Single-pot synthesis of spiroannulated dihydrofurans by iodine-ammonium acetate-mediated reaction of dimedone with aldehydes

Article abstract of DOI:10.1080/00397910902763938

Iodine-ammonium acetate-mediated annealation of dimedone with aldehydes led to facile formation of spirodihydrofuran in good yields through tandem Knoevenagel-Michael iodonation and cyclodehydroiodonation reactions in a single pot.

Full text of DOI:10.1080/00397910902763938

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Single-Pot Synthesis of
Spiroannulated Dihydrofurans
by Iodine–Ammonium
Acetate–Mediated Reaction of
Dimedone with Aldehydes
Devi Prasad Sahu a , Santosh Kumar Giri a , Vandana
Varshney a & Shailesh Kumar a
a Medicinal and Process Chemistry Division, Central
Drug Research Institute, Lucknow, India
Version of record first published: 04 Sep 2009.
To cite this article: Devi Prasad Sahu , Santosh Kumar Giri , Vandana Varshney &
Shailesh Kumar (2009): Single-Pot Synthesis of Spiroannulated Dihydrofurans by
Iodine–Ammonium Acetate–Mediated Reaction of Dimedone with Aldehydes, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:19, 3406-3419
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Synthetic Communications1, 39: 3406–3419, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902763938
Single-Pot Synthesis of Spiroannulated
Dihydrofurans by Iodine–Ammonium
Acetate–Mediated Reaction of Dimedone
with Aldehydes
Devi Prasad Sahu, Santosh Kumar Giri, Vandana Varshney,
and Shailesh Kumar
Medicinal and Process Chemistry Division, Central Drug Research
Institute, Lucknow, India
Abstract: Iodine–ammonium acetate–mediated annealation of dimedone with
aldehydes led to facile formation of spirodihydrofuran in good yields through
tandem Knoevenagel–Michael iodonation and cyclodehydroiodonation reactions
in a single pot.
Keywords: Dimedone, Hantzsch condensation, iodine, spirodihydrofuran
INTRODUCTION
Spiro-cyclic compounds have generated a great deal of interest among the
organic chemists not only for aesthetic structural features but for their
reactivity pattern and biological activities.[1] The spiro dihydrofuran
diterpenoid nepetaefolin was reported to exhibit biological activities such
as hypertensive, sedative, bactericidal, insecticidal, antiviral, and other
activities.[2] The synthetic spirocycles having a spiro furan framework have
drawn attention because of their antibacterial,[3] antitumor,[4] and hypocho-
lesterolemic activities.[5] The adducts obtained from cyclic 1,3-ketone and
Received November 5, 2008.
CDRI Communication No. 7163.
Address correspondence to Devi Prasad Sahu, Medicinal and Process
Chemistry Division, Central Drug Research Institute, Lucknow, UP 226001,
India. E-mail: dp_sahu@cdri.res.in; dpsahuin@yahoo.com
3406

Spiroannulated Dihydrofurans
3407
Scheme 1. NH4OAc, I2, 80ꢀC, 8–10 h. Ar ¼ 4-methoxyphenyl.
aldehydes are reported to posses antibacterial, fungicidal,[6a] antioxidant,[6b]
and insecticidal activities.[7] Thus, spiro dihydrofurans derived from cyclic
1,3-diketones and aldehydes should have potent pharmacological activities.
Spiro dihydrofurans have been synthesized either by oxidative
1,3-dipolar cyclo-addition of 1,3-dicarbonyl compounds with exocyclic
alkenes,[8] N-heterocyclic carbine–mediated cyclo-addition with cyclic
1,2-diketones,[9] or a three-step protocol of addition, halogenation, and
cyclo-dehydrohalogenation of cyclic 1,3-diones with aldehydes.[10]
Multicomponent condensation[11] of cyclic 1,3-ketones with aldehydes
in the presence of several substrates have been extensively studied to
synthesize structurally divergent bioactive heterocycles such as
1,4-dihydropyridine,[12] octahydro acridine,[13] polyhydroquinoline,[14]
polyhydroxanthines,[15] oxabicycles,[16] tetrahydrobenzo[b]pyran,[17]
quinazolinone,[18] pyridopyrimidine,[19] pyrimido[4,5-b]quinolinones,[20]
and 1H-pyridazino[1,2-a] indazole-1,6,9(2H,11H)-triones[21] under micro-
wave irradiation[22] or harsh reaction conditions. Herein we report an
iodine–ammonium acetate-mediated, single-pot, facile synthesis of spiro
dihydrofuran from dimedone and aldehydes under mild condition and
in excellent yield, in contrast to the reported formation of acridine, the
Hanzsch adduct, or xanthone derivatve (Scheme 1).
RESULT AND DISCUSSION
On refluxing a mixture of dimedone, 4-anisaldehyde acetylacetone, and
ammonium acetate in ethanol under conventional Hantzsch reaction
conditions for a prolonged period of time, no desired product (i.e., poly-
hydroquinoline) could be isolated. Recently, Ko et al.[23] claimed iodine
catalyzed a facile synthesis of polyhydroquinoline from cyclic 1,3-dike-
tone, aldehyde, and ß-keto ester under ambient conditions. Following a
similar protocol condensation reaction in the presence of molecular
iodine, we were able to isolate product 1i from the reaction mixture
(Scheme 2). Combustion analysis of 1i indicated it was devoid of nitrogen,

