Cu-catalyzed reaction of 1,2-dihalobenzenes with 1,3-cyclohexanediones for the synthesis of 3,4-dihydrodibenzo[b,d]furan-1(2H)-ones

Article abstract of DOI:10.1021/jo3014275

The Cu(I)-catalyzed reaction of 1-bromo-2- iodobenzenes and other 1,2-dihalobenzenes with 1,3-cyclohexanediones in DMF at 130 °C using Cs ₂CO₃ as a base and pivalic acid as an additive selectively delivers 3,4- dihydrodibenzo[b,d]fur

Full text of DOI:10.1021/jo3014275

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pubs.acs.org/joc
Cu-Catalyzed Reaction of 1,2-Dihalobenzenes with
1,3-Cyclohexanediones for the Synthesis of
3,4-Dihydrodibenzo[b,d]furan-1(2H)‑ones
Nayyef Aljaar,† Chandi C. Malakar,† Jurgen Conrad,† Sabine Strobel,‡ Thomas Schleid,‡
̈
and Uwe Beifuss*,†
†Bioorganische Chemie, Institut fur Chemie, Universitat Hohenheim, Garbenstraße 30, D-70599 Stuttgart, Germany
̈
̈
‡Institut fur Anorganische Chemie, Universitat Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany
̈
̈
S
* Supporting Information
ABSTRACT: The Cu(I)-catalyzed reaction of 1-bromo-2-
iodobenzenes and other 1,2-dihalobenzenes with 1,3-cyclo-
hexanediones in DMF at 130 °C using Cs2CO3 as a base
and pivalic acid as an additive selectively delivers 3,4-
dihydrodibenzo[b,d]furan-1(2H)-ones with yields ranging
from 47 to 83%. The highly regioselective domino process is
based on an intermolecular Ullmann-type C-arylation followed by an intramolecular Ullmann-type O-arylation. Substituted
products are accessible by employing substituted 1-bromo-2-iodobenzenes and substituted 1,3-cyclohexanediones as substrates.
Reaction with an acyclic 1,3-diketone yields the corresponding benzo[b]furan.
need for new methods that avoid the use of complex substrates,
expensive reagents, additives, and catalysts and allow for the
straightforward synthesis of dibenzo[b,d]furans from readily
available starting materials. Recently, we reported on Cu-
catalyzed domino reactions for the synthesis of a number of
carbocycles and heterocycles,14 such as the reaction between
2-halobenzyl halides and amidines for the preparation of
quinazolines14a and the reaction between 2-halobenzyl halides
and β-ketoesters for the synthesis of naphthalenes and 4H-
chromenes.14c It was assumed that the synthesis of dibenzo-
[b,d]furans could be achieved by a domino intermolecular
C-arylation/intramolecular O-arylation of a 1,2-dihalobenzene
and a 1,3-cyclohexanedione (I + II → III → IV) (Scheme 1).
Needless to say, if successful, this approach could be extended
to the synthesis of numerous other O-heterocyclic systems. The
Cu-catalyzed reaction between 1,2-dihalobenzenes and 1,3-
diketones has not been reported so far. However, Ma et al. have
achieved the Cu-catalyzed reaction between 1,2-dihalobenzenes
and β-ketoesters for the preparation of benzo[b]furans.15
In recent years, there was great interest in the transition-
metal-catalyzed arylation of 1,3-dicarbonyls with aryl halides.16
The Pd-catalyzed C-arylation of 1,3-dicarbonyls dates back to
the 1980s17 and has been further developed over the years.18
Meanwhile, it is considered as a highly useful synthetic method.
The only disadvantage of the Pd-catalyzed transformation is the
need for expensive Pd reagents and ligands. This is the reason
why there is a strong interest in replacing the Pd reagents
by much cheaper Cu reagents. Early examples for the Cu-
catalyzed arylation of 1,3-dicarbonyls include the reaction of
INTRODUCTION
■
Numerous molecules with a benzo[b]furan or a dibenzo[b,d]-
furan skeleton1 have been isolated from natural sources. Typical
examples include the karnatakafurans A and B from Aspergillus
karnatakaensis Frisvad,2a achyrofuran from Achyrocline satu-
reioides,2b the porric acids A−C from Allium porrum L,2c popolo-
huanone E from a Pohnpei sponge Dysidea sp.,2d eriobofuran
from Eriobotrya japonica L,2e and the α-, β-, and γ-pyrufurans
from Pyrus communis L2f,g (Figure 1). Compounds that contain a
dibenzo[b,d]furan structure element exhibit a wide range of
biological activities including antimalarial,2a antimicrobial,2a
antifungal,2c,e cytotoxic,2d antitubercular,3a,b and antimycobacterial
properties.3c,d
There has been continuing interest in the development of
novel synthetic methods for the efficient preparation of
dibenzo[b,d]furans. Over the years, various routes have been
reported for the synthesis of this skeleton. They include the
ring closure of 2-phenoxybenzene diazonium salts which was
first reported by Graebe and Ullmann,4 intermolecular Diels−
Alder reactions between 2- or 3-nitrobenzofurans and electron-
rich dienes,5 the reaction of benzofuran-3-ones with 2H-pyran-
2-ones,6 and the reaction of o-silyl aryltriflates with iodonium
ylides.7 More recently, the focus was on the development of
methods based on transition-metal-catalyzed transformations.
Among them are the Pd-catalyzed cyclization of 1-halo-2-
phenoxybenzenes,8 the Pd-catalyzed oxidative cyclization of
diphenyl ethers,9 the Pd- or Cu-catalyzed intramolecular O-
arylation of 2-halobiphenyl-2′-ols,10 the Pd- or Cu-catalyzed
oxidative cyclization of 2-arylphenols,11 the Pd-catalyzed
intramolecular cyclization of 1-carboxyl-2-phenoxybenzenes,12
and the Au-catalyzed reaction between O-arylhydroxylamines
and 1,3-dicarbonyls.13 Despite these advances, there is still a
Received: July 13, 2012
Published: August 23, 2012
© 2012 American Chemical Society
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Figure 1. Selected natural products with a dibenzo[b,d]furan skeleton.
Scheme 1. Proposed Route for the Cu-Catalyzed Synthesis of 3,4-Dihydrodibenzo[b,d]furan-1(2H)-ones
o-bromobenzoic acid with several 1,3-dicarbonyls.19 However,
many of these transformations need comparably harsh reaction
conditions, like high reaction temperatures and/or strong bases.
Meanwhile, a number of protocols are known that allow for
milder reaction conditions as well as better yields. Typical
examples are the reactions of aryl iodides and aryl bromides
with 1,3-dicarbonyls and related compounds, such as malonic
esters, β-ketoesters, β-diketones, cyanoacetates, and malononi-
trile.20 The scope of the Cu-catalyzed C-arylation of 1,3-
dicarbonyls can be extended tremendously when they are
combined with other transformations to new domino
processes. Using this approach, a number of heterocycles can
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be synthesized efficiently. Typical examples are related to the pre-
paration of N- and O-heterocycles such as indoles,21 isoquino-
lines,22 benzimidazoisoquinolines,23 and 4H-chromenes.14c
Herein, we disclose a new and straightforward approach for
the selective synthesis of dibenzo[b,d]furan derivatives that is
based on the Cu-catalyzed domino reaction between 1,2-
dihalobenzenes 1 and 1,3-cyclohexanediones 2.
extending the reaction time (Table 1, entries 2−5). When the
experiment was run for 28 h, 3a was isolated in 71% yield as the
sole product (Table 1, entry 5).
Next, the influence of the amount of CuI on the outcome of
the reaction was studied. The yield dropped from 71% to 59%
when the reaction was run in the presence of 5 mol % of CuI
(Table 1, entry 6). Remarkably enough, the yield could not be
improved by increasing the amount of CuI to 15 mol % or even
to 20 mol % (Table 1, entries 7 and 8). The effect of the
amount of pivalic acid on the result of the reaction was also of
interest. The use of 0.6 equiv of pivalic acid led to a significant
24% yield drop (Table 1, entry 9). Interestingly, an increase of
the amount of pivalic acid to 1.8 equiv did not pay off as well
(Table 1, entry 10). Furthermore, it was established that the
amount of Cs2CO3 can be reduced to 1.5 equiv without affecting
the yield (Table 1, entry 11). When the reaction was conducted
with 3 equiv of Cs2CO3, the yield of 3a decreased to 52% (Table 1,
entry 12). The highest yield of 3a (75%) was obtained when
the amount of 2a was increased from 1 to 1.5 equiv (Table 1,
entry 13). A further increase of 2a to 2 equiv did not pay off
(Table 1, entry 14). Performing the reaction at 100 and 150 °C
did not bring any improvement. Instead, the yield of 3a dropped
to 69% and 55%, respectively (Table 1, entries 15 and 16).
On the basis of the reaction conditions given in the Table 1,
entry 13, the influence of different bases and solvents on the
model reaction was investigated (Table 2). It was interesting to
RESULTS AND DISCUSSION
■
The reaction between 1-bromo-2-iodobenzene (1a) and 1,
3-cyclohexanedione (2a) was chosen as a model reaction.
