Metal-catalyzed thermal reactions of cyclic β-Dicarbonyl Phenyliodonium Ylide with Styrenes

Article abstract of DOI:10.1021/jo502611x

A cyclic β-dicarbonyl phenyliodonium ylide reacted with various substituted styrenes under Rh₂(OAc)₄ catalysis to give cyclopropanes and dihydrofurans in a highly regioselective fashion. When styrenes with electron-donating substituents or disubstituted were employed, only dihydrofurans were isolated instead. A mechanism involving two competing pathways rationalizes the results.

Full text of DOI:10.1021/jo502611x

Note
pubs.acs.org/joc
Metal-Catalyzed Thermal Reactions of Cyclic β‑Dicarbonyl
Phenyliodonium Ylide with Styrenes
Alexandra-Eleni Bosnidou, Dimitra Kalpogiannaki, Sofia Karanestora, John A. Nixas,
and Lazaros P. Hadjiarapoglou*
Department of Chemistry, University of Ioannina, GR-45110 Ioannina, Greece
S
* Supporting Information
ABSTRACT: A cyclic β-dicarbonyl phenyliodonium ylide
reacted with various substituted styrenes under Rh2(OAc)4
catalysis to give cyclopropanes and dihydrofurans in a highly
regioselective fashion. When styrenes with electron-donating
substituents or disubstituted were employed, only dihydrofurans
were isolated instead. A mechanism involving two competing pathways rationalizes the results.
he metal-catalyzed decomposition reactions1 of α-diazo
Scheme 1. Possible Mechanistic Pathways
Tcarbonyl compounds have found broad utility as powerful
approaches to generate metal carbenoids, which may sub-
sequently lead to potentially useful transformations, such as
cyclopropanation, ylide generation, and X−H bond insertion.
However, when the metal carbenoids are appropriately stabilized,
other reaction pathways are possible. These processes are also
synthetically useful2 and include 1,3-dipolar cycloadditions
between carbenoids, derived from diazocarbonyls, and olefins,
acetylenes, and nitriles as trapping agents. The actual structure of
the zwitterionic intermediate in these reactions is open to debate
since questions such as the role of the metal, or the relative rates
on bond cleavage and formation are difficult to answer.
The employment of iodonium ylides in such chemistry has
shown interesting complementary reactivity to that of diazo
compounds without their major drawbacks such as health and
explosive hazards. The increased reactivity of iodonium ylides
agent. On the other hand, the thermal isomerization9 of a
cyclopropyl ketone to dihydrofuran, the heteroanalogue of
vinylcyclopropanes to cyclopentene rearrangement, requires
elevated temperatures to occur. Therefore, in an attempt to shift
the major product away from a dihydrofuran to a cyclopropane,
electron-withdrawing substituents were introduced in the alkene.
We now disclose that the thermal Rh2(OAc)4-catalyzed
reaction of phenyliodonium ylide 2 with styrene derivatives 3
yields mixtures of cyclopropanes 4 and dihydrofurans 5, while
photochemical activation gives exclusively the dihydrofuran
derivatives 5.
The β-dicarbonyl phenyliodonium ylide 2 was readily
prepared7a,10 from the corresponding 1,3-cyclohexanedione 1
by treatment with iodobenzene diacetate at room temperature
(Scheme 2). All photochemical or thermal Rh2(OAc)4-catalyzed
reactions of phenyliodonium ylide 2 were run with an excess of
styrene. The cyclopropanes 4 and dihydrofurans 5 (Table 1)
were isolated by flash chromatography on silica gel in up to 89%
yield. There is a comparison of the photochemically activated
compared to diazo compounds is attributed to the hyper-leaving
group ability of aryl-λ3-iodanyl groups. Under photochemical or
metal-catalyzed thermal activation, an iodonium ylide manifests
itself in the form of a transylidation reaction,3 or in a C−H
insertion reaction,4 or in an intra- and intermolecular cyclo-
addition reaction.5 This reactivity could be explained by the
assumption of carbene (or carbenoid) intermediates, but such an
involvement has been questioned.6 However, this enhanced
reactivity has allowed various cycloadditions7 to be performed
under milder conditions, with better yields, even leading to the
development of more enantioselective methods.
Previous studies have shown7a that the photochemically
activated decomposition of cyclic β-dicarbonyl phenyliodonium
ylides in the presence of alkenes affords dihydrofurans in good
yields. This could occur either by ring opening of an initially
formed cyclopropane or by direct [3 + 2] cycloaddition of a
dipolar intermediate with alkenes (Scheme 1). The dipolar
intermediate pathway leading to dihydrofuran is expected8 to be
stabilized either by the second electron-withdrawing keto
substituent in the cyclic β-dicarbonyl phenyliodonium ylide or
with electron-donating substituents in the olefinic trapping
Received: November 19, 2014
Published: December 22, 2014
© 2014 American Chemical Society
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The Journal of Organic Chemistry
Note
under photochemical activation or thermal Rh2(OAc)4 catalysis.
