Microwave-Promoted Pd-Catalyzed Synthesis of Dibenzofurans from Ortho-Arylphenols

Article abstract of DOI:10.1002/jhet.2704

ortho-Aryl phenols, synthesized via protecting group free Suzuki–Miyaura coupling of ortho-halophenols and arene boronic acids, undergo a cyclization to dibenzofurans via oxidative C–H activation. The reaction proceeds under microwave irradiation in short reaction times using catalytic amounts of Pd(OAc)₂ without additional ligands.

Full text of DOI:10.1002/jhet.2704

Month 2016
Microwave-Promoted Pd-Catalyzed Synthesis of Dibenzofurans from
Ortho-Arylphenols
*
Bernd Schmidt and Martin Riemer
Universitaet Potsdam, Institut fuer Chemie (Organische Synthesechemie), Karl-Liebknecht-Straße 24-25, D-14476
Potsdam-Golm, Germany
*
E-mail: bernd.schmidt@uni-potsdam.de
Received February 8, 2016
DOI 10.1002/jhet.2704
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
ortho-Aryl phenols, synthesized via protecting group free Suzuki–Miyaura coupling of ortho-halophenols
and arene boronic acids, undergo a cyclization to dibenzofurans via oxidative C–H activation. The reaction
proceeds under microwave irradiation in short reaction times using catalytic amounts of Pd(OAc)2 without
additional ligands.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
transformations of the Pschorr type, has been of limited use
in the case of dibenzofuran synthesis [13]. Electrochemical
oxidative coupling of phenols has been found to furnish
dibenzofurans; however, selectivities and isolated yields
are not yet synthetically useful [14]. A viable free radical
approach to dibenzofurans based on a Pschorr-type cycli-
zation of ortho-borylated diphenylethers has recently been
reported [15]. Many successful syntheses of dibenzofurans
(1) are based on transition metal-catalyzed coupling
reactions. These approaches can be roughly classified as
outlined in Scheme 1.
Routes a and b start from diaryl ethers 2 or 3, respec-
tively. Route a employs diaryl ethers substituted with a
leaving group (e.g. Br, I, OTos, N+2) ortho to the aryloxy
substituent and Pd(0) catalysts. The dibenzofuran forma-
tion proceeds via oxidative addition of the C–X bond,
intramolecular C–H activation, and reductive elimination
[16–23]. Route b, which uses diarylethers 3 without
ortho-leaving groups, was developed before route a,
originally with stoichiometric or even overstoichiometric
amounts of Pd(OAc)2 as coupling reagent [24,25]. This
approach relies on the high electrophilicity of Pd2+, which
reacts first in an intermolecular and then in an intramolec-
ular carbopalladation and eventually undergoes reductive
elimination to the dibenzofuran 1 and Pd(0). An attempt
to make this synthesis catalytic in Pd was made shortly
afterwards by using air as oxidant, but under the original
conditions, numerous by-products were formed [26]. Later,
improved protocols for Pd2+-catalyzed aryl couplings
using air as oxidant were described by Åkermark and
coworkers, who identified Sn(OAc)2 as efficient cocatalyst
[27] and by Fagnou and coworkers, who found that pivalic
acid is a better solvent for these reactions than the more
Although dibenzofurans have received considerably less
attention from the synthetic community than benzofurans
[1], recent reviews discussing their role as natural products
[2,3] or as environmental pollutants [4] suggest that their
relevance as targets for organic synthesis has so far proba-
bly been underestimated. Bioactivities and biological
sources of naturally occurring dibenzofurans are diverse
and range from anticancer activity (e.g. kehokorin C,
isolated from the slime mold Trichia favoginea) [5] via
antibacterial activity against Staphyllococcus aureus (e.g.
porric acid D, isolated from the marine fungus Alternaria
sp.) [6] to activity as phytoalexins (e.g. eriobofuran, which
is produced in apple shoots after infection with the fire
blight bacterium) [7]. Polychlorinated dibenzodioxins and
dibenzofurans are formed inter alia during municipal solid
waste incineration [4]. They are highly toxic and can
promote tumor growth, which has for instance been
investigated for 2,3,4,7,8-pentachlorodibenzofuran (PCDF),
one of the most toxic polychlorinated aromatic hydrocar-
bons (Fig. 1) [8].
Until today, variations of the classical Graebe–Ullmann
cyclization [9] are often used for the synthesis of dibenzo-
furans. The method requires ortho-phenoxy arene diazo-
nium salts, which undergo upon dediazonation a free
radical cyclization to the desired dibenzofurans. In order
to overcome limitations of the scope and to avoid unde-
sired side reactions, such as hydrodediazonation, numerous
attempts to find improved conditions have been undertaken
over the decades, e.g. by using hydroquinone [10] or cop-
per salts [11] as promoters. Photoredox catalysis [12],
although highly successful for promoting many free radical
© 2016 Wiley Periodicals, Inc.

B. Schmidt and M. Riemer
publications describing
Vol 000
a
Pd-catalyzed synthesis of
dibenzofurans via route d. Liu and coworkers reported that
2-hydroxybiaryls 5 undergo oxidative cycloetherification
in the presence of air, using Pd(OAc)2 in combination with
an NHC ligand and mesitylcarboxylate as the catalyst
system [44]. A substantial improvement was achieved by
adding 4,5-diazafluoren-9-one, an ancillary ligand
previously developed for the aerobic allylic oxidation
[45]. Almost simultaneously, Wei and Yoshikai found
that the same transformation can be achieved by using 5
or 10mol% of Pd(OAc)2 as a precatalyst, 3-nitropyridine
as an ancillary ligand, and the unsymmetrical peroxide
Figure 1. Structure of some bioactive dibenzofurans.
BzOOBut as the oxidant [46].
A
mixture of
hexafluorobenzene and N,N′-dimethyl-imidazolinone was
identified as the optimum solvent for this protocol.
We became interested in oxidative cycloetherifications
of 2-hydroxybiaryls 5 following our investigations into
the protecting group-free synthesis of biphenols through
Pd/C-catalyzed, microwave-promoted, and fluoride-
accelerated Suzuki–Miyaura coupling reactions in water
[47–49]. In the course of these investigations, we discov-
ered that the 2-hydroxybiaryl substitution pattern 5,
required as the starting material for route d, is particularly
good accessible using our aqueous-heterogeneous Suzuki–
Miyaura coupling conditions. As both steps of the dibenzo-
furan synthesis depicted in Scheme 2 are Pd-catalyzed, we
thought that a process that combines Suzuki–Miyaura
coupling and oxidative cycloetherification to an assisted
tandem catalysis might in principle be viable but that the
reaction conditions of the individual steps had to be
mutually adapted. As a first step, we investigated
the compatibility of the oxidative cycloetherification
protocol devised by Wei and Yoshikai [46] with the
microwave conditions required for our Suzuki–Miyaura
protocol [47].
