Synthesis of 6,7-Dibromoflavone and Its Regioselective Diversification via Suzuki-Miyaura Reactions

Article abstract of DOI:10.1055/s-0036-1588376

The first synthesis pathway to 6,7-dibromoflavone and its transformations to 7-aryl-6-bromo- and 6,7-diarylflavones by Suzuki-Miyaura reactions are presented. Due to the different electronic effects of bromo substituents, the first attack proceeded with good site selectivity at position 7.

Full text of DOI:10.1055/s-0036-1588376

SYNTHESIS
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1
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–J
paper
A
S. Jordán et al.
Paper
Synthesis
Synthesis of 6,7-Dibromoflavone and Its Regioselective Diversifi-
cation via Suzuki–Miyaura Reactions
Sándor Jordána
Dávid Pajtása
R
O
Tamás Patonay †a
9 examples,
Peter Langer*b,c
Krisztina Kónya*a
pure isolated
yields: 56–90%
R
RC6H4B(OH)2
O
R
a Department of Organic Chemistry, University of Debrecen,
4032 Debrecen, Egyetem tér 1, Hungary
b Department of Chemistry, Organic Chemistry, University of
Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
c Leibniz-Institute for Catalysis e.V. at the University of
Rostock (LIKAT), Albert-Einstein-Str. 3a, 18059 Rostock,
Germany
O
RC6H4B(OH)2
Br
Br
O
O
Br
OH
5 examples,
pure isolated
yields: 38–59%
Br
4 steps
O
R1
R2
O
O
1) R1C6H4B(OH)2
2) R2C6H4B(OH)2
konya.krisztina@science.unideb.hu
5 examples,
pure isolated
yields: 35–57%
Dedicated to the memory of Prof. Tamás Patonay
Received: 23.10.2016
Accepted after revision: 20.11.2016
Published online: 10.01.2017
ing groups, following the order of reactivity: Ar–I > Ar–Br >
Ar–OTf > Ar–Cl > Ar–OTs.8 A successful coupling reaction
can be carried out with several type of catalysts and li-
gands.9
DOI: 10.1055/s-0036-1588376; Art ID: ss-2016-n0513-op
Abstract The first synthesis pathway to 6,7-dibromoflavone and its
transformations to 7-aryl-6-bromo- and 6,7-diarylflavones by Suzuki–
Miyaura reactions are presented. Due to the different electronic effects
of bromo substituents, the first attack proceeded with good site selec-
tivity at position 7.
In the Suzuki–Miyaura reaction of dihalogenated mate-
rials, containing only one type of leaving group, the regio-
selectivity is controlled by steric and electronic factors.10
1
Handy and Zhang suggested a simple guide, based on H
NMR spectroscopic chemical shift values, suitable to pre-
dict the regioselectivity of palladium(0)-catalyzed cross-
coupling reactions.10d In the last few years, regioselective
Suzuki–Miyaura coupling has become a useful approach to
increase the diversity of arylated flavone derivatives pro-
viding new differently substituted flavones.11
Key words palladium, Suzuki–Miyaura reaction, flavones, catalysis,
regioselectivity
Flavones (2-aryl-4H-1-benzopyran-4-ones) are com-
mon molecules in nature mostly as plant metabolites.1 Fla-
vone derivatives show versatile biological activities, e.g. an-
tioxidant, antimicrobial, antiproliferative, and anti-inflam-
matory properties, and central nervous system protective
effects were also detected.1–4 The syntheses of flavones are
mostly based on the corresponding chromone (4H-1-ben-
zopyran-4-one) core structure by conventional methods.2,3
Different biological activities were observed in the case
of arylated flavone derivatives, e.g. antiviral, antibacterial,
anti-inflammatory, enzyme inhibition, cytotoxic and even
DNA repairing properties have been reported.5 The Suzuki–
Miyaura reaction6 is a palladium-catalyzed C–C coupling
reaction using boronic acids and an aryl halide, triflate, or
tosylate substrate that may be a suitable method for syn-
thesizing arylated flavones.
In Nature many plants are known that show different
biological effects and a number contain 6,7-disubstituted
flavonoid compounds (Figure 1). For example, gan cao,12
also known as licorice, includes roots and or rhizomes of
Glycyrrhiza inflata Batal, G. uralensis Fisch, and G. glabra L.
is recorded in Chinese Pharmacopoeia. NQO1 and tumor
angiogenesis assay suggested three effective flavonoids, one
of them is licoflavone B, as being responsible for the che-
mopreventive effect. Its chemical and biological results in-
dicated that flavonoids from the residue of gan cao are
promising natural cancer chemopreventive agents with low
toxicity. Another example is G. sagittatum13 the roots of
which have been traditionally used in the Peruvian Amazon
as an anti-inflammatory, analgesic, and diuretic remedy,
whereas the infusion from the leaves is used to treat asth-
ma and anemia. Nowadays G. sagittatum is used as a com-
ponent of a herbal medicine for the treatment of female in-
fertility. From methanol and ethyl acetate extracts of this
plant, 6-hydroxy-7,4′-dimethoxyflavone and 6,7,4′-tri-
Besides the commercial availability of common boronic
acids, the advantages of the Suzuki–Miyaura reaction over
other palladium-catalyzed reactions are high functional
group tolerance and mild reaction conditions.7 The chemo-
selectivity of the reaction depends on the type of the leav-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

B
S. Jordán et al.
Paper
Synthesis
methoxyflavone were isolated among other flavonoids.
Moreover, one of the constituents of M. erythrocalyx
Gagnep,14 a plant growing in the central part of Thailand, is
millettocalyxin B; and the bark of this plant has been used
by the local people to treat stomach pain.
Herewith, we report the first synthesis of 6,7-dibromo-
flavone and its regioselective Suzuki–Miyaura reactions re-
sulting in 6,7-diarylflavone derivatives. The acylation and
Fries rearrangement of the commercially available 3-bro-
mophenol (1) resulted in 4′-bromo-2′-hydroxyacetophe-
none (2). Its further bromination led to 4′,5′,-dibromo-2′-
hydroxyacetophenone (3) in moderate yield, and this com-
pound was transformed into dibromochalcone
4 by
Claisen–Schmidt condensation.15 Using a catalytic amount
of iodine in hot dimethyl sulfoxide16 the ring closure of 4
provided the corresponding dibromoflavone 5 in excellent
yield (Scheme 1).
OH
1
8
7
6
2
HO
O
3
4
5
O
For the preparation of 4′,5′-dibromo-2′-hydroxyace-
tophenone (3) the key step is the bromination of acetophe-
none 2. The optimization of this step was carried out by
varying the solvent, the Lewis acid catalyst, and the amount
of bromine (Table 1).
licoflavone B
OMe
OMe
MeO
HO
O
O
MeO
MeO
O
O
Table 1 Optimization of the Synthesis of 3
compounds from Gynerium sagittatum
Br2 (equiv)
Solvent
Lewis acid (equiv)
Yielda (%) of 3
O
O
MeO
O
O
1.10
1.10
1.10
1.10
1.29
1.10
CS2
BF3·Et2O (1.1)
BF3·Et2O (1.1)
ZnCl2 (1.1)
ZnCl2 (1.1)
ZnCl2 (1.1)
ZnCl2 (2.2)
3
18
12
32
24
48
benzene
benzene
CS2
O
millettocalyxin B
Figure 1 6,7-Disubstituted flavonoids from natural sources
CS2
CS2
In order to increase the members of this family, we
planned to synthesize 6,7-dibromoflavone as a new sub-
strate since its detailed procedure is not known in the liter-
ature according to our current knowledge. In this manner
the synthesis and the transformation of 6,7-dibromofla-
vone can open a new gate to the synthesis of analogues of
other 6,7-disubstituted flavone compounds for further bio-
logical assays.
a Yields refer to pure isolated products.
Through these experiments, our aim was to find condi-
tions under which the formation of the byproduct 3′,4′,5′-
tribromo-2′-hydroxyacetophenone does not take place.
This is essential because the separation of the byproduct is
particularly difficult due to its low solubility in any kind of
solvent. During our optimization efforts more solvents
were examined and, as the results showed, the use of ben-
zene gave full conversion of 2, but the product was mainly
3′,4′,5′-tribromo-2′-hydroxyacetophenone. Therefore car-
bon disulfide was utilized and the amount of byproduct
was decreased in all cases. The use of soft Lewis acids, such
as boron trifluoride and zinc chloride, was examined and
the yield of 3 significantly increased in the presence of zinc
chloride in carbon disulfide. Increasing the equivalents of
bromine up to 1.29 caused the formation of a larger amount
of 3′,4′,5′-tribromo-2′-hydroxyacetophenone. Thus, ace-
tophenone 3 was isolated in the highest yield when the
amount of zinc chloride was raised to 2.2 equivalents and
the bromine was added in 1.10 equivalents in carbon disul-
fide.
Br
OH
Br
OH
Br
OH
i, ii
iii
Br
O
O
1
3 (48%)
iv
2 (73%)
Br
Br
OH
Br
Br
O
O
v
O
4 (98%)
5 (96%)
Scheme 1 Synthesis of 5. Reagents and conditions: (i) 1, Ac2O (6.88
equiv), anhyd NaOAc (2.11 equiv), reflux, 2.5 h; (ii) AlCl3, 170 °C, 3 h;
(iii) 2, Br2 (1.06 equiv), anhyd ZnCl2 (2.20 equiv), CS2, 0 °C–r.t., 24 h; (iv)
3, PhCHO (1.1 equiv), 50% aq NaOH (4.0 equiv), EtOH, r.t., 24 h; (v) 4, I2
(0.06 equiv), DMSO, 180 °C, 15 min.
The Suzuki–Miyaura reaction of 5 with arylboronic
acids 6a–i (2.3 equiv) afforded 6,7-diarylflavones 7a–i in
moderate to good yields (Table 2).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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S. Jordán et al.
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Synthesis
Table 2 Synthesis of 7a–ia
Table 3 Formation of 8a,ba
R
Ar
O
Br
Br
O
O
Br
Br
O
i
i
RC6H4B(OH)2
ArB(OH)2
6j,k
R
6a–i
O
O
O
O
8a,b
5
7a–i
5
6
8
Ar
Yieldb (%) of 8
6
7
R
Time (h)
Yieldb (%) of 7
6j
6k
8a
8b
2,4-Me2C6H3
39c
43
6a
6b
6c
6d
6e
6f
7a
7b
7c
7d
7e
7f
H
6
67
75
70
56
59
66
90
72
76
2,4,6-Me3C6H2
3-OMe
4-OMe
3-F
2.5
4
a Formation of 8a,b byproducts. Reaction conditions: (i) 5 (1.0 equiv), 6j,k
(2.3 equiv), Pd(PPh3)4 (10 mol%), 2 M aq Cs2CO3 solution (3.0 equiv), 1,4-
dioxane/MeOH (5:1), argon atmosphere, 100 °C, 16 h.
b Yields refer to pure isolated products.
2.5
3.5
2.5
2.5
5.5
2
c Solvent: 1,4-dioxane/H2O (5:1): no reaction; solvent: 1,4-dioxane/MeOH
(5:1): 70% 8a.
4-F
3-Cl
6g
6h
6i
7g
7h
7i
4-Cl
3-CF3
4-CF3
good yields and with very good site selectivity (Table 4).
Both electron-poor and electron-rich arylboronic acids
were successfully employed. The first coupling occurred in
position 7 with very good site selectivity; the isomer by-
product was not isolated. The conversion was high, but af-
ter the purification only moderate yields were achieved due
to the poor solubility of the products 9a–e. The best yields
were achieved using only 1.0 equiv boronic acid with
Pd(PPh3)4 (4 mol%) in 1,4-dioxane/methanol mixture at 70
°C.
a Reaction conditions: (i) 5, 6a–i (2.3 equiv), Pd(PPh3)4 (10 mol%), 2 M aq
Cs2CO3 solution (3.0 equiv), 1,4-dioxane/MeOH (5:1), argon atmosphere,
100 °C, 2–6 h.
b Yields refer to pure isolated products.
Both electron-rich and electron-poor arylboronic acids
were successfully used. The electronic and steric effects of
the boronic acid influenced the rate of the reaction. In every
case the reaction was monitored until full conversion. First,
the monocoupled molecule appeared, and then the diaryl-
ated 7a–i product began to form before the substrate 5
completely disappeared. The reactions were carried out us-
ing Pd(PPh3)4 (10 mol%) as catalyst and Cs2CO3 (3.0 equiv) in
aqueous solution as base in 1,4-dioxane/methanol mixture
at 100 °C in a pressure tube.
Using boronic acids 6j,k the corresponding monocou-
pled product formed, but instead of undergoing the second
coupling, dehalogenation occurred which resulted in by-
products 8a,b (Table 3). This result is explained by the con-
siderable steric hindrance of the ortho-substituted arylbo-
ronic acids.
In order to check the role of the water and methanol in
the dehalogenation process, the experiments with 2,6-di-
methylphenylboronic acid were repeated. Performing the
reaction in aqueous solution of 1,4-dioxane gave no reac-
tion. However, if the reaction was repeated in methanolic
solution of 1,4-dioxane without water the dehalogenated
compound 8a was isolated in 70% yield. Since, we were in-
terested in the dehalogenation, we have checked the litera-
ture and found that the used of an alcohol (in our case
MeOH) was the reason for the dehalogenation.18
Table 4 Synthesis of 9a–ea
R
Br
Br
O
O
i
RC6H4B(OH)2
6e,i,l-n
Br
O
O
9a–e
5
6
9
R
Time (h)
Yieldb (%) of 9
6e
6i
9a
4-F
4
53
38
57
49
59
9b
9c
9d
9e
4-CF3
4-Me
4-t-Bu
4-Ph
9
6l
4.5
6
6m
6n
4.5
a Reaction conditions: (i) 5, 6e,i,l–n (1.0 equiv), Pd(PPh3)4 (4 mol%), 2 M aq
Cs2CO3 solution (3.0 equiv), 1,4-dioxane/MeOH (5:1), 70 °C, argon atmo-
sphere, 4–9 h.
b Yields refer to pure isolated products.
According to Handy and Zhang’s method, which uses
1
the H NMR chemical shifts of the non-halogenated parent
compounds in the case of polyhalogenated heteroaromat-
ics, the predicted regioselectivity of 6,7-dibromoflavone (5)
is C-7 > C-6 (Δδ ≅ 0.40). In this case, the manifested elec-
tronic difference through the chemical shift differences be-
tween C-6 and C-7 is sufficient to direct the first coupling
6,7-Dibromoflavone (5) was also transformed into 7-
aryl-6-bromoflavones 9a–e in a Suzuki–Miyaura reaction
using arylboronic acids 6e,i,l–n (1.0 equiv). The reactions
provided the corresponding products 9a–e in moderate to
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D
S. Jordán et al.
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Synthesis
to the more electron-deficient C-7 site. The first attack oc-
curred at the more electron deficient center C-7, providing
7-monoaryl-6-bromoflavones in good yields. The second
bromide (C-6) also could take part in the coupling reaction,
although it requires more vigorous conditions as our exper-
iments showed.
Table 5 Synthesis of 10a–ea
R1
R2
O
O
Br
Br
O
i, ii
1) R1C6H4B(OH)2
2) R2C6H4B(OH)2
O
All products were characterized by spectroscopic meth-
ods. The structural characterization of products 9a–e was
supported by 2D NMR experiments (HMBC, NOESY) as well.
Figure 2 shows the structure and the NOESY spectra of the
product 9b, which clearly proves the order of the coupling
by the NOE effect of H-8 and H-2′′.
10a–e
5
6
R1
Time (h)
6
R2
10
10a
Yieldb (%) of 10
6i
4-CF3
4-CF3
4-Ph
4-Ph
4-Ph
7.5
7.5
5
6b
6c
6c
6e
6i
3-MeO
4-MeO
4-MeO
4-F
53
35
57
62
39
6i
10b
10c
10d
10e
6n
6n
6n
5
5
4-CF3
a Reaction conditions: (i) 5, 6i or 6n (1.0 equiv), Pd(PPh3)4 (4 mol%), 2 M aq
Cs2CO3 solution (3.0 equiv), 1,4-dioxane/MeOH (5:1), argon atmosphere,
75 °C, 5–7.5 h; (ii) 6b, 6c, 6e, or 6i (1.3 equiv), Pd(PPh3)4 (6 mol%), 100 °C,
2 h.
b Yields refer to pure isolated products.
over, the reaction of 6-bromo-7-monoarylflavones with
different boronic acids did not show electronic effects of
substituents on the boronic acid.
All reactions were carried out in oven-dried pressure tubes under an
argon atmosphere. Reagents were purchased from commercial sourc-
es (Sigma Aldrich, TCI, Alfa Aesar). Column chromatography was per-
formed on silica gel (Merck 60, 0.043–0.06 mm). TLC was performed
on Merck precoated aluminum plates (Si 60 F254). NMR spectra were
recorded with Bruker Avance 250 II, Bruker Avance 300 III, Bruker 360
AM Avance, Bruker DRX 400, and Bruker Avance 500 spectrometers.
1
13C and H NMR spectra were referenced to signals of the deuterated
solvents (CHCl3, δ = 7.26 1H NMR; δ = 77.00 13C NMR). IR spectra were
recorded with a Perkin–Elmer FT IR 1600 spectrophotometer (ATR)
and with a Perkin-Elmer 16PC FT-IR spectrophotometer (KBr). The
purity of the compounds was established by GC-MS (Agilent 7890,
Agilent 5975 MS detector) with positive EI at 70 eV. HPLC-MS was
performed using an Accela HPLC system (Thermo Electron Corp., San
Jose, CA, USA). The LC system was coupled with a Thermo LTQ XL
mass spectrometer (Thermo Electron Corp., San Jose, CA, USA) operat-
ed in a full scan positive ion ESI mode. The elementary analysis was
carried out with an Elementar Vario Microtube instrument. Melting
point data were determined by using Büchi B-540 equipment.
Figure 2 NOESY spectrum of 9b
The Suzuki–Miyaura reaction of 6,7-dibromoflavone (5)
was also studied as a one-pot reaction. In the first step, af-
ter the full conversion of substrate 5 with Ar1B(OH)2, the
second type of boronic acid Ar2B(OH)2 was added along
with extra 6 mol% catalyst. This method operated with very
good regioselectivity providing differently substituted di-
arylflavone derivatives in good isolated yields (Table 5).
In summary, we have demonstrated the synthesis of a
variety of arylated flavones via site-selective Suzuki–
Miyaura reaction of 6,7-dibromoflavone. Numerous boronic
acids reacted easily under mild conditions, providing differ-
ent mono-/bis-/diarylated derivatives of flavone in moder-
ate to excellent yields. In these reactions, the first attack oc-
curred at the more electron-deficient carbon atom (C-7),
providing 6-bromo-7-monoarylflavones in good yields. The
Suzuki–Miyaura reaction of 6,7-dibromoflavone as a one-
pot reaction was also studied, where the second bromide
(C-6) also could take part in the coupling reaction. More-
6,7-Dibromoflavone (5)
4′-Bromo-2′-hydroxyacetophenone (2)
Commercially available 3-bromophenol (1, 50 g, 0.289 mol) was add-
ed to a mixture of Ac2O (187.5 mL, 1.987 mol) and anhyd NaOAc (50 g,
0.6095 mol) in a round-bottom flask. The mixture was refluxed and
stirred for 2.5 h. The mixture was poured into ice-water (400 mL).
The organic phase was separated, washed with water (200 mL) and
sat. aq NaHCO3 solution (100 mL). The combined aqueous phases
were extracted with CH2Cl2 (3 × 80 mL), the combined organic phases
were dried (MgSO4), then filtered. The solvent was evaporated in vac-
uo to give the pure 3-bromophenyl acetate17 (50.4 g, 81%) as pale yel-
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S. Jordán et al.
Paper
Synthesis
low oil; Rf = 0.62 (toluene/EtOAc, 4:1). 3-Bromophenyl acetate was
transferred into a three-neck flask and AlCl3 (103 g, 0.7724 mol) was
added in small portions. The mixture was heated and stirred at 170 °C
for 3 h. The mixture was cooled to approx. 60 °C, and then ice (200 g)
and 10% HCl solution (100 mL) were added and the mixture was
stirred and distilled using steam. From the distillate white crystals
were filtered off to give product 219 (45 g, 90%); Rf = 0.55 (toluene);
mp 39–40 °C.
GC-MS: m/z (%) = 380.9 [M+, 100], 304.9 [M+ – Br], 277.8, 249.8, 222.9,
165.1, 131.0, 104.1, 77.0.
Anal. Calcd for C15H10Br2O2: C, 47.16; H, 2.64. Found: C, 47.25; H, 2.67.
6,7-Dibromoflavone (5)
To the solution of 4′,5′-dibromo-2′-hydroxychalcone (4, 7.9 g, 20.678
mmol) in DMSO (120 mL), I2 (315 mg, 1.24 mmol) was added and the
mixture was moderately refluxed for 15 min. The mixture was poured
into ice-water mixture (2 L), and then Na2SO3 was added and the mix-
ture was stirred. The solid product 5 was filtered off as off-white crys-
tals and washed with water (2 × 20 mL) and i-Pr2O (2 × 15 mL); yield:
7.54 g (96%); Rf = 0.58 (toluene/EtOAc, 4:1); mp 230–231 °C.
Its spectral data are identical with the literature.20
IR (KBr): 3082, 3039, 3010, 1636, 1610, 1462, 1348, 1315, 1232, 1201,
967, 890, 735, 626, 497 cm–1
.
1H NMR (360 MHz, CDCl3): δ = 2.61 (s, 3 H, Me), 7.04 (dd, J = 2.5, 8.5
Hz, 1 H, 5′-H), 7.18 (d, J = 2.5 Hz, 1 H, 3′-H), 7.58 (d, J = 8.5 Hz, 1 H, 6′-
H), 12.34 (s, 1 H, OH).
IR (KBr): 3444, 3054, 3008, 1637, 1610, 1592, 1454, 1415, 1349, 911,
903, 769, 683 cm–1
.
1H NMR (360 MHz, CDCl3): δ = 6.82 (s, 1 H, 3-H), 7.52–7.58 (m, 3 H, 3′-
H, 4′-H, 5′-H), 7.88–7.90 (d, J = 6.5 Hz, 2 H, 2′-H, 6′-H), 7.93 (s, 1 H, 8-
H), 8.45 (s, 1 H, 5-H).
13C NMR (90 MHz, CDCl3): δ = 107.8 (C-3), 121.8 (C-6), 123.6 (C-8),
124.3 (C-4a), 126.5 (C-2′, C-6′), 129.3 (C-3′, C-5′), 130.3 (C-4′), 130.6
(C-7), 131.2 (C-1′), 132.2 (C-5), 154.8 (C-8a), 163.9 (C-2), 176.6 (C-4).
4′,5′-Dibromo-2′-hydroxyacetophenone (3)
To a solution of 4′-bromo-2′-hydroxyacetophenone (2, 15 g, 69.75
mmol) in CS2 (220 mL), cooled with an ice bath, was added anhyd Zn-
Cl2 (28.52 g, 209 mmol) with stirring. After 15 min Br2 (3.8 mL, 74.17
mmol) was added, the temperature was allowed to warm up to r.t.,
and stirring was continued for 2 d. 5% aq Na2S2O3 solution (200 mL)
was poured into the mixture and the organic phase was separated
and the aqueous phase was extracted with CH2Cl2 (3 × 50 mL). The
combined organic phases were dried (MgSO4) and filtered. The sol-
vent was evaporated in vacuo, and the solid residue was washed with
i-Pr2O (2 × 15 mL) and filtered to give product 3 (10.31 g, 48%) as off-
white crystals; Rf = 0.58 (toluene); mp 131–133.3 °C.
GC-MS: m/z (%) = 379.9 [M+, 100], 351.9, 277.8, 249.8, 163.0, 140.9,
102.0.
Anal. Calcd for C15H8Br2O2: C, 47.41; H, 2.12. Found: C, 47.36; H, 2.11.
Diarylation of 6,7-Dibromoflavone (5); General Procedure for 7a–i
To a mixture of 6,7-dibromoflavone (5, 95 mg, 0.25 mmol), 2 M aq
Cs2CO3 solution (0.75 mmol), and boronic acid (0.58 mmol) in 1,4-di-
oxane/MeOH (5:1, 3.6 mL), in a pressure tube under argon, was added
Pd(PPh3)4 (28.9 mg, 0.025 mmol). The mixture was stirred and heated
at 100 °C in an aluminum heating block for the time given in Tables 2
and 3, until complete conversion. The mixture was dried (MgSO4) and
filtered off. The solvent was removed under reduced pressure; the
residue was purified by column chromatography to give the pure
cross-coupled product 7a–i.
IR (KBr): 3444, 3079, 3041, 3009, 1645, 1603, 1456, 1422, 1367, 1325,
1311, 1252, 1216, 967, 895, 785, 743, 635, 487 cm–1
.
1H NMR (360 MHz, CDCl3): δ = 2.61 (s, 3 H, Me), 7.28 (s, 1 H, 3′-H),
7.91 (s, 1 H, 6′-H), 12.11 (s, 1 H, OH).
13C NMR (100 MHz, CDCl3): δ = 26.8 (C-2), 113.4 (C-5′), 120.1 (C-1′),
123.8 (C-3′), 133.1 (C-4′), 134.4 (C-6′), 161.2 (C-2′), 203.2 (C-1).
GC-MS: m/z (%) = 293.9 [M+], 278.8 [M+ – Me, 100], 250.8 [M+ – Ac],
222.8, 142.9.
Anal. Calcd for C8H6Br2O2: C, 32.69; H, 2.06. Found: C, 32.75; H, 2.05.
6,7-Diphenylflavone (7a)
Pale yellow crystals; yield: 63 mg (67%); mp 132–134 °C; Rf = 0.26
4′,5′-Dibromo-2′-hydroxychalcone (4)
(heptane/EtOAc, 4:1).
To the suspension of 4′,5′-dibromo-2′-hydroxyacetophenone (3, 10 g,
34.02 mmol) and EtOH (200 mL) was added 50% aq NaOH (7.12 mL,
136 mmol) to give a homogenous solution. To the solution benzalde-
hyde (3.8 mL, 37.42 mmol) was added and the mixture was stirred for
30 min and then it was allowed to stand at r.t. for 2 d. 10% HCl solu-
tion was added to reach pH 1; the precipitate was filtered off and
washed with water (3 × 30 mL) to give 4 (12.790 g, 98%) as yellow
crystals; Rf = 0.80 (toluene/EtOAc, 4:1); mp 144.4–145.8 °C.
IR (ATR): 3401, 3059, 3024, 2926, 1633, 1614, 1602, 1451, 1425, 1356,
777, 764, 695 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 6.92 (s, 1 H, 3-H), 7.16–7.30 (m, 10 H,
2′′-H, 3′′-H, 4′′-H, 5′′-H, 6′′-H, 1′′′-H, 2′′′-H, 3′′′-H, 4′′′-H, 5′′′-H), 7.54–
7.57 (m, 3 H, 3′-H, 4′-H, 5′-H), 7.66 (s, 1 H, 8-H), 7.96–7.99 (dd, 2 H, 2′-
H, 6′-H), 8.29 (s, 1 H, 8-H).
13C NMR (75 MHz, CDCl3): δ = 107.8 (C-3), 119.8 (C-8), 122.8 (C-4a),
126.4 (C-2′, C-6′), 127.1, 127.4 (C-4′′, C-4′′′), 127.7 (C-4′), 128.1, 128.3
(C-2′′,C-6′′, C-2′′′, C-6′′′), 129.2 (C-3′, C-5′), 129.7, 130.0 (C-3′′, C-5′′, C-
3′′′, C-5′′′), 131.8 (C-5), 131.9 (C-1′), 138.6 (C-6), 139.8, 139.9 (C-1′′, C-
1′′′), 146.9 (C-7), 155.5 (C-8a), 163.8 (C-2), 178.4 (C-4).
IR (KBr): 3444, 3061, 3023, 2924, 1639, 1567, 1454, 1360, 1329, 1191,
1033, 729 cm–1
.
1H NMR (360 MHz, 298 K, CDCl3): δ = 7.37 (s, 1 H, 3′-H), 7.46–7.48 (m,
3 H, 3-H, 4-H, 5-H), 7.50–7.54 (d, J = 15.5 Hz, 1 H, β-H), 7.68–7.70 (m,
2 H, 2-H, 6-H), 7.95–7.99 (d, J =15.1 Hz, 1 H, α-H), 8.11 (s, 1 H, 6′-H),
12.75 (s, 1 H, OH).
13C NMR (100 MHz, 298 K, CDCl3): δ = 113.5 (C-5′), 119.1 (C-β), 120.5
(C-1′), 124.0 (C-3′), 129.1 (C-2, C-6), 129.3 (C-3, C-5), 131.6 (C-4),
133.0 (C-4′), 133.4 (C-6′), 134.2 (C-1), 147.2 (C-α), 162.4 (C-2′), 192.3
(C-γ).
Anal. Calcd for C27H18O2: C, 86.61; H, 4.85. Found: C 86.50; H 4.79.
6,7-Bis(3-methoxyphenyl)flavone (7b)
Yellow crystals; yield: 81 mg (75%); mp 158–159 °C; Rf = 0.16 (hep-
tane/EtOAc, 4:1).
IR (ATR): 3058, 2938, 2833, 1636, 1603, 1574, 1450, 1427, 1417, 1355,
1287, 1220, 1206, 1020, 770, 684 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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S. Jordán et al.
Paper
Synthesis
1H NMR (300 MHz, CDCl3): δ = 3.65 (s, 3 H), 3.66 (s, 3 H) (3′′-OMe, 3′′′-
OMe), 6.71–6.74 (m, 2 H, 4′′-H, 4′′′-H), 6.78–6.86 (m, 4 H, 2′′-H, 6′′-H,
2′′′-H, 6′′′-H), 6.93 (s, 1 H, 3-H), 7.14–7.24 (m, 2 H, 5′′-H, 5′′′-H), 7.53–
7.57 (m, 3 H, 3′-H, 4′-H, 5′-H), 7.68 (s, 1 H, 8-H), 7.96–7.99 (m, 2 H, 2′-
H, 6′-H), 8.30 (s, 1 H, 5-H).
13C NMR (75 MHz, CDCl3): δ = 55.3 (C-3′′-OMe, C-3′′′-OMe), 107.8 (C-
3), 113.4, 113.9 (C-4′′, C-4′′′), 115.0, 115.2 (C-2′′, C-2′′′), 119.7 (C-8),
122.1, 122.5 (C-6′′, C-6′′′), 122.9 (C-4a), 126.5 (C-2′, C-6′), 127.3 (C-4′),
129.2, 129.2 (C-5′′, C-5′′′), 129.4 (C-3′, C-5′), 131.84 (C-5), 131.87 (C-
1′), 138.4 (C-6), 141.2, 141.2 (C-1′′, C-1′′′), 146.7 (C-7), 155.5 (C-8a),
159.4, 159.4 (C-3′′, C-3′′′), 163.8 (C-2), 178.3 (C-4).
1H NMR (300 MHz, CDCl3): δ = 6.88 (s, 1 H, 3-H), 6.92–7.02 (m, 4 H,
3′′-H, 5′′-H, 3′′′-H, 5′′′-H), 7.09–7.19 (m, 4 H, 2′′-H, 6′′-H, 2′′′-H, 6′′′-H),
7.52–7.58 (m, 3 H, 3′-H, 4′-H, 5′-H), 7.61 (s, 1 H, 8-H), 7.94–7.97 (m, 2
H, 2′-H, 6′-H), 8.22 (s, 1 H, 5-H).
13C NMR (75 MHz, CDCl3): δ = 107.8 (C-3), 115.12–115.41, 115.32–
115.61 (C-3′′, C-5′′, C-3′′′, C-5′′′, J = 21.3 Hz), 119.8 (C-8), 123.0 (C-4a),
126.4 (C-2′, C-6′), 127.4 (C-4), 129.2 (C-3′, C-5′), 131.33–131.43,
131.53–131.63 (C-2′′, C-6′′, C-2′′′, C-6′′′, J = 8.1 Hz), 131.8 (C-1′), 131.8
(C-5), 135.61–135.65, 135.66–135.71 (C-1′′, C-1′′′, J = 3.6 Hz), 137.3
(C-6), 145.6 (C-7), 155.5 (C-8a), 160.5–163.8, 160.8–164.1 (C-4′′, C-
4′′′, J = 246.0 Hz), 163.7 (C-2), 178.1 (C-4).
Anal. Calcd for C29H22O4: C, 80.17; H, 5.10. Found: C, 80.05; H, 5.11.
GC-MS: m/z (%) = 410.1 [M+, 100], 306.9, 280.0, 251.0, 207.0, 102.0.
Anal. Calcd for C27H16F2O2: C, 79.02; H, 3.93. Found: C, 79.10; H, 3.89.
6,7-Bis(4-methoxyphenyl)flavone (7c)
Yellow crystals; yield: 76 mg (70%); mp 192–194 °C; Rf = 0.16 (hep-
6,7-Bis(3-chlorophenyl)flavone (7f)
tane/EtOAc, 4:1).
Yellow crystals; yield: 74 mg (66%); mp 161.5–163.7 °C; Rf = 0.27
IR (ATR): 3073, 3023, 2997, 2951, 2928, 2901, 2833, 1643, 1606, 1513,
(heptane/EtOAc, 4:1).
IR (ATR): 3444, 3061, 1649, 1620, 1449, 1356, 788, 774, 687 cm–1
1448, 1433, 1353, 1245, 1176, 1020, 829, 782, 692 cm–1
.
.
1H NMR (300 MHz, CDCl3): δ = 3.81 (s, 3 H), 3.81 (s, 3 H) (4′′-OMe, 4′′′-
OMe), 6.78–6.84 (