Novel dipolar cycloaddition reactions of zwitterionic species generated from dimethoxycarbene and dimethyl acetylenedicarboxylate with carbonyl compounds: Facile synthesis of dihydrofuran derivatives

Article abstract of DOI:10.1055/s-2003-40192

The reaction of 1:1 zwitterionic species, generated in situ by the addition of dimethoxycarbene to dimethyl acetylenedicarboxylate, towards carbonyl compounds is described. The reactions presented offer a one-pot synthesis of dihydrofuran and spiro dihydrofuran derivatives in high yields.

Full text of DOI:10.1055/s-2003-40192

1446
SPECIAL TOPIC
Novel Dipolar Cycloaddition Reactions of Zwitterionic Species Generated
from Dimethoxycarbene and Dimethyl Acetylenedicarboxylate with Carbonyl
Compounds: Facile Synthesis of Dihydrofuran Derivatives
F
acile Synthesis of
i
D
ihyd
j
rofuran
a
Derivative
y
s
Nair,* S. Bindu, V. Sreekumar, Lakshmi Balagopal
Organic Chemistry Division, Regional Research Laboratory (CSIR), Trivandrum, India
Fax +91(471)2491712; E-mail: vijaynair_2001@yahoo.com
Received 30 April 2003
This paper is dedicated with best regards to Professor Dr. Rolf Huisgen.
reaction, the nucleophile is eliminated from the system af-
Abstract: The reaction of 1:1 zwitterionic species, generated in situ
by the addition of dimethoxycarbene to dimethyl acetylenedicar-
boxylate, towards carbonyl compounds is described. The reactions
presented offer a one-pot synthesis of dihydrofuran and spiro dihy-
drofuran derivatives in high yields.
ter a series of transformations and thus the effective role
played by the nucleophile is to ‘conduct’ a reaction in-
volving two components. In this type of two-component
reactions catalyzed by nucleophiles, Ph3P has been the
most studied nucleophilic species. The chemistry of the
zwitterionic species generated by the addition of Ph3P to
activated alkynes has been studied in detail.3,4,8 Our own
investigations in this area have proved the successful par-
ticipation of quinonoid compounds in the two component
reaction with DMAD catalyzed by Ph3P.9 Subsequently
we have shown that, the 1:1 zwitterionic intermediate
generated by the addition of isocyanides to DMAD could
be intercepted efficiently with electrophiles ranging from
aldehydes to quinones leading to various heterocycles,
thereby constituting novel multicomponent reactions.10
Against this literature scenario, and in the context of our
general interest in devising novel multicomponent reac-
tions based on nucleophilic carbenes, we were intrigued
by the possibility of trapping the 1:1 zwitterionic interme-
diate generated by the addition of dimethoxycarbene to
DMAD with various electrophiles. Nucleophilic carbenes
such as dialkoxycarbenes have gained considerable atten-
tion recently.11 The rich and fascinating chemistry of these
species stems from the inherent nucleophilic properties
which is the direct consequence of donation of lone pairs
of the heteroatoms into the formally vacant p-orbital of
the carbene carbon. Even though the reactivity of
dimethoxycarbene toward DMAD has been studied by
Hoffmann12 and later by Warkentin,13 to date, no attempts
have been made to intercept the 1:1 zwitterion of
dimethoxycarbene and DMAD with a third component.
Our investigations in this avenue succeeded and the reac-
tion led to a one-pot synthesis of highly functionalized di-
hydrofuran derivatives as presented in a preliminary
report.14 In this paper we report the results of our detailed
investigations defining the scope of the reaction.
Key words: aldehydes, carbenes, nucleophilic additions, ketones,
quinones
Introduction
The advent of the Huisgen reaction1 heralded a new era in
heterocyclic chemistry by providing a unique and power-
ful method for the synthesis of five membered
heterocycles2 comparable in its import to the Diels–Alder
reaction for the construction of six membered carbocy-
cles. Even today, the generation of 1,3-dipolar species and
their cycloaddition to suitable -systems (dipolarophiles)
is the method of choice for the synthesis of a large variety
of heterocycles. Consequent to the success of these reac-
tions, the concept of generating and trapping a variety of
zwitterionic species leading to heterocycles appeared at-
tractive. Zwitterionic species often results from the addi-
tion of nucleophiles to activated alkynes like dimethyl
acetylenedicarboxylate (DMAD).3 A variety of nucleo-
philes such as triphenyl phosphine (Ph3P),4 pyridine,5 ter-
tiary amine6, dimethyl sulfoxide,7 etc. has been known to
generate zwitterionic species by this pathway (Figure 1).
These intermediates can be trapped by suitable substrates
and this interception can either be a two-component reac-
tion or a multicomponent reaction. In the two-component
E
Nu
E
Nu = PPh3, R-NC, DMSO, etc.
E = -CO2Me, -SO2R, -CN, -COR, etc.
Results and Discussion
Reaction with Aldehydes
Figure 1 1:1 Zwitterionic species generated by the addition of nu-
cleophiles to activated acetylenes
Our studies were set in motion by exposing p-tolualde-
hyde (1) to the zwitterionic species resulting from the re-
action of DMAD (2) and dimethoxycarbene, the latter
Synthesis 2003, No. 9, Print: 03 07 2003.
Art Id.1437-210X,E;2003,0,09,1446,1456,ftx,en;C01503SS.pdf.
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Facile Synthesis of Dihydrofuran Derivatives
1447
being generated in situ by the thermolysis of 2,2- Table 1 Reaction of Aryl Aldehydes with DMAD/Dimethoxycar-
benea
dimethoxy- 3-1,3,4-oxadiazoline (3)15 in refluxing tolu-
ene following the Warkentin prescription. A facile reac-
tion leading to the formation of dihydrofuran derivative 4
in 81% yield occurred (Scheme 1).
Entry Aldehyde
Product
Yield
(%)b
1
2
81
77
CHO
MeO2C
H
CO2Me
CO2Me
CHO
+
MeO2C
H
OMe
OMe
CO2Me
N N
O
Toluene, Ar
OMe
OMe
+
O
OMe
OMe
110 °C, 15 h
81%
Me
O
CO2Me
6
Me
7
1
2
3
4
CHO
CO2Me
MeO2C
H
Scheme 1
OMe
OMe
O
O2N
O2N
The structure of the product 4 was elucidated by spectro-
scopic analysis. The IR spectrum showed characteristic
peaks at 1735 and 1725 cm–1 corresponding to the two
8
9
3
4
75
66
MeO2C
H
CHO
CO2Me
1
methoxycarbonyl groups. In the H NMR spectrum, the
OMe
OMe
signal due to the p-methyl group was seen at = 2.34 ppm
as a singlet, and the sharp singlets at = 3.40 and 3.46
ppm were attributed to the protons of the two methoxy
groups. The peaks corresponding to protons of the two
methoxycarbonyl groups were seen at = 3.65 and 3.87
ppm. The benzylic proton resonated as a sharp singlet at
= 5.84 ppm. The aromatic protons afforded two separate
doublets at = 7.14 (J = 7.9 Hz) and 7.24 (J = 7.9 Hz)
ppm. In the 13C NMR spectrum, signal due to the p-methyl
carbon was discernible at = 21.2 ppm while the peaks at
161.6 and 162.4 ppm were attributed to the ester carbon-
yls. All the other signals were also in good agreement with
the proposed structure.
O
Cl
Cl
10
11
CHO
CO2Me
MeO2C
H
OMe
OMe
O
Cl
Cl
12
13
5
69
CHO
MeO2C
H
CO2Me
OMe
OMe
O
Mechanistically, the reaction is considered to involve the
initial formation of a 1:1 zwitterionic intermediate by the
reaction of dimethoxycarbene with DMAD. The zwitteri-
on 5 adds to the carbonyl group to afford a dipolar species,
which undergoes cyclization to furnish the product. From
another perspective, the reaction may be considered to in-
volve the 1,3 dipolar cycloaddition of 5 with the carbonyl
group (Scheme 2).