Scheme 1. Transition metal-catalyzed approaches to dibenzofurans.
commonly used acetic acid [28]. In the course of a total
synthesis, Koert and coworkers found that Fagnou’s C–H
activation conditions can be used for the synthesis of a
polysubstituted dibenzofuran but that AgOAc is a better
oxidant [29]. An interesting variant of route b has been
developed by Larock and coworkers. Their approach to
dibenzofurans is catalytic in Pd(0) and does not require
any oxidants. It proceeds through
a
tandem
carbopalladation of aryl iodides, subsequent vinyl-to-aryl
migration of the Pd, intramolecular C–H activation, and
eventually reductive elimination [30]. In routes c and d,
biaryl compounds 4 and 5 are used as starting materials
and the dibenzofuran formation is completed by an
etherification. Biaryls 4, substituted with a leaving group
in the 2′ position, can undergo cyclization via a base-
mediated SNAr pathway [31], a copper mediated [32] or
catalyzed [33] Ullmann-type reaction [34], or a Pd-
catalyzed O-arylation. The latter method, developed by
Buchwald and coworkers for the intermolecular synthesis
of diaryl ethers [35] has later been expanded to the synthe-
sis of dibenzofurans from biaryls 4 [36,37]. By far, the
least explored way to dibenzofurans is represented by route
d and relies on transition metal-catalyzed activation of
C–H bonds with subsequent intramolecular etherification
[38,39]. For example, Cu-catalyzed transformations of 2-
hydroxybiaryls 5 to dibenzofurans 1 have been developed
by Zhu and coworkers, who identified carboxylates [40],
in particular pivalate, as rate accelerating agents and air
as a suitable oxidant [41–43]. We are aware of only two
RESULTS AND DISCUSSION
Adaptation of oxidative cyclization conditions for
microwave irradiation.
Wei and Yoshikai found that
their oxidative cycloetherification requires BzOOBut as
an oxidant and that other peroxides, hydroperoxides, or
other oxidants fail completely under the conditions tested
by these authors [46]. For these reasons, we started our
Scheme 2. Two-step Suzuki–Miyaura coupling/oxidative cycloetherification.
Journal of Heterocyclic Chemistry
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Dibenzofurans via Pd-Catalyzed C–H Activation
investigation into a microwave-promoted variant of this
reaction by keeping the oxidant BzOOBut and varying
the solvent. As a test reaction, the conversion of 2-
phenylphenol (5a) to dibenzofuran (1a) in the presence of
a catalytic amount of Pd(OAc)2 and two equivalents of
BzOOBut under microwave irradiation at 150°C was
chosen (Table 1). The first solvent to be tested was water,
because this solvent had previously been successfully
used by us for the Suzuki–Miyaura coupling of 2-
halophenols [47]. Under these conditions, 1a was formed
only in trace amounts, while the major part of the starting
material was recovered unchanged (entry 1). With other
undried protic (entries 2, 5) and aprotic (entries 3, 4) polar
solvents, the same result was obtained. Only insubstantial
conversion was observed in dry methanol (entry 6), and it
was therefore concluded that protic solvents are generally
not suitable for this transformation. While the yields in dry
acetonitrile and dioxane (entries 7, 9) were only moderate,
dry benzene (entry 8) and the ethereal solvents THF,
methy-tert-butyl ether (MTBE), and dimethoxyethane
(DME) (entries 10–12) resulted in synthetically useful
yields. To avoid excessive pressure increase under
Table 1
Optimization of reaction conditions for Pd-catalyzed oxidative cyclization.
Entry
Oxidant
n (equiv.)
Solvent
Dried?
Yield of 1a
1
2
3
4
5
6
7
8
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
None
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
—
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.0
3.0
4.0
2.0
2.0
Water
Ethylene glycol
DMSO
Pyridine
Polyethylene glycol
Methanol
Acetonitrile
Benzene
Dioxane
THF
—
No
No
No
No
Yes
Yes
Yes
No
Yes
Yes
Yes
No
<5%d
<5%d
<5%d
<5%d
<5%d
<5%d
20%
61%
31%
60%
49%
58%
33%
<5%
56%
49%
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31e
32f
MTBE
DME
DME
DME
DME
DDME
DDMEc
DME
DME
DME
DME
DME
DME
DME
DME
DME
DME
DME
Yesa
Yesb
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
60%
<5%
<5%
<5%
<5%
<5%
<5%
<5%
<5%
<5%
<5%d
24%
Ag2CO3
IBX
H2O2
m-CPBA
CumOOH
ButOOH
CumOOCum
ButOOBut
BzOOBz
BzOOBut
BzOOBut
BzOOBut
BzOOBut
BzOOBut
DME
DME
DME
DME
48%
54%
45%
<5%
DDME, diethyleneglycoldimethylether; IBX, ortho-iodoxybenzoic acid; Cum, cumyl.
aAddition of water (20 vol%) as a cosolvent.
bAddition of molecular sieves (3 Å, 40 wt%) to the solvent.
cReaction was run under conventional heating conditions (oil bath) and slow addition of the oxidant via syringe pump.
dProduct observed in trace amounts by 1H NMR.
ePd(OAc)2 (5 mol%), BzOOBut (2.0 equiv.), 5a in DME, 20°C, 3 h; then μ-wave, 150°C, 0.5 h.
fBzOOBut (2.0 equiv.), 5a in DME, μ-wave, 150°C, 0.5 h; then add Pd(OAc)2 (5 mol%), μ-wave, 150°C, 0.5 h.
Journal of Heterocyclic Chemistry
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B. Schmidt and M. Riemer
Vol 000
microwave conditions, we focused in further studies on the
highest boiling of these solvents, DME. First, we checked
whether the use of dry DME is really necessary but
discovered that the isolated yield of dibenzofuran (1a) is
significantly lower with undried and unpurified solvent
(entry 13). When dried and purified DME was used
together with water as a cosolvent, the reaction failed
completely and unreacted 5a was recovered (entry 14). On
the other hand, addition of 3Å molecular sieves to dried
and purified DME did not lead to a notably improved
yield (entry 15).
dibenzofuran occurs, which could be isolated in 45% yield
(entry 31). If the reaction mixture is subjected to microwave
irradiation in the absence of the Pd catalyst, the oxidant de-
composes quantitatively, but the starting material 5a is not
affected by the thermal peroxide decomposition. Upon addi-
tion of the Pd catalyst and renewed irradiation, no conver-
sion to the product is observed, which indicates that the
oxidant is indeed completely decomposed (entry 32).
Attempts toward a tandem Suzuki coupling-oxidative
cyclization sequence.
In an attempt to combine the
biaryl synthesis and its oxidative cyclization to a tandem
sequence, equimolar amounts of ortho-iodophenol (6a)
and phenylboronic acid (7a) were subjected to
microwave irradiation in DME in the presence of K2CO3
(the base required for the Suzuki coupling), the oxidant
BzOOBut (for the oxidative cyclization), and Pd(OAc)2
as a precatalyst for both transformations. We could not
detect the dibenzofuran from the crude reaction mixture
but identified the Suzuki coupling product 5a, which was
formed along with other unidentified by-products in
minor amounts. Obviously, the presence of the peroxide,
which is supposed to oxidize a Pd(II) intermediate to a
Pd(IV) intermediate during the oxidative cyclization, does
not fully inhibit the cross-coupling step, which relies on
the oscillation between Pd(0) and Pd(II) intermediates.
However, it is evident that the peroxide interferes
adversely with the Suzuki coupling, and we investigated
for this reason a stepwise addition of the reagents
required for the individual steps. o-Iodophenol (6a) and
the boronic acid 7a reacted upon microwave irradiation
smoothly and selectively in the presence of K2CO3 as a
base to the expected 2-phenylphenol (5a). The oxidant
BzOOBut was then added to the reaction mixture, and
microwave irradiation was continued. However, no
dibenzofuran could be detected in the reaction mixture.
