The question of electrophilic vs nucleophilic addition of cyclic β-dicarbonyl phenyliodonium ylides: Electrophilic cycloaddition of diphenylketene

Article abstract of DOI:10.1021/jo3020787

The reaction of β-dicarbonyl phenyliodonium ylides with diphenylketene at room temperature affords mixtures of lactone and aurone derivatives. The initial electrophilic attack of the iodonium ylide on the C_β position of the diphenylketene, followed by cyclization of the zwitterionic species, and subsequent ejection of iodobenzene, affords the lactone and aurone cycloadducts. Treatment of β-dicarbonyl iodonium ylides with acyl chlorides yields α-chloroenones with good to excellent yields.

Full text of DOI:10.1021/jo3020787

Note
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The Question of Electrophilic vs Nucleophilic Addition of Cyclic
β‑Dicarbonyl Phenyliodonium Ylides: Electrophilic Cycloaddition of
Diphenylketene
Anna Antos,‡ Yiannis Elemes, Adonis Michaelides,§ John, A. Nyxas, Stavroula Skoulika,§
and Lazaros P. Hadjiarapoglou*
Department of Chemistry, University of Ioannina, GR-45110 Ioannina, Greece
S
* Supporting Information
ABSTRACT: The reaction of β-dicarbonyl phenyliodonium
ylides with diphenylketene at room temperature affords mixtures
of lactone and aurone derivatives. The initial electrophilic attack of
the iodonium ylide on the Cβ position of the diphenylketene,
followed by cyclization of the zwitterionic species, and subsequent
ejection of iodobenzene, affords the lactone and aurone cycloadducts. Treatment of β-dicarbonyl iodonium ylides with acyl
chlorides yields α-chloroenones with good to excellent yields.
odonium ylides1 have been used quite often as rather
cyclization with ejection of iodobenzene should produce a
Ireactive synthetic equivalents to diazo ketones without major mixture of lactone 3 and aurone 5.
We now disclose that the reaction of various cyclic β-
dicarbonyl iodonium ylides with diphenylketene at room
temperature yields a mixture of lactone 3 and aurone 5.
Phenyliodonium ylide 2a, prepared by reaction of 1,3-
cyclopentanedione (1a) with iodobenzene diacetate in
tetrahydrofuran at room temperature (Scheme 2), was collected
by filtration. Ylide 2a is highly insoluble in common organic
solvents but stable, recrystallized from methanol, and can be
stored in a freezer for a long time without any decomposition.
An X-ray crystallographic study of a single crystal of 2a
confirms the structure. The other β-dicarbonyl phenyliodonium
ylides 2b−f were readily prepared11 from the corresponding
1,3-cyclohexanediones 1b−f by treatment with iodobenzene
diacetate in dichloromethane at room temperature, followed by
washing with 5% aqueous KOH solution (Scheme 2). All
reactions of ylides 2 were run with a slight excess (2.0 equiv) of
diphenylketene until complete consumption of the ylide (TLC
monitoring). Lactones 3 and aurones 5 were isolated by flash
chromatography on silica gel (Table 1), quantitatively.
When iodonium ylide 2a was treated with diphenylketene at
room temperature for 48 h, 3,3-diphenyl-5,6-dihydro-2H-
cyclopenta[b]furan-2,4(3H)-dione (3a), 2,2-diphenyl-5,6-dihy-
dro-2H-cyclopenta[b]furan-3,4(2H)-dione (5a), and 2-iodo-3-
phenoxy-cyclopent-2-enone (6a) were isolated in 12%, 53%,
and 33% yields, respectively (entry 1, Table 1). Iodoether 6a is
the typical3c decomposition product of a β-dicarbonyl
iodonium ylide. When iodonium ylide 2b was treated with
diphenylketene at room temperature for 72 h, 3,3-diphenyl-6,7-
dihydrobenzofuran-2,4(3H,5H)-dione (3b) and 2,2-diphenyl-
6,7-dihydrobenzofuran-3,4(2H,5H)-dione (5b) were isolated in
drawbacks such as explosive and health hazards. Iodonium
ylides are easily prepared2 from the condensation reaction of an
active methylene compound with a hypervalent iodine
precursor. Their fascinating chemical behavior consists of
decomposition3 in various solvents, transylidation reactions,4
C−H insertion reactions,5 and intra- and intermolecular
cycloaddition reactions6 under photochemical or metal-
catalyzed thermal activation. This reactivity could be explained
by the assumption of carbene (or carbenoid) intermediates, but
such an involvement has been questioned.7 However, in
solution at room temperature without any metal catalyst or
photochemical activation, a β-dicarbonyl iodonium ylide could
initially behave as an enolate due to its keto-stabilized
carbanionic center or as an electrophile through its positively
charged iodonium center. The incentive of the present study
was to distinguish between these mechanistic possibilities by
examining the reaction of β-dicarbonyl iodonium ylides with
diphenylketene.
Ketenes are unusual alkenes as well as carbonyl compounds
that are reactive8 toward both electrophiles and nucleophiles.
Experimental and theoretical studies showed9 that nucleophiles
will approach in the plane at Ca position while electrophiles
attack ketene perpendicular to the molecule plane on oxygen or
Cb positions. Diphenylketene,10 a stable ketene derivative, can
be easily prepared from the action of triethylamine on
diphenylacetyl chloride.
