Concise total synthesis of flavone C-glycoside having potent anti-inflammatory activity

Article abstract of DOI:10.1016/j.tet.2004.08.015

The total synthesis of anti-inflammatory active flavone C-glycoside isolated from oolong tea extract is achieved. Introducing a C-glucosyl moiety to an aryl system and constructing a fused tetracyclic ring characteristic to this natural product were condu

Full text of DOI:10.1016/j.tet.2004.08.015

Tetrahedron 60 (2004) 9375–9379
Concise total synthesis of flavone C-glycoside having potent
anti-inflammatory activity
Takumi Furuta, Tomoyuki Kimura, Sachiko Kondo, Hisashi Mihara, Toshiyuki Wakimoto,
*
Haruo Nukaya, Kuniro Tsuji and Kiyoshi Tanaka
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Received 18 June 2004; revised 6 August 2004; accepted 9 August 2004
Abstract—The total synthesis of anti-inflammatory active flavone C-glycoside isolated from oolong tea extract is achieved. Introducing a
C-glucosyl moiety to an aryl system and constructing a fused tetracyclic ring characteristic to this natural product were conducted based on
the O-to-C rearrangement of sugar moiety and the successive intramolecular Mitsunobu reaction, respectively. This concise and efficient
synthetic pathway is applicable to the large-scale synthesis of target flavone and for constructing a large library of related compounds.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Naturally-occurring aryl C-glycosides1 exhibit interesting
biological activities. Especially, C-glycosyl flavonoids
show a variety of bioactivities such as antiviral,2 cytotoxic,3
and DNA binding4 activities. Recently, a novel, anti-
inflammatory active flavone C-glycoside 1, which connects
a mannose sugar moiety at the 6-position of a flavone
Figure 1. Anti-inflammatory active flavone C-glycoside.
skeleton, has been isolated as minor constituent of oolong
tea extract.5 The activity of 1 is exceptionally significant
and evaluation based on the suppression of contact
hypersensitivity in mice induced by the treatment of
2,4-dinitrofluorobenzene indicates that 1 is w1000 times
stronger than the conventionally used anti-inflammatory
drug, dexamethasone. On the other hand, this flavone is
structurally characterized by the fused tetracyclic ring
system composed of a mannosyl moiety, A, and C rings
of flavone framework. The intriguing biological activity,
unique structural features, and limited natural sources
promoted us to undertake a synthetic study of this flavone.
The first total synthesis of 1 was accomplished recently by
Nakatsuka and co-workers.6 Herein, concise and efficient
total synthesis of 1 based on O-to-C rearrangement7 and
intramolecular Mitsunobu reaction8 for the C-glycoside
formation and the construction of its tetracyclic ring system,
respectively, is described (Fig. 1).
2. Results and discussion
Scheme 1 depicts the retrosynthetic pathway for compound
1, where the fused tetracyclic ring system may be feasibly
constructed by the regioselective intramolecular Mitsunobu
reaction between the 2-position of the glucosyl moiety and
the phenolic hydroxyl group of isovitexin derivative 2.
Mono-acylated aryl C-glycoside 3, which can be prepared
from 4, was selected as a precursor for forming the flavone
ring. The C-glycosidic linkage of 4 can be formed by an
O-to-C rearrangement using acetophenone derivative 5 and
the glycosyl donor 6 in the presence of Lewis acid catalyst.
According to the retrosynthetic pathway, the benzyl
protected C-glucoside 9 was selected as a key intermediate
(Scheme 2). Schmidt and co-workers prepared compound 9
via a four-step synthetic manipulation, including the O-to-C
rearrangement of the corresponding a-O-glucoside, which
was prepared by O-glucosidation using a TBS-protected
acetophenone derivative followed by deprotection–protec-
tion sequence.9
Keywords: Flavone C-glycoside; O-to-C rearrangement; Mitsunobu reac-
tion; Anti-inflammatory activity.
* Corresponding author. Tel.: C81-54-264-5746; fax: C81-54-264-5745;
e-mail: tanakaki@u-shizuoka-ken.ac.jp
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.08.015

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T. Furuta et al. / Tetrahedron 60 (2004) 9375–9379
Scheme 1. Retrosynthetic analysis of 1.