In both cases, only the corresponding dihydrofurans 5b,c were
isolated exclusively (entries 3−6, Table 1). The addition of
electron-withdrawing groups on the styrene disfavored the
dipolar intermediate. Although the photochemically activated
cycloaddition of ylide 2 with p-chlorostyrene 3d yields
exclusively dihydrofuran 5d in 59% yield (entry 7, Table 1),
the thermal Rh2(OAc)4-catalyzed reaction of ylide 2 with styrene
3d affords a mixture of cyclopropane 4d and dihydrofuran 5d in
35% and 39% yields, respectively (entry 8, Table 1). m-
Nitrostyrene 3e reacts similarly; cyclopropane 4e and
dihydrofuran 5e were isolated in 18% and 31% yields,
respectively, from the thermal Rh2(OAc)4-catalyzed reaction of
ylide 2 with m-nitrostyrene 3e (entry 10, Table 1), while
dihydrofuran 5e was isolated in 46% yield from the photo-
chemical reaction of ylide 2 with m-nitrostyrene 3e (entry 9,
Table 1). Cyclopropane 4e was detected in the crude reaction
mixture of the latter process. Although the photochemically
activated reaction of ylide 2 with o-chlorostyrene 3f yields
exclusively dihydrofuran 5f in 45% yield (entry 11, Table 1), the
thermal Rh2(OAc)4-catalyzed cycloaddition of ylide 2 with o-
chlorostyrene 3f results in the formation of cyclopropane 4f and
dihydrofuran 5f in 35% and 32% yields, respectively (entry 12,
Table 1).
The stability of cyclopropane 4a under the conditions of the
thermal reaction was verified [Rh2(OAc)4 at 110 °C for 1 h], and
it was found that the cyclopropane 4a does not rearrange to
dihydrofuran 5a. Thus, the thermal Rh(II)-catalyzed reaction of
styrenes 3 with phenyliodonium ylide 2 proceeds via two
competing pathways. The stability of cyclopropanes 4a under the
conditions of the photochemical activation was also verified
(CH3CN solution, irradiation for 1 h), and it was found that
cyclopropane 4a rearranges completely to dihydrofuran 5a
(Scheme 3). Thus, the photochemically activated reaction of
styrenes 3 with ylide 2 may proceed via two competing pathways.
Scheme 2. Cycloaddition of Ylide 2 with Styrenes 3
a
Table 1. Cycloadditions of Iodonium Ylide 2 with Styrenes 3
b
c
entry
Ar
method
time (min)
products (% yield)
1
2
C6H5
C6H5
A
B
A
B
A
B
A
B
A
B
A
B
60
1
5a (72)
4a (26), 5a (42)
5b (66)
3
p-CH3C6H4
p-CH3C6H4
p-CH3OC6H4
p-CH3OC6H4
p-ClC6H4
50
2
4
5b (72)
5
50
2
5c (89)
6
5c (43)
7
50
2
5d (59)
8
p-ClC6H4
4d (35), 5d (39)
d
9
m-NO2C6H4
m-NO2C6H4
o-ClC6H4
210
2
5e (46)
10
11
12
4e (18), 5e (31)
5f (45)
70
2
o-ClC6H4
4f (35), 5f (32)
a
Method A: All reactions were carried out by irradiating a solution of
iodonium ylide 2 (2.01−2.10 mmol), styrene 3 (6.71−9.61 mmol) in
acetonitrile (10 mL) for 50−210 min. Method B: All reactions were
carried out by heating at 110 °C, a mixture of iodonium ylide 2 (2.01−
2.10 mmol), styrene 3 (6.71−9.61 mmol), and Rh2(OAc)4 (1.0−3.0
b
mg) for 1−2 min. Time required for the completion of the reaction.
c
d
Yield of isolated product after column chromatography. Cyclopro-
Scheme 3. Photochemical Isomerization of Cyclopropane 4a
into Dihydrofuran 5a
pane 4e was detected in the crude reaction mixture.
cycloaddition of iodonium ylide 2 with styrenes (method A) with
the results obtained from the thermal Rh2(OAc)4-catalyzed
reaction of iodonium ylide 2 with styrenes (method B). Other
catalysts, such as RuCl3, Pd(OAc)2, and Cu(acac)2, have been
employed in the thermal metal-catalyzed reaction of iodonium
ylide 2 with styrene, yielding mixtures of 2-iodo-3-phenoxy-
cyclohex-2-enone, the decomposition product11 of ylide 2, and
dihydrofuran 5a.
