral HPLC). Although,
2. Results and discussion
Our retrosynthesis is shown in Scheme 1. We selected
lactonization as a ring-closing step. The precursor for the
lactonization A would be prepared from aldehyde B and
sulfone C via one-pot Julia coupling.3 The aldehyde and the
sulfone would be obtained by Sharpless asymmetric
dihydroxylation4 of olefins D and E, respectively. During
our work in progress, other groups5–10 also reported the total
synthesis of microcarpalide, all of them using ring-closing
metathesis as a key step.
The synthesis of the sulfone unit is shown in Scheme 2. The
known olefinic alcohol 211 was protected with PMB group
and subjected to Sharpless asymmetric dihydroxylation4,12
Keywords: Microcarpalide; Microfilament disrupting agent; Macrolactoni-
zation; Julia olefination; Sharpless asymmetric dihydroxylation.
*
Corresponding author. Tel.: C81 3 5841 5181; fax: C81 3 5841 8019;
e-mail: aishig@mail.ecc.u-tokyo.ac.jp
Figure 1.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.05.057

K. Ishigami et al. / Tetrahedron 61 (2005) 7546–7553
7547
Scheme 1. Synthetic plan.
Scheme 2. Reagents and conditions: (a) PMBCl, NaH, TBAB, THF, reflux, quant.; (b) AD-mix-a, MeSO2NH2, t-BuOH, H2O, 95% ee; (c) recrystn., O99% ee,
74% in two steps; (d) DDQ, CH2Cl2; (e) MOMCl, i-Pr2EtN, CH2Cl2; (f) AcOH, H2O, THF, 82% in three steps; (g) PTSH, PPh3, DIAD, THF; (h)
(NH4)6Mo7O24$4H2O, H2O2, EtOH; (i) TBSOTf, 2,6-lutidine, CH2Cl2, 91% in three steps.
Scheme 3. Reagents and conditions: (a) BnBr, NaH, TBAI, THF; (b) MeC(OMe)3, EtCO2H, 140 8C, 48% in two steps; (c) LiOH, THF, H2O, 95%; (d) AD-
mix-b, MeSO2NH2, t-BuOH, H2O; (e) 2,2-dimethoxypropane, HCl, acetone, 74% in two steps; (f) AD-mix-b, MeSO2NH2, t-BuOH, H2O, 95% ee, 83%; (g)
recrystn., O99% ee, 86%; (h) LiOH, THF, H2O; (i) 2,2-dimethoxypropane, acetone; (j) CH2N2, Et2O, EtOAc, 88% in three steps; (k) H2, 10% Pd/C, i-PrOH,
quant.; (l) 4-MeO-TEMPO, KBr, NaOCl, NaHCO3, CH2Cl2, H2O, ca. 70%.
the yield in methanolysis of the lactone 14 was low
(!40%), hydrolysis and subsequent protection afforded 13
in much better yield. After hydrogenolysis, 15 was
successfully oxidized to the corresponding aldehyde 16
mediated by oxoammonium salt.18
cation, we tried other conditions employing additives to
prevent this chelation. When 18-c-6 was added (entry 6),
trans-olefin 17 was successfully obtained in good yield and
high selectivity. Separation of 17 from cis-isomer was easily
succeeded by silica gel column chromatography.
Now that both of the two units were obtained enantioselec-
tively, we tried one-pot Julia coupling3,13,19 in several
conditions (Table 1). The reaction employing LiHMDS as a
base gave the desired olefin 17 in poor yield (entries 1 and
2). On the other hand, good yield was realized when
KHMDS was used as a base, but E/Z selectivity was not so
high (entries 3 and 4). Because the low selectivity seemed to
be caused by some chelation effects of oxygen functional
groups in the sulfone 9 and the aldehyde 16 with potassium
Final steps including lactonization are shown in Scheme 4.
The trans-olefin 17 was treated with TBAF and hydrolyzed
to give hydroxy acid 19, a lactonization precursor. It was
subjected to Yamaguchi’s method20 to afford 10-membered
lactone 20 in excellent yield. Formation of dimeric lactone
was observed in higher concentration, but not in 1 mmol/L.
Deprotection of 20 was performed in the similar method as
Marco et al.5 to give microcarpalide (1) successfully
together with small amount of partially deprotected

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K. Ishigami et al. / Tetrahedron 61 (2005) 7546–7553
Table 1.
Entry
Base
Temperature (8C)
Additive
E:Z
Yield (%)
1
2
3
4
5
6
LiHMDS
LiHMDS
KHMDS
KHMDS
KHMDS
KHMDS
K78
K108
K78
K108
K108
K108
—
—
—
—
HMPA
18-c-6
3:1
10:1
2:1
2:1
3:1
10
32
64
77
71
72
10:1
Scheme 4. Reagents and conditions: (a) TBAF, THF, 99%; (b) LiOH, H2O, THF; (c) 2,4,6-trichlorobenzoyl chloride, Et3N, THF, then DMAP, benzene, 94%;
(d) BF3$OEt2, (CH2SH)2, CH2Cl2, K20 to K10 8C, 69% (1), 15% (21).