3408
D. P. Sahu et al.
Scheme 2. NH4OAc, I2, 30–50ꢀC, 4–8 h.
1
and its H NMR spectrum did not have signals for four sets of methyl
protons as in the desired product.
As 1i instead of 2 was the sole product isolated from the reaction mix-
ture and acetylacetone was not incorporated in the Hantzsch condensation
reaction, we examined the annulation of dimedone with 4-anisaldehyde in
the presence of ammonium acetate and iodine under similar experimental
conditions, which afforded the same product 1i. The infrared (IR) spec-
trum of 1i showed absorbance of 3500 and 1730, 1660 cmꢁ1 indicating
1
the presence of keto carbonyl and enol functionalities. In the H NMR
spectrum of 1i, there were three sets of singlets, accounting for four methyl
groups in a ratio of 1:1:2 between d 0.87 and 1.3 ppm. A singlet at d 2.8 for
two methylene protons and two sets of multiplets for six methylene pro-
tons between d 2.1 and 3.1 ppm indicated nonsymmetry in 1i as it shoud
have in the Hantzsch adduct. The 13C NMR spectra of 1i showed four
signals at d 198, 197, 193, and 175 ppm, indicating the presence of three
anisochronous carbonyl or enol carbons and one carbon linked to oxygen.
The heteronuclear multiple bond correlation (HMBC) experiment of
1i conclusively established spiro hydrofuran structure 1i. The spectra
clearly showed connectivity between C3-H appearing at d 4.43 ppm with
C2 and C9 carbon atoms resonating at d 175 and 118 ppm, respectively,
as well as C8, C4 (resonating at 193 and 198 ppm, respectively) and C1
(resonating at 197 ppm) (Figs. 1 and 2).
In the FAB mass spectra, appearance of base peak at 396 accounted
for spiro dihydrofuran structure of 1i. Thus the structure of product 1i
was unequivocally established to be spiro dihydrofuran rather than the
reported 9-aryl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione derivative
3 (Hantzsch product) or 9-aryl-1,2,3,4,5,6,7,8,9,10-decahydroxanthine-1,8-
dione 4 (Scheme 1). Both acridine 3 and xanthone 4 have plane of symme-
try, and hence the signal for 12 methyl protons appeared as two singlets
accounting for two gem methyl groups each and eight methylene protons
appeared as two sets of singlets.

Spiroannulated Dihydrofurans
3409
1
Figure 1. Selected H–13C HMBC correlations of 1i in CDCl3.
Li et al.[13] have synthesized ABT-598, a fused dihydropyridine
(DHP), in two steps from an aldehyde and a cyclic 1,3-dione through
the intermediary of dione–aldehyde adduct. Several fused hexahydroqui-
nolines, novel KATP (ATP-sensitive potassium channel) openers, have
been synthesized from aldehyde, cyclic 1,3- dione, and ammonium salt
in a single pot under conventional Hantzsch conditions.[12] Condensation
of the aromatic aldehyde with dimedone in refluxing alcohol in the pre-
sence of an acid reportedly furnish xanthone 4 or fused pyran, depending
upon the type of aldehyde.[24]
To explore the mechanism of facile formation of spiro dihydrofuran
under mild conditions instead of Hantzsch product 3 or xanthone 4, we
Figure 2. 1H–13C HMBC correlations of 1i in CDCl3.