As for the specific styrenes examined herein, the photochemi-
cally activated cycloaddition of iodonium ylide 2 with styrene 3a
yields exclusively dihydrofuran 5a in 72% yield (entry 1, Table
1); however, the thermal Rh2(OAc)4-catalyzed reaction of ylide 2
with styrene 3a results in the formation of cyclopropane 4a (26%
yield) together with dihydrofuran 5a (42% yield) (entry 2, Table
1). It is worth mentioning that the cycloaddition yielding
dihydrofuran 5 exhibits high regioselectivity. One of the two
carbonyl oxygens of iodonium ylide 2 added exclusively onto the
more substituted carbon of the double bond; i.e., only 2-
substituted dihydrofurans were isolated exclusively. The other
possible regioisomer was not detected at all. A dipolar
intermediate is enhanced8 by the introduction of electron-
donating substituents into the styrene. On the basis of this
expectation, the cycloadditions of iodonium ylide 2 with p-
methylstyrene 3b and p-methoxystyrene 3c were carried out
At this stage, we decide to apply this strategy to disubstituted
styrene derivatives 6, which are expected to favor the dipolar
intermediate pathway. Indeed, the reaction of iodonium ylide 2
with styrene derivatives 6, either photochemically or Rh2(OAc)4-
catalyzed, yields only dihydrofurans 77a in good yields (Scheme
4).
All photochemical or thermal Rh2(OAc)4-catalyzed reactions
of phenyliodonium ylide 2 were run with excess disubstituted
styrenes 6. The dihydrofurans 7 were isolated by flash
Scheme 4. Cycloaddition of Ylide 2 with Disubstituted
Styrenes 6
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Note
a
Table 2. Cycloadditions of Iodonium Ylide 2 with Styrenes 6
b
c
entry
R1
R2
R3
R4
method
time (min)
product
yield (%)
1
2
3
4
5
6
CH3
CH3
H
H
H
C6H5
C6H5
H
A
B
A
B
A
B
50
2
7a
7a
7b
7b
7c
7c
64
49
50
72
55
23
H
C6H4CH2
C6H4CH2
H
105
1
H
H
pCH3OC6H4
pCH3OC6H4
H
H
CH3
CH3
H
40
2
H
a
Method A: All reactions were carried out by irradiating a solution of iodonium ylide 2 (2.01−2.10 mmol), styrene 3 (6.71−9.61 mmol) in
acetonitrile (10 mL) for 50−210 min. Method B: All reactions were carried out by heating at 110 °C, a mixture of iodonium ylide 2 (2.01−2.10
b
c
mmol), styrene 3 (6.71−9.61 mmol), and Rh2(OAc)4 (1.0−3.0 mg) for 1−2 min. Time required for the completion of the reaction. Yield of
isolated product after column chromatography.
chromatography on silica gel in up to 72% yield, irrespective of
the method employed. There is a comparison of the photo-
chemically activated cycloaddition of iodonium ylide 2 with
disubstituted styrenes 6 (method A) with the results obtained
from the thermal Rh2(OAc)4-catalyzed reaction of iodonium
ylide 2 with disubstituted styrenes 6 (method B) (Table 2).
The relative photochemically activated reactivities of
iodonium ylide 2 with certain olefin pairs have been determined.
Irradiation of ylide 2 in mixtures of styrene 3a (5 equiv) and p-
methoxystyrene 3c (5 equiv) in acetonitrile (10 mL) gave
dihydrofurans 5a and 5c in 17% and 35% yields, respectively. The
ratio of 5c to 5a, and thus the relative reactivity of p-
methoxystyrene to styrene, is 2.06. In a second competitive
experiment, irradiation of ylide 2 in mixtures of styrene 3a (5
equiv) and α-methylstyrene 6a (5 equiv) in acetonitrile (10 mL)
gave dihydrofurans 5a and 7a in 25.3% and 39.3% yields,
respectively. The relative reactivity of α-methylstyrene to styrene
is 1.55. In another competitive experiment, irradiation of ylide 2
in mixtures of styrene 3a (5 equiv) and indene 6b (5 equiv) in
acetonitrile (10 mL) gave dihydrofurans 5a and 7b in 23.4% and
43.8% yields, respectively. The relative reactivity of indene to
styrene is 1.87. Finally, irradiation of ylide 2 in mixtures of
styrene 3a (5 equiv) and trans-anethole 6c (5 equiv) in
acetonitrile (10 mL) gave dihydrofurans 5a and 7c in 39.3%
and 24.8% yields, respectively. The relative reactivity of trans-
anethole to styrene is 0.63. The relative rate experiments thus
reveal that (1) the reactivities of the olefins studied are p-
methoxy styrene > indene > α-methylstyrene > trans-anethole,
(2) the photochemically activated cycloadditions of iodonium
ylide 2 on styrenes are electrophilic in nature, and (3) steric
hindrance plays an important role on this cycloaddition.