Scheme 5. Reagents and conditions: (a) DOWEXw-50W, MeOH, H2O, 50 8C, 98%; (b) BF3$OEt2, (CH2SH)2, CH2Cl2, 0 8C, 70%; (c) 2,2-dimethoxypropane,
PPTS, acetone; separation, 74% (23), 14% (24); (d) PPTS, MeOH, 85%.
compound 21. The analytical and spectroscopic data of
synthesized 1 were identical to the reported data.1,5–10 As
reported, the NMR spectra of 1 was observed as a mixture of
two conformers in the ratio about 3.5:1.
was clarified in the course of our examination of
deprotection conditions as shown in Scheme 5. Treating
20 with DOWEX-50W (MeOH, H2O, 50 8C, 4 days) or
BF3$OEt2 and (CH2SH)2 (CH2Cl2, 0 8C, 2 h) gave
inseparable mixture of microcarpalide (1) and small amount
of unknown compound 22. For structural determination of
Interestingly, acid-catalyzed isomerization of microcarpalide

K. Ishigami et al. / Tetrahedron 61 (2005) 7546–7553
7549
22, this mixture was treated with 2,2-dimethoxypropane and
PPTS to afford the corresponding acetonides, expected 10-
membered lactone 23 and another lactone 24. These
compounds were easily separated and the structure of 24
(4.8 g, 50.5 mmol) in ButOH (240 mL) and water (240 mL)
was stirred at room temperature for 30 min. The mixture
was cooled down to 0 8C and then, 3 (13.8 g, 50 mmol) was
added to it. Stirred at 4 8C overnight, Na2SO3 (100 g) was
added to the mixture. After stirring at room temperature for
30 min, the reaction mixture was extracted with ethyl
acetate. The organic layer was washed with saturated
NaHCO3 solution and brine, dried with anhydrous mag-
nesium sulfate and concentrated in vacuo. The residue was
chromatographed over silica gel. Elution with hexane/ethyl
acetate (3:1) gave crude 4 (95% ee) as colorless crystals.
Crude product was recrystallized from hexane/EtOAc
(20:1) to yield pure 4 (11.5 g, 74% recovery, O99% ee)
as colorless crystals. HPLC [column: Daicel Chiralcel OD
(0.46 cm!25 cm), eluent: hexane/ethanol (98:2), flow rate:
1.0 mL/min, detection: UV (254 nm)]: tRZ21 min [0.3%,
(R,R)-isomer], 25 min [99.7%, (S,S)-isomer]. MpZ49.5–
50.0 8C. [a]2D9 K2.2 (c 1.1, CHCl3). IR (KBr): nZ3464,
1
was confirmed to be 11-membered lactone by H-COSY
spectrum. Deprotection of the isolated 24 gave 22 as a single
product and its 1H NMR spectrum was identical with that of
the previous minor component in the inseparable mixture (1
and 22). Similarly, microcarpalide (1) was found to be
partially isomerized affording the mixture of 1 and 22 by
treatment with TsOH. 1H NMR spectrum (in CD3CN, 24 8C)
showed this mixture comprised the major conformer of 1, the
minor conformer of 1 and 11-memberd lactone 22 (5:1.5:1).
In conclusion, we have accomplished a convergent and
stereoselective synthesis of microcarpalide. All of the four
chiral centers were introduced by Sharpless asymmetric
dihydroxylation. One-pot Julia olefination gave the desired
trans-olefin in good yield and high selectivity in the
presence of crown ether and Yamaguchi’s macrolactoniza-
tion was also successful in excellent yield. The total yield
was 23% in 13 steps. We also observed an interesting acid-
catalyzed isomerization of microcarpalide.
1
3374, 1513, 1249, 1086 cmK1. H NMR (CDCl3): dZ0.88
(3H, t, JZ6.6 Hz,), 1.2–1.6 (10H, m), 1.7–1.9 (2H, m), 2.47
(1H, d, JZ5.5 Hz), 3.17 (1H, d, JZ4.5 Hz), 3.42 (1H, br
m), 3.6–3.75 (3H, m), 3.81 (3H, s), 4.46 (2H, s), 6.89 (2H, d,
JZ9.0 Hz), 7.24 (2H, d, JZ9.0 Hz). Anal. Calcd for
C18H30O4: C, 69.64; H, 9.74. Found: C, 69.69; H, 9.81.
3. Experimental
3.1. General
3.2.3. (1S)-1-[(4S)-2-(4-Methoxyphenyl)-1,3-dioxan-4-yl]
heptan-1-ol (5). DDQ (5.8 g, 19 mmol) was added to a
solution of diol (4) in CH2Cl2 (120 mL) at 0 8C. After
stirring at room temperature for 1 h, the reaction mixture
was poured into 10% Na2S2O3 solution and extracted with
ether. The organic layer was washed with saturated
NaHCO3 solution and brine, dried with anhydrous sodium
sulfate and concentrated in vacuo to provide p-methoxy-
benzylidene acetal 5 (5.8 g) as a yellow oil. This crude
product was used in the next reaction without further
Optical rotations were recorded with a JASCO DIP-1000
polarimeter. IR spectra were measured with a JASCO FT/
IR-230 spectrophotometer. 1H and 13C NMR were recorded
on JEOL JNM AL300. Mass spectra were recorded on JEOL
JMS-700T. Column chromatography was performed using
Merck silica gel 60 (0.060–0.200 mm). TLC was carried out
on Merck glass plates precoated with silica gel 60 F254
(0.25 mm). HPLC was performed using SHOWA DENKO
shodex DS-4. Melting points are uncorrected values.
1
purification. H NMR (C6D6): dZ0.91 (3H, t, JZ6.6 Hz),
1.2–1.5 (10H, m), 1.6–1.8 (2H, m), 2.30 (1H, d, JZ4.0 Hz),
3.26 (3H, s), 3.35–3.5 (3H, m), 3.96 (1H, ddd, JZ1.0, 5.0,
11.0 Hz), 5.34 (1H, s), 6.82 (2H, d, JZ11.0 Hz), 7.54 (2H,
d, JZ11.0 Hz).