OCH2Ph
CHO
PhH2CO
14
15
6
7
8
43
70
90
MeO2C
CO2Me
H
OMe
OMe
O
OMe
CHO
MeO
16
17
CO2Me
MeO2C
R
MeO2C
CO2Me
OMe
CO2Me
MeO2C
H
CO2Me
MeO
MeO
OMe
OMe
+
H
R
OMe
OMe
5
MeO
O
O
Cl
Cl
CO2Me
Cl
O
Cl
R= p-tolyl
18
19
MeO2C
Scheme 2
CHO
CO2Me
H
OMe
OMe
The reaction was carried out with a number of aromatic al-
dehydes containing both electron-donating and electron-
withdrawing groups; the dihydrofuran derivatives were
obtained in moderate to excellent yields (Table 1).
O
20
21
The reaction was found to be applicable to aliphatic alde-
hydes also; isobutyraldehyde (22) furnished the corre-
sponding dihydrofuran derivative 23 in moderate yield
(Scheme 3).
a Reaction conditions: toluene, 110 °C, 15 h, argon.
b Isolated yield.
Synthesis 2003, No. 9, 1446–1456 ISSN 1234-567-89 © Thieme Stuttgart · New York

1448
V. Nair et al.
SPECIAL TOPIC
CO2Me
ed with DMAD and the carbene precursor 3 in refluxing
toluene under argon for 16 hours, a facile reaction leading
to the formation of the dihydrofuran derivative 35 in 81%
yield occurred (Scheme 6).
CO2Me
OMe
MeO2C
O
N
N
Toluene, Ar
H
Me
OMe
OMe
+
+
Me
H
110 °C, 15 h
40%
O
O
OMe
Me
22
CO2Me
Me
2
3
23
Scheme 3
H3C
O
MeO2C
H3C
CO2Me
OMe
CO2Me
+
N
N
OMe
OMe
Toluene, 110 °C
+
O
sealed tube, 16 h
81%
When paraformaldehyde (24) was employed, the reaction
afforded the corresponding dihydrofuran derivative 25 in
50% yield (Scheme 4). The structure of the product was
established by spectroscopic analysis.
O
OMe
CO2Me
NO2
O2N
34
2
3
35
Scheme 6
CO2Me
+ +
H
CO2Me
OMe
MeO2C
O
N
N
Toluene, Ar
OMe
OMe
H
H
H
When fluorenone (36) was employed in the multicompo-
nent reaction with DMAD and dimethoxycarbene, the
corresponding dihydrofuran derivative 37 was obtained in
moderate yield (Scheme 7).
110 °C, 15 h
50%
O
O
OMe
CO2Me
24
2
3
25
Scheme 4
OMe
CO2Me
CO2Me
O
CO2Me
MeO
It was observed that the dihydrofuran derivatives, ob-
tained by the above-mentioned multicomponent reaction,
lost methanol slowly on standing at room temperature for
several hours, to afford the corresponding furan deriva-
tives. Subsequently, it was found that either microwave ir-
radiation or the addition of a Lewis acid catalyst
accelerated this transformation. A typical example involv-
ing the the conversion of dihydrofuran 4 to furan 26 is
shown in Scheme 5.
N N
O
Toluene, 110 °C
OMe
OMe
O
+
+
sealed tube, 16 h
50%
CO2Me
36
2
3
37
Scheme 7
Inexplicably, acetophenone and p-chloroacetophenone
did not furnish any dihydrofuran derivatives when treated
with DMAD and dimethoxycarbene; the ketones and
DMAD were recovered quantitatively.
Silica gel
MeO2C
CO2Me
OMe
microwave 800W
5 min, 90%
CO2Me
OMe
MeO2C
O
OMe
Me
Reaction with , -Unsaturated Carbonyl Com-
pounds
O
4
SnCl4,
Me
26
CH2Cl2, 1 h,
95%
In the next phase of our studies we turned our attention to
, -unsaturated carbonyl compounds to examine the
chemoselectivity in the multicomponent reaction of these
compounds with DMAD and dimethoxycarbene. The , -
unsaturated carbonyl compounds selected for our studies
include various substituted cinnamaldehydes and chal-
cones. We initiated our experiments by treating cinnama-
ldehyde (38a) with DMAD and the oxadiazoline in
refluxing toluene under argon atmosphere for 15 hours
and the reaction afforded the corresponding dihydrofuran
derivative 39a in about 70% yield (Scheme 8). No product
resulting from the addition of the zwitterion to the conju-
gated double bond was observed.
Scheme 5
The IR spectrum of 26 showed strong carbonyl absorption
1
peaks at 1732 and 1707 cm–1. In the H NMR spectrum,
the peaks at = 4.19 and 3.88 were assigned to the protons
corresponding to the two methoxycarbonyl groups while
the sharp singlet at 3.81 was assigned to the protons of the
methoxy group. In the 13C NMR spectrum, the peaks cor-
responding to the two ester carbonyls were discernible at
= 164.9 and 162.2 ppm, while the carbon bearing the
methoxy group in the furan ring resonated at 160.6 ppm.
The reaction has been extended to almost all dihydrofuran
derivatives in order to convert them to the stable furan de-
rivatives and the results are summarized in Table 2.
O
CO2Me
+
MeO2C
H
CO2Me
OMe
N N
O
Toluene, 110 °C
sealed tube, 15 h
OMe
OMe
H
+
O
OMe
CO2Me
R
3
2
39
38
39a R = H
R
Reaction with Ketones
70%
39b R = -2-OMe
39c R = -4-Cl
40%
60%
In view of the encouraging results obtained in the case of
aldehydes, it was of interest to extend the present reaction
also to ketones. When p-nitroacetophenone (34) was treat- Scheme 8
Synthesis 2003, No. 9, 1446–1456 ISSN 1234-567-89 © Thieme Stuttgart · New York

SPECIAL TOPIC
Facile Synthesis of Dihydrofuran Derivatives
Product
Yield (%)b
1449
Table 2 Formation of Furan Derivatives from Dihydrofuransa
Entry
1
Substrate
MeO2C
CO2Me
OMe
85
CO2Me
MeO2C
O2N
27
OMe
OMe
H
O
O
O2N
9
2
3
88
90
MeO2C
H
CO2Me
CO2Me
OMe
MeO2C
Cl
OMe
OMe
O
O
Cl
28
11
CO2Me
MeO2C
H
CO2Me
OMe
MeO2C
OMe
OMe
O
O
Cl
29
Cl
13
4
88
MeO2C
CO2Me
OMe
MeO2C
H
CO2Me
OMe
OMe
O
O
PhH2CO
30
PhH2CO
15
5
6
7
85
90
92
MeO2C
CO2Me
OMe
MeO2C
CO2Me
H
OMe
OMe
O
O
MeO
31
MeO
17
CO2Me
OMe
MeO2C
H
CO2Me
MeO2C
Cl
Cl
OMe
OMe
O
O
Cl
Cl
32
19
MeO2C
CO2Me
CO2Me
OMe
MeO2C
H
OMe
OMe
O
O
33
21
a Reaction conditions: SnCl4, CH2Cl2, 1 h.
b Isolated yield.
The structure of the product was established by spectro- and the carbon attached to two methoxy groups. All other
scopic analysis. The IR spectrum of 39a showed strong signals were in good agreement with the proposed struc-
1
carbonyl absorption peak at 1746 cm–1. The H NMR ture. The reaction was extended to other substituted cinna-
spectrum was in good agreement with the assigned struc- maldehydes 38b,c; moderate yields of dihydrofuran
ture. Signals due to the methoxy and methoxycarbonyl derivatives 39b,c were obtained and the results are sum-
protons were discernible at = 3.44, 3.51, 3.71 and 3.74 marized in Scheme 8.
ppm. The methine proton in the dihydrofuran ring showed
Prompted by the successful participation of cinnamalde-
its resonance peak as a singlet at = 4.83 ppm. The 13C
hydes in the multicomponent reaction with DMAD and
NMR spectrum was also in good agreement with the as-
dimethoxycarbene, it was reasonable to extend the reac-
signed structure. The peaks at = 163.9 and 161.7 ppm
tion also to , -unsaturated ketones such as chalcones. In
were typical of the two ester carbonyls. The peaks at
=
a typical reaction, benzylideneacetophenone (40a) was
103.7 and 122.0 ppm were assigned to the methine carbon
Synthesis 2003, No. 9, 1446–1456 ISSN 1234-567-89 © Thieme Stuttgart · New York

1450
V. Nair et al.
SPECIAL TOPIC
treated with DMAD and 2,2-dimethoxyoxadiazoline in groups appeared as a sharp singlet at = 3.56, while the
refluxing toluene under argon for 24 hours and this result- peak corresponding to the methoxycarbonyl groups was
ed in the formation of the corresponding dihydrofuran de- discernible at = 3.85 ppm. The olefinic protons provided
rivative 41a in 70% yield (Scheme 9). In this case also, no two doublets centered at = 6.53 (J = 16 Hz) and 7.26
product resulting from the addition of the zwitterion to the ppm (J = 16 Hz). The aromatic protons were visible as a
C–C double bond was observed.
multiplet between = 7.56 and 6.96 ppm. The 13C NMR
spectrum showed characteristic peaks corresponding to
the two ester carbonyls at = 162.3 and 161.8 ppm. The
sp2 carbons attached to the two methoxycarbonyl groups
resonated at = 141.4 and 135.3 ppm.