The current results support the mechanistic scenario displayed
in Scheme 5 for the reaction of iodonium ylide 2 with styrene 3. It
is reasonable to assume that the cycloaddition between the
iodonium ylide 2 with styrene 3 might proceed via the
zwitterionic intermediate A, either generated directly by
nucleophilic attack of the double bond on the electrophilic
iodine atom of the ylide (path B) or electron transfer takes place
between the two reactants, to afford the radical ion pair and the
latter leads on coupling to the zwitterionic intermediate A (path
A). In such a case, the Rh(II) catalyst must promote the electron
transfer reaction.12 In the absence of the catalyst, only the known
thermal isomerization11 of iodonium ylide 2, with 1,4-phenyl
migration, into 2-iodo-3-phenoxycyclohex-2-enone was ob-
served. Intermediate A is expected to have a T-shaped structure
for the trivalent iodine functionality,13 a fact that forces the
carbanionic site away from the benzyl positive center. Thereby,
ring closure to a four-membered ring cyclic iodinane species is
prevented, which, on subsequent iodobenzene extrusion, would
Scheme 5. Plausible Mechanism for the Formation of
Cyclopropane 4 and Dihydrofuran 5
afford the cyclopropane product. Instead, nucleophilic attack by
the enolic oxygen atom on the benzyl cationic center leads to six-
membered cyclic iodinane B. Iodobenzene extrusion affords the
observed dihydrofuran 5. Since the dipolar cycloaddition has an
electrophilic nature, the employment of electron-rich styrene,
such as p-methylstyrene 3b, p-methoxystyrene 3c, and the
disubstituted styrenes 6, would lead exclusively to dihydrofurans
5b,c and 7 via path A or B. When the employed styrene is less
reactive, the rhodium(II) acetate catalyst behaves also as a
trapping agent that generates the rhodium(II) carbenoid
complex C (path C). The latter reacts with styrenes 3a,d,e,f,
leading to the formation of the corresponding cyclopropanes 4.
Under photochemical activation, two competing pathways
could operate also, i.e., the carbene pathway leading to
cyclopropane and the dipolar cycloaddition pathway, either
directly or via electron transfer, leading to dihydrofuran. The
detection of cyclopropane 4e in the photochemically activated
reaction of ylide 2 with styrene 3e is an evidence for such a
mechanism. However, the complete photochemical isomer-
ization of cyclopropane 4a to dihydrofuran 5a complicates the
picture.
The photochemical activated or thermal Rh2(OAc)4-catalyzed
reactions of a six-membered cyclic phenyliodonium ylide with
various substituted styrenes have been studied. These cyclo-
additions provide easy access to highly substituted cyclopropanes
and dihydrofurans. A mechanism involving two competing
pathways, i.e., dipolar cycloaddition vs Rh(II) carbenoid
complex, rationalizes these results. It may be concluded that
the presence of electron-donating substituents in the styrene
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Note
201.8, 133.6, 131.8, 130.7, 128.1, 49.7, 47.5, 39.9, 39.2, 21.5, 17.7;
HRMS (ESI−TOF): Calcd for C14ClH14O2 249.0677; Found 249.0682.
2-(p-Chlorophenyl)-2,3,6,7-tetrahydrobenzofuran-4-(5H)-one 5d as a
colorless oil (0.19 g, 39% yield): IR (neat): 3056, 2952, 1636, 1402,
1230, 1182, 912, 732 cm−1; 1H NMR (250 MHz, CDCl3): δ = 7.34 and
7.25 (AA′BB′ system, 4H), 5.70 (dd, J = 10.5, 8.0 Hz, 1H), 3.30−3.23
(m, 1H), 2.83−2.77 (m, 1H), 2.51−2.48 (m, 2H), 2.39−2.36 (m, 2H),
2.07 (quint, J = 6.4 Hz, 2H); 13C (62.5 MHz, CDCl3): δ = 195.2, 176.8,
139.1, 134.0, 129.4, 127.7, 112.7, 85.8, 36.9, 34.5, 24.3, 22.2; HRMS
(ESI−TOF): Calcd for C14ClH14O2 249.0677; Found 249.0676.
Reaction of Iodonium Ylide 2 with m-Nitrostyrene 3e. From
iodonium ylide 2 (0.66 g, 2.10 mmol), m-nitrostyrene 3e (1.0 g, 6.71
mmol), and Rh2(OAc)4 (3.0 mg) heated at 110 °C for 2 min.