When 1 equiv of 1a and 2 equiv of 2a were reacted under the
reaction conditions that have been developed by Ma et al. for
the synthesis of substituted benzo[b]furans from 1-bromo-2-
iodobenzenes 1 and acyclic β-ketoesters, i.e., 10 mol % of CuI,
3 equiv of K2CO3 in THF at 100 °C for 24 h, not even a trace
of the desired dibenzo[b,d]furan was formed. Pivalic acid as an
additive is known to improve the yield of several Pd-catalyzed
inter- and intramolecular arylations that are based on the
activation of C−H bonds.24 Very recently, there was also a
report on the Cu-catalyzed oxidative C(sp2)−H cyclo-
etherification of o-arylphenols using pivalic acid to facilitate
the C−H bond activation.11a Although there was no hint for
the use of pivalic acid as an additive in transition-metal-
catalyzed reactions between aryl halides and 1,3-dicarbonyls, it
seemed worthwhile to investigate the influence of pivalic acid
on the Cu-catalyzed model reaction between 1a and 2a. When
equimolar amounts of 1a and 2a were reacted in the presence
of 10 mol % of CuI, 2 equiv of Cs2CO3, and 1.2 equiv of pivalic
acid in DMF at 130 °C for 7 h, 3,4-dihydrodibenzo[b,d]-
furan1(2-H)-one (3a) could be isolated in 16% yield (Table 1,
Table 2. Influence of Bases and Solvents on the Outcome of
a
the Model Reaction 1a + 2a → 3a
Table 1. Optimization of the Reaction between 1-Bromo-2-
iodobenzene (1a) and 1,3-Cyclohexanedione (2a) To Yield
3,4-Dihydrodibenzo[b,d]furan-1(2H)-one (3a)
entry
base
solvent
DMF
T (°C) time (h) yield of 3a (%)
1
2
K3PO4
K2CO3
130
130
130
130
130
100
130
130
100
100
100
28
28
24
24
28
24
28
28
24
28
24
70
62
DMF
3
DMF
4
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
DMSO
DMA
74
71
66
56
42
52
35
15
5
molar
ratio
1a:2a
pivalic
acid
6
CH3CN
NMP
CuI
Cs2CO3
T
time yield of
(h) 3a (%)
7
entry
(mol %) (equiv)
(equiv) (°C)
8
1-nitropropane
THF
1
2
1:1
10
10
10
10
10
5
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
0.6
1.8
1.2
1.2
1.2
1.2
1.2
1.2
2
130
130
130
130
130
130
130
130
130
130
130
130
130
130
100
150
7
16
20
24
28
28
28
28
28
28
28
28
28
28
36
28
16
51
61
64
71
59
71
68
47
70
72
52
75
69
69
55
9
1:1
2
10
11
i-PrOH
C2H4Cl2
3
1:1
2
4
1:1
2
a
In all cases, 1 equiv of 1a was reacted with 1.5 equiv of 2a.
5
1:1
2
6
1:1
2
find that Cs2CO3 can be replaced with cheap bases like K3PO4
or K2CO3. Use of K3PO4 afforded 3a with 70% yield (Table 2,
entry 1), and with K2CO3 3a could be isolated with 62% yield
(Table 2, entry 2). As expected, in the absence of any base no
product was formed (Table 2, entry 3). The following
experiments focused on the influence of the solvent. Therefore,
the model reaction was run in a variety of different solvents
(Table 2). It was observed that the transformation can be run
not only in polar aprotic solvents like DMSO, DMA, CH3CN,
NMP, and 1-nitropropane but also in solvents like i-PrOH,
THF, and C2H4Cl2. The best yields were obtained with DMSO
and DMA, but in no case the yield did exceed the yield
obtained in DMF.
7
1:1
15
20
10
10
10
10
10
10
10
10
2
8
1:1
2
9
1:1
2
10
11
12
13
14
15
16
1:1
2
1:1
1.5
3
1:1
1:1.5
1:2
1.5
1.5
1.5
1.5
1:1.5
1:1.5
entry 1). Encouraged by this result, further experiments were
conducted. The yield of 3a could easily be increased by
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It was then studied whether other carboxylic acids than
pivalic acid can be used as acidic additives (Table 3). The
Table 4. Reactions of Different 1,2-Dihalobenzenes 4 with
1,3-Cyclohexanedione (2a)
a
Table 3. Influence of the Cu Source and Additives on the
Outcome of the Model Reaction 1a + 2a → 3a
entry
4
Hal1
Hal2
yield of 3a (%)
1
2
3
a
b
c
I
I
72
70
40
Br
Cl
Br
Cl
entry
additive
Cu source
yield of 3a (%)
a
1
2
acetic acid
CuI
60
64
70
46
In all cases, 1 equiv of 4 was reacted with 1.5 equiv of 2a.
propionic acid
isovaleric acid
benzoic acid
CuI
3
CuI
number of mono- and disubstituted 1,3-cyclohexanediones
2b−h. The results are summarized in Table 5. With most 1,3-
cyclohexanediones (i.e., 2b−e,h,i), the domino reaction
delivered the corresponding dihydrodibenzo[b,d]furan-1(2H)-
ones 3 exclusively. The yields were in the range between 62 and
80% (Table 5, entries 1−4 and 7). Surprisingly, with 5-(4-
methoxyphenyl)-1,3-cyclohexanedione (2f) and with 5-(4-
chlorophenyl)-1,3-cyclohexanedione (2g) as the substrates
not a trace of the expected dihydrodibenzo[b,d]furan-1(2H)-
ones was formed. Instead, the corresponding unsaturated
dibenzo[b,d]furan-1-ols 3f and 3g were isolated in 64% and
61% yield, respectively. So far, the reasons for the occurrence
of the oxidized products remain unclear. In addition to the 1,
3-cyclohexanediones the reaction was also run with 2,4-
pentanedione (2i) as the 1,3-dicarbonyl to yield 1-(2-
methylbenzofuran-3-yl)ethanone (3i) with 83% yield. This
experiment proved that the domino reaction is not restricted to
cyclic 1,3-dicarbonyls.
As a control experiment, the reaction between 1a and the
acyclic β-diketone 2i was conducted under the conditions
developed for the reaction of 1a with β-ketoesters in Ma’s
laboratory, i.e., 10 mol % of CuI, 3 equiv of K2CO3, THF, 100
°C, 24 h (Scheme 2). Under these conditions, not even a trace
of the expected product 3i was formed. This result emphasizes
that the success of Cu(I)-catalyzed domino processes with
different types of 1,3-dicarbonyls often depends on the careful
choice of catalysts, additives, solvents, and reaction conditions.
On the other hand, when 1a was reacted with ethyl
acetoacetate (5) under the conditions optimized for cyclic
β-diketones 2 the corresponding ethyl 2-methylbenzofuran-3-
carboxylate (6) was isolated in 63% yield (Scheme 2).
Then, the scope of the dibenzo[b,d]furan synthesis with
respect to the 1-bromo-2-iodobenzenes was studied (Table 6).
For this purpose, several 1-bromo-2-iodobenzenes with an
additional substituent in the 4- or 5-position were reacted with
1,3-cyclohexanedione (2a). The corresponding dihydro-
dibenzo[b,d]furans 3j−n were isolated with yields ranging
from 47 to 77%. In all cases, the domino process proceeds
highly regioselective, i.e., only a single regioisomer was formed.
With o-bromoiodobenzenes 1c,d,f carrying an additional
substituent in the para-position to iodine, only the 7-
substituted products 3k,l,n were formed. The meta-substituted
substrates 1b and 1e delivered exclusively the 8-substituted
products 3j and 3m.
4
CuI
5
CuI
6
pivalic acid
pivalic acid
pivalic acid
pivalic acid
pivalic acid
pivalic acid
CuCl
CuBr
CuCN
Cu2O
Cu
63
66
30
64
32
6
7
8
9
10
a
In all cases, 1 equiv of 1a was reacted with 1.5 equiv of 2a.
model reaction could be performed with different carboxylic
acids like acetic acid, propionic acid, isovaleric acid, and benzoic
acid, but in all cases the yields were inferior compared to pivalic
acid. A control experiment demonstrated that in the absence of
an acidic additive not even a trace of 3a was formed (Table 3,
entry 5). Finally, we focused on the role of different Cu sources.
For this purpose, the model reaction was run with several Cu(I)
compounds as well as with elemental copper under the
condition given in Table 1, entry 13. It was found that with
CuBr, CuCl, and Cu2O the yields of 3a were higher than 60%
and that 3a was even formed with elemental copper as the Cu
source. However, in no case did the yield exceed the yield
obtained with CuI. A control experiment established that the
domino reaction does not take place in the absence of a Cu
source (Table 3, entry 10).
Control experiments clearly established that the reaction
between 1a and 2a cannot be run successfully in the absence of
a base (Table 2, entry 3), an acidic additive (Table 3, entry 5),
and of course, a Cu source (Table 3, entry 10). In none of the
three control experiments could the product 3a be detected.
After successful optimization of the reaction conditions, we
began to study the scope of the domino process with respect
to both the 1,2-dihalobenzene and the 1,3-dicarbonyl. First,
we examined whether 1-bromo-2-iodobenzene (1a) can be
replaced with other 1,2-dihalobenzenes (Table 4). The
experiments revealed that 1a can be replaced by 1,2-
diiodobenzene (4a) and 1,2-dibromobenzene (4b) without
any significant yield loss of 3a. 1,2-Dichlorobenzene (4c) can
also be used as a substrate for the Cu(I)-catalyzed dibenzofuran
synthesis. However, the yield of 3a was much lower (Table 4,
entry 3). All further reactions were conducted with 1-bromo-2-
iodobenzenes as the substrate. This was not only because of the
excellent yields obtained with 1a but also because only the use
of a mixed 1,2-dihalobenzene opens the possibility for
regioselective reactions with substituted dihalobenzenes.
To study the scope of the dibenzofuran synthesis, the
reaction of 1-bromo-2-iodobenzene (1a) was carried out with a
The high regioselectivity of the transformation requires that
the first step of the domino process is either a C,C-bond
formation between the C−I bond of 1b−f and C-2 of the 1,3-
diketone 2a or a C,O-bond formation between the C−Br bond
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Table 5. Reaction of 1-Bromo-2-iodobenzene (1a) with
Different 1,3-Dicarbonyls 2
Scheme 2. Reaction of 1a with 2i and 5 under Different
Reaction Conditions
a
Table 6. Reaction of 1,3-Cycohexanedione (2a) with
a
Different 1-Bromo-2-iodobenzenes 1
a
In all cases, 1 equiv of 1a was reacted with 1.5 equiv 2.
of 1b−f and an oxygen atom of the 1,3-dicarbonyl 2a. To
explore the mechanistic alternatives, two control experiments
were performed; i.e., the reactions between iodobenzene (7a)
and bromobenzene (7b) with acetylacetone (2i) (Scheme 3).
Both reactions were performed under our optimized reaction
conditions for 3 and 4.5 h, respectively. In both experiments,
only 8, i.e., the C-arylation product, was formed. Not even a
trace of the corresponding O-arylation product was isolated.
This is a clear indicator that the C,C-bond formation between 1
and 2 takes place as the first step of the formation of 3.
This result also supports the view that the new C,C bond
originates from the reaction between the C−I bond of 1a and
C-2 of the 1,3-diketone 2a. This assumption requires that the
C−Br bond is less reactive than the C−I bond. Therefore, a
competition experiment between 7a/7b and 2i was performed.
For this purpose, a 1:1 mixture of 7a (1 mmol) and 7b
a
In all cases, 1 equiv 1 was reacted with 1.5 equiv 2a.
(1 mmol) was reacted with 2i (1 mmol) under the conditions
of our optimized protocol. After 5 h, 58% of 8 and 28% of a
mixture of 7a and 7b in a 24:76 ratio were isolated. These
results clearly indicate that the C−I bond of 7a is much more
reactive than the C−Br bond of 7b. In summary, the results
obtained strongly support the view that the first step of the
domino process proceeds as an intermolecular C,C-bond
formation between C-2 of the 1,3-diketone and the aromatic
carbon atom carrying the iodo substituent. The second step is
an intramolecular C,O-bond formation between an O-atom of
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two rings A and C are linked by the four carbons C-4a, C-9b,
C-9a, and C-5a as shown in Figure 2.
Scheme 3. Reactions between Iodobenzene (7a) and
Bromobenzene (7b) with Acetylacetone (2i)
Unequivocal evidence for the structure of the 3j was
produced by X-ray structure analysis. For this purpose, crystals
of 3j were studied by X-ray crystal structure analysis (see the
Supporting Information).25
CONCLUSIONS
■
In summary, we have developed a simple and efficient method for
the regioselective preparation of 3,4-dihydro[b,d]furan-1(2H)-
ones by reaction between 1-bromo-2-iodobenzenes 1 and 1,3-
cyclohexanediones 2. The CuI-catalyzed reaction is regarded as a
domino intermolecular Ullmann C-arylation/intramolecular Ull-
mann O-arylation that delivers the products with high selectivity
and with yields ranging from 47 to 83%. The domino process can
also be achieved with 1,2-diiodobenzene and 1,2-dibromobenzene
as the aromatic substrate and with acetylacetone or ethyl
acetoacetate as the 1,3-dicarbonyl.
Scheme 4. Proposed Reaction Mechanism
EXPERIMENTAL SECTION
■
General Remarks. All commercially available reagents were used
without further purification. Glassware was dried for 4 h in 140 °C.
Solvents used in reactions were distilled over appropriate drying agents
prior to use. Solvents used for extraction and purification were distilled
prior to use. Reaction temperatures are reported as bath temperature.
Thin-layer chromatography (TLC) was performed on TLC silica gel
60 F254. Compounds were visualized with UV light (λ = 254 nm)
and/or by immersion in an ethanolic vanillin solution or by immersion
in KMnO4 solution followed by heating. Products were purified by
flash chromatography on silica gel, 0.04−0.063 mm. Melting points
were obtained on a melting point apparatus with open capillary tubes
and are uncorrected. IR spectra were measured on a FT-IR
spectrometer. UV/vis spectra were recorded with a spectrophotom-
eter. 1H (13C) NMR spectra were recorded at 300 (75) and 500 (125)
MHz using CDCl3 or CD3OD as the solvent. The 1H and 13C
chemical shifts were referenced to residual solvent signals at δ H/C
7.26/77.00 (CDCl3) and 3.31/49.1 (CD3OD) relative to TMS as
internal standard. HSQC, HMBC, NOESY, ROESY, HSQMBC, and
COSY spectra were recorded on a NMR spectrometer at 500 and 300
MHz. Coupling constants J (Hz) were directly taken from the spectra
and are not averaged. Splitting patterns are designated as s (singlet), d
(doublet), t (triplet), q (quartet), quin (quintet), m (multiplet), and br
(broad). 1D and 2D homonuclear NMR spectra were measured with
standard pulse sequences. Low-resolution electron impact mass spectra
(MS) and exact mass electron impact mass spectra (HRMS) were
obtained at 70 eV using a double-focusing sector field mass
spectrometer. Intensities are reported as percentages relative to the
base peak (I = 100%).
the 1,3-dicarbonyl and the aromatic carbon carrying the bromo
atom (Scheme 4).
The structures of all compounds were unambiguously
elucidated by NMR spectroscopy and mass spectrometry.
Structure elucidation of all compounds and full assignment of
1
the H and 13C chemical shifts were achieved by evaluating
their gCOSY, gHSQC, and gHMBC spectra. For example,
compound 3j contains two scalar coupled 1H spin systems, one
consisting of alicyclic protons at C-2,C-3 and C-4-H (ring A)
and the other of aromatic protons 6-H, 7-H, 9-H (ring B). The
sequence of the protons in both spin systems was determined
by analysis of the gCOSY spectrum. To prove the proposed
structure, we used gHMBC optimized for 3JCH = 8 Hz to fix the
positions of the six quaternary carbons C-1, C-4a, C-5a, C-8,
C-9a, and C-9b. Carbon C-9b showed strong 3J-HMBC
correlations to protons 2-H, 4-H, and 9-H, C-9a to proton
6-H, C-5a to protons 7-H and 9-H, C-1′ to protons 9-H and
7-H as well as C-4a to 3-H. These findings established that the
General Procedure. An oven-dried sealed tube was flushed with
argon and charged with pivalic acid (122 mg, 1.2 mmol), Cs2CO3
(651 mg, 1.5 mmol), a 1,2-dihaloarene 1 (1 mmol), a 1,3-diketone 2
(1.5 mmol), and CuI (19 mg, 0.1 mmol). The tube was evacuated and
backfilled with argon two times, and dry DMF (2 mL) was added. The
reaction mixture was stirred at 130 °C until the 1,2-dihaloarene 1 was
1
Figure 2. H spin system and important HMBC correlations (H→C) for 3j.
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consumed. After being cooled to room temperature, the reaction
mixture was partitioned between EtOAc (30 mL) and saturated
ammonium chloride (20 mL). The organic layer was isolated, and the
aqueous layer was extracted with EtOAc (3 × 30 mL). The combined
organic layers were dried over anhydrous MgSO4 and concentrated in
vacuum. The residue was purified by flash chromatography on silica gel
to afford the desired product.
(222 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 24 h. Flash chromatography
over silica gel (cyclohexane/EtOAc = 10:1) gave 3c as a yellow solid in
80% yield (172 mg, 0.80 mmol): mp 121−122 °C (lit.17 mp 120.8−
1
121.1 °C); Rf = 0.50 (cyclohexane/EtOAc = 3:1); H NMR (300
MHz, CDCl3) δ 1.20 (s, 6H, 1′-H, 1″-H), 2.49 (s, 2H, 2-H), 2.90 (s,
2H, 4-H), 7.28−7.32 (m, 1H, 7-H), 7.30−7.35 (m, 1H, 8-H), 7.46−
7.49 (m, 1H, 6-H), 8.03−8.06 (m, 1H, 9-H); 13C NMR (75 MHz,
CDCl3) δ 28.6 (C-1′, C-1″), 35.2 (C-3), 37.7 (C-4), 52.2 (C-2), 111.1
(C-6), 115.3 (C-9b), 121.7 (C-9), 123.6 (C-9a), 124.4 (C-8), 124.8
(C-7), 154.9 (C-5a), 169.9 (C-4a), 194.1 (C-1); MS (EI, 70 eV) m/z
214 (28) [M+], 199 (52) [M − CH3]+, 158 (8) [199 − C3H5]+.