Instead, the Suzuki coupling product 5a was isolated in
high yield (Scheme 3).
In an earlier, unrelated study on Ru-catalyzed allylic
oxidation reactions with hydroperoxides as oxidants [50],
we had discovered that yields and selectivities improve
significantly if the oxidant is slowly added, preferably with
a syringe pump. The required experimental setup cannot be
combined routinely with a microwave apparatus. For these
reasons, we investigated the effect of slow oxidant addition
under conventional heating conditions in the similarly polar,
but higher boiling solvent diethyleneglycoldimethylether
(DDME) (entry 17). The isolated yield of 1a was, however,
very similar to the yield obtained in benzene, THF, or
DME. For comparison, DDME was also used for the oxida-
tive cyclization under microwave irradiation, with the full
quantity of oxidant present from the beginning (entry 16).
Under these conditions, a lower yield of 1a was obtained
than for DME (entry 12) or syringe pump addition of the
oxidant (entry 17). In Wei and Yoshikai’s pioneering study
on the oxidative cyclization of 2-arylphenols, several oxi-
dants were screened under their standard conditions, with
the result that only BzOOBut leads to a notable conversion
to the desired dibenzofurans [46]. As our conditions are
markedly different with respect to the solvent and the
heating conditions, we repeated the oxidant screening. As
expected, no conversion was observed in the absence of
any oxidant (entry 18), and several other oxidants (entries
19–26) turned out to be equally ineffective, including two
hydroperoxides (entries 23, 24) and two symmetrical
peroxides (entries 25, 26). Trace amounts of 1a were
observed with BzOOBz, but the conversion was too low
to allow isolation of the product (entry 27). Further
investigations revealed that an amount of two equivalents
of BzOOBut (entry 12) is optimal, as both lower (entry
28) and higher (entries 29, 30) quantities result in
decreased conversions and isolated yields. To gain
additional insight into the stability of the oxidant under
the oxidative cyclization conditions, two final experiments
were performed. When Pd(OAc)2, the oxidant, and 5a were
stirred at ambient temperature for 3h, no conversion to the
product was observed. Neither the starting material nor the
oxidant decompose to a notable extent, and the Pd catalyst
also appears to be unaffected by the presence of the oxidiz-
ing agent. If, after this time, the reaction mixture is irradi-
ated in the microwave reactor, conversion to the
Scheme 3. Attempted tandem Suzuki coupling-oxidative cyclization
sequence.
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Dibenzofurans via Pd-Catalyzed C–H Activation
These observations suggest that one of the reagents
required for the Suzuki coupling, or one of the by-
products, inhibit the oxidative cyclization step. To check
this hypothesis, we repeated the oxidative cyclization of
5a to 1a under optimized conditions but in the presence
of additives known to promote Suzuki couplings. Remark-
ably, the oxidative cyclization is nearly completely
inhibited if K2CO3 is present; the standard base used for
the microwave-promoted Suzuki coupling. With
tetrabutylammonium fluoride (TBAF)-trihydrate, the di-
benzofuran was detected only in trace amounts, but this
might be attributed to the adverse effect of water rather
than to the fluoride ion. KF, in contrast, does not
completely inhibit the oxidative cyclization but leads to a
decreased yield of 24%. If NaOAc was added to the mix-
ture, virtually the same yield of 1a was obtained as for
additive-free conditions (Scheme 4).
Unfortunately, NaOAc turned out to be ineffective to pro-
mote the Suzuki coupling under the conditions required for
the envisaged tandem sequence. We tried to mend this prob-
lem by using potassium phenyltrifluoroborate as an
alternative organoboron reagent [51,52], but to no avail. Nei-
ther with or without basic or nucleophilic rate accelerating
additives did ortho-iodophenol (6a) react with K[F3BPh] to
the intermediate 5a. Most likely, the reasons for this failure
are the strictly anhydrous conditions, which are mandatory
for the oxidative cyclization but disadvantageous for Suzuki
couplings of organotrifluoroborates, because the formation
of the actual reactive species, the boronic acid, through slow
hydrolysis is not possible [53]. These rather disappointing re-
sults prompted us to pursue the development of a tandem
Suzuki coupling-oxidative cyclization sequence not further.
Scope and limitations of microwave-promoted oxidative
cyclization of 2-arylphenols. Scope and limitations of the
oxidative cyclization under the conditions optimized for
microwave irradiation (refer to Table 1) were evaluated
for a set of ortho-arylphenols 5. Starting materials 5a, b
[47] and 5f–h [48] are either commercially available or
were synthesized via Pd/C-catalyzed Suzuki coupling
under the aqueous protecting group-free conditions
previously disclosed by us. Monoprotected 2,2′-biphenols
5c–e were synthesized from 5b through monoalkylation
or monsilylation (Table 2).
The 2-phenyl phenols 5k, l were obtained via heteroge-
neously catalyzed Suzuki coupling of iodoarenes 6k, l with
phenylboronic acid 7a in aqueous media and under
conventional heating conditions, following our previously
published procedure. For the synthesis of 5k, the standard
additive K2CO3 was replaced by KF and the reaction was
run in a water/ethanol mixture to improve the solubility
of the reactants (Scheme 5) [48].
For the synthesis of 5i′, j, m, and n, ortho-boronophenol
(7b) was used as the coupling partner for aryl iodides
6i′, j, n and aryl bromide 6 m. The coupling of 2-
bromonaphthalene (6m) required microwave irradiation at
150°C, while the aryl iodides reacted at 80°C under
conventional heating conditions (Table 3) [48].
Scheme 4. Effect of additives on the oxidative cyclization sequence.
Scheme 5. Syntheses of 5k and 5l.
Table 2
Synthesis of monoprotected 2,2′-biphenols.
Entry
Reaction conditions
R
Product
Yield
1
2
3
Allyl bromide (1.0 equiv.), K2CO3 (1.0 equiv.), DMF, 70°C 14 h
Benzyl bromide (1.0 equiv.), KOBut (1.0 equiv.), THF, 65°C, 14 h
TBSCl (1.0 equiv.), imidazol (1.1 equiv.), CH2Cl2, 20°C, 14 h
OAllyl
OBn
OTBS
5c
5d
5e
95%
90%
96%
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B. Schmidt and M. Riemer
Vol 000
Table 3
Synthesis of 2-arylphenols 5i′, j, m, n.
Entry
6
X
R1
R2
Conditions
5
Yield
1
2
3
4
6i′
6j
6m
6n
I
I
Br
I
NO2
H
H
NO2
A
A
B
A
5i′
5j
5m
5n
96%
88%
94%
88%
CH=CHCH=CH
H
Me
2-Phenyl-4-nitrophenol (5i) was synthesized from
2-phenylphenol (5a) by regioselective nitration with nitric
acid (Scheme 6).
attributed to the location of the electron-donating
substituent in para-position to the C–H activation site,
which would enhance the nucleophilicity and faciliate
electrophilic palladation. However, it is evident that other
factors play a significant role, as the yield for all
methoxysubstituted dibenzofurans is much lower than the
yield obtained for the parent compound 1a. As examples
for electron-deficient 2-arylphenols, three nitrosubstituted
derivatives were investigated (entries 15–17). Compounds
5i and 5i′ react to the same 4-nitrodibenzofuran (1i).
