Fused dihydrofurans from the one-pot, three-component reaction of 1,3-cyclohexanedione, iodobenzene diacetate and alkenes

Article abstract of DOI:10.1016/j.tet.2012.12.006

The one-pot, three-component reactions of substituted 1,3- cyclohexanediones, iodobenzene diacetate and alkenes, under photochemical activation, yields fused dihydrofuran derivatives in good yield via the in situ formation of iodonium ylides.

Full text of DOI:10.1016/j.tet.2012.12.006

Tetrahedron 69 (2013) 1566e1575
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Fused dihydrofurans from the one-pot, three-component reaction
of 1,3-cyclohexanedione, iodobenzene diacetate and alkenes
Dimitra Kalpogiannaki, Catherine-Irene Martini y, Aggeliki Nikopoulou y, John A. Nyxas,
y
*
Vassiliki Pantazi , Lazaros P. Hadjiarapoglou
Department of Chemistry, University of Ioannina, GR-45110 Ioannina, Greece
a r t i c l e i n f o
a b s t r a c t
Article history:
The one-pot, three-component reactions of substituted 1,3-cyclohexanediones, iodobenzene diacetate
and alkenes, under photochemical activation, yields fused dihydrofuran derivatives in good yield via the
in situ formation of iodonium ylides.
Received 12 September 2012
Received in revised form 12 November 2012
Accepted 3 December 2012
Available online 10 December 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
One-pot cycloaddition
1,3-Cyclohexanedione
Fused dihydrofuran
Iodonium ylide
Iodobenzene diacetate
1. Introduction
starting from terminal alkenes. It should be realized that the fused
cyclohexenone ring might be aromatized7 or appropriately modi-
The dihydrofuran moiety is a common structural feature of
numerous natural products with great biological and pharmaceu-
tical interest.1,2 Hence, many synthetic approaches have been re-
fied8 through established enolate methodology.
In order to extend the scope of this synthetic methodology, we
decided to explore the one-pot, three-component reaction, using
six-membered cyclic 1,3-diketones, iodobenzene diacetate and al-
kenes (Scheme 1). Since a catalyst is necessary for PhI(OAc)2 vicinal
oxygenation9 of alkenes, we anticipated that 1,3-cyclohexanedione
as a nucleophile could react with PhI(OAc)2 in a ligand exchange
ported, such as decomposition3 of diazo ketones or -elimination4
a
of dibromo ketones in the presence of olefinic trapping agents.
However, the search for new methodologies proceeding that are
efficient and involve readily available starting materials still re-
mains an active area of research.
The employment of iodonium ylides in this chemistry has
shown interesting complementary reactivity to that of diazo com-
pounds without the common major drawbacks. Because of the
hyper-leaving group ability of aryl-l
3-iodanyl groups, the reactivity
of iodonium ylides is higher than the corresponding diazo com-
pounds. This fact has allowed various cycloadditions5 to be per-
formed under milder conditions, with better yields, even leading to
the development of more enantioselective methods.
In the course of our studies focused on the development of new
synthetic applications of iodonium ylides,6 we recently disclosed6a
a
straightforward approach to fused dihydrofurans from in-
expensive alkenes and iodonium ylides. By following this synthetic
route, a large variety of fused dihydrofurans could be prepared
* Corresponding author. Tel.: þ30 26510 08380; fax: þ30 26510 08799; e-mail
address: lxatziar@uoi.gr (L.P. Hadjiarapoglou).
y
Scheme 1. One-pot synthesis of dihydrofuran 3aa.
Undergraduate Research Participants.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.12.006

D. Kalpogiannaki et al. / Tetrahedron 69 (2013) 1566e1575
1567
reaction yielding the corresponding iodonium salt 5a,10 which
subsequently might lose a molecule of acetic acid to give the stable
iodonium ylide 4a. Under photochemical activation the in situ
generated iodonium ylide should react with alkenes furnishing
fused dihydrofurans.
In this work, we report an efficient process for the synthesis of
fused dihydrofurans via a one-pot, three-component reaction of
1,3-cyclohexanedione derivatives, iodobenzene diacetate and
alkenes.
2. Results and discussion
In our initial study to test our hypothesis, the three-component
reaction of 1,3-cyclohexanedione (1a), iodobenzene diacetate and
styrene 2a was employed to develop appropriate reaction condi-
tions (Scheme 1). The best yield (66%) of dihydrofuran 3aa was
obtained when a CH2Cl2-solution of 1a, PhI(OAc)2 and 2a(excess)
was irradiated for 1 h at room temperature. Alternatively, stirring
a dichloromethane solution of 1a, and PhI(OAc)2 at room temper-
ature for 1 h, followed by addition of styrene 2a (excess) and irra-
diation for 1 h at room temperature yields dihydrofuran 3aa in 62%
yield. For comparison, a 67% yield of dihydrofuran 3aa was isolated
when a solution of iodonium ylide 4a and styrene 2a was irradiated
for 1 h at room temperature, while without irradiation, a 30% yield
of dihydrofuran 3aa was isolated after stirring at room temperature
for 30 d.
To gain more information about dihydrofuran formation the
reaction mixture of 1,3-cyclohexanedione and iodobenzene diac-
etate was analyzed by 1H NMR spectroscopy at 0 ꢀC and room
temperature (Fig. 1). The proton spectra of iodonium ylide 4a as
well as iodobenzene diacetate and 1,3-cyclohexanedione were
compared to determine their content in the reaction medium. It is
evident that iodonium ylide 4a was quickly generated at the be-
ginning of the reaction, presumably the initially-formed iodonium
salt 5 is rather unstable at ambient temperature. Evaporation of the
solvent under reduced pressure and trituration of the residue with
hexane, yields iodonium ylide 4a quantitatively.
Fig. 1. (a) 1H NMR spectrum of 1,3-cyclohexanedione 1a; (b) 1H NMR spectrum of
iodobenzene diacetate; (c) 1H NMR spectrum of the reaction mixture of 1,3-
cyclohexanedione 1a and iodobenzene diacetate at 0 ꢀC; (d) 1H NMR spectrum of
the reaction mixture of 1,3-cyclohexanedione 1a and iodobenzene diacetate at 20 ꢀC;
(e) 1H NMR spectrum of iodonium ylide 4a.
To further demonstrate the potential application of this one-pot,
three-component reaction, additional reactions of other substituted
1,3-cyclohexanediones 1 with styrene 2a were next investigated. The
reactions proceed at room temperature under photochemical acti-
vation within 60 min in moderate to good yields (Table 1). For ex-
ample, a CH2Cl2-solution of 5-methyl-1,3-cyclohexanedione 1b,
iodobenzene diacetate and styrene 2a was irradiated for 1 h at room
temperature. The solvent was subsequently evaporated and the
residue was flash chromatographed on silica gel to afford dihy-
drofuran 3ba11 in 45% yield (entry 1, Table 1). Under similar condi-
tions, 5-phenyl-1,3-cyclohexanedione (1c), 5-(p-methoxyphenyl)-
1,3-cyclohexanedione (1d) and 5,5-dimethyl-1,3-cyclohexanedione
(1e), were converted to the corresponding dihydrofuran derivatives
3baefa11(entries 2e5, Table 1). There is a comparison of the in situ
procedure (method A) with the results obtained from the reaction of
styrene 2a with the corresponding iodonium ylides 4 under photo-
chemical activation (method B). In general, the yields of dihy-
drofuran derivatives are similar in both methods.
Table 1
One-pot, three-component reactionsa of 1,3-cyclohexanediones 1 with styrene 2a
Entry Cyclohexanedione R1
R2
H
Method Product Yieldb (%)
1
1a
H
A
B
C
D
A
B
A
B
A
B
A
B
3aa
66
67
62
30
55
59
55
56
57
60
83
85
2
3
4
5
1b
1c
1d
1e
CH3
H
3ba
3ca
3da
3ea
It had been reported,12 that dihydrofuran 3ea was isolated in
71% yield by stirring a mixture of dimedone 1e, PhI(OAc)2 and
styrene 2a at 0 ꢀC for 1.5 h. When this procedure was repeated for
1,3-cyclohexadione 1a and dimedone 1e, dihydrofurans 3aa or 3ea
were not detected in the crude reaction mixture; instead the cor-
responding iodonium ylides 4 were isolated quantitatively.