If the iodonium ylide reacts initially as a nucleophile, attack at
the Ca position of the ketene would produce enolate A, which
on subsequent intramolecular ring closure with ejection of
iodobenzene should afford a mixture of lactone 3 and ketene
acetal 4 (Scheme 1). In contrast, if the iodonium ylide reacts
initially as an electrophile, attack at the Cb position of the
ketene would produce an acylium ion B, which on subsequent
Received: September 25, 2012
Published: November 16, 2012
© 2012 American Chemical Society
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The Journal of Organic Chemistry
Note
Scheme 1. Possible Mechanistic Pathways
2f on diphenylketene. On the other hand, a similar aurone
derivative was isolated12 upon catalytic carbonylation of
iodonium ylide 2f via the intermediate ketene, which was
thought to be the primary unstable product of the carbon-
ylation reaction.
Scheme 2. Reaction of Iodonium Ylides 2 with
Diphenylketene
The structure of lactones and aurones is in accord with
1
HRMS, IR, H, 13C, and 2D NMR spectroscopy as illustrated
for representative examples 3b and 5b (Figure 1). Lactone 3b
Figure 1. 13C chemical shifts of lactone 3b and aurone 5b.
a
Table 1. Reaction of β-Dicarbonyl Iodonium Ylides 2 with
Diphenylketene
b
entry
n
R1
R2
Time(d)
products (% yield)
was identified by the IR carbonyl absorption of the lactone
moiety at 1801 cm−1 and the corresponding absorption of the
enone moiety at 1647 cm−1. The 13C resonance at δ 192.4 ppm
reveals the presence of an unsaturated 6-membered carbonyl
group, and the 13C resonance at δ 175.7 ppm reveals the
presence of a lactone carbonyl group. An X-ray crystallographic
study of a single crystal of 3b confirms the structure deduced
from NMR spectroscopic studies. Aurone 5b displays an IR
absorption at 1720 cm−1 for its 5-membered enone and at 1655
cm−1 for the 6-membered unsaturated carbonyl moiety. The
13C resonance at δ 191.8 ppm reveals the presence of an
unsaturated 6-membered carbonyl group, and the 13C
resonance at δ 193.9 ppm reveals the presence of an
unsaturated 5-membered carbonyl group. The structure
determined from an X-ray crystallographic study of a single
crystal of 5b confirms the structure deduced from NMR
spectroscopic studies.
It was anticipated that treatment of iodonium ylides 2 with
an in situ generated ketene, from the appropriate acetyl
chloride 7 and triethylamine, would afford mixtures of lactones
and aurones. However, treatment of iodonium ylide 2b with in
situ prepared dimethylketene afforded neither the expected
lactone or aurone derivative. Instead, a new compound was
isolated whose spectroscopic study suggested to be α-
chloroenone 8. It is known that is difficult to complete the
dehydrohalogenation of the appropriately substituted acetyl
chloride with triethylamine, since the formation of ketenes from
the acyl ammonium salts is reversible.13 Presumably, the
iodonium ylide reacts faster with the substituted acetyl chloride
than with ketene shifting the equilibrium to the left.
1
2
3
4
5
6
0
1
1
1
1
1
H
H
2
3
1
1
1
3
3a (12), 5a (53), 6a (33)
3b (42), 5b (55)
3c (66), 5c (34)
3d (45), 5d (54)
3e (39), 5e (43)
3f (58), 5f (42)
H
H
CH3
C6H5
H
H
p-CH3OC6H4
CH3
H
CH3
a
All reactions were carried out on a 2.0 mmol scale with 1.0 equiv of 2
and 2.0 equiv of diphenylketene in 10 mL of CH2Cl2. Isolated yield.
b
42% and 55% yields, respectively (entry 2, Table 1). Similarly,
the reaction of iodonium ylides 2c−e with diphenylketene at
room temperature furnishes mixtures of lactones 3c−e and
aurones 5c−e (entries 3−5 of Table 1), easily separable with
column chromatography. Phenyliodonium ylide 2f reacts with
diphenylketene to give 6,6-dimethyl-3,3-diphenyl-6,7-dihydro-
benzofuran-2,4-(3H,5H)-dione (3f)11b and 6,6-dimethyl-2,2-
diphenyl-6,7-dihydro-benzofuran-3,4(2H,5H)-dione (5f) in
58% and 42% yields, respectively (entry 6, Table 1). The
formation of iodoether 6 was only observed, when a fresh batch
of iodonium ylide 2 comes in contact with diphenylketene. In
such a case, an exothermic reaction occurs yielding, within
minutes, mixtures of lactones 3, aurones 5, and iodoether 6.
The same products 3, 5 were observed under photochemical or
Rh2(OAc)4-catalyzed thermal activation but in a shorter time.
It had been reported11b that when phenyliodonium ylide 2f
was allowed to react with diphenylketene in dichloromethane at
room temperature, lactone 3f and ketene acetal 4f were isolated
in 32% and 44% yields, respectively. This was explained as a
consequence of a formal 1,3-addition of phenyliodonium ylide
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The Journal of Organic Chemistry
Note
Indeed, the reaction of iodonium ylides 2 with substituted
acetyl chloride 7 in dichloromethane at room temperature
yields the corresponding α-chloroenones 814 with good to
excellent yields (Scheme 3). All reactions were run at room
temperature (ca. 20 °C) until complete consumption of the
ylide (TLC monitoring).