3.2. Synthetic studies
3.2.1. (E)-1-(4-Methoxybenzyloxy)-3-decene (3). To a
solution of alcohol (2, 8.8 g, 56 mmol) in THF (160 mL)
were added NaH (60%, 3.0 g, 78 mmol), PMBCl (9.0 mL,
66 mmol) and tetra-n-butylammonium bromide (100 mg,
0.31 mmol). The reaction mixture was heated under reflux
for 2 days, poured into saturated NH4Cl solution and the
mixture was extracted with ethyl acetate. The organic layer
was washed with water and brine, dried with anhydrous
magnesium sulfate and concentrated in vacuo. The residue
was chromatographed over silica gel. Elution with hexane/
ethyl acetate (10:1) gave 3 (15.5 g, quant.) as a colorless oil.
n2D5Z1.4957. IR (film): nZ1613, 1514, 1464, 1248, 1099,
1038 cmK1. 1H NMR (CDCl3): dZ0.88 (3H, t, JZ6.5 Hz,),
1.2–1.4 (8H, m), 1.98 (2H, br q, JZ6.0 Hz), 2.30 (2H, br q,
JZ6.5 Hz), 3.45 (2H, t, JZ7.0 Hz), 3.81 (3H, s), 4.45 (2H,
s), 5.41 (1H, dt, JZ15.0, 6.0 Hz), 5.47 (1H, dt, JZ15.0,
6.0 Hz), 6.88 (2H, d, JZ8.5 Hz), 7.26 (2H, d, JZ8.5 Hz).
Anal. Calcd for C18H28O2: C, 78.21; H, 10.21. Found: C,
78.00; H, 10.12.
3.2.4. (1S)-1-Methoxymethoxy-1-[(4S)-2-(4-methoxyphe-
nyl)-1,3-dioxan-4-yl]heptane (6). To a solution of crude p-
methoxybenzylidene acetal (5.8 g) in CH2Cl2 (180 mL) was
added Pri2EtN (9.0 mL, 52 mmol) and MOMCl (3.0 mL,
40 mmol). This solution was stirred at room temperature
overnight, poured into water and extracted with ether. The
organic layer was washed with saturated NaHCO3 solution
and brine, dried with anhydrous sodium sulfate and
concentrated in vacuo to give MOM ether 6 (5.9 g) as a
yellow oil. This crude product was used in the next reaction
without further purification. 1H NMR (C6D6): dZ0.90 (3H,
t, JZ6.6 Hz,), 1.07 (1H, d, JZ13.0 Hz), 1.2–1.85 (11H, m),
3.24 (6H, s), 3.56 (1H, dt, JZ2.5, 12.0 Hz), 3.69 (1H, br m),
3.83 (1H, ddd, JZ2.5, 6.0, 12.0 Hz), 4.02 (1H, br dd, JZ
5.0, 12.0 Hz), 4.66 (1H, d, JZ6.5 Hz), 4.81 (1H, d, JZ
6.5 Hz), 5.42 (1H, s), 6.80 (2H, d, JZ8.5 Hz), 7.61 (2H, d,
JZ8.5 Hz).
3.2.5. (3S,4S)-4-(Methoxymethoxy)decane-1,3-diol (7). A
mixture of crude 6 (5.9 g), acetic acid (5.0 mL), water
(5.0 mL) and THF (15 mL) was refluxed for 2 h. The
reaction mixture was poured into saturated NaHCO3
3.2.2. (3S,4S)-1-(4-Methoxybenzyloxy)decane-3,4-diol
(4). A mixture of AD-mix-a (70 g) and methanesulfonamide

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K. Ishigami et al. / Tetrahedron 61 (2005) 7546–7553
solution and extracted with ethyl acetate. The organic layer
was washed with saturated NaHCO3 solution and brine,
dried with anhydrous magnesium sulfate and concentrated
in vacuo. The residue was chromatographed over silica gel.
Elution with hexane/ethyl acetate (1:1–1:3) gave 7 (3.6 g,
82% in three steps) as a colorless oil. n2D3Z1.4527. [a]D22
C24 (c 1.0, CHCl3). IR (film): nZ3400, 1468, 1152, 1100,
1039 cmK1. 1H NMR (CDCl3): dZ0.86 (3H, t, JZ6.9 Hz,),
1.25–1.6 (10H, m), 1.65–1.75 (2H, m), 2.81 (1H, t, JZ
5.5 Hz), 3.37 (1H, ddd, JZ4.5, 6.5, 6.5 Hz), 3.43 (3H, s),
3.48 (1H, d, JZ3.0 Hz), 3.7–1.8 (1H, m), 3.85 (2H, q, JZ
5.5 Hz), 4.69 (1H, d, JZ7.0 Hz), 4.73 (1H, d, JZ7.0 Hz).
FAB-HRMS m/z calcd for C12H27O4 [MCH]C 235.1909,
found 235.1906.
3.2.8. (E)-6-Benzyloxyhex-4-enoic acid methyl ester (11).
According to the reported manner,15,21 diol 10 (32 g,
0.36 mol) was treated with benzyl bromide to give mono-
benzyl ether as the mixture of primary and secondary
alcohols. Propionic acid (1.6 mL) was added to the solution
of this mixture in trimethyl orthoacetate (280 mL). The
reaction mixture was refluxed for 2 h with absorbing
˚
generated methanol by molecular sieves 4 A. After cooling,
the reaction mixture was diluted with ethyl acetate and
washed with saturated NaHCO3 solution and brine, dried
with anhydrous magnesium sulfate and concentrated in
vacuo. The residue was chromatographed over silica gel.
Elution with hexane/ethyl acetate (5:1) gave 11 (41 g, 48%
in two steps) as a colorless oil. n2D6Z1.5042. IR (film): nZ
1739, 1437, 1362, 1166, 1116 cmK1. 1H NMR (CDCl3): dZ
2.35–2.45 (4H, m), 3.68 (3H, s), 3.97 (2H, d, JZ5.0 Hz),
4.50 (2H, s), 5.6–5.8 (2H, m), 7.25–7.35 (5H, m). Anal.
Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C, 71.27; H,
7.77.
3.2.6. (3S,4S)-4-(Methoxymethoxy)-1-(1-phenyl-1H-tet-
razole-5-sulfonyl)decan-3-ol (8). The 40% solution of
diisopropyl azodicarboxylate in toluene (5.8 mL, 11 mmol)
was added to a solution of diol 7 (2.0 g, 8.5 mmol), PPh3
(2.3 g, 8.8 mmol) and 1-phenyl-5-mercapto-1H-tetrazole
(1.9 g, 11 mmol) in THF (60 mL) at K20 8C. Stirred at
0 8C for 20 min, the reaction mixture was poured into water
and extracted with ethyl acetate. The organic layer was
washed with saturated NaHCO3 solution and brine, dried
with anhydrous magnesium sulfate and concentrated in
vacuo. The residue was chromatographed over silica gel.