Several other acyclic dicarbonyl compounds were investigated;
however, the results indicated that methyl acetoacetate and di-
methyl malonate were not suitable for this reaction. On the other
hand, when a dichloromethane solution of 2,2-dimethyl-1,3-dioxa-
4,6-cyclohexanedione (1f), iodobenzene diacetate and styrene 2a
C6H5
H
p-CH3C6H4
CH3
H
CH3
a
Reaction conditions: 1 (0.96e1.96 mmol), PhI(OAc)2 (0.99e1.99 mmol), 2a
(method A); (0.99e4.14 mmol), 2a
(4.81e14.42 mmol), CH2Cl2 or CH3CN(10 mL), h (method B); 1 (1 mmol), PhI(OAc)2
(1 mmol), CH2Cl2 (10 mL), rt, 45 min, than 2a (4.81 mmol), h , 45 min (method C); 4
(4.81e9.62 mmol), CH2Cl2 (10 mL),
h
n
4
n
n
(2.0 mmol), 2a (9.62 mmol), CH3CN(10 mL), rt, 30 d (method D).
b
Isolated yield.

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D. Kalpogiannaki et al. / Tetrahedron 69 (2013) 1566e1575
was irradiated for 2 h at room temperature, cyclopropane 613 was
isolated in 48% yield (Scheme 2). Cyclopropane 6 is the typical
product of the metal- or photochemically catalyzed cycloaddition
of the corresponding iodonium ylide with styrene 2a. It is well
To explore the generality and scope of this tandem reaction,
a range of alkenes 2 and 1,3-cyclohexanedione 1a were surveyed
(Table 2). A wide range of acyclic as well as cyclic alkenes can ef-
fectively participate in the reaction with good yields. There is
a comparison of the in situ procedure (method A) with the results
obtained from the reaction of alkenes 2 with iodonium ylides 4a
under photochemical activation (method B). The yields are rather
similar in both examined methods.
It is worth mentioning that the reaction exhibits high regiose-
lectivity. The carbonyl oxygen of the 1,3-cyclohexanedione 1a
added exclusively onto the more substituted carbon of the double
bond, i.e., terminal alkenes afforded 2-substituted dihydrofuran
exclusively, the other possible regioisomer was not detected at all.
For example, ethyl vinyl acetate 2b and vinyl acetate 2c afforded 2-
ethoxy- and 2-acetoxy-2,3-dihydrofuran derivatives 3ab,ac,8c re-
spectively (entries 1,2 of Table 2). The lower yields of the one-pot,
three-component reaction (method A) when compared to the
corresponding cycloaddition of iodonium ylide 4a (method B)
should arise from the small excess of alkenes 2b,c employed (13.9
or 11.6 mmol vs 10 mL). Phenylthioethylene 2d reacts also via the
known that the acidity of cyclic six-membered
b-diketones is
around pKa 5, putting it close to acetic acid, while their acyclic
analogues are less acidic. This acidity of the 1,3-diketone seems to
play an important role in this tandem reaction, especially for the in
situ formation of the iodonium ylide. The acetoxylation of acyclic
1,3-diketones under the influence of iodobenzene diacetate is
a well-known procedure.14
Scheme 2. One-pot synthesis of cyclopropane 6.
Table 2
Cycloadditionsa of 1,3-cyclohexanedione 1a with alkenes 2
Entry
1
Alkene
Method
A
Product
Yieldb (%)
60
B
A
B
A
B
A
B
86
45
81
67
71
51
64
2
3
4
5
6
A
B
66
61
A
B
68
56
7
A
B
83c
77c

D. Kalpogiannaki et al. / Tetrahedron 69 (2013) 1566e1575
1569
Table 2 (continued )
Entry
Alkene
Method
A
Product
Yieldb (%)
8
34
39
B
9
A
B
71
68
10
A
B
55
50
A
B
59
55
11
a
Reaction conditions: 1 (1.00e2.00 mmol), PhI(OAc)2 (1.00e2.00 mmol), 2 (4.05e14.71 mmol), CH2Cl2 (10 mL), hn (method A); 4 (1.00e6.37 mmol), 2 (4.00e130 mmol),
CH2Cl2 or CH3CN(10 mL), h
n
(method A).
b
Isolated yield.
c
E/Z ratio¼60:40.
one-pot, three-component reaction with 1,3-cyclohexanedione 1a
yielding dihydrofuran 3ad15 in 67% yield (entry 3, Table 2). Under
cycloadducts were unambiguously identified with IR, 1H and 13C
NMR spectroscopy and HRMS spectra. All the cycloadducts 3
exhibited IR absorptions at 1628e1694 cmꢁ1 due to the charac-
similar reaction conditions,
a-methylstyrene 2e and 1,1-
diphenylethylene 2f yielded 2-methyl-2-phenyl- and 2,2-
diphenyl-2,3-dihydrofuran derivatives 3ae,af, respectively (entries
4,5 of Table 2).
teristic feature of
tional group. All the cycloadducts 3 showed 13C resonance at about
194e196 ppm revealing the presence of a six-membered
unsaturated carbonyl group. Furthermore, the -carbon atom of the
enone moiety was found to be present at 175e178 ppm.
a,b-unsaturated six-membered carbonyl func-
d
a,b-
Reactions of (E)- and (Z)-anethole 2g with 1,3-cyclohexanedione
1a were carried out to examine the stereochemistry of this tandem
reaction. From both alkenes, (E)-2-(p-methoxyphenyl)-3-methyl-4-
oxo-2,3,4,5,6,7-hexahydrobenzo[b]furan (3ag) was obtained, in-
dicating that the reaction proceeded in a non-stereospecific way
(entry 6, Table 2). Such a trans stereochemistry is a common
structural moiety present in many neolignan natural products.16 In
a similar fashion, the reaction of 1,3-cyclohexanedione 1a with 1-
(phenylthio)-1-propene 2h (ratio E/Z¼50:50) yields 2-(phenyl-
thio)-3-methyl-4-oxo-2,3,4,5,6,7-hexahydrobenzo[b]furan 3ah11,17
in 83% yield (entry 7, Table 2). The reaction was regioselective,
but a mixture of stereoisomers was formed in a ratio of E/Z¼60:40.
It is known that both isomers can be converted into fur-
anoterpenoids by oxidation followed by elimination.18
b
d
The observed selectivities have literature precedent. The stereo-
and regio-selectivities of the dihydrofurans 3 determined by 2-D
NMR studies, is exemplified for cycloadducts 3ad, 3ag, 3ak. The
1H NMR spectrum of 3ad displays signals at
d 7.54e7.52 (m, 2H),
7.35e7.32 (m, 3H), 6.09 (dd, J¼9.9, 6.0 Hz, 1H), 3.28 (dd, J¼15.7,
9.9 Hz, 1H), 2.83 (dd, J¼15.7, 6.0 Hz, 1H), 2.46e2.43 (m, 2H),
2.33e2.30 (m, 2H), 2.06e2.09 (m, 2H) attributable only to dihy-
drofuran structure 3ad. The H-2 and 3-CH2 hydrogens, related by
H,H-COSY correlation, appeared as double doublets at 6.09 (J¼9.9,
6.0 Hz), 3.28 (J¼15.7, 9.9 Hz) and 2.83 ppm (J¼15.7, 6.0 Hz), re-
spectively. The double doublet signal at
d 6.09 showed a C,H-COSY
correlation with the carbon signal at 91.0 ppm and HMBCs (Fig. 2)
d
Cyclic alkenes can effectively participate in this tandem cyclo-
addition. cis-2,3-Dihydrofuran 3ai was obtained, as a single isomer,
in 34% yield, when cyclopentane 2i was allowed to undergo re-
action with 1,3-cyclohexanedione 1a and iodobenzene diacetate
under photochemical activation (entry 8, Table 2). The reaction
with 2,3-dihydrofuran 2j was also considered. The one-pot, three-
component cycloaddition of 1,3-cyclohexanedione 1a, iodobenzene
diacetate and dihydrofuran 2j gives the fused dihydrofuran cyclo-
adduct 3aj,3c,19 as a single diastereomer in 71% yield (entry 9, Table
2). Indene 2k, is also compatible for this reaction. Fused dihy-
drofuran 3ak was isolated in 55% yield, as a single diastereomer,
when a dichloromethane solution of 1,3-cyclohexanedione 1a,
iodobenzene diacetate and indene 2k was irradiated at room
temperature (entry 10, Table 2). Similarly, acenaphthylene 2l was
reacted with 1,3-cyclohexanedione 1a and iodobenzene diacetate
under photochemical activation to afford cycloadduct 3al, as a sin-
gle diastereomer, in 59% yield (entry 11, Table 2).Structures of all
Fig. 2. Chemical shifts and selected HMBCs in 3ad.