Scheme 4. Plausible Mechanism for the Formation of
Lactones 3 and Aurones 5
Scheme 3. Reaction of Iodonium Ylides 2 with
Diphenylacetyl Chloride
The α-chloroenones 8 (Table 2) were isolated by flash
chromatography on silica gel in good to excellent yields. The
reaction of iodonium ylide 2a with diphenylacetyl chloride 7a
gives 2-chloro-3-oxocyclopent-1-enyl 2,2-diphenylethanoate
(8a) in 89% yield (entry 1, Table 2). Treatment of iodonium
ylide 2b with acyl chlorides 7b−d yields α-chloro enones 8b−d
in excellent yields (entries 2−4, Table 1). The reaction of
iodonium ylide 2b with an equimolar amount of diphenylace-
tylchloride gave 2-chloro-3-oxocyclohex-1-enyl 2,2-diphenyle-
thanoate (8e) in 58% yield. The yield was improved to 96%
when double equivalents of Ph2CHCOCl were employed
(entry 5, Table 1). Similarly, α-chloro enones 8f−g were
isolated in moderate to good yields, when iodonium ylides 2c−
f were treated with diphenylacetyl chloride 7a at room
temperature (entries 6−9, Table 2). The structure of 8e is
easily identified by the two carbonyl absorptions at 1767 and
1624 cm−1 associated with a vinyl ester and an enone moiety.
Figure 2. Resonance structures of iodonium ylide 2a.
while, reactivity from the nucleophilic oxygen atom of an
enolate is rather uncommon, the oxygen atom is typically the
site of protonation. This carbanionic center of the enolate
species (form I, Figure 2) is sterically hindered by three
electron withdrawing groups to act as a nucleophile in
bimolecular reactions and attack nucleophilically in the plane
at the Ca position of diphenylketene. However, the positively
charged iodonium functionality of the ylide, without steric
hindrance, could attack electrophilically perpendicular to the
molecular plane at the Cb position of the diphenylketene.
Either electron transfer takes place between the two reactants
to afford a radical ion pair (not shown), and the latter leads on
coupling to the acylium species B, or alternatively, the acylium
intermediate B may be generated directly by the electrophilic
attack of the iodonium functionality of the ylide to the
diphenylketene, perpendicular to the plane of the ketene. In the
next step, the ring closure may occur via attack of the
nucleophilic oxygen atom (path a) or the nucleophilic carbon
atom (path b) to the acylium carbon atom leading to 6-
membered or 4-membered15 cyclic iodine compounds C and
D, respectively. Elimination of iodobenzene from C leads to the
1
The H NMR spectrum displays the signal of the methinic
proton as a singlet at δ 5.28 ppm. The 13C NMR spectrum
shows the signal of the enone carbon atom at δ 191.3 ppm,
while the methinic carbon atom appears at δ 56.6 ppm.
For the mechanism of the formation of cycloadducts 3 and 5,
we can only offer a simple proposal (Scheme 4) that falls back
on steps known from classical organic chemistry. One could
assume that is unlikely that phenyliodonium ylides 2
decompose into carbenes under the mild reaction conditions
without any metal-catalyzed thermal or photochemical
activation. With the carbene route discounted, we could
consider the enolate resonance forms I and II of iodonium
ylide 2 (Figure 2) and recall that an enolate ion is an ambient
anion. It is well-known that the carbon atom of an enolate is
normally the site of bimolecular reactions as a nucleophile
Table 2. Reaction of Iodonium Ylides 2 with Acetyl Chlorides 7
b
entry
n
R1
R2
R3
R4
time (h)
product
yield (%)
1
2
3
4
5
6
7
8
9
0
1
1
1
1
1
1
1
1
H
H
H
H
H
H
H
H
H
Me
Ph
Me
Ph
Me
Ph
Ph
Ph
Ph
Ph
Ph
H
12
6
8a
8b
8c
8d
8e
8f
89
80
96
88
96
85
46
79
68
H
H
H
6
H
Me
Ph
Ph
Ph
Ph
Ph
12
12
12
2
H
Me
Ph
8g
8h
8i
pMeOC6H4
Me
12
12
a
b
All reactions with carried out on a 2.0 mmol scale with 1.0 equiv of 2 and 2.0 equiv of acyl chloride 7 in 10 mL of CH2Cl2. Isolated yield.
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Note
(3H,5H)-dione (3b) as white crystals (0.32 g, 42% yield): mp
156−158 °C (EtOAc−hexanes); Rf 0.31 (CH2Cl2); H NMR (250
isolation of lactone 3, while iodobenzene elimination from D
results in the formation of aurone derivative 5a.
1
MHz, CDCl3) δ 7.33 (s, 10H), 2.78−2.74 (m, 2H), 2.49−2.44 (m,
2H), 2.23−2.12 (m, 2H); 13C NMR (62.5 MHz, CDCl3) δ 192.4,
175.7, 170.8, 138.4, 128.4, 128.3, 127.9, 121.8, 61.0, 37.6, 23.2, 20.8; IR
(KBr) ν (cm−1) 3059, 2959, 1801, 1674, 1647, 1493, 1447, 1369,
1184, 1134, 1042, 976, 899, 756, 698; HRMS (ESI-TOF) calcd for
C20H17O3 305.1169, found 305.1172. 2,2-Diphenyl-6,7-dihydroben-
zofuran-3,4(2H,5H)-dione (5b) as white needles (0.42 g, 55% yield):
In conclusion, we have defined that exposure of β-dicarbonyl
iodonium ylides to diphenylketene yields mixtures of lactone
and aurone derivatives, via the initial electrophilic attack of the
iodonium ylide on the Cβ position of the diphenylketene.