3410
D. P. Sahu et al.
Scheme 3. Various adducts obtained from dimedone and aromatic aldehydes.
condensed dimedone and 4-chlorobenzaldehyde in refluxing methanol in
the presence of iodine alone. Instead of spiro dihydrofuran 1d, 9-(4-
chlorophenyl)-1,2,3,4,5,6,7,8,9,10-decahydroxanthine-1,8-dione 4d was
isolated in good yield as evidenced by its PMR, CMR, and mass spectra.
On heating a mixture of dimedone, 4-chlorobenzaldehyde, and ammo-
nium acetate for a period of 6 h in methanol, dimedone–aldehyde adduct
5 was isolated from the reaction mixture. On heating 5 in a microwave
oven, it smoothly furnished decahydroacridine 1,8-dione, the Hantzsch
adduct 4d. (Scheme 3).
The facile formation of spiro dihydrofuran from dimedone and
aldehydes mediated by ammonium acetate and iodine is unprecedented
in the literature. Evidently ammonium acetate facilitates the formation
of dimedone–aldehyde adduct
5 via tandem Knoevenagel and
Michael additions. Probably in the presence of ammonium acetate, both
iodination and cyclodehydrorohalogenation of 5 furnish spiro dihydro-
furan 1 under mild conditions. The probable mechanism is depicted in
Scheme 4.
The yields of the product were found to be dependent on the ratio of
iodine and ammonium acetate employed. The optimum yields were
obtained when 1 equivalent of aldehyde was condensed with 2 equiva-
lents of dimedone in the presence of 1 equivalent of iodine and 1.5
equivalents of ammonium acetate. To explore the scope of the novel spiro
dihydrofuran synthesis, structurally divergent aromatic aldehydes were
condensed with dimedone in the presence of ammonium acetate and
iodine at 40–50ꢀC in methanol. Spiro dihydrofurans were isolated either
by filtration followed by crystallization or by column chromatography in
good to excellent yields. All the compounds were characterized by spec-
tral and analytical data (Table 1).

Spiroannulated Dihydrofurans
3411
Scheme 4. Probable mechanism of formation of spiro dihydrofuran.
Table 1. 2-Spiro(3-aryl-6,6-dimethyl-4-oxo-2,3,4,5,6,7-hexahydrobenzofuran)-20-
(50,50-dimethyl cyclohexane-10,30-diones 1
Entry
Compound
Ar
Yield (%)
Mp (ꢀC)
1
1a
63
232
2
1b
67
233
3
4
5
1c
1d
1e
70
68
74
245–247
258–260
271–27
6
7
8
1f
1g
1h
78
88
79
250 (dec.)
336–341
215–218
9
1i
83
223–224
(Continued )

3412
D. P. Sahu et al.
Table 1. Continued
Entry
Compound
Ar
Yield (%)
Mp (ꢀC)
261–263
10
1j
86
84
11
12
1k
239–241
245–250
1l
78
Annealation of cinnamaldehyde with dimedone in the presence of
hydrochloric acid in ethanol has been reported[24b] to furnish hexahydro-
flavin derivative, but the present experimental protocol leads to facile
formation of 2-spiro(3-styryl-6,6-dimethyl-4-oxo-2,3,4,5,6,7-hexahydro-
benzofuran)-20-(50,50-dimethylcyclohexane-10,30- diones 1l.
CONCLUSION
The synthesis of novel spiro dihydrofuran 1 from dimedone and aromatic
aldehyde under mild conditions in the presence of iodine and ammonium
acetate instead of xanthine 3 or decahydroacridine-1,8-dione 4 (Hantzsch
product) has been reported for the first time. The spiro dihydrofuran motif
occurs in many natural products and potentially has biodynamic properties.
EXPERIMENTAL
Thin-layer chromatography (TLC) was performed on precoated silica-gel
plates (F254, Merck). Chromatography was performed on silica gel (SRL
1
100–200 mesh). Melting points are uncorrected. H NMR spectra were
obtained with a Varian 200- or 300-MHz spectrometer and are reported
as parts per million (ppm) downfield to tetramethylsilane (TMS). The infra-
red (IR) spectra were recorded in a Perkin-Elmer Fourier transform (FT)–
IR 1600 spectrometer. All new compounds have satisfactory microanalysis.