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D. Kalpogiannaki et al. / Tetrahedron 69 (2013) 1566e1575
with C-7a at 175.8, C-3a at 113.2 ppm. Both double doublet signals
at 3.28 and 2.83 ppm showed C,H-COSY correlation with the same
carbon signal at 32.9 ppm, thus the large gem-coupling constant
(J¼15.7 Hz). The other coupling constants J¼9.9 and J¼6.0 Hz shows
the cis and trans relation, respectively.17 These signals showed
HMBCs with C-7a at 175.8 and C-3a at 113.2 ppm. The 6-CH2 hy-
carbene 8. Direct 1,3-dipolar cycloaddition of dipole 9 yields dihy-
drofuran 3aa (path B). The third possible route (path C) involves the
initial formation of cyclopropane 10. This stable cyclopropane was
completely rearranged21 into dihydrofuran 3aa under the same
reaction conditions.
d
d
drogens appearing as a multiplet at
H,H-COSY correlation with the multiplet signals at
d
2.06e2.09 ppm are related by
2.46e2.43 and
d
2.33e2.30 ppm enabling its assignment to the C-6 position. This
multiplet is related by C,H-COSY correlation with the carbon signal
at
at 175.8 and C-4 at 194.8 ppm. The 7-CH2 hydrogens appeared as
a multiplet at 2.46e2.43 ppm, and is related by C,H-COSY corre-
lation with the carbon signal at 23.8 ppm and showed HMBCs
with C-6 at 21.4, C-5 at 36.2, C-3a at 113.2 and C-7a at 175.8 ppm.
The 5-CH2 hydrogens appeared as a multiplet at 2.33e2.30 ppm,
is related by C,H-COSY correlation with the carbon signal at
36.2 ppm and showed HMBCs with C-6 at 21.4, C-7 at 23.8, C-3a at
d 21.4 ppm and showed HMBCs with C-7 at 23.8, C-5 at 36.2, C-7a
d
d
d
d
113.2 and C-4 at 194.8 ppm.
The stereochemistry of cycloadduct 3ag was clearly assigned as
trans since the coupling constant (J¼7.0 Hz) between C-2 and C-3
hydrogens compared more favourably with the trans coupling
constant of 6.0 Hz than cis coupling constant of 9.9 Hz. The exis-
tence of NOESY signals between the C-3 hydrogen with the ortho-
hydrogens of the aryl group at C-2 position clearly indicates the
trans configuration in the dihydrofuran ring.
The stereochemistry between C-2 and C-3 hydrogens of cyclo-
adduct 3ak was clearly assigned as cis since the coupling constant
(J¼8.9 Hz) compared more favourably with the cis coupling con-
stant of 9.9 Hz than trans coupling constant of 6.0 Hz. The C-2 hy-
drogen appeared as doublet (J¼8.9 Hz) showed C,H-COSY
correlation with the carbon signal at
d 93.2 ppm, and is related by
H,H-COSY correlation only with the C-3 hydrogen (Fig. 3). The C-3
hydrogen appeared as a multiplet at 4.01e3.94 and showed C,H-
COSY correlation with the carbon signal at 41.7 ppm and is related
d
d
by H,H-COSY correlation with the C-2 hydrogen and the five-
membered methylene hydrogens. The latter appeared as double
doublets at
d
3.31 (J¼17.1, 8.3 Hz) and 3.13 (J¼17.1, 2.3 Hz) showed
C,H-COSY correlation with the carbon signal at d 37.3 ppm and is
related by H,H-COSY correlation only with the C-3 hydrogen.
Scheme 3. A speculative but plausible mechanism.
3. Conclusion
In summary, we have developed a simple efficient protocol for
the synthesis of substituted fused dihydrofurans. This reaction is
performed using inexpensive starting materials in a safe reaction
medium. The regioselectivity is extremely high, only one regio-
siomer is obtained. This tandem cycloaddition exhibited wide
generality: a series of substituted alkenes reacted with 1,3-
cyclohexanedione to generate fused dihydrofurans with good
yields.
Fig. 3. Key H,H-COSY correlation in 3ak.
The speculative but plausible reaction mechanism in Scheme 3
is proposed to rationalize this one-pot multicomponent reaction.
It is reasonable to assume20 that the first step of this one-pot, three-
component reaction occurs via the initial nucleophilic substitution
on the tricoordinate iodine of iodobenzene diacetate by 1,3-
cyclohexanedione 1a to give iodonium salt 5a as the first in-
termediate. Since the reaction takes place at room temperature, the
unstable iodonium salt 5a subsequently loses a molecule of acetic
acid under the influence of heat to give the stable iodonium ylide
4a, which is the actual reaction intermediate of the dihydrofuran-
forming reaction. The cycloaddition reaction between the iodo-
nium ylide 4a with the various alkenes, i.e., styrene 2a, might
proceeds via the zwitterionic intermediate 7, generated directly by
electrophilic attack of the iodonium ylide 4a on styrene 2a. The ring
closure and subsequent iodobenzene extrusion affords the ob-
served dihydrofuran 3aa (path A). Under photochemical activation,
iodonium ylide 4a might lose iodobenzene serving as a source of
4. Experimental section
4.1. General experimental details
All commercial reagents and solvents were used without further
purification. TLC analysis was performed on Merck silica gel 60 F254
plates. The spots were visualized either by UV irradiation (254 nm)
or KMnO4. Silica gel (0.040e0.063 mm) from Merck was used for
flash column chromatography. 1H and 13C NMR, as well as DEPT-135
experiments, were recorded on Bruker Avance AV250 and AV500
instruments. The residual solvent protons (1H) or the solvent car-
bon atoms (13C) were used as internal standards. The 1H NMR

D. Kalpogiannaki et al. / Tetrahedron 69 (2013) 1566e1575
1571
spectroscopic data are presented as follows: chemical shift in parts
per million relative to tetramethylsilane (multiplicity, coupling
constant, integration). The following abbreviations are used: s,
singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublets;
ddd, doublet of doublet of doublets; m, multiplet. High resolution
mass spectra were determined using ES ionization techniques on
a Thermo LTQ Orbitrap XL instrument. IR spectra were recorded
with a PerkineElmer Spectrum BX spectrophotometer. Melting
points (uncorrected) were determined on a Buchi B-510 apparatus.
The photochemical reactions were performed by using solutions in
heavy-duty wall test tubes immersed in water at room temperature
(external cooling) in a reactor cage fitted with a naked 250W Philips
5H), 7.31e7.25 (m, 5H), 5.86e5.78 (m, 1H), 3.57e3.44 (m, 1H),
3.41e3.27 (m, 1H), 3.00e2.88 (m, 1H), 2.79e2.72 (m, 2H), 2.69e2.65
(m, 2H). dC (62.5 MHz, CDCl3) 194.17, 194.12, 176.64, 176.61, 142.45,
142.42, 140.39, 140.27, 128.77, 128.58, 128.53, 127.08, 126.71, 126.69,
125.92, 125.76, 113.00, 112.79, 87.01, 86.74, 43.77, 43.68, 40.36, 40.25,
33.79, 33.76, 31.46, 31.43. HRMS (ESI-TOF): MHþ, found 291.1381;
C20H19O2 requires 291.1380.
4.2.4. 6-(4-Methoxyphenyl)-2-phenyl-2,3,6,7-tetrahydrobenzofuran-
4(5H)-one (3da). From 5-(4-methoxyphenyl)-1,3-cyclohexanedione
(1d) (0.22 g, 1.01 mmol), iodobenzene diacetate (0.32 g,
0.99 mmol) and styrene 2a (0.5 g, 4.81 mmol) in dichloromethane
(10 mL), irradiated for 60 min. Purification by flash chromatography
(dichloromethane/ethyl acetate 9:1) gave 6-(4-methoxyphenyl)-2-
phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3da) (0.19 g, 59%
yield) as white crystals (racemic mixture); Rf (CH2Cl2) 0.067; mp
165e167 ꢀC (MeOH). nmax (KBr) 3032, 2949, 1632, 1512, 1400, 1248,
HPL-N250WE40 HG lamp from
a
10 cm distance. 1,3-
Cyclohexanedione 2b,22 2c,23 2d,23 phenylthioethylene 2d24 and
1-(phenylthio)-1-propene (2g)25 were synthesized following the
literature procedures.
