Synthesis of polyfunctionalized furans from 3-acetyl-1-aryl-2-pentene-1,4-diones

Article abstract of DOI:10.1016/S0040-4020(02)01597-1

The BF₃-catalyzed cyclization of 3-acetyl-1-aryl-2-pentene-1,4-diones 1a-e in the presence of water in boiling tetrahydrofuran gave bis(3-acetyl-5-aryl-2-furyl)methanes 2a-e in 26-79% yields along with a small amount of 3-acetyl-5-aryl-2-methylfurans 3a-e. The exact structure of 2a was determined by X-ray crystallography. The use of a half volume of the solvent for the reaction of 1a resulted in the formation of 2,4-bis(3-acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-phenylfuran (4) together with 2a and 3a. A similar reaction of 1a was carried out in the presence of 3-acetyl-5-(4-methylphenyl)-2-methylfuran (3d) to afford 4-(3-acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-(4-methylphenyl)-2-methylfuran (5) in 49% yield. The BF₃-catalyzed reaction of 1a with 2,4-pentanedione in dry tetrahydrofuran at 23°C gave 3-(3-acetyl-5-phenyl-2-furfuryl)-4-hydroxy-3-penten-2-one (6a) and 3-(3-acetyl-2-methyl-4-phenyl-5-furyl)-4-hydroxy-3-penten-2-one (7a) in 66 and 24% yields, respectively. The product distribution depended on the reaction temperature. A similar reaction of 1b-e also yielded the corresponding trisubstituted furans 6b-e and tetrasubstituted furans 7b-e in good yields. These results suggested the presence of the furfuryl carbocation intermediate A during the reaction. The one-pot synthesis of 6a and 7a was also achieved by a similar reaction using phenylglyoxal. The deoxygenation of 1a with triphenylphosphine gave 3a in 88% yield, while 1a was treated with concentrated hydrochloric acid to yield 3-acetyl-2-chloromethyl-5-phenylfuran (8) which was quantitatively transformed in ethanol into 3-acetyl-2-ethoxymethyl-5-phenylfuran (9) and in water into 3-acetyl-5-phenylfurfuryl alcohol (10), respectively. In addition, the Diels-Alder reaction of cyclopantadiene with 1a gave the corresponding [4+2] cycloaddition products 11 and 12.

Full text of DOI:10.1016/S0040-4020(02)01597-1

Tetrahedron 59 (2003) 755–765
Synthesis of polyfunctionalized furans from
3-acetyl-1-aryl-2-pentene-1,4-diones
*
Satoaki Onitsuka and Hiroshi Nishino
Department of Chemistry, Faculty of Science, Kumamoto University, Kurokami 2-39-1, Kumamoto 860-8555, Japan
Received 18 November 2002; revised 11 December 2002; accepted 11 December 2002
Abstract—The BF3-catalyzed cyclization of 3-acetyl-1-aryl-2-pentene-1,4-diones 1a–e in the presence of water in boiling tetrahydrofuran
gave bis(3-acetyl-5-aryl-2-furyl)methanes 2a–e in 26–79% yields along with a small amount of 3-acetyl-5-aryl-2-methylfurans 3a–e. The
exact structure of 2a was determined by X-ray crystallography. The use of a half volume of the solvent for the reaction of 1a resulted in the
formation of 2,4-bis(3-acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-phenylfuran (4) together with 2a and 3a. A similar reaction of 1a was carried
out in the presence of 3-acetyl-5-(4-methylphenyl)-2-methylfuran (3d) to afford 4-(3-acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-(4-
methylphenyl)-2-methylfuran (5) in 49% yield. The BF3-catalyzed reaction of 1a with 2,4-pentanedione in dry tetrahydrofuran at 238C
gave 3-(3-acetyl-5-phenyl-2-furfuryl)-4-hydroxy-3-penten-2-one (6a) and 3-(3-acetyl-2-methyl-4-phenyl-5-furyl)-4-hydroxy-3-penten-2-
one (7a) in 66 and 24% yields, respectively. The product distribution depended on the reaction temperature. A similar reaction of 1b–e also
yielded the corresponding trisubstituted furans 6b–e and tetrasubstituted furans 7b–e in good yields. These results suggested the presence of
the furfuryl carbocation intermediate A during the reaction. The one-pot synthesis of 6a and 7a was also achieved by a similar reaction using
phenylglyoxal. The deoxygenation of 1a with triphenylphosphine gave 3a in 88% yield, while 1a was treated with concentrated hydrochloric
acid to yield 3-acetyl-2-chloromethyl-5-phenylfuran (8) which was quantitatively transformed in ethanol into 3-acetyl-2-ethoxymethyl-5-
phenylfuran (9) and in water into 3-acetyl-5-phenylfurfuryl alcohol (10), respectively. In addition, the Diels–Alder reaction of
cyclopantadiene with 1a gave the corresponding [4þ2] cycloaddition products 11 and 12. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
Furans and their derivatives are widely present in nature1
and not only one of the most important heterocyclic
compounds in organic chemistry,2 but also building blocks
which are essential for the total synthesis of the complicated
naturally
occurring
metabolites.3
Furthermore,
polyfunctionalized furans are versatile and convenient
synthetic starting materials for the preparation of a variety
of heterocyclic and acyclic compounds.4 In connection with
our study of the synthesis and reaction of substituted furan
derivatives,5 we recently found that endoperoxide inter-
mediates6 obtained by the photosensitized oxygenation of
furans7 were selectively transformed into pentenediones 1
and oxiranes depending on the reaction conditions (Scheme
1).8 As the pentenediones 1 were not very stable in air due to
the extremely electron-deficient alkene, it prompted us to
explore the reactivity of the pentenediones 1.9 Since the
acid-catalyzed cyclization of 1,4-diketones is well-
known,4c,10 we first examined the BF3-catalyzed cyclization
of the pentenediones 1.11 Surprisingly, the pentenediones 1
Scheme 1.
were converted into very stable crystalline bis(furyl)-
methane derivatives. Furthermore, the presence of a strong
nucleophile in a similar reaction led to the formation of
polyfunctionalized furans. Although the synthesis of furans
has been well-documented over the past three decades2,4,12
and a very new methodology for the facile synthesis of
substituted furans by palladium-catalyzed reaction was also
reported,13 we scrutinized the typical BF3-catalyzed reac-
tion of the pentenediones 1 from the standpoint of the
synthesis of the polyfunctionalized furans. In addition, the
synthetic applications using the pentenediones 1 were also
investigated in order to evaluate their synthetic utility.
Keywords: BF3-catalyzed cyclization; 3-acetyl-1-aryl-2-pentene-1,4-
diones; polyfunctionalized furans; bis(furyl)methanes; trisubstituted
furans; tetrasubstituted furans; furfuryl carbocation intermediate; Diels–
Alder reaction.
*
Corresponding author. Tel./fax: þ81-96-342-3374;
e-mail: nishino@aster.sci.kumamoto-u.ac.jp
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01597-1

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S. Onitsuka, H. Nishino / Tetrahedron 59 (2003) 755–765
ture of 2a was characterized by spectroscopic means,
elemental analysis, and finally X-ray crystallography, and
found to be bis(3-acetyl-5-phenyl-2-furyl)methane which
showed C2 symmetry at the methylene group (Fig. 1). The
treatment of the pentenediones 1b–e with BF3·Et2O under
the same reaction conditions preferentially gave the
corresponding bis(furyl)methanes 2b–e together with a
small amount of the trisubstituted furans 3b–e (entries
6–9).
In order to scrutinize the reaction, the reaction of 1a was
carried out in a half volume of the solvent, thus leading to
the decrease of the yield of 2a and the new production of the
trimeric furan derivative 4 which was determined to be 2,4-
bis(3-acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-phenylfuran
based on the spectroscopic data (FAB MS m/z 583, Mþ1)
and elemental analysis (entry 4). On the other hand, a
similar reaction under dilute conditions resulted in the
Scheme 2.
Table 1. BF3-Catalyzed cyclization of 3-acetyl-1-aryl-2-pentene-1,4-diones 1a–e
Entry
Substrate
Water (equiv.)
Conc.a (mol/dm3)
Time (h)
Product (yield, %)b
1
2
3
4
5
6
7
8
9
1a: Ar¼Ph
0
5
0.2
0.2
0.1
0.2
0.04
0.1
0.1
0.1
0.1
0.5
0.5
1.5
1
6
2
2
2
2
2a (21)
2a (62)
2a (79)
2a (62)
2a (61)
2b (67)
2c (63)
2d (65)
2e (26)
1a: Ar¼Ph
1a: Ar¼Ph
10
10
10
10
10
10
10
3a (4)
3a (3)
3a (13)
3b (6)
3c (3)
3d (5)
3e (10)
1a: Ar¼Ph
4 (15)
1a: Ar¼Ph
1b: Ar¼4-F-C6H4
1c: Ar¼4-Cl-C6H4
1d: Ar¼4-Me-C6H4
1e: Ar¼4-MeO-C6H4
The reaction of the pentenedione 1 (0.5 mmol) with BF3·Et2O (5.0 mmol) was carried out in tetrahydrofuran (0.5–12.5 mL) containing water (5.0 mmol except
for entries 1 and 2) at the reflux temperature.
a
The concentration of 1 in tetrahydrofuran.
Isolated yield based on the amount of pentenedione 1 used.
b
2. Results and discussion
increased yield of 3a (entry 5). Since the trimeric furan 4
seemed to be formed by the reaction of 2a with the
corresponding furfuryl carbocation intermediate, we
examined the BF3-catalyzed reaction of 1a in the
presence of an electron-rich furan derivative such as
2.1. BF3-Catalyzed cyclization of 3-acetyl-1-aryl-2-
pentene-1,4-diones 1a–e
In order to prepare a practical amount of 3-acetyl-1-phenyl-
2-pentene-1,4-dione (1a), we developed the synthesis of 1a
using phenylglyoxal and 2,4-pentanedione.9 The Lewis
acid-catalyzed crossed Aldol condensation in tetrahydro-
furan afforded 1a in low yield.14 The Knoevenagel
condensation using pyridine in boiling tetrahydrofuran
gave 1a in 87% yield.9,15 Finally we obtained 1a in
quantitative yield (98%) by the reaction in boiling
acetonitrile for 12 h in the absence of catalyst. Since we
had enough 1a on hand, we examined the BF3-catalyzed
cyclization of 1a.
The pentenedione 1a was allowed to react with BF3·Et2O in
boiling tetrahydrofuran. Although the reaction was compli-
cated, we managed to isolate the dimeric furan 2a (Scheme 2
and Table 1, entry 1). We postulated that some nucleophilic
reagents such as water were necessary to control the
reaction. As expected, the addition of water led to the
increased yield of 2a (entry 2). When 10 equiv. of water
based on 1a was added to the mixture, the maximum yield
of 2a (79%) was achieved along with a small amount of
3-acetyl-2-methyl-5-phenylfuran (3a) (entry 3). The struc-
Figure 1. ORTEP diagram of bis(furyl)methane 2a.

S. Onitsuka, H. Nishino / Tetrahedron 59 (2003) 755–765
757
hydrofuran at 238C. It was a mild exothermic reaction, and
the trisubstituted furan 6a and tetrasubstituted furan 7a were
obtained in 66 and 24% yields, respectively (Scheme 4 and
Table 2, entry 2). Since the mass spectra of 6a and 7a
showed the same molecular ion peak (m/z 298), both
1
products were isomers of each other. The H NMR spectra
of 6a and 7a revealed a broad singlet at d 16.88 and 16.75,
respectively, which were assigned to the intramolecular
hydrogen-bonded hydroxyl proton. The IR spectra also
showed weak intramolecular hydrogen-bonded hydroxyl
broad absorptions at 3700–3200 cm21, and the enolizable
b-diketocarbonyl absorptions appeared at 1673–1678 and
1610–1600 cm21. These spectroscopic data indicated the
1
presence of the 4-hydroxy-3-penten-2-one moiety. The H
and 13C NMR spectra of 6a were similar to those of 3a
except for the (4-hydroxy-2-oxo-3-penten-3-yl)methyl
group in place of the methyl group at the C-20 carbon.
Therefore, it was easy to characterize the structure of 6a
which was the 3-(3-acetyl-5-phenyl-2-furfuryl)-4-hydroxy-
3-penten-2-one. Since the furan 7a was substituted by four
different functional groups, several regioisomers of 7a were
postulated. However, it was difficult to deduce the structure
of 7a based on the spectroscopic method.16 The exact
structure of 7a was eventually determined by an X-ray
single crystal analysis as 3-(3-acetyl-2-methyl-4-phenyl-5-
furyl)-4-hydroxy-3-penten-2-one (Fig. 2). It was found that
both the 4-hydroxy-3-penten-2-one moiety and the phenyl
Scheme 3.
Scheme 4.
Table 2. BF3-Catalyzed reaction of 3-acetyl-1-aryl-2-pentene-1,4-diones 1a–e with 2,4-pentanedione
Entry
Substrate
Temperature (8C)
Time (h)
Product (yield, %)a
6a (34)
1
2
3
4
5
6
7
1a: Ar¼Ph
0
23
Reflux
23
23
2
7a (52)
7a (24)
7a (16)
7b (23)
7c (8)
1a: Ar¼Ph
0.5
0.5
0.5
0.5
0.5
0.5
6a (66)
6a (77)
6b (53)
6c (76)
6d (34)
6e (15)
1a: Ar¼Ph
1b: Ar¼4-F-C6H4
1c: Ar¼4-Cl-C6H4
1d: Ar¼4-Me-C6H4
1e: Ar¼4-MeO-C6H4
23
23
7d (53)
7e (59)
The reaction was carried out in dry tetrahydrofuran (5 mL) at the molar ratio of 1 (1.0 mmol)/2,4-pentanedione/BF3·Et2O¼1:10:10.
a
Isolated yield based on the amount of pentenedione 1 used.
3-acetyl-5-(4-methylphenyl)-2-methylfuran (3d)5c,8 to trap
the furfuryl carbocation intermediate. The pentenedione 1a
was allowed to react with 3 equiv. of 3d in the presence of
BF3·Et2O in tetrahydrofuran containing water at 238C for
30 min, giving a dimeric furan 5 in 49% yield (Scheme 3).
The irradiation of the H-40 proton in the 1H NMR spectrum
of 5 showed an enhancement of the ortho phenyl proton (d
7.46–7.43) and the acetyl proton (d 2.56) signals. There-
fore, the structure of 5 was determined to be 4-(3-acetyl-5-
phenyl-2-furfuryl)-3-acetyl-5-(4-methyl-phenyl)-2-methyl-
furan. Since we obtained evidence for the presence of the
furfuryl carbocation intermediate in the BF3-catalyzed
cyclization of the pentenediones, we next investigated the
reaction using more reactive nucleophiles such as the 2,4-
pentanedionate ion.
2.2. BF3-Catalyzed reaction of pentenediones 1a–e with
2,4-pentanedione9
A mixture of 1a and 2,4-pentanedione (10 equiv.) was
allowed to react with BF3·Et2O (10 equiv.) in dry tetra-
Figure 2. ORTEP drawing of tetrasubstituted furan 7a.

758
S. Onitsuka, H. Nishino / Tetrahedron 59 (2003) 755–765
substituent were not on the same plane of the furan ring in
the solid state because of the steric repulsion of each other.
is liable to occur 6000 times faster at the a position than at
the b one.17 It was easy to prove the existence of the furfuryl
alcohol since the treatment of 3-acetyl-2-chloromethyl-5-
phenylfuran (8) with water gave the corresponding furfuryl
alcohol which was transformed into the corresponding
bis(furyl)methane 2a under the same reaction conditions in
the presence of BF3·Et2O (vide infra). In addition, the
presence of the furfuryl carbocation intermediate A was also
supported by the fact that the trimeric furan 4 would be
obtained by the reaction of the furfuryl carbocation
intermediate A with 2a formed in situ under the concen-
tration conditions (Table 1, Entry 4) and the dimeric furan 5
would be produced by the reaction of the electron-rich furan
3d with the furfuryl carbocation intermediate A. Although
gaseous formaldehyde was not trapped by 2,4-dinitrophe-
nylhydrazine in DMF, it clearly formed formaldehyde since
the reduction product 3a of the corresponding furfuryl
carbocation intermediate A was formed under the dilute
conditions besides 2a (Table 1, entry 5). The reaction
pathway for the formation of the bis(furyl)methanes 2a–e
and furans 3a–e is depicted in Scheme 5.
When a similar reaction of 1a with 2,4-pentanedione was
carried out at 08C for 2 h, the tetrasubstituted furan 7a was
formed rather than 6a (entry 1), whereas the reaction at the
reflux temperature preferentially gave the trisubstituted
furan 6a (entry 3). The reaction of the pentenediones 1b and
1c substituted by an electron-attracting group on the phenyl
ring at 238C preferentially gave the trifunctionalized furans
6b and 6c, respectively (entries 4 and 5). On the other hand,
the pentenediones 1d and 1e having an electron-releasing
group on the phenyl substituent were allowed to react under
similar reaction conditions, mainly affording the tetra-
substituted furans 7d and 7e (entries 6 and 7).
2.3. Mechanistic aspect
When the reaction of the pentenediones 1a–e was carried
out under wet reaction conditions, the BF3-induced
intramolecular cyclization would occur during the first
stage of the reaction to give a relatively stable furfuryl
carbocation intermediate A (Scheme 5). The intermediate A
might be equilibrated to the corresponding furfuryl alcohol
B under the wet reaction conditions, which would be
attacked by another furfuryl cation A at the C-2 position to
complete the electrophilic substitution along with releasing
formaldehyde, giving the bis(furyl)methanes 2a–e.
During the reaction with a strong nucleophile such as the
2,4-pentanedione-BF3 enolate complex under dry con-
ditions, when the electrophilicity of the aroyl carbon in
1b,c would be relatively high because of the presence of
electron-withdrawing groups such as the 4-fluoro- and
4-chloro-phenyl groups or the reaction was carried out
under reflux temperature, the intramolecular cyclization of
the pentendiones 1a–e would preferentially take place to
give the thermodynamically stable furfuryl carbocation
intermediate A (path a in Scheme 6), which would react
with the 2,4-pentanedione-BF3 enolate complex to form
trisubstituted furans 6 (Table 2, entries 3–5). While the
aroyl carbon would not be sufficiently electrophilic such as
1d,e or the reaction was conducted at 08C, fast nucleophilic
addition of a strong nucleophile such as the 2,4-pentane-
dione-BF3 enolate complex to the aroyl carbon should
predominantly occur to afford the intermediate C (path b in
Scheme 6) and subsequent cyclization would give the
It is well-known that the electrophilic substitution of furans
Scheme 5.
Scheme 6.

S. Onitsuka, H. Nishino / Tetrahedron 59 (2003) 755–765
759
tetrasubstituted furans 7 (Table 2, entries 1, 6, 7). The
trisubstituted furans 6a–e seem to be thermodynamically
controlled and the tetrasubstituted furans 7a–e might just be
kinetically controlled reaction products.
The Diels–Alder reaction of cyclopentadiene with the
electron-deficient alkene 1a deserves comment.20 In
general, endo adducts should be predominantly formed
during the [4þ2] cycloaddition, however, the reaction of the
cyclopentadiene with 1a gave the corresponding exo and
endo adducts 11 together with a unique 2-oxabicyclo[3.3.0]-
octene 12 in 96% total yield (11-exo/11-endo/12¼53:12:35)
(Scheme 7).21 The structures of these 11-exo, 11-endo, and
12 products were established by difference NOE experi-
ments. The bicyclic compound 12 might be formed by the
intramolecular rearrangement of the endo adduct 11.
2.4. Synthetic applications
Although the BF3-catalyzed condensation of phenylglyoxal
with a stoichiometric amount of 2,4-pentanedione in dry
tetrahydrofuran at 238C gave the pentenedione 1a in 29%
yield, in order to develop the one-pot synthesis of 6a and 7a,
we examined the reaction using excess amounts of 2,4-
pentanedione.9 As a result, we achieved the one-pot
synthesis of 6a and 7a using 10 equiv. of 2,4-pentanedione
in the BF3-catalyzed condensation of phenylglyoxal at 238C
for 15 min, giving 6a and 7a in 37 and 56% yields,
respectively (Scheme 7).
3. Conclusion
We revealed that the furfuryl carbocation A was an
important key intermediate in the synthesis of polyfunction-
alized furans using 3-acetyl-1-aryl-2-pentene-1,4-diones
1a–e. In the presence of a weak nucleophile such as
water, the BF3-catalyzed cyclization of 1a–e gave bis-
(furyl)methanes 2a–e in good yields along with small
amounts of the reduction products 3a–e. On the other hand,
a strong nucleophile such as the 2,4-pentanedione-BF3
enolate complex reacted with the carbocation A to give the
tri- and tetra-substituted furans 6a–e and 7a–e. Although
there are many synthetic methods for furan derivatives, for
example, the acid-catalyzed dehydration of 1,4-diketones,4c
the reduction of 2-butene-1,4-diones with tin(II) chloride,22
phosphites,23 zinc powder,24 or lithium aluminum
hydride,25 and the addition of 2-butene-1,4-diones with
acetyl chloride26 or Grignard reagent,27 our methodology
for the synthesis of polyfunctionalized furan derivatives
using the BF3-catalyzed cyclization of pentenediones 1 is
also useful and convenient since many pentenedione
derivatives could be prepared from arylglyoxals9,15b,28 and
many kinds of active methylene compounds could be used
as strong nucleophiles. In addition, we could also demon-
strate the synthetic utility of the pentenediones 1.
The pentenediones 1a–e are quite unique and extremely
electron-deficient alkenes so that they would be useful for
organic synthesis. For example, the deoxygenation of 1a
with triphenylphosphine gave 3a in 88% yield (Scheme 7).18
The pentenedione 1a was treated with concentrated
hydrochloric acid at 238C to yield the 3-acetyl-2-chloro-
methyl-5-phenylfuran (8) in 87% yield.19 The chloro-
methylfuran 8 was quantitatively transformed into
2-ethoxymethylfuran 9 in boiling ethanol.19 The hydrolysis
of 8 gave the corresponding furfuryl alcohol 10 which was
allowed to react with BF3·Et2O under typical reaction
conditions to yield 2a in 82% yield (Scheme 7).
4. Experimental
1
The melting points are uncorrected. All of the H and 13C
NMR spectra were recorded at 300 MHz for 1H and 75 MHz
for 13C, respectively, with tetramethylsilane as the internal
standard. The chemical shifts are reported in d values (ppm).
The IR spectra are expressed in cm21. The elemental
analyses were performed at the Analytical Center of
Kumamoto University, Kumamoto, Japan, or the Elemental
Analysis Center of Kyusyu University, Fukuoka, Japan.
The 3-acetyl-1-aryl-2-pentene-1,4-diones (1b–e) were pre-
pared according to the literature method.8 BF3·Et2O, 2,4-
pentanedione, and triphenyl phosphine were purchased from
Wako Pure Chemical Ind., Ltd, and were used as received.
Phenylglyoxal monohydrate was purchased from Tokyo
Chemical Industry Co., Ltd, and was used as received.
4.1. Knoevenagel condensation of phenylglyoxal with
2,4-pentanedione
Phenylglyoxal (1.52 g, 10 mmol) and 2,4-pentanedione
(1.03 mL, 10 mmol) were dissolved in acetonitrile (5 mL)
Scheme 7.

760
S. Onitsuka, H. Nishino / Tetrahedron 59 (2003) 755–765
and the mixture was heated under reflux for 12 h. The
solvent was removed under reduced pressure and the residue
was separated by flash column chromatography (Fuji Silysia
BW-300 silica gel) with hexane/ethyl acetate (4:1 v/v) as the
eluting solvent, thus affording 1a (2.05 g, 95%) as a pale
yellow solid.
27.2 (–CH2–). Anal. calcd for C25H18O4F2: C, 71.42; H,
4.32. Found: C, 71.34; H, 4.26.
4.2.3. Bis[3-acetyl-5-(4-chlorophenyl)-2-furyl]methane
(2c). Colorless microcrystals (from MeOH); mp 201–
2028C; IR (KBr) n 1670 (CvO); 1H NMR (300 MHz,
CDCl3) d 7.53–7.50 (4H, m, arom. H), 7.34–7.32 (4H, m,
arom. H), 6.89 (2H, s, H-40), 4.92 (2H, s, –CH2–), 2.52 (6H,
s, Ac£2); 13C NMR (75 MHz, CDCl3) d 193.7 (2C, CvO),
154.3 (2C, C-50), 151.7 (2C, C-20), 133.8 (2C, arom. CCl),
129.0 (4C, arom. CH), 128.1 (2C, arom. C), 125.0 (4C,
arom. CH), 124.1 (2C, C-30), 105.6 (2C, C-40), 29.2 (2C,
Ac), 27.3 (–CH2–). Anal. calcd for C25H18O4Cl2: C, 66.24;
H, 4.00. Found: C, 66.14; H, 4.13.
4.1.1. 3-Acetyl-1-phenyl-2-pentene-1,4-dione (1a). Pale
yellow needles; mp 68.58C (lit.,7f mp 69–718C); IR (CHCl3)
n 1706, 1666 (CvO), 1597 (CvC–CvO); 1H NMR
(CDCl3) d 8.00–7.40 (5H, m, arom. H), 7.59 (1H,
s,vCH–), 2.46 (3H, s, Ac), 2.42 (3H, s, Ac); 13C NMR
(CDCl3) d 202.9, 196.4, 189.9 (CvO), 151.9 (vCr), 136.1
(arom. C), 134.4 (arom. CH), 130.2 (vCH–), 129.0 (2C),
128.7 (2C) (arom. CH), 30.7, 27.2 (Ac). Anal. calcd for
C13H12O3: C, 72.21; H, 5.59. Found: C, 72.37; H, 5.59.
4.2.4. Bis[3-acetyl-5-(4-methylphenyl)-2-furyl]methane
(2d). Colorless microcrystals (from MeOH); mp 174–
1758C; IR (KBr) n 1682 (CvO); 1H NMR (300 MHz,
CDCl3) d 7.49–7.47 (4H, m, arom. H), 7.17–7.14 (4H, m,
arom. H), 6.82 (2H, s, H-40), 4.91 (2H, s, –CH2–), 2.51 (6H,
s, Ac£2), 2.33 (6H, s, Me£2); 13C NMR (75 MHz, CDCl3) d
193.9 (2C, CvO), 153.9 (2C, C-50), 152.9 (2C, C-20), 137.9
(2C, arom. CMe), 129.4 (4C, arom. CH), 126.9 (2C, arom. C),
123.9 (2C, C-30), 123.8 (4C, arom. CH), 104.3 (2C, C-40), 29.2
(2C, Ac), 27.3 (–CH2–), 21.3 (2C, Me). Anal. calcd for
C27H24O4: C, 78.62; H, 5.86. Found: C, 78.43; H, 5.87.
4.2. BF3-Catalyzed cyclization of pentenediones 1a–e
The pentenediones 1a–e (0.5 mmol) were dissolved in THF
(5 mL) containing water (90 mL, 5.0 mmol). BF3·Et2O
(635 mL, 5.0 mmol) was added to the solution and the
mixture was heated under reflux for 30 min. The yellow
color of the reaction mixture then turned red. Water (20 mL)
and a saturated aqueous solution of sodium hydrogencarbo-
nate (30 mL) were added to the reaction mixture, and the
aqueous mixture was extracted with chloroform. The extract
was washed with water (100 mL) and concentrated to
dryness. The residue was separated by flash column
chromatography (Fuji Silysia BW-300 silica gel) with
chloroform as the eluting solvent, then giving the bis-
(furyl)methanes 2a–e and 3-acetyl-5-aryl-2-methylfurans
3a–e.5c The bis(furyl)methanes 2a–e were further purified
by silica gel TLC and recrystallized from methanol or
dichloromethane/hexane. The exact structure of the bis-
(furyl)methane 2a was determined by X-ray
crystallography.
4.2.5. Bis[3-acetyl-5-(4-methoxyphenyl)-2-furyl]-
methane (2e). Reddish-orange microcrystals (from
MeOH); mp 128–1298C; IR (KBr) n 1676, 1661 (CvO);
1H NMR (300 MHz, CDCl3) d 7.53–7.50 (4H, m, arom. H),
6.90–6.87 (4H, m, arom. H), 6.75 (2H, s, H-40), 4.90 (2H, s,
–CH2–), 3.81 (6H, s, MeO£2), 2.51 (6H, s, Ac£2); 13C
NMR (75 MHz, CDCl3) d 193.9 (2C, CvO), 159.5 (2C,
arom. CO), 153.7 (2C, C-50)0 , 152.8 (2C, C-20), 125.3 (4C,
arom. CH), 124.0 (2C, C-3 ), 122.7 (2C, arom. C), 114.2
(4C, arom. CH), 103.5 (2C, C-40), 55.3 (2C, MeO£2), 29.2
(2C, Ac), 27.3 (–CH2–). Anal. calcd for C27H24O6: C,
72.96; H, 5.44. Found: C, 72.86; H, 5.60.
4.2.1. Bis(3-acetyl-5-phenyl-2-furyl)methane (2a). Color-
less cubes (from dichloromethane/hexane); mp 2198C; IR
(KBr) n 1678 (CvO); 1H NMR (300 MHz, CDCl3) d 7.60–
7.58 (4H, m, arom. H), 7.38–7.33 (4H, m, arom. H), 7.29–
7.24 (2H, m, arom. H), 6.89 (2H, s, H-40), 4.93 (2H, s,
–CH2–), 2.53 (6H, s, Ac£2); 13C NMR (75 MHz, CDCl3) d
193.9 (2C, CvO), 154.3 (2C, C-50), 152.8 (2C, C-20), 129.7
(2C, arom. C), 128.8 (4C, arom. CH), 128.0 (2C, arom. CH),
124.0 (2C, C-30), 123.8 (4C, arom. CH), 105.1 (2C, C-40),
29.2 (2C, Ac), 27.4 (–CH2–); MS m/z (rel. intensity), 384
(22, Mþ), 341 (100), 237 (9), 207 (9), 165 (9), 128 (8), 115
(11), 105 (68), 77 (52), 43 (77). Anal. calcd for C25H20O4:
C, 78.11; H, 5.24. Found: C, 78.03; H, 5.21. The crystal-
lographic data deposition number: CCDC 198377.
4.2.6. 2,4-Bis(3-acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-
phenylfuran (4). Colorless microcrystals (from MeOH);
mp 127–1288C; IR (KBr) n 1666 (CvO); 1H NMR
(300 MHz, CDCl3) d 7.59–7.56 (4H, m, arom. H), 7.44–
7.20 (11H, m, arom. H), 6.89 (1H, s, H-4 or 40), 6.86 (1H, s,
H-40 or 4), 4.90 (2H, s, –CH2–), 4.68 (2H, s, –CH2–), 2.53
(3H, s, Ac), 2.52 (3H, s, Ac), 2.51 (3H, s, Ac); 13C NMR
(75 MHz, CDCl3) d 194.6, 194.2, 194.0 (CvO), 157.8 (C-5),
154.0, 153.5 (C-50), 153.0, 152.1 (C-20), 150.8 (C-2), 129.8,
129.7, 129.5 (arom. C), 128.8, 128.7, 128.6 (2C, arom. CH),
128.2, 128.1, 127.7 (arom. CH), 126.8 (2C, arom. CH), 125.0
(C-3), 123.8 (2C, arom. CH), 123.7 (C-30), 123.05 (2C, arom.
CH), 122.9 (C-30), 114.8 (C-4), 105.2, 105.1 (C-4 ), 30.5, 29.3,
29.2 (Ac), 27.9, 24.7 (–CH2–); FAB MS m/z (rel. intensity),
583 (30, Mþ1), 539, (36), 397 (30), 307 (18), 199 (100), 154
(47), 105, 45), 77 (15). Anal. calcd for C38H30O6: C, 78.33; H,
5.19. Found: C, 78.12; H, 5.19.
4.2.2. Bis[3-acetyl-5-(4-fluorophenyl)-2-furyl]methane
(2b). Colorless microcrystals (from MeOH); mp 172–
1748C; IR (KBr) n 1676 (CvO); 1H NMR (300 MHz,
CDCl3) d 7.49–7.44 (4H, m, arom. H), 6.99–6.93 (4H, m,
arom. H), 6.74 (2H, s, H-40), 4.82 (2H, s, –CH2–), 2.43 (6H,
s, Ac£2); 13C NMR (75 MHz, CDCl3) d 193.8 (2C, CvO),
162.4 (2C, d, J¼247.9 Hz, arom. CF), 154.1 (2C, C-50),
151.8 (2C, C-20), 125.9 (2C, d, J¼3.7 Hz, arom. C), 125.6
(4C, d, J¼8.1 Hz, arom. CH), 124.0 (2C, 0C-30), 115.8 (4C,
d, J¼22.4 Hz, arom. CH), 104.8 (2C, C-4 ), 29.2 (2C, Ac),
4.3. Reaction of 1a with trisubstituted furan 3d in the
presence of BF3·Et2O
The pentenedione 1a (108 mg, 0.5 mmol) and 3-acetyl-5-(4-
methylphenyl)-2-methylfuran (3d, 321 mg, 1.5 mmol) were

S. Onitsuka, H. Nishino / Tetrahedron 59 (2003) 755–765
761
dissolved in THF (2 mL) containing water (90 mL,
5.0 mmol), and BF3·Et2O (1.27 mL, 10 mmol) was added
to the mixture. The mixture was stirred at 238C for 30 min.
After normal work-up, the residue was separated by silica
gel TLC (Wakogel B-10) using hexane/ethyl acetate (1:1
v/v) as the developing solvent, thus affording the product 5
(103 mg, 49%) which was further purified by recrystalliza-
tion from methanol.
4.4.2. 3-[3-Acetyl-5-(4-fluorophenyl)-2-furfuryl]-4-
hydroxy-3-penten-2-one (6b). Colorless needles (from
MeOH); mp 152.5–153.58C; IR (KBr) n 3700–3300
1
(OH), 1678 (CvO); H NMR (300 MHz, CDCl3) d 16.89
(1H, OH), 7.56–7.51 (2H, m, arom. H), 7.12–7.06 (2H, m,
arom. H), 6.79 (1H, s, H-40), 4.12 (2H, s, –CH2–), 2.49 (3H,
s, Ac), 2.24 (6H, s, Ac£2); 13C NMR (75 MHz, CDCl3) d
194.5 (CvO), 192.1 (2C, C-2 and C-4), 162.5 (d,
J¼248.5 Hz, arom. CF), 158.5 (C-20), 151.7 (C-50), 125.9
(d, J¼3.1 Hz, arom. C), 125.5 (2C, d, J¼8.1 Hz, arom. CH),
122.4 (C-30), 1160.0 (2C, d, J¼22.4 Hz, arom. CH), 106.1
(C-3), 104.7 (C-4 ), 29.4 (Ac), 26.1 (CH2), 23.5 (2C, Me);
FAB HRMS (acetone-NBA) calcd for C18H17O4F
316.1111. Found 316.1111.
4.3.1. 4-(3-Acetyl-5-phenyl-2-furfuryl)-3-acetyl-5-(4-
methylphenyl)-2-methylfuran (5). Colorless needles
(from MeOH); mp 1538C; IR (KBr) n 1677, 1662 (CvO);
1H NMR (300 MHz, CDCl3) d 7.51–7.48 (2H, m, arom. H
of 4-MeC6H4–), 7.46–7.43 (2H, m, arom. H of Ph), 7.32–
7.27 (2H, m, arom. H of Ph), 7.25–7.22 (1H, m, arom. H of
Ph), 7.21–7.18 (2H, m, arom. H of 4-MeC6H4–), 6.87 (1H,
s, H-40), 4.34 (2H, s, –CH2–), 2.66 (3H, s, Ac), 2.53 (3H, s,
Ac), 2.42 (3H, s, Me), 2.35 (3H, s, Me–C6H4–); 13C NMR
(75 MHz, CDCl3) d 194.4, 194.2 (CvO), 158.4 (C-5),
157.0 (C-50), 151.9 (C-20), 150.1 (C-2), 129.9 (arom. C),
129.4, 128.7 (2C, arom. CH), 127.7 (arom. CH0), 127.3
(arom. C), 126.7 (2C, arom. CH), 123.9 (C-3 or 3 ), 1230.6
(2C, arom. CH), 123.0 (C-3 or 30), 114.3 (C-4), 105.3 (C-4 ),
30.6, 29.3 (Ac), 24.8 (–CH2–), 21.3 (Me), 15.5
(MeC6H4–). Anal. calcd for C27H24O4: C, 78.62; H, 5.86.
Found: C, 78.79; H, 5.89.
4.4.3. 3-[3-Acetyl-5-(4-chlorophenyl)-2-furfuryl]-4-
hydroxy-3-penten-2-one (6c). Colorless needles (from
MeOH); mp 1778C; IR (KBr) n 3700–3300 (OH), 1675,
1
1609 (CvO); H NMR (300 MHz, CDCl3) d 16.87 (1H,
OH), 7.50–7.48 (2H,0m, arom. H), 7.37–7.34 (2H, m, arom.
H), 6.84 (1H, s, H-4 ), 4.12 (2H, s, –CH2–), 2.49 (3H, s,
Ac), 2.23 (6H, s, Ac£2); 13C NMR (75 MHz, CDCl3) d
194.4 (CvO), 192.1 (2C, C-2 and C-4), 158.8 (C-20), 151.5
(C-50), 134.0 (arom. C), 129.2 (2C, aro0m. CH), 128.0 (arom.
C), 124.9 (2C, arom. CH), 122.5 (C-3 ), 106.0 (C-3), 105.5
(C-40), 29.4 (Ac), 26.2 (CH2), 23.5 (2C, Me). Anal. calcd for
C18H17ClO4: C, 64.97; H, 5.15. Found: C, 65.16; H, 5.27.
4.4. BF3-Catalyzed reaction of pentenediones 1a–e with
2,4-pentanedione9
4.4.4. 3-[3-Acetyl-5-(4-methylphenyl)-2-furfuryl]-4-
hydroxy-3-penten-2-one (6d). Colorless needles (from
MeOH); mp 145–1468C; IR (KBr) n 3700–3300 (OH),
1-Aryl-2-pentene-1,4-diones 1a–e (1.0 mmol)8 was dis-
solved in THF (5 mL), and 2,4-pentanedione (1.03 mL,
10 mmol) and BF3·Et2O (1.27 mL, 10 mmol) were simul-
taneously added to the solution. The mixture was stirred at
238C for 15 min. The reaction was exothermic and the
yellow color of the solution turned red. Water (20 mL) and a
saturated aqueous solution of sodium hydrogencarbonate
(30 mL) were added to the reaction mixture, and the
aqueous mixture was extracted with chloroform. The
combined extract was washed with water (100 mL), dried
over anhydrous MgSO4, and concentrated to dryness. The
residue was separated by flash column chromatography
(Fuji Silysia BW-300 silica gel) with chloroform as the
eluting solvent. The obtained products were further purified
by silica gel TLC (Wakogel B-10) using hexane/ethyl
acetate (1:1 v/v) as the developing solvent, followed by
recrystallization from methanol.
1679, 1597 (CvO); H NMR (300 MHz, CDCl3) d 16.88
1
(1H, OH), 7.46–7.44 (2H, m, arom. H), 7.20–7.18 (2H, m,
arom. H), 6.78 (1H, s, H-40), 4.11 (2H, s, –CH2–), 2.48 (3H,
s, Ac), 2.37 (Me), 2.24 (6H, s, Ac£2); 13C NMR (75 MHz,
CDCl3) d 194.6 (CvO), 192.2 (2C, C-2 and C-4), 158.2
(C-20), 152.8 (C-50), 138.2, (arom. C), 129.6 (2C, arom.
CH), 126.8 (arom. C), 123.7 (2C, arom. CH), 122.3 (C-30),
106.2 (C-3), 104.3 (C-40), 29.4 (Ac), 26.2 (CH2), 23.5 (2C,
Me), 21.3 (Me). Anal. calcd for C19H20O4: C, 73.06; H,
6.45. Found: C, 73.08; H, 6.25.
4.4.5. 3-[3-Acetyl-5-(4-methoxyphenyl)-2-furfuryl]-4-
hydroxy-3-penten-2-one (6e). Colorless needles (from
MeOH); mp 142–1458C; IR (KBr) n 3700–3300 (OH),
1
1675, 1609 (CvO); H NMR (300 MHz, CDCl3) d 16.88
(1H, OH), 7.51–7.48 (2H, m, arom. H), 6.93–6.91 (2H, m,
arom. H), 6.70 (1H, s, H-40), 4.10 (2H, s, –CH2–), 3.84 (3H,
s, MeO), 2.48 (3H, s, Ac), 2.24 (6H, s, Ac£2); 13C NMR
(75 MHz, CDCl3) d 194.7 (CvO), 192.2 (2C, C-2 and C-4),
159.6 (arom. CO), 157.9 (C-20), 152.60 (C-50), 125.2 (2C,
arom. CH), 122.5 (arom. C), 0122.3 (C-3 ), 114.3 (2C, arom.
CH), 106.2 (C-3), 103.4 (C-4 ), 55.4 (MeO), 29.4 (Ac), 26.1
(CH2), 23.5 (2C, Me). Anal. calcd for C19H20O5: C, 69.50;
H, 6.14. Found: C, 69.46; H, 6.05.
4.4.1. 3-(3-Acetyl-5-phenyl-2-furfuryl)-4-hydroxy-3-pen-
ten-2-one (6a). Colorless needles (from MeOH); mp 1278C;
IR (KBr) n 3700–3300 (OH), 1673, 1610 (CvO); 1H NMR
(300 MHz, CDCl3) d 16.88 (1H, OH), 7.58–7.57 (2H, m,
arom. H), 7.41–7.36 (2H, m, arom. H), 7.32–7.26 (1H, m,
arom. H), 6.85 (1H, s, H-40), 4.12 (2H, s, –CH2–), 2.49 (3H,
s, Ac), 2.24 (6H, s, Ac£2); 13C NMR (75 MHz, CDCl3) d
194.6 (CvO), 192.2 (2C, C-2 and C-4), 158.5 (C-20), 152.5
(C-50), 129.5 (arom. C), 128.9 (2C), 128.2, 123.7 (2C)
(arom. CH), 122.4 (C-30), 106.1 (C-3), 105.0 (C-40), 29.4
(Ac), 26.2 (CH2), 23.5 (2C, Me); MS m/z (rel. intensity),
298 (33, Mþ), 279 (10), 255 (12), 213 (9), 43 (100). Anal.
calcd for C18H18O4: C, 72.47; H, 6.08. Found: C, 72.63; H,
6.08.
4.4.6. 3-(3-Acetyl-2-methyl-4-phenyl-5-furyl)-4-
hydroxy-3-penten-2-one (7a). Colorless needles (from
MeOH); mp 59–608C; IR (KBr) n 3700–3300 (OH),
1
1679, 1610 (CvO); H NMR (300 MHz, CDCl3) d 16.75
(1H, OH), 7.37–7.35 (3H, m, arom. H), 7.17–7.14 (2H, m,
arom. H), 2.59 (3H, s, Ac), 2.00 (3H, s, Me), 1.92 (6H, s,
Ac£2); 13C NMR (75 MHz, CDCl3) d 196.1 (CvO), 193.7

762
S. Onitsuka, H. Nishino / Tetrahedron 59 (2003) 755–765
(2C, C-2 and C-4), 158.1 (C-20), 144.7 (C-50), 132.9 (arom.
C), 129.1 (2C), 128.8 (2C), 127.9 (arom. CH), 125.5 (C-40),
123.3 (C-30), 103.9 (C-3), 30.8 (Ac), 23.9 (2C, Me), 14.5
(Me); MS m/z (rel. intensity), 298 (100, Mþ), 279 (71), 255
(75), 241 (52), 237 (44), 213 (75), 195 (47), 153 (38), 128
(28), 115 (28), 77 (25), 43 (100). Anal. calcd for C18H18O4:
C, 72.47; H, 6.08. Found: C, 72.66; H, 6.31. The crystal-
lographic data deposition number: CCDC 198379.
4.4.7. 3-[3-Acetyl-4-(4-fluorophenyl)-2-methyl-5-furyl]-
4-hydroxy-3-penten-2-one (7b). Colorless liquid; IR
(KBr) n 3700–3300 (OH), 1676 (C–O); 1H NMR
(300 MHz, CDCl3) d 16.76 (1H, OH), 7.14–7.08 (4H, m,
arom. H), 2.60 (3H, s, Ac), 2.04 (3H, s, Me), 1.92 (6H, s,
Ac£2); 13C NMR (75 MHz, CDCl3) d 195.6 (CvO), 193.6
(2C,0C-2 and C-4),0 162.3 (d, J¼247.5 Hz, arom. CF), 158.3
(C-2 ), 145.0 (C-5 ), 130.8 (2C, d, J¼8.1 Hz, arom. CH),
128.9 (d, J¼3.2 Hz, arom. C), 124.5 (C-40), 123.2 (C-30),
115.9 (2C, d, J¼21.1 Hz, arom. CH), 103.7 (C-3), 30.8
(Ac), 23.8 (2C, Me), 14.6 (Me); FAB HRMS (acetone-
NBA) calcd for C18H17O4F 316.1111. Found 316.1115.
4.4.8. 3-[3-Acetyl-4-(4-chlorophenyl)-2-methyl-5-furyl]-
4-hydroxy-3-penten-2-one (7c). Colorless needles (from
MeOH); mp 138–1408C; IR (KBr) n 3700–3300 (OH),
1
Figure 3. ORTEP drawing of tetrasubstituted furan 7e.
1676 (CvO); H NMR (300 MHz, CDCl3) d 16.76 (1H,
OH), 7.37–7.34 (2H, m, arom. H), 7.11–7.08 (2H, m, arom.
H), 2.60 (3H, s, Ac), 2.01 (3H, s, Me), 1.91 (6H, s, Ac£2);
13C NMR (75 MHz, CDCl3) d 195.4 (CvO), 193.6 (2C, C-2
and C-4), 158.3 (C-20), 145.0 (C-50), 133.9, 131.4 (arom. C),
130.4 (2C), 129.0 (2C) (arom. CH), 124.4 (C-40), 123.1
(C-30), 103.6 (C-3), 30.9 (Ac), 23.9 (2C, Me), 14.6 (Me).
Anal. calcd for C18H17ClO4: C, 64.97; H, 5.15. Found: C,
64.84; H, 5.28.
4.5. Reaction of phenylglyoxal with 2,4-pentanedione in
the presence of BF3·Et2O
Phenylglyoxal (152 mg, 1.0 mmol) was dissolved in THF
(1 mL), and 2,4-pentanedione (1.03 mL, 10 mmol) and
BF3·Et2O (1.27 mL, 10 mmol) were simultaneously added
to the solution. The mixture was stirred at 238C for 15 min.
After the usual work-up, 6a (111 mg, 37%) and 7a (166 mg,
56%) were obtained.
4.4.9. 3-[3-Acetyl-4-(4-methylphenyl)-2-methyl-5-furyl]-
4-hydroxy-3-penten-2-one (7d). Colorless needles (from
MeOH); mp 1088C; IR (KBr) n 3700–3300 (OH), 1681,
4.6. Reaction of 1a with triphenylphosphine
1
1654, 1639 (CvO); H NMR (300 MHz, CDCl3) d 16.73
(1H, OH), 7.18–7.15 (2H, m, arom. H), 7.05–7.02 (2H, m,
arom. H), 2.58 (3H, s, Ac), 2.36 (3H, s, Me), 2.00 (3H, s,
Me), 1.92 (6H, s, Ac£2); 13C NMR (75 MHz, CDCl3) d
196.2 (CvO), 193.6 (2C, C-2 and C-4), 158.0 (C-20), 144.6
(C-50), 137.6, 129.9 (arom. C), 129.5 (2C), 128.9 (2C)
(arom. CH), 125.5 (C-40), 123.4 (C-30), 104.0 (C-3), 30.8
(Ac), 23.9 (2C, Me), 21.2 (Me–C6H4), 14.4 (Me). Anal.
calcd for C19H20O4: C, 73.06; H, 6.45. Found: C, 72.90; H,
6.49.
The pentenedione 1a (108 mg, 0.5 mmol) and triphenyl-
phosphine (197 mg, 0.75 mmol) were dissolved in chloro-
form (1 mL), and the mixture was heated under reflux for
30 min. Upon cooling, the solvent was removed under
reduced pressure, and the residue was separated by silica gel
TLC (Wakogel B-10) using chloroform as the developing
solvent, thus giving the furan 3a (88 mg, 88%).
4.7. Treatment of 1a with hydrochloric acid
4.4.10. 3-[3-Acetyl-4-(4-methoxyphenyl)-2-methyl-5-
furyl]-4-hydroxy-3-penten-2-one (7e). Colorless needles
(from MeOH); mp 138–1408C; IR (KBr) n 3700–3300
Concentrated hydrochloric acid (1 mL) was dropwise added
to the pentenedione 1a (216 mg, 1.0 mmol) in THF (1 mL),
and the mixture was stirred at 238C for 30 min. The yellow
color of the solution then turned red, and crystals were
formed. Water (50 mL) was added to dilute the mixture, and
the aqueous mixture was extracted with chloroform. The
combined extract was washed with a saturated aqueous
solution of sodium hydrogencarbonate and water (50 mL),
dried over anhydrous MgSO4, and concentrated to dryness.
The residue was separated by flash column chromatography
(Fuji Silysia BW-300 silica gel) with chloroform as the
eluting solvent, and the 3-acetyl-2-chloromethyl-5-phenyl-
furan (8) was obtained in 87% yield. The product 8 was
further purified by recrystallization from dichloromethane/
1
(OH), 1673 (CvO); H NMR (300 MHz, CDCl3) d 16.74
(1H, OH), 7.08–7.05 (2H, m, arom. H), 6.91–6.88 (2H, m,
arom. H), 3.82 (3H, MeO), 2.58 (3H, s, Ac), 2.02 (3H, s,
Me), 1.92 (6H, s, Ac£2); 13C NMR (75 MHz, CDCl3) d
196.2 (CvO), 193.7 (2C,0 C-2 and C-4), 159.2 (arom. CO),
158.0 (C-20), 144.6 (C-5 ), 130.20 (2C, arom. CH), 125.1
(C-40), 124.9 (arom. C), 123.4 (C-3 ), 114.2 (2C, arom. CH),
104.0 (C55.2 (MeO), 30.8 (Ac), 23.9 (2C, Me), 14.5 (Me).
Anal. calcd for C19H20O5: C, 69.50; H, 6.14. Found: C,
69.46; H, 6.05. The crystallographic data deposition
number: CCDC 198378 (Fig. 3).

S. Onitsuka, H. Nishino / Tetrahedron 59 (2003) 755–765
763
hexane. The chloromethylfuran 8 (117 mg, 0.5 mmol) was
heated under reflux in ethanol (5 mL) for 30 min to
quantitatively transform it into 3-acetyl-2-ethoxymethyl-5-
phenylfuran (9).
purified by recrystallization from dichloromethane/hexane,
and the mixture of 11-endo and bicyclic compound 12 was
further purified by silica gel column chromatography
eluting with chloroform.
4.7.1. 3-Acetyl-2-chloromethyl-5-phenylfuran (8). Color-
less needles (from dichloromethane/hexane); mp 128–
1298C; IR (KBr) n 1673 (CvO); 1H NMR (300 MHz,
CDCl3) d 7.71–7.68 (2H, m, arom. H), 7.45–7.39 (2H, m,
arom. H), 7.36–7.31 (1H, m, arom. H), 6.87 (1H, s, H-4),
4.98 (2H, s, –CH2–), 2.51 (3H, s, Ac); 13C NMR (75 MHz,
CDCl3) d 193.7 (CvO), 154.1 (C-5), 153.2 (C-2), 129.2
(arom. C), 128.9 (2C), 128.7 (arom. CH), 124.9 (C-3), 124.2
(2C, arom. CH), 105.3 (C-4), 36.2 (–CH2–), 29.2 (Ac).
Anal. calcd for C13H11ClO2: C, 66.53; H, 4.72. Found: C,
66.54; H, 4.87.