Scheme 2. Synthesis of isovitexin and vitexin derivatives. Reagents and conditions: (a) O-(2,3,4,6-tetra-O-benzyl-a-D-glucopyranosyl) trichloroacetimidate
(8), TMSOTf, CH2Cl2, 0 8C to rt, 69%; (b) 4-(methoxymethoxy)benzoic acid (10), DCC, DMAP, CH2Cl2, rt, 82%; (c) K2CO3, pyridine, reflux, 1 h, 12 (17%),
14 (15%); (d) Pd(OH)2, H2, EtOH, 35 8C, 95%.
We envisaged that 9 could be directly formed from mono-
benzyl protected acetophenone derivative 7,10 which is
readily available from phloroglucinol on the gram scale, as a
starting glycosyl acceptor. Using improvements from
previous preparations, the direct synthesis of 9 from 7 was
attempted. As expected, glycosylation of 7 with O-(2,3,4,6-
tetra-O-benzyl-a-D-glucopyranosyl)trichloroacetimidate
(8)11 in the presence of catalytic amounts of TMSOTf12
gave the desired b-configured 9 via O-to-C rearrangement in
69% yield. Subsequent condensation of 9 with 4-(methoxy-
methoxy)benzoic acid (10)13 selectively afforded mono-
acylated derivative 11. The appearance of two sets of peaks
in the 1H and 13C NMR spectra, which both agree with the
structure of 11, suggests that 11 exists as a rotational isomer
at ambient temperature on the NMR time-scale.
Although the many synthetic flavonoid studies are reported,
reliable and mild reaction conditions for C ring formation
are not readily available. Both of the following synthetic
methods, (i) Baker–Venkataraman rearrangement-succes-
sive acid catalyzed cyclization,9 and (ii) chalcone forma-
14
tion-oxidative cyclization using I2 or another oxidant,15
have been widely used for this purpose. However, both
cyclizations often require strongly acidic or basic conditions
to obtain the desired flavones in satisfactory chemical
yields. We decided to apply the cyclization conditions,16

T. Furuta et al. / Tetrahedron 60 (2004) 9375–9379
9377
Scheme 3. Completion of the synthesis of the target flavone. Reagents and conditions: (a) 1,10-azobis(N,N-dimethylformamide), Bu3P, THF, 50 8C; (b) 4 N
HCl–dioxane, MeOH, rt, 32% (two steps).
which were previously employed for preparing flavonol
derivatives. Thus, upon refluxing a pyridine solution of 11 in
the presence of K2CO3, both the isovitexin-type flavone 12
and vitexin-type derivative 14 were obtained as separable
mixture in 17 and 15% yields, respectively. The formation
of both isomeric flavones indicated that the C ring
construction occurred via Baker–Venkataraman rearrange-
ment of the acyl group and successive cyclization under
these reaction conditions.
spectra were measured on a JEOL MStation JMS-700
spectrometer. THF was distilled from sodium benzo-
phenone ketyl, CH2Cl2, MeOH and pyridine were from
calcium hydride, magnesium and NaOH, respectively.
Unless otherwise noted, all reactions were run under an
argon atmosphere. All extractive organic solutions were
dried over anhydrous MgSO4, filtered and then concentrated
under reduced pressure. Column chromatography was
carried out with silica gel 60N spherical (63–210 mesh,
KANTO CHEMICAL) or Sephadex LH-20 (Amersham
Biosciences).
Removing the benzyl protecting groups of 12 by hydro-
genation with Pearlman’s catalyst in EtOH provided 13 in
excellent yield.
4.1.1. O-to-C Rearrangement to 4-benzyloxy-2,6-dihy-
droxy-3-(2,3,4,6-tetra-O-benzyl-b-D-glucopyranosyl)-
acetophenone (9). To a mixture of 4-benzyloxy-2,6-
dihydroxyacetophenone (7)10 (1.4 g, 5.4 mmol) and
O-(2,3,4,6-tetra-O-benzyl-a-D-glucopyranosyl)trichloro-
acetimidate (8)11 (3.7 g, 5.4 mmol) in CH2Cl2 (40 mL) was
added TMSOTf (97 mL, 0.54 mmol) at 0 8C. After being
stirred at room temperature for 18 h, the mixture was added
H2O at 0 8C and the organic layer was separated. The
aqueous phase was extracted with CH2Cl2 and the combined
organic layer was washed with brine, dried and evaporated
to give a residue, which was purified by column chroma-
tography (SiO2, toluene–EtOAcZ9/1) to afford 99 (2.9 g,
69%) as a colorless oil.