Spiroannulated Dihydrofurans
3413
General Procedure for Synthesis of 2-Spiro(3-aryl-6,6-dimethyl-4-oxo-
2,3,4,5,6,7-hexahydrobenzofuran)-20-(50,50-dimethylcyclohexane-
10,30-diones 1
Iodine (0.13 g) was added to a stirred solution of dimedone (0.28 g,
2 mmol) and aldehyde (1 mmol) in methanol (15 ml), after its dissolution,
ammonium acetate (0.15 g) was added. The resulting mixture was further
stirred for 6–8 h at 40–50ꢀC. The precipitated product was filtered and
recrystallized from alcohol or appropriate solvent. In cases where there
was no precipitation, the product mixture was evaporated to dryness
and was extracted with dichloromethane (2 ꢂ 15 ml). The combined
extracts were successively washed with sodium thiosulfite solution and
brine, dried over anhydrous sodium sulfate, and evaporated. The residual
mass was either recrystallized from alcohol or chromatographed over
silica gel (100–200 mesh) using an ethyl acetate–hexane mixture as eluent,
followed by crystallization, to furnish 1.
Data
2-Spiro-(3-phenyl-6,6-dimethyl-4-oxo-2,3,4,6,7-hexahydrobenzofuran-
20-(50,50dimethylcyclohexane-1030-dione), 1a
IR (KBr) n: 3432 (bs), 2926, 2362, 1713, 1640, 1458, 1391, 1231 cmꢁ1
;
ESI-MS (m=z): [M þ H]þ ¼ 366; 1H NMR (200 Hz, CDCl3) d: 0.83 (s, 3H),
1.15 (s, 6H), 1.25 (s, 2H), 1.64 (bs, 1H), 1.94 (d, 1H, J¼ 14.6 Hz), 2.09 (m,
3H), 2.50 (d, 1H, J¼ 14.6), 2.56 (s, 2H), 3.07 (d, 1H, J¼ 14.6), 4.43 (s,
1H), 7.14 (d, 2H, J¼ 5 Hz), 7.28 (m, 3H). 13C NMR (75MHz, CDCl3)d:
26.27, 28.83, 28.93, 29.43, 32.92, 36.20, 48.75, 49.83, 52.41, 53.76, 51.11,
102.51, 112.35, 117.27, 127.26, 127.65, 135.81, 175.35, 191.79, 197.12, 198.00.
2-Spiro-(3-(4-methylphenyl)-6,6-dimethyl-4-oxo-2,3,4,6,7-hexahydroben-
zofuran-20-(50,50dimethylcyclohexane-1030-dione), 1b
IR (KBr) n: 3427, 2928, 2329, 1712, 1635, 1390, 1352 cmꢁ1; ESI-MS
1
(m=z): [M þ H]þ 380; H NMR (300 Hz, CDCl3) d0.85 (s, 3H), 1.13 (s,
3H), 1.17 (s, 6H), 1.97 (d, 1H, J ¼ 15 Hz), 2.17 (m, 3H), 2.31 (s, 3H),
2.51 (dd, 1H, J ¼ 3 Hz, 15 Hz), 2.66 (s, 2H), 3.06 (d, 1H, J ¼ 15 Hz),
4.42 (s, 1H), 7.04 (d, 2H, J ¼ 9 Hz), 7.17 (d, 2H, J ¼ 9Hz); 13C NMR
(75 MHz, DMSO d6) d: 21.56, 26.72, 28.79, 29.30, 30.92, 34.62, 37.68,
50.41, 51.51, 54.18, 55.19, 104.25, 114.10, 128.77, 130.08, 133.37,
138.81, 176.87, 193.59, 199.39, 199.81.