Elution with hexane/ethyl acetate (2:1) gave crude sulfide as
a colorless oil. To the solution of crude sulfide in ethanol
(100 mL) was added the mixture of (NH4)6Mo7O24$4H2O
(1.5 g, 1.2 mmol) and 30% H2O2 solution (6.0 mL,
53 mmol) at 0 8C. Stirred at room temperature for 6 h, the
reaction mixture was poured into 10% Na2S2O3 solution and
extracted with ethyl acetate. The organic layer was washed
with saturated NaHCO3 solution and brine, dried with
anhydrous sodium sulfate and concentrated in vacuo. The
residue was chromatographed over silica gel. Elution with
hexane/ethyl acetate (4:1) gave crude 8 as a colorless oil.
This crude product was used in the next reaction without
further purification. 1H NMR (CDCl3): dZ0.88 (3H, t, JZ
6.6 Hz), 1.2–1.6 (10H, m), 2.0–2.2 (2H, m), 3.17 (1H, d, JZ
5.0 Hz), 3.35 (1H, dt, JZ6.5, 5.5 Hz), 3.41 (3H, s), 3.5–3.7
(1H, m), 3.8–4.1 (2H, m), 4.68 (1H, d, JZ6.5 Hz), 4.70 (1H,
d, JZ6.5 Hz), 7.6–7.7 (5H, m).
3.2.9. (5R)-5-[(1R)-2-Benzyloxy-1-hydroxyethyl]tetrahy-
drofuran-2-one (14). The mixture of AD-mix-b (160 g)
and methanesulfonamide (11 g, 0.12 mol) in ButOH
(550 mL) and water (550 mL) was stirred at room
temperature for 30 min. The mixture was cooled down to
0 8C and then 11 (27 g, 0.12 mol) was added to it. Stirred at
4 8C overnight, Na2SO3 (50 g) was added to the mixture.
After stirring at room temperature for 30 min, the reaction
mixture was extracted with ethyl acetate. The organic layer
was washed with saturated NaHCO3 solution and brine,
dried with anhydrous magnesium sulfate and concentrated
in vacuo. The residue was chromatographed over silica gel.
Elution with hexane/ethyl acetate (2:1–1:1) gave crude 14
(22.5 g, 83%, 95% ee) as a colorless crystal. Crude product
was recrystallized from hexane–EtOAc to yield pure 14
(19.3 g, 86% recovery, O99% ee) as colorless crystals.
HPLC [column: Daicel Chiralcel OD-H (0.46 cm!25 cm),
eluent: hexane/PriOH (9:1), flow rate: 1.0 mL/min, detec-
tion: UV (254 nm)]: tRZ19.4 min [99.9%, (R,R)-isomer],
22.3 min [0.1%, (S,S)-isomer]. MpZ105.0–106.5 8C. [a]D27
K47 (c 1.0, CHCl3). IR (KBr): nZ3469, 1759, 1197,
1083 cmK1. 1H NMR (CDCl3): dZ2.2–2.3 (2H, m), 2.4–2.7
(3H, m), 3.60 (2H, d, JZ6.0 Hz), 3.83 (1H, m), 4.56 (2H, s),
4.55–4.6 (1H, m), 7.3–7.4 (5H, m). Anal. Calcd for
C13H16O4: C, 66.09; H, 6.83. Found: C, 66.11; H, 6.84.
3.2.7. (3S,4S)-3-(tert-Butyldimethylsilyloxy)-4-(methoxy-
methoxy)-1-(1-phenyl-1H-tetrazole-5-sulfonyl)decane
(9). To a solution of crude 8 in CH2Cl2 (80 mL) was added
TBSOTf (2.6 mL, 11 mmol) and 2,6-lutidine (1.7 mL,
15 mmol). The reaction mixture was stirred at room
temperature for 30 min, poured into water and extracted
with ethyl acetate. The organic layer was washed with
saturated NaHCO3 solution and brine, dried with anhydrous
magnesium sulfate and concentrated in vacuo. The residue
was chromatographed over silica gel. Elution with hexane/
ethyl acetate (20:1) gave 9 (4.2 g, 91% in three steps) as a
colorless oil. nD24Z1.4951. [a]D24 K18 (c 1.0, CHCl3). IR
3.2.10. 3-[(4R,5R)-5-Benzyloxymethyl-2,2-dimethyl-1,3-
dioxolan-4-yl]propionic acid methyl ester (13). Lithium
hydroxide monohydrate (4.0 g, 95 mmol) was added to the
mixture of lactone 14 (10 g, 43 mmol), THF (100 mL) and
water (100 mL). Stirred at room temperature for 1 h, the
reaction mixture was poured into 0.3 N HCl and extracted
with ethyl acetate. The organic layer was washed with water
and brine, dried with anhydrous magnesium sulfate and
concentrated in vacuo. The residue was dissolved in 2,2-
dimethoxypropane (50 mL) and acetone (100 mL) and
stirred at room temperature overnight. After evaporation,
the residue was dissolved in ethyl acetate (100 mL) and
treated with a solution of CH2N2 in ether. The reaction
mixture was washed with saturated NaHCO3 solution and
brine, dried with anhydrous magnesium sulfate and
concentrated in vacuo. The residue was chromatographed
over silica gel. Elution with hexane/ethyl acetate (5:1) gave
(film): nZ1344, 1151, 1097, 1039 cmK1 1H NMR
.
(CDCl3): dZ0.10 (3H, s), 0.11 (3H, s), 0.88 (3H, t, JZ
6.5 Hz), 0.90 (9H, s), 1.25–1.7 (10H, m), 2.01 (1H, m), 2.24
(1H, m), 3.38 (3H, s), 3.45 (1H, m), 3.82 (2H, m), 3.95 (1H,
ddd, JZ4.2, 4.2, 8.4 Hz), 4.61 (1H, d, JZ7.0 Hz), 4.67 (1H,
d, JZ7.0 Hz), 7.6–7.7 (5H, m). FAB-HRMS m/z calcd for
C25H45N4O5SSi [MCH]C 541.2880, found 541.2877.

K. Ishigami et al. / Tetrahedron 61 (2005) 7546–7553
7551
13 (11 g, 88%) as a colorless oil. n2D5Z1.4879. [a]D26 C15 (c
2.0 (2H, m), 2.15 (1H, ddd, JZ7.5, 8.5, 15.0 Hz), 2.3–2.6
(3H, m), 3.37 (3H, s), 3.35–3.45 (1H, m), 3.6–3.7 (1H, m),
3.67 (3H, s), 3.75 (1H, dt, JZ8.5, 4.3 Hz), 3.98 (1H, t, JZ
7.5 Hz), 4.62 (1H, d, JZ6.6 Hz), 4.69 (1H, d, JZ6.6 Hz),
5.46 (1H, dd, JZ7.5, 15.0 Hz), 5.85 (1H, dt, JZ15.0,
7.5 Hz). Anal. Calcd for C28H54O7Si: C, 63.36; H, 10.25.
Found: C, 63.36; H, 10.31.
1.5, CHCl3). IR (film): nZ1739, 1449, 1373, 1081 cmK1
.
1H NMR (CDCl3): dZ1.39 (3H, s), 1.40 (3H, s), 1.8–2.05
(2H, m), 2.4–2.6 (2H, m), 3.5–3.6 (2H, m), 3.67 (3H, s),
3.8–3.9 (2H, m), 4.59 (2H, s), 7.3–7.4 (5H, m). Anal. Calcd
for C17H24O5: C, 66.21; H, 7.84. Found: C, 65.90; H, 7.66.
3.2.11. 3-[(4R,5R)-5-Hydroxymethyl-2,2-dimethyl-1,3-
dioxolan-4-yl]propionic acid methyl ester (15). To a
solution of 13 (5.0 g, 17 mmol) in PriOH (135 mL) was
added 10% Pd/C (400 mg) and the mixture was stirred
overnight under H2 atmosphere. The mixture was filtered
through Celitew and concentrated in vacuo. The residue was
chromatographed over silica gel. Elution with hexane/ethyl
acetate (2:1) gave 15 (3.7 g, quant.) as a colorless oil. n2D7Z
1.4472. [a]2D4 C29 (c 1.0, CHCl3). IR (film): nZ3476, 1739,
1441, 1375, 1250, 1166, 1073 cmK1. 1H NMR (CDCl3): dZ
1.40 (6H, s), 1.8–2.1 (3H, m), 2.4–2.6 (2H, m), 3.6–3.85
(3H, m), 3.69 (3H, s), 3.91 (1H, dt, JZ3.3, 8.1 Hz). FAB-
HRMS m/z calcd for C10H19O5 [MCH]C 219.1233, found
219.1237.
3.2.14. 3-[(4R,5R)-5-{(1E,4S,5S)-4-Hydroxy-5-methoxy-
methoxyundec-1-enyl}-2,2-dimethyl-1,3-dioxolan-4-yl]
propionic acid methyl ester (18). To a solution of 17
(530 mg, 1.0 mmol) in THF (10 mL) was added 1.0 M
TBAF solution in THF (2.0 mL, 2 mmol) and the solution
was stirred at room temperature for 2 h. The reaction
mixture was poured into water and extracted with ethyl
acetate. The organic layer was washed with saturated
NaHCO3 solution and brine, dried with anhydrous mag-
nesium sulfate and concentrated in vacuo. The residue was
chromatographed over silica gel. Elution with hexane/ethyl
acetate (4:1) gave 18 (412 mg, 99%) as a colorless oil. n2D7Z
1.4621. [a]2D7 C13 (c 0.90, CHCl3). IR (film): nZ3482,
1740, 1441, 1373, 1221, 1163, 1037 cmK1 1H NMR
.
(CDCl3): dZ0.88 (3H, t, JZ6.6 Hz), 1.25–1.65 (10H, m),
1.34 (6H, s), 1.75–2.0 (2H, m), 2.2–2.6 (4H, m), 2.75 (1H, d,
JZ4.8 Hz), 3.38 (1H, m), 3.41 (3H, s), 3.59 (1H, m), 3.67
(3H, s), 3.6–3.7 (1H, m), 4.01 (1H, t, JZ8.0 Hz), 4.69 (2H,
s), 5.52 (1H, dd, JZ8.0, 15.3 Hz), 5.90 (1H, dt, JZ15.3,
7.5 Hz). FAB-HRMS m/z calcd for C22H41O7 [MCH]C
417.2852, found 417.2866.
3.2.12. 3-[(4R,5S)-5-Formyl-2,2-dimethyl-1,3-dioxolan-
4-yl]propionic acid methyl ester (16). 4-Methoxy-
2,2,6,6-tetramethylpiperidine 1-oxyl (750 mg, 4.0 mmol)
was added to a mixture of alcohol 15 (2.8 g, 13 mmol),
0.8 M NaOCl solution (19 mL, 15 mmol), KBr (750 mg,
6.3 mmol), NaHCO3 (1.6 g, 19 mmol), CH2Cl2 (160 mL)
and water (80 mL) at 0 8C and the mixture was stirred at
0 8C for 15 min. The reaction mixture was poured into 10%
Na2S2O3 solution and extracted with CH2Cl2. The organic
layer was washed with saturated NaHCO3 solution and
brine, dried with anhydrous magnesium sulfate and
concentrated in vacuo. The residue was chromatographed
over silica gel. Elution with hexane/ethyl acetate (2:1–1:1)