Next, we turned our attention to constructing the tetracyclic
ring system that corresponds to the left part of the molecule.
Intramolecular cyclization of 13 under modified Mitsunobu
conditions8b,c in THF followed by the removal of the MOM
protecting group by treating with 4 N HCl–dioxane in
MeOH to yield target flavone 1 in 32% for two steps without
generation of another flavone isomers (Scheme 3). It is
noteworthy that flavone 15 was synthesized as a dominant
product in the first step even in the presence of reactive
primary and phenolic hydroxyl groups in substrate 13.
3. Conclusion
4.1.2. 4-Benzyloxy-2-hydroxy-6-(4-methoxymethoxybenz-
oyloxy)-3-(2,3,4,6-tetra-O-benzyl-b-D-glucopyranosyl)-
acetophenone (11). A mixture of 9 (509 mg, 0.65 mmol),
In summary, the total synthesis of compound 1 was
accomplished by combining C-glycoside formation, flavone
ring construction, and intramolecular Mitsunobu reaction as
key steps. This concise and efficient synthetic protocol,
which consists of six steps from known acetophenone
derivative 7 in 3% overall yield, could be employed not only
for large-scale synthesis of target flavone, but also for
preparing related derivatives that would be useful for
studying structure–activity relationship. Synthetic efforts
for preparing a series of flavone derivatives based on this
synthetic pathway and evaluating their biological activities
are currently under investigation in our laboratory.
4-(methoxymethoxy)benzoic
acid
(10)13(117 mg,
0.65 mmol), DCC (161 mg, 0.78 mmol) and DMAP
(8.0 mg, 65 mmol) in CH2Cl2 (15 mL) was stirred at room
temperature for 12 h. After the addition of H2O, the mixture
was extracted with CH2Cl2. The organic layer was washed
with brine, dried and evaporated to give a residue. The
residue was purified by column chromatography (SiO2,
toluene–EtOAcZ10/1) to afford 11 (504 mg, 82%) as a
colorless oil.
[a]2D0ZK12.1 (c 1.3, CHCl3); 1H NMR (C6D6, rotamers): d
14.48, 13.59 (s, 1H, OH), 8.03 (d, 2H, JZ8.5 Hz, Ar), 7.40–
7.00 (m, 25H, Bn), 6.91 (d, 2H, JZ8.5 Hz, Ar), 6.20, 6.10
(s, 1H, Ar), 5.57, 5.31 (d, 1H, JZ9.4 Hz, sugar H-1), 5.00–
4.20 (m, 10H, Bn), 4.72, 4.65 (dd, 1H, JZ9.4, 10 Hz, sugar
H-2), 4.65 (s, 2H, MOM), 4.02, 3.98 (t, 1H, JZ8.8 Hz,
sugar H-4), 3.88, 3.80 (dd, 1H, JZ8.8, 10 Hz, sugar H-3),
3.76, 3.64 (m, 1H, sugar H-6), 3.58, 3.49 (m, 1H, sugar
H-5), 2.97 (s, 3H, MOM), 2.22, 2.18 (s, 3H, Ac); 13C NMR
(C6D6, rotamers): d 201.8, 201.4 (Ac), 164.8, 164.4 (Ar),
163.7, 162.2 (Ar), 162.2 (Ar), 162.1 (Ar), 154.0, 153.3 (Ar),
4. Experimental
4.1. General
Melting points are uncorrected. Optical rotations were
measured on a JASCO P-1030 polarimeter. H and 13C
1
NMR spectra were obtained on JEOL ECA-500 at 500 and
125 MHz, respectively, with chemical shifts being reported
as d ppm from tetramethylsilane as an internal standard. IR
spectra were recorded on a JASCO WS/IR-8000. The mass

9378
T. Furuta et al. / Tetrahedron 60 (2004) 9375–9379
139.7–139.1 (Bn), 132.4 (Ar), 130.0–125.0 (Bn), 116.2
(Ar), 112.9, 112.4 (Ar), 110.9, 109.3 (Ar), 100.3, 100.1 (Ar),
93.8 (MOM), 88.1, 87.9 (sugar C-3), 80.1, 79.8 (sugar C-5),
79.2, 78.9 (sugar C-2), 75.2, 75.1 (sugar C-4), 74.7, 74.6
(sugar C-1), 75.0–70.0 (Bn), 69.2, 69.4 (sugar C-6), 55.6
(MOM), 31.7, 31.5 (Ac); IR (CHCl3): 3011, 1738, 1607,
1283, 1244; MS (FAB) m/z 945 (MCH)C; HRMS calcd for
C58H57O12 (MCH)C 945.3850, found 945.3846.