4.2. General procedure for the one-pot, three-component
synthesis of dihydrofurans 3
1034, 831, 702 cmꢁ1
. dH (250 MHz, CDCl3) 7.41e7.31 (m, 5H), 7.20 and
6.90 (AA0BB0 system, 4H), 5.85e5.76 (m, 1H), 3.80 (s, 3H), 3.51e3.27
(m, 2H), 2.98e2.87 (m, 1H), 2.83e2.54 (m, 4H). dC (62.5 MHz, CDCl3)
194.13, 194.08, 176.52, 176.48, 158.50, 140.47, 140.34, 134.62, 134.59,
128.75, 128.53, 128.49, 127.66, 127.63, 125.89, 125.73, 114.09, 112.96,
112.76, 86.92, 86.65, 55.21, 44.09, 44.02, 39.62, 39.50, 33.81, 31.73,
31.71. HRMS (ESI-TOF): MHþ, found 321.1473. C21H21O3 requires
321.1485.
A solution of 1,3-cyclohexanedione 1 (1.00e2.00 mmol), iodo-
benzene
diacetate
(1.00e2.00
mmol) and
alkene
2
(4.05e14.71 mmol) in dichloromethane (10 mL) was irradiated
(250 W) at room temperature for 40e360 min. The solvent was
evaporated under reduced pressure, and the residue was purified
by flash chromatography to afford fused dihydrofuran 3.
4.2.5. 6,6-Dimethyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-
one (3ea). From 5,5-dimethyl-1,3-cyclohexanedione (1e) (0.14 g,
1.00 mmol), iodobenzene diacetate (0.32 g, 0.99 mmol) and styrene
2a (0.5 g, 4.81 mmol) in dichloromethane (10 mL), irradiated for
60 min. Purification by flash chromatography (dichloromethane/
4.2.1. 2-Phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3aa). From
1,3-cyclohexanedione (1a) (0.22 g, 1.96 mmol), iodobenzene diac-
etate (0.64 g, 1.99 mmol) and styrene 2a (1.0 g, 9.62 mmol) in
dichloromethane (10 mL), irradiated for 60 min. Purification by flash
chromatography (dichloromethane/ethyl acetate 4:1) gave 2-
phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3aa) (0.28 g, 66%
yield) as a colourless oil; Rf (CH2Cl2) 0.05; nmax (liquid film) 3052,
ethyl
acetate
9:1)
gave
6,6-dimethyl-2-phenyl-2,3,6,7-
tetrahydrobenzofuran-4(5H)-one (3ea) (0.20 g, 83% yield) as a col-
ourless oil; Rf (20% EtOAc/CH2Cl2) 0.40; nmax (liquid film) 3030,
2947, 1632, 1400, 1230, 1180, 1061, 760, 702 cmꢁ1
.
dH (250 MHz,
2961, 1635, 1404, 1216, 1041, 762, 703 cmꢁ1
. dH (250 MHz, CDCl3)
CDCl3) 7.39e7.26 (m, 5H), 5.72 (dd, J¼10.5, 8.0 Hz, 1H), 3.31e3.20 (m,
1H), 2.89e2.79 (m, 1H), 2.50e2.44 (m, 2H), 2.38e2.33 (m, 2H), 2.05
(dd, J¼12.7, 6.4 Hz, 2H). dC (62.5 MHz, CDCl3) 194.4, 176.4, 140.0,
127.9, 127.6, 125.0, 112.0, 85.3, 35.7, 33.3, 23.0, 20.9. HRMS (ESI-TOF):
MNaþ, found 237.0884. C14H14O2Na requires 237.0887.
7.39e7.27 (m, 5H), 5.75 (dd, J¼10.5, 7.8 Hz, 1H), 3.32e3.22 (m, 1H),
2.90e2.80 (m, 1H), 2.35 (s, 2H), 2.25 (s, 2H), 1.12 (s, 6H). dC
(62.5 MHz, CDCl3) 194.7, 176.1, 140.6, 128.6, 128.3, 125.6, 111.2, 86.4,
50.8, 37.6, 34.0, 33.7, 28.7, 28.4. HRMS (ESI-TOF): MHþ, found
243.1380. C16H19O2 requires 243.1380.
4.2.2. 6-Methyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3ba). From 5-methyl-1,3-cyclohexanedione (1b) (0.12 g,1.07 mmol),
iodobenzene diacetate (0.32 g, 0.99 mmol) and styrene 2a (0.5 g,
4.81 mmol) in dichloromethane (10 mL), irradiated for 60 min. Pu-
rification by flash chromatography (dichloromethane/ethyl acetate
9:1) gave 6-methyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-
one (3ba)11 (0.10 g, 45% yield) as a colourless oil (racemic mixture); Rf
(20% EtOAc/CH2Cl2) 0.45; nmax (liquid film) 2958, 1634, 1402, 1212,
4.2.6. 2-Ethoxy-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3ab). From
1,3-cyclohexanedione (1a) (0.22 g, 1.96 mmol), iodobenzene diac-
etate (0.64 g, 1.99 mmol) and ethyl vinyl ether 2b (1.0 g, 13.90 mmol)
in dichloromethane (10 mL), irradiated for 60 min. Purification by
flash chromatography (dichloromethane/ethyl acetate 4:1) gave 2-
ethoxy-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3ab) (0.21 g, 60%
yield) as a colourless oil; Rf (Et2O) 0.28; nmax (liquid film) 3056, 2976,
1634,1406,1376,1178, 1112, 900, 736 cmꢁ1
. dH (250 MHz, CDCl3) 5.52
1052, 736, 700 cmꢁ1
.
dH (250 MHz, CDCl3) 7.39e7.26 (m, 5H),
(dd, J¼7.3, 3.4 Hz, 1H), 3.68 (ddd, J¼14.2, 9.5, 7.1 Hz, 1H), 3.43 (ddd,
J¼14.2, 9.5, 7.1 Hz, 1H), 2.74e2.64 (m, 1H), 2.47e2.38 (m, 1H),
2.29e2.24 (m, 2H), 2.15e2.10 (m, 2H), 1.95e1.73 (m, 2H), 1.03 (t,
J¼7.1 Hz, 3H). dC (62.5 MHz, CDCl3) 194.6, 175.2, 111.8, 108.0, 64.5,
35.9, 32.3, 23.4, 21.1, 14.5. HRMS (ESI-TOF): MHþ, found 183.1009.
C10H15O3 requires 183.1016.
5.78e5.70 (m, 1H), 3.29e3.19 (m, 1H), 2.89e2.79 (m, 1H), 2.59e2.52
(m, 1H), 2.47e2.27 (m, 2H), 2.22e2.09 (m, 2H), 1.12 (d, J¼6.2 Hz, 3H).