gave crude 16 (1.95 g, ca. 70%) as a colorless oil. This crude
product was used in the next reaction without further
purification. 1H NMR (CDCl3): dZ1.41 (6H, s), 1.85–2.15
(2H, m), 2.4–2.6 (2H, m), 3.69 (3H, s), 3.98 (1H, dd, JZ2.0,
7.5 Hz), 4.10 (1H, dt, JZ4.5, 7.5 Hz), 9.74 (1H, d, JZ
2.0 Hz).
3.2.15. 3-[(4R,5R)-5-{(1E,4S,5S)-4-Hydroxy-5-methoxy-
methoxyundec-1-enyl}-2,2-dimethyl-1,3-dioxolan-4-yl]
propionic acid (19). A mixture of 18 (368 mg, 0.88 mmol),
LiOH$H2O (75 mg, 1.8 mmol), THF (7 mL) and water
(5 mL) was stirred at room temperature for 2 h. The reaction
mixture was poured into 10% tartaric acid solution and
extracted with ethyl acetate. The organic layer was washed
with water and brine, dried with anhydrous magnesium
sulfate and concentrated in vacuo. The residue was
suspended in CHCl3, filtered through Celitew and concen-
trated in vacuo. The residue was chromatographed over
silica gel. Elution with hexane/ethyl acetate (1:1) gave crude
19 (400 mg) as a colorless oil. This crude product was used
in the next reaction without further purification. IR (film):
nZ3446, 3300–2500 (br), 1714, 1377, 1219, 1157, 1101,
1038 cmK1. 1H NMR (CDCl3): dZ0.89 (3H, t, JZ6.6 Hz),
1.25–1.65 (10H, m), 1.40 (6H, s), 1.8–2.05 (2H, m), 2.2–2.6
(4H, m), 3.35–3.45 (1H, m), 3.42 (3H, s), 3.6–3.75 (2H, m),
4.03 (1H, t, JZ8.0 Hz), 4.70 (2H, s), 5.53 (1H, m), 5.90
(1H, dt, JZ15.0, 7.2 Hz).
3.2.13. 3-[(4R,5R)-5-{(1E,4S,5S)-4-tert-Butyldimethylsi-
lyloxy-5-(methoxymethoxy)undec-1-enyl}-2,2-dimethyl-
1,3-dioxolan-4-yl]propionic acid methyl ester (17). To a
solution of sulfone 9 (1.0 g, 1.9 mmol) and 18-crown-6
(740 mg, 2.8 mmol) in THF (40 mL) was added 0.5 M
solution of KHMDS in toluene (4.4 mL, 2.2 mmol) at
K100 8C. Stirred at K100 8C for 30 min, a solution of
aldehyde 16 (600 mg, 2.78 mmol) in THF (10 mL) was
dropped into this solution. The reaction mixture was
allowed to warm to room temperature during 2 h and
poured into saturated NH4Cl solution. This mixture was
extracted with ethyl acetate and the organic layer was
washed with saturated NaHCO3 solution and brine. After
drying with anhydrous magnesium sulfate, solvent was
removed in vacuo and the residue was chromatographed
over silica gel. Elution with hexane/ethyl acetate (10:1)
gave 17 (645 mg, 66%) and cis-isomer (62 mg, 6%) as
colorless oils. nD25Z1.4550. [a]D25 K20 (c 0.60, CHCl3). IR
3.2.16. 4,5-O-Isopropylidene-10-O-methoxymethylmi-
crocarpalide (20). Triethylamine (280 mL, 2.0 mmol) and
2,4,6-trichlorobenzoyl chloride (200 mL, 1.3 mmol) were
added to a solution of the crude hydroxy acid 19 (400 mg) in
THF (7 mL). The reaction mixture was stirred at room
temperature for 5 h and then filtered through Celitew under
argon. The resultant solution was slowly added over 22 h
using syringe pump to a refluxing solution of DMAP (2.2 g,
18 mmol) in dry benzene (1000 mL). After the addition was
complete, the reaction mixture was stirred for additional 2 h
and then concentrated in vacuo. The residue was dissolved
in ethyl acetate and washed with 1 N HCl, saturated
(film): nZ1743, 1252, 1162, 1044 cmK1 1H NMR
.
(CDCl3): dZ0.05 (6H, s), 0.89 (9H, s), 0.85–0.95 (3H,
m), 1.25–1.5 (9H, m), 1.39 (6H, s), 1.5–1.7 (1H, m), 1.75–

7552
K. Ishigami et al. / Tetrahedron 61 (2005) 7546–7553
NaHCO3 solution and brine. The organic layer was dried
with anhydrous magnesium sulfate and concentrated in
vacuo. The residue was chromatographed over silica gel.
Elution with hexane/ethyl acetate (6:1) gave 20 (320 mg,
94%) as a colorless oil. n2D6Z1.4742. [a]D24 K37 (c 0.60,
CHCl3). IR (film): nZ1735, 1456, 1372, 1236, 1163,
0.15 mmol) was dissolved in 2,2-dimethoxypropane (1 mL)
and acetone (1 mL) and treated with PPTS (10 mg,
0.04 mmol). Stirred at room temperature overnight, the
reaction mixture was diluted with ethyl acetate and washed
with saturated NaHCO3 solution and brine, dried with
anhydrous magnesium sulfate and concentrated in vacuo.
The residue was purified by preparative TLC [hexane/ethyl
acetate (3:1)] to give 23 (38 mg, 74%) and 24 (7 mg, 14%)
both as colorless oils.
1
1063 cmK1. H NMR (CD3CN, observed as a mixture of
two conformers in a ratio of 3:1) Major conformer: dZ0.89
(3H, t, JZ6.6 Hz), 1.25–1.65 (10H, m), 1.41 (6H, s), 1.9–
1.25 (2H, m), 2.25–2.7 (4H, m), 3.41 (3H, s), 3.6–3.7 (2H,
m), 3.93 (1H, t, JZ9.0 Hz), 4.68 (1H, d, JZ7.2 Hz), 4.71
(1H, d, JZ7.2 Hz), 4.93 (1H, dt, JZ8.7, 3.5 Hz), 5.33 (1H,
dd, JZ9.0, 15.0 Hz), 5.74 (1H, ddd, JZ4.5, 11.0, 15.0 Hz).
Minor conformer: dZ0.89 (3H, t, JZ6.6 Hz), 1.25–1.65
(11H, m), 1.41 (6H, s), 2.25–2.7 (5H, m), 3.41 (3H, s), 3.6–
3.7 (1H, m), 3.76 (1H, dt, JZ2.5, 9.5 Hz), 3.8–3.9 (1H, m),
4.68 (1H, d, JZ7.2 Hz), 4.71 (1H, d, JZ7.2 Hz), 5.09 (1H,
br m), 5.7–5.8 (1H, m), 5.90 (1H, dt, JZ16.0, 8.0 Hz). FAB-
HRMS m/z calcd for C21H37O6 [MCH]C 385.2590, found
385.2596.
Compound 23. [a]D27 K36 (c 0.40, CHCl3). 1H NMR
(CDCl3, observed as a mixture of two conformers in a ratio
of 3.5:1) Major conformer: d (ppm) 0.88 (3H, t, JZ6.5 Hz),
1.2–1.5 (10H, m), 1.41 (6H, s), 1.97 (1H, dddd, JZ3.5, 8.0,
12.0, 15.0 Hz), 2.09 (1H, br ddd, JZ4.5, 5.5, 15.0 Hz), 2.32
(1H, ddd, JZ4.5, 12.0, 13.5 Hz), 2.42 (1H, br ddd, JZ2.5,
4.5, 12.0 Hz), 2.54 (1H, ddd, JZ3.5, 5.5, 13.5 Hz), 2.67
(1H, ddd, JZ9.0, 11.0, 12.0 Hz), 3.6–3.7 (2H, m), 3.92 (1H,
t, JZ9.0 Hz), 4.71 (1H, ddd, JZ2.5, 4.5, 9.0 Hz), 5.33 (1H,
dd, JZ9.5, 15.5 Hz), 5.78 (1H, ddd, JZ4.5, 11.0, 15.5 Hz).
Minor conformer: d (ppm) 0.88 (3H, t, JZ6.5 Hz), 1.2–1.7
(11H, m), 1.41 (6H, s), 2.0–2.7 (5H, m), 3.6–3.65 (1H, m),
3.77 (1H, br dt, JZ4.0, 10.0 Hz), 3.8–3.9 (1H, m), 4.94 (1H,
br m), 5.65–5.75 (1H, m), 5.85–5.95 (1H, m). FAB-HRMS
m/z calcd for C19H33O5 [MCH]C 341.2328, found
341.2301.
3.2.17. Microcarpalide (1). To a solution of 20 (89 mg,
0.23 mmol) and 1,2-ethanedithiol (90 mL, 1.1 mmol) in
CH2Cl2 (10 mL) was added BF3$OEt2 (55 mL, 0.43 mmol)
at K20 8C and the mixture was stirred at K20–K10 8C for
40 min. The reaction mixture was poured into water and
extracted with ethyl acetate. The organic layer was washed
with saturated NaHCO3 solution and brine, dried with
anhydrous magnesium sulfate and concentrated in vacuo.
The residue was chromatographed over silica gel. Elution
with CHCl3/MeOH (20:1) gave 1 (46 mg, 66%) and MOM
ether 21 (12 mg, 15%) both as colorless oils. n1D9Z1.4965.
[a]2D6 K29 (c 0.67, MeOH). IR (film): nZ3438, 2929, 2857,
1712, 1225, 1155, 1065 cmK1. 1H NMR (CD3CN, observed
as a mixture of two conformers in a ratio of 3.5:1) Major
conformer: d (ppm) 0.88 (3H, t, JZ6.9 Hz), 1.2–1.4 (8H,
m), 1.3–1.5 (2H, m), 1.7–1.8 (1H, m), 2.0–2.2 (2H, m), 2.1–
2.3 (2H, m), 2.4–2.6 (1H, m), 2.8–2.9 (2H, br m), 3.12 (1H,
br d), 3.54 (1H, br m), 3.77 (1H, br), 4.10 (1H, br), 4.81 (1H,
ddd, JZ3.3, 4.8, 11.1 Hz), 5.49 (1H, dddd, JZ2.1, 5.1, 9.9,
15.6 Hz), 5.69 (1H, dd, JZ2.4, 15.6 Hz). Minor conformer:
d (ppm) 0.88 (3H, t, JZ6.9 Hz), 1.2–1.4 (8H, m), 1.3–1.5
(2H, m), 1.7–1.8 (1H, m), 2.0 (1H, m), 2.0–2.2 (1H, m), 2.2–
2.4 (1H, m), 2.4–2.6 (2H, m), 2.8–2.9 (2H, br m), 3.2–3.3
(2H, br m), 3.5–3.6 (2H, m), 4.60 (1H, ddd, JZ2.7, 4.5,
8.1 Hz), 5.05 (1H, dd, JZ9.3, 15.6 Hz), 5.6–5.7 (1H, m).
13C NMR (CD3CN, observed as a mixture of two
conformers): d (ppm) 14.4, 23.3, 26.1, 26.3, 26.3, 26.4,
29.0, 29.9, 32.1, 32.2, 32.5, 33.8, 34.1, 35.9, 36.7, 72.4,
72.8, 73.4, 73.8, 76.4, 76.9, 79.5, 79.7, 126.6, 130.0, 133.7,
134.5, 173.5, 176.4. FAB-HRMS m/z calcd for C16H29O5
[MCH]C 301.2015, found 301.2003.
Compound 24. 1H NMR (CDCl3): dZ0.87 (3H, t, JZ
6.5 Hz), 1.2–1.8 (10H, m), 1.39 (3H, s), 1.40 (3H, s), 2.05–
2.55 (6H, m), 3.63 (1H, m), 3.87 (1H, dt, JZ9.0, 5.0 Hz),
3.97 (1H, t, JZ8.5 Hz), 4.92 (1H, dd, JZ5.0, 9.0 Hz), 5.53
(1H, dd, JZ8.5, 16.0 Hz), 5.84 (1H, dt, JZ16.0, 8.0 Hz).
FAB-HRMS m/z calcd for C19H33O5 [MCH]C 341.2328,
found 341.2301.
3.2.19. (4R,5R,6E,9S,10S)-4,5,9-Trihydroxy-6-hexade-
cen-10-olide (22). To a solution of 24 (6.0 mg,
0.018 mmol) in MeOH (1.5 mL) was added PPTS (1 mg,
0.004 mmol) and the mixture was stirred at room
temperature for 3 days. The reaction mixture was poured
into water and extracted with ethyl acetate. The organic
layer was washed with saturated NaHCO3 solution and
brine, dried with anhydrous magnesium sulfate and
concentrated in vacuo. The residue was purified by
preparative TLC [CHCl3/MeOH (10:1)] to give 22
(4.5 mg, 85%) as a colorless oil. [a]2D6 K17 (c 0.32,
MeOH). 1H NMR (CD3CN): d (ppm) 0.87 (3H, t, JZ
6.5 Hz), 1.2–1.35 (8H, m), 1.60 (2H, m), 1.8–1.9 (2H, m),
2.1–2.2 (2H, m), 2.3–2.4 (2H, m), 2.97 (1H, d, JZ7.0 Hz),
3.11 (1H, d, JZ3.5 Hz), 3.20 (1H, d, JZ3.5 Hz), 3.40 (1H,
m), 3.63 (1H, dt, JZ3.5, 7.0 Hz), 3.88 (1H, tt, JZ2.5,
7.0 Hz), 4.81 (1H, dt, JZ2.5, 7.0 Hz), 5.47 (1H, ddt, JZ7.0,
15.0, 1.0 Hz), 5.76 (1H, dt, JZ15.0, 7.0 Hz). FAB-HRMS
m/z calcd for C16H29O5 [MCH]C 301.2015, found
301.2036.
3.2.18. 4,5-O-Isopropylidene-microcarpalide (23) and
(4R,5R,6E,9S,10S)-4,5-Isopropylidenedioxy-9-hydroxy-
6-hexadecen-10-olide (24). To a solution of 20 (112 mg,
0.29 mmol) in MeOH (6 mL) and water (1.2 mL) was added
DOWEXw-50W X8 (1.0 g) and the mixture was stirred at
50 8C for 5 days. The reaction mixture was diluted with
ethyl acetate and filtered through Celitew. After concen-
tration, the residue was chromatographed over silica gel.
Elution with CHCl3/MeOH (20:1) gave a mixture of 1 and
22 (86 mg, 98%) as a colorless oil. This mixture (45 mg,
Acknowledgements
Financial support has been granted by a Grant-in-Aid for
Scientific Research on Priority Areas (A) ‘Exploitation of
Multi-Element Cyclic Molecules’ from Ministry of Edu-
cation, Culture, Sports, Science and Technology. We

K. Ishigami et al. / Tetrahedron 61 (2005) 7546–7553
7553
9. Chavan, S. P.; Praveen, C. Tetrahedron Lett. 2005, 46,
1939–1941.
sincerely thank Ms. Hiroko Naito, University of Tokyo, for
elemental analyses, and Mr. Yusuke Nakatani and Mr. Akira
Nakanishi, University of Tokyo, for mass spectroscopy.
10. Davoli, P.; Fava, R.; Morandi, S.; Spaggiari, A.; Prati, F.
Tetrahedron 2005, 61, 4427–4436.
11. Schlosser, M.; Tuong, H. B.; Schaub, B. Tetrahedron Lett.
1985, 26, 311–314.
12. Mori, K.; Abe, K. Liebigs Ann. 1995, 943–948.
13. Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A.
Synlett 1998, 26–28.
References and notes
1. Ratnayake, A. S.; Yoshida, W. Y.; Moonberry, S. L.;
Hemscheidt, T. Org. Lett. 2001, 3, 3479–3481.
2. Ishigami, K.; Kitahara, T. Heterocycles 2004, 63, 785–790.
3. Baudin, J. B.; Hareau, G.; Julia, S. A.; Ruel, O. Tetrahedron
Lett. 1991, 32, 1175–1178.
14. Schultz, H. S.; Freyermuth, H. B.; Buc, S. R. J. Org. Chem.
1963, 28, 1140–1142.
15. Rao, A. V. R.; Bose, D. S.; Gurjar, M. K.; Ravindranathan, T.
Tetrahedron 1989, 45, 7031–7040.
16. Johnson, W. S.; Werthemann, L.; Bartlett, W. R.; Brocksom,
T. J.; Li, T.-T.; Faulkner, D. J.; Petersen, M. R. J. Am. Chem.
Soc. 1970, 92, 741–743.
4. Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.;
Hartung, J.; Jeong, K.-S.; Kwong, H.-L.; Morikawa, K.; Wang,
Z.-M.; Xu, D.; Zhang, X.-L. J. Org. Chem. 1992, 57,
2768–2771.
17. Wipf, P.; Lim, S. J. Am. Chem. Soc. 1995, 117, 558–559.
18. Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org. Chem.
1987, 52, 2559–2562.
5. Murga, J.; Falomir, E.; Garcia-Fortanet, J.; Carda, M.; Marco,
J. A. Org. Lett. 2002, 4, 3447–3449.
19. Blakemore, P. B. J. Chem. Soc., Perkin Trans. 1 2002,
2563–2585.
6. Gurjar, M. K.; Nagaprasad, R.; Ramana, C. V. Tetrahedron
Lett. 2003, 44, 2873–2875.
20. Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M.
Bull. Chem. Soc. Jpn. 1979, 52, 1989–1993.
21. Marguet, F.; Cavalier, J.-F.; Verger, R.; Buono, G. Eur. J. Org.
Chem. 1999, 1671–1678.
7. Davoli, P.; Spaggiari, A.; Castagnetti, L.; Prati, F. Org.
Biomol. Chem. 2004, 2, 38–47.
8. Banwell, M. G.; Loong, D. T. J. Heterocycles 2004, 62,
713–734.