(Ar) 105.5 (Ar), 93.9 (MOM), 96.4 (Ar), 88.5 (sugar C-3),
79.9 (sugar C-5), 78.6 (sugar C-4), 78.5 (sugar C-2), 80.0–
70.0 (Bn), 75.5 (sugar C-1), 68.8 (sugar C-6), 55.5 (MOM);
IR (CHCl3): 3011, 2934, 2870, 1653, 1607, 1589, 1431,
1360; MS (FAB) m/z 927 (MCH)C; HRMS calcd for
C58H55O11 (MCH)C 927.3745, found 927.3740.
4.2.3. 6-(b-D-Glucopyranosyl)-5,7-dihydroxy-2-(4-meth-
oxymethoxyphenyl)-4H-1-benzopyran-4-one (13). A
mixture of 12 (10 mg, 11 mmol) and Pd(OH)2 (2.0 mg) in
EtOH (3.0 mL) was stirred at 35 8C for 1 h under hydrogen.
After concentration of the reaction mixture, the residue was
purified by column chromatography (SiO2, CHCl3–
MeOHZ5/1) to afford 13 (5.0 mg, 95%).
4.2. Flavone ring formation to isovitexin and vitexin
derivatives
A mixture of 11 (693 mg, 0.74 mmol), K2CO3 (507 mg,
˚
3.7 mmol) and MS 4 A (70 mg) in pyridine (148 mL) was
stirred under reflux for 1 h. After concentration of the
reaction mixture, the residue was diluted with EtOAc and
washed with saturated CuSO4. The organic layer was
washed with brine, dried and evaporated to give a residue.
The residue was purified by column chromatography (SiO2,
toluene–EtOAcZ20/1) to afford the less polar fraction
containing vitexin derivative 14 and the pure isovitexin
derivative 12 (115 mg, 17%) as a polar fraction. Further
purification of the less polar fraction by preparative HPLC
(YMC-pack ODS-A S-5 SH-343-5, CH3CN, 6 mL/min,
tRZ20.7 min) gave vitexin derivative 14 (100 mg, 15%).
Mp 175–177 8C; yellow needles (from acetone–H2O);
[a]2D0ZC28.0 (c 0.25, MeOH); 1H NMR (acetone-d6C
D2O): d 8.00 (d, JZ8.6 Hz, 2H), 7.20 (d, JZ8.6 Hz, 2H),
6.69 (s, 1H), 6.54 (s, 1H), 5.30 (s, 2H), 4.94 (d, JZ9.8 Hz,
1H), 3.9–3.7 (m, 3H), 3.7–3.3 (m, 3H), 3.45 (s, 3H); 13C
NMR (acetone-d6CD2O): d 183.0, 164.3, 163.8, 161.0,
160.7, 157.7, 128.7, 124.9, 117.1, 108.5, 104.8, 104.5, 95.3,
94.6, 81.6, 79.0, 75.0, 72.9, 70.4, 61.5, 56.1; IR (Nujol):
3380, 1653, 1634, 1609, 1574, 1244, 1154, 984; MS (FAB)
m/z 477 (MCH)C; HRMS calcd for C23H25O11 (MCH)C
477.1397, found 477.1353.
4.2.1. 7-Benzyloxy-5-hydroxy-2-(4-methoxymethoxy-
phenyl)-6-(2,3,4,6-tetra-O-benzyl-b-D-glucopyranosyl)-
4H-1-benzopyran-4-one (isovitexin derivative) (12). Pale
4.2.4. Transformation to target flavone 1. To a mixture of
13 (16 mg, 34 mmol), 1,10-azobis(N,N-dimethylformamide)
(12 mg, 68 mmol) in THF (2.0 mL) was added n-Bu3P
(17 mL, 68 mmol) at 0 8C. After stirring at 50 8C for 24 h, the
mixture was concentrated and the residue was subjected to
column chromatography (SiO2, CHCl3–MeOHZ50/1) to
afford the mixture (14.6 mg) containing compound 15. Part
of the mixture (6.7 mg) was dissolved in MeOH (1.0 mL)
and treated with 4 N HCl–dioxane (0.2 mL). After stirring at
room temperature for 30 min, the reaction mixture was
evaporated to give a residue containing the target flavone 1.