Treatment of β-dicarbonyl iodonium ylides with acyl chlorides,
precursors of the in situ ketenes, yields α-chloro enones with
good to excellent yields.
1
mp 168−170 °C (EtOAc); Rf 0.07 (CH2Cl2); H NMR (250 MHz,
CDCl3) δ 7.46−7.42 (m, 4H), 7.33−7.22 (m, 6H), 2.93−2.88 (m,
2H), 2.46−2.41 (m, 2H), 2.18−2.08 (m, 2H); 13C NMR (62.5 MHz,
CDCl3) δ 200.1, 193.9, 191.8, 136.8, 128.8, 128.5, 126.5, 112.9, 94.8,
37.4, 26.5, 20.5; IR (KBr) ν (cm−1) 3055, 2955, 2905, 1720, 1655,
1578, 1458, 1435, 1412, 1354, 1261, 1072, 960, 760, 690; HRMS (ESI-
TOF) calcd for C20H17O3 305.1169, found 305.1165.
EXPERIMENTAL SECTION
■
Preparation of Iodonium ylide 2a. A mixture of 1,3-cyclo-
pentanedione (1a) (0.98 g, 10.00 mmol) and iodobenzene diacetate
(3.22 g, 10.00 mmol) in tetrahydrofuran (20 mL) was stirred at room
temperature for 4.0 h. The iodonium ylide 2a was collected by
filtration, washed with hexanes (100 mL), and air-dried: mp 125−126
Reaction of Diphenylketene with Iodonium Ylide 2c. From
diphenylketene (0.83 g, 4.28 mmol) and iodonium ylide 2c (0.66 g,
2.01 mmol) in dichloromethane (10 mL), stirred at room temperature
for 1.0 d. Purification by flash chromatography (CH2Cl2) gave the
following compounds. 3,3-Diphenyl-6-methyl-6,7-dihydro-benzofur-
an-2,4(3H,5H)-dione (3c) as white crystals (0.42 g, 66% yield): mp
94−96 °C (hexanes); Rf 0.35 (CH2Cl2); 1H NMR (250 MHz, CDCl3)
δ 7.34−7.28 (m, 10H), 2.86−2.77 (m, 1H), 2.56−2.47 (m, 3H), 2.30−
2.19 (m, 1H), 1.18 (d, J = 5.8 Hz, 3H); 13C NMR (62.5 MHz, CDCl3)
δ 192.3, 175.8, 170.3, 138.4, 138.3, 128.4, 128.3, 128.2, 127.9, 127.8,
121.3, 61.0, 45.9, 31.0, 29.0, 20.8; IR (KBr) ν (cm−1) 3063, 2955,
2928, 1807, 1670, 1493, 1447, 1381, 1204, 1134, 984, 937, 922, 895,
752, 694; HRMS (ESI-TOF) calcd for C21H19O3 319.1329, found
319.1322. 2,2-Diphenyl-6-methyl-6,7-dihydrobenzofuran-3,4-
(2H,5H)-dione (5c) as white needles (0.22 g, 34% yield): mp
209−211 °C (EtOAc); Rf 0.09 (CH2Cl2); 1H NMR (250 MHz,
CDCl3) δ 7.47−7.40 (m, 4H), 7.36−7.26 (m, 6H), 3.02−2.94 (m,
2H), 2.69−2.40 (m, 3H), 2.28−2.17 (m, 1H), 1.19 (d, J = 6.4 Hz,
3H); 13C NMR (62.5 MHz, CDCl3) δ 199.6, 193.6, 191.3, 136.8,
136.7, 128.9, 128.8, 128.5, 126.6, 126.4, 112.6, 95.2, 45.9, 34.3, 28.7,
20.8; IR (KBr) ν (cm−1) 3063, 2939, 1724, 1663, 1574, 1439, 1323,
1231, 1072, 960, 736, 702; HRMS (ESI-TOF) calcd for C21H19O3
319.1329, found 319.1316.
1
°C (MeOH); H NMR (250 MHz, CDCl3) δ 7.84−7.78 (m, 2H),
7.59−7.52 (m, 1H), 7.43−7.35 (m, 2H), 2.72 (s, 4H); 13C NMR (62.5
MHz, CDCl3) δ 197.1, 133.3, 132.0, 131.9, 113.6, 83.4, 33.9; IR (KBr)
ν (cm−1) 3053, 2919, 1567, 1470, 1310, 1286, 989, 726.