dC (62.5 MHz, CDCl3) 195.09, 195.05, 176.93, 140.54, 140.44, 128.64,
128.36, 128.34, 125.74, 125.63, 112.52, 112.35, 86.58, 86.34, 44.83,
33.76, 31.80, 29.81, 29.64, 20.90, 20.86. HRMS (ESI-TOF): MHþ, found
229.1223. C15H17O2 requires 229.1223.
4.2.7. 2-Acetoxy-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3ac). From
1,3-cyclohexanedione (1a) (0.22 g, 1.96 mmol), iodobenzene diac-
etate (0.64 g, 1.99 mmol) and vinyl acetate 2c (1.0 g, 11.60 mmol) in
dichloromethane (10 mL), irradiated for 60 min. Purification by flash
chromatography (dichloromethane/ethyl acetate 9:1) gave 2-
acetoxy-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3ac)8c (0.17 g,
45% yield) as a colourless oil; Rf (CH2Cl2) 0.03; nmax (liquid film) 2952,
4.2.3. 2,6-Diphenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3ca). From 5-phenyl-1,3-cyclohexanedione (1c) (0.18 g, 0.96 mmol),
iodobenzene diacetate (0.32 g, 0.99 mmol) and styrene 2a (0.5 g,
4.81 mmol) in dichloromethane (10 mL), irradiated for 60 min. Pu-
rification by flash chromatography (dichloromethane/ethyl acetate
9:1) gave 2,6-diphenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3ca) (0.15 g, 55% yield), as white crystals (racemic mixture); Rf (20%
Et2OAc/CH2Cl2) 0.50; mp 134e136 ꢀC (EtOH). nmax (KBr) 3030, 1634,
1760, 1636, 1428,1406, 1380, 1266, 1240,1216, 1166, 936, 736 cmꢁ1
. dH
(250 MHz, CDCl3) 6.69 (dd, J¼7.5, 2.6 Hz, 1H), 3.08e2.96 (m, 1H),
1404, 1208, 910, 734, 700 cmꢁ1
. dH (250 MHz, CDCl3) 7.45e7.34 (m,
2.80e2.71 (m, 1H), 2.49e2.43 (m, 2H), 2.36e2.31 (m, 2H), 2.08 (s,

1572
D. Kalpogiannaki et al. / Tetrahedron 69 (2013) 1566e1575
3H), 2.09e1.98 (m, 2H). dC (62.5 MHz, CDCl3) 195.1,175.3, 169.4, 112.2,
98.5, 36.3, 31.9, 23.4, 21.4, 20.8. HRMS (ESI-TOF): MHþ, found
197.0815. C10H13O4 requires 197.0808.
(phenylthio)-1-propene (2h) (1.0 g, 6.67 mmol) in dichloromethane
(10 mL), irradiated for 120 min. Purification by flash chromatog-
raphy (eluant: dichloromethane/ethyl acetate 9:1) gave (E)-2-
(phenylthio)-3-methyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(E-3ah)17 (0.26 g, 50% yield) as a colourless oil; Rf (20% EtOAc/
CH2Cl2) 0.56; nmax (liquid film) 3055, 2955, 1637, 1400, 1225, 1180,
4.2.8. 2-Phenylthio-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3ad). From 1,3-cyclohexanedione (1a) (0.22 g, 1.96 mmol), iodo-
benzene diacetate (0.64 g, 1.99 mmol) and phenylthio-ethylene 2d
(1.0 g, 7.35 mmol) in dichloromethane (10 mL), irradiated for 60 min.
Purification by flash chromatography (dichloromethane/ethyl ace-
tate 9:1) gave 2-phenylthio-2,3,6,7-tetrahydrobenzofuran-4(5H)-
one (3ad)15 (0.32 g, 67% yield) as a colourless oil; Rf (20% EtOAc/
CH2Cl2) 0.37; nmax (liquid film) 3060, 2946, 1642, 1398, 1222, 1182,
900, 739 cmꢁ1
. dH (250 MHz, CDCl3) 7.52e7.46 (m, 2H), 7.39e7.29
(m, 3H), 5.54 (d, J¼5.4 Hz, 1H), 3.23e3.17 (m, 1H), 2.48e2.40 (m,
2H), 2.35e2.26 (m, 2H), 2.07e1.97 (m, 2H), 1.30 (d, J¼6.8 Hz, 3H).
dC (62.5 MHz, CDCl3) 195.5, 175.9, 132.8, 131.9, 129.0, 128.0, 117.9,
98.1, 41.4, 36.4, 24.0, 21.5, 18.7. HRMS (ESI-TOF): MHþ, found
261.0949. C15H17O2S requires 261.0944 and (E)-2-(phenylthio)-3-
methyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (Z-3ah)17 (0.17 g,
33% yield) as a colourless oil; Rf (20% EtOAc/CH2Cl2) 0.53; nmax
(liquid film) 3057, 2949, 1634, 1396, 1379, 1223, 1180, 1136, 903,
900, 872, 740 cmꢁ1
. dH (250 MHz, CDCl3) 7.54e7.52 (m, 2H),
7.35e7.32 (m, 3H), 6.09 (dd, J¼9.9, 6.0 Hz, 1H), 3.28 (dd, J¼15.7,
9.9 Hz, 1H), 2.83 (dd, J¼15.7, 6.0 Hz, 1H), 2.46e2.43 (m, 2H),
2.33e2.30 (m, 2H), 2.06e2.09 (m, 2H). dC (62.5 MHz, CDCl3) 194.8,
175.8, 132.5, 132.1, 129.0, 128.1, 113.2, 91.0, 36.2, 32.9, 23.8, 21.4.
HRMS (ESI-TOF): MHþ, found 247.0786. C14H15O2S requires 247.0787.
739 cmꢁ1
. dH (250 MHz, CDCl3) 7.51e7.49 (m, 2H), 7.39e7.29 (m,
3H), 6.09 (d, J¼9.0 Hz, 1H), 3.64e3.52 (m, 1H), 2.51e2.42 (m, 2H),
2.38e2.29 (m, 2H), 2.09e1.99 (m, 2H), 1.37 (d, J¼7.0 Hz, 3H). dC
(62.5 MHz, CDCl3) 195.0, 175.7, 133.8, 131.3, 129.0, 127.6, 118.0, 97.2,
38.2, 36.7, 23.8, 21.5, 14.4. HRMS (ESI-TOF): MHþ, found 261.0945.
C15H17O2S requires 261.0944.
4.2.9. 2-Methyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3ae). From 1,3-cyclohexanedione (1a) (0.22 g, 1.96 mmol), iodo-
benzene diacetate (0.64 g,1.99 mmol) and a-methylstyrene 2e (1.0 g,
8.47 mmol) in dichloromethane (10 mL), irradiated for 40 min. Pu-
rification by flash chromatography (dichloromethane/ethyl acetate
9:1) gave 2-methyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-
one (3ae) (0.23 g, 51% yield) as a colourless oil; Rf (10% EtOAc/CH2Cl2)
0.36; nmax (liquid film) 3058, 2946,1636,1402,1372,1252,1184,1000,
4.2.13. 1,2,3,3a,5,6,7,8b-Octahydro-8H-cyclopenta[b]benzo-furan-8-
one (3ai). From 1,3-cyclohexanedione (1a) (0.22 g, 1.96 mmol),
iodobenzene diacetate (0.64 g, 1.99 mmol) and cyclopentene 2i
(1.0 g, 14.71 mmol) in dichloromethane (10 mL), irradiated for
30 min. Purification by flash chromatography (dichloromethane/
ethyl acetate 4:1) gave 1,2,3,3a,5,6,7,8b-octahydro-8H-cyclo-
penta[b]benzofuran-4(5H)-one (3ai)(0.12 g, 34% yield) as a col-
ourless oil; Rf (20% EtOAc/CH2Cl2) 0.43; nmax (liquid film) 2950,
736 cmꢁ1
. dH (250 MHz, CDCl3) 7.35e7.22 (m, 5H), 3.10e2.95 (m, 2H),
2.51e2.43 (m, 2H), 2.35e2.30 (m, 2H), 2.07e1.96 (m, 2H), 1.69 (s,
3H). dC (62.5 MHz, CDCl3) 195.0, 175.4, 145.1, 128.0, 127.0, 123.7,
112.01, 92.0, 40.2, 36.0, 29.2, 23.6, 21.2. HRMS (ESI-TOF): MHþ, found
229.1213. C15H17O2 requires 229.1223.
1634, 1404, 1240, 1180, 1138, 1000, 946, 922 cmꢁ1
. dH (250 MHz,
CDCl3) 5.13 (dd, J¼7.5, 5.8 Hz, 1H), 3.52e3.47 (m, 1H), 2.35e2.29
(m, 2H), 2.25e2.20 (m, 2H), 1.97e1.89 (m, 3H), 1.79e1.72 (m,
1H), 1.66e1.55 (m, 3H), 1.41e1.28 (m, 1H). dC (62.5 MHz, CDCl3)
195.4, 178.1, 115.8, 91.6, 43.4, 36.4, 34.8, 31.6, 23.7, 22.9, 21.6.
HRMS (ESI-TOF): MHþ, found 179.1055. C11H15O2 requires
179.1067.
4.2.10. 2,2-Diphenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3af). From 1,3-cyclohexanedione (1a) (0.22 g, 1.96 mmol), iodo-
benzene diacetate (0.64 g, 1.99 mmol) and 1,1-diphenylethylene 2f
(1.0 g, 5.56 mmol) in dichloromethane (10 mL), irradiated for
90 min. Purification by flash chromatography (dichloromethane/
ethyl acetate 4:1) gave 2,2-diphenyl-2,3,6,7-tetrahydrobenzofuran-
4(5H)-one (3af) (0.38 g, 66% yield) as a colourless oil; Rf (20% EtOAc/
CH2Cl2) 0.30; nmax (liquid film) 3055, 2947, 1636, 1400, 1250, 737,
4.2.14. 2,3,3a,6,7,8a-Hexahydro-furo[2,3-b]benzofuran-4(5H)-one
(3aj). From 1,3-cyclohexanedione (1a) (0.22 g, 1.96 mmol), iodo-
benzene diacetate (0.64 g, 1.99 mmol) and 2,3-dihydrofuran 2j
(1.0 g, 14.29 mmol) in dichloromethane (10 mL), irradiated for
60 min. Purification by flash chromatography (dichloromethane/
ethyl acetate 4:1) gave 2,3,3a,6,7,8a-hexahydrofuro[2,3-b]benzo-
furan-4(5H)-one (3aj)19 (0.25 g, 71% yield) as a colourless oil; Rf
(20% EtOAc/CH2Cl2) 0.36; nmax (liquid film) 2952, 2882, 1634, 1406,
702 cmꢁ1
. dC (250 MHz, CDCl3) 7.38e7.17 (m, 10H), 3.56 (s, 2H),
2.51e2.47 (m, 2H), 2.31e2.26 (m, 2H), 2.00e1.90 (m, 2H). dC
(62.5 MHz, CDCl3) 194.8, 175.2, 144.1, 128.0, 127.3, 127.2, 112.2, 94.9,
40.2, 35.9, 23.4, 21.2. HRMS (ESI-TOF): MHþ, found 291.1369.
C20H19O2 requires 291.1380.
1244, 1086, 950, 898, 734 cmꢁ1
. dH (250 MHz, CDCl3) 6.13 (d,
4.2.11. (E)-2-(4-Methoxyphenyl)-3-methyl-2,3,6,7-tetrahyd-
robenzofuran-4(5H)-one (3ag). From 1,3-cyclohexanedione (1a)
(0.11 g, 1.00 mmol), iodobenzene diacetate (0.32 g, 0.99 mmol) and
trans-anethole 2g (0.6 g, 4.05 mmol) in dichloromethane (10 mL),
irradiated for 50 min. Purification by flash chromatography
(dichloromethane/ethyl acetate 4:1) gave (E)-2-(4-methoxyphenyl)-
3-methyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3ag) (0.17 g, 68%
yield) as a colourless oil; Rf (20% EtOAc/CH2Cl2) 0.46; nmax (liquid film)
J¼5.9 Hz, 1H), 3.99e3.95 (m, 1H), 3.63e3.47 (m, 2H), 2.48e2.43
(m, 2H), 2.23 (t, J¼6.5 Hz, 2H), 2.03e1.85 (m, 4H). dC (62.5 MHz,
CDCl3) 194.9, 177.2, 113.3, 112.5, 67.6, 43.5, 36.3, 30.0, 23.4, 21.3.
HRMS (ESI-TOF): MHþ, found 181.0858. C10H13O3 requires
181.0859.
4.2.15. 4b,6,7,8,9b,10-Hexahydro-9H-benz[b]indeno[2,1-d]-furan-9-
one (3ak). From 1,3-cyclohexanedione (1a) (0.22 g, 1.96 mmol),
iodobenzene diacetate (0.64 g, 1.99 mmol) and indene 2k (1.0 g,
8.62 mmol) in dichloromethane (10 mL), irradiated for 45 min.
Purification by flash chromatography (dichloromethane/ethyl ace-
tate 4:1) gave 4b,6,7,8,9b,10-hexahydro-9H-benz[b]indeno[2,1-d]
furan-9-one (3ak) (0.24 g, 55% yield) as white crystals;
mp¼131e133 ꢀC (EtOAc/hexanes). Rf (20% EtOAc/CH2Cl2) 0.48; nmax
2958, 1628, 1516, 1400, 1250, 1176, 1034, 912, 734 cmꢁ1
. dH (250 MHz,
CDCl3) 7.19 and 6.85 (AA0BB0 system, 4H), 5.05 (d, J¼7.0 Hz, 1H), 3.74
(s, 3H), 3.25e3.19 (m, 1H), 2.53e2.35 (m, 2H), 2.33e2.28 (m, 2H),
2.06e1.96 (m, 2H), 1.30 (d, J¼6.7 Hz, 3H). dC (62.5 MHz, CDCl3) 195.7,
176.8, 159.6, 131.8, 127.1, 117.0, 113.9, 93.7, 55.0, 42.3, 36.6, 23.8, 21.6,
18.9. HRMS (ESI-TOF): MHþ, found 259.1322. C16H19O3 requires
259.1329.
(KBr) 3052, 2946, 1634, 1402, 1368, 1234, 1174, 1060, 988, 760 cmꢁ1
.
dH (250 MHz, CDCl3) 7.46e7.43 (m, 1H), 7.33e7.21 (m, 3H), 6.14 (d,
J¼8.9 Hz, 1H), 4.01e3.94 (m, 1H), 3.31 (dd, J¼17.1, 8.3 Hz, 1H), 3.13
(dd, J¼17.1, 2.3 Hz, 1H), 2.39e2.20 (m, 4H), 1.98e1.79 (m, 2H). dC
(62.5 MHz, CDCl3) 195.5, 176.5, 143.3, 139.2, 129.7, 126.9, 125.7,
4.2.12. 2-(Phenylthio)-3-methyl-2,3,6,7-tetrahydrobenzofuran-
4(5H)-one (3ah). From 1,3-cyclohexanedione (1a) (0.23 g,
2.05 mmol), iodobenzene diacetate (0.64 g, 1.99 mmol) and 1-

D. Kalpogiannaki et al. / Tetrahedron 69 (2013) 1566e1575
1573
125.5, 116.6, 93.2, 41.7, 37.3, 36.5, 23.9, 21.5. HRMS (ESI-TOF): MHþ,
found 227.1058. C15H15O2 requires 227.1067.
HRMS (ESI-TOF): MHþ, found 391.0159. C18H16IO2 requires
391.0189.
4.2.16. 8,9,10,11b-Tetrahydroacenaphtho[1,2-b]benzo[d]-furan-
11(6bH)-one (3al). From 1,3-cyclohexanedione (1a) (0.22 g,
1.96 mmol), iodobenzene diacetate (0.65 g, 2.02 mmol) and ace-
naphthylene 2l (1.0 g, 6.58 mmol) in dichloromethane (10 mL), ir-
radiated for 240 min. Purification by flash chromatography
(dichloromethane/ethyl acetate 8:1) gave 8,9,10,11b-tetrahy-
droacenaphtho[1,2-b]benzo[d]furan-11(6bH)-one (3al) (0.30 g, 59%
yield) as brown crystals; mp¼152e153 ꢀC (EtOAc/hexanes). Rf
(CH2Cl2) 0.081; nmax (KBr) 3076, 2957, 2934, 1649, 1630, 1394, 1169,
4.3.4. [2,6-Dioxo-4-(4-methoxyphenyl)cyclohexyl]phenyliodonium
inner salt (4d). From 5-(4-methoxyphenyl)-1,3-cyclohexanedione
1d (2.18 g, 10.00 mmol) and iodobenzene diacetate (3.22 g,
10.00 mmol) in dichloromethane (100 mL), stirred for 2 h. Usual
work-up gave [2,6-dioxo-4-(4-methoxyphenyl)cyclohexyl]phenyl-
iodonium inner salt (4d) (3.20 g, 76% yield) as a white solid; mp
129e131 ꢀC; nmax (KBr) 3051, 2939, 1605, 1527, 1470, 1305, 1250,
1180, 1038, 991, 829, 721 cmꢁ1
. dH (250 MHz, CDCl3) 7.83e7.79 (m,
2H), 7.55e7.48 (m, 1H), 7.38e7.31 (m, 2H), 7.13 and 6.82 (AA; BB;
system, 4H), 3.77 (s, 3H), 3.39e3.27 (m, 1H), 2.92e2.72 (m, 4H). dC
(62.5 MHz, CDCl3) 188.0, 158.3, 134.7, 133.9, 131.6, 131.4, 127.6, 114.0,
111.6, 96.0, 55.2, 44.1, 37.9. HRMS (ESI-TOF): MNaþ, found 421.0265.
C19H17IO3Na requires 421.0295.
1016, 791 cmꢁ1
.
dH (250 MHz, CDCl3) 7.83 (d, J¼7.9 Hz, 1H), 7.77 (d,
J¼6.9 Hz, 1H), 7.70e7.49 (m, 4H), 6.57 (d, J¼7.9 Hz, 1H), 5.17 (d,
J¼5.9 Hz, 1H), 2.51e2.22 (m, 4H), 2.10e1.88 (m, 2H). dC (62.5 MHz,
CDCl3) 194.9, 177.2, 143.5, 139.9, 136.9, 131.1, 128.5, 127.6, 125.9,
123.0, 121.7, 121.5, 115.1, 90.6, 49.3, 36.4, 23.8, 21.2. HRMS (ESI-TOF):
MHþ, found 263.1075. C18H15O2 requires 263.1067.
4.3.5. (2,6-Dioxo-4,4-dimethylcyclohexyl)phenyliodonium inner salt
(4e). From 5,5-dimethyl-1,3-cyclohexanedione (1e) (2.80 g,
20.00 mmol) and iodobenzene diacetate (6.40 g, 19.88 mmol) in
dichloromethane (100 mL), stirred for 2 h. Usual work-up gave (2,6-
dioxo-4,4-dimethylcyclohexyl)phenyliodonium inner salt (4e)
(6.27 g, 92% yield) as a white solid; mp 129e130 ꢀC; lit.27 mp 130 ꢀC;
4.3. General procedure for the preparation of iodonium ylides
4
A solution of 1,3-cyclohexanedione 1 (10.00e30.00 mmol) and
iodobenzene diacetate (10.00e30.00 mmol) in dichloromethane
(200 mL) was stirred at room temperature for 120e180 min. The
yellow solution was then washed with an aqueous 5% KOH solution
(2ꢂ100 mL), water (2ꢂ50 mL) and dried (MgSO4). The solvent was
evaporated under reduced pressure (water bath below 30 ꢀC), the
solid residue triturated with hexanes (100 mL) and filtered to afford
iodonium ylide 4.
nmax (KBr) 3052, 2930, 1519, 1352, 998, 739 cmꢁ1
. dH (250 MHz,
CDCl3) 7.74e7.72 (m, 2H), 7.43e7.40 (m, 1H), 7.28e7.24 (m, 2H),
2.40 (s, 4H), 0.96 (s, 6H). dC (62.5 MHz, CDCl3) 188.4, 133.8, 131.5,
131.3, 111.9, 94.5, 50.6, 31.9, 28.0. HRMS (ESI-TOF): MHþ, found
343.0186. C14H16IO2 requires 343.0189.
4.4. General procedure for the cycloaddition of iodonium
ylides with alkenes
4.3.1. (2,6-Dioxocyclohexyl)phenyliodonium inner salt (4a). From
1,3-cyclohexanedione 1a (3.36 g, 30.00 mmol), and iodobenzene
diacetate (9.66 g, 30.00 mmol) in dichloromethane (200 mL), stir-
red for 2 h. Usual work-up gave (2,6-dioxocyclohexyl)phenyl-
iodonium inner salt (4a) (7.33 g, 78% yield) as a white solid; mp
126e128 ꢀC; lit.26 mp 109e110 ꢀC; nmax (KBr) 3055, 2939, 1535,
A solution of iodonium ylide 4 (1.00e4.14 mmol), and alkene 2
(4.05e145 mmol) in dichloromethane (10 mL) or acetonitrile
(10 mL) was irradiated (250 W) at room temperature for
40e360 min. The solvent was evaporated under reduced pressure,
and the residue was purified by flash chromatography to afford
fused dihydrofuran 3.
1362, 1288, 1188, 964, 741 cmꢁ1
. dH (250 MHz, CDCl3) 7.82e7.79 (m,
2H), 7.52e7.46 (m, 1H), 7.36e7.26 (m, 2H), 2.60e2.56 (m, 4H),
1.93e1.88 (m, 2H). dC (62.5 MHz, CDCl3) 189.4, 133.9, 131.5, 131.3,
111.3, 96.6, 37.0, 20.8. HRMS (ESI-TOF): MHþ, found 314.9876.
C12H12IO2 requires 318.9878.
4.4.1. 2-Phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3aa). From
iodonium ylide 4a (1.30 g, 4.14 mmol) and styrene 2a (1.5 g,
14.42 mmol) in acetonitrile (10 mL), irradiated for 75 min. Purifi-
cation by flash chromatography (dichloromethane/ethyl acetate
4:1) gave 2-phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3aa)
(0.59 g, 67% yield) as a colourless oil.
4.3.2. (2,6-Dioxo-4-methylcyclohexyl)phenyliodonium inner salt
(4b). From 5-methyl-1,3-cyclohexanedione 1b (1.26 g,10.00 mmol)
and iodobenzene diacetate (3.24 g, 10.06 mmol) in dichloro-
methane (100 mL), stirred for 2 h. Usual work-up gave (2,6-dioxo-
4-methylcyclohexyl)phenyliodonium inner salt (4b) (2.80 g, 85%
yield) as a white solid; mp 104e105 ꢀC; nmax (KBr) 3050, 2951, 1605,
4.4.2. 6-Methyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3ba). From iodonium ylide 4b (0.66 g, 2.01 mmol), and styrene 2a
(1.0 g, 9.62 mmol) in acetonitrile (10 mL), irradiated for 1 h. Puri-
fication by flash chromatography (dichloromethane/ethyl acetate
9:1) gave 6-methyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-
one (3ba) (0.27 g, 59% yield) as a colourless oil (racemic mixture).
1558, 1528, 1443, 1346, 1254, 1134, 1007, 987, 872, 744 cmꢁ1
. dH
(250 MHz, CDCl3) 7.74e7.70 (m, 2H), 7.43e7.37 (m, 1H), 7.28e7.21
(m, 2H), 2.58e2.52 (m, 2H), 2.24e2.08 (m, 3H), 0.95 (d, J¼5.9 Hz,
3H). dC (62.5 MHz, CDCl3) 188.7, 133.4, 131.2, 130.9, 111.8, 96.2, 44.7,
28.1, 20.3. HRMS (ESI-TOF): MHþ, found 329.0013. C13H14IO2 re-
quires 329.0033.
4.4.3. 2,6-Diphenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3ca). From iodonium ylide 4c (0.78 g, 2.00 mmol), and styrene 2a
(1.0 g, 9.62 mmol) in acetonitrile (10 mL), irradiated for 1 h. Puri-
fication by flash chromatography (dichloromethane/ethyl acetate
4:1) gave 2,6-diphenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3ca) (0.20 g, 35% yield), as white crystals (racemic mixture).
4.3.3. (2,6-Dioxo-4-phenylcyclohexyl)phenyliodonium inner salt
(4c). From 5-phenyl-1,3-cyclohexanedione 1c (1.88 g, 10.00 mmol)
and iodobenzene diacetate (3.22 g, 10.00 mmol) in dichloro-
methane (200 mL), stirred for 3 h. Usual work-up gave (2,6-dioxo-
4-phenylcyclohexyl)phenyliodonium inner salt (4c) (3.36 g, 86%
yield) as a white solid; mp 126e127 ꢀC; nmax (KBr) 3055, 2939,1605,
4.4.4. 6-(4-Methoxyphenyl)-2-phenyl-2,3,6,7-tetrahydrobenzo-fu-
ran-4(5H)-one (3da). From iodonium ylide 4d (0.80 g, 1.90 mmol),
styrene 2a (1.0 g, 9.62 mmol) in acetonitrile (10 mL), irradiated
for 2 h. Purification by flash chromatography (dichloromethane/
ethyl acetate 4:1) gave 6-(4-methoxyphenyl)-2-phenyl-2,3,6,7-
1528, 1470, 1439, 1350, 1288, 991, 760, 721, 698 cmꢁ1
. dH (250 MHz,
CDCl3) 7.86e7.82 (m, 2H), 7.57e7.50 (m, 1H), 7.40e7.22 (m, 7H),
3.46e3.34 (m, 1H), 2.91e2.85 (m, 4H). dC (62.5 MHz, CDCl3) 188.1,
142.7, 134.1, 131.7, 131.6, 128.7, 126.8, 126.7, 111.5, 95.9, 43.9, 38.8.