Starting from 5i, with the electron-withdrawing substituent
located para to the OH group, the isolated yield of 1i is
low (entry 15), but for the cyclization of 5i′ (with the nitro
group para to the C–H activation site), a comparable yield
could only be achieved by the addition of the ancillary
ligand 3-nitropyridine (entry 16). Moving the electron-
withdrawing group to the position meta to the C–H
activation site results, as expected, in a higher but still
moderate yield (entry 17). While Wei and Yoshikai do
not report any examples for the oxidative cyclization of
2-arylphenols substituted with strongly electron-
withdrawing substituents [46], Liu and coworkers
observed high yields for some of these substrates, inter
alia 5i′, with their catalyst system [44]. These authors
could also show that under their conditions (using a
Pd-NHC catalyst, a carboxylate ancillary ligand, and air
as an oxidant), an α,β-unsaturated ester moiety is tolerated.
With the example of 5k, we included such a derivative in
our study but discovered that the standard conditions
result in complete decomposition (entry 18). We reasoned
that the C–C double bond is prone to oxidative cleavage
and that a reduced amount of oxidant might be beneficial.
With 1.0 equiv. of BzOOBut, we could indeed isolate
the dibenzofuran 1k, but conversion remained incomplete
The 2-arylphenols 5a–n were next subjected to the
oxidative cyclization conditions under microwave irradiation
(Table 4). As Wei and Yoshikai reported a beneficial effect
of 3-nitropyridine as an ancillary ligand, we repeated the
oxidative cyclization of 5a to 1a in the presence of 5mol
% of this ligand. For this example, we could indeed observe
a substantially higher yield of 80% (entry 2). Larger
amounts of 3-nitropyridine (entry 3) or phosphine ligands
(entries 4, 5) were detrimental. 2,2′-Biphenol (5b) and its
monoalkylated derivatives 5c and 5d gave the correspond-
ing dibenzofurans only in trace amounts (entries 6–8).
While 5b did not react under these conditions, presumably
because of chelation of the Pd by both OH groups, 5c and
5d underwent extensive decomposition, which is probably
initiated by allylic or benzylic oxidation of the O–CH2
moiety. Only the tert-butyldimethylsilyl (TBS)-protected
derivative 5e could be cyclized to 1e in a moderate yield
(entries 9 and 10). Comparable yields of 25 and 22%, re-
spectively, were obtained for the oxidative cyclization of
the isomeric methyl ethers 5f and 5h (entries 11 and 14),
whereas the yield of 4-methoxydibenzofuran (1g) from 5g
was considerably higher (entry 12). In this case, addition
of 3-nitropyridine resulted only in a slightly increased yield
(entry 13). We reason that the increased yield can be
Scheme 6. Synthesis of 5i via regioselective nitration of 5a.
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Dibenzofurans via Pd-Catalyzed C–H Activation
Table 4
Scope and limitations of microwave-promoted oxidative cyclization.a
Entry
5
R1
R2
R3
R4
R5
BzOOBut (equiv.)
1
Yield
1
5a
5a
5a
5a
5a
5b
5c
5d
5e
5e
5f
5g
5g
5h
5i
5in
5j
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
NO2
H
H
H
H
H
H
OH
OAllyl
OBn
OTBS
OTBS
OMe
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OMe
OMe
H
H
NO2
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OMe
H
H
NO2
H
H
2.0
2.0
2.0
2.0
2.0
4.0
2.0
2.0
2.0
4.0
2.0
2.0
2.0
2.0
4.0
2.0
2.0
2.0
1.0
2.0
2.0
2.0
2.0
1a
1a
1a
1a
1a
1b
1c
1d
1e
1e
1f
1g
1g
1h
1i
1i
1j
58%
80%
43%
10%
20%
<5%
<5%
<5%
34%
44%
25%
38%
46%
22%
22%
21%
33%
<5%
16%
62%
69%
<60%
62%
2b
3c
4d
5e
6
7
8
9
10
11
12
13b
14
15
16b
17b
18
19
20
21b
H
5k
5k
5l
5l
5m
5n
OMe
OMe
OMe
OMe
H
CH=CHCO2Et
CH=CHCO2Et
1k
1k
1l
1l
1m
1n
CHO
CHO
H
H
H
H
H
H
H
H
,
22b f
CH=CHCH=CH
Me
23b
H
H
H
aOptimized conditions as stated in Table 1, entry 12, unless otherwise stated.
bWith addition of 3-nitropyridine (5 mol%).
cWith addition of 3-nitropyridine (2.0 equiv.).
dWith addition of PCy3 (20 mol%).
eWith addition of PPh3 (20 mol%).
fIsolated together with numerous impurities.
and the isolated yield was very low (entry 19). The
successful conversion of 5l to 1l illustrates that an
oxidation-sensitive carbaldehyde group is tolerated under
the oxidative cyclization conditions. In this case, addition
of 3-nitropyridine leads only to a marginally improved
yield (entries 20 and 21). A rather sluggish reaction was
observed for the naphthalene derivative 5m (entry 22):
While the expected naphto[2,3-b]benzofuran (1m) is
clearly the main product and could be identified via its
spectroscopical data, the reaction mixture was contami-
nated with a substantial amount of by-products that could
not be removed, even after repeated chromatography. A
reason for the poor selectivity in this case might be partial
oxidative degradation of the naphthalene moiety. In
contrast, oxidation of alkyl side chains does not seem to
be a significant problem under the oxidative cyclization
conditions, as the tolylderivative 5n was converted to
3-methyldibenzofuran (1n) in good selectivity and yield
(entry 23).
CONCLUSION
In summary, we have investigated a tandem synthesis of
dibenzofurans from haloarenes and boronic acids that
proceeds via Suzuki coupling and oxidative cyclization.
Our results show that the tandem concept has clear
limitations, in particular if—as in the present case—solvent
compatibility issues cannot be resolved. In the course of
this investigation, we have identified alternative reaction
conditions for the Pd-catalyzed oxidative cyclization of
ortho-arylphenols that differ from previously reported
conditions by using a less elaborate solvent and microwave
irradiation to achieve reduced reaction times.
EXPERIMENTAL
General. 1H NMR spectra were obtained at 300 MHz
in CDCl3 with CHCl3 (δ= 7.26 ppm) as an internal
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

B. Schmidt and M. Riemer
Vol 000
standard or in methanol-d4 with CHD2OD (δ= 3.31ppm)
as an internal standard. Coupling constants (J) are given
in Hz. 13C NMR spectra were recorded at 75MHz in
CDCl3 with CHCl3 (δ= 77.0 ppm) as an internal standard
or in methanol-d4 with CD3OD (δ= 49.2ppm) as an
internal standard. IR spectra were recorded as ATR-FTIR
spectra. Wavenumbers (ν) are given in cmÀ1. The peak
intensities are defined as strong (s), medium (m), or weak
(w). Low- and high-resolution mass spectra were
obtained by EI- or ESI-TOF. Microwave reactions were
carried out in an Anton-Paar monowave-300 reactor at
150°C (monowave, maximum power 850 W, temperature
control via IR sensor, vial volume: 20 mL). These starting
materials were purchased or synthesized following
literature procedures: 5a–5b [47] and 5f–h [48].
for C19H16O2 [M+] 276.1150, found 276.1146. Anal.
Calcd for C19H16O2 (276.33): C, 82.6; H, 5.8. Found: C,
82.2; H, 6.0.
2′-((tert-Butyldimethylsilyl)oxy)-[1,1′-biphenyl]-2-ol (5e). To a
solution of 5b (3.72 g, 20.00 mmol) and imidazol (1.50 g,
22.00 mmol) in dry and degassed CH2Cl2 (100 mL) was
added TBSCl (3.01 g, 20.00 mmol), and the mixture was
stirred at ambient temperature for 14 h. The reaction
mixture was washed with a saturated aqueous solution of
NH4Cl (30 mL); the aqueous layer was separated and
extracted with MTBE. The combined organic extracts
were dried with MgSO4, filtered, and evaporated. The
residue was purified by column chromatography on silica
using hexane-MTBE mixtures as eluent to yield 5e
(5.96 g, 19.84 mmol, 96%). Colorless oil; 1H NMR
(300 MHz, CDCl3): δ (ppm) = 7.40–7.32 (m, 2H), 7.29–
7.26 (m, 1H), 7.15 (td, J = 7.5, 1.2 Hz, 1H), 7.08–6.98 (m,
3H), 6.53 (s, 1H), 0.87 (s, 9H), 0.00 (s, 6H); 13C NMR
(75 MHz, CDCl3): δ (ppm) = 153.9, 151.8, 132.5, 131.2,
130.4, 129.3, 129.1, 127.1, 123.2, 121.1, 120.8, 117.9,
25.6, 18.1, À4.6; IR (ATR) cmÀ1: 3406 (bw), 1497 (m),
1478 (m), 1223 (m), 834 (s); HRMS (EI) calcd for
C18H24O2Si [M+] 300.1546, found 300.1524. Anal. Calcd
for C18H24O2Si (300.47): C, 72.0; H, 8.1. Found: C,
71.5; H, 7.8.
Syntheses and Analytical Data of Ortho-Arylphenols 5.
2′-(Allyloxy)-[1,1′-biphenyl]-2-ol (5c) [54]. To a solution
of 5b (1.86 g, 10.00 mmol) in dry and degassed DMF
(20 mL) was added K2CO3 (1.38 g, 10.00 mmol). Allyl
bromide (0.86 mL, 10.00mmol) was added, and the
mixture was stirred at 70°C for 14 h. Aqueous HCl (1 M,
25mL) was added, and the mixture was extracted with
MTBE. The combined organic extracts were dried with
MgSO4, filtered, and evaporated. The residue was
chromatographed to furnish 5c (2.14 g, 9.47mmol, 95%).
1
Colorless liquid; H NMR (300 MHz, CDCl3) δ (ppm)
5-Nitro-[1,1′-biphenyl]-2-ol (5i) [41]. To a solution of 5a
(1.70 g, 10.0mmol) in CH2Cl2 (20 mL) was added a
solution of aqueous nitric acid (68 wt%, 1.00 mL,
22.0 mmol) in CH2Cl2 (5 mL). The mixture was stirred at
ambient temperature for 12h, diluted with brine (20 mL),
and then extracted with ethyl acetate. The combined
organic extracts were dried with MgSO4, filtered, and
evaporated. The residue was chromatographed on silica
using hexane-MTBE mixtures as eluent to give 5i (1.17g,
5.4 mmol, 54%). Yellow oil; 1H NMR (300MHz,
CDCl3): δ (ppm) = 8.21–8.15 (m, 2H), 7.60–7.43 (m,
5H), 7.07 (d, J = 8.6 Hz, 1H), 6.13 (s, 1H); 13C NMR
(75 MHz, CDCl3): δ (ppm) =158.3, 141.9, 134.8, 129.9,
129.2, 129.1, 128.8, 126.4, 125.3, 116.5; IR (ATR)
cmÀ1: 3372 (bw), 1587 (w), 1498 (m), 1337 (s), 1286
(s); HRMS (EI) calcd for C12H9O3N [M+] 215.0577,
found 215.0579. Anal. Calcd for C12H9O3N (215.21): C,
67.0; H, 4.2; N, 6.5. Found C, 66.9; H, 4.1; N, 6.6.
3′-Nitro-[1,1′-biphenyl]-2-ol (5i′) [56]. To a suspension of
6i′ (747 mg, 3.00mmol), 7b (558mg, 3.90 mmol), and
K2CO3 (1.66 g, 12.00 mmol) in water (12 mL) and ethanol
(6mL) was added Pd/C (10 wt%, 60 mg, 2mol%). The
mixture was heated to 80°C for 2.5h, then cooled to
ambient temperature, and quenched by addition of aqueous
HCl (1M, 10 mL). It was extracted with MTBE (three times
50 mL); the combined organic extracts were dried with
MgSO4, filtered, and evaporated. The residue was purified
by chromatography on silica using hexane-MTBE mixtures
as eluent to furnish 5i′ (622 mg, 2.89mmol, 96%). Yellow
= 7.56–7.41 (m, 4H), 7.28–7.10 (m, 4H), 6.69 (s, 1H),
6.07 (ddt, J= 17.1, 10.4, 5.1 Hz, 1H), 5.45 (ddd, J =17.3,
2.7, 1.3Hz, 1H), 5.35 (ddd, J = 11.0, 2.6, 1.3 Hz, 1H),
4.67 (d, J =5.1Hz, 2H); 13C NMR (75 MHz, CDCl3): δ
(ppm) = 154.5, 153.7, 132.4, 132.2, 131.3, 129.1, 129.1,
127.7, 126.3, 122.3, 120.8, 118.0, 117.4, 113.4, 69.8; IR
(ATR) cmÀ1: 3392 (bw), 1574 (w), 1479 (m), 1441 (m),
1223 (m), 991 (m); HRMS (EI) calcd for C15H14O2 [M+]
226.0994, found 226.0991.
2′-(Benzyloxy)-[1,1′-biphenyl]-2-ol (5d) [55].
To
a
solution of 5b (186 mg, 1.00 mmol) in dry and degassed
THF (20 mL) was added KOBut (112 mg, 1.00mmol).
Benzyl bromide (0.12 mL, 1.00mmol) was added, and
the mixture was stirred at 65°C for 14 h. The solvent was
removed in vacuo, and the residue was mixed with
aqueous HCl (1 M, 10 mL). The mixture was extracted
three times with MTBE; the combined organic extracts
were dried with MgSO4, filtered, and evaporated. The
residue was purified by chromatography on silica using
hexane-MTBE mixtures as eluent to give 5d (248mg,
1
0.90mmol, 90%). Colorless solid, mp 96–99°C; H NMR
(300 MHz, CDCl3):
δ (ppm) = 7.42–7.35 (m, 2H),
7.35–7.27 (m, 7H), 7.18–7.09 (m, 2H), 7.07–7.00 (m,
2H), 6.33 (s, 1H), 5.13 (s, 2H); 13C NMR (75 MHz,
CDCl3): δ (ppm) = 155.0, 153.8, 136.2, 132.7, 131.4,
129.4, 129.4, 128.7, 128.3, 128.2, 127.4, 126.4, 122.9,
121.1, 117.6, 114.6, 72.0; IR (ATR) cmÀ1: 3393 (bw),
1579 (w), 1440 (s), 1222 (s), 1126 (m); HRMS (EI) calcd
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Dibenzofurans via Pd-Catalyzed C–H Activation
solid, mp 99–100°C; 1H NMR (300 MHz, CDCl3): δ (ppm)
=8.43 (t, J=1.9Hz, 1H), 8.21 (ddd, J=8.2, 2.3, 1.1Hz,
1H), 7.89 (ddd, J= 7.7, 1.6, 1.1Hz, 1H), 7.61 (t, J=8.0Hz,
1H), 7.40–7.24 (m, 2H), 7.05 (td, J=7.5, 1.1Hz, 1H), 6.94
(d, J=8.0Hz, 1H), 5.15 (s, 1H); 13C NMR (75MHz,
CDCl3): δ (ppm)=152.5, 148.6, 139.6, 135.5, 130.7, 130.1,
(414 mg, 2.00 mmol), 7b (359mg, 2.60 mmol), and KOH
(448 mg, 8.00 mmol) in water (12 mL) and ethanol
(6 mL). Pd/C (10 wt%, 40mg, 2 mol%) was added, and
the mixture was irradiated in a dedicated microwave
reactor at 150°C for 0.5 h, then cooled to ambient
temperature, and quenched by addition of aqueous HCl
(1 M, 10mL). It was extracted with MTBE (three times
50mL); the combined organic extracts were dried with
MgSO4, filtered, and evaporated. The residue was
purified by chromatography on silica using hexane-
MTBE mixtures as eluent to furnish 5m (412mg,
129.6, 126.2, 124.4, 122.3, 121.7, 116.5; IR (ATR) cmÀ1
:
3448 (bw), 1522 (s), 1347 (s), 749 (m), 727 (m); HRMS
(EI) calcd for C12H9O3N [M+] 215.0577, found 215.0574.
4′-Nitro-[1,1′-biphenyl]-2-ol (5j) [57].
Following the
procedure stated in the preceding texts for 5i′, 6j
(747 mg, 3.00mmol) and 7b (558 mg, 3.90mmol) were
coupled to give 5j (570mg, 2.65mmol, 88%). Yellow
1
1.87 mmol, 94%). Colorless solid, mp 92–95°C; H NMR
(300 MHz, CDCl3):
δ (ppm) = 8.05–7.95 (m, 2H),
1
solid, mp 119–120°C; H NMR (300 MHz, methanol-d4):
7.95–7.88 (m, 2H), 7.65–7.48 (m, 3H), 7.43–7.30 (m,
2H), 7.11–7.01 (m, 2H), 5.35 (s, 1H); 13C NMR
(75 MHz, CDCl3): δ (ppm) =152.7, 134.6, 133.7, 132.8,
130.6, 129.4, 129.3, 128.2, 128.0, 127.9, 127.9, 127.3,
126.8, 126.6, 121.1, 116.0; IR (ATR) cmÀ1: 3532 (bw),
1489 (w), 1450 (w), 1279 (w), 752 (s); HRMS (EI) calcd
for C16H12O [M+] 220.0883, found 220.0883.
δ (ppm) = 8.24 (d, J= 9.0 Hz, 2H), 7.81 (d, J= 9.0 Hz,
2H), 7.32 (dd, J= 7.9, 1.7 Hz, 1H), 7.22 (ddd, J = 8.3, 7.4,
1.7Hz, 1H), 6.98–6.88 (m, 2H); 13C NMR (75 MHz,
methanol-d4): δ (ppm) = 155.9, 147.8, 147.4, 131.5,
131.3, 131.0, 127.5, 124.0, 121.1, 117.3; IR (ATR)
cmÀ1: 3448 (bw), 1597 (m), 1509 (m), 1452 (m), 1341
(s); HRMS (EI) calcd for C12H9O3N [M+] 215.0577,
found 215.0567.
4′-Methyl-[1,1′-biphenyl]-2-ol (5n) [60].
Following the
procedure stated in the preceding texts for 5i′, 6n
(436 mg, 2.00mmol) and 7b (359mg, 2.60mmol) were
coupled to give 5n (323mg, 1.76mmol, 88%). Colorless
oil; 1H NMR (300MHz, CDCl3): δ (ppm) = 7.37 (d,
J = 8.2 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 7.26–7.19 (m,
2H), 7.03–6.96 (m, 2H), 5.25 (s, 1H), 2.43 (s, 3H); 13C
NMR (75 MHz, CDCl3): δ (ppm) =152.6, 137.9, 134.1,
130.3, 130.1, 129.1, 129.1, 128.2, 120.9, 115.8, 21.4; IR
(ATR) cmÀ1: 3535 (bw), 1481 (m), 1448 (m), 1780 (m),
750 (s); HRMS (EI) calcd for C13H12O [M+] 184.0883,
found 184.0891.
Syntheses and Analytical Data of Dibenzofurans 1.
General procedure for the microwave-promoted synthesis of
dibenzofurans 1 via oxidative cyclization. The appropriate
ortho-arylphenol 5 (1.00mmol), Pd(OAc)2 (11.2mg,
5 mol%), BzOOBut (372 μL, 2.00mmol), and 3-
nitropyridine (optional—refer to Table 2, 7.7 mg, 5mol%)
were dissolved in dry and degassed dimethoxyethane
(5 mL) in a vessel suited for microwave irradiation. The
vessel was sealed, placed in a dedicated microwave
reactor, and irradiated at 150°C for 0.5 h. After cooling
the reaction mixture to ambient temperature, ethyl acetate
was added (20 mL) and the solution was washed with a
saturated aqueous solution of Na2CO3 (10 mL). The
organic layer was separated, dried with MgSO4, filtered,
and evaporated. The residue was purified by
chromatography on silica using hexane-MTBE mixtures
of increasing polarity as eluent.
Ethyl-(E)-3-(6-hydroxy-5-methoxy-[1,1′-biphenyl]-3-yl)acrylate
(5k).
Following the procedure stated in the preceding
texts for 5i, 6k (1.67 g, 5.0 mmol) and 7a (732mg,
6.50mmol) were coupled to give 5k (1.30 g, 4.36mmol,
1
87%). Colorless solid, mp 111°C; H NMR (300MHz,
CDCl3): δ (ppm) = 7.66 (d, J = 15.9Hz, 1H), 7.59 (d,
J =8.3 Hz, 2H), 7.45 (t, J = 7.3 Hz, 2H), 7.36 (tm,
J =7.3 Hz, 1H), 7.18 (d, J = 1.8 Hz, 1H), 7.04 (d,
J =1.9 Hz, 1H), 6.34 (d, J = 15.9Hz, 1H), 6.11 (s, 1H),
4.26 (q, J = 7.1Hz, 2H), 3.98 (s, 3H), 1.34 (t, J= 7.1 Hz,
3H); 13C NMR (75 MHz, CDCl3): δ (ppm) =167.4, 147.2,
145.1, 144.8, 137.0, 129.2, 128.5, 128.0, 127.7, 126.7,
124.4, 116.1, 108.3, 60.5, 56.4, 14.5; IR (ATR) cmÀ1
:
1698 (m), 1633 (m), 1417 (m), 1263 (m), 1158 (s);
HRMS (EI) calcd for C18H18O4 [M+] 298.1205, found
298.1208.
6-Hydroxy-5-methoxy-[1,1′-biphenyl]-3-carbaldehyde
(5l)
[58].
Following the procedure stated in the preceding
texts for 5i′, 6l (1.39 g, 5.0 mmol) and 7a (0.73 g,
6.5 mmol) were coupled to give 5l (1.10 g, 4.8 mmol,
97%). The reaction was run in water instead of the water-
ethanol mixture used for the synthesis of 5i′. Colorless
solid, mp 109–110°C; 1H NMR (300 MHz, CDCl3): δ
(ppm) = 9.88 (s, 1H), 7.65–7.60 (m, 2H), 7.52 (d,
J = 1.7 Hz, 1H), 7.50–7.33 (m, 4H), 6.45 (s, 1H), 4.02 (s,
3H); 13C NMR (75 MHz, CDCl3): δ (ppm) 191.1, 148.8,
147.6, 136.4, 129.5, 129.2, 128.8, 128.6, 127.9, 127.8,
107.6, 56.6; IR (ATR) cmÀ1: 3356 (bw), 1679 (m), 1591
(m), 1423 (m), 1311 (s); HRMS (EI) calcd for C14H12O3
[M+] 228.0786, found 228.0780.
Dibenzo[b,d]furan (1a) [61]. Obtained from 5a (170mg,
1.00 mmol). Yield of 1a without added 3-nitropyridine:
97mg (0.58mmol, 58%); yield of 1a with added 3-
nitropyridine: 135mg (0.80 mmol, 80%). 1H NMR
(300 MHz, CDCl3): δ (ppm) = 8.00 (d, J= 7.6 Hz, 2H),
2-(Naphthalene-2-yl)phenol (5m) [59]. In a vessel suited
for microwave irradiation was placed a suspension of 6m
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

B. Schmidt and M. Riemer
Vol 000
7.63 (d, J = 8.2Hz, 2H), 7.51 (td, J = 7.9, 1.0 Hz, 2H), 7.39
(t, J= 7.5Hz, 2H); 13C NMR (75 MHz, CDCl3): δ (ppm)
= 156.3, 127.2, 124.3, 122.8, 120.7, 111.8; IR (ATR)
cmÀ1: 3046 (w), 1596 (w), 1444 (s), 1189 (m), 719 (s);
HRMS (EI) calcd for C12H8O [M+] 168.0575, found
168.0565.
2-Nitrodibenzo[b,d]furan (1i) [41].
Obtained from 5i
(108 mg, 0.50 mmol). Yield of 1i without added 3-
nitropyridine: 22mg (0.10mmol, 21%). Obtained from
5i′ (108 mg, 0.50mmol). Yield of 1i with added 3-
nitropyridine: 23mg (0.11 mmol, 22%). Yellow solid, mp
1
143–146°C; H NMR (300MHz, CDCl3): δ (ppm) = 8.85
tert-Butyl(dibenzo[b,d]furan-1-yloxy)dimethylsilane (1e). Obtained
from 5e (300 mg, 1.00mmol). Yield of 1e without
addition of 3-nitropyridine: 132mg, 0.44 mmol, 44%).
(d, J =2.4 Hz, 1H), 8.38 (dd, J = 9.0, 2.4 Hz, 1H), 8.01 (d,
J = 7.7 Hz, 1H), 7.66–7.60 (m, 2H), 7.56 (tm, J = 7.5Hz,
1H), 7.44 (tm, J = 7.5 Hz, 1H); 13C NMR (75 MHz,
CDCl3): δ (ppm) =159.3, 157.6, 144.0, 129.1, 125.2,
124.1, 123.2, 123.1, 121.4, 117.2, 112.4, 112.1; IR
(ATR) cmÀ1: 2924 (w), 1522 (s), 1337 (s), 1182 (m),
893 (m); HRMS (EI) calcd for C12H7O3N [M+]
213.0420, found 213.0418.
1H NMR (300 MHz, CDCl3):
δ (ppm) = 8.23 (d,
J =7.6 Hz, 1H), 7.61 (d, J = 7.9 Hz, 1H), 7.48 (td, J = 7.6,
0.9Hz, 1H), 7.41 (t, J =6.7 Hz, 1H), 7.35 (d, J= 8.0 Hz,
1H), 7.26 (d, J= 8.2 Hz, 1H), 6.84 (d, J= 7.9Hz, 1H),
1.19 (s, 9H), 0.44 (s, 6H); 13C NMR (75 MHz, CDCl3):
δ (ppm) = 157.9, 155.7, 151.8, 127.6, 126.3, 123.8, 122.8,
122.7, 116.3, 112.4, 111.2, 104.8, 26.1, 18.6, À3.8; IR
(ATR) cmÀ1: 2930 (w), 1597 (m), 1448 (s), 1235 (m),
1053 (s).
3-Nitrodibenzo[b,d]furan (1j) [62].
Obtained from 5j
(108 mg, 0.50mmol). Yield of 1j with added 3-
nitropyridine: 35mg (0.16 mmol, 33%). 1H NMR
(300 MHz, CDCl3): δ (ppm) = 8.42 (d, J= 1.9 Hz, 1H),
8.26 (dd, J =8.5, 2.0 Hz, 1H), 8.03 (d, J = 8.6 Hz, 1H),
8.01 (dm, J =7.5 Hz, 1H), 7.64 (dm, J= 8.2 Hz, 1H), 7.59
(ddd, J = 8.2, 7.2, 1.2 Hz, 1H), 7.43 (td, J = 7.2, 1.3 Hz,
1H); 13C NMR (75 MHz, CDCl3): δ (ppm) =158.4,
155.2, 146.9, 130.3, 129.7, 123.9, 122.6, 121.9, 120.6,
118.6, 112.4, 108.1; IR (ATR) cmÀ1: 1525 (s), 1458 (w),
1347 (s), 1196 (w), 821 (w); HRMS (EI) calcd for
C12H7O3N [M+] 213.0426, found 213.0432.
tert-Butyl(dibenzo[1-methoxydibenzo[b,d]furan
(1f)
[46]. Obtained from 5f (100 mg, 0.50 mmol). Yield of
1f without added 3-nitropyridine: 25 mg (0.25mmol,
25%). 1H NMR (300 MHz, CDCl3): δ (ppm) = 8.16 (d,
J =7.6 Hz, 1H), 7.56 (d, J= 8.1 Hz, 1H), 7.46 (tm,
J =7.5 Hz, 1H), 7.41 (td, J = 8.2, 1.0 Hz, 1H), 7.37 (tm,
J =7.4 Hz, 1H), 7.21 (d, J = 8.3 Hz, 1H), 6.80 (d,
J =8.1 Hz, 1H), 4.06 (s, 3H); 13C NMR (75 MHz, CDCl3):
δ (ppm) = 157.5, 156.0, 155.6, 128.0, 126.3, 123.7, 123.0,
122.9, 113.7, 111.1, 104.5, 103.9, 55.8.
Ethyl-(E)-3-(4-methoxydibenzo[b,d]furan-2-yl)acrylate
(1k).
Obtained from 5k (149mg, 0.50 mmol) with a
2-Methoxydibenzo[b,d]furan (1g) [46]. Obtained from 5g
(100 mg, 0.50 mmol). Yield of 1g without added 3-
nitropyridine: 38 mg (0.19 mmol, 38%); yield of 1g with
added 3-nitropyridine: 46 mg (0.23 mmol, 46%). 1H
NMR (300 MHz, CDCl3): δ (ppm) = 7.92 (d, J= 7.6 Hz,
1H), 7.56 (d, J = 8.2 Hz, 1H), 7.53–7.43 (m, 2H), 7.43 (d,
J =2.5 Hz, 1H), 7.33 (td, J= 7.6, 0.9 Hz, 1H), 7.06 (dd,
J =8.9, 2.7Hz, 1H), 3.92 (s, 3H); 13C NMR (75 MHz,
CDCl3): δ (ppm) = 157.1, 156.0, 151.1, 127.2, 124.8,
124.6, 122.5, 120.7, 115.3, 112.2, 111.9, 103.9, 56.2; IR
(ATR) cmÀ1: 1481 (s), 1437 (m), 1186 (s), 1167 (s),
1034 (m); HRMS (EI) calcd for C13H10O2 [M+]
198.0681, found 198.0689.
reduced amount of oxidant (1.0 equiv.). Yield of 1k
without added 3-nitropyridine: 24mg (0.08 mmol, 16%).
Colorless solid, mp 45–47°C; 1H NMR (300MHz,
CDCl3): δ (ppm) = 7.95 (d, J =7.4 Hz, 1H), 7.83 (d,
J = 15.9Hz, 1H), 7.72 (d, J = 1.0 Hz, 1H), 7.63 (d,
J = 8.2 Hz, 1H), 7.50 (td, J = 7.5, 1.4 Hz, 1H), 7.38 (td,
J = 7.6, 1.0 Hz, 1H), 7.16 (d, J = 1.2 Hz, 1H), 6.49 (d,
J = 15.9Hz, 1H), 4.32 (q, J= 7.1 Hz, 2H), 4.10 (s, 3H),
1.38 (t, J= 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ
(ppm) = 167.1, 156.7, 146.7, 145.9, 145.0, 130.6, 127.8,
126.2, 124.0, 123.4, 121.0, 117.6, 113.9, 112.3, 108.5,
60.6, 56.4, 14.5; IR (ATR) cmÀ1: 2929 (w), 1705 (s),
1269 (m), 1146 (s), 748 (m); HRMS (EI) calcd for
C18H16O4 [M+] 296.1049, found 296.1063.
3-Methoxydibenzo[b,d]furan (1h) [46].
Obtained from
5h (100 mg, 0.50 mmol). Yield of 1h without added 3-
nitropyridine: 22 mg (0.11 mmol, 22%). Colorless solid,
mp 79–81°C; 1H NMR (300 MHz, CDCl3): δ (ppm)
= 7.86 (dd, J = 7.3, 1.1 Hz, 1H), 7.81 (d, J = 8.5 Hz, 1H),
7.53 (d, J= 7.6Hz, 1H), 7.38 (td, J = 7.7, 1.5Hz, 1H),
7.31 (td, J = 7.4, 1.1 Hz, 1H), 7.10 (d, J = 2.2 Hz, 1H),
6.95 (dd, J= 8.5, 2.2 Hz, 1H), 3.91 (s, 3H); 13C NMR
(75 MHz, CDCl3): δ (ppm) = 160.1, 157.7, 156.5, 125.8,
124.6, 122.9, 121.1, 119.9, 117.5, 111.5, 111.1, 96.7,
55.9; IR (ATR) cmÀ1: 2934 (w), 1605 (m), 1457 (s),
1277 (s), 1144 (s); HRMS (EI) calcd for C13H10O2 [M+]
198.0675, found 198.0680.
4-Methoxydibenzo[b,d]furan-2-carbaldehyde (1l). Obtained
from 5l (114mg, 0.50mmol). Yield of 1l without added 3-
nitropyridine: 70mg (0.31mmol, 62%); yield of 1l with
added 3-nitropyridine: 78mg (0.35mmol, 69%). Colorless
solid, mp 101–103°C; 1H NMR (300MHz, CDCl3): δ
(ppm)= 9.99 (s, 1H), 7.95 (d, J= 1.3 Hz, 1H), 7.90 (d,
J=7.7Hz, 1H), 7.59 (d, J= 8.3 Hz, 1H), 7.47 (ddd, J=8.2,
7.5, 1.1 Hz, 1H), 7.45 (d, J= 1.3 Hz, 1H), 7.35 (td, J=7.5,
0.9Hz, 1H), 4.05 (s, 3H); 13C NMR (75MHz, CDCl3): δ
(ppm)= 191.2, 156.7, 148.9, 146.2, 133.0, 128.1, 125.8,
123.6, 123.6, 120.9, 117.9, 112.2, 107.6, 56.3; IR (ATR)
cmÀ1: 2936 (w), 1687 (s), 1585 (m), 1345 (m), 1134 (s);
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Dibenzofurans via Pd-Catalyzed C–H Activation
HRMS (EI) calcd for C14H10O3 [M+] 226.0624, found
226.0630.
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Naphtho[2,3-b]benzofuran (1m) [22]. Obtained from 5m
(110 mg, 0.50mmol), contaminated with impurities. Yield
of 1m with added 3-nitropyridine: <60 mg (<0.30mmol,
1
<60%). H NMR (300 MHz, CDCl3): δ (ppm) = 8.41 (s,
1H), 8.09 (dm, J= 8.0 Hz, 1H), 8.06 (dm, J =7.6Hz, 1H),
8.00 (d, J = 8.1Hz, 1H), 7.95 (s, 1H), 7.59–7.49 (m, 4H),
7.40 (td, J= 7.4, 1.2 Hz, 1H); 13C NMR (75 MHz,
CDCl3): δ (ppm) = 157.8, 155.0, 133.2, 130.3, 128.5,
128.0, 127.9, 125.9, 125.6, 124.4, 124.1, 122.9, 121.4,
119.3, 111.7, 107.1; IR (ATR) cmÀ1: 3051 (w), 1463
(m), 1201 (m), 870 (m), 739 (s); HRMS (EI) calcd for
C16H10O [M+] 218.0726, found 218.0720.
3-Methyldibenzo[b,d]furan (1n) [33]. Obtained from 5n
(92 mg, 0.50 mmol). Yield of 1n with added 3-
nitropyridine: 56 mg (0.31 mmol, 62%). Colorless solid,
mp 56–59°C; 1H NMR (300 MHz, CDCl3): δ (ppm)
= 7.94 (dd, J = 7.6, 0.7 Hz, 1H), 7.84 (d, J = 7.9 Hz, 1H),
7.59 (dd, J= 8.2, 0.7 Hz, 1H), 7.45 (td, J = 7.3, 1.4 Hz,
1H), 7.41 (s, 1H), 7.35 (td, J = 7.5, 1.0 Hz, 1H), 7.19 (d,
J =7.9 Hz, 1H), 2.56 (s, 3H); 13C NMR (75 MHz,
CDCl3): δ (ppm) = 156.8, 156.3, 137.8, 126.6, 124.5,
124.1, 122.7, 121.8, 120.4, 120.3, 112.0, 111.7, 22.1; IR
(ATR) cmÀ1: 2921 (w), 1457 (m), 1206 (w), 1127 (w),
809 (m); HRMS (EI) calcd for C13H10O [M+] 182.0726,
found 182.0731.
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Acknowledgments. We thank Evonik Oxeno for generous donations
of solvents and Umicore (Hanau, Germany) for generous donations
of Pd catalysts. Support from the equal opportunities fund of the
faculty of Science for M. R. is gratefully acknowledged.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet