Efficient synthesis of 1,4-dihydronaphthalenelignans from 5-methylene-4-substituted-2(5H)-furanones and a concise synthesis of solafuranone

Article abstract of DOI:10.1016/j.tet.2005.10.054

A short synthetic strategy for synthesis of lignan analogues involving 5-methylene-4-substituted-2(5H)-furanones as the key intermediates has been developed. Various lignans including the natural product solafuranone and analogues of dihydrotaiwanin C and

Full text of DOI:10.1016/j.tet.2005.10.054

Tetrahedron 62 (2006) 1258–1272
Efficient synthesis of 1,4-dihydronaphthalenelignans from
5-methylene-4-substituted-2(5H)-furanones and a concise
synthesis of solafuranone
*
Vishal A. Mahajan, Hanumant B. Borate and Radhika D. Wakharkar
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune 411 008, India
Received 29 July 2005; revised 30 September 2005; accepted 20 October 2005
Available online 18 November 2005
Abstract—A short synthetic strategy for synthesis of lignan analogues involving 5-methylene-4-substituted-2(5H)-furanones as the key
intermediates has been developed. Various lignans including the natural product solafuranone and analogues of dihydrotaiwanin C and
deoxydehydropodophyllotoxin were synthesized in good yields.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
them an attractive target for synthetic chemists. The
different methods reported12 for the synthesis of naturally
occurring lignan lactones and their analogues include
cyclization of substituted propiolic acids, propiolic esters
or oxazolines and a Pummerer–Diels–Alder reaction
sequence. In our endeavor to develop methods for synthesis
of novel lignans, the 5-methylene-4-substituted-2(5H)-
furanones (1) obtained from arylidenelevulinic acids were
used as the building blocks (Scheme 1).
The furanone moiety is the structural feature of a large
number of biologically active compounds such as
alkaloids,1 lignans,2 and pheromones3 and g-alkylidene
furanones constitute an important subclass of the furanone
family with a wide range of biological activity.4
Considering the importance of this class of compounds,
we recently reported5a the synthesis of 5-methylene-
4-substituted-2(5H)-furanones involving Stobbe conden-
sation of ethyl levulinate with substituted aryl aldehydes
to give arylidenelevulinic acids followed by treatment with
sodium acetate and acetic anhydride. We envisioned the
utility of 5-methylene-4-substituted-2(5H)-furanones in the
synthesis of various lignan derivatives. The wide spectrum
of biological activity including anti-cancer activity,6 anti-
inflammatory activity,7 analgesic activity,8 anti-fungal
activity,9 anti-asthmatic activity10 and anti-rheumatic
activity11 exhibited by lignans and their analogues make
The 5-methylene-4-substituted-2(5H)-furanones (1) were
reacted with various aromatic aldehydes to obtain the
acyclic lignans 2 which were further transformed into a
number of cyclic lignans 3 with a wide variety of
substituents and the detailed results are reported herein.
The utility of 5-methylene-4-substituted-2(5H)-furanones
(1) was further explored for the synthesis of naphthalene
lignan derivatives as many naturally occurring naphthalene
lignans, with a wide spectrum of biological activity, have a
O
O
O
O
R
R
O
O
R
HO
R1
R1
2
3
1
Scheme 1.
Keywords: Lignans; Furanones; Exomethylene furanones; Podophyllotoxin; Dihydrotaiwanin; Solafuranone.
*
Corresponding author. Tel.: C91 20 25902284; fax: C91 20 5893614; e-mail: rd.wakharkar@ncl.res.in
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.10.054

V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
1259
O
O
O
O
CHO
CH3
OH
i
+
+
OH
CH3
OEt
R
R
R
O
iii
O
4
6
5
7
ii
O
O
AcO
+
O
+
R
O
R
R
O
OAc
1
9
8
Scheme 2. Reagents and conditions: (i) Aq. NaOH, ethanol, K10 8C, 4–5 h, (7, 80–95%); (ii) Anhydr. NaOAc, Ac2O, 80 8C, 3 h; (iii) Aq. NaOH, ethanol, rt,
2–3 h.
Table 1. 5-Methylene-4-substituted-2(5H)-furanones
Comp. no.
Structure
Yield (%)a
Comp. no.
Structure
MeO
Yield (%)a
O
O
O
O
1a
52
1j
48
O
MeO
OMe
O
O
O
1b
1c
1d
1e
64
67
72
56
1k
1l
57
67
61
62
O
O
MeO
MeO
MeO
O
O
O
O
OMe
OMe
MeO
MeO
O
O
1m
1n
O
O
OMe
O
O
O
O
MeO
OMe
O
O
MeO
O
O
O
1f
55
1o
52
O
O
O
OMe
OMe
OMe
O
1g
1h
75
63
1p
1q
58
57
O
Cl
S
MeO
O
OMe
O
O
O
O
MeO
O
I
OMe
MeO
MeO
O
O
O
1i
57
1r
64
O
OMe
OMe
a Isolated yield.

1260
V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
MeO
MeO
MeO
MeO
MeO
O
O
O
O
ii
O
O
i
MeO
HO
OMe
OMe
OMe
iii
1d
R
R
1
1
12
O
MeO
MeO
HO
OMe
10
Scheme 3. Reagents and conditions: (i) LDA, substituted arylaldehydes, K78 8C; (ii) TFA, dichloromethane, rt; (iii) n-BuLi, K78 8C, 40%.
lactone moiety as the core unit in their structure.13
number of novel naphthalene lignans including analogues
of dihydrotaiwanin and deoxydehydropodophyllotoxin
were synthesized from 5-methylene-4-substituted-2(5H)-
A
furanones (1) demonstrating the importance of these easily
accessible chemical entities. Extension of the work on
exploitation of 5-methylene-4-substituted-2(5H)-furanones
(1) for the synthesis of natural products having furanone as
Table 2. Hydroxy lignans prepared
Comp. no.
Structure
Yield (%)a
Comp. no.
Structure
Yield (%)a
MeO
MeO
MeO
MeO
O
O
O
O
OH
11a
48
11f
52
OMe
OH
OMe
MeO
MeO
OMe
OMe
MeO
MeO
MeO
MeO
MeO
O
O
OH
O
OH
11b
11c
11d
55
52
60
11g
11h
11i
75
57
55
O
OMe
OH
OMe
OMe
MeO
MeO
MeO
MeO
O
O
O
OH
O
OMe
O
OH
OMe
MeO
OMe
OMe
O
MeO
MeO
MeO
MeO
O
O
O
OMe
OH
OH
OMe
O
OMe
O
O
OMe
MeO
MeO
MeO
MeO
O
O
O
O
OH
OMe
OH
11e
OMe
49
11j
57
NO2
OMe
OMe
a Isolated yields.

V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
1261
Table 3. Novel lignans prepared
Comp. no.
Structure
Yield (%)a
Comp. no.
Structure
Yield (%)a
MeO
MeO
MeO
MeO
O
O
O
O
12a
78
12e
81
OMe
MeO
OMe
OMe
OMe
OMe
MeO
MeO
MeO
MeO
O
O
O
O
OMe
OMe
12b
OMe
74
12f
63
OH
OMe
OMe
MeO
MeO
MeO
MeO
O
O
O
O
OMe
12c
91
12g
89
OMe
O
O
OMe
MeO
MeO
O
O
12d
61
OMe
MeO
a Isolated yields.
a structural feature resulted in the first synthesis of
solafuranone,14 a folk medicine used as an analgesic for
toothache and rhinitis.
We envisaged that the furanones 1 could be utilized as
valuable intermediates in the synthesis of various lignan
derivatives by generation of an anion on the carbon a to the
lactone carbonyl function of furanones 1 and reaction with
various aldehydes to result in the formation of hydroxy
lignans 2 (Scheme 1). Cyclization of these hydroxy lignans
under acidic conditions would lead to the cyclic lignan
lactones that would have potential to generate a wide variety
of novel lignan derivatives with a unique structural
ensemble.
2. Results and discussion
The various 5-methylene-4-substituted-2(5H)-furanones
(1)5a were synthesized by a two-step reaction sequence
(Scheme 2).
A number of methods are reported for a-alkylation of the
saturated lactones using various bases while the alkylation
of unsaturated lactones is less explored.15 To study the
a-alkylation of furanone derivatives, furanone 1d was
selected as the 3,4,5-trimethoxy group is commonly present
Stobbe condensation5b of substituted aryl aldehydes 4 with
ethyl levulinate (5) in the presence of ethanolic sodium
hydroxide5a afforded a mixture of arylidene levulinic acids 6
and 7 in varying amounts depending upon the temperature
of the reaction and the substitution pattern of the aromatic
aldehydes 4. The required acid 6 was obtained in maximum
amount at lower temperature (K10 8C) while the acid 7 was
the exclusive product when the condensation was performed
in the presence of DBU in refluxing THF. In some cases it
was possible to isolate pure acids 6 and 7 while in some
cases the acids were obtained as an inseparable mixture and
the characterization was done by comparison of the spectral
data of analogous acids obtained in pure form. Reaction of
acid 6 with anhydrous sodium acetate and acetic anhydride
afforded the desired furanones 1 in 48–75% yield (Table 1)
along with 10–32% mixed anhydrides 8 and 2–20%
naphthalene derivatives 9. The structures of the furanones
1 were assigned on the basis of spectral data.
H
H
H
A
H
H
5
5
MeO
MeO
MeO
MeO
3
3
4
4
6
6
O
B
9
2
C
O
A
C
B
2
9
1
O
OMe
1
7
7
8
8
O
OMe
H
H
OMe
OMe
H
D
D
OMe
OMe
A
B
Figure 1. Selected COSY and NOESY correlations.

1262
V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
O
O
O
O
O
O
O
O
HO
i
ii
O
O
O
O
52%
82%
O
O
1
13
14
O
O
O
O
O
ii
85 %
O
O
O
iii
55%
O
HO
O
MeO
OMe
MeO
OMe
OMe
15
OMe
16
Scheme 4. Reagents and conditions: (i) 3,4-Methylene dioxybenzaldehyde, LDA, THF, K78 8C; (ii) TFA, CH2Cl2, rt; (iii) 3,4,5-Trimethoxybenzaldehyde,
LDA, THF, K78 8C.
O
O
i
ii
O
O
MeO
O
HO
53%
86%
O
MeO
MeO
OMe
MeO
1r
MeO
OMe
OMe
OMe
18
17
Scheme 5. Reagents and conditions: (i) 3,4,5-Trimethoxy benzaldehyde, LDA, THF, K78 8C; (ii) TFA, CH2Cl2, rt.
in naturally occurring bioactive lignans. It is noteworthy
that in the preliminary screening study of base for
anion generation, in the presence of n-butyllithium
exomethylene furanone derivative 1d underwent addition
of n-butyl group followed by rearrangement to give
serendipitously 4-hydroxy-4-butyl-cyclopentenone deriva-
tive 10 (Scheme 3) while the aldehydes that were added
remained unreacted. LDA was found to be the best choice to
generate a-vinyl carbanion of exomethylenefuranone 1
without disturbing its basic molecular skeleton. The
presence of exomethylene moiety on furanone 1 facilitated
the exclusive generation of a-carbanion rather than
g-carbanion formation to afford the desired products 11.
The formation of a-carbanion was confirmed by quenching
it with D2O and disappearance of proton at d 5.85 in the 1H
NMR spectrum. The spectral data for hydroxy lignans 11
were in good agreement with the assigned structures.
Various exomethylenefuranones 1 were reacted with a
number of aldehydes to generate a wide array of novel
hydroxylignans 11 as shown in Table 2.
obtain a number of novel lignans in a few steps using easily
available chemicals.
The structures of the lignans 3 were assigned on the basis of
spectral data. The benzylic protons exhibited long-range
coupling, which was confirmed by 1H–1H COSY and
NOESY spectra of selected molecules (Figure 1).
The potential of this strategy for synthesis of exomethylene
analogues of various natural products was evident from the
products obtained from the reaction of furanone 1e with
piperonaldehyde and 3,4,5-trimethoxybenzaldehyde
(Scheme 4). The corresponding hydroxylignans 13 and 15
on cyclization with trifluoroacetic acid afforded the
compounds 14 and 16, the analogues of biologically active
1,4-dihydrotaiwanin C16 and podophyllotoxin,17
respectively.
MeO
O
MeO
i
The potential of these new chemical entities as inter-
mediates in the synthesis of natural as well as synthetic
lignans was evident from the structural diversity of the
hydroxy lignans prepared in the present work.
MeO
O
O
OMe
MeO
64%
O
OMe
N
Me
1d
19
The hydroxy lignan lactones 11 were treated with
trifluoroacetic acid to afford the desired cyclic lignans 12
in good yields as shown in Table 3. It was gratifying to
Scheme 6. Reagents and conditions: (i) (a) N-Methyl indole-3-carbox-
aldehyde, LDA, THF, K78 8C; (b) Dilute acetic acid.

V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
1263
O
O
CH3
O
CH3
CH3
H
i
ii
O
OMe
OH
88%
78%
CH3
CH3
CH3
O
22
20
21
CH3
O
O
CH3
iv
iii
83%
O
O
48%
OMe
CH3
24
CH3
23
Scheme 7. Reagents and conditions: (i) aq. NaOH, methanol, K10 8C, 4–5 h; (ii) CH2N2, methanol, rt; (iii) H2, Pd/C, methanol, rt; (iv) CH3MgI, ether,
K78 8C, 5 h.
The versatility of this synthetic sequence was demonstrated
by the synthesis of angular lignan 18 from the corresponding
4-(60-methoxynaphthalen-2-yl)methyl-5-methylene-2(5H)-
furanone (1r) as shown in Scheme 5.
and 50.3 MHz, respectively) spectrometer. IR spectra were
recorded on Perkin-Elmer Spectrum 683 B or 160S FT IR
spectrophotometer. Elemental analysis was performed on a
Perkin-Elmer Model 2400 analyser. Thin layer chromato-
graphy was performed on silica/alumina plates. Column
chromatography was performed on silica gel (60–120
mesh).
It was noteworthy that the reaction of N-methylindole-3-
carboxaldehyde with furanone 1d in the presence of LDA
followed by acidic work up afforded the cyclic lignan 19
directly and the intermediate hydroxylignan was not
isolated. This represents a convergent three-step synthesis
of highly functionalized heterocyclic lignan 19 starting from
3,4,5-trimethoxybenzaldehyde (Scheme 6).
4.1. A typical procedure for the synthesis of acid 6
To a well-stirred mixture of substituted benzaldehyde
(12.7 mmol) and ethyl levulinate (31.7 mmol) in methanol
(25 mL), aqueous sodium hydroxide solution (31.7 mmol)
was added dropwise at K10 8C. After complete addition,
reaction mixture was stirred at same temperature for 4–5 h
and the reaction was monitored by thin layer chromato-
graphy. After completion of reaction, methanol was
removed under vacuum, reaction mixture was diluted with
water (20 mL), washed with ethyl acetate (2!10 mL) and
aqueous layer was acidified with conc HCl (3 mL). The
yellow oil separated was extracted with ethyl acetate
(2!20 mL) and it was repeatedly washed with water to
remove traces of levulinic acid followed by brine, dried over
sodium sulfate and evaporated to yield the desired acid 6
(yield ranges from 45 to 85%).
The utility of the present work for the synthesis of natural
products was further exemplified by the synthesis of
solafuranone 24 as depicted in Scheme 7.
Thus, Stobbe condensation of 2,6-dimethyl benzaldehyde
with ethyl levulinate afforded the arylidenelevulinic acid
21 as a major component along with the minor
regioisomer which was esterified with diazomethane to
give the ester 22 in quantitative yield. The ester 22 was
hydrogenated and reacted with methylmagnesium iodide
in presence of anhydrous cerium chloride to afford
racemic solafuranone 24.
4.1.1. 3-Acetyl-4-(4-methoxyphenyl)-but-3-enoic acid
(6a). Yellow solid; Yield: 1.78 g, 60%; Mp: 138–140 8C
(lit.5b 142 8C); IR (Chloroform): n 3020, 1716, 1663, 1217,
3. Conclusion
In summary, we have developed a short synthetic sequence
for novel lignans involving 5-methylene-4-substituted-
2(5H)-furanones (1) as the key intermediates. It has
potential for wide application in organic synthesis as it is
possible to have various functional groups at the desired
positions of the products. The strategy has been exemplified
by the synthesis of the natural product solafuranone and
lignan analogues including analogues of 1,4-dihydro-
taiwanin C and deoxydehydropodophyllotoxin as new
chemical entities, which can be studied for their biological
activity18 as well as used as important intermediates in
organic synthesis.
1
757 cmK1; H NMR (200 MHz, CDCl3CCCl4): d 2.44 (s,
3H), 3.52 (s, 2H), 3.80 (s, 3H), 6.92 (d, JZ8.0 Hz, 2H), 7.34
(d, JZ8.0 Hz, 2H), 7.66 (s, 1H), 9.46 (br s, 1H); MS (ES):
m/z 234 (MC), 257 (MCCNa); Anal. Calcd for C13H14O4:
C, 66.66; H, 5.98; Found: C, 66.80; H, 5.73%.
4.1.2. 3-Acetyl-4-(2,4-dimethoxyphenyl)-but-3-enoic
acid (6b). White solid; Yield: 2.07 g, 62%; Mp: 114 8C;
IR (Chloroform): n 3022, 1715, 1630, 1506, 1430, 1216,
1
756 cmK1; H NMR (200 MHz, CDCl3CCCl4): d 2.44 (s,
3H), 3.43 (s, 2H), 3.76 (s, 6H), 6.38–6.55 (m, 2H), 7.23 (d,
JZ8.0 Hz, 1H), 7.82 (s, 1H), 9.55 (br s, 1H); 13C NMR
(50 MHz, CDCl3CCCl4): d 200.2, 176.8, 162.4, 158.8,
139.5, 132.6, 130.9, 116.3, 104.6, 98.3, 55.4 (2C), 33.2,
25.3; MS (ES): m/z 265 (MCC1), 283 (MC1CH2O);
Anal. Calcd for C14H16O5: C, 63.63; H, 6.06; Found: C,
66.69; H, 6.18%.
4. Experimental
1
Melting points are uncorrected. H NMR and 13C NMR
spectra were recorded on a Bruker Avance DPX 200 (200

1264
V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
4.1.3. 3-Acetyl-4-(3,4-dimethoxyphenyl)-but-3-enoic
125.6, 32.5, 25.1, 14.8; MS (ES): m/z 251 (MCC1); Anal.
Calcd for C13H14O3S: C, 62.40; H, 5.60; S, 12.80; Found: C,
62.38; H, 5.82; S, 12.64%.
acid (6c). Yellow thick oil;5b Yield: 2.58 g, 77%; IR
(Chloroform): n 2922, 1698, 1654, 1504, 1281, 1209 cmK1
;
1H NMR (200 MHz, CDCl3CCCl4): d 2.42 (s, 3H), 3.50 (s,
2H), 3.76 (s, 6H), 6.75–6.93 (m, 2H), 7.31 (d, JZ8.0 Hz,
1H), 7.63 (s, 1H), 9.55 (br s, 1H); 13C NMR (50 MHz,
CDCl3CCCl4): d 208.2, 174.2, 160.5, 142.1, 136.4, 135.9,
127.0, 125.9, 107.3, 106.6, 55.1 (2C), 33.4, 30.6; MS (ES):
m/z 265 (MCC1), 283 (MC1CH2O); Anal. Calcd for
C14H16O5: C, 63.63; H, 6.06; Found: C, 66.48; H, 5.90%.
4.1.9. 3-Acetyl-4-(2-iodo-3,4,5-trimethoxyphenyl)-but-3-
enoic acid (6i). Brown solid; Yield: 3.62 g, 68%; Mp:
120–122 8C; IR (Chloroform): n 3013, 1710, 1672, 1477,
1382, 1201, 1104, 755 cmK1; 1H NMR (200 MHz, CDCl3):
d 2.52 (s, 3H), 3.36 (s, 2H), 3.80 (s, 3H), 3.88 (s, 6H), 6.85
(s, 1H), 7.62 (s, 1H), 10.20 (br s, 1H); 13C NMR (50 MHz,
CDCl3CCCl4): d 199.2, 176.3, 158.5, 153.6, 153.1, 146.6,
142.1, 134.5, 133.6, 108.9, 60.8, 60.6, 56.0, 32.6, 26.3; MS:
m/z 420 (MC), 438 (MCCH2O); Anal. Calcd for
C15H17O6I: C, 42.85; H, 4.04; Found: C, 42.90; H, 4.27%.
4.1.4. 3-Acetyl-4-(3,4,5-trimethoxyphenyl)-but-3-enoic
acid (6d). Yellow solid; Yield: 2.80 g, 75%; Mp:
118–120 8C; IR (Chloroform): n 3016, 1709, 1655, 1581,
1239, 1129, 755 cmK1 1H NMR (200 MHz, CDCl3C
;
CCl4): d 2.55 (s, 3H), 3.55 (s, 2H), 3.86 (s, 9H), 6.68 (s, 2H),
7.67 (s, 1H), 8.80 (br s, 1H); 13C NMR (50 MHz, CDCl3): d
199.4, 176.1, 153.0, 143.4, 138.8 (2C), 133.8, 129.8, 106.3
(2C), 60.6 (2C), 55.9, 32.8, 25.1; MS (m/z): 295 (MC1),
313 (MC1CH2O); Anal. Calcd for C15H18O6: C, 61.22; H,
6.12; Found: C, 60.97; H, 6.25%.
4.1.10. 3-Acetyl-4-(4-allyloxy-3-methoxyphenyl)-but-3-
enoic acid (6j). Semisolid; Yield: 2.20 g, 60%; IR (Chloro-
form): n 3029, 1716, 1680, 1210, 756 cmK1 1H NMR
;
(200 MHz, CDCl3CCCl4): d 2.50 (s, 3H), 3.59 (s, 2H), 3.85
(s, 3H), 4.60–4.68 (m, 2H), 5.28–5.46 (m, 2H), 6.01–6.15
(m, 1H), 6.72–7.03 (m, 3H), 7.70 (s, 1H), 8.20 (br s, 1H);
13C NMR (50 MHz, CDCl3CCCl4): d 199.6, 175.2, 148.7,
148.6, 143.2, 132.5, 132.3, 127.1, 122.5, 117.8, 112.4,
112.2, 69.1, 55.4, 32.3, 24.8; MS: m/z 290, 249, 175, 151,
116, 91; Anal. Calcd for C16H18O5: C, 66.20; H, 6.20;
Found: C, 66.32; H, 5.16%.
4.1.5. 3-Acetyl-4-benzo [1,3] dioxol-5-yl-but-3-enoic acid
(6e). Pink solid; Yield: 2.33 g, 74%; Mp: 148–150 8C (lit.5b
152 8C); IR (Chloroform): n 3010, 1732, 1680, 1486, 1236,
1038, 933, 697 cmK1; 1H NMR (200 MHz, CDCl3CCCl4):
d 2.29 (s, 3H), 3.30 (s, 2H), 5.85 (s, 2H), 6.51 (d, JZ2.0 Hz,
1H), 6.58–6.64 (m, 1H), 6.68 (d, JZ8.0 Hz, 1H), 7.44 (s,
1H); 13C NMR (50 MHz, CDCl3): d 198.5, 172.7, 147.4,
141.6, 133.8, 128.4, 123.7, 119.5, 108.6, 108.0, 100.9, 32.1,
25.0; MS (ESI): m/z 249 (MCC1), 266 (MCCH2O); Anal.
Calcd for C13H12O5: C, 62.90; H, 4.83; Found: C, 63.11; H,
4.98%.
4.1.11. 3-Acetyl-4-(3-allyloxy-4-methoxyphenyl)-but-3-
enoic acid (6k). Thick liquid; Yield: 2.50 g, 68%; IR
1
(Chloroform): n 3029, 1718, 1686, 1212, 758 cmK1; H
NMR (200 MHz, CDCl3CCCl4): d 2.49 (s, 3H), 3.56 (s,
2H), 3.91 (s, 3H), 4.62–4.68 (m, 2H), 5.24–5.45 (m, 2H),
5.97–6.15 (m, 1H), 6.90–7.08 (m, 3H), 7.67 (s, 1H), 9.48 (br
s, 1H); MS (ES): m/z 291 (MCC1), 308 (MCH2O); Anal.
Calcd for C16H18O5: C, 66.20; H, 6.20; Found: C, 66.13; H,
6.18%.
4.1.6. 3-Acetyl-4-(7-methoxybenzo[1,3]dioxol-5-yl)-but-
3-enoic acid (6f). Brown solid; Yield: 2.01 g, 57%; Mp:
113–115 8C; IR (Chloroform): n 2998, 1710, 1682, 1510,
1221 cmK1; 1H NMR (200 MHz, CDCl3CCCl4): d 2.48 (s,
3H), 3.54 (s, 2H), 3.90 (s, 3H), 6.02 (s, 2H), 6.59 (br s, 1H),
6.66 (br s, 1H), 7.61 (s, 1H), 8.96 (br s, 1H); 13C NMR
(50 MHz, CDCl3CCCl4): d 197.7, 171.4, 146.5, 140.8,
132.5, 127.5, 122.9, 119.1, 107.0, 105.2, 100.2, 53.6, 30.9,
23.7; MS: m/z 278, 233, 263, 247, 233, 203, 189, 161, 103,
77; Anal. Calcd for C14H14O6: C, 60.43; H, 5.03; Found: C,
60.24; H, 5.23%.
4.1.12. 3-Acetyl-4-naphthalen-1-yl-but-3-enoic acid (6l).
Yellow solid; Yield: 1.87 g, 58%; Mp: 118–120 8C; IR
(Chloroform): n 3020, 1719, 1680, 1488, 1183, 1041, 757,
1
668 cmK1; H NMR (200 MHz, CDCl3CCCl4): d 2.62 (s,
3H), 3.43 (s, 2H), 7.28–7.60 (m, 4H), 7.82–7.92 (m, 3H),
8.24 (s, 1H); 13C NMR (50 MHz, CDCl3): d 207.9, 176.3,
148.7, 148.5, 143.0, 137.1, 136.2, 133.0, 128.4, 123.5,
109.3, 103.1, 102.8, 102.1, 37.1, 28.9; MS (ES): m/z 255
(MCC1), 272 (MCCH2O); Anal. Calcd for C16H14O3: C,
75.59; H, 5.51; Found: C, 75.62; H, 5.60%.
4.1.7. 3-Acetyl-4-(4-chloro-2,5-dimethoxyphenyl)-but-3-
enoic acid (6g). Yellow solid; Yield: 3.22 g, 85%; Mp:
127–130 8C; IR (Chloroform): n 3020, 1712, 1670, 1495,
4.1.13. 3-Acetyl-4-(2-methoxynaphthalen-1-yl)-but-3-
enoic acid (6m). Yellow solid; Yield: 1.62 g, 45%; Mp:
148–151 8C; IR (Chloroform): n 3030, 1722, 1667, 1512,
1
1215, 758 cmK1; H NMR (200 MHz, CDCl3CCCl4): d
2.52 (s, 3H), 3.53 (s, 2H), 3.81 (s, 3H), 3.85 (s, 3H), 6.67 (s,
1H), 6.69 (s, 1H), 7.81 (s, 1H); MS: m/z 298, 268, 196, 152,
89; Anal. Calcd for C14H15O5Cl: C, 56.37; H, 5.03; Cl,
11.91; Found: C, 56.39; H, 5.28; Cl, 12.20%.
1
1212, 755 cmK1; H NMR (200 MHz, CDCl3CCCl4): d
2.17 (s, 3H), 3.49 (s, 2H), 3.80 (s, 3H), 6.82 (d, JZ8.0 Hz,
1H), 7.40–7.58 (m, 3H), 7.75–7.95 (m, 1H), 8.21 (s, 1H);
MS (ES): m/z 284 (MC), 307 (MCCNa); Anal. Calcd for
C17H16O4: C, 71.83; H, 5.63; Found: C, 71.60; H, 5.69%.
4.1.8. 3-Acetyl-4-(4-methylsulfanylphenyl)-but-3-enoic
acid (6h). Yellow solid; Yield: 2.28 g, 72%; Mp:
121–124 8C; IR (Chloroform): n 3021, 1786, 1653, 1593,
1419, 1217, 978, 756 cmK1; 1H NMR (200 MHz, CDCl3C
CCl4): d 2.03 (s, 3H), 2.56 (s, 3H), 3.50 (s, 2H), 7.12 (d,
JZ8.0 Hz, 2H), 7.22 (d, JZ8.0 Hz, 2H), 7.65 (s, 1H), 10.49
(br s, 1H); 13C NMR (50 MHz, CDCl3CCCl4): d 199.4,
176.1, 142.7, 140.9, 134.1, 133.7, 130.7, 129.5, 126.2,
4.1.14. 3-Acetyl-4-(4-methoxynaphthalen-1-yl)-but-3-
enoic acid (6n). Greenish yellow solid; Yield: 2.59 g,
72%; Mp: 131–133 8C; IR (Chloroform): n 3020, 1784,
1
1719, 1613, 1503, 1216, 757 cmK1; H NMR (200 MHz,
CDCl3CCCl4): d 2.60 (s, 3H), 3.48 (s, 2H), 4.02 (s, 3H),
6.86 (d, JZ8.0 Hz, 1H), 7.25–7.60 (m, 3H), 7.77–7.79

V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
1265
(m, 1H), 8.25–8.40 (m, 2H); MS (ES): m/z 284 (MC), 307
(MCCNa); Anal. Calcd for C17H16O4: C, 71.83; H, 5.63;
Found: C, 71.72; H, 5.56%.
4.2.1. 4-(4-Methoxybenzyl)-5-methylene-2(5H)-furanone
(1a). Viscous oil; Yield: 1.14 g, 52%; IR (Chloroform): n
3020, 1764, 1513, 1249 cmK1 1H NMR (200 MHz,
;
CDCl3CCCl4): d 3.72 (s, 2H), 3.81 (s, 3H), 4.94 (d,
JZ2.7 Hz, 1H), 5.15–5.19 (m, 1H), 5.81 (br s, 1H), 6.87 (d,
JZ8.6 Hz, 2H), 7.11 (d, JZ8.6 Hz, 2H); 13C NMR
(50 MHz, CDCl3CCCl4): d 168.3, 158.4, 155.1 (2C),
129.5 (2C), 127.5, 117.7, 113.9 (2C), 94.5, 54.8, 31.3;
MS: m/z 216, 201,145,121, 77; Anal. Calcd for (C13 H12O3):
C, 72.22; H, 5.55; Found: C, 72.29; H, 5.37%.
4.1.15. 3-Acetyl-4-(2,7-dimethoxynaphthalen-1-yl)-but-
3-enoic acid (6o). Brownish yellow solid; Yield: 1.83 g,
46%; Mp: 98–100 8C; IR (Chloroform): n 3019, 1714, 1670,
1
1215, 757 cmK1; H NMR (200 MHz, CDCl3CCCl4): d
2.63 (s, 3H), 3.57 (s, 2H), 3.82 (s, 3H), 3.93 (s, 3H),
6.85–7.12 (m, 3H), 7.55–7.85 (m, 3H); MS (ES): m/z 315
(MCC1), 332 (MCCH2O); Anal. Calcd for C18H18O5: C,
68.78; H, 5.73; Found: C, 68.83; H, 5.61%.
4.2.2. 4-(2,4-Dimethoxybenzyl)-5-methylene-2(5H)-
furanone (1b). Viscous oil; Yield: 1.61 g, 64%; IR
(Chloroform): n 3021, 1764, 1216 cmK1
;
1H NMR
4.1.16. 3-Acetyl-4-(4,8-dimethoxynaphthalen-1-yl)-but-
3-enoic acid (6p). Brownish yellow solid; Yield: 2.31 g,
58%; Mp: 153–155 8C; IR (Chloroform): n 3029, 1720,
(200 MHz, CDCl3CCCl4): d 3.71 (s, 2H), 3.78 (s, 3H),
3.80 (s, 3H), 5.01 (d, JZ2.7 Hz, 1H), 5.13–5.17 (m, 1H),
5.75 (br s, 1H), 6.44–6.53 (m, 2H), 7.02 (d, JZ8 Hz, 1H);
13C NMR (50 MHz, CDCl3CCCl4): d 168.4, 158.3, 157.5,
155.1, 130.1, 116.9, 116.2, 107.9, 104.0, 98.1, 93.9, 54.7
(2C), 25.9; MS (ESI): m/z 247 (MH)C; Anal. Calcd for
C14H14O4: C, 68.29; H, 5.69; Found: C, 68.16, H, 5.74%.
1680, 1513, 755 cmK1 1H NMR (200 MHz, CDCl3C
;
CCl4): d 2.16 (s, 3H), 3.48 (s, 2H), 3.88 (s, 3H), 3.96 (s, 3H),
6.70 (d, JZ8.0 Hz, 1H), 6.92 (t, JZ8.0, 2.0 Hz, 2H), 7.39 (t,
JZ8.0, 2.0 Hz, 1H), 7.81–7.90 (m, 2H), 9.75 (br s, 1H); MS
(ES): m/z 314 (MC); Anal. Calcd for C18H18O5: C, 68.78;
H, 5.73; Found: C, 68.69; H, 5.75%.
4.2.3. 4-(3,4-Dimethoxybenzyl)-5-methylene-2(5H)-
furanone (1c). Viscous oil; Yield: 1.68 g, 67%; IR (Chloro-
1
form): n 3020, 1778, 1760, 1709, 1502, 1237 cmK1; H
4.1.17. 3-Acetyl-4-(6-methoxynaphthalen-2-yl)-but-3-
enoic acid (6q). Yellow solid; Yield: 2.41 g, 67%; Mp:
122–123 8C; IR (Chloroform): n 3019, 1718, 1686, 1530,
NMR (200 MHz, CDCl3CCCl4): d 3.71 (br s, 2H), 3.82 (s,
3H), 3.83 (s, 3H), 4.91 (d, JZ2.7 Hz, 1H), 5.11–5.14 (m,
1H), 5.79 (br s, 1H), 6.66 (dd, JZ7.8, 2.0 Hz, 1H), 6.73 (dd,
JZ7.8, 2.0 Hz, 1H), 6.79 (d, JZ7.8 Hz, 1H); 13C NMR
(50 MHz, CDCl3): d 168.5, 158.2, 155.2, 149.0, 148.0,
128.0, 120.7, 117.9, 111.6, 111.3, 94.7, 55.6 (2C), 32.0; MS
(ESI): m/z 246 (MH)C; Anal. Calcd for C14H14O4: C, 68.29;
H, 5.69; Found: C, 68.35; H, 5.66%.
1
1216, 757 cmK1; H NMR (200 MHz, CDCl3CCCl4): d
2.52 (s, 3H), 3.63 (s, 2H), 3.93 (s, 3H), 7.11–7.20 (m, 2H),
7.46 (d, JZ8.0 Hz, 1H), 7.73–7.86 (m, 4H), 10.14 (br s,
1H); 13C NMR (50 MHz, CDCl3CCCl4): d 202.1, 158.6,
143.5, 134.7, 130.0, 129.2, 128.4, 127.1, 126.7, 125.2,
123.2, 119.5, 105.5, 55.2, 32.1, 25.3; MS (ES): m/z 285
(MCC1), 302 (MCCH2O); Anal. Calcd for C17H16O4: C,
71.83; H, 5.63; Found: C, 71.89; H, 5.58%.
4.2.4. 5-Methylene-4-(3,4,5-trimethoxybenzyl)-2(5H)-
furanone (1d). White solid; Yield: 2.03 g, 72%; Mp:
115–117 8C; IR (Chloroform): n 3016, 1753, 1500, 1217,
1
1037, 756 cmK1; H NMR (200 MHz, CDCl3CCCl4): d
4.1.18. 3-Acetyl-4-(1,4-dimethoxynaphthalen-2-yl)-but-
3-enoic acid (6r). Brownish yellow solid; Yield: 2.19 g,
55%; Mp: 117–120 8C; 1H NMR (200 MHz, CDCl3C
CCl4): d 2.16 (s, 3H), 3.57 (s, 2H), 3.80 (s, 3H), 3.92 (s, 3H),
6.47 (s, 1H), 7.11(s, 1H), 7.50–7.53 (m, 2H), 8.08–8.17 (m,
2H), 10.23 (br s, 1H); MS (ES): m/z 314 (MC), 332 (MCC
H2O); Anal. Calcd for C18H18O5: C, 68.78; H, 5.73; Found:
C, 68.82; H, 5.65%.
3.74 (s, 2H), 3.84 (s, 9H), 4.96 (d, JZ2.9 Hz, 1H),
5.16–5.21 (m, 1H), 5.85 (br s, 1H), 6.39 (s, 2H); 13C
NMR (50 MHz, CDCl3CCCl4): d 168.4, 157.8, 155.7,
153.8 (2C), 137.6, 131.5, 118.6, 106.2 (2C), 94.6, 60.8, 56.2
(2C), 33.0; MS (ESI): m/z 276 (MC), 261, 245, 217, 181,
166; Anal. Calcd for C15H16O5: C, 65.21; H, 5.79; Found: C,
65.45; H, 5.58%.
4.2.5. 4-(1,3-Benzodioxol-5-ylmethyl)-5-methylene-
2(5H)-furanone (1e). Viscous oil; Yield: 1.31 g, 56%; IR
4.2. Typical procedure for the synthesis of 4-benzyl
(substituted)-5-methylene-2(5H)-furanones (1)
1
(Chloroform): n 3018, 1787, 1764, 1217 cmK1; H NMR
(200 MHz, CDCl3CCCl4): d 3.71 (s, 2H), 4.93 (d, JZ
2.3 Hz, 1H), 5.13–5.17 (m, 1H), 5.84 (br s, 1H), 5.95 (s,
2H), 6.60–6.69 (m, 2H), 6.75 (d, JZ8.5 Hz, 1H); 13C NMR
(50 MHz, CDCl3CCCl4): d 168.2, 157.9, 155.0, 147.6,
129.2, 121.5, 117.8, 108.7, 108.1 (2C), 100.8, 94.5, 31.8;
MS (ESI): m/z 231 (MH)C; Anal. Calcd for C13H10O4: C,
67.82; H, 4.31; Found: C, 67.61; H, 4.26%.
The carboxylic acid 6 (10.2 mmol) was mixed with acetic
anhydride (4.8 mL, 51 mmol) and anhydrous sodium
acetate (20.4 mmol) and allowed to stir at 85 8C under
nitrogen atmosphere for 3 h. The mixture was allowed to
cool to room temperature, the reaction mixture was poured
over ice (100 g), stirred vigorously for 30 min and extracted
with ethyl acetate (100 mL). The organic layer was washed
repeatedly with fresh portions of water followed by dilute
sodium bicarbonate solution to remove all traces of acetic
anhydride and acetic acid. The organic layer was washed
with brine, dried over anhydrous sodium sulfate and
concentrated under reduced pressure. Purification of residue
by column chromatography (EtOAc/petroleum ether 1:4)
provided desired furanones in 48–75% yields.
4.2.6. 4-[(7-Methoxy-1,3-benzodioxol-5-yl)methyl]-5-
methylene-2(5H)-furanone (1f). Brownish yellow solid;
Yield: 1.46 g, 55%; Mp: 150 8C; IR (Chloroform): n 3020,
1788, 1766, 1512, 1215 cmK1 1H NMR (200 MHz,
;
CDCl3CCCl4): d 3.69 (unresolved doublet, 2H), 3.86 (s,
3H), 4.93 (d, JZ2.7 Hz, 1H), 5.12–5.18 (m, 1H), 5.83

1266
V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
(br s, 1H), 5.94 (s, 2H), 6.34 (unresolved doublet, 2H); 13
C
128.2, 121.4, 118.2, 117.6, 114.7, 112.4, 94.4, 70.0, 55.9,
32.0; MS (ESI): m/z 273 (MC1), 291 (MHCCH2O); Anal.
Calcd for C16H16O4: C, 70.58; H, 5.88; Found: C, 70.61; H,
5.97%.
NMR (50 MHz, CDCl3CCCl4): d 169.2, 157.8, 155.2,
149.1, 143.6, 130.0, 118.2, 108.3, 108.2, 102.7, 101.4, 94.8,
56.5, 32.7; MS (ESI): m/z 261 (MH)C; Anal. Calcd for
C14H12O5: C, 64.61; H, 4.61; Found: 64.53; H, 4.49%.
4.2.12.
5-Methylene-4-(1-naphthylmethyl)-2(5H)-
4.2.7. 4-(4-Chloro-2,5-dimethoxybenzyl)-5-methylene-
2(5H)-furanone (1g). Pale yellow solid; Yield: 2.15 g,
75%; Mp: 115–117 8C; IR (Chloroform): n 3019, 1788,
furanone (1l). Pinkish white solid; Yield: 1.61 g, 67%;
Mp: 115 8C; IR (Chloroform): n 2926, 1768, 1719,
1
1220 cmK1; H NMR (200 MHz, CDCl3CCCl4): d 4.24
1763, 1499, 1216 cmK1
;
1H NMR (200 MHz, CDCl3C
(s, 2H), 5.13 (d, JZ2.7 Hz, 1H), 5.25–5.30 (m, 1H), 5.57 (br
s, 1H), 7.30–7.56 (m, 4H), 7.80–7.95 (m, 3H); 13C NMR
(50 MHz, CDCl3CCCl4): d 168.4, 157.6, 155.2, 133.7,
131.7, 131.2, 128.8, 128.2, 127.2, 126.4, 125.8, 125.3,
123.2, 118.5, 94.5, 29.9; MS (ESI): m/z 237 (MH)C, 254
(MCH2O); Anal. Calcd for C16H12O2: C, 81.35; H, 5.08.;
Found C, 81.47; H, 5.10%.
CCl4): d 3.73 (s, 2H), 3.77 (s, 3H), 3.82 (s, 3H), 4.98 (d, JZ
2.9 Hz, 1H), 5.13–5.18 (m, 1H), 5.74 (br s, 1H), 6.73 (s,
1H), 6.92 (s, 1H); 13C NMR: (50 MHz, CDCl3CCCl4): d
168.6, 157.3, 155.5, 151.3, 149.3, 123.7, 122.1, 118.0,
115.1, 113.5, 94.4, 57.0, 56.0, 26.9; MS (ESI): m/z 282 and
280 (MC), 244, 221, 185, 158, 89; Anal. Calcd for C14
H13O4Cl: C, 59.89; H, 4.64; Found: C, 60.12; H, 4. 70%.
4.2.13. 4-[(2-Methoxy-1-naphthyl)methyl]-5-methylene-
2(5H)-furanone (1m). Pale yellow solid; Yield: 1.66 g,
61%; Mp: 135 8C; IR (Chloroform): n 3020, 1770, 1768,
4.2.8. 5-Methylene 4-(4-thiomethyl)benzyl-2(5H)-
furanone (1h). Yellow solid; Yield: 1.49 g, 63%; Mp:
55–57 8C; IR (Chloroform): n 3021, 1788, 1765, 1652,
1212 cmK1; 1H NMR (200 MHz, CDCl3CCCl4): d 2.42 (s,
3H), 3.72 (s, 2H), 4.91 (d, JZ3.1 Hz, 1H), 5.08–5.13 (m,
1H), 5.76 (br s, 1H), 7.07 (d, JZ8 Hz, 2H), 7.17 (d, JZ
8 Hz, 2H); 13C NMR (50 MHz, CDCl3CCCl4): d 168.2,
157.6, 155.1, 137.2, 132.3, 129.0 (2C), 126.5 (2C), 118.0,
94.6, 31.6, 15.3; MS (ESI): m/z 232 (MC); Anal. Calcd for
C13H12O2S: C, 67.24; H, 5.17; S, 13.79; Found C, 67.13, H,
4.95; S, 13.68%.
1
1530, 1212 cmK1; H NMR (200 MHz, CDCl3CCCl4): d
3.97 (s, 3H), 4.24 (s, 2H), 5.22 (d, JZ2.9 Hz, 1H),
5.24–5.28 (m, 1H), 5.46 (br s, 1H), 7.30–7.53 (m, 3H),
7.68 (d, JZ8.0 Hz, 1H), 7.79–7.91 (m, 2H); 13C NMR
(50 MHz, CDCl3CCCl4): d 168.8, 158.0, 155.6, 154.4,
132.4, 129.2, 128.9, 128.5, 126.8, 123.4, 122.2, 117.6,
116.5, 112.6, 94.0, 56.1, 21.9; MS (ESI): m/z 266 (M)C,
251, 236, 221, 171, 77; Anal. Calcd for C17H14O3: C, 63.90;
H, 5.26; Found: C, 63.93; H, 5.27%.
4.2.9. 4-(2-Iodo-3,4,5-trimethoxybenzyl)-5-methylene-
2(5H)-furanone (1i). Pinkish brown solid; Yield: 2.34 g,
57%; Mp: 109 8C; IR (Chloroform): n 3016, 1788, 1764,
4.2.14. 4-[(4-Methoxy-1-naphthyl)methyl]-5-methylene-
2(5H)-furanone (1n). Pale yellow solid; Yield: 1.68 g,
62%; Mp: 82 8C; IR (Chloroform): n 3019, 1787, 1765,
1
1
1562, 1228 cmK1; H NMR (200 MHz, CDCl3CCCl4): d
1653, 1216 cmK1; H NMR (200 MHz, CDCl3CCCl4): d
3.80 (s, 2H), 3.81 (s, 6H), 3.84 (s, 3H), 4.99 (d, JZ3.1 Hz,
1H), 5.12–5.15 (m, 1H), 5.65 (br s, 1H), 6.63 (s, 1H); 13C
NMR (50 MHz, CDCl3CCCl4): d 168.2, 156.6, 155.0,
153.7 (2C), 153.3, 141.0, 134.4, 118.2, 109.2, 94.5, 60.7,
60.5, 55.9, 37.8; MS (ESI): m/z 403 (MH)C, 420 (MC
H2O); Anal. Calcd for C15H15O5I: C, 44.77; H, 3.73; Found
C, 44.52; H, 3.64%.
4.00 (s, 3H), 4.09 (s, 2H), 5.07 (d, JZ2.7 Hz, 1H),
5.21–5.23 (m, 1H), 5.55 (br s, 1H), 6.76 (d, JZ7.8 Hz,
1H), 7.24 (d, JZ7.8 Hz, 1H); 7.46 –7.55 (m, 2H), 7.64–7.73
(m, 1H), 8.31–8.38 (m, 1H); 13C NMR (50 MHz, CDCl3C
CCl4): d 168.3, 158.1, 155.2, 155.0, 131.9, 127.2, 126.7,
125.8, 125.0, 123.5, 123.0, 122.6, 118.2, 103.0, 94.2, 55.2,
29.3; MS (ESI): m/z 266 (M)C; Anal. Calcd for C17H14O3:
C, 63.90; H, 5.26; Found: C, 64.13; H, 5.32%.
4.2.10. 4-[4-(Allyloxy)-3-methoxybenzyl]-5-methylene-
2(5H)-furanone (1j). Viscous oil; Yield: 1.23 g, 48%; IR
4.2.15. 4-(4,8-Dimethoxy-naphthalen-1-ylmethyl)-5-
methylene-2(5H)-furanone (1o). Pale yellow solid;
Yield: 1.57 g, 52%; Mp: 129 8C; IR (Chloroform): n 2926,
1
(Chloroform): n 3015, 1788, 1765, 1215 cmK1; H NMR
(200 MHz, CDCl3CCCl4): d 3.71 (br s, 2H), 3.83 (s, 3H),
4.54–4.59 (m, 2H), 4.91 (d, JZ2.9 Hz, 1H), 5.12–5.16 (m,
1H), 5.21–5.42 (m, 2H), 5.79 (br s, 1H), 5.95–6.14 (m, 1H),
6.61–6.75 (m, 2H), 6.81 (d, JZ8.7 Hz, 1H); 13C NMR
(50 MHz, CDCl3CCCl4): d 168.2, 157.8, 155.2, 149.5,
147.0, 132.9, 128.3, 120.5, 117.9, 117.5, 113.6, 112.1, 94.2,
69.5, 55.6, 31.8; MS (ESI): m/z 272 (MC), 231, 203, 137,
77; Anal. Calcd for C16H16O4: C, 70.58; H, 5.88; Found: C,
70.63; H, 5.77%.
1765, 1744, 1500, 1215 cmK1 1H NMR (200 MHz,
;
CDCl3CCCl4): d 3.76 (s, 3H), 4.01 (s, 3H), 4.28 (s, 2H),
5.09 (d, JZ2.5 Hz, 1H), 5.23–5.26 (m, 1H), 5.34 (br s, 1H),
6.77 (d, JZ7.8 Hz, 1H), 6.84 (d, JZ7.8 Hz, 1H), 7.17 (d,
JZ7.8 Hz, 1H), 7.40 (t, JZ8.2 Hz, 1H), 7.95 (d, JZ8.2 Hz,
1H); 13C NMR (50 MHz, CDCl3): d 169.2, 161.4, 156.0,
154.7, 129.0 (2C), 128.0, 125.3, 124.3, 123.3, 116.0, 114.9,
106.4, 103.7, 93.3, 55.3, 54.9, 34.5; MS (ESI): m/z 297
(MH)C; Anal. Calcd for C18H16O4: C, 72.97; H, 5.40;
Found: C, 73.18; H, 5.29%.
4.2.11. 4-[3-(Allyloxy)-4-methoxybenzyl]-5-methylene-
2(5H)-furanone (1k). Pale yellow gum; yield: 1.58 g,
57%; IR (Chloroform): n 3015, 1788, 1765, 1215 cmK1; 1H
NMR (200 MHz, CDCl3CCCl4): d 3.74 (br s, 2H), 3.88 (s,
3H), 4.61 (d, JZ6.0 Hz, 2H), 4.95 (d, JZ2.5 Hz, 1H), 5.20
(d, JZ2.5 Hz, 1H), 5.28–5.42 (m, 2H), 5.83 (s, 1H),
5.88–6.18 (m, 1H), 6.70–6.88 (m, 3H); 13C NMR (50 MHz,
CDCl3CCCl4): d 168.4, 158.0, 155.5, 149.0, 148.3, 133.2,
4.2.16.
4-[(2,7-Dimethoxy-1-naphthyl)methyl]-5-
methylene-2(5H)-furanone (1p). Pale yellow solid; Yield:
1.75 g, 58%; Mp: 85 8C; IR (Chloroform): n 3019, 1768,
1
1605, 1215 cmK1; H NMR (200 MHz, CDCl3CCCl4): d
3.85 (s, 3H), 3.93 (s, 3H), 4.16 (unresolved doublet, 2H),
5.19–5.27 (m, 2H), 5.53 (br s, 1H), 6.88 (d, JZ2.0 Hz, 1H),

V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
1267
7.03 (dd, JZ8.0, 2.0 Hz, 1H), 7.15 (d, JZ8.0 Hz, 1H), 7.74
(t, JZ8.0 Hz, 2H); 13C NMR (50 MHz, CDCl3): d 168.8,
158.5, 158.1, 155.7, 155.0, 133.8, 130.1, 129.0, 124.4, 117.6,
115.7, 115.5, 110.0, 101.3, 94.1, 56.0, 55.0, 22.1; MS (ESI):
m/z 296 (M)C, 268, 253, 237, 216, 201, 185, 165, 105, 77;
Anal. Calcd for C18H16O4: C, 72.97; H, 5.40; Found: C,
72.83; H, 5.51%.
CCl4): d 205.8, 160.1, 153.2 (2C), 145.2, 136.2, 133.7,
128.5, 106.0 (2C), 60.9, 56.0 (2C), 49.3, 40.2, 31.2, 26.4,
22.9, 13.9; MS (ESI): m/z 335 (MH)C, 352 (MCH2O);
Anal. Calcd for C19H26O5: C, 68.26; H, 7.78; Found: C,
68.31; H, 7.54%.
4.3. A typical procedure for the synthesis of 5-methylene-
3,4-dibenzyl (substituted)-2(5H)-furanones
4.2.17. 4-[(6-Methoxy-2-naphthyl)methyl]-5-methylene-
2(5H)-furanone (1q). Pale yellow solid; Yield: 1.55 g,
57%; Mp: 122 8C; IR (Chloroform): n 3019, 1778, 1765,
A solution of furanone 1 (0.72 mmol) in dry tetrahydrofuran
(2 mL) was added dropwise into a solution of lithium
diisopropylamide (0.90 mmol) in dry tetrahydrofuran
(7 mL) at K78 8C over 10 min and stirred further for
20 min. Aldehyde (0.72 mmol) in dry tetrahydrofuran
(10 mL) was added dropwise to the brick red reaction
mixture, the reaction was allowed to stir at same
temperature for 1 h and then it was quenched with saturated
ammonium chloride (5 mL) containing acetic acid (2 mL).
The reaction mixture was extracted with ethyl acetate (2!
15 mL), organic layer was washed with water (15 mL),
dilute sodium bicarbonate solution (15 mL) followed by
brine (10 mL) and dried over sodium sulfate. After
evaporation, the residue was chromatographed on silica
gel with petroleum ether-ethyl acetate as an eluent to collect
the title compounds (yield ranges from 35 to 66%).
1
1215 cmK1; H NMR (200 MHz, CDCl3Cacetone-d6): d
3.92 (br s, 5H), 4.96 (d, JZ2.9 Hz, 1H), 5.15–5.21 (m, 1H),
5.85 (br s, 1H), 7.10–7.28 (m, 3H), 7.57 (br s, 1H), 7.69 (t,
JZ8.0 Hz, 2H); 13C NMR (50 MHz, CDCl3CCCl4): d
167.6, 157.6, 157.2, 155.0, 133.1, 130.6, 128.4 (2C), 126.7,
126.6 (2C), 118.6, 117.7, 105.1, 93.9, 54.5, 31.8; MS (ESI):
m/z 266 (M)C, 251, 177, 91; Anal. Calcd for C17H14O3: C,
63.90; H, 5.26; Found: C, 63.76; H, 5.13%.
4.2.18.
4-[(1,4-Dimethoxy-2-naphthyl)methyl]-5-
methylene-2(5H)-furanone (1r). Pale yellow solid;
Yield: 1.93 g, 64%; Mp: 87 8C; IR (Chloroform): n 2920,
1768, 1717, 1672, 1221 cmK1 1H NMR (200 MHz,
;
CDCl3): d 3.88 (s, 3H), 3.96 (s, 3H), 4.01 (br s, 2H), 5.12
(d, JZ2.9 Hz, 1H), 5.20–5.25 (m, 1H), 5.88 (br s, 1H),
7.49–7.65 (m, 3H), 8.04 (dd, JZ8.0, 2.0 Hz, 1H), 8.26 (dd,
JZ8.0, 2.0 Hz, 1H); MS (ESI): m/z 296 (MC); Anal. Calcd
for C18H16O4: C, 72.97; H, 5.40; Found: C, 72.93; H, 5.38%.
4.3.1. 3-[Hydroxy-5-methylene-4-(3,4,5-trimethoxy-
benzyl)-(3,4,5-trimethoxyphenyl)methyl]-2(5H)-
furanone (11a). Pale yellow gum; Yield: 0.16 g, 48%; IR
1
(Chloroform): n 3515, 1766, 1713, 1655, 1223 cmK1; H
4.2.19. Mixed anhydride 8a. Pale brown solid; Yield:
0.58 g, 17%; Mp: 65–67 8C, IR (Chloroform): n 3019, 1778,
NMR (200 MHz, CDCl3CCCl4): d 3.71 (s, 6H), 3.74 (s,
6H), 3.75–3.95 (m including s at 3.79, 8H), 4.92 (d, JZ
2.9 Hz, 1H), 5.22 (d, JZ2.9 Hz, 1H), 5.68 (br s, 1H), 6.24
(s, 2H), 6.59 (s, 2H); 13C NMR (50 MHz, CDCl3CCCl4): d
169.0, 154.7 (2C), 153.3 (4C), 148.6, 136.9, 136.5, 132.1,
131.3, 105.3 (2C), 102.9 (2C), 96.0, 68.6, 60.6 (2C), 55.9
(4C), 30.5; MS (ESI): m/z 472 (MC); Anal. Calcd for
C25H28O9: C, 63.55; H, 5.93; Found: C, 63.47; H, 6.05%.
1717, 1662, 1515, 1263, 1216, 757 cmK1 1H NMR
;
(200 MHz, CDCl3): 1.73 (s, 3H), 1.98 (s, 3H), 3.50 (q,
JZ4.0 Hz, 2H), 3.81 (s, 3H), 3.83 (s, 6H), 5.69 (s, 1H), 6.38
(s, 2H); 13C NMR (50 MHz, CDCl3): d 199.0, 168.5, 167.6,
153.2 (2C), 137.2, 131.2, 130.1, 118.4, 106.1, 105.5, 60.5,
55.9 (2C), 33.4, 23.4, 21.1; MS (ESI): m/z 354 (MCH2O)C,
337 (MH)C; Anal. Calcd for C17H20O7: C, 60.71; H, 5.99;
Found: C, 60.61; H, 6.07%.
4.3.2.
3-[Hydroxy-(3-hydroxy-4-methoxyphenyl)-
4.2.20. 4-Butyl-4-hydroxy-2-(3,4,5-trimethoxybenzyl)-
cyclopent-2-enone. A solution of furanone 1d (0.20 g,
0.72 mmol) in dry tetrahydrofuran (2 mL) was added
dropwise into a solution of n-butyllithium (0.90 mmol) in
dry tetrahydrofuran (15 mL) at K78 8C over 30 min. 3,4,5-
Trimethoxybenzaldehyde (0.142 g, 0.72 mmol) in dry
tetrahydrofuran (5 mL) was added dropwise to the brick
red colored reaction mixture and the reaction was allowed to
stir at 0 8C for 1 h. It was then quenched with saturated
ammonium chloride (10 mL). The reaction mixture was
extracted with ethyl acetate (2!15 mL), organic layer was
washed with water (20 mL) followed by brine (15 mL) and
dried over sodium sulfate. After evaporation, the residue
was chromatographed over silica gel with petroleum ether–
ethyl acetate as an eluent to afford the title compound.
methyl]-5-methylene-4-(3,4,5-trime-thoxybenzyl)-
2(5H)-furanone (11b). Thick yellow gum; Yield: 0.17 g,
55%; IR (Chloroform): n 3540, 3019. 1765, 1592, 1508,
1215 cmK1; 1H NMR (200 MHz, CDCl3CCCl4): d 3.73 (s,
6H), 3.80 (s, 3H), 3.86 (s, 3H), 3.89 (s, 2H), 4.91 (d, JZ
2.9 Hz, 1H), 5.19 (d, JZ2.9 Hz, 1H), 5.65 (br s, 1H), 5.74
(br s, 1H), 6.27 (s, 2H), 6.76 (d, JZ8.0 Hz, 1H), 6.87 (d, JZ
8.0 Hz, 1H), 6.89 (s, 1H); 13C NMR (50 MHz, CDCl3C
CCl4): d 169.0, 154.8, 153.5 (2C), 148.7, 145.9, 143.9,
134.3, 132.1, 131.3, 129.6, 117.8, 112.5, 110.7, 107.1,
105.7, 96.1, 68.5, 60.7, 56.2, 56.0, 55.9, 30.7; MS (ESI): m/z
428 (MH)C; Anal. Calcd for C23H24O8: C, 64.48; H, 5.60;
Found: C, 64.54; H, 5.62%.
4.3.3. 3-[Hydroxy-(7-methoxybenzo[1,3]dioxol-5-yl)-
methyl]-5-methylene-4-(3,4,5-trimethoxybenzyl)-2(5H)-
furanone (11c). Thick yellow gum; Yield: 0.17 g, 52%; IR
Pale yellow thick oil; Yield: 0.11 g, 45%; IR (Chloroform):
n 3500, 2940, 1720, 1580, 1220 cmK1; 1H NMR (200 MHz,
CDCl3CCCl4): d 0.86 (t, JZ6.0 Hz, 3H), 1.18–1.30 (m,
2H), 1.50–1.80 (m, 2H), 2.43 (d, JZ20.0 Hz, 1H), 2.57 (d,
JZ20.0 Hz, 1H), 3.35 (s, 2H), 3.78 (s, 3H), 3.80 (s, 6H),
6.36 (s, 2H), 6.87 (br s, 1H); 13C NMR (50 MHz, CDCl3C
1
(Chloroform): n 3438, 1763, 1637, 1508, 1215 cmK1; H
NMR (200 MHz, CDCl3CCCl4): d 3.75 (s, 6H), 3.81 (s,
3H), 3.82 (s, 3H), 3.90 (br s, 2H), 4.94 (d, JZ2.9 Hz, 1H),
5.22 (d, JZ2.9 Hz, 1H), 5.64 (s, 1H), 5.94 (s, 2H), 6.27

1268
V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
(s, 2H), 6.50 (br s, 1H), 6.59 (br s, 1H); MS (ESI): m/z 456
(MC), 473 (MCNH3), Anal. Calcd for C24H24O9: C, 61.11;
H, 5.55; Found: C, 61.28; H, 5.67%.
(MCH2O), 463 (MH)C; Anal. Calcd for C27H26O7: C,
70.12; H, 5.62; Found: C, 69.93; H, 5.49%.
4.3.8. 3-[(2,7-Dimethoxynaphthalen-1-yl)-hydroxy-
methyl]-5-methylene-4-(3,4,5-trimethoxybenzyl)-2(5H)-
furanone (11h). Pale yellow gum; Yield: 0.20 g, 57%; IR
4.3.4. 3-(Hydroxy-benzo[1,3]dioxol-5-yl-methyl)-5-
methylene-4-(3,4,5-trimethoxybenzyl)-2(5H)-furanone
(11d). Thick pale yellow gum; Yield: 0.18 g, 60%; IR
(Chloroform): n 3418, 3015, 2900, 1778, 1615, 1212 cmK1
;
1H NMR (200 MHz, CDCl3CCCl4): d 3.57 (s, 6H), 3.74 (s,
2H), 3.84 (s, 9H), 4.81 (d, JZ2.9 Hz, 1H), 4.89 (br s, 1H),
5.16 (d, JZ2.9 Hz, 1H), 5.84 (s, 2H), 6.67 (br s, 1H), 6.95
(dd, JZ2.0, 6.6 Hz, 2H), 7.40 (d, JZ2.0 Hz, 1H), 7.65 (t,
JZ7.0 Hz, 2H); 13C NMR (50 MHz, CDCl3CCCl4): d
169.7, 158.6, 155.2, 154.5, 152.9 (2C), 147.3, 136.2, 133.2,
131.7, 131.4, 130.4, 130.1, 124.7, 119.5, 116.4, 110.2, 104.4
(2C), 101.6, 95.6, 63.8, 60.6, 56.1, 55.7 (2C), 55.2, 30.0; MS
(ESI): m/z 492 (M)C; Anal. Calcd for C28H28O8: C, 68.29;
H, 5.69; Found: C, 68.08; H, 5.81%.
(Chloroform): n 3498, 3018, 1763, 1592, 1505, 1216 cmK1
;
1H NMR (200 MHz, CDCl3CCCl4): d 3.74 (s, 6H), 3.80 (s,
3H), 3.90 (s, 2H), 4.93 (d, JZ2.9 Hz, 1H), 5.21 (d, JZ
2.9 Hz, 1H), 5.65 (br s, 1H), 5.93 (s, 2H), 6.27 (s, 2H), 6.72
(d, JZ8.0 Hz, 1H), 6.76–6.89 (m, 2H); 13C NMR (50 MHz,
CDCl3CCCl4): d 169.0, 154.7(2C), 153.4(2C), 148.0,
147.4, 134.9, 132.0, 131.1 (2C), 119.6, 108.2, 106.0,
105.4 (2C), 101.1, 96.3, 68.7, 60.8, 56.0 (2C), 26.8; MS
(ESI): m/z 426 (MC), 443 (M-1CH2O); Anal. Calcd for
C23H22O8: C, 64.78; H, 5.16; Found: C, 64.70; H, 5.23%.
4.3.9. 3-[(4,8-Dimethoxy-naphthalen-1-yl)-hydroxy-
methyl]-5-methylene-4-(3, 4, 5-trimethoxybenzyl)-
2(5H)-furanone (11i). Brownish yellow solid; Yield:
0.19 g, 55%; Mp: 197 8C; IR (Chloroform): n 3400, 3018,
4.3.5. 3-[Hydroxy-(4-methoxy-3-nitrophenyl)methyl]-5-
methylene-4-(3,4,5-trimethoxybenzyl)-2(5H)-furanone
(11e). Thick tan gum; Yield: 0.16 g, 49%; IR (Chloroform):
n 3515, 3015, 1766, 1713, 1655, 1592, 1492, 1223 cmK1
;
2938, 1772, 1599, 1215 cmK1 1H NMR (200 MHz,
;
1H NMR (200 MHz, CDCl3CCCl4): d 3.75 (s, 6H), 3.80 (s,
3H), 3.85 (s, 2H), 3.93 (s, 3H), 5.02 (d, JZ2.9 Hz, 1H), 5.29
(d, JZ2.9 Hz, 1H), 5.71 (br s, 1H), 6.28 (s, 2H), 6.98 (d, JZ
8.0 Hz, 1H), 7.48 (dd, JZ8.0, 2.0 Hz, 1H), 7.76 (d, JZ
2.0 Hz, 1H); 13C NMR (50 MHz, CDCl3): d 168.7, 159.7,
154.9, 153.7 (2C), 152.6, 149.6, 137.6, 133.3, 131.7, 131.5,
130.2, 123.2, 113.7, 105.7 (2C), 96.8, 67.4, 60.8, 56.6, 56.2
(2C), 30.7; MS (ESI): m/z 457 (M)C, 475 (MCH2O); Anal.
Calcd for C23H23NO9: C, 60.39; H, 5.32; N, 3.06; Found: C,
60.41; H, 5.38; N, 3.13%.
CDCl3CCCl4): d 3.33 (d, JZ14.0 Hz, 1H), 3.48 (d, JZ
14.0 Hz, 1H), 3.67 (s, 6H), 3.78 (s, 3H), 3.87 (s, 3H), 3.96 (s,
3H), 4.82 (d, JZ2.9 Hz, 1H), 5.12 (d, JZ2.9 Hz, 1H), 6.23
(s, 2H), 6.69 (d, JZ8.3 Hz, 1H), 6.75–6.92 (m, 2H), 7.36 (t,
JZ8.3 Hz, 1H), 7.61 (d, JZ8.3 Hz, 1H), 7.91 (d, JZ
8.3 Hz, 1H); 13C NMR (50 MHz, CDCl3CCCl4): d 169.1,
154.8, 153.5 (2C), 148.7, 143.8, 143.3 (2C), 141.8, 140.9,
139.4, 132.0, 131.3, 126.9, 126.8, 125.0, 124.8, 123.8, 119.9
(2C), 105.6 (2C), 96.2, 69.2, 60.7, 56.0 (2C), 36.8; MS
(ESI): m/z 474 (M-H2O)C; Anal. Calcd for C28H28O8: C,
68.29; H, 5.69; Found: C, 68.30; H, 5.74%.
4.3.6. 3-[Hydroxy-(2-methoxynaphthalen-1-yl)methyl]-
5-methylene-4-(3,4,5-trimethoxybenzyl)-2(5H)-
furanone (11f). Thick pale yellow gum; Yield: 0.17 g, 52%;
IR (Chloroform): n 3421, 3019, 1760, 1595, 1508,
4.3.10.
3-[Hydroxy-(6-methoxynaphthalen-2-yl)-
methyl]-5-methylene-4-(3,4,5-trimethoxybenzyl)-2(5H)-
furanone (11j). Yellow solid; Yield: 0.19 g, 57%; MP:
82 8C; IR (Chloroform): n 3435, 3018, 1764, 1594, 1506,
1216 cmK1; 1H NMR (200 MHz, CDCl3CCCl4): d 3.55 (s,
6H), 3.75 (s, 3H), 3.80–3.85 (m, 2H), 3.90 (s, 3H), 4.90 (d,
JZ2.9 Hz, 1H), 5.19 (d, JZ2.9 Hz, 1H), 5.88 (s, 1H), 6.18
(s, 2H), 7.04–7.15 (m, 2H), 7.43 (d, JZ8.0 Hz, 1H), 7.58–
7.70 (m, 3H); 13C NMR (50 MHz, CDCl3CCCl4): d 169.1,
159.6, 158.0, 154.7, 153.3(2C), 148.9, 137.0, 136.0, 134.2,
132.0, 131.2, 129.4, 128.6, 127.4, 124.7, 124.4, 119.2,
105.5, 105.4, 96.1, 68.9, 60.7, 55.8 (2C), 55.2, 30.8; MS
(ESI): m/z 462 (M)C; Anal. Calcd for C27H26O7: C, 70.12;
H, 5.67; Found: C, 70.23; H, 5.55%.
1
1215 cmK1; H NMR (200 MHz, CDCl3CCCl4): d 3.33–
3.65 (m, 2H), 3.61 (s, 6H), 3.76 (s, 3H), 3.87 (s, 3H), 4.84 (d,
JZ2.9 Hz, 1H), 5.18 (d, JZ2.9 Hz, 1H), 5.88 (s, 2H), 6.68
(s, 1H), 7.15 (d, JZ9.2 Hz, 1H), 7.30–7.52 (m, 2H), 7.77
(dd, JZ9.2, 2.4 Hz, 2H), 8.06 (d, JZ8.3 Hz, 1H); 13C NMR
(50 MHz, CDCl3CCCl4): d 169.2, 158.5, 154.9, 153.2,
150.0, 146.9, 137.1, 131.7, 130.8 (2C), 129.4, 128.7, 127.1,
123.7 (2C), 123.0, 113.3, 109.2, 105.3 (2C), 96.1, 63.8,
60.6, 56.4, 56.0 (2C), 30.1; MS (ESI): m/z 462 (M)C, 444
(M-H2O); Anal. Calcd for C27H26O7: C, 70.12; H, 5.62;
Found: C, 70.27; H, 5.72%.
4.3.7. 3-[Hydroxy-(4-methoxynaphthalen-1-yl)methyl]-
5-methylene-4-(3,4,5-trimethoxybenzyl)-2(5H)-furanone
(11g). Brownish yellow gum; Yield: 0.25 g, 75%; IR
(Chloroform): n 3426, 3015, 2939, 1764, 1594, 1592,
4.3.11. 3-(Benzo[1,3]dioxol-5-yl-hydroxymethyl)-4-
benzo[1,3]dioxol-5-ylmethyl-5-methylene-2(5H)-
furanone (13). Thick gum; Yield: 0.14 g, 52%; IR
(Chloroform): n 3446, 2935, 1743, 1593, 1240, 756 cmK1
;
1239 cmK1; H NMR (200 MHz, CDCl3CCCl4): d 3.54 s,
1H NMR (200 MHz, CDCl3CCCl4): d 3.80 (d, JZ14.0 Hz,
1H), 3.90 (d, JZ14.0 Hz, 1H), 4.92 (d, JZ2.0 Hz, 1H), 5.22
(d, JZ2.0 Hz, 1H), 5.65 (s, 1H), 5.95 (br s, 2H), 6.56 (d, JZ
8.0 Hz, 2H), 6.72–6.83 (m, 4H); 13C NMR (50 MHz,
CDCl3CCCl4): d 172.2, 154.1, 149.2 (2C), 147.8, 136.3,
131.8, 120.7, 118.6, 115.1 (2C), 108.2, 107.3, 107.1, 105.9,
100.2 (2C), 95.2, 94.7, 67.3, 29.3; MS (ESI): m/z 381
(MH)C, 399 (MHC18); Anal. Calcd for C21H16O7: C,
55.26; H, 4.21; Found: C, 55.31; H, 4.23%.
1
6H), 3.66 (br s, 2H), 3.72 (s, 3H), 3.97 (s, 3H), 4.94 (d, JZ
2.9 Hz, 1H), 5.25 (d, JZ2.9 Hz, 1H), 6.03 (s, 2H), 6.37 (s,
1H), 6.67 (d, JZ8.0 Hz, 1H), 7.30–7.60 (m, 3H), 8.00 (dd,
1H, JZ8.0, 2.0 Hz, 1H), 8.28 (dd, JZ8.0, 2.0 Hz, 1H); 13C
NMR (50 MHz, CDCl3CCCl4): d 169.7, 155.7, 154.7,
153.0 (2C), 150.0, 136.4, 131.7, 131.3, 130.8, 127.6, 127.0
(2C), 125.1, 124.0, 123.0, 122.6, 105.0 (2C), 102.4, 96.3,
65.2, 60.6, 55.6, 55.3 (2C), 30.6; MS (ESI): m/z 480

V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
1269
4.3.12. 4-Benzo[1,3]dioxol-5-ylmethyl-3-[hydroxy-(3,4,5-
trimethoxyphenyl)-methyl]-5-methylene-2(5H)-
furanone (15). Pale yellow gum; Yield: 0.17 g, 55%; IR
4.4.2. 9-(3-Hydroxy-4-methoxyphenyl)-3-methylene-
6,7,8-trimethoxy-4,9-dihydro-3H-naphtho[2,3-c]furan-
1-one (12b). Yellow brownish solid; Mp: 87 8C; Yield:
0.61 g, 74%; IR (Chloroform): n 3408, 3019, 1766, 1653,
(Chloroform): n 3446, 3018, 1755, 1708, 1217, 756 cmK1
;
1H NMR (200 MHz, CDCl3CCCl4): d 3.74 (s, 3H), 3.79 (s,
3H), 3.81 (m, 2H), 3.84 (s, 3H), 4.88 (d, JZ2.0 Hz, 1H),
5.18 (d, JZ2.0 Hz, 1H), 5.68 (br s, 1H), 5.92 (s, 2H),
6.52–6.69 (m, 5H); 13C NMR (50 MHz, CDCl3CCCl4): d
168.92, 154.4, 153.0 (2C), 148.8, 146.7, 146.6, 136.2, 130.7,
130.3, 120.9, 115.7, 108.3, 108.1, 103.4, 102.6, 100.8, 96.3,
68.6, 60.5, 55.6 (2C), 29.7; MS (ESI): m/z 426 (MC), 443
(M-1CH2O); Anal. Calcd for C23H22O8: C, 64.78; H, 5.16;
Found: C, 64.83; H, 5.21%.
1423, 1215 cmK1; H NMR (200 MHz, CDCl3CCCl4): d
1
3.47 (s, 3H), 3.69–4.05 (m including s at 3.81, 3.84 and 3.90,
11H), 4.86 (d, JZ2.4 Hz, 1H), 5.14 (br s, 2H), 5.55 (br s,
1H), 6.52 (d, JZ2.0 Hz, 1H), 6.61 (s, 1H), 6.75 (d, JZ
8.3 Hz, 1H), 6.92 (dd, JZ8.3, 2.0 Hz, 1H); MS (ESI): m/z
411 (MH)C; Anal. Calcd for C23H22O7: C, 56.09; H, 5.36;
Found: C, 57.21; H, 5.30%.
4.4.3. 9-Benzo[1,3]-dioxol-5-yl-3-methylene-6,7,8-tri-
methoxy-4,9-dihydro-3H-naphtho[2,3-c]furan-1-one
(12c). Yellow gum; Yield: 0.74 g, 91%; IR (Chloroform): n
4.3.13. 3-[Hydroxy-(3,4,5-trimethoxyphenyl)-methyl]-4-
(6-methoxynaphthalen-2-yl-methyl)-5-methylene-2(5H)-
furanone (17). Thick yellow foam; Yield: 0.18 g, 53%; IR
1
3018, 1762, 1592, 1216, 758 cmK1; H NMR (500 MHz,
CDCl3CCCl4): d 3.40 (s, 3H), 3.64–3.87 (m including s at
3.72 and 3.80, 8H), 4.77 (br s, 1H), 5.04 (br s, 2H), 5.79 (br
s, 2H), 6.53 (br s, 2H), 6.56–6.64 (dd, JZ8.0, 2.0 Hz, 2H);
13C NMR (125 MHz, CDCl3CCCl4): d 167.7, 153.6, 153.0,
151.7, 147.5, 146.7, 146.2, 141.5, 136.4, 131.0, 126.6,
123.2, 121.5, 108.6, 108.0, 106.8, 100.8, 92.9, 60.6, 60.2,
55.9, 37.6, 26.6; MS (ESI): m/z 409 (MH)C; Anal. Calcd for
C23H20O7: C, 67.64; H, 4.90; Found: C, 67.78; H, 5.12%.
(Chloroform): n 3401, 3019, 1773, 1653, 1507, 1215 cmK1
;
1H NMR (200 MHz, CDCl3CCCl4): d 3.58 (s, 6H), 3.77 (s,
3H), 3.85 (s, 3H), 4.03 (d, JZ14.0 Hz, 1H), 4.16 (d, JZ
14.0 Hz, 1H), 4.92 (d, JZ2.9 Hz, 1H), 5.19 (d, JZ2.9 Hz,
1H), 5.70 (br s, 1H), 6.53 (s, 2H), 6.55 (d, JZ8.0 Hz, 1H),
7.05–7.18 (m, 2H), 7.38 (br s, 1H), 7.56 (d, JZ8.0 Hz, 1H),
7.62 (d, JZ8.0 Hz, 1H); 13C NMR (50 MHz, CDCl3C
CCl4): d 169.0, 157.8, 155.0, 153.3 (2C), 148.8, 137.6,
136.6, 136.4, 133.4, 131.7, 131.3, 128.9, 127.3, 126.7,
126.5, 119.2, 105.7, 104.1, 103.4, 96.1, 69.1, 60.6, 56.0,
55.9, 55.2, 30.3; MS (ESI): m/z 480 (MCH2O), 462 (M)C;
Anal. Calcd for C27H26O7: C, 70.12; H, 5.67; Found: C,
70.19; H, 5.64%.
4.4.4. 3-Methylene-9-(2-methoxynaphthalen-1-yl)-6,7,8-
trimethoxy-4,9-dihydro-3H-naphtho[2,3-c]furan-1-one
(12d). Pale yellow crystalline solid; Yield: 0.54 g, 61%;
Mp: 219 8C; IR (Chloroform): n 3019, 1775, 1600, 1515,
1215 cmK1; 1H NMR (200 MHz, CDCl3CCCl4): d 2.67 (br
s, 3H), 3.46 (br s, 3H), 3.71 (s, 3H), 3.86 (br s, 5H), 4.84 (br
s, 1H), 5.08 (br s, 1H), 5.99 (br s, 1H), 6.58 (s, 1H), 7.07 (d,
JZ8.0 Hz, 1H), 7.37–7.42 (m, 1H), 7.66–7.74 (m, 3H); 8.63
(d, JZ8.0 Hz, 1H); 13C NMR (50 MHz, CDCl3CCCl4): d
168.7, 158.7, 157.8, 155.2, 153.7, 151.7, 151.2, 148.3,
132.9, 129.0 (2C), 128.0, 126.4, 123.7, 123.4, 123.1, 116.5,
114.3, 111.4, 106.1, 93.0, 60.3, 59.0, 56.7, 55.5, 30.0, 26.8;
MS (ESI): m/z 463 (MHCH2O)C; Anal. Calcd for
C27H24O6: C, 72.97; H, 5.40; Found: C, 72.68; H, 5.35%.
4.4. A typical procedure for the synthesis of cyclic
naphthalene lignan analogues
Hydroxy lignans (2 mmol) were taken in dry dichloro-
methane (15 mL) under nitrogen atmosphere and cooled to
0 8C. Trifluoroacetic acid (0.23 mL, 3 mmol) was added
dropwise within 5 min. The reaction mixture became dark
blue in color. It was allowed to stir at room temperature and
the reaction was monitored by thin layer chromatography.
After completion of reaction (1–4 h), the mixture was
diluted with water (15 mL) and extracted with dichloro-
methane (2!20 mL). The organic layer was washed with
dilute sodium bicarbonate solution (20 mL) followed by
water (20 mL) and brine (25 mL) and dried over anhydrous
sodium sulfate. After removal of solvent the residue was
chromatographed on silica gel with petroleum ether–
acetone (8:2) as an eluent to collect the cyclized products
(yield ranges from 60 to 90%).
4.4.5. 9-(4-Methoxynaphthalen-1-yl)-3-methylene-6,7,8-
trimethoxy-4,9-dihydro-3H-naphtho[2,3-c]furan-1-one
(12e). Pale yellow crystalline solid; Yield: 0.72 g, 81%; Mp:
113–115 8C; IR (Chloroform): n 3018, 1780, 1594, 1507,
1216 cmK1; 1H NMR (500 MHz, CDCl3CCCl4): d 2.89 (s,
3H), 3.77 (s, 3H), 3.90–3.95 (m including s at 3.92 and 3.93,
7H), 4.13 (dd, JZ18.0, 1.9 Hz, 1H) 4.88 (d, JZ2.9 Hz, 1H),
5.11 (d, JZ2.9 Hz, 1H), 5.94 (bt, JZ1.9 Hz, 1H), 6.63 (d,
JZ8.0 Hz, 1H), 6.67 (s, 1H), 6.87 (d, JZ8.0 Hz, 1H), 7.53
(t, JZ8.0 Hz, 1H), 7.68 (t, JZ8.0, 2.0 Hz, 1H), 8.30 (d, JZ
8.0 Hz, 1H), 8.61–8.64 (m, 1H); 13C NMR (50 MHz,
CDCl3CCCl4): d 167.5, 154.1, 154.0 (2C), 152.9, 151.8,
146.1, 141.8, 132.4, 131.9, 126.5, 125.8, 125.5 (2C), 124.2
(2C), 122.1, 106.8, 103.4 (2C), 92.3, 60.5, 59.4, 56.0, 55.3,
32.8, 26.8; MS (ESI): m/z 445 (MH)C; Anal. Calcd for
C27H24O6: C, 72.97; H, 5.40; Found: C, 72.91; H, 5.57%.
4.4.1. 3-Methylene-6,7,8-trimethoxy-9-(3,4,5-tri-
methoxyphenyl)-4,9-dihydro-3H-naphtho[2,3-c]furan-1-
one (12a). Yellow brownish solid; Yield: 0.70 g, 78%; Mp:
56 8C; IR (Chloroform): n 2920, 1768, 1717, 1450, 1221,
1150 cmK1; 1H NMR (200 MHz, CDCl3CCCl4): d 3.50 (s,
3H), 3.65–4.50 (m including s at 3.77, 3.82 and 3.91, 17H),
4.87 (d, JZ2.4 Hz, 1H), 5.15 (d, JZ2.4 Hz, 1H), 5.20 (br s,
1H), 6.41 (s, 2H), 6.63 (s, 1H); 13C NMR (50 MHz,
CDCl3CCCl4): d 169.0, 153.0 (2C), 152.7 (4C), 137.1,
134.1, 130.9, 128.7, 123.5 (2C), 105.3, 104.9 (2C), 96.2,
72.8, 60.3 (2C), 55.6 (4C), 32.6; MS (ESI): m/z 455 (MH)C;
Anal. Calcd for C25 H26O8: C, 66.07; H, 5.72; Found: C,
66.32; H, 5.79%.
4.4.6. 9-(4,8-Dimethoxynaphthalen-1-yl)-3-methylene-
6,7,8-trimethoxy-4,9-dihydro-3H-naphtho[2,3-c]furan-
1-one (12f). Yellow crystalline solid; Yield: 0.60 g, 63%;
Mp: 119 8C; IR (Chloroform): n 2925, 1772, 1635, 1460,
1220 cmK1; 1H NMR (500 MHz, CDCl3CCCl4): d 3.00 (s,
3H), 3.76 (s, 3H), 3.84 (dd, JZ18.0, 3.0 Hz, 1H), 3.88

1270
V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
(s, 3H), 3.90 (s, 3H), 4.05 (dd, JZ18.0, 3.0 Hz, 1H), 4.10 (s,
3H), 4.81 (d, JZ2.9 Hz, 1H), 5.07 (d, JZ2.9 Hz, 1H), 6.57
(d, JZ8.0 Hz, 1H), 6.62 (s, 1H), 6.70 (d, JZ8.0 Hz, 1H),
7.10 (d, JZ8.0 Hz, 1H), 7.35 (t, JZ2.9 Hz, 1H), 7.39 (t, JZ
8.0 Hz, 1H), 7.91 (d, JZ8.0 Hz, 1H); 13C NMR (50 MHz,
CDCl3CCCl4): d 167.3, 158.5, 154.0, 153.8, 152.5, 151.8,
144.5, 141.5, 133.0, 132.7, 127.6, 126.7, 125.8, 125.4, 124.9
(2C), 114.8, 108.0, 106.3, 103.7, 91.4, 60.5, 59.6, 56.2, 55.8,
55.3, 34.4, 26.4; MS (ESI): m/z 475 (MH)C; Anal. Calcd for
C28H26O7: C, 70.88; H, 5.48; Found: C, 70.86; H, 5.52%.
JZ2.0 Hz, 1H), 6.47 (s, 2H), 7.13 (dd, JZ8.0, 2.0 Hz, 1H),
7.17 (d, JZ2.0 Hz, 1H), 7.44 (d, JZ8.0 Hz, 1H), 7.77
(d, JZ8.0 Hz, 1H), 7.83 (d, JZ8.0 Hz, 1H); MS (ESI): m/z
445 (MH)C; Anal. Calcd for C27H24O6: C, 72.97; H, 5.40;
Found: C, 73.12; H, 5.26%.
4.4.11. 6,7,8-Trimethoxy-3-methylene-9-(1-methyl-1H-
indol-3-yl)-4,9-dihydro-3H-naphtho[2,3-c]furan-1-one
(19). White crystalline solid; Yield: 0.53 g, 64%; Mp 128–
130 8C; IR (Chloroform): n 3019, 1767, 1658, 1537,
1
1215 cmK1; H NMR (300 MHz, CDCl3CCCl4): d 3.40
4.4.7. 9-(6-Methoxynaphthalen-2-yl)-3-methylene-6,7,8-
trimethoxy-4,9-dihydro-3H-naphtho[2,3-c]furan-1-one
(12g). Yellow crystalline solid; Yield: 0.79 g, 89%; Mp
118 8C; IR (Chloroform): n 3019, 1772, 1605, 1465,
(s, 3H), 3.63–4.19 (m including s at 3.72, 3.80 and 3.92,
11H), 4.83 (d, JZ2.9 Hz, 1H), 5.09 (d, JZ2.9 Hz, 1H), 5.50
(t, JZ2.9 Hz, 1H), 6.66 (s, 1H), 6.96 (t, JZ8.0 Hz, 1H),
6.98 (s, 1H), 7.12 (t, JZ8.0 Hz, 1H), 7.17–7.23 (m, 2H); 13C
NMR (50 MHz, CDCl3CCCl4): d 167.9, 153.7, 152.8,
152.2, 146.3, 141.6, 136.9, 131.2, 127.7, 126.6, 123.6,
121.3, 121.2, 119.3, 118.9, 115.1, 109.1(2C), 106.9, 92.3,
60.6, 60.2, 56.0, 32.5, 26.8; MS (ESI): m/z 416 (M-1)C;
Anal. Calcd for C25H23NO5: C, 71.93; H, 5.55; N, 3.36;
Found: C, 72.10; H, 5.51; N, 3.43%.
1
1215 cmK1; H NMR (200 MHz, CDCl3CCCl4): d 3.33
(s, 3H), 3.75–4.12 (m including s at 3.80, 3.87 and 3.91, 11
H), 4.87 (d, JZ2.7 Hz, 1H), 5.12 (d, JZ2.7 Hz, 1H), 5.35 (t,
JZ3.9 Hz, 1H), 6.67 (s, 1H), 7.08 (dd, JZ8.0, 2.0 Hz, 2H),
7.31 (dd, JZ8.6, 1.9 Hz, 1H), 7.55 (d, JZ1.9 Hz, 1H), 7.63
(dd, JZ8.6, 2.0 Hz, 2H); 13C NMR (50 MHz, CDCl3C
CCl4): d 167.6, 157.6, 153.9, 153.1, 152.0, 146.6, 141.6,
137.8, 133.5, 131.3, 129.3, 128.9, 127.1, 126.9, 126.7,
123.5, 118.7 (2C), 106.8, 105.6, 92.7, 60.6, 60.2, 56.0, 55.2,
38.1, 26.8; MS (ESI): m/z 445 (MH)C; Anal. Calcd for
C27H24O6: C, 72.97; H, 5.40; Found: C, 72.89; H, 5.60%.
4.5. 3-Acetyl-4-(2,6-dimethylphenyl)-but-3-enoic
acid (21)
To a well-stirred mixture of 2,6-dimethyl benzaldehyde
20 (1.00 g, 7.42 mmol) and ethyl levulinate (3.22 g,
22.2 mmol) in methanol (250 mL), aqueous sodium
hydroxide solution (0.32 g, 22.2 mmol) was added dropwise
at K10 8C. After complete addition, reaction mixture was
stirred at same temperature for 4–5 h and the reaction was
monitored by thin layer chromatography. After completion
of reaction, methanol was removed under vacuum, reaction
mixture was diluted with water (100 mL) and washed with
ethyl acetate (2!50 mL) and aqueous layer was acidified
with conc. HCl. The yellow oil separated was extracted with
ethyl acetate (3!20 mL) and it was repeatedly washed with
water to remove traces of levulinic acid, followed by brine,
dried over sodium sulfate and evaporated to yield acid 21 as
an oil which crystallized on standing.
4.4.8. 5-Benzo-[1,3]dioxol-5-yl-8-methylene-5,9-dihydro-
8H-furo[30,40:6,7]naphtha[2,3-d][1,3]dioxol-6-one (14).
Off-white crystalline solid; Yield: 0.59 g, 82%; Mp:
117–119 8C; IR (Chloroform): n 2898, 1786, 1764, 1652,
1490 cmK1; 1H NMR (CDCl3CCCl4): d 3.76 (dd, JZ22.0,
6.0 Hz, 1H), 3.93 (dd, JZ22.0, 6.0 Hz, 1H), 4.84 (t, JZ
6.0 Hz, 1H), 4.90 (d, JZ2.5 Hz, 1H), 5.18 (d, JZ2.5 Hz,
1H), 5.89 (s, 2H), 5.92 (d, JZ10.0 Hz, 2H), 6.08 (d, JZ
2.8 Hz, 1H), 6.51 (s, 1H), 6.59 (s, 1H), 6.72 (br s, 3H); MS
(ESI): m/z 363 (MC1); Anal. Calcd for C21H14O6: C, 69.61;
H, 3.85; Found: C, 69.41; H, 3.93%.
4.4.9. 8-Methylene-5-(3,4,5-trimethoxyphenyl)-5,9-
dihydro-8H-furo[30,40:6,7]naphtha[2,3-d] [1,3]dioxol-6-
one (16). Off-white crystalline solid; Yield: 0.69 g, 85%;
Mp: 102–104 8C; IR (Chloroform): n 3019, 1788, 1763,
White crystalline solid; Yield: 1.34 g, 78%; Mp: 97 8C; IR
1
(Chloroform): n 3020, 1712, 1670, 1466, 1215 cmK1; H
1607, 1490, 1215 cmK1 1H NMR (200 MHz, CDCl3C
;
NMR (200 MHz, CDCl3): d 1.72 (s, 3H), 2.21 (s, 6H), 3.50
(s, 2H), 7.05–7.15 (m, 4H), 7.97 (br s, 1H); 13C NMR
(50 MHz, CDCl3): d 201.4, 177.2, 139.5, 136.5, 135.1 (2C),
135.0, 127.9, 127.5 (2C), 39.5, 28.9, 20.1 (2C); MS: 232
(M)C; Anal calcd for C14H16O3: C, 72.41; H, 6.89; Found:
C, 72.52; H, 6.91%.
CCl4): d 3.79 (s, 9H), 3.82–3.88 (m, 2H), 4.88 (t, JZ4.0 Hz,
1H), 4.91 (d, JZ4.0 Hz, 1H), 5.18 (d, JZ4.0 Hz, 1H), 5.96
(br s, 2H), 6.35 (s, 2H), 6.63 (s, 1H), 6.75 (s, 1H); 13C NMR
(50 MHz, CDCl3CCCl4): d 168.6, 153.2 (2C), 146.9, 138.3,
131.2, 128.7 (2C), 123.2, 115.7, 108.9, 107.6, 107.5, 105.3,
105.1(2C), 93.2, 60.4, 55.7 (2C), 42.5, 26.5; MS (ESI): m/z
409 (MH)C; Anal. Calcd for C23H20O7 C, 67.64; H, 4.94;
Found: C, 67.83; H, 5.23%.
4.6. 3-Acetyl-4-(2,6-dimethylphenyl)-but-3-enoic acid
methyl ester (22)
4.4.10. 3-Methoxy-8-methylene-11-(3,4,5-trimethoxy-
phenyl)-7,11-dihydro-7H-9-oxa-cyclopenta[b]phenan-
thren-10-one (18). Pale yellow crystalline solid; Yield:
0.76 g, 86%; Mp: 135 8C; IR (Chloroform): n 3019, 1764,
Acid 21 (0.80 g, 3.44 mmol) was dissolved in distilled
methanol (15 mL) and the solution was cooled to 0 8C. To
this solution, diazomethane in ether (50 mL) prepared from
nitrosomethylurea (1.77 g, 17.2 mmol) was added slowly
with constant stirring. After being stirred for 1 h, solvent
was evaporated under vacuum and the crude ester was
purified by column chromatography using 10% acetone in
petroleum ether as an eluent to afford pure ester.
1589, 1215, 757 cmK1 1H NMR (500 MHz, CDCl3C
;
CCl4): d 3.72 (s, 6H), 3.78 (s, 3H), 3.93 (s, 3H), 3.98 (dd,
JZ18.0, 2.0 Hz, 1H), 4.04 (dd, JZ2.0, 18.0 Hz, 1H), 4.96
(d, JZ2.9 Hz, 1H), 5.21 (d, JZ2.9 Hz, 1H), 5.69 (d,

V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
1271
Yellow oil; Yield: 0.75 g, 88%; IR (Chloroform): n 3019,
1775, 1715, 1466, 1215 cmK1 1H NMR (200 MHz,
Acknowledgements
;
We thank Dabur Research Foundation, Ghaziabad, India
for biological activity of some of the compounds. We
also thank the Department of Science and Technology,
New Delhi for the financial support. V.A.M. thanks
CSIR, New Delhi for the award of senior research
fellowship.
CDCl3): d 1.38 (s, 3H), 1.88 (s, 6H), 3.13 (s, 2H), 3.36 (s,
3H), 6.67–6.78 (m, 4H); 13C NMR (50 MHz, CDCl3): d
201.2, 171.9, 139.0, 137.3, 135.8 (2C), 135.2, 128.0, 127.7
(2C), 51.9, 39.6, 29.1, 20.3 (2C); MS (ESI): m/z 246 (M)C;
Anal Calcd for C15H18O3: C, 72.58; H, 7.25; Found: C,
72.60; H, 7.19%.
4.7. 3-(2,6-Dimethylbenzyl)-4-oxo-pentanoic acid methyl
ester (23)
References and notes
Ester 22 (0.72 g, 2.92 mmol) was dissolved in distilled
methanol (15 mL) in two-necked round bottom flask,
purged with nitrogen gas and charged with 10% Pd/C
(10 mg). Then the reaction was flushed with hydrogen gas
and stirred for 1 h under H2 gas (balloon). Reaction mixture
was then filtered through Whatman filter paper, filtrate was
evaporated to dryness and the residue was purified by
column chromatography using 5% acetone in pet ether as an
eluent to afford pure ester 23.
1. Takadoi, M.; Katon, T.; Ishiwata, A.; Terashima, S. Tetrahedron
Lett. 1999, 40, 3399–3402. (ii) Bruggemann, M.;
McDonald, A. I.; Overmann, L. E.; Rosen, M. D.; Schiwink,
L.; Scott, J. P. J. Am. Chem. Soc. 2003, 125, 15284–15285.
2. Rao, C. B. S. Chemistry of Lignans; Andhra University Press:
Waltair, 1978.
3. (a) de March, P.; Figueredo, M.; Font, J.; Raya, J. Org. Lett.
2000, 2, 163–165. (b) Harcken, C.; Bruckner, R. Angew.-
Chem., Int. Ed. 1997, 36, 2750–2752.
4. (a) Fang, X.; Anderson, J. E.; Chang, C.; McLaughlin, J. L.
Tetrahedron 1991, 47, 9751–9758. (b) Yang, X.; Shimizu, Y.;
Steineer, J. R.; Clardy, J. Tetrahedron Lett. 1993, 34, 761–764.
(c) Siegel, K.; Bruckner, R. Chem. Eur. J. 1998, 4, 1116–1122.
(d) Kuhnt, D.; Anke, T.; Besl, H.; Bross, M.; Hermann, R.;
Mocek, U.; Steffan, B.; Steglich, W. J. Antibiot. 1990, 43,
1413–1420. (e) Siegel, K.; Bruckner, R. Synlett 1999,
1227–1230. (f) Seegal, B. C.; Holden, M. Science 1945, 101,
413–415. (g) Miao, S.; Andersen, R. J. J. Org. Chem. 1991, 56,
6275–6280. (h) Shaw, E. J. Am. Chem. Soc. 1946, 68,
2510–2511. (i) Grundmann, C.; Kober, E. J. Am. Chem. Soc.
1955, 77, 2332–2333.
Yellow oil; Yield: 0.60 g, 83%; IR (Chloroform): n 3022,
1771, 1714, 1585, 756 cmK1; 1H NMR (200 MHz, CDCl3):
d 2.17 (s, 3H), 2.32 (s, 6H), 2.67–2.98 (m, 4H), 3.28–3.50
(m, 1H), 3.59 (s, 3H), 7.02 (br s, 3H); MS (ESI): m/z 249
(MC1); Anal. Calcd for C15H20O3: C, 72.58; H, 8.06;
Found: C, 72.67; H, 8.17%.
4.8. 4-(2,6-Dimethylbenzyl)-5,5-dimethyl-dihydro-
2(3H)-furanone14 (24)
5. (a) Mahajan, V. A.; Shinde, P. D.; Borate, H. B.;
Wakharkar, R. D. Tetrahedron. Lett. 2005, 46, 1009–1012.
(b) Swaminathan, B. V. Ind. J. Chem. 1976, 14, 620.
6. (a) Nvarro, E.; Alonso, S. J.; Trujillo, J. E.; Jorge, C.; Perez, C.
J. Nat. Prod. 2001, 64, 134–135. (b) Joseph, H.; Gleye, J.;
Molis, C.; Mensah, L. J.; Roussakis, C.; Gratas, C. J. Nat.
Prod. 1988, 51, 599–600.
To a suspension of activated magnesium metal (0.02 g,
0.79 mmol) in dry THF (5 mL) was added iodomethane
(0.14 g, 0.10 mmol) dropwise over 10 min at room
temperature. To the resultant solution of methyl magnesium
iodide, suspension of CeCl3 (0.24 g, 1.01 mmol) in dry THF
(2 mL) was added followed by ester 23 (0.20 g, 0.8 mmol)
in dry THF (1 mL) over a period of 10 min at 0 8C. The
reaction mixture was stirred at same temperature for 4 h
after which the reaction was quenched with dilute HCl
(50%, 2 mL). The resulting suspension was stirred for
another 10 min and then extracted with ethyl acetate (2!
25 mL). Organic layer was washed with water (15 mL),
brine (15 mL) and dried over sodium sulfate. Evaporation of
the solvent gave crude lactone, which was purified on silica
gel column using 10% acetone in pet ether as an eluent to
afford the pure lactone 24.
7. Cho, J. Y.; Sook Yoo, K. U. B. E.; Yoshikawa, K.; Park, M. H.
J. Nat. Prod. 2000, 63, 1205–1209.
8. Borsato, M. L. C.; Grael, C. F. F.; Souza, G. E. P.; Lopes, N. P.
Phytochemistry 2000, 55, 809–813.
9. Kemp, M. S.; Burden, R. S. Phytochemistry 1986, 25,
1261–1269.
10. (a) Ukita, T.; Sugahara, M.; Terakawa, Y.; Kuroda, T.;
Wada, K.; Nakata, A.; Ohmachi, Y.; Kikkawa, H.; Ikezawa, K.;
Naito, K. J. Med. Chem. 1999, 42, 1088–1099. (b) Ukita, T.;
Nakamura, Y.; Kubo, A.; Yamamoto, Y.; Takahashi, M.;
Kotera, J.; Ikeo, T. J. Med. Chem. 1999, 42, 1293–1305.
11. Ademar, A. F.; Albuquerque, S.; Silva, L. A.; Eberlin, M. N.;
Tomazela, M.; Bastos, K. J. Nat. Prod. 2004, 67, 42–45.
12. (a) Homes, T. L.; Stevenson, R. J. Org. Chem. 1971, 36,
3450–3452. (b) Heller, H. G.; Strydon, P. J. J. Chem. Soc.,
Chem. Commun. 1976, 50–52. (c) Plumann, H. P.; Smith, J. G.;
Rodrigo, R. J. Chem. Soc., Chem. Commun. 1980, 354–357.
(d) Cochran, J. E.; Padawa, A. J. Org. Chem. 1995, 60,
3938–3939. (e) Meyers, A. I.; Avila, W. B. J. Org. Chem.
1981, 46, 3881–3886. (f) Cow, C.; Laung, D.; Charlton, J. L.
Can. J. Chem. 2000, 78, 553–561. (g) Kobayashi, K.;
White crystalline solid; Yield: 0.09 g, 48%; Mp: 132–
133 8C (lit.14 132–133 8C); IR (Chloroform): n 3019,
1
2978, 1761, 1522, 1474, 1215, 1121, 929, 669 cmK1; H
NMR (200 MHz, CDCl3): d 1.44 (s, 3H), 1.58 (s, 3H),
2.25–2.50 (m including s at 2.33, 9H), 2.63–2.85 (m, 2H),
7.04 (br s, 3H); 13C NMR (50 MHz, CDCl3): d 175.3,
135.9 (2C), 135.6, 128.7 (2C), 126.4, 86.5, 45.8, 34.4, 28.5,
26.9, 21.6, 20.2 (2C); MS (ESI): m/z 233 (MH)C; Anal.
Calcd for C15H20O2: C, 77.58; H, 8.62; Found: C, 77.49; H,
8.92%.

1272
V. A. Mahajan et al. / Tetrahedron 62 (2006) 1258–1272
14. Syu, W.; Don, M.; Lee, G.; Sun, C. J. Nat. Prod. 2001, 64,
Tokimatsu, J.; Maeda, K.; Morikawa, O.; Konishi, H.
J. Chem. Soc., Perkin Trans. 1 1995, 3013–3016. (h)
Tanabe, Y.; Seko, S.; Nishii, Y.; Yoshida, T.; Utsumib, N.;
Suzukamo, G. J. Chem. Soc., Perkin Trans. 1 1996,
2157–2165. (i) Kuroda, T.; Takahashi, M.; Ogiku, T.;
Ohmizu, H.; Nishitani, T.; Kondo, K.; Iwasaki, T. J. Org.
Chem. 1994, 59, 7353–7357.
1232–1233.
15. Pattenden, G.; Clemo, N. G. Tetrahedron Lett. 1982, 23,
581–584.
16. Rajasekhar, D.; Subbaraju, G. V. Tetrahedron 1998, 54,
13227–13236.
17. Gordaliza, M.; Garcia, P. A.; Migueldel Corral, J. M.; Corral,
M. A.; Castro, M. A.; Gomez-Zurita, M. A. Toxicon 2004, 44,
441–449.
13. (a) Ward, R. S. Tetrahedron 1990, 46, 5029–5041. (b)
Ward, R. S. Synthesis 1992, 719–730. (c) Ramos, A. C.;
Clairac, R. P.; Medarde, M. Heterocycles 1999, 51,
1443–1470. (d) Madrigal, B.; Puebla, P.; Pelaez, R.;
Caballero, E.; Medarde, M. J. Org. Chem. 2003, 68,
854–864.
18. Some of the new chemical entities described in this manuscript
were screened for anticancer and antifungal activity and have
exhibited potential cytotoxicity as well as antifungal activity.
The results will be published elsewhere.