Purification by flash chromatography gave the following compounds. 1-
(3-Nitrophenyl)spiro[2.5]octa-4,8-dione 4e as a colorless oil (0.10 g,
18% yield): IR (neat): 2950, 1748, 1634, 1532, 1348, 1230, 1182, 1062,
738 cm−1; 1H NMR (250 MHz, CDCl3): δ = 8.07−8.04 (m, 2H), 7.54−
7.40 (m, 2H), 3.32 (t, J = 8.8 Hz, 1H), 2.76−2.66 (m, 2H), 2.56−2.43
(m, 2H), 2.37−2.27 (m, 2H), 2.11−2.06 (m, 2H); 13C (62.5 MHz,
CDCl3): δ = 205.6, 202.4, 148.2, 136.0, 135.8, 129.2, 124.8, 123.0, 49.1,
46.3, 40.4, 39.5, 23.0, 17.9; HRMS (ESI−TOF): Calcd for C14H14NO4
260.0918; Found 260.0912. 2-(3-Nitrophenyl)-2,3,6,7-tetrahydro-
benzofuran-4-(5H)-one 5e as a colorless oil (0.17 g, 31% yield): IR
(neat): 3054, 2870, 1632, 1532, 1402, 1230, 1182, 1062, 736 cm−1; 1H
NMR (250 MHz, CDCl3): δ = 8.17−8.15 (m, 2H), 7.64−7.52 (m, 2H),
5.86−5.79 (m, 1H), 3.39−3.28 (m, 1H), 2.84−2.75 (m, 1H), 2.57−2.50
(m, 2H), 2.40−2.36 (m, 2H), 2.14−1.89 (m, 2H); 13C (62.5 MHz,
CDCl3): δ = 195.1, 176.6, 147.9, 142.4, 131.2, 129.4, 122.8, 120.2, 112.0,
84.0, 35.9, 33.8, 23.3, 21.1; HRMS (ESI−TOF): Calcd for
C14H13NO4Na 282.0737; Found 282.0723.
Reaction of Iodonium Ylide 2 with o-Chlorostyrene 3f. From
iodonium ylide 2 (0.63 g, 2.01 mmol), o-chlorostyrene 3f (1.0 g, 7.22
mmol), and Rh2(OAc)4 (1.5 mg) heated at 110 °C for 2 min.
Purification by flash chromatography gave the following compounds. 1-
(2-Chlorophenyl)spiro[2.5]octa-4,8-dione 4f as a colorless oil (0.17 g,
35% yield): IR (neat): 3062, 2958, 1681, 1573, 1323, 1184, 912, 730
cm−1; 1H NMR (250 MHz, CDCl3): δ = 7.46−7.15 (m, 4H), 3.27−3.18
(m, 1H), 2.88−2.78 (m, 1H), 2.76−2.55 (m, 1H), 2.51−2.39 (m, 2H),
2.31−2.15 (m, 2H), 2.13−1.86 (m, 2H); 13C (62.5 MHz, CDCl3): δ =
206.0, 202.4, 135.4, 132.0, 131.2, 129.1, 128.7, 126.3, 48.0, 46.0, 39.5,
39.2, 23.1, 18.0; HRMS (ESI−TOF): Calcd for C14ClH14O2 249.0677;
Found 249.0662. 2-(o-Chlorophenyl)-2,3,6,7-tetrahydrobenzofuran-4-
(5H)-one 5d as a colorless oil (0.16 g, 32% yield): IR (neat): 3062, 2950,
1634, 1404, 1232, 1184, 954, 736 cm−1; 1H NMR (250 MHz, CDCl3): δ
= 7.39−7.18 (m, 4H), 6.06−5.99 (m, 1H), 3.43−3.33 (m, 1H), 2.71−
2.65 (m, 1H), 2.57−2.52 (m, 2H), 2.38−2.33 (m, 2H), 2.12−2.01 (m,
2H); 13C (62.5 MHz, CDCl3): δ = 195.8, 177.4, 138.5, 131.4, 129.7,
129.2, 127.0, 125.9, 112.8, 83.0, 36.2, 33.6, 23.7, 21.6; HRMS (ESI−
TOF): Calcd for C14ClH14O2 249.0677; Found 249.0668.
enhances the dipolar cycloaddition pathway, while less reactive
styrenes exert the Rh(II) carbenoid complex pathway. Further
transformations of these products will bring diversity to highly
substituted compounds of chemical and biological interest.
EXPERIMENTAL SECTION
■
General Procedure for the Thermal Rh2(OAc)4-Catalyzed
Reaction. A mixture of iodonium ylide 2 (2.01−2.10 mmol), styrene 3
(6.71−9.61 mmol), and Rh2(OAc)4 (1.0−3.0 mg) was heated at 110 °C
for 1−2 min. The reaction mixture was chromatographed on silica gel
[CH2Cl2, (8:1) CH2Cl2−EtOAc] to afford cyclopropane 4 and
dihydrofuran 5.
Reaction of Iodonium Ylide 2 with Styrene 3a. From iodonium
ylide 2 (0.66 g, 2.10 mmol), styrene 3a (1.0 g, 9.61 mmol), and
Rh2(OAc)4 (1.0 mg) heated at 110 °C for 1 min. Purification by flash
chromatography gave the following compounds. 1-Phenylspiro[2.5]-
octa-4,8-dione 4a as white crystals (0.12 g, 26% yield): mp 98−100 °C
(CHCl3−hexanes); IR (KBr): 3031, 3010, 2945, 1704, 1677, 1326,
1024, 760 cm−1; 1H NMR (500 MHz, CDCl3): δ = 7.31−7.28 (m, 2H),
7.27−7.24 (m, 1H), 7.23−7.21 (m, 2H), 3.28 (t, J = 9.0 Hz, 1H), 2.76
(ddd, J = 17.4, 7.9, 4.8 Hz, 1H), 2.64 (ddd, J = 17.4, 7.9, 4.8 Hz, 1H), 2.54
(dd, J = 9.0, 3.9 Hz, 1H), 2.49−2.43 (m, 1H), 2.33 (dd, J = 9.0, 3.9 Hz,
1H), 2.31−2.25 (m, 1H), 2.16−2.05 (m, 2H); 13C (125 MHz, CDCl3):
δ = 205.9, 201.9, 133.2, 129.4, 128.0, 127.9, 49.9, 48.8, 39.9, 21.1, 17.9;
HRMS (ESI − TOF): Calcd for C14H15O2 215.1067; Found 215.1068.
2-Phenyl-2,3,6,7-tetrahydrobenzofuran-4-(5H)-one 5a as a colorless oil
(0.19 g, 42% yield): IR (neat): 3058, 2943, 1643, 1454, 1400, 1230,
1
1180, 1060, 906, 702 cm−1; H NMR (250 MHz, CDCl3): δ = 7.40−
7.26 (m, 5H), 5.72 (dd, J = 10.5, 8.0 Hz, 1H), 3.31−3.20 (m, 1H), 2.90−
2.79 (m, 1H), 2.50−2.45 (m, 2H), 2.39−2.34 (m, 2H), 2.10−2.08 (m,
2H); 13C (62.5 MHz, CDCl3): δ = 195.3, 177.1, 140.5, 128.6, 128.3,
125.7, 112.8, 86.2, 36.3, 33.9, 23.8, 21.6; HRMS (ESI−TOF): Calcd for
C14H15O2 215.1067; Found 215.1060.
Reaction of Iodonium Ylide 2 with p-Methylstyrene 3b. From
iodonium ylide 2 (0.63 g, 2.01 mmol), p-methylstyrene 3b (1.0 g, 8.47
mmol), and Rh2(OAc)4 (2.5 mg) heated at 110 °C for 2 min.
Purification by flash chromatography gave 2-p-tolyl-2,3,6,7-tetrahydro-
benzofuran-4-(5H)-one 5b as colorless crystals (0.32 g, 72% yield): mp
97−99 °C (hexanes); IR (KBr): 3056, 3031, 2941, 1631, 1402, 1228,
1180, 918, 813 cm−1; 1H NMR (250 MHz, CDCl3): δ = 7.24 and 7.14
(AA′BB′ system, 4H), 5.72 (dd, J = 10.5, 8.1 Hz, 1H), 3.25 (dd, J = 14.6,
10.5 Hz, 1H), 2.88 (dd, J = 14.6, 8.1 Hz, 1H), 2.49 (t, J = 6.3 Hz, 2H),
2.40−2.37 (m, 2H), 2.36 (s, 3H), 2.11−2.05 (m, 2H); 13C (62.5 MHz,
CDCl3): δ = 195.2, 177.0, 138.2, 137.5, 129.3, 125.8, 112.9, 86.3, 36.4,
33.7, 23.8, 21.6, 21.0; HRMS (ESI−TOF): Calcd for C15H16O2Na
251.1043; Found 251.1030.
Reaction of Iodonium Ylide 2 with p-Methoxystyrene 3c. From
iodonium ylide 2 (0.63 g, 2.01 mmol), p-methoxystyrene 3c (1.0 g, 7.46
mmol), and Rh2(OAc)4 (1.6 mg) heated at 110 °C for 2 min.
Purification by flash chromatography gave gave 2-p-methoxyphenyl-
2,3,6,7-tetrahydrobenzofuran-4-(5H)-one 5c as colorless crystals (0.21
g, 43% yield): mp 69−71 °C (CHCl3−hexanes); IR (KBr): 3051, 2958,
Reaction of Iodonium Ylide 2 with α-Methylstyrene 6a. From
iodonium ylide 2 (0.63 g, 2.01 mmol), α-methylstyrene 6a (1.0 g, 8.47
mmol), and Rh2(OAc)4 (2.5 mg) heated at 110 °C for 2 min.
Purification by flash chromatography gave the 2-methyl-2-phenyl-
2,3,6,7-tetrahydrobenzofuran-4-(5H)-one7a 6a as a colorless oil (0.22 g,
49% yield).
Reaction of Iodonium Ylide 2 with Indene 6b. From iodonium ylide
2 (0.63 g, 2.01 mmol), indene 6b (1.0 g, 8.62 mmol), and Rh2(OAc)4
(1.9 mg) heated at 110 °C for 2 min. Purification by flash
chromatography gave the 4b,6,7,8,9b,10-hexahydro-9H-benz[b]indeno-
[2,1-d]furan-9-one7a 6a as white crystals (0.15 g, 33% yield).
1
1622, 1514, 1402, 1228, 1176, 1033, 827 cm−1; H NMR (250 MHz,
CDCl3): δ = 7.29 and 6.94 (AA′BB′ system, 4H), 5.72 (dd, J = 10.4, 8.1
Hz, 1H), 3.84 (s, 3H), 3.29−3.22 (m, 1H), 2.94−2.88 (m, 1H), 2.52−
2.49 (m, 2H), 2.43−2.40 (m, 2H), 2.10 (quint, J = 6.4 Hz, 2H); 13C
(62.5 MHz, CDCl3): δ = 195.5, 177.1, 159.8, 132.5, 127.6, 114.1, 113.0,
86.5, 55.3, 36.5, 33.6, 24.0, 21.7; HRMS (ESI−TOF): Calcd for
C15H17O3 245.1172; Found 245.1169.
Reaction of Iodonium Ylide 2 with p-Chlorostyrene 3d. From
iodonium ylide 2 (0.63 g, 2.01 mmol), p-chlorostyrene 3d (1.0 g, 7.22
mmol), and Rh2(OAc)4 (1.5 mg) heated at 110 °C for 2 min.
Purification by flash chromatography gave the following compounds. 1-
(4-Chlorophenyl)spiro[2.5]octa-4,8-dione 4d as white crystals (0.17 g,
35% yield): mp 118−120 °C (CHCl3−hexanes); IR (KBr): 3058, 2950,
Reaction of Iodonium Ylide 2 with trans-Anethole 6c. From
iodonium ylide 2 (0.63 g, 2.01 mmol), trans-anethole 6c (1.0 g, 8.47
mmol), and Rh2(OAc)4 (2.2 mg) heated at 110 °C for 1 min.
Purification by flash chromatography gave the (E)-2-(4-methoxy-
phenyl)-3-methyl-2,3,6,7-tetrahydrobenzofuran-4-(5H)-one7a 6c as
colorless crystals (0.12 g, 23% yield).
General Procedure for the Photochemically Activated
Reaction. A solution of iodonium ylide 2 (2.01−2.10 mmol) and
styrene 3 (6.71−9.61 mmol) in acetonitrile (10 mL) was irradiated (400
W medium pressure Hg street lamp) at room temperature for 50−210
1
1708, 1678, 1492, 1330, 1095, 1026, 827 cm−1; H NMR (400 MHz,
CDCl3): δ = 7.25 and 7.13 (AA′BB′ system, 4H) 3.22 (t, J = 8.9 Hz, 1H),
2.77−2.71 (m, 1H), 2.66−2.62 (m, 1H), 2.49−2.44 (m, 2H), 2.33−2.29
(m, 2H), 2.11−2.00 (m, 2H) ; 13C (62.5 MHz, CDCl3): δ = 205.5,
1282
DOI: 10.1021/jo502611x
J. Org. Chem. 2015, 80, 1279−1283

The Journal of Organic Chemistry
Note
min. The solvent was evaporated under reduced pressure and the
residue was chromatographed on silica gel [CH2Cl2, (8:1) CH2Cl2−
EtOAc] to afford dihydrofuran 5.
Photochemical Reaction of Iodonium Ylide 2 with Styrene 3a.
From iodonium ylide 2 (0.63 g, 2.01 mmol), styrene 3a (1.0 g, 9.61
mmol), in acetonitrile (10 mL) irradiated at room temperature for 60
min. Purification by flash chromatography gave 2-phenyl-2,3,6,7-
tetrahydrobenzofuran-4-(5H)-one 5a as a colorless oil (0.31 g, 72%
yield).