The chemical yield (32%) of 1 from 13 was obtained from
the HPLC quantification (YMC-pack ODS R-ODS-5A,
MeOH–H2OZ1/1, 0.3 mL/min, tRZ37.0 min).
1
yellow oil; [a]D20ZK18.0 (c 1.2, CHCl3); H NMR (C6D6,
rotamers): d 14.34, 14.27 (s, 1H, OH), 7.53–6.80 (m, 25H,
Bn), 7.32 (m, 2H, Ar), 6.91 (m, 2H, Ar), 6.36, 6.34 (s, 1H,
Ar), 6.14, 6.06 (s, 1H, Ar), 5.55, 5.38 (d, 1H, JZ9.5 Hz,
sugar H-1), 5.05, 4.63 (t, 1H, JZ9.5 Hz, sugar H-2), 5.00–
4.40 (m, 10H, Bn), 4.65 (s, 2H, MOM), 4.06, 4.04 (t, 1H,
JZ9.2 Hz, sugar H-4), 3.90, 3.87 (m, 1H, sugar H-3), 3.85,
3.76, 3.72, 3.64 (m, 2H, sugar H-6), 3.67, 3.57 (m, 1H, sugar
H-5), 3.02 (s, 3H, MOM); 13C NMR (C6D6, rotamers): d
182.5 (C]O), 163.8, 162.2 (Ar), 163.0 (Ar), 161.7, 161.0
(Ar), 160.2 (Ar), 157.7, 157.6 (Ar), 130.0–127.0 (Bn), 128.5
(Ar), 125.5 (Ar), 116.4 (Ar), 110.9, 110.6 (Ar), 105.8 (Ar)
106.0, 105.5 (Ar), 93.5 (MOM), 91.7, 91.0 (Ar), 87.5
(sugar C-3), 80.5 (sugar C-5), 79.3, 78.9 (sugar C-2), 78.7
(sugar C-4), 75.2–73.5 (Bn), 73.2, 73.0 (sugar C-1), 69.2
(sugar C-6), 56.2 (MOM); IR (CHCl3): 3011, 2930, 2866,
1655, 1609, 1454, 1348; MS (FAB) m/z 927 (MCH)C;
HRMS calcd for C58H55O11 (MCH)C 927.3745, found
927.3782.
Under the same Mitsunobu conditions started from 13
(19 mg, 40 mmol) and subsequent deprotection by 4 N HCl–
dioxane gave 1 (3.3 mg, 20%) after purification by column
chromatography (Sephadex LH-20, MeOH). The synthetic
1 was identical with the authentic sample in terms of the 1H
and 13C NMR spectroscopic data5 as well as the retention
time in HPLC analysis.
4.2.2. 7-Benzyloxy-5-hydroxy-2-(4-methoxymethoxy-
phenyl)-8-(2,3,4,6-tetra-O-benzyl-b-D-glucopyranosyl)-
4H-1-benzopyran-4-one (vitexin derivative) (14). Pale
yellow oil; [a]D20ZK20.5 (c 1.2, CHCl3); 1H NMR (C6D6):
d 14.02 (s, 1H, OH), 7.70–6.50 (m, 25H, Bn), 7.91 (d, 2H,
JZ9.2 Hz, Ar), 7.06 (m, 2H, Ar), 6.36 (s, 1H, Ar), 6.35 (s,
1H, Ar), 5.33 (d, 1H, JZ9.9 Hz, sugar H-1), 5.00–4.00 (m,
10H, Bn), 4.68 (s, 2H, MOM), 4.34 (m, 1H, sugar H-2), 4.19
(m, 1H, sugar H-4), 3.83 (t, 1H, JZ8.8 Hz, sugar H-3), 3.71
(dd, 1H, JZ3.5, 10.7 Hz, sugar H-6a), 3.52 (dd, 1H, JZ1.2,
10.7 Hz, sugar H-6b), 3.40 (d, 1H, JZ9.9 Hz, sugar H-5),
2.99 (s, 3H, MOM); 13C NMR (C6D6): d 182.8 (C]O),
163.8 (Ar), 163.3 (Ar), 162.5 (Ar), 160.4 (Ar), 155.9 (Ar),
140.0–125.0 (Bn), 129.6 (Ar), 125.2 (Ar), 117.7 (Ar), 106.1
Mp 229–232 8C; yellow needles (from MeOH); [a]2D0Z
K174.5 (c 0.17, MeOH); IR (Nujol): 3345, 1672, 1626, 1611,
1574, 1561, 1252, 1086; MS (FAB) m/z 415 (MCH)C;
HRMS calcd for C21H19O9 (MCH)C 415.1029, found
415.1032.