3-Isopropyl-3,4-dihydrodibenzo[b,d]furan-1(2H)-one (3d).
3,4-Dihydrodibenzo[b,d]furan-1(2H)-one (3a).7,13
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1a (283 mg, 1 mmol), 2a
(183 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 28 h. Flash chromatography
over silica gel (cyclohexane/EtOAc = 8:1) gave 3a as a pale yellow oil in
75% yield (139 mg, 0.75 mmol): Rf = 0.26 (cyclohexane/EtOAc = 3:1);
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1a (283 mg, 1 mmol), 2d
(248 mg, 1.5 mmol), and CuI (19 mg, 0.1 mol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 24 h. Flash chromatography
over silica gel (cyclohexane/EtOAc = 8:1) gave 3d as a colorless oil in
80% yield (182 mg, 0.80 mmol): Rf = 0.55 (cyclohexane/EtOAc =
1H NMR (300 MHz, CDCl3) δ 2.28 (quin, J (2-H, 3-H) = 6.2 Hz, J
(3-H, 4-H) = 6.2 Hz, 2H, 3-H), 2.61 (t, 3J (2-H, 3-H) = 6.2 Hz, 2H, 2-
H), 3.04 (t, 3J (3-H, 4-H) = 6.2 Hz, 2H, 4-H), 7.28−7.32 (m, 1H, 7-H),
7.31−7.35 (m, 1H, 8-H), 7.45−7.48 (m, 1H, 6-H), 8.04−8.07 (m, 1H,
9-H); 13C NMR (75 MHz, CDCl3) δ 22.5 (C-3), 23.8 (C-4), 37.9 (C-2),
111.0 (C-6), 116.5 (C-9b), 121.8 (C-9), 123.7 (C-9a), 124.4 (C-8), 125.0
(C-7), 154.5 (C-5a), 170.8 (C-4a), 194.8 (C-1); MS (EI, 70 eV) m/z 186
(60) [M+], 158 (80) [186 − C2H4]+, 130 (56) [158 − CO]+.
3
3
3:1); IR (ATR) ν
̃
1663 (CO), 1590, 1449, 1171, 1039, 833, 750,
670 cm−1; UV (MeCN) λmax (log ε) 289 (3.61), 265 (3.90), 249
(3.94), 227 (4.18) nm; 1H NMR (300 MHz, CDCl3) δ 1.02 (d, 3J (1′-
3
H, 2′-H) = 6.9 Hz, 3H, 2′-H), 1.02 (d, J (1′-H, 3′-H) = 6.9 Hz, 3H,
3-Methyl-3,4-dihydrodibenzo[b,d]furan-1(2H)-one (3b).
3′-H), 1.69−1.96 (m, 1H, 1′-H), 2.13−2.29 (m, 1H, 3-H), 2.40 (dd, 3J
(2-Ha, 3-H) = 1.3 Hz, 2J (2-Ha, 2-Hb) = 15.9 Hz, 1H, 2-Ha), 2.67 (dd,
2
3J (2-Hb, 3-H) = 3.7 Hz, J (2-Ha, 3-Hb) = 16.1 Hz, 1H, 2-Hb), 2.78
(dd, 3J (3-H, 4-Ha) = 10.7 Hz, 2J (4-Ha, 4-Hb) = 17.3 Hz, 1H, 4-Ha),
3.07 (dd, 3J (3-H, 4-Hb) = 5.0 Hz, 2J (4-Ha, 4-Hb) = 17.5 Hz, 1H, 4-
Hb), 7.27−7.32 (m, 1H, 7-H), 7.31−7.36 (m, 1H, 8-H), 7.42−7.51
(m, 1H, 6-H), 7.99−8.08 (m, 1H, 9-H); 13C NMR (75 MHz, CDCl3)
δ 19.62 (C-3′), 19.85 (C-2′), 27.4 (C-4), 32.0 (C-1′), 42.05 (C-3),
42.16 (C-2), 111.1 (C-6), 116.3 (C-9b), 121.7 (C-9), 123.6 (C-9a),
124.4 (C-8), 124.9 (C-7), 154.8 (C-5a), 171.1 (C-4a), 194.7 (C-1);
MS (EI, 70 eV) m/z 228 (88) [M+], 213 (4) [M − CH3]+, 185 (10)
[213 − C2H4]+, 158 (100) [185 − C2H3]+, 130 (38) [158 − CO]+;
HRMS (EI; M+) calcd for C15H16O2 (228.1150), found 228.1146.
3-Phenyl-3,4-dihydrodibenzo[b,d]furan-1(2H)-one (3e).
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1a (283 mg, 1 mmol), 2b
(201 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 20 h. Flash chromatography
over silica gel (cyclohexane/EtOAc = 8:1) gave 3b as a white solid in
78% yield (156 mg, 0.78 mmol): mp 96−97 °C; Rf = 0.43
(cyclohexane/EtOAc = 3:1); IR (ATR) ν
̃
1663 (CO), 1596,
1449, 1169, 1039, 885, 748, 666 cm−1; UV (MeCN) λmax (log ε) 227
(4.28), 249 (4.02) nm; 1H NMR (500 MHz, CDCl3) δ 1.24 (d, 3J (1′-H,
3-H) = 6.4 Hz, 3H, 1′-H), 2.36 (dd, 3J (2-Ha, 3-H) = 11.0 Hz, 2J (2-Ha,
3
2-Hb) = 15.8 Hz, 1H, 2-Ha), 2.42−2.61 (m, 1H, 3-H), 2.65 (dd, J
(2-Hb, 3-H) = 3.6 Hz, 2J (2-Ha, 2-Hb) = 15.8 Hz, 1H, 2-Hb), 2.71 (dd, 3J
(3-H, 4-Ha) = 9.4 Hz, 2J (4-Ha, 4-Hb) = 17.2 Hz, 1H, 4-Ha), 3.11 (dd, 3J
(3-H, 4-Hb) = 4.7 Hz, 2J (4-Ha, 4-Hb) = 17.2 Hz, 1H, 4-Hb), 7.27−7.32
(m, 1H, 7-H), 7.31−7.36 (m, 1H, 8-H), 7.45−7.48 (m, 1H, 6-H), 8.0−
8.09 (m, 1H, 9-H); 13C NMR (125 MHz, CDCl3) δ 21.0 (C-1′), 30.6
(C-3), 31.7 (C-4), 46.3 (C-2), 111.0 (C-6), 116.1 (C-9b), 121.6 (C-9), 123.6
(C-9a), 124.4 (C-8), 124.9 (C-7), 154.7 (C-5a), 170.4 (C-4a), 194.3
(C-1); MS (EI, 70 eV) m/z 200 (64) [M+], 185 (4) [M − CH3]+, 158
(100) [185 − C2H3]+, 130 (52) [158 − CO]+; HRMS (EI, M+) calcd
for C13H12O2 (200.0837), found 200.0827.
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1a (283 mg, 1 mmol), 2e
(282 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 24 h. Flash chromatography
over silica gel (cyclohexane/EtOAc = 10:1) gave 3e as a white solid in
62% yield (162 mg, 0.62 mmol): mp 156−157 °C; Rf = 0.53
(cyclohexane/EtOAc = 3:1); IR (ATR) ν
̃
1652 (CO), 1587, 1482,
1402, 1168, 1043, 833, 759, 740, 694, 668 cm−1; UV (MeCN) λmax
3,3-Dimethyl-3,4-dihydrodibenzo[b,d]furan-1(2H)-one (3c).13
1
(log ε) 265 (3.85), 249 (3.96), 227 (4.34) nm; H NMR (300 MHz,
3
CDCl3) δ 2.83−2.98 (m, 2H, 2-H), 3.24 (dd, J (3-H, 4-Ha) = 10.6
Hz, 2J (4-Ha, 4-Hb) = 17.6 Hz, 1H, 4-Ha), 3.34 (dd, 3J (3-H, 4-Hb) =
2
5.4 Hz, J (4-Ha, 4-Hb) = 17.6 Hz, 1H, 4-Hb), 3.62−3.75 (m, 1H,
3-H), 7.27−7.37 (m, 2H, 2′-H, 6′-H), 7.30−7.40 (m, 3H, 7-H, 8-H,
4′-H), 7.35−7.44 (m, 2H, 3′-H, 5′-H), 7.45−7.53 (m, 1H, 6-H), 8.05−
8.13 (m, 1H, 9-H); 13C NMR (75 MHz, CDCl3) δ 31.6 (C-4), 41.2
(C-3), 45.2 (C-2), 111.2 (C-6), 116.5 (C-9b), 121.8 (C-9), 123.5
(C-9a), 124.6 (C-8), 125.1 (C-7), 126.8 (C-2′), 127.3 (C-4′), 128.9
(C-3′), 142.2 (C-1′), 154.9 (C-5a), 169.9 (C-4a), 193.3 (C-1); MS
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1a (283 mg, 1 mmol), 2c
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(EI, 70 eV) m/z 262 (56) [M+], 158 (100) [M − C8H8]+, 130 (32)
[158 − CO]+; HRMS (EI; M+) calcd for C18H14O2 (262.0994), found
262.0996.
4,4-Dimethyl-3,4-dihydrodibenzo[b,d]furan-1(2H)-one (3h).
3-(4-Methoxyphenyl)dibenzo[b,d]furan-1-ol (3f).
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1a (283 mg, 1 mmol), 2h
(222 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 24 h. Flash chromatography
over silica gel (cyclohexane/EtOAc = 10:1) gave 3h as a colorless oil
in 78% yield (167 mg, 0.78 mmol): Rf = 0.57 (cyclohexane/EtOAc =
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1a (283 mg, 1 mmol), 2f
(327 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 26 h. Flash chromatography
over silica gel (cyclohexane/EtOAc = 6:1) gave 3f as a white solid
in 64% yield (187 mg, 0.64 mmol): mp 181−182 °C; Rf = 0.32
3:1); IR (ATR) ν
̃
1666 (CO), 1588, 1478, 1405, 1172, 1040, 749,
671 cm−1; UV (MeCN) λmax (log ε) 282 (3.81), 260 (3.98), 249
1
(4.07), 227 (4.36) nm; H NMR (300 MHz, CDCl3) δ 1.24 (s, 6H,
1′-H, 1″-H), 2.10 (brt, 3J (3-H, 4-H) = 6.2 Hz, 2H, 3-H), 3.05 (brt, 3J
(3-H, 4-H) = 6.3 Hz, 2H, 4-H), 7.30−7.35 (m, 1H, 7-H), 7.34−7.39
(partially overlapped, 1H, 8-H); 7.45−7.54 (m, 1H, 6-H), 8.05−8.14
(m, 1H, 9-H); 13C NMR (75 MHz, CDCl3) δ 21.4 (C-4), 24.1 (C-1′),
36.3 (C-3), 42.2 (C-2), 111.0 (C-6), 114.7 (C-9b), 121.8 (C-9), 124.3
(C-8), 124.3 (the chemical shift was overlapped indirectly by HMBC,
C-9a); 124.8 (C-7), 154.9 (C-5a), 169.0 (C-4a), 199.7 (C-1); MS (EI,
70 eV) m/z 214 (16) [M+], 199 (6) [M − CH3]+,158 (36) [199 −
C3H5]+, 130 (16) [158 − CO]+, 102 (8); HRMS (EI, M+) calcd for
C14H14O2 (214.0994), found 214.0973.
̃
(cyclohexane/EtOAc = 3:1); IR (ATR) ν 3396 (O−H), 1601,
1517, 1426, 1406, 1227, 1054, 1018, 850, 816, 807, 743, 716 cm−1
;
1
UV (MeCN) λmax (log ε) 292 (4.38), 225 (4.36) nm; H NMR
(300 MHz, CD3OD) δ 3.02 (s, 3H, OCH3), 6.96 (d, 4J
(2-H, 4-H) = 1.0 Hz, 1H; 2-H), 6.98−7.02 (m, 2H, 3′-H, 5′-H),
4
4
7.22 (d, J (2-H, 4-H) = 1.0 Hz, 1H, 4-H), 7.30 (ddd, J (6-H, 8-H) =
1.2 Hz, 3J (7-H, 8-H) = 7.3 Hz, 3J (8-H, 9-H)= 7.3 Hz, 1H, 8-H), 7.38
(ddd, 4J (7-H, 9-H) = 1.3 Hz, 3J (6-H, 7-H) = 7.5 Hz, 3J (7-H, 8-H) =
3
7.5 Hz, 1H, 7-H), 7.50 (bd J (6-H, 7-H) = 7.4 Hz, 1H, 6-H), 7.57−
1-(2-Methylbenzofuran-3-yl)ethanone (3i).7,13
4
3
7.60 (m, 2H, 2′-H, 6′-H), 8.08 (dd, J (7-H, 9-H) = 1.5 Hz, J (8-H,
9-H) = 7.6 Hz, 1H, 9-H); 13C NMR (75 MHz, CD3OD) δ 55.9
(OCH3), 101.8 (C-4), 108.3 (C-2), 111.8 (C-6), 112.5 (C-9b), 115.4
(C-3′), 123.6 (C-9), 123.9 (C-8), 125.1 (C-9a), 127.0 (C-7), 129.3
(C-2′), 135.0 (C-1′), 143.0 (C-3), 155.1 (C-1), 157.3 (C-5a), 159.8
(C-4a), 161.0 (C-4′); MS (EI, 70 eV) m/z 290 (100) [M+], 275 (44)
[M − CH3]+, 247 (20) [275 − CO]+, 218 (6), 189 (8), 145 (10);
HRMS (EI, M+) calcd for C19H14O3 (290.0943), found 290.0933.
3-(4-Chlorophenyl)dibenzo[b,d]furan-1-ol (3g).
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1a (283 mg, 1 mmol), 2i
(150 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 22 h. Flash chromatography
over silica gel (dichloromethane/EtOAc = 99:1) gave 3i as a pale
yellow oil in 83% yield (144 mg, 0.83 mmol): Rf = 0.45 (cyclohexane/
EtOAc= 3:1); 1H NMR (300 MHz, CDCl3) δ 2.65 (s, 3H, 1′-H), 2.78
(s, 3H, 2″-H), 7.28−7.32 (m, 1H, 6-H), 7.31−7.35 (m, 1H, 5-H),
7.44−7.47 (m, 1H, 7-H), 7.93−7.96 (m, 1H, 4-H); 13C NMR (75
MHz, CDCl3) δ 15.4 (C-1′), 31.2 (C-2″), 111.0 (C-7), 117.6 (C-3),
121.3 (C-4), 124.0 (C-3a), 124.4(C-5), 126.0 (C-6), 153.5 (C-7a),
162.8 (C-2), 194.3 (C-1″); MS (EI, 70 eV) m/z 174 (20) [M+], 159
(42) [M − CH3]+,103 (4).
According to the general procedure, a mixture of pivalic acid
(122 mg,1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1a (283 mg,
1 mmol), 2g (334 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was
reacted in dry DMF (2 mL) in a sealed vial at 130 °C for 26 h. Flash
chromatography over silica gel (cyclohexane/EtOAc = 6:1) gave 3g as
an orange solid in 61% yield (180 mg, 0.61 mmol): mp 165−166 °C;
8-Methyl-3,4-dihydrodibenzo[b,d]furan-1(2H)-one (3j).
̃
Rf = 0.45 (cyclohexane/EtOAc = 3:1); IR (ATR) ν 3410 (O−H),
1601, 1483, 1453, 1424, 1227, 1188, 1048, 847, 821, 750, 724, 685
cm−1; UV (MeCN) λmax (log ε) 291 (4.39), 232 (4.37), 225 (4.38)
1
4
nm; H NMR (300 MHz, CD3OD) δ 6.96 (d, J (2-H, 4-H) = 0.9
Hz, 1H, 2-H), 7.27 (d, 4J (2-H, 4-H) = 0.9 Hz, 1H, 4-H), 7.31 (ddd,
4J (6-H, 8-H) = 1.2 Hz, J (7-H, 8-H) = 7.4 Hz, J (8-H, 9-H) =
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1b (297 mg, 1 mmol), 2a
(183 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 23 h. Flash chromatography
over silica gel (dichloromethane/EtOAc = 20:1) gave 3j as a white
solid in 77% yield (154 mg, 0.77 mmol): mp 86−87 °C; Rf = 0.36
3
3
4
3
7.4 Hz, 1H, 8-H), 7.40 (ddd, J (7-H, 9-H) = 1.7 Hz, J (6-H, 7-H) =
8.0 Hz, 3J (7-H, 8-H) = 8.0 Hz, 1H, 7-H), 7.40−7.45 (m, 2H, 3′-H, 5′-
H), 7.51 (bd, 3J (6-H, 7-H) = 8.1 Hz, 1H, 6-H), 7.60−7.65 (m, 2H, 2′-
H, 6′-H), 8.09 (dd, 4J (7-H, 9-H) = 1.6 Hz, 3J (8-H, 9-H) = 7.7 Hz, 1H,
9-H); 13C NMR (75 MHz, CDCl3) δ 102.3 (C-2), 108.5 (C-4), 111.9
(C-6), 113.4 (C-9b), 123.8 (C-9), 124.0 (C-8), 124.9 (C-9a), 127.3
(C-7), 129.8 (C-2′), 130.0 (C-3′), 134.6 (C-3), 141.3 (C-1′), 141.7 (C-4′),
155.2 (C-1), 157.4 (C-5a), 159.7 (C-4a); MS (EI, 70 eV) m/z 294
(100) [M+], 265 (8), 231 (10), 202 (12), 147 (8); HRMS (EI; M+)
calcd for C18H11ClO2 (294.0448) found, 294.0427.
(cyclohexane/EtOAc = 3:1); IR (ATR) ν
̃
1663 (CO), 1586, 1456,
1395, 1175, 1056, 1002, 883, 814, 801, 778 cm−1; UV (MeCN) λmax
1
(log ε) 287 (3.61), 252 (3.96), 232 (4.26) nm; H NMR (300 MHz,
3
3
CDCl3) δ 2.45 (s, 3H, 1′-H), 2.27 (quin, J (2-H, 3-H) = 6.2 Hz, J
(3-H, 4-H) = 6.2 Hz, 2H, 3-H), 2.60 (brt, 3J (2-H, 3-H) = 6.2 Hz, 2H,
3
4
2-H), 3.02 (brt, J (3-H, 4-H) = 6.3 Hz, 2H, 4-H), 7.11 (dd, J (7-H,
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3
3
9-H) = 1.0 Hz, J (6-H, 7-H) = 8.4 Hz, 1H, 7-H), 7.34 (d, J (6-H,
7-H) = 8.4 Hz, 1H, 6-H), 7.86 (brs, 1H, 9-H); 13C NMR (75 MHz,
CDCl3) δ 21.3 (C-1′), 22.5 (C-3), 23.9 (C-4), 37.9 (C-2), 110.5 (C-
6), 116.3 (C-9b), 121.7 (C-9), 123.7 (C-9a), 126.0 (C-7), 134.2 (C-8),
153.0 (C-5a), 170.9 (C-4a), 194.9 (C-1); MS (EI, 70 eV) m/z 200
(98) [M+], 172 (100) [200 − C2H4]+, 144 (62) [172 − CO]+, 115
(20); HRMS (EI; M+) calcd for C13H12O2 (200.0837), found
200.0854.
8-Fluoro-3,4-dihydrodibenzo[b,d]furan-1(2H)-one (3m).
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1e (300 mg, 1 mmol), 2a
(183 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 20 h. Flash chromatography
over silica gel (dichloromethane/EtOAc = 20:1) gave 3m as a colorless
oil in 64% yield (130 mg, 0.64 mmol): Rf = 0.30 (cyclohexane/EtOAc =
7-Chloro-3,4-dihydrodibenzo[b,d]furan-1(2H)-one (3k).
3:1); IR (ATR) ν 1658 (CO), 1596, 1582, 1449, 1395, 1165, 1133,
̃
1004, 869, 804, 784, 681 cm−1; UV (MeCN) λmax (log ε) 285 (3.49),
1
3
252 (3.88), 228 (4.20); H NMR (500 MHz, CDCl3) δ 2.28 (quin, J
(2-H, 3-H) = 6.2 Hz, 3J (3-H, 4-H) = 6.2 Hz, 2H, 3-H), 2.61 (t, 3J (2-H,
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1c (317 mg, 1 mmol), 2a
(183 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 20 h. Flash chromatography
over silica gel (dichloromethane/EtOAc = 20:1) gave 3k as a colorless
oil in 71% yield (157 mg, 0.71 mmol): Rf = 0.29 (cyclohexane/EtOAc =
3
3-H) = 6.2 Hz, 2H, 2-H), 3.04 (t, J (3-H, 4-H) = 6.3 Hz, 2H, 4-H),
7.02 (ddd, 4J (7-H, 9-H) = 2.6 Hz, 3J (6-H, 7-H) = 9.1 Hz, 3J (F,7-H) =
9.1 Hz, 1H, 7-H), 7.40 (dd, 3J (6-H, 7-H) = 8.9 Hz, 4J (F, 6-H) = 3.9,
1H, 6-H), 7.72 (dd, 4J (7-H, 9-H) = 2.7 Hz, 3J (F, 9-H) = 8.1, 1H, 9-H);
13C NMR (125 MHz, CDCl3) δ 22.4 (C-3), 23.9 (C-4), 37.7 (C-2),
107.8 (d, 2J (19F, 13C) = 26.2 Hz, C-9), 111.7 (d, 2J (19F, 13C) = 9.7 Hz,
C-6), 112.5 (d, 3J (19F, 13C) = 26.0 Hz, C-7), 116.7 (C-9b), 124.7 (d, 3J
3:1); IR (ATR) ν
̃
1652 (CO), 1582, 1472, 1404, 1169, 1053, 1006,
896, 829, 722 cm−1; UV (MeCN) λmax (log ε) 289 (3.63), 281 (3.75),
253 (4.17), 227 (4.34) nm; 1H NMR (300 MHz, CDCl3) δ 2.28 (quin,
3J (2-H, 3-H) = 6.3 Hz, 3J (3-H, 4-H) = 6.3 Hz, 2H, 3-H), 2.61 (brt, 3J
(2-H, 3-H) = 6.6 Hz, 2H, 2-H), 3.03 (brt, 3J (3-H, 4-H) = 6.2 Hz, 2H,
4-H), 7.31 (dd, 4J (6-H, 8-H) = 1.7 Hz, 3J (8-H, 9-H) = 8.3 Hz, 1H, 8-
H), 7.48 (d, 4J (6-H, 8-H) = 1.7 Hz, 1H, 6-H), 7.95 (d, 3J (8-H, 9-H) =
8.4 Hz, 1H, 9-H); 13C NMR (75 MHz, CDCl3) δ 22.4 (C-3), 23.8
(C-4), 37.8 (C-2), 111.8 (C-6), 116.3 (C-9b), 122.3 (C-9), 122.4 (C-9a),
125.1 (C-8), 130.8 (C-7), 154.5 (C-5a), 171.3 (C-4a), 194.4 (C-1);
MS (EI, 70 eV) m/z 220 (82) [M+], 192 (100) [M − C2H4]+, 164
(68) [192 − CO]+, 136 (38); HRMS (EI; M+) calcd for C12H9ClO2
(220.0291), found 220.0275.
(19F, 13C) = 11.5 Hz, C-9a), 150.7 (d, J (19F, 13C) = 1.0 Hz, C-5a),
4
160.2 (d, 1J (19F, 13C) = 240.6 Hz, C-8), 172.2 (C-4a), 194.4 (C-1); MS
(EI, 70 eV) m/z 204.2 (62) [M+], 176 (90) [M − C2H4]+, 148 (74)
[176 − CO]+, 120 (78); HRMS (EI; M+) calcd for C12H9FO2
(204.0587), found 204.0578.
7-Trifluoromethyl-3,4-dihydrodibenzo[b,d]furan-1(2H)-one (3n).
7-Fluoro-3,4-dihydrodibenzo[b,d]furan-1(2H)-one (3l).
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1f (351 mg, 1 mmol), 2a
(183 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 100 °C for 28 h. Flash chromatography
over silica gel (dichloromethane/EtOAc = 20:1) gave 3n as a colorless
oil in 47% yield (119 mg, 0.47 mmol): Rf = 0.27 (cyclohexane/EtOAc =
3:1); IR (ATR) ν
̃
1673 (CO), 1587, 1408, 1322, 1161, 1112, 1004,
904, 876, 826, 689 cm−1; UV (MeCN) λmax (log ε) 281 (3.58), 252
(4.28) nm; 1H NMR (300 MHz, CDCl3) δ 2.31 (quin, 3J (2-H, 3-H) =
6.3 Hz, 3J (3-H, 4-H) = 6.3 Hz, 2H, 3-H), 2.64 (t, 3J (2-H, 3-H) = 6.2
Hz, 2H, 2-H), 3.09 (t, 3J (3-H, 4-H) = 6.3 Hz, 2H, 4-H), 7.61 (brd, 3J
(8-H, 9-H) = 8.4 Hz, 1H, 8-H), 7.74 (brs, 1H, 6-H), 8.15 (d, 3J (8-H,
9-H) = 8.1, 1H, 9-H); 13C NMR (75 MHz, CDCl3) δ 22.3 (C-3), 23.9
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1d (300 mg, 1 mmol), 2a
(183 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 20 h. Flash chromatography
over silica gel (dichloromethane/EtOAc = 20:1) gave 3l as a colorless
oil in 66% yield (136 mg, 0.66 mmol): Rf = 0.28 (cyclohexane/EtOAc =
(C-4), 37.8 (C-2), 108.7 (d, J (19F, 13C) = 4.2 Hz, C-6), 116.3 (C-
3
3:1); IR (ATR) ν
̃
1666 (CO), 1595, 1488, 1407, 1172, 1094, 1007,
9b), 121.6 (d, 3J (19F, 13C) = 3.6 Hz, C-8), 122.2 (brs, C-9), 124.5 (q,
1J (19F, 13C) = 270.6 Hz, C-1′), 126.8 (C-9a), 127.3 (d, 2J (19F, 13C) =
32.6 Hz, C-7), 153.7 (C-5a), 172.9 (C-4a), 194.3 (C-1); MS (EI, 70
eV) m/z 254 (60) [M+], 235 (28) [M − F]+, 226 (100), 204 (12), 198
(46), 176 (10), 170 (40), 138 (8); HRMS (EI; M+) calcd for
C13H9F3O2 (254.0555), found 254.0558.
936, 865, 818, 787, 769 cm−1; UV (MeCN) λmax (log ε) 285 (3.85), 276
(3.90), 260 nm (3.93); 1H NMR (500 MHz, CDCl3) δ 2.28 (quin, 3J (2-
H, 3-H) = 6.2 Hz, 3J (3-H, 4-H) = 6.2 Hz, 2H, 3-H), 2.60 (t, 3J (2-H, 3-
H) = 6.0 Hz, 2H, 2-H), 3.03 (t, 3J (3-H, 4-H) = 6.2 Hz, 2H, 4-H), 7.08
(ddd, 4J (6-H, 8-H) = 2.2 Hz, 3J (8-H, 9-H) = 9.2 Hz, 3J (F, 8-H) = 9.2
Hz, 1H, 8-H), 7.19 (dd, 4J (6-H, 8-H) = 2.2 Hz, 3J (F, 6-H) = 8.6, 1H, 6-
Ethyl 2-Methylbenzofuran-3-carboxylate (6).7,13
4
3
H), 7.97 (dd, J (F, 9-H) = 5.6 Hz, J (8-H, 9-H) = 8.7, 1H, 9-H); 13C
NMR (125 MHz, CDCl3) δ 22.5 (C-3), 23.8 (C-4), 37.7 (C-2), 99.2 (d,
2
2J (19F, 13C) = 27.0 Hz, C-6), 112.5 (d, J (19F, 13C) = 23.5 Hz, C-8),
4
3
116.3 (C-9b), 120.0 (d, J (19F, 13C) = 1.9 Hz, C-9a), 122.2 (d, J (19F,
13C) = 9.8 Hz, C-9), 154.5 (d, 3J (19F, 13C) = 12.9 Hz, C-5a), 161.0 (d, 1J
(19F, 13C) = 243.4 Hz, C-7), 171.2 (d, J (19F, 13C) = 3.0, C-4a), 194.5
5
(C-1); MS (EI, 70 eV) m/z 204 (64) [M+], 176 (90) [M − C2H4]+, 148
(72) [176 − CO]+, 120 (78); HRMS (EI; M+) calcd for C12H9FO2
(204.0587), found 204.0606.
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 1a (283 mg, 1 mmol), 5
7801
dx.doi.org/10.1021/jo3014275 | J. Org. Chem. 2012, 77, 7793−7803

The Journal of Organic Chemistry
Featured Article
(195 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 24 h. Flash chromatography
over silica gel (cyclohexane/EtOAc = 15:1) gave 6 as a brown oil in
63% yield (129 mg, 0.63 mmol): Rf = 0.53 (cyclohexane/EtOAc =
5:1); 1H NMR (300 MHz, CDCl3) δ 1.45 (t, 3J = 7.3, 3H, CH2CH3),
(3) (a) Termentzi, A.; Khouri, I.; Gaslonde, T.; Prado, S.; Saint-
Joanis, B.; Bardou, F.; Amanatiadou, E. P.; Vizirianakis, I. S.;
Kordulakova, J.; Jackson, M.; Brosch, R.; Janin, Y. L.; Daffe, M.;
́
Tillequin, F.; Michel, S. Eur. J. Med. Chem. 2010, 45, 5833. (b) Prado,
S.; Ledeit, H.; Michel, S.; Koch, M.; Darbord, J. C.; Cole, S. T.;
Tillequin, F.; Brodin, P. Bioorg. Med. Chem. 2006, 14, 5423. (c) Prado,
S.; Janin, Y. L.; Saint-Joanis, B.; Brodin, P.; Michel, S.; Koch, M.; Cole,
S. T.; Tillequin, F.; Bost, P.-E. Bioorg. Med. Chem. 2007, 15, 2177.
(d) Prado, S.; Toum, V.; Saint-Joanis, B.; Michel, S.; Koch, M.; Cole,
S. T.; Tillequin, F.; Janin, Y. L. Synthesis 2007, 1566.
3
2.78 (s, 3H, 2-CH3), 4.42 (q, J = 7.3, 2H, CH2CH3), 7.25−7.32 (m,
2H), 7.42−7.45 (m, 1H), 7.94−7.98 (m, 1H); 13C NMR (75 MHz,
CDCl3) δ 14.4, 60.2, 109.0, 110.7, 121.7, 123.7, 124.2, 126.2, 153.6,
163.6, 164.5.
3-Phenylpentane-2,4-dione (8).20f
(4) (a) Wassmundt, F. W.; Pedemonte, R. P. J. Org. Chem. 1995, 60,
4991. (b) Graebe, C.; Ullmann, F. Chem. Ber. 1896, 29, 1876.
(5) Della Rosa, C. D; Sanchez, J. P; Kneeteman, M. N; Mancini, P.
M. E. Tetrahedron Lett. 2011, 52, 2316.
(6) Dixit, M.; Raghunandan, R.; Kumar, B.; Maulik, P. R.; Goel, A.
Tetrahedron 2007, 63, 1610.
(7) Huang, X.-C.; Liu, Y.-L.; Liang, Y.; Pi, S.-F.; Wang, F.; Li, J.-H.
Org. Lett. 2008, 10, 1525.
According to the general procedure, a mixture of pivalic acid (122 mg,
1.2 mmol), Cs2CO3 (651 mg, 1.5 mmol), 7a (204 mg, 1 mmol), 2i
(150 mg, 1.5 mmol), and CuI (19 mg, 0.1 mmol) was reacted in dry
DMF (2 mL) in a sealed vial at 130 °C for 3 h. Flash chromatography
over silica gel (cyclohexane/EtOAc = 20:1) gave 8 as a colorless oil in
61% yield (107 mg, 0.61 mmol): Rf = 0.58 (cyclohexane/EtOAc =
(8) (a) Xu, H.; Fan, L.-L. Chem. Pharm. Bull. 2008, 56, 1496. (b) Liu,
Z.; Larock, R. C. Tetrahedron 2007, 63, 347. (c) Campeau, L.-C.;
Parisien, M.; Jean, A.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 581.
(d) Liu, Z.; Larock, R. C. Org. Lett. 2004, 6, 3739. (e) Ames, D. E.;
Opalko, A. Synthesis 1983, 234.
1
5:1); H NMR (300 MHz, CDCl3) δ 1.89 (s, 6H), 7.16−7.20 (m,
́
(9) (a) Liegault, B.; Lee, D.; Huestis, M. P.; Stuart, D. R.; Fagnou, K.
2H), 7.32−7.41 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 24.1, 115.2,
J. Org. Chem. 2008, 73, 5022. (b) Hellwinkel, D.; Kistenmacher, T.
Liebigs Ann. Chem. 1989, 945. (c) Shiotani, A.; Itatani, H. Angew.
Chem., Int. Ed. Engl. 1974, 13, 471.
127.5, 128.8, 131.1, 136.9, 190.9.
ASSOCIATED CONTENT
* Supporting Information
Copies of NMR spectra for all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
(10) (a) Liu, J.; Fitzgerald, A. E.; Mani, N. S. J. Org. Chem. 2008, 73,
2951. (b) Kawaguchi, K.; Nakano, K.; Nozaki, K. J. Org. Chem. 2007,
72, 5119.
(11) (a) Zhao, J.; Wang, Y.; He, Y.; Liu, L.; Zhu, Q. Org. Lett. 2012,
14, 1078. (b) Wei, Y.; Yoshikai, N. Org. Lett. 2011, 13, 5504. (c) Xiao,
B.; Gong, T.-J.; Liu, Z.-J.; Liu, J.-H.; Luo, D.-F.; Xu, J.; Liu, L. J. Am.
Chem. Soc. 2011, 133, 9250.
(12) Wang, C.; Piel, I.; Glorius, F. J. Am. Chem. Soc. 2009, 131, 4194.
(13) Liu, Y.; Qin, J.; Lou, S.; Xu, Z. J. Org. Chem. 2010, 75, 6300.
(14) (a) Malakar, C. C.; Baskakova, A.; Conrad, J.; Beifuss, U.
Chem.Eur. J. 2012, 18, 8882. (b) Malakar, C. C.; Sudheendran, K.;
Imrich, H.-G.; Mika, S.; Beifuss, U. Org. Biomol. Chem. 2012, 10, 3899.
(c) Malakar, C. C.; Schmidt, D.; Conrad, J.; Beifuss, U. Org. Lett. 2011,
8, 1972.
■
S
AUTHOR INFORMATION
Corresponding Author
*E-mail: ubeifuss@uni-hohenheim.de.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank Ms. Sabine Mika for recording the NMR spectra and
Dr. Alevtina Baskakova for recording the mass spectra.
■
(15) Lu, B.; Wang, B.; Zhang, Y.; Ma, D. J. Org. Chem. 2007, 72,
5337.
(16) For reviews on the transition-metal-catalyzed arylation of 1,3-
dicarbonyls with aryl halides, see: (a) Liu, Y.; Wan, J.-P. Org. Biomol.