General Procedure for the Preparation of Iodonium Ylides
2b−f. A solution of 1,3-cyclohexanedione 1b−f (10.00−30.00 mmol)
and iodobenzene diacetate (10.00−30.00 mmol) in dichloromethane
(200 mL) was stirred at room temperature for 120−180 min. The
yellow solution was then washed with an aqueous 5% KOH solution
(2 × 100 mL) and water (2 × 50 mL) and dried (MgSO4). The
solvent was evaporated under reduced pressure (water bath below 30
°C), and the solid residue triturated with hexanes (100 mL) and
filtered to afford iodonium ylide 2b−f. The spectral data were
consistent with those reported in the literature.11
General Procedure for the Reaction of Diphenylketene with
Iodonium Ylides. A solution of iodonium ylide 2 (2.00−2.55 mmol)
and diphenylketene (4.12−5.15 mmol) in dichloromethane (10 mL)
was stirred at room temperature (ca. 20 °C) for 1−3 d. The solvent
was evaporated under reduced pressure. Purification of the residue by
flash chromatography (CH2Cl2) afforded lactone derivative 3 and
aurone derivative 5.
Reaction of Diphenylketene with Iodonium Ylide 2a. From
diphenylketene (0.8 g, 4.12 mmol) and iodonium ylide 2a(0.60 g, 2.00
mmol) in dichloromethane (10 mL), stirred at room temperature for
2.0 d. Purification by flash chromatography (CH2Cl2) gave the
following compounds. 3,3-Diphenyl-5,6-dihydro-2H-cyclopenta[b]-
furan-2,4(3H)-dione (3a) as white crystals (0.07 g, 12% yield): mp
Reaction of Diphenylketene with Iodonium Ylide 2d. From
diphenylketene (0.80 g, 4.12 mmol) and iodonium ylide 2d (0.78 g,
2.00 mmol) in dichloromethane (10 mL), stirred at room temperature
for 1.0 d. Purification by flash chromatography (CH2Cl2) gave the
following compounds. 3,3,6-Triphenyl-6,7-dihydrobenzofuran-2,4-
(3H,5H)-dione (3d) as white crystals (0.34 g, 45% yield): mp 80−82
°C (EtOAc−hexanes); Rf 0.37 (CH2Cl2); 1H NMR (250 MHz,
CDCl3) δ 7.43−7.26 (m, 15H), 3.71−3.58 (m, 1H), 3.07−3.04 (m,
2H), 2.80−2.76 (m, 2H); 13C NMR (62.5 MHz, CDCl3) δ 191.4,
175.7, 170.0, 141.4, 138.4, 138.2, 129.0, 128.5, 128.4, 128.3, 128.1,
128.0, 127.5, 126.6, 121.7, 61.1, 44.9, 39.4, 30.8; IR (KBr) ν (cm−1)
3059, 3028, 2959, 2924, 1821, 1674, 1655, 1578, 1493, 1447, 1381,
1246, 1130, 980, 926, 764, 698; HRMS (ESI-TOF) calcd for C26H21O3
381.1485, found 381.1476. 2,2,6-Triphenyl-6,7-dihydrobenzofuran-
3,4(2H,5H)-dione (5d) as white needles (0.41 g, 54% yield): mp
1
151−153 °C (EtOAc−hexanes); Rf 0.28 (CH2Cl2); H NMR (250
MHz, CDCl3) δ 7.40 (br s, 10H), 3.10−3.06 (m, 2H), 2.73−2.69 (m,
2H); 13C NMR (62.5 MHz, CDCl3) δ 200.1, 183.2, 167.6, 136.8,
128.9, 128.6, 127.9, 87.2, 33.4, 29.9; IR (KBr) ν (cm−1) 3059, 3028,
2924, 1775, 1697, 1601, 1450, 1312, 1254, 1192, 1088, 918, 748, 694;
HRMS (ESI-TOF) calcd for C19H14O3Na 313.0835, found 313.0836.
2-Iodo-3-phenoxycyclopent-2-enone (6a) as white crystals (0.20 g,
33% yield): mp 137−140 °C (EtOAc−hexanes); Rf 0.21 (CH2Cl2); 1H
NMR (250 MHz, CDCl3) δ7.43−7.35 (m, 2H), 7.30−7.24 (m, 1H),
7.13−7.08 (m, 2H), 2.62−2.52 (m, 4H); 13C NMR (62.5 MHz,
CDCl3) δ 199.8, 187.8, 152.9, 129.8, 126.4, 120.9, 76.7, 32.7, 28.3; IR
(KBr) ν (cm−1) 3047, 2932, 1686, 1601, 1574, 1489, 1331, 1269,
1250, 1227, 1173, 1153, 918, 771, 702; HRMS (ESI-TOF) calcd for
C11H9O2INa 322.9539, found 322,9543. 2,2-Diphenyl-5,6-2H-
cyclopenta[b]furan-3,4-dione (5a) as white needles (0.31 g, 53%
1
130−132 °C (EtOAc−hexanes); Rf 0.14 (CH2Cl2); H NMR (250
MHz, CDCl3) δ 7.58−7.26 (m, 15H), 3.65−3.53 (m, 1H), 3.19−3.16
(m, 2H), 2.82−2.78 (m, 2H); 13C NMR (62.5 MHz, CDCl3) δ 199.2,
193.6, 190.8, 141.0, 136.69, 136.67, 129.1, 128.7, 128.6, 127.4, 126.8,
126.6, 126.5, 113.0, 95.8, 57.1, 44.9, 39.0, 34.0; IR (KBr) ν (cm−1)
3063, 3024, 1728, 1701, 1578,1497, 1439, 1223, 933, 748, 698; HRMS
(ESI-TOF) calcd for C26H21O3 381.1485, found 381.1468.