1574
D. Kalpogiannaki et al. / Tetrahedron 69 (2013) 1566e1575
tetrahydrobenzofuran-4(5H)-one (3da) (0.37 g, 61% yield) as
white crystals (racemic mixture).
irradiated for 60 min. Purification by flash chromatography
(dichloromethane/ethyl acetate 4:1) gave 1,2,3,3a,5,6,7,8b-octahy-
dro-8H-cyclopenta[b]benzofuran-4(5H)-one (3ai) (0.14 g, 39%
yield) as a colourless oil.
4.4.5. 6,6-Dimethyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-
one (3ea). From iodonium ylide 4e (0.68 g, 1.99 mmol), and styrene
2a (0.5 g, 4.81 mmol) in acetonitrile (10 mL), irradiated for 1 h. Pu-
rification by flash chromatography (dichloromethane/ethyl acetate
9:1) gave 6,6-dimethyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-
4(5H)-one (3ea) (0.41 g, 85% yield) as a colourless oil.
4.4.14. 2,3,3a,6,7,8a-Hexahydro-furo[2,3-b]benzofuran-4(5H)-one
(3aj). From iodonium ylide 4a (0.60 g, 1.91 mmol) and 2,3-
dihydrofuran 2j (1.0 mL, 13.24 mmol) in acetonitrile (10 mL), irra-
diated for 30 min. Purification by flash chromatography
(dichloromethane/ethyl acetate 4:1) gave 2,3,3a,6,7,8a-hexahy-
drofuro[2,3-b]benzofuran-4(5H)-one (3aj) (0.23 g, 68% yield) as
a colourless oil.
4.4.6. 2-Ethoxy-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3ab). From
iodonium ylide 4a (0.60 g, 1.91 mmol) and ethyl vinyl ether 2b
(10 mL) in dichloromethane (10 mL), irradiated for 120 min. Purifi-
cation by flash chromatography (dichloromethane/ethyl acetate 9:1)
4.4.15. 4b,6,7,8,9b,10-Hexahydro-9H-benz[b]indeno[2,1-d]-furan-9-
one (3ak). From iodonium ylide 4a (2.00 g, 6.37 mmol), and indene
2k (3.0 mL) in acetonitrile (20 mL), irradiated for 105 min. Purifi-
cation by flash chromatography (dichloromethane/ethyl acetate
4:1) gave 4b,6,7,8,9b,10-hexahydro-9H-benz[b]indeno[2,1-d]furan-
9-one (3ak) (0.72 g, 50% yield) as white crystals.
gave
2-ethoxy-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3ab)
(0.30 g, 86% yield) as a colourless oil.
4.4.7. 2-Acetoxy-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3ac). From
iodonium ylide 4a (0.60 g, 1.91 mmol), and ethyl vinyl ether 2c
(10 mL) in dichloromethane (10 mL), irradiated for 2 h. Purification by
flash chromatography (dichloromethane/ethyl acetate 9:1) gave 2-
acetoxy-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3ac) (0.30 g, 81%
yield) as a colourless oil.
4.4.16. 8,9,10,11b-Tetrahydroacenaphtho[1,2-b]benzo[d]furan-
11(6bH)-one (3al). From iodonium ylide 4a (0.60 g, 1.91 mmol), and
acenaphthylene 2l (1.0 g, 5.68 mmol) in acetonitrile (10 mL), irra-
diated for 300 min. Purification by flash chromatography
(dichloromethane/ethyl acetate 4:1) gave 8,9,10,11b-tetrahy-
droacenaphtho[1,2-b]benzo[d]furan-11(6bH)-one (3al) (0.30 g, 55%
yield) as brown crystals.
4.4.8. 2-Phenylthio-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3ad).
From iodonium ylide 4a (1.20 g, 3.82 mmol), and phenylthio-
ethylene 2d (2.0 g, 14.71 mmol) in acetonitrile (15 mL), irradiated
for 1 h. Purification by flash chromatography (dichloromethane/
ethyl
acetate
9:1)
gave
2-phenylthio-2,3,6,7-
4.4.17. 6,6-Dimethyl-1-phenyl-5,7-dioxaspiro[2.5]octane-4,8-dione
(6). A solution of 2,2-dimethyl-1,3-dioxa-4,6-cyclohexanedione
(1f) (0.29 g, 2.01 mmol), iodobenzene diacetate (0.64 g,
1.99 mmol) and styrene 2a (1.0 g, 9.62 mmol) in dichloromethane
(10 mL) was irradiated at room temperature for 120 min. The sol-
vent was evaporated under reduced pressure. Purification by flash
chromatography (hexanes/ethyl acetate 4:1) gave 6,6-dimethyl-1-
phenyl-5,7-dioxaspiro[2.5]octane-4,8-dione (6) (0.23 g, 48% yield)
as white crystals; mp¼131e133 ꢀC (EtOAc/hexanes); lit.13 mp
133e134 ꢀC; Rf (CH2Cl2) 0.56; dH (250 MHz, CDCl3) 7.32 (s, 5H), 3.43
(t, J¼9.4 Hz, 1H), 2.65 (dd, J¼9.4, 4.8 Hz, 1H), 2.50 (dd, J¼9.4, 4.8 Hz,
1H), 1.69 (s, 6H). dC (62.5 MHz, CDCl3) 167.6, 163.3, 131.1, 129.4,
128.6, 128.3, 104.8, 44.4, 33.0, 27.8, 27.5, 22.8. HRMS (ESI-TOF):
MNaþ, found 269.0774. C14H14O4Na requires 269.0784.
tetrahydrobenzofuran-4(5H)-one (3ad) (0.65 g, 71% yield) as
a colourless oil.
4.4.9. 2-Methyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3ae). From iodonium ylide 4a (0.61 g, 1.94 mmol), and
a-methyl-
styrene 2e (1.0 g, 8.47 mmol) in acetonitrile (10 mL), irradiated for
50 min. Purification by flash chromatography (dichloromethane/ethyl
acetate 9:1) gave 2-methyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-
4(5H)-one (3ae) (0.28 g, 64% yield) as a colourless oil.
4.4.10. 2,2-Diphenyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3af). From iodonium ylide 4a (0.59 g, 1.88 mmol), and 1,1-
diphenylethylene 2f (1.0 g, 5.56 mmol) in acetonitrile (10 mL), ir-
radiated for 50 min. Purification by flash chromatography
(dichloromethane/ethyl acetate 4:1) gave 2,2-diphenyl-2,3,6,7-
tetrahydrobenzofuran-4(5H)-one (3af) (0.33 g, 61% yield) as a col-
ourless oil.
Acknowledgements
We thank the NMR center of the University of Ioannina for
measuring low temperature and 2D NMR spectra, and the ORBI-
TRAP mass unit of the University of Ioannina for measuring HRMS.
I.A.N. thanks the Propondis Foundation for a Ph.D fellowship.
4.4.11. (E)-2-(4-Methoxyphenyl)-3-methyl-2,3,6,7-tetrahydrobe-
nzofuran-4(5H)-one (3ag). From iodonium ylide 4a (0.63 g,
2.01 mmol), and 0.6 g trans-anethole 2g (0.81 g, 5.47 mmol) in
acetonitrile (10 mL), irradiated for 120 min. Purification by flash
chromatography (dichloromethane/ethyl acetate 4:1) gave (E)-2-
(4-methoxyphenyl)-3-methyl-2,3,6,7-tetrahydrobenzofuran-
4(5H)-one (3ag) (0.29 g, 56% yield) as a colourless oil.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.12.006.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
4.4.12. 2-(Phenylthio)-3-methyl-2,3,6,7-tetrahydrobenzofuran-
4(5H)-one (3ah). From iodonium ylide 4a (0.63 g, 2.01 mmol), and
1-(phenylthio)-1-propene (2h) (1.0 g, 6.67 mmol) in acetonitrile
(10 mL), irradiated for 1 h. Purification by flash chromatography
(eluant: dichloromethane/ethyl acetate 4:1) gave 2-(phenylthio)-3-
methyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3ah)(0.40 g, 77%
yield) as a colourless oil (E/Z ratio¼60:40).
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