Chem. 2011, 9, 6873. (b) Cacchi, S.; Fabrizi, G.; Goggiamani, A. Org.
Biomol. Chem. 2011, 9, 641. (c) Bellina, F.; Rossi, R. Chem. Rev. 2010,
110, 1082. (d) Johansson, C. C. C.; Colacot, T. J. Angew. Chem., Int.
Ed. 2010, 49, 676. (e) Monnier, F.; Taillefer, M. Angew. Chem., Int. Ed.
2009, 48, 6954−6971. (f) Evano, G.; Blanchard, N.; Toumi, M. Chem.
Rev. 2008, 108, 3054−3131. (g) Ma, D.; Cai, Q. Acc. Chem. Res. 2008,
41, 1450−1460. (h) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem.
Rev. 2004, 248, 2337.
(17) (a) Ciufolini, M. A.; Qi, H.-B.; Browne, M. E. J. Org. Chem.
1988, 53, 4149. (b) Sakamoto, T.; Katoh, E.; Kondo, Y.; Yamanaka, H.
Chem. Pharm. Bull. 1988, 36, 1664. (c) Ciufolini, M. A.; Browne, M. E.
Tetrahedron Lett. 1987, 28, 171. (d) Uno, M.; Seto, K.; Masuda, M.;
Ueda, W.; Takahashi, S. Tetrahedron Lett. 1985, 26, 1553. (e) Uno, M.;
Seto, K.; Ueda, W.; Masuda, M.; Takahashi, S. Synthesis 1985, 506.
(f) Uno, M.; Seto, K.; Takahashi, S. J. Chem. Soc., Chem. Commun.
1984, 932.
REFERENCES
■
(1) For reviews, see: (a) Benassi, R. Furan and their Benzo
Derivatives: Structure. In Comprehensive Heterocyclic Chemistry II;
Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon Press:
Oxford, 1996; Vol. 2, 259. (b) Heaney, H; Ahn, J. S. Furan and their
Benzo Derivatives: Reactivity. In Comprehensive Heterocyclic Chemistry
II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon
Press: Oxford, UK, 1996; Vol. 2, p 297. (c) Friedrichsen, W. Furan and
their Benzo Derivatives: Synthesis. In Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.;
Pergamon Press: Oxford, UK, 1996; Vol. 2, p 351. (d) Keay, B. A.;
Dibble, P. W. Furan and their Benzo Derivatives: Applications. In
Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W.,
Scriven, E. F. V., Eds.; Pergamon Press: Oxford, UK, 1996; Vol. 2, p
395.
(2) (a) Manniche, S.; Sprogøe, K.; Dalsgaard, P. W.; Christophersen,
C.; Larsen, T. O. J. Nat. Prod. 2004, 67, 2111. (b) Carney, J. R.;
Krenisky, J. M.; Williamson, R. T.; Luo, J. J. Nat. Prod. 2002, 65, 203.
(c) Carotenuto, A.; Fattorusso, E.; Lanzotti, V.; Magno, S. Eur. J. Org.
Chem. 1998, 661. (d) Carney, J. R; Scheuer, P. J. Tetrahedron Lett.
1993, 34, 3727. (e) Miyakodo, M.; Watanabe, K.; Ohno, N.; Nonaka,
F.; Morita, A. J. Pesticide Sci. 1985, 10, 101. (f) Kemp, M. S.; Burden,
R. S. J. Chem. Soc., Perkin Trans. 1 1984, 1441. (g) Kemp, M. S.;
Burden, R. S.; Loeffler, R. S. T. J. Chem. Soc., Perkin Trans. 1 1983,
2267.
(18) (a) Schnyder, A.; Indolese, A. F.; Maetzke, T.; Wenger, J.;
Blaser, H.-U. Synlett 2005, 3167. (b) Gao, C.; Tao, X.; Qian, Y.;
Huang, J. Chem. Commun. 2003, 1444. (c) You, J.; Verkade, J. G.
Angew. Chem., Int. Ed. 2003, 42, 5051. (d) Gao, C.; Tao, X.; Qian, Y.;
Huang, J. Synlett 2003, 1716. (e) Aramendía, M. A.; Borau, V.;
Jimen
́
ez, C.; Marinas, J. M.; Ruiz, J. R.; Urbano, F. J. Tetrahedron Lett.
2002, 43, 2847. (f) Djakovitch, L.; Kohler, K. J. Organomet. Chem.
2000, 606, 101. (g) Fox, J. M.; Huang, X.; Chieffi, A.; Buchwald, S. L.
̈
7802
dx.doi.org/10.1021/jo3014275 | J. Org. Chem. 2012, 77, 7793−7803

The Journal of Organic Chemistry
Featured Article
J. Am. Chem. Soc. 2000, 122, 1360. (h) Kawatsura, M.; Hartwig, J. F. J.
Am. Chem. Soc. 1999, 121, 1473.
(19) (a) McKillop, A.; Rao, D. P. Synthesis 1977, 759. (b) Bruggink,
A.; McKillop, A. Tetrahedron 1975, 31, 2607. (c) Bruggink, A.;
McKillop, A. Angew. Chem., Int. Ed. 1974, 13, 340. (d) Hurtley, W. R.
H. J. Chem. Soc. 1929, 1870.
(20) (a) Chen, L.; Shi, M.; Li, C. Org. Lett. 2008, 10, 5285. (b) Yip, S.
F.; Cheung, H. Y.; Zhou, Z.; Kwong, F. Y. Org. Lett. 2007, 9, 3469.
(c) Fang, Y.; Li, C. J. Org. Chem. 2006, 71, 6427. (d) Xie, X.; Chen, Y.;
Ma, D. J. Am. Chem. Soc. 2006, 128, 16050. (e) Xie, X.; Cai, G.; Ma, D.
Org. Lett. 2005, 7, 4693. (f) Jiang, Y.; Wu, N.; Wu, H.; He, M. Synlett
2005, 2731. (g) Cristau, H.-J.; Cellier, P. P.; Spindler, J.-F.; Taillefer,
M. Chem.Eur. J. 2004, 10, 5607. (h) Hennessy, E. J.; Buchwald, S. L.
Org. Lett. 2002, 4, 269. (i) Hang, H. C.; Drotleff, E.; Elliott, G. I.;
Ritsema, T. A.; Konopelski, J. P. Synthesis 1999, 398. (j) Okuro, K.;
Furuune, M.; Miura, M.; Nomura, M. J. Org. Chem. 1993, 58, 7606.
(21) (a) Ali, M. A.; Punniyamurthy, T. Synlett 2011, 623. (b) Yang,
X.; Fu, H.; Qiao, R.; Jiang, Y.; Zhao, Y. Adv. Synth. Catal. 2010, 5,
1033. (c) Chen, Y.; Wang, Y.; Sun, Z.; Ma, D. Org. Lett. 2008, 10, 625.
(d) Tanimori, S.; Ura, H.; Kirihata, M. Eur. J. Org. Chem. 2007, 3977.
(e) Chen, Y.; Xie, X.; Ma, D. J. Org. Chem. 2007, 72, 9329.
(22) (a) Wang, F.; Liu, H.; Fu, H.; Jiang, Y; Zhao, Y. Org. Lett. 2009,
11, 2469. (b) Wu, Y.; Zhang, Y.; Jiang, Y.; Ma, D. Tetrahedron Lett.
2009, 50, 3683. (c) Wang, B.; Lu, B.; Jiang, Y.; Zhang, Y.; Ma, D. Org.
Lett. 2008, 10, 2761.
(23) Lu, J.; Fu, H. J. Org. Chem. 2011, 76, 4600.
(24) (a) Kitahara, M.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M. J.
Am. Chem. Soc. 2011, 133, 2160. (b) Malakar, C. C.; Schmidt, D.;
Conrad, J.; Beifuss, U. Org. Lett. 2011, 6, 1378. (c) Rousseaux, S.; Davi,
M.; Sofack-Kreutzer, J.; Pierre, C.; Kefalidis, C. E.; Clot, E.; Fagnou,
K.; Baudion, O. J. Am. Chem. Soc. 2010, 132, 10706. (d) Zhao, D.;
Wang., W.; Lian, S.; Yang, F.; Lan, J.; You, J. Chem.Eur. J. 2009, 15,
1337. (e) Lafrance, M.; Lapointe, D.; Fagnou, K. J. Tetrahedron 2008,
64, 6015. (f) Lafrance, M.; Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc.
2007, 129, 14570. (g) García-Cuadrado, D.; Braga, A. A. C.; Maseras,
F.; Echavarren, A. M. J. Am. Chem. Soc. 2006, 128, 1066. (h) Lafrance,
M.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 16496.
(25) CCDC-867350 (3j) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of charge
from the Cambridge Crystallographic Data Centre viawww.ccdc.cam.
ac.uk/data_request/cif.
NOTE ADDED AFTER ASAP PUBLICATION
■
The version published ASAP September 4, 2012 contained errors.
A correction was made to Figure 1 and the General Remarks and
the paper reposted September 10, 2012.
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