References and notes
1. (a) Postema, M. H. D. Tetrahedron 1992, 48, 8545.
(b) Postema, M. H. D. C-Glycoside Synthesis; CRC: London,

T. Furuta et al. / Tetrahedron 60 (2004) 9375–9379
9379
1995. (c) Levy, D. E.; Tang, C. The Chemistry of C-Glyco-
sides; Pergamon: Tarrytown, NY, 1995.
8. (a) Mitsunobu, O. Synthesis 1981, 1. (b) Tsunoda, T.; Otsuka,
ˆ
J.; Yamamiya, Y.; Ito, S. Chem. Lett. 1994, 539. (c) Tsunoda,
ˆ
T.; Yamamiya, Y.; Kawamura, Y.; Ito, S. Tetrahedron Lett.
2. Nagai, T.; Miyaichi, Y.; Tomimori, T.; Suzuki, Y.; Yamada,
H. Chem. Pharm. Bull. 1990, 38, 1329.
1995, 36, 2529.
3. Hirobe, C.; Qiao, Z.-S.; Takeya, K.; Itokawa, H. Phyto-
chemistry 1997, 46, 521.
9. Mahling, J.-A.; Jung, K.-H.; Schmidt, R. R. Liebigs Ann. 1995,
461.
4. Carte, B. K.; Carr, S.; DeBrosse, C.; Hemling, M. E.;
MacKenzie, L.; Offen, P.; Berry, D. E. Tetrahedron 1991,
47, 1815.
10. Cairns, H. Tetrahedron 1972, 28, 359.
11. Schmidt, R. R.; Stumpp, M. Liebigs Ann. Chem. 1983, 1249.
12. Mahling, J.-A.; Schmidt, R. R. Synthesis 1993, 325.
13. Inouye, M.; Chiba, J.; Nakazumi, H. J. Org. Chem. 1999, 64,
8170.
5. Ishikura, Y.; Tsuji, K.; Nukaya, H. Jpn. Kokai Tokkyo Koho
2002, 194828.
6. The compound 1 was synthesized by 14 steps from the
commercially available glucal derivative in 0.2% overall
yield: Nakatsuka, T.; Tomimori, Y.; Fukuda, Y.; Nukaya, H.
Bioorg. Med. Chem. Lett. 2004, 14, 3201.
14. (a) Pinto, D. C. G. A.; Silva, A. M. S.; Cavaleiro, J. A. S.
Tetrahedron Lett. 1994, 35, 9459. (b) Kumazawa, T.;
Minatogawa, T.; Matsuba, S.; Sato, S.; Onodera, J. Carbohydr.
Res. 2000, 329, 507.
7. For examples, see: (a) Matsumoto, T.; Katsuki, M.; Suzuki, K.
Tetrahedron Lett. 1988, 29, 6935. (b) Matsumoto, T.; Katsuki,
M.; Jona, H.; Suzuki, K. J. Am. Chem. Soc. 1991, 113, 6982.
(c) Kumazawa, T.; Ohki, K.; Ishida, M.; Sato, S.; Onodera, J.;
Matsuba, S. Bull. Chem. Soc. Jpn. 1995, 68, 1379. (d) Herzner,
H.; Palmacci, E. R.; Seeberger, P. H. Org. Lett. 2002, 4, 2965.
(e) Kanai, A.; Kamino, T.; Kuramochi, K.; Kobayashi, S. Org.
Lett. 2003, 5, 2837.
´ ´
15. Litkei, G.; Gulacsi, K.; Antus, S.; Blasko, G. Liebigs Ann.
1995, 1711.
16. (a) Lynch, H. M.; O’Toole, T. M.; Wheeler, T. S. J. Chem. Soc.
1952, 2063. (b) Tanaka, H.; Stohlmeyer, M. M.; Wandless,
T. J.; Taylor, L. P. Tetrahedron Lett. 2000, 41, 9735.