3414
D. P. Sahu et al.
2-Spiro-(3-(4-fluorophenyl)-6,6-dimethyl-4-oxo-2,3,4,6,7-hexahydroben-
zofuran-20-(50,50dimethylcyclohexane-1030-dione), 1c
IR (KBr) n: 3459, 2927, 1741, 1711, 1642, 1601, 1511, 1392 cmꢁ1; ESI-MS
(m=z): [M þ H]þ ¼ 385; 1H NMR (200 Hz, CDCl3) d: 0.84 (s, 3H), 1.14 (s,
6H), 1.25 (s, 3H), 1.19 (d, 1H, J ¼ 16 Hz), 2.17 (d, 2H, J ¼ 5 Hz), 2.21 (m,
1H), 2.50 (d, 1H, J ¼ 15 Hz), 2.65 (s, 2H), 3.01 (d, 1H, J ¼ 15 Hz), 4.43 (s,
1H), 7.00 (d, 2H, J ¼ 8 Hz), 7.10 (d, 2H, J ¼ 8 Hz); 13C NMR (75 MHz,
DMSO d6) d: 27.12, 27.52, 28.32, 29.24, 30.62, 32.62, 32.95, 36.02,
45.75, 49.80, 52.94, 102.21, 112.33, 114.58, 114.87, 128.86, 128.97,
175.41, 191.83, 197.45, 197.74.
2-Spiro-(3-(4-chlorophenyl)-6,6-dimethyl-4-oxo-2,3,4,6,7-hexahydroben-
zofuran-20-(50,50dimethylcyclohexane-1030-dione), 1d
IR (KBr) n: 3436, 1740, 1708, 1595 cmꢁ1; ESI-MS (m=z): [M þ H]þ ¼ 400;
1H NMR (200 Hz, CDCl3) d: 0.84 (s, 3H), 1.14 (s, 6H), 1.25 (s, 3H), 1.93
(d, 1H, J ¼ 14 Hz), 2.19 (d, 2H, J ¼ 14 Hz), 2.57 (dd, 2H, J ¼ 3, 15 Hz),
2.65 (s, 2H), 3.05 (d, 1H, J ¼ 14 Hz), 4.40 (s, 1H), 7.09 (d, 2H, J ¼ 8 Hz),
7.28 (d, 2H, J ¼ 8 Hz); 13C NMR (75 MHz, CDCl3) d: 22.61, 26.17,
25.32, 28.32, 28.75, 29.62, 30.52, 34.21, 37.20, 49.91, 50.96, 53.85, 54.09,
103.43, 113.49, 129.17, 129.76, 134.54, 176.81, 193.10, 198.59, 198.91.
2-Spiro-(3-(4-nitrophenyl)-6,6-dimethyl-4-oxo-2,3,4,6,7-hexahydroben-
zofuran-20-(50,50dimethylcyclohexane-1030-dione), 1e
IR (KBr) n: 3448, 2957, 1710, 1639, 1395, 1346 cmꢁ1; ESI-MS (m=z):
[M þ H]þ ¼ 411; 1H NMR (300 Hz, CDCl3) d: 0.88 (s, 3H), 1.16 (s,
6H), 1.19 (s, 3H), 1.95 (d, 1H, J ¼ 15 Hz), 2.21 (d, 1H, J ¼ 9 Hz), 2.58
(dd, 1H, J ¼ 3 Hz, 15 Hz), 2.63 (s, 2H), 3.04 (d, 1H, J ¼ 15 Hz), 4.52 (s,
1H), 7.36 (d, 2H, J ¼ 9 Hz), 8.18 (d, 2H, J ¼ 9 Hz); 13C NMR (75 MHz,
CDCl3) d 26.25, 28.78, 29.23, 30.83, 31.08, 34.77, 37.66, 50.03, 51.31,
54.35, 54.42, 103.56, 113.85, 124.56, 129.93, 143.83, 148.30, 177.78,
193.45, 198.60, 198.81.
2-Spiro-(3-(4-N,N-dimethylaminophenyl)-6,6-dimethyl-4-oxo-2,3,4,6,7-
hexahydrobenzofuran-20-(50,50dimethylcyclohexane-1030-dione), 1f
IR (KBr) n: 3432, 2957, 1711, 1635, 1527, 1389, 1353 cmꢁ1; ESI-MS
1
(m=z): [M þ H]þ ¼ 409 H NMR (200 Hz, CDCl3) d 0.84 (s, 3H), 1.15
(s, 6H), 1.25 (s, 6H), 1.33 (s, 3H), 2.08 (m, 2H), 2.12 (dd, 1H, J ¼ 3,

Spiroannulated Dihydrofurans
3415
15 Hz), 2.17 (d, 1H), 2.54 (d, 1H, J ¼ 14.6 Hz), 2.64 (s, 2H), 2.91 (s, 3H),
3.04 (d, 1H, J ¼ 14.6 Hz), 4.38 (s, 1H), 6.63 (d, 2H, J ¼ 8 Hz) 7.01 (d, 2H,
J ¼ 8 Hz); 13C NMR (75 MHz, DMSO d6) d: 26.73, 28.71, 29.24, 30.82,
32.22, 34.12, 37.63, 40.35, 50.40, 51.51, 54.04, 55.11, 104.212, 112.70,
113.97, 123.22, 129.58, 150.67, 176.52, 193.62, 199.73, 200.12.
2-Spiro-(3-(4-hydroxyphenyl)-6,6-dimethyl-4-oxo-2,3,4,6,7-hexahydro-
benzofuran-20-(50,50dimethylcyclohexane-1030-dione), 1g
IR (KBr) n: 3365, 2363, 1713, 1629, 1511, 1391 cmꢁ1. ESI-MS (m=z):
1
[M þ H]þ ¼ 382 H NMR (200 Hz, DMSO-d6) d: 0.80 (s, 3H), 1.15(s,
6H), 1.25 (s, 3H), 2.07 (m, 4H), 2.58 (m, 4H), 4.53 (s, 1H), 5.41 (s,
1H), 6.70 (d, 2H), 6.94 (d, 2H); 13C NMR (75 MHz, DMSO-d6) 25.16,
27.08, 27.22, 28.60, 29.30, 33.09, 35.54, 48.50, 49.85, 51.56, 52.22,
104.61, 112.17, 114.23, 125.92, 129.09, 156.26, 175.25, 191.44, 198.30,
199.62.
2-Spiro-(3-(3-methoxyphenyl)-6,6-dimethyl-4-oxo-2,3,4,6,7-hexahydro-
benzofuran-20(50,50dimethylcyclohexane-1030-dione), 1h
IR (KBr) n: 2961, 1711, 1638, 1393, 1263, 1038 cmꢁ1; ESI-MS (m=z):
1
[M þ H]þ ¼ 396; H NMR (200 Hz, CDCl3): 0.83 (s, 3H), 1.11 (s, 3H),
1.16 (s, 6H), 2.05 (d, 1H, J ¼ 14.43 Hz), 2.12 (d, 1H, J ¼ 3 Hz), 2.18 (d,
2H, J ¼ 4 Hz), 2.55 (dd, 1H, J ¼ 3.14.7 Hz), 2.65 (s, 2H), 3.04 (d, 1H,
J ¼ 14.7 Hz), 3.75 (s, 3H), 4.40 (s, 1H), 6.64 (d, 1H), 6.77 (m, 2H), 7.18
(dd, 1H, J ¼ 2.8 Hz); 13C NMR (75 MHz, CDCl3) 26.70, 28.74, 29.326,
30.935, 37.686, 50.389, 51.484, 54.048, 55.375, 55.624, 104.23, 113.92,
114.36, 114.75, 121.32, 130.38, 137.99, 160.25, 177.04, 193.57, 199.28,
199.72.
2-Spiro-(3-(4-methoxyhenyl)-6,6-dimethyl-4-oxo-2,3,4,6,7-
hexahydrobenzofuran-20-(50,50dimethylcyclohexane-1030-dione), 1i
IR (KBr) n: 3431, 2958, 1713, 1644, 1389, 1353 cmꢁ1; ESIMS (m=z):
[M þ H]þ ¼ 396; 1H NMR (200 Hz, CDCl3) d: 0.83 (s, 3H), 1.12 (s,
3H), 1.15 (s, 6H), 2.12 (d, 1H, J ¼ 15 Hz), 2.14 (d, 1H), 2.17 (s, 2H),
2.55 (dd, 1H, J ¼ 3.5 Hz), 2.64 (s, 2H), 3.02 (d, 1H, J ¼ 15 Hz), 3.77
(s, 3H), 4.41 (s, 1H), 6.82 (d, 2H, J ¼ 8.6 Hz), 7.07 (d, 2H, J ¼ 8.6 Hz);
13C NMR (75 MHz, CDCl3) d: 22.61, 25.32, 27.58, 29.21, 32.92, 36.02,
48.78, 49.85, 52.51, 53.27, 53.92, 102.43, 112.36, 113.09, 126.66, 128.36,
158.37, 175.15, 191.96, 197.81, 198.14.

3416
D. P. Sahu et al.
2-Spiro-(3-(3-methoxy-4-hydroxyphenyl)-6,6-dimethyl-4-oxo-2,3,4,6,7-
hexahydrobenzofuran-20-(50,50dimethylcyclohexane-1030-dione), 1j
IR (KBr) n: 3452, 2960, 1710, 1639, 1392, 1254, 1133 cmꢁ1; ESIMS (m=z):
1
[M þ H]þ ¼ 412; H NMR (200 Hz, DMSOd6) d: 0.90 (s, 3H), 0.92 (s,
3H), 1.17 (s, 3H), 1.11 (s, 3H), 1.632 (m, 4H), 2.04 (d, 1H), 2.20 (s,
2H), 3.01 (d, 1H), 3.375 (s, 3H), 4.42 (s, 1H), 6.79 (m, 2H), 7.24 (m,
1H); 13C NMR (75 MHz, DMSO-d6) d: 26.34, 27.97, 28.57, 29.82,
30.51, 34.27, 30.51, 36.73, 49.67, 51.00, 53.20, 53.32, 55.96, 103.84,
109.47, 113.26, 115.59, 121.83, 127.90, 146.68, 147.74, 176.45, 192.66,
199.57, 200.79.
2-Spiro-(3-(3,4-methylenedioxyphenyl)-6,6-dimethyl-4-oxo-2,3,4,6,7-
hexahydrobenzofuran-20-(50,50dimethylcyclohexan-1030-dione), 1k
IR (KBr n: 3452, 2960, 1710, 1639, 1392, 1254, 1133 cmꢁ1; ESIMS (m=z):
1
[M þ H]þ ¼ 410; H NMR: 0.91 (s, 3H), 1.15 (s, 6H), 1.22 (s, 3H), 1.73
(bs, 1H, exchangeable with D2O); 2.22 (s, 2H); 2.51–3.04 (m, 4H), 3.15
(d, 1H, J ¼ 15 Hz), 4.1 (s, 2H), 4.42 (s, 1H), 6.79 (m, 2H), 7.24 (m,
1H),13C NMR (75 MHz, DMSO-d6) d: 25.10, 27.22, 27.34, 29.19,
32.94, 36.08, 48.89, 49.99, 50.89, 53.09, 101.25, 110.09, 121.57, 125.54,
127.11, 127.33, 133.84, 134.37, 175.67, 175.67, 192.17, 197.88, 198.06.
2-Spiro-(3-styryl-6,6-dimethyl-4-oxo-2,3,4,6,7-hexahydro benzofuran-
20-(50,50dimethylcyclohexane-1030-dione), 1l
IR (KBr) n: 3433, 2959, 1710, 1639, 1391, 1243 cmꢁ1; ESI-MS (m=z):
[M þ H]þ ¼ 410; 1H NMR: 0.85 (s, 3H), 1.16 (s, 9H), 2.13 (d, 2H,
J ¼ 15 Hz), 2.19 (dd, 2H, J ¼ 3.15 Hz), 2.65 (s, 2H), 3.04 (d, 1H,
J ¼ 15 Hz), 4.38 (d, 1H), 5.95 (dd, 1H), 6.56 (d, 1H), 6.73 (m, 2H), 7.38
(m, 3H); 13C NMR (75 MHz, CDCl3) d: 25.03, 27.22, 27.50, 29.22,
32.93, 36.00, 48.72, 49.86, 52.55, 53.37, 100.09, 102.36, 107.18, 112.36,
120.94, 128.47, 146.61, 146.91, 175.28, 191.95, 197.59, 197.95.
ACKNOWLEDGMENTS
Authors are thankful to SAIF at the Central Drug Institute for spectral
analyses of the synthesized compounds. V. V. and S. K. are thankful to
the Council of Scientific and Industrial Research and the University
Grants Commission, New Delhi, respectively, for the award of Senior
research fellowships.

Spiroannulated Dihydrofurans
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