Photochemical Reaction of Iodonium Ylide 2 with p-Methylstyr-
ene 3b. From iodonium ylide 2 (0.63 g, 2.01 mmol), p-methylstyrene 3b
(1.0 g, 8.47 mmol), in acetonitrile (10 mL) irradiated at room
temperature for 50 min. Purification by flash chromatography gave 2-p-
tolyl-2,3,6,7-tetrahydrobenzofuran-4-(5H)-one 5b as colorless crystals
(0.30 g, 66% yield).
Photochemical Reaction of Iodonium Ylide 2 with p-Methox-
ystyrene 3c. From iodonium ylide 2 (0.63 g, 2.01 mmol), styrene 3a
(1.0 g, 7.46 mmol), in acetonitrile (10 mL) irradiated at room
temperature for 50 min. Purification by flash chromatography gave 2-(p-
methoxyphenyl)-2,3,6,7-tetrahydrobenzofuran-4-(5H)-one 5c as color-
less crystals (0.43 g, 89% yield). Photochemical reaction of iodonium
ylide 2 with p-chlorostyrene 3d. From iodonium ylide 2 (0.63 g, 2.01
mmol), p-chlorostyrene 3d (1.0 g, 7.22 mmol), in acetonitrile (10 mL)
irradiated at room temperature for 50 min. Purification by flash
chromatography gave 2-(p-chlorophenyl)-2,3,6,7-tetrahydrobenzo-
furan-4-(5H)-one 5d as a colorless oil (0.29 g, 59% yield).
Photochemical Reaction of Iodonium Ylide 2 with m-Nitrostyrene
3e. From iodonium ylide 2 (0.66 g, 2.10 mmol), m-nitrostyrene 3e (1.0
g, 6.71 mmol), in acetonitrile (10 mL) irradiated at room temperature
for 210 min. Purification by flash chromatography gave 2-(3-
nitrophenyl)-2,3,6,7-tetrahydrobenzofuran-4-(5H)-one 5a as colorless
oil (0.25 g, 46% yield).
Photochemical Reaction of Iodonium Ylide 2 with o-Chlorostyr-
ene 3f. From iodonium ylide 2 (0.63 g, 2.01 mmol), o-chlorostyrene 3f
(1.0 g, 7.22 mmol), in acetonitrile (10 mL) irradiated at room
temperature for 70 min. Purification by flash chromatography gave 2-(2-
chlorophenyl)-2,3,6,7-tetrahydrobenzofuran-4-(5H)-one 5f as colorless
oil (0.22 g, 45% yield).
Photochemical Reaction of Iodonium Ylide 2 with α-Methylstyr-
ene 6a. From iodonium ylide 2 (0.61 g, 1.94 mmol), α-methylstyrene 6a
(1.0 g, 8.47 mmol), in acetonitrile (10 mL) irradiated at room
temperature for 50 min. Purification by flash chromatography gave the
2-methyl-2-phenyl-2,3,6,7-tetrahydrobenzofuran-4-(5H)-one7a 6a as a
colorless oil (0.28 g, 64% yield).
ACKNOWLEDGMENTS
■
We gratefully acknowledge the NMR center and the ORBITRAP
mass unit of the University of Ioannina for NMR and HRMS
measurements. J.A.N. thanks the Propondis Foundation for a
Ph.D. fellowship.
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Photochemical Reaction of Iodonium Ylide 2 with Indene 6b.
From iodonium ylide 2 (0.63 g, 2.01 mmol), indene 6b (1.0 g, 8.62
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(0.23 g, 54% yield).
Photochemical Reaction of Iodonium Ylide 2 with trans-Anethole
6c. From iodonium ylide 2 (0.63 g, 2.01 mmol), trans-anethole 6c (1.0 g,
8.47 mmol), in acetonitrile (10 mL) irradiated at room temperature for
40 min. Purification by flash chromatography gave the (E)-2-(4-
methoxyphenyl)-3-methyl-2,3,6,7-tetrahydrobenzofuran-4-(5H)-one7a
6c as colorless crystals (0.29 g, 56% yield).
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ASSOCIATED CONTENT
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■
S
* Supporting Information
1H and 13C spectra of 2, 4a, 4d−f, 5a−f, and 7a−c. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*Tel.: +30-26510-08380. Fax: +30-26510-08799. E-mail:
lxatziar@uoi.gr (L.P.H.).
Notes
The authors declare no competing financial interest.
1283
DOI: 10.1021/jo502611x
J. Org. Chem. 2015, 80, 1279−1283