4.9.1. rel-(1R,4S,6S)-5,5-Diacetyl-6-benzoylbicyclo-
[2.2.1]hept-2-ene (11-exo). Colorless cubes (from dichloro-
methane/hexane); mp 94–958C; IR (KBr) n 1697, 1674
(CvO); 1H NMR (300 MHz, CDCl3) d 8.10–8.07 (2H, m,
arom. H), 7.63–7.58 (1H, m, arom. H), 7.53–7.48 (2H, m,
arom. H), 6.38 (1H, dd, J¼5.6, 3.1 Hz, H-2), 6.12 (1H, dd,
J¼5.6, 2.8 Hz, H-3), 4.65 (1H, d, J¼1.6 Hz, H-6), 3.70–
3.67 (1H, m, H-4), 2.94–7.90 (1H, m, H-1), 2.21 (1H, dt,
J¼9.1, 1.6 Hz, H-7), 2.11 (3H, s, Ac), 1.93 (3H, s, Ac), 1.57
(1H, dq, J¼9.1, 1.6 Hz, H-7); 13C NMR (75 MHz, CDCl3) d
204.0, 203.3 (sCvO, Ac), 199.9 (sCvO, Bz), 139.8
(vCH–, C-2), 136.9 (arom. C), 135.1 (vCH–, C-3), 133.5,
128.8 (2C), 128.7 (2C) (arom. CH), 79.6 (sCr, C-5), 52.3
(sCH–, C-6), 49.1 (sCH–, C-1), 48.2 (sCH–, C-4), 46.4
(sCH2, C-7), 29.6, 27.1 (CH3, Ac); FAB HRMS (acetone-
NBA) calcd for C18H19O3 283.1334 (Mþ1). Found
283.1336. Anal. calcd for C18H18O3·1/8H2O: C, 75.97; H,
6.37. Found: C, 76.05; H, 6.25.
4.7.2. 3-Acetyl-2-ethoxymethyl-5-phenylfuran (9). Color-
1
less oil; IR (CHCl3) n 1681 (CvO); H NMR (300 MHz,
CDCl3) d 7.70–7.67 (2H, m, arom. H), 7.42–7.37 (2H, m,
arom. H), 7.32–7.30 (1H, m, arom. H), 6.89 (1H, s, H-4),
4.82 (2H, s, –CH2–), 3.62 (2H, q, J¼7.0 Hz, –CH2–), 2.50
(3H, s, Ac), 1.25 (3H, t, J¼7.0 Hz, CH3); 13C NMR
(75 MHz, CDCl3) d 194.0 (CvO), 155.7 (C-5), 153.4 (C-2),
129.6 (arom. C), 128.8 (2C), 128.2 (arom. CH), 125.6 (C-3),
124.1 (2C, arom. CH), 105.1 (C-4), 66.3, 63.6 (–CH2–),
29.3 (Ac), 15.2 (Me); FAB HRMS (acetone-NBA) calcd for
C15H16O3 244.1100. Found 244.1099.
4.8. Hydrolysis of 8
The furfuryl chloride 8 (56.6 mg, 0.24 mmol) was hydro-
lyzed in a mixture of water (2.5 mL) and tetrahydrofuran
(2.5 mL) at the reflux temperature for 3 h to give 3-acetyl-5-
phenylfurfuryl alcohol (10) in 82% yield. The alcohol 10
(50.7 mg, 0.234 mmol) was allowed to react with BF3·Et2O
(296 mL, 2.34 mmol) in dry THF (2.34 mL) at the reflux
temperature for 1 h to yield bis(furyl)methane 2a in 82%
yield.
4.9.2. rel-(1R,4S,6R)-5,5-Diacetyl-6-benzoylbicyclo-
1
[2.2.1]hept-2-ene (11-endo). H NMR (300 MHz, CDCl3)
d 8.07–8.02 (2H, m, arom. H), 7.60–7.45 (3H, m, arom. H),
6.72 (1H, dd, J¼5.4, 3.2 Hz, H-3), 5.82 (1H, dd, J¼5.4,
2.9 Hz, H-3), 5.39 (1H, d, J¼3.7 Hz, H-6), 3.44 (1H, dq,
J¼3.2, 1.6 Hz, H-4), 3.19–7.15 (1H, m, H-1), 2.23 (3H, s,
Ac), 1.88 (3H, s, Ac), 1.41 (1H, dt, J¼8.8, 1.7 Hz, H-7),
1.27 (1H, dt, J¼8.8, 1.6 Hz, H-7); 13C NMR (75 MHz,
CDCl3) d 204.7, 203.7 (sCvO, Ac), 198.3 (sCvO, Bz),
137.4 (vCH–, C-3), 136.4 (arom. C), 134.0 (vCH–, C-2),
133.2, 128.7 (2C), 128.4 (2C) (arom. CH), 82.0 (sCr, C-5),
53.8 (sCH–, C-6), 49.8 (sCH–, C-4), 48.7 (sCH–, C-1),
45.6 (sCH2, C-7), 30.1, 26.1 (CH3, Ac); FAB HRMS
(acetone-NBA) calcd for C18H19O3 283.1334 (Mþ1).
Found 283.1335.
4.8.1. 3-Acetyl-2-hydroxymethyl-5-phenylfuran (10).
Colorless oil; IR (KBr) n 3600–3100 (OH), 1678 (CvO);
1H NMR (300 MHz, CDCl3) d 7.68–7.65 (2H, m, arom. H),
7.43–7.38 (2H, m, arom. H), 7.34–7.29 (1H, m, arom. H),
6.87 (1H, s, H-4), 4.80 (2H, s, sCH2), 4.41 (1H, br, OH),
2.52 (3H, s, Ac); 13C NMR (75 MHz, CDCl3) d 196.3
(sCvO, Ac), 160.1 (sCv, C-2), 152.4 (sCv, C-5), 129.2
(arom. C), 128.7 (2C, arom. CH), 128.2 (arom. CH), 124.6
(sCv, C-3), 123.9 (2C, arom. CH), 105.1 (vCH–, C-4),
57.6 (sCH2), 28.7 (CH3, Ac); FAB HRMS (acetone-NBA)
calcd for C15H16O3 216.0786. Found 216.0785.
4.9. Diels–Alder reaction of cyclopentadiene with
pentenedione 1a
The pentenedione 1a (108.1 mg, 0.50 mmol) was allowed to
react with freshly distilled cyclopentadiene (500 mL,
6.0 mmol) in ethyl acetate (1 mL) at 238C for 2 h. The
yellowish solution decolorized during the reaction. The
solvent was removed in vacuo and the residue was separated
by silica gel column chromatography (Wako gel C-300)
eluting with chloroform to give 11-exo and a mixture of 11-
endo and a bicyclic compound 12. The 11-exo was further
4.9.3. 4-Diacetylmethylene-3-phenyl-2-oxabicyclo-
[3.3.0]oct-7-ene (12). 1H NMR (300 MHz, CDCl3) d

764
S. Onitsuka, H. Nishino / Tetrahedron 59 (2003) 755–765
8.07–8.02 (2H, m, arom. H), 7.60–7.45 (3H, m, arom. H),
6.08 (1H, ddd, J¼5.7, 2.7, 1.8 Hz, H-3), 5.97–5.92 (1H, m,
H-2), 4.95 (1H, ddd, J¼6.5, 2.5, 1.5 Hz, H-1), 4.75 (1H, s,
H-7), 2.81–2.71 (1H, m, H-5), 2.57 (1H, dddd, J¼16.6, 7.8,
2.7, 1.6 Hz, H-4), 2.31 (3H, s, Ac), 2.28 (3H, s, Ac),
2.36–2.22 (1H, m, H-4); 13C NMR (75 MHz, CDCl3) d
200.7, 197.0, 1 (sCvO, Ac), 168.6 (sCv, C-6), 137.6
(vCH–, C-3), 135.9 (arom. C), 132.8 (arom. CH), 130.7
(vCH–, C-2), 128.5 (2C), 128.5 (2C) (arom. CH), 110.3
(sCv, C-10), 80.1 (sCH–, C-1), 41.8 (sCH–, C-7), 38.6
(sCH–, C-4), 36.7 (sCH2, C-3), 30.7, 22.5 (CH3, Ac); FAB
HRMS (acetone-NBA) calcd for C18H19O3 283.1334
(Mþ1). Found 283.1335.
No.14044078, from the Ministry of Education, Culture,
Sports, Science and Technology, Japan, and also by a Grant-
in-Aid for Scientific Research, No. 13640539, from the
Japan Society for the Promotion of Science. We thank
Professor Emeritus Kazu Kurosawa, Kumamoto University,
Japan, for his helpful discussions and suggestions. We also
gratefully acknowledge Professor Teruo Shinmyozu and Dr
Mikio Yasutake, Insutitute for Fundamental Research of
Organic Chemistry, Kyushu University, Japan, for their
crystallographic assistance.
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˚
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1
copies of H NMR, 13C NMR, DEPT, HH COSY, and HC
COSY spectra for 11-exo, a mixture of 11-endo and 12.
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