1
yield): mp 198−199 °C (EtOAc); Rf 0.14 (CH2Cl2); H NMR (250
MHz, CDCl3) δ 7.50−7.36 (m, 10H), 2.98−2.97 (m, 4H); 13C NMR
(62.5 MHz, CDCl3) δ 214.3, 191.7, 188.6, 136.4, 129.2, 128.7, 126.5,
119.7, 106.9, 40.0, 24.5; IR (KBr) ν (cm−1) 3063, 2970, 1736, 1682,
1566, 1443, 1408, 1335, 910, 768, 748, 698; HRMS (ESI-TOF) calcd
for C19H15O3 291.1016, found 291.1014.
Reaction of Diphenylketene with Iodonium Ylide 2e. From
diphenylketene (0.81 g, 4.18 mmol) and iodonium ylide 2e (0.84 g,
2.00 mmol) in dichloromethane (10 mL), stirred at room temperature
for 1.0 d. Purification by flash chromatography (CH2Cl2) gave the
following compounds. 3-Diphenyl-6-(p-methoxyphenyl)-6,7-dihy-
drobenzofuran-2,4(3H,5H)-dione (3e) as white crystals (0.32 g,
Reaction of Diphenylketene with Iodonium Ylide 2b. From
diphenylketene (1.0 g, 5.15 mmol) and iodonium ylide 2b (0.80 g,
2.55 mmol) in dichloromethane (10 mL), stirred at room temperature
for 3.0 d. Purification by flash chromatography (CH2Cl2) gave the
following compounds. 3,3-Diphenyl-6,7-dihydrobenzofuran-2,4-
1
39% yield): mp 119−121 °C (hexanes); Rf 0.31 (CH2Cl2); H NMR
(250 MHz, CDCl3) δ 7.51−7.47 (m, 2H), 7.40−7.35 (m, 8H), 7.21
and 6.94 (AA′BB′ system, 4H), 3.82 (s, 3H), 3.65 3.52 (m, 1H), 3.01−
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Note
2.98 (m, 2H), 2.75−2.72 (m, 2H); 13C NMR (62.5 MHz, CDCl3) δ
191.3, 175.6, 170.0, 158.5, 138.2, 138.1, 133.4, 128.29, 128.26, 128.2,
128.1, 127.84, 127.76, 127.5, 121.3, 114.0, 60.9, 55.0, 44.9, 38.4, 30.7;
IR (KBr) ν (cm−1) 3059, 2932, 1821, 1674, 1512, 1447, 1377, 1250,
1180, 1130, 1034, 980, 926, 829, 698; HRMS (ESI-TOF) calcd for
C27H23O4 411.1590, found 411.1577. 2,2-Diphenyl-6-(p-methoxy-
phenyl)-6,7-dihydrobenzofuran-3,4(2H,5H)-dione (5e) as white
needles (0.35 g, 43% yield): mp 205−208 °C (EtOAc); Rf 0.09
(CH2Cl2); 1H NMR (250 MHz, CDCl3) δ 7.50−7.33 (m, 10H), 7.18
and 6.90 (AA′BB′ system, 4H), 3.81 (s, 3H), 3.60−3.47 (m, 1H),
3.26−3.11 (m, 2H), 2.75−2.70 (m, 2H); 13C NMR (62.5 MHz,
CDCl3) δ 199.0, 193.5, 190.4, 158.8, 136.7, 136.6, 133.1, 128.93,
128.86, 128.6, 128.5, 127.6, 126.7, 126.4, 114.4, 112.9, 95.5, 55.2, 45.2,
38.3, 34.3; IR (KBr) ν (cm−1) 3059, 2955, 2924, 1724, 1666, 1574,
1512, 1427, 1400, 1308, 1246, 1180, 1030, 953, 829, 764, 698; HRMS
(ESI-TOF) calcd for C27H23O4 411.1590, found 411.1591.
IR (KBr) ν (cm−1) 2978, 2937, 1763, 1697, 1626, 1578, 1340, 1277,
1173, 1080, 1013, 972, 827; HRMS (ESI-TOF) calcd for
C10H13ClO3Na 239.0445, found 239.0434.
2-Chloro-3-oxocyclohex-1-enyl 2,2-diphenylethanoate (8e): col-
1
orless oil; 0.51 g, 96% yield; Rf 0.50 (CH2Cl2); H NMR (250 MHz,
CDCl3) δ 7.42−7.26 (m, 10H), 5.28 (s, 1H), 2.65−2.42 (m, 4H),
2.05−1.95 (m, 2H); 13C NMR (62.5 MHz, CDCl3) δ 191.2, 168.0,
164.2, 137.0, 128.6, 128.4, 127.6, 122.1, 56.5, 37.1, 29.4, 20.0; IR
(KBr) ν (cm−1) 3032, 2978, 1767, 1694, 1624, 1497, 1273, 1182,
1095, 1016, 976, 741; HRMS (ESI-TOF) calcd for C20H17ClO3Na
363.0758, found 363.0729.