Characterization of the product is based on conventional
spectroscopic data. The IR spectrum of 41a showed car-
bonyl absorption peaks at 1728 and 1740 cm–1, corre-
1
sponding to the two methoxycarbonyl groups. In the H
NMR spectrum, the signals of the two methoxy groups The reaction was found to be applicable to a number of
were seen as singlets at = 3.33 and 3.49 ppm, while the substituted divinyl ketones 42b–g and the distyrenyl dihy-
peaks corresponding to the methoxycarbonyl protons drofurans 43b–g were obtained in moderate to good yields
were discernible at = 3.75 and 3.86 ppm. In the 13C (Scheme 10).
NMR spectrum, typical ester carbonyl peaks were visible
at = 162.4 and 162.1 ppm. The two quaternary carbons
to the ring oxygen were seen at = 89.8 and 123.1 ppm.
Reaction with 1,4-Benzoquinones
The reaction was found to be applicable to a number of In view of the encouraging results obtained with alde-
substituted chalcones 40b–d, and the dihydrofuran deriv- hydes and other carbonyl compounds and in the context of
atives 41b–d were obtained in good yields (Scheme 9).
our general interest in the addition of zwitterionic species
to quinones,17,10b we extended the reaction to quinones al-
so. An illustrative example involving p-benzoquinone
(44a) leading to a spiro-dihydrofuran derivative 45a is
Reaction with 1,4-Dienones
When 1,4-dienone 42a was employed as the third compo- presented in Scheme 11. The reaction appears to be appli-
nent in the multicomponent reaction with DMAD and cable to other p-benzoquinones, e.g. 45b (Scheme 11).14
dimethoxycarbene, generated in situ from 3, the distyre-
When 1,4-naphthoquinone (46) was employed in the mul-
nyl dihydrofuran derivative 43a was obtained in good
ticomponent reaction with DMAD and oxadiazoline, the
corresponding dihydrofuran 47 was obtained in low yield
(Scheme 12).
yields (Scheme 10).16 As usual, the structure of the prod-
uct 43a was established by spectroscopic methods.
The IR spectrum showed lactone and carbonyl vibrations
at 1735 cm–1 and 1728 cm–1 respectively. In the 1H NMR
spectrum, the protons corresponding to the methoxy
O
CO2Me
MeO2C
CO2Me
N N
O
Toluene, 110 °C
OMe
OMe
+
+
OMe
OMe
sealed tube, 24 h
70 %
R'
O
R'
CO2Me
40
3
2
41
R
41c R = 4-Cl, R' = H
65%
41a R = H, R' = H
70%
41d R = -4-OMe, R'= H 38%
41b R = -4-Me, R'= H 60%
R
Scheme 9
OMe
MeO
CO2Me
O
CO2Me
N
N
OMe
OMe
O
Toluene, sealed tube
110 °C, 24 h, 70%
+
CO2Me
+
O
CO2Me
X
R
3
2
42
43
X
R
43a X = R = 3-Cl
43b X = R = 2-Cl
43c X = R = H
43d X = R = 2-CH3
43e X = R= 2-CF3
43f X = R= 3,4-Cl2
91 %
73 %
53 %
81 %
77 %
43g X = H, R= 4-CH3 65 %
Scheme 10
Synthesis 2003, No. 9, 1446–1456 ISSN 1234-567-89 © Thieme Stuttgart · New York

SPECIAL TOPIC
Facile Synthesis of Dihydrofuran Derivatives
1451
offers an easy route for the synthesis of highly functional-
ized dihydrofuran derivatives in good yields, thereby con-
stituting novel multicomponent reactions. It is interesting
to note that furan and dihydrofuran motifs are present in a
number of biologically active natural products and other
heterocyclic compounds. It is conceivable that the novel
multicomponent reactions described herein will find ap-
plication in the synthesis of a variety of heterocyclic com-
pounds, and in natural product synthesis.
OMe
CO2Me
MeO
R1
O
O
R1
CO2Me
CO2Me
N
N
Toluene, Ar
110 °C, 15 h
OMe
OMe
+
R2
+
O
R2
CO2Me
O
O
44
2
3
45
45a R1 = R2 = H
45b R1 = R2 =-CH3
75%
65%
Scheme 11
Melting points were recorded on a Büchi melting point apparatus
and are uncorrected. NMR spectra were recorded at 300 (1H) and 75
(13C) MHz, respectively on a Bruker DPX-300 MHz NMR spec-
trometer. Chemical shifts ( ) are reported relative to TMS (1H) and
CDCl3 (13C) as the internal standards. Coupling constant (J) are re-
ported in Hertz (Hz). Mass spectra were recorded under EI/HRMS
(at 5000 resolution) using Jeol JMS 600H mass spectrometer. IR
spectra were recorded on a Nicolet Impact 400D FT-IR spectropho-
tometer. Elemental analyses were performed on a Perkin Elmer-
2400 Elemental Analyzer. Dimethyl acetylenedicarboxylate
(DMAD, 2) was purchased from Aldrich Chemical Co. and was
used without further purification. The dimethoxycarbene precursor,
2,2-dimethoxy- 3-1,3,4-oxadiazoline (3) was prepared according
to a known literature procedure.15 Commercial grade solvents were
distilled prior to use. Analytical TLC was performed on glass plates
coated with silica gel containing CaSO4 binder. Gravity column
chromatography was performed using 100–200 mesh silica gel and
mixtures of hexane–EtOAc were used for elution.
OMe
CO2Me
MeO
O
O
CO2Me
+
N
N
O
Toluene, Ar
CO2Me
OMe
OMe
+
O
110 °C, 15 h
31%
CO2Me
O
46
2
47
3
Scheme 12
Similar reaction was also observed in the case of 1,4-an-
thraquinone (48), affording the spiro-dihydrofuran deriv-
ative 49 in 52% yield (Scheme 13).
OMe
CO2Me
O
MeO
CO2Me
+
Dimethyl 2,2-Dimethoxy-5-(4-methylphenyl)-2,5-dihydrofu-
ran-3,4-dicarboxylate (4); Typical Procedure
N
N
Toluene, Ar
O
CO2Me
OMe
OMe
+
O
A mixture of p-tolualdehyde (1; 100 mg, 0.83 mmol), DMAD (2;
177 mg, 1.24 mmol) and oxadiazoline 3 (265 mg, 1.66 mmol) was
refluxed in anhyd toluene under argon for 15 h. The solvent was re-
moved under vacuum and the residue was subjected to chromatog-
raphy on a silica gel column using 80:20 hexane–EtOAc solvent
mixture to afford 4 as a colorless viscous liquid (226 mg, 81%).
110 °C, 15 h
52%
CO2Me
O
O
48
49
2
3
Scheme 13
IR (neat): 3015, 2944, 2843, 1735, 1725, 1607, 1513, 1445, 1251,
1102, 983, 808, 750 cm–1.
1H NMR: = 7.24 (d, J = 7.9 Hz, 2 H), 7.14 (d, J = 7.9 Hz, 2 H),
5.84 (s, 1 H), 3.87 (s, 3 H), 3.65 (s, 3 H), 3.46 (s, 3 H), 3.40 (s, 3 H),
2.34 (s, 3 H).
13C NMR: = 162.4, 161.6, 141.1, 138.7, 133.8, 129.3, 127.6,
125.4, 123.9, 83.9, 52.6, 52.3, 51.4, 50.9, 21.2.
Reaction with 1,2-Benzoquinones
The attempted interception of the zwitterion with the o-
benzoquinone 50 also gave the corresponding product as
a mixture of regioisomers 51 and 52 in a ratio of 2:1, albeit
in very low yield. This may be due to the reduction of the
quinonoid moiety by electron transfer during the course of
the reaction (Scheme 14).
Dimethyl 2, 2-Dimethoxy-5-phenyl-2,5-dihydrofuran-3,4-dicar-
boxylate (7)
Colorless viscous liquid.
IR (neat): 3016, 2962, 2847, 1742, 1728, 1694, 1445, 1351, 1283,
1249, 1115, 1081, 1027, 980, 919, 798, 703 cm–1.
Conclusion
1H NMR: = 7.35–7.28 (m, 5 H), 5.87 (s, 1 H), 3.86 (s, 3 H), 3.63
(s, 3 H), 3.36 (s, 3 H), 3.26 (s, 3 H).
In conclusion, it has been shown that the one-pot reaction
of carbonyl compounds, DMAD and dimethoxycarbene
OMe
OMe
CO2Me
O
N
N
O
Toluene, Ar
O
O
+
OMe
OMe
+
+
CO2Me
CO2Me
110 °C, 15 h
20%
O
O
OMe
OMe
CO2Me
O
MeO2C
51
CO2Me
50
2
3
52
Scheme 14
Synthesis 2003, No. 9, 1446–1456 ISSN 1234-567-89 © Thieme Stuttgart · New York

1452
V. Nair et al.
SPECIAL TOPIC
13C NMR: = 162.2, 161.4, 140.5, 136.7, 135.3, 128.8, 128.5,
127.5, 123.9, 83.9, 52.5, 52.2, 50.9, 50.8.
1H NMR: = 7.49–7.42 (m, 2 H), 7.27–7.22 (m, 1 H), 5.81 (s, 1 H),
3.89 (s, 3 H), 3.70 (s, 3 H), 3.49 (s, 3 H), 3.40 (s, 3 H).
13C NMR: = 162.2, 161.1, 139.2, 137.4, 136.8, 133.1, 132.8,
130.6, 129.7, 126.8, 124.3, 82.8, 52.8, 52.5, 51.3, 50.9.
Dimethyl 2,2-Dimethoxy-5-(3-nitrophenyl)-2,5-dihydrofuran-
3,4-dicarboxylate (9)
Pale yellow viscous liquid.
Dimethyl 2,2-Dimethoxy-5-(1-naphthyl)-2,5-dihydrofuran-3,4-
dicarboxylate (21)
Colorless viscous liquid.
IR (neat): 3090, 3001, 2955, 2854, 1748, 1728, 1640, 1539, 1445,
1351, 1263, 1202, 1162, 1115, 1047, 1013, 987, 912, 818, 744 cm–1.
1H NMR: = 8.78 (s, 1 H), 8.33–8.27 (m, 2 H), 7.62 (t, J = 8 Hz, 1
H), 4.27 (s, 1 H) 3.78 (s, 3 H), 3.70 (s, 3 H), 3.51 (s, 6 H).
IR (neat): 2999, 2942, 2843, 1740, 1731, 1681, 1432, 1332, 1276,
1232, 1113, 976, 782 cm–1
13C NMR: = 163.2, 160.6, 147.7, 135.3, 130.1, 129.7, 128.7,
125.4, 124.6, 121.7, 119.9, 104.6, 55.5, 52.8, 52.4, 51.5, 50.8.
1H NMR: = 8.22 (d, J = 8.2 Hz, 1 H), 7.87–7.82 (m, 2 H), 7.58–
7.41 (m, 4 H), 6.75 (s, 1 H), 3.91 (s, 3 H), 3.61 (s, 3 H), 3.51 (s, 3
H), 3.27(s, 3 H).
Dimethyl 5-(3-Chlorophenyl)-2,2-dimethoxy-2,5-dihydrofuran-
3,4-dicarboxylate (11)
Colorless viscous liquid.
13C NMR: = 162.3, 161.9, 141.5, 136.1, 133.8, 132.7, 131.7,
129.6, 128.7, 126.6, 126.2, 125.9, 125.2, 124.2, 123.2, 79.7, 52.7,
52.4, 51.3, 50.9.
IR (neat): 3070, 2996, 2948, 2840, 1742, 1730, 1647, 1566, 1438,
1330, 1290, 1196, 1094, 987, 784, 724 cm–1.
1H NMR: = 7.37–7.27 (m, 4 H), 5.83 (s, 1 H), 3.88 (s, 3 H), 3.68
(s, 3 H), 3.49 (s, 3 H), 3.41 (s, 3 H).
Dimethyl 5-Isopropyl-2,2-dimethoxy-2,5-dihydrofuran-3,4-di-
carboxylate (23)
Colorless viscous liquid.
IR (neat): 2998, 2962, 1742, 1620, 1445, 1270, 1108, 1007, 791
cm–1.
1H NMR: = 4.86 (d, J = 3.1 Hz, 1 H), 3.78 (s, 6 H), 3.46 (s, 3 H),
3.30 (s, 3 H), 2.72–2.10 (m, 1 H), 1.07 (d, J = 6.8 Hz, 3 H), 0.87 (d,
J = 6.8 Hz, 3 H).
13C NMR: = 162.3, 161.2, 139.8, 139.0, 136.0, 134.5, 129.8,
129.1, 128.4, 125.7, 124.2, 83.3, 52.8, 52.4, 51.2, 50.9.
Dimethyl 5-(4-Chlorophenyl)-2,2-dimethoxy-2,5-dihydrofuran-
3,4-dicarboxylate (13)
Colorless viscous liquid.
13C NMR: = 162.5, 162.1, 142.5, 134.0, 123.1, 86.9, 58.4, 51.3,
50.7, 50.2, 20.6, 20.03, 19.4.
IR (neat): 3002, 2962, 2847, 1755, 1721, 1634, 1600, 1492, 1438,
1337, 1256, 1196, 1115, 1054, 1027, 899, 784, 690 cm–1.
Dimethyl 2,2-Dimethoxy-2,5-dihydrofuran-3,4-dicarboxylate
(25)
Colorless viscous liquid.
1H NMR: = 7.87 (d, J = 8.6 Hz, 2 H), 7.38 (d, J = 8.6 Hz, 2 H),
5.83 (s, 1 H), 3.76 (s, 3 H), 3.66 (s, 3 H), 3.40 (s, 6 H).
13C NMR: = 164.8, 161.9, 160.7, 141.8, 132.8, 128.2, 125.8,
124.5, 122.6, 115.3, 58.4, 52.7, 52.5, 51.4.
IR (neat): 3002, 2955, 2054, 1735, 1613, 1445, 1330, 1256, 1074,
960, 804, 757, 703 cm–1.
Dimethyl 5-[4-(Benzyloxy)phenyl]-2,2-dimethoxy-2,5-dihydro-
furan-3,4-dicarboxylate (15)
1H NMR: = 4.73 (d, J = 9 Hz, 1 H), 4.49 (d, J = 9 Hz, 1 H), 4.02
(s, 3 H), 3.75 (s, 3 H), 3.72 (s, 3 H), 3.34 (s, 3 H)
Colorless viscous liquid.
13C NMR: = 164.2, 162.1, 146.7, 144.6, 124.5, 123.6, 58.5, 51.7,
51.4.
IR (neat): 3009, 2948, 2845, 1755, 1721, 1681, 1627, 1519, 1431,
1283, 1243, 1189, 1121, 987, 933, 852, 751, 697 cm–1.
Dimethyl 2-Methoxy-5-(4-methylphenyl)furan-3,4-dicarboxy-
late (26)
1H NMR: = 7.14–6.92 (m, 9 H), 5.83 (s, 1 H), 5.03 (s, 2 H), 3.87
(s, 3 H), 3.65 (s, 3 H), 3.46 (s, 3 H), 3.40 (s, 3 H).
SnCl4 (58 mg, 0.22 mmol) was added to a solution of the dihydro-
furan 4 (150 mg, 0.44 mmol) in anhyd CH2Cl2. After stirring for 1
h at r.t., H2O was added to the reaction mixture and it was extracted
with CH2Cl2. The combined organic extracts were washed with
brine and dried (Na2SO4). After the removal of solvent, the residue
was subjected to chromatography on a silica gel column using 80:20
hexane–EtOAc mixture to afford analytically pure 26 as a colorless
crystalline solid (127 mg, 95%); colorless crystalline solid; mp
112–113 °C (CH2Cl2–hexane).
13C NMR: = 162.4, 161.7, 159.3, 141.1, 136.7, 135.2, 129.1,
129.0, 128.5, 128.2, 127.9, 127.4, 125.3, 123.9, 83.7, 69.9, 52.6,
52.3, 51.1, 51.0.
Dimethyl 2,2-Dimethoxy-5-(4-methoxyphenyl)-2,5-dihydrofu-
ran-3,4-dicarboxylate (17)
Colorless viscous liquid.
IR (neat): 2999, 2948, 2854, 1748, 1729, 1607, 1519, 1465, 1256,
1189, 1232, 1108, 976, 782 cm–1.
1H NMR: = 7.98 (d, J = 8.8 Hz, 2 H), 7.46 (d, J = 8.8 Hz, 2 H),
4.09 (s, 1 H), 3.80 (s, 3 H), 3.74 (s, 3 H), 3.72 (s, 3 H), 3.58 (s, 3 H),
3.36 (s, 3 H).
IR (KBr): 3012, 2956, 1732, 1707, 1601, 1457, 1264, 1095, 952,
814, 750 cm–1.
1H NMR: = 7.46 (d, J = 8 Hz, 2 H), 7.17 (d, J = 8 Hz, 2 H), 4.19
(s, 3 H), 3.88 (s, 3 H), 3.81 (s, 3 H), 2.36 (s, 3 H).
13C NMR: = 164.8, 162.2, 160.4, 159.8, 142.8, 128.6, 127.3,
121.3, 114.6, 113.8, 68.5, 55.1, 52.3, 51.5, 51.4.
13C NMR: = 164.9, 162.2, 160.6, 142.5, 138.6, 129.6, 129.4,
125.8, 125.5, 58.4, 52.5, 51.5, 21.4.
Anal. Calcd for C16H16O6: C, 63.15, H, 5.90. Found: C, 63.0, H,
5.21.
Dimethyl 5-(3,4-Dichlorophenyl)-2,2-dimethoxy 2,5-dihydro-
3,4-furandicarboxylate (19)
Colorless viscous liquid.
Dimethyl 2-Methoxy-5-(3-nitrophenyl)furan-3,4-dicarboxylate
(27)
Yellow crystalline solid; mp 184–185 °C (CH2Cl2–hexane).
IR (neat): 2998, 2952, 2839, 1732, 1672, 1606, 1560, 1474, 1434,
1401, 1334, 1281, 1241, 1202, 1175, 1109, 1036, 983, 917, 811,
764, 665 cm–1.
Synthesis 2003, No. 9, 1446–1456 ISSN 1234-567-89 © Thieme Stuttgart · New York

SPECIAL TOPIC
Facile Synthesis of Dihydrofuran Derivatives
1453
IR (KBr): 3007, 2952, 2840, 1738, 1703, 1600, 1524, 1469, 1441,
1345, 1221, 1103, 1048, 985, 820, 763 cm–1.
Dimethyl 2-(3,4-Dichlorophenyl)-5-methoxyfuran-3,4-dicar-
boxylate (32)
Colorless crystalline solid; mp 124–125 °C (CH2Cl2–hexane).
1H NMR: = 8.44 (s, 1 H), 8.15 (d, J = 7.4 Hz, 1 H), 7.92 (d, J = 7.1
Hz, 1 H), 7.57 (t, J = 7.8 Hz, 1 H), 4.25 (s, 3 H), 3.94 (s, 3 H), 3.83
(s, 3 H).
IR (KBr): 3002, 2962, 2837, 1735, 1682, 1560, 1464, 1281, 1109,
1036, 983, 764, 665 cm–1.
13C NMR: = 164.2, 161.7, 148.6, 146.9, 139.3, 130.6, 130.2,
129.8, 122.8, 120.1, 55.8, 52.9, 51.7.
1H NMR: = 7.66 (s, 1 H), 7.43 (s, 2 H), 4.21 (s, 3 H), 3.82 (s, 3 H),
3.71 (s, 3 H).
Anal. Calcd for C15H13NO8: C, 53.74, H, 3.91, N, 4.18. Found: C,
54.02, H, 3.93, N, 4.31.
13C NMR: = 164.2, 161.7, 160.8, 139.5, 133.1, 130.7, 126.9,
124.4, 122.6, 116.5, 58.6, 52.7, 51.6.
Anal. Calcd for C15H12Cl2O6: C, 50.16, H, 3.37. Found: C, 50.20, H,
3.15.
Dimethyl 2-(3-Chlorophenyl)-5-methoxyfuran-3,4-dicarboxy-
late (28)
Colorless crystalline solid; mp 100–101 °C (CH2Cl2–hexane).
Dimethyl 2-Methoxy-5-(1-naphthyl)furan-3,4-dicarboxylate
IR (KBr): 3009, 2962, 2840, 1735, 1721, 1600, 1573, 1485, 1438,
1357, 1243, 1108, 1054, 966, 885, 784, 724 cm–1.
(33)
Colorless viscous liquid.
1H NMR: = 7.55 (s, 1 H), 7.47–7.44 (m, 1 H), 7.33–7.26 (m, 2 H),
4.21 (s, 3 H), 3.91 (s, 3 H), 3.81 (s, 3 H).
IR (neat): 3012, 2840, 1726, 1607, 1451, 1345, 1239, 1095, 1052,
802, 777, 652 cm–1.
13C NMR: = 164.4, 161.9, 160.8, 140.3, 134.8, 130.2, 130.0,
128.4, 125.3, 125.2, 116.2, 58.5, 52.72, 51.6.
1H NMR: = 7.91–7.85 (m, 3 H), 7.63 (d, J = 6.6 Hz, 1 H), 7.51–
7.48 (m, 3 H), 4.13 (s, 3 H), 3.84 (s, 3 H), 3.64 (s, 3 H).
Anal. Calcd for C15H13ClO6: C, 55.48, H, 4.04. Found: C, 55.69, H,
4.08.
13C NMR: = 163.6, 162.1, 161.2, 143.6, 133.5, 131.7, 130.2,
129.0, 128.4, 126.7, 126.1, 125.1, 124.9, 117.8, 79.7, 58.4, 52.0,
51.5.
Dimethyl 2-(4-Chlorophenyl)-5-methoxyfuran-3,4-dicarboxy-
late (29)
Colorless crystalline solid; mp 105–106 °C; (CH2Cl2–hexane).
Dimethyl 2,2-Dimethoxy-5-methyl-5-(4-nitrophenyl)-2,5-dihy-
drofuran-3,4-dicarboxylate (35)
Colorless viscous liquid.
IR (KBr): 3015, 2999, 2949, 1734, 1729, 1607, 1470, 1426, 1338,
1245, 1089, 1039, 821,794, 689 cm–1.
1H NMR: = 7.52 (d, J = 8.6 Hz, 2 H), 7.34 (d, J = 8.5 Hz, 2 H),
IR (neat): 2996, 2969, 2847, 1735, 1672, 1607, 1526, 1438, 1344,
1270, 1121, 980, 858, 789, 696 cm–1.
1H NMR: = 8.19 (d, J = 8.7 Hz, 2 H), 7.72 (d, J = 8.7 Hz, 2 H),
4.19 (s, 3 H), 3.89 (s, 3 H), 3.81 (s, 3 H).
3.81 (s, 3 H), 3.73 (s, 3 H), 3.46 (s, 3 H), 3.43 (s, 3 H), 2.01 (s, 3 H).
13C NMR: = 161.9, 161.6, 148.13, 147.6, 143.5, 135.5, 127.1,
123.2, 122.8, 86.6, 52.4, 51.2, 50.6, 24.2.
13C NMR: = 163.9, 161.8, 160.6, 142.1, 134.4, 132.8, 128.9,
126.9, 126.6, 123.1, 58.4, 52.5, 51.5.
Anal. Calcd for C15H13ClO6: C, 55.48, H, 4.04. Found: C, 55.43, H,
4.12.
Dimethyl 5 ,5 -Dimethoxyspiro[9H-fluorene-9,2 (5 H)-furan]-
3,4-dicarboxylate (37)
Colorless viscous liquid.
Dimethyl 2-[4-(Benzyloxy)phenyl]-5-methoxyfuran-3,4-dicar-
boxylate (30)
Colorless crystalline solid; mp 111–112 °C (CH2Cl2–hexane).
IR (neat): 3009, 2948, 2847, 1735, 1674, 1452, 1337, 1290, 1175,
1135, 1034, 987, 939, 789, 764 cm–1.
1H NMR: = 7.62 (d, J = 7.4 Hz, 2 H), 7.49 (d, J = 7.4 Hz, 2 H),
7.38 (t, J = 7.4 Hz, 2 H), 7.26 (t, J = 7.4 Hz, 2 H), 3.82 (s, 3 H), 3.55
(s, 6 H), 3.37 (s, 3 H).
13C NMR: = 162.2, 160.9, 143.1, 143.0, 140.7, 136.9, 129.9,
128.1, 124.7, 123.3, 120.1, 91.8, 52.6, 52.1, 51.4.
IR (KBr): 3030, 2943, 2854, 1738, 1688, 1607, 1482, 1413, 1351,
1219, 1176, 1107, 1051, 1013, 826, 780, 716, 698 cm–1.
1H NMR: = 7.52–6.90 (m, 9 H), 5.06 (s, 2 H), 4.15 (s, 3 H), 3.84
(s, 3 H), 3.78 (s, 3 H).
13C NMR: = 167.2, 164.6, 159.1, 136.7, 128.6, 127.1, 127.4,
127.4, 121.7, 115.1, 104.9, 70.1, 58.4, 52.3, 49.6.
Anal. Calcd for C22H20O7: C, 66.66, H, 5.09. Found: C, 66.83, H,
5.04.
Dimethyl 2,2-Dimethoxy-5-[(E)-2-phenylethenyl]-2,5-dihydro-
furan-3,4-dicarboxylate (39a)
Colorless viscous liquid.
Dimethyl 2-(Methoxy)-5-(4-methoxyphenyl)furan-3,4-dicar-
boxylate (31)
Colorless crystalline solid; mp 121–122 °C (CH2Cl2–hexane).
IR (neat): 3000, 2956, 2848, 1746, 1695, 1644, 1638, 1593, 1447,
1256, 1205, 1105, 1020, 766, 702 cm–1.
1H NMR: = 7.39–7.27 (m, 5 H), 6.77 (d, J = 15.7 Hz, 1 H), 6.17–
6.09 (m, 1 H), 5.51 (d, J = 7.2 Hz, 1 H), 3.99 (s, 3 H), 3.78 (s, 3 H),
3.48 (s, 3 H), 3.41 (s, 3 H).
13C NMR: = 163.9, 161.7, 148.0, 144.5, 133.4, 132.4, 131.7,
130.6, 129.2, 126.6, 122.0, 102.4, 54.9, 52.0, 50.5.
IR (KBr): 3002, 2955, 2840, 1735, 1681, 1512, 1431, 1256, 1101,
1034, 973, 790, 650 cm–1.
1H NMR: = 7.54 (d, J = 8.7 Hz, 2 H), 6.90 (d, J = 8.7 Hz, 2 H),
4.17 (s, 3 H), 3.87 (s, 3 H), 3.82 (s, 3 H), 3.81 (s, 3 H).
13C NMR: = 164.6, 162.1, 160.04, 143.0, 140.1, 127.3, 123.3,
121.4, 113.1, 55.7, 55.1, 52.1, 51.6
Dimethyl 2,2-Dimethoxy-5-[(E)-2-(2-methoxyphenyl)ethenyl]-
2,5-dihydrofuran-3,4-dicarboxylate (39b)
Colorless viscous liquid.
Anal. Calcd for C16H16O7: C, 60.0, H, 5.05. Found: C, 60.4, H, 5.14.
IR (neat): 3063, 2948, 2847, 1742, 1634, 1593, 1438, 1249, 1108,
1027, 784, 757 cm–1.
Synthesis 2003, No. 9, 1446–1456 ISSN 1234-567-89 © Thieme Stuttgart · New York

1454
V. Nair et al.
SPECIAL TOPIC
1H NMR: = 7.60–7.53 (m, 1 H), 7.27–7.22 (m, 2 H), 7.02–6.76 (m,
3 H), 4.15 (s, 1 H), 3.84 (s, 3 H), 3.76 (s, 3 H), 3.73 (s, 3 H), 3.70 (s,
3 H), 3.41 (s, 3 H).
HRMS (EI): m/z Calcd for C24H23ClO7 [M+]: 458.1132. Found:
458.1109.
Dimethyl 2,2-Dimethoxy-5-[(E)-2-(4-methoxyphenyl)ethenyl]-
5-phenyl-2,5-dihydrofuran-3,4-dicarboxylate (41d)
Colorless viscous liquid.
13C NMR: = 164.2, 162.5, 157.8, 148.2, 144.3, 132.3, 131.0,
129.8, 127.1, 126.4, 121.9, 115.0, 102.9, 54.8, 52.2, 51.1, 50.7,
50.6.
IR (neat): 3009, 2955, 1742, 1613, 1512, 1276, 1182, 1034, 966,
912, 811, 703 cm–1.
1H NMR: = 7.44–7.34 (m, 2 H), 7.31–7.26 (m, 5 H), 6.87–6.81 (m,
3 H), 6.65 (d, J = 16 Hz, 1 H), 3.86 (s, 3 H), 3.79 (s, 3 H), 3.72 (s,
3 H), 3.48 (s, 3 H), 3.33 (s, 3 H).
13C NMR: = 162.4, 162.2, 159.6, 143.3, 140.3, 135.3, 131.0,
129.2, 128.2, 128.0, 127.3, 127.1, 126.1, 123.0, 89.9, 55.1, 52.7,
52.4, 51.6. 51.1.
HRMS (EI): m/z Calcd for C19H22O8 [M+]: 378.1315. Found:
378.1292.
Dimethyl 5-[(E)-2-(4-Chlorophenyl)ethenyl]-2,2-dimethoxy-
2,5-dihydrofuran-3,4-dicarboxylate (39c)
Colorless viscous liquid.
IR (neat): 3012, 2955, 2840, 1742, 1708, 1640, 1485, 1438, 1317,
1249, 1108, 1013, 838, 744, 663cm–1.
1H NMR: = 7.87 (d, J = 8.4 Hz, 2 H), 7.37 (d, J = 8.4 Hz, 2 H),
6.8 (m, 1 H), 6.3(d, J = 15.6 Hz, 1 H), 4.22 (d, J = 6 Hz, 1 H), 3.74
(s, 3 H), 3.65 (s, 3 H), 3.36 (s, 6 H).
13C NMR: = 163.3, 162.1, 146.9, 141.2, 135.6, 134.8, 132.6,
129.6, 128.7, 127.8, 126.8, 103.0, 55.4, 52.1, 51.1, 50.5.
HRMS (EI): m/z Calcd for C18H19ClO7 [M+]: 382.0819. Found:
382.0899.
Dimethyl 2,2-Bis[(E)-2-(3-Chlorophenyl)ethenyl]-5,5-dimeth-
oxy-2,5-dihydrofuran-3,4-dicarboxylate (43a)
Pale yellow viscous liquid.
IR (neat): 3012, 2948, 2840, 1738, 1728, 1674, 1600, 1566, 1472,
1438, 1270, 1115, 980, 784, 683 cm–1.
1H NMR: = 7.38–7.24 (m, 8 H), 6.76 (d, J = 15.9 Hz, 2 H), 6.53
(d, J = 15.9 Hz, 2 H), 3.85 (s, 6 H), 3.50 (s, 6 H).
Dimethyl 2,2-Dimethoxy-5-phenyl-5-[(E)-2-phenylethenyl]-2,5-
dihydrofuran-3,4-dicarboxylate (41a)
Colorless viscous liquid.
13C NMR: = 162.4, 161.6, 141.0, 138.0, 135.5, 134.6, 130.4,
130.1, 129.8, 128.8, 128.4, 128.1, 126.7, 125.0, 123.1, 87.6, 52.8,
52.5, 51.4, 50.6.
IR (neat): 3002, 2955, 2847, 1740, 1728, 1452, 1431, 1283, 987,
933, 752, 703 cm–1.
HRMS (EI): m/z Calcd for C26H24Cl2O7 [M+]: 518.0899. Found:
518.0870.
1H NMR: = 7.21–7.47 (m, 10 H), 6.92 (d, J = 16 Hz, 1 H), 6.76
(d, J = 16 Hz, 1 H), 3.86 (s, 3 H), 3.75 (s, 3 H), 3.49 (s, 3 H), 3.33
(s, 3 H).
13C NMR: = 162.4, 162.1, 142.9, 140.1, 136.4, 135.6, 134.4,
131.4, 128.6, 128.4, 128.3, 126.8, 123.7, 123.1, 89.8, 52.5, 52.4,
51.4, 50.0.
Dimethyl 2,2-Bis[(E)-2-(2-chlorophenyl)ethenyl]-5,5-
dimethoxy-2,5-dihydrofuran-3,4-dicarboxylate (43b)
Pale yellow viscous liquid.
IR (neat): 3002, 2948, 2847, 1735, 1728, 1681, 1600, 1479, 1445,
1283, 1182, 1128, 1047, 980, 764, 697 cm–1.
1H NMR: = 7.56–6.96 (m, 8 H), 7.26 (d, J = 16 Hz, 2 H), 6.53 (d,
J = 16 Hz, 2 H), 3.85 (s, 6 H), 3.56 (s, 6 H).
13C NMR: = 162.3, 161.8, 141.4, 135.3, 134.5, 133.6, 130.1,
129.7, 129.0, 127.8, 127.1, 126.8, 123.2, 87.8, 52.7, 51.6.
HRMS (EI): m/z Calcd for C26H24Cl2O7 [M+] : 518.0899. Found:
HRMS (EI): m/z Calcd for C24H24O7 [M+]: 424.1522. Found:
424.1534
Dimethyl 2,2-Dimethoxy-5-[(E)-2-(4-methylphenyl)ethenyl]-5-
phenyl-2,5-dihydrofuran-3,4-dicarboxylate (41b)
Colorless viscous liquid.
518.0902.
IR (neat): 3012, 2948, 2834, 1735, 1675, 1445, 1270, 1128, 980,
697 cm–1.
1H NMR: = 7.46–7.44 (m, 2 H), 7.33–7.31 (m, 5 H), 7.12 (d,
J = 7.9 Hz, 2 H), 6.88 (d, J = 16 Hz, 1 H), 6.70 (d, J = 16 Hz, 1 H),
3.87 (s, 3 H), 3.75 (s, 3 H), 3.48 (s, 3 H), 3.33 (s, 3 H), 2.03 (s, 3 H).
13C NMR: = 162.5, 162.1, 142.9, 140.1, 137.8, 135.7, 134.6,
133.5, 131.3, 129.3, 129.2, 128.3, 127.1, 126.8, 123.0, 89.9, 52.6,
52.5, 51.5, 51.1, 21.2.
Dimethyl 2,2-Dimethoxy-5,5-bis[(E)-2-phenylethenyl]-2,5-di-
hydrofuran-3,4-dicarboxylate (43c)
Pale yellow viscous liquid.
IR (neat): 3110, 2915, 2847, 1735, 1728, 1681, 1600, 1452, 1270,
1121, 980, 764, 703 cm–1.
1H NMR: = 7.41–7.21 (m, 10 H), 6.82 (d, J = 16 Hz, 2 H), 6.52
(d, J = 16 Hz, 2 H), 3.81 (s, 6 H), 3.51 (s, 6 H).
HRMS (EI): m/z Calcd for C25H26O7 [M+]: 438.1679. Found:
438.1671
13C NMR: = 162.5, 161.8, 142.1, 136.2, 134.8, 131.7, 130.1,
128.5, 128.2, 128.1, 127.5, 126.8, 126.4, 123.0, 87.9, 52.7, 52.6,
51.4.
Dimethyl 2-[(E)-2-(4-Chlorophenyl)ethenyl]-5,5-dimethoxy-2-
phenyl-2,5-dihydrofuran-3,4-dicarboxylate (41c)
Colorless viscous liquid.
HRMS (EI): m/z Calcd for C26H26O7 [M+]: 450.1678. Found:
450.1655.
IR (neat): 3015, 2948, 2840, 1735, 1667, 1492, 1324, 1263, 1175,
1020, 966, 845, 730 cm–1.
1H NMR: = 7.45–7.26 (m, 9 H), 6.88 (d, J = 16 Hz, 1 H), 6.75 (d,
Dimethyl 2,2-Dimethoxy-5,5-bis[(E)-2-(2-methylphenyl)ethe-
nyl]-2,5-dihydrofuran-3,4-dicarboxylate (43d)
Colorless viscous liquid.
J = 16 Hz, 1 H), 3.87 (s, 3 H), 3.76 (s, 3 H), 3.49 (s, 3 H), 3.32 (s, 3
H).
IR (neat): 3022, 2955, 2853, 1741, 1721, 1687, 1444, 1269, 1181,
1121, 993, 960, 797, 753 cm–1.
13C NMR: = 162.3, 162.1, 142.8, 140.1, 136.1, 135.7, 135.3,
134.6, 133.8, 128.4, 128.2, 127.0, 125.5, 123.1, 89.7, 52.7, 52.4,
51.2, 50.7.
1H NMR: = 7.45–7.13 (m, 8 H), 7.09 (d, J = 15.9 Hz, 2 H), 6.41
(d, J = 15.9 Hz, 2 H), 3.83 (s, 6 H), 3.37 (s, 6 H), 2.01 (s, 6 H).
Synthesis 2003, No. 9, 1446–1456 ISSN 1234-567-89 © Thieme Stuttgart · New York

SPECIAL TOPIC
Facile Synthesis of Dihydrofuran Derivatives
1455
13C NMR: = 162.3, 161.9, 142.8, 135.6, 135.4, 134.2, 130.2,
129.6, 128.9, 127.9, 126.0, 125.8, 123.0, 88.2, 52.5, 51.3, 19.7.
HRMS (EI): m/z Calcd for C28H30O7 [M+]: 478.1992. Found:
1H NMR: = 6.44 (d, J = 1.1 Hz, 1 H), 6.16 (d, J = 1.1 Hz, 1 H),
3.86 (s, 3 H), 3.70 (s, 3 H), 3.51 (s, 3 H), 3.47 (s, 3 H), 1.97 (d,
J = 1.1 Hz, 3 H), 1.91 (d, J = 1.1 Hz, 3 H).
13C NMR: = 185.23, 161.46, 160.82, 142.27, 138.78, 137.16,
136.48, 128.94, 123.81, 83.20, 52.84, 52.71, 51.50, 51.15, 18.32,
15.41.
478.1978
Dimethyl 2,2-Dimethoxy-5,5-bis{[(E)-2-(2-triflouromethyl)phe-
nyl]ethenyl}-2,5-dihydro-5,5-dimethoxyfuran-3,4-dicarboxy-
late (43e)
Anal. Calcd for C17H20O8: C, 57.95; H, 5.72. Found: C, 58.06; H,
5.58.
Colorless viscous liquid.
IR (neat): 3050, 2957, 2854, 1740, 1728, 1573, 1503, 1442, 1317,
1279, 1116, 981, 774 cm–1.
Spiro[naphthalene-1(2H)-4,4-dimethoxy-2,3-bis(methoxycar-
bonyl)furan]-8-one (47)
Yellow crystalline solid; mp 122–124 °C (CH2Cl2–hexane).
1H NMR: = 7.63–7.32 (m, 8 H), 7.26 (d, J = 15.8 Hz, 2 H), 6.53
(d, J = 15.8 Hz, 2 H), 3.85 (s, 6 H), 3.53 (s, 6 H).
13C NMR: = 162.2, 161.8, 141.1, 135.7, 135.4, 131.9, 131.7,
128.4, 128.0, 127.7, 127.6, 126.0, 125.8, 125.7, 125.7, 123.2, 122.3,
87.59, 52.6, 51.3.
HRMS (EI): m/z Calcd for C28H24F6O7 [M+]: 586.1426. Found:
586.1377
IR (KBr): 3061, 3018, 2955, 2843, 1741, 1729, 1671, 1594, 1426,
1288, 1251, 1113 cm–1.
1H NMR: = 8.12 (d, J = 7.8 Hz, 1 H), 7.67–7.46 (m, 3 H), 6.85 (d,
J = 10.1 Hz, 1 H), 6.51 (d, J = 10.1 Hz, 1 H), 3.90 (s, 3 H), 3.57 (s,
3 H), 3.53 (s, 3 H), 3.52 (s, 3 H).
13C NMR: = 183.3, 162.0, 160.1, 143.8, 140.5, 139.5, 138.1,
133.1, 130.9, 130.6, 129.1, 127.0, 126.6, 123.9, 81.6, 52.9, 52.4,
51.6, 51.1
Dimethyl 2,2-Bis[(E)-2-(3,4-dichlorophenyl)ethenyl]-5,5-
dimethoxy-2,5-dihydrofuran-3,4-dicarboxylate (43f)
Pale yellow viscous liquid.
Anal. Calcd for C19H18O8: C, 60.96; H, 4.85. Found C, 61.25; H,
5.17.
IR (neat): 3008, 2955, 2847, 1740, 1728, 1687, 1485, 1451, 1283,
1121, 1040, 993, 932, 797, 683 cm–1.
1H NMR: = 7.47–7.21 (m, 6 H), 6.73 (d, J = 15.9 Hz, 2 H), 6.52
(d, J = 15.9 Hz, 2 H), 3.86 (s, 6 H), 3.50 (s, 6 H).
Spiro[antharcene-1(2H)-4,4-dimethoxy-2,3-bis(methoxycarbo-
nyl)furan]-8-one (49)
Colorless crystalline solid; mp 136–137 °C (CH2Cl2–hexane).
IR (KBr): 3074, 2955, 2843, 1750, 1731, 1663, 1600, 1432, 1319,
1276, 1238, 1182, 1107, 1051 cm–1.
1H NMR: = 8.28 (d, J = 7.6 Hz, 2 H), 7.81 (d, J = 7.7 Hz, 2 H),
7.66 (uneven triplet, J1 = 7.8, J2 = 7.2 Hz, 2 H), 7.53 (uneven triplet,
J1 = 7.7, J2 = 7.2 Hz, 2 H), 3.92 (s, 3 H), 3.56 (s, 6 H) 3.38 (s, 3 H).
13C NMR: = 162.2, 161.4, 140.4, 136.1, 135.7, 132.7, 131.8,
130.4, 129.3, 129.1, 128.8, 128.4, 125.8, 123.1, 87.3, 52.7, 51.4.
HRMS (EI): m/z Calcd for C26H22Cl4O7 [M+]: 586.0120. Found:
586.0090.
Dimethyl 2,2-Dimethoxy-5-[(E)-2-(4-Methylphenyl)ethenyl]-5-
[(E)-2-phenylethenyl]-2,5-dihydrofuran-3,4-dicarboxylate
(43g)
13C NMR: = 182.9, 163.1, 160.3, 141.3, 140.1, 137.5, 133.6,
131.4, 129.2, 127.5, 127.2, 123.5, 83.1, 53.0, 52.4, 51.3.
Anal. Calcd for C23H20O8: C, 65.09; H, 4.75. Found: C, 65.46; H,
4.74.
Pale yellow viscous liquid.
IR (neat): 3043, 2989, 2948, 1742, 1721, 1681, 1445, 1276,
1121,1034, 933, 825, 764 cm–1.
1H NMR: = 7.40–7.08 (m, 8 H), 6.85–6.76 (m, 2 H), 6.76–6.43 (m,
2 H), 3.83 (s, 3 H), 3.80 (s, 3 H), 3.26 (s, 6 H), 2.31 (s, 3 H).
13C NMR: = 162.3, 161.7, 142.3, 137.8, 136.2, 134.6, 133.4,
131.6, 131.5, 129.1, 128.4, 127.5, 126.7, 126.6, 126.4, 122.9, 87.9,
52.4, 51.2, 21.1.
Dimethyl 7,9-Di(tert-butyl)-2,2-dimethoxy-10-oxa-1-ox-
ospiro[4.5]deca-3,6,8-triene-3,4-dicarboxylate (51) and Dimeth-
yl 6,8-Di(tert-butyl)-2,2-dimethoxy-10-oxa-1-oxospiro[4.5]deca-
3,6,8-triene-3,4-dicarboxylate (52)
Yellow amorphous solid.
IR (neat): 2962, 2915, 2881, 1796, 1742, 1694, 1452, 1351, 1290,
1222, 1054 cm–1.
Dimethyl 2,2-Dimethoxy-8-oxo-1-oxaspiro[4.5]deca-3,6,9-
triene-3,4-dicarboxylate (45a)
Colorless crystalline solid; mp 164–166 °C (CH2Cl2–hexane).
1H NMR: = 7.14 (d, J = 2.0 Hz, 0.66 H), 6.93 (d, J = 2.1 Hz, 0.66
H), 6.82 (d, J = 2.1 Hz, 0.33 H), 5.75 (d, J = 2.1 Hz, 0.33 H), 3.85
(s, 2 H), 3.74 (s, 1 H), 3.68 (s, 1 H), 3.66 (s, 2 H), 3.61 (s, 2 H), 3.58
(s, 1 H), 3.54 (s, 1 H), 3.46 (s, 2 H), 1.40 (s, 6 H), 1.28 (s, 6 H), 1.26
(s, 3 H), 1.16 (s, 3 H).
13C NMR: = 197.3, 163.7, 161.8, 155.2, 144.9, 126.4, 124.4,
122.0, 121.9, 117.6, 83.1, 77.4, 53.7, 52.9, 52.5, 52.4, 52.2, 51.8,
51.6, 51.4, 38.5, 37.2, 35.7, 35.3, 30.5, 28.4, 28.2, 27.9.
IR (KBr): 3055, 3005, 2949, 2837, 1743, 1727, 1673, 1632, 1444,
1394, 1332, 1276, 1119, 1034, 985, 760 cm–1.
1H NMR: = 6.69 (d, J = 9.9 Hz, 2 H), 6.32 (d, J = 9.9 Hz, 2 H),
3.88 (s, 3 H), 3.71 (s, 3 H), 3.48 (s, 6 H).
13C NMR: = 184.1, 161.6, 160.3, 143.7, 139.4, 138.4, 130.5,
123.8, 116.0, 80.0, 52.9, 52.7, 51.4.
Acknowledgments
Dimethyl 2,2-Dimethoxy-6,9-dimethyl-8-oxo-1-oxaspiro-
[4.5]deca-3,6,9-triene-3,4-dicarboxylate (45b)
Colorless crystalline solid;, mp 110–112 °C (CH2Cl2–hexane).
S.B thanks CSIR New Delhi for a research fellowship. Thanks are
also due to S. Viji and Saumini Mathew for providing NMR Spec-
tra, elemental analyses and High Resolution Mass Spectra.
IR (neat): 2955, 2849, 1744, 1727, 1681, 1645, 1438, 1326, 1263,
1113 cm–1.
Synthesis 2003, No. 9, 1446–1456 ISSN 1234-567-89 © Thieme Stuttgart · New York

1456
V. Nair et al.
SPECIAL TOPIC
(8) (a) Winterfeldt, E.; Dillinger, H. J. Chem. Ber. 1966, 99,
1558. (b) Nozaki, K.; Sato, N.; Ikeda, K.; Takaya, H. J. Org.
Chem. 1996, 61, 4516.
(9) Nair, V.; Nair, J. S.; Vinod, A. U. J. Chem. Soc., Perkin
Trans 1 1998, 3129.
(10) (a) Nair, V.; Vinod, A. U. Chem. Commun. 2000, 1019.
(b) Nair, V.; Vinod, A. U.; Nair, J. S.; Sreekanth, A. R.; Rath,
N. P. Tetrahedron Lett. 2000, 41, 6675. (c) Nair, V.; Vinod,
A. U.; Rajesh, C. J. Org. Chem. 2001, 66, 4427.
(11) Warkentin, J. J. Chem. Soc., Perkin Trans. 1 2000, 2161; and
references cited therein.
(12) Hoffmann, R. W.; Lilienblum, W.; Dittrich, B. Chem. Ber.
1974, 107, 3395.
(13) Lu, X.; Warkentin, J. Tetrahedron Lett. 1999, 40, 1483.
(14) Nair, V.; Bindu, S.; Balagopal, L. Tetrahedron Lett. 2001,
42, 2043.
(15) Couture, P.; Terlow, J. K.; Warkentin, J. J. Am. Chem. Soc.
1996, 118, 4214.
(16) Nair, V.; Bindu, S.; Sreekumar, V.; Chiaroni, A. Org. Lett.
2002, 4, 2821.
References
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Synthesis 2003, No. 9, 1446–1456 ISSN 1234-567-89 © Thieme Stuttgart · New York