2-Chloro-5-methyl-3-oxocyclohex-1-enyl 2,2-diphenylethanoate
(8f): colorless oil; 0.60 g, 85% yield; Rf 0.55 (CH2Cl2); 1H NMR (250
MHz, CDCl3) δ 7.39−7.30 (m, 10H), 5.31 (s, 1H), 2.66−2.39 (m,
3H), 2.31−2.18 (m, 2H), 1.04 (d, J = 6.0 Hz, 3H); 13C NMR (62.5
MHz, CDCl3) δ 191.3, 168.2, 163.7, 137.2, 128.8, 128.6, 127.8, 122.0,
56.7, 45.2, 37.3, 28.0, 20.3; IR (KBr) ν (cm−1) 3026, 2966, 2891, 1747,
1691, 1635, 1265, 1188, 1113, 1088, 984, 750; HRMS (ESI-TOF)
calcd for C21H19ClO3Na 377.0915, found 377.0889.
2-Chloro-3-oxo-5-phenylcyclohex-1-enyl 2,2-diphenylethanoate
(8g): white crystals; 0.38 g, 46% yield; mp 110−111 °C; Rf 0.48
(CH2Cl2); 1H NMR (250 MHz, CDCl3) δ 7.35−7.22 (m, 15H), 5.29
(s, 1H), 3.54−3.41 (m, 1H), 3.03 (dd, J = 17.8, 11.0 Hz, 1H), 2.96−
2.73 (m, 3H); 13C NMR (62.5 MHz, CDCl3) δ 190.3, 168.2, 163.1,
141.1, 137.1, 137.0, 128.9, 128.8, 128.7, 128.6, 127.7, 127.5, 126.5,
122.3, 56.7, 44.2, 38.6, 37.1; IR (KBr) ν (cm−1) 3059, 3030, 1763,
1690, 1637, 1495, 1277, 1095, 974, 735, 698; HRMS (ESI-TOF) calcd
for C26H21ClO3Na 439.1071, found 439.1041.
2-Chloro-5-(p-methoxyphenyl)-3-oxocyclohex-1-enyl 2,2-diphe-
nylethanoate (8h): colorless oil; 0.70 g, 79% yield; Rf 0.40
(CH2Cl2). 1H NMR (250 MHz, CDCl3) δ 7.47−7.34 (m, 10H),
7.15 and 6.92 (AA′BB′ system, 4H), 5.36 (s, 1H), 3.80 (s, 3H), 3.46−
3.33 (m, 1H), 3.04−2.89 (m, 1H), 2.84−2.69 (m, 3H); 13C NMR
(62.5 MHz, CDCl3) δ 190.1, 168.0, 163.0, 158.5, 136.9, 133.0, 128.6,
128.5, 128.4, 127.5, 127.4, 122.1, 114.0, 56.4, 55.0, 44.2, 37.5, 37.1; IR
(KBr) ν (cm−1) 3024, 2954, 1763, 1701, 1569, 1512, 1321, 1254,
1223, 1177, 1097, 1008, 831; HRMS (ESI-TOF) calcd for C27H24ClO4
447.1363, found 447.1389.
Reaction of Diphenylketene with Iodonium Ylide 2f. From
diphenylketene (1.0 g, 5.15 mmol) and iodonium ylide 2f (0.85 g, 2.49
mmol) in dichloromethane (10 mL), stirred at room temperature for
3.0 d. Purification by flash chromatography (CH2Cl2) gave the
following compounds. 6,6-Dimethyl-3,3-diphenyl-6,7-dihydrobenzo-
furan-2,4(3H,5H)-dione (3f) as white crystals (0.49 g, 58% yield):
1
mp 104−105 °C (hexanes); Rf 0.67 (CH2Cl2); H NMR (250 MHz,
CDCl3) δ 7.31 (s, 10H), 2.66 (s, 2H), 2.36 (s, 2H), 1.19 (s, 6H); 13
C
NMR (62.5 MHz, CDCl3) δ 192.1, 176.0, 169.4, 138.5, 128.4, 128.3,
127.9, 120.8, 61.1, 51.8, 37.0, 33.8, 28.6; IR (KBr) ν (cm−1) 3059,
2959, 1813, 1647, 1493, 1447, 1381, 1223, 1130, 987, 926, 768, 699;
HRMS (ESI-TOF) calcd for C22H21O3 333.1491, found 333.1485. 6,6-
Dimethyl-2,2-diphenyl-6,7-dihydrobenzofuran-3,4(2H,5H)-dione
(5f) as white needles (0.35 g, 42% yield): mp 197−200 °C (EtOAc);
1
Rf 0.18 (CH2Cl2); H NMR (250 MHz, CDCl3) δ 7.45−7.33 (m,
10H), 2.79 (s, 2H), 2.38 (s, 2H), 1.18 (s, 6H); 13C NMR (62.5 MHz,
CDCl3) δ 199.1, 193.6, 191.0, 136.8, 128.8, 128.5, 126.5, 111.8, 95.4,
51.8, 40.2, 33.7, 28.4; IR (KBr) ν (cm−1) 3059, 2955, 1724, 1666,
1578, 1439, 1408, 1331, 1238, 1072, 953, 768, 698; HRMS (ESI-TOF)
calcd for C22H21O3 333.1491, found 333.1494.
General Procedure for the Reaction of Diphenylacetyl
Chloride with Iodonium Ylides 2. A solution of iodonium ylide
2 (1.91−2.01 mmol) and diphenylacetyl chloride (1.91−4.40 mmol)
in dichloromethane (10 mL) was stirred at room temperature for 2−
12 h. The solvent was evaporated under reduced pressure. The
product was isolated by silica gel column chromatography with
dichloromethane.
2-Chloro-5,5-dimethyl-3-oxocyclohex-1-enyl 2,2-diphenyletha-
noate (8i): white solid; 0.51 g, 68% yield; mp 132−134 °C
1
(EtOAc); Rf 0.62 (CH2Cl2); H NMR (250 MHz, CDCl3) δ 7.42−
7.32 (m, 10H), 5.27 (s, 1H), 2.52 (s, 2H), 2.45 (s, 2H), 1.10 (s, 6H);
13C NMR (62.5 MHz, CDCl3) δ 191.1, 168.4, 162.4, 137.1, 128.8,
128.6, 127.7, 121.6, 56.6, 51.0, 43.0, 32.6, 27.8; IR (KBr) ν (cm−1)
3059, 2957, 1772, 1690, 1634, 1456, 1265, 1153, 1095, 1022, 943,
760;. HRMS (ESI-TOF) calcd for C22H21ClNaO3 391.1071, found
391.1070.
2-Chloro-3-oxocyclopent-1-enyl 2,2-diphenylethanoate (8a):
white solid; 0.58 g, 89% yield; mp 110−112 °C (EtOAc−hexanes);
1
Rf 0.35 (CH2Cl2); H NMR (250 MHz, CDCl3) δ 7.43−7.31 (m,
10H), 5.33 (s, 1H), 2.92−2.88 (m, 2H), 2.53−2.50 (m, 2H); 13C
NMR (62.5 MHz, CDCl3) δ 197.4, 174.0, 167.4, 136.6, 128.6, 128.3,
127.6, 119.6, 56.8, 32.9, 26.6; IR (KBr) ν (cm−1) 3064, 3028, 2937,
1776, 1724, 1635, 1265, 1204, 1094, 878, 737; HRMS (ESI-TOF)
calcd for C19H15ClNaO3 349.0602, found 349.0601.
ASSOCIATED CONTENT
■
2-Chloro-3-oxocyclohex-1-enyl 2-methylethanoate (8b):14 color-
S
* Supporting Information
less oil; 0.33 g, 80% yield; Rf 0.42 (CH2Cl2). H NMR (250 MHz,
1H and 13C spectra of 2a, 3a−f, 5a−f, 6a, and 8a-I, X-ray
studies of phenyliodonium ylide 2a; X-ray studies of lactone 3b
aurone derivative 5b. This material is free of charge via the
Internet at http://pubs.acs.org.
1
CDCl3) δ 2.59−2.54 (m, 2H), 2.50−2.41 (m, 4H), 2.01−1.91 (m,
2H), 1.10 (t, J = 7.5 Hz, 3H); 13C NMR (62.5 MHz, CDCl3) δ 191.1,
169.5, 164.4, 121.4, 37.0, 29.6, 27.1, 19.9, 8.5; IR (KBr) ν (cm−1)
1946, 1774, 1690, 1628, 1460, 1420, 1342, 1278, 1166, 1114, 1076,
1016, 984, 840, 824.
AUTHOR INFORMATION
2-Chloro-3-oxocyclohex-1-enyl 2-phenylethanoate (8c): colorless
oil; 0.51 g, 96% yield; Rf 0.42 (CH2Cl2); 1H NMR (250 MHz, CDCl3)
δ 7.33 (s, 3H), 3.83 (s, 2H), 2.64−2.52 (m, 4H), 2.03−1.96 (m, 2H);
13C NMR (62.5 MHz, CDCl3) δ 191.2, 166.8, 164.3, 132.1, 129.2,
128.6, 127.4, 121.8, 40.6, 37.0, 29.6, 19.6; IR (KBr) ν (cm−1) 3030,
2961, 1763, 1684, 1576, 1340, 1327, 1109, 1014, 972, 700; HRMS
(ESI-TOF) calcd for C14H13ClO3Na 287.0445, found 287.0430.
2-Chloro-3-oxocyclohex-1-enyl 2,2-dimethylethanoate (8d): col-
■
Corresponding Authors
*Tel: +30-26510-08380. Fax: +30-26510-08799. E-mail:
lxatziar@cc.uoi.gr.
§Authors to whom questions regarding X-ray analysis should be
addressed.
Notes
1
orless oil; 0.38 g, 88% yield; Rf 0.38 (CH2Cl2); H NMR (250 MHz,
The authors declare no competing financial interest.
CDCl3) δ 2.77−2.66 (m, 1H), 2.64−2.59 (m, 2H), 2.56−2.50 (m,
2H), 2.07−1.97 (m, 2H), 1.22 (d, J = 7.0 Hz, 6H); 13C NMR (62.5
MHz, CDCl3) δ 191.2, 172.3, 164.6, 121.7, 37.1, 34.0, 29.8, 20.0, 18.5;
‡Erasmus student from Technical University of Lot
spring 2009.
́
z, Poland,
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Note
ACKNOWLEDGMENTS
■
We gratefully acknowledge the NMR center and the ORBI-
TRAP mass unit of the University of Ioannina for NMR and
HRMS measurements. J.A.N. thanks Propondis Foundation for
a Ph.D. fellowship. We also thank Dr. C. Dolka for measuring
HRMS and Prof. Dr. A. de Meijere, University of Goettingen,
for donation of 1,3-cyclopentanedione.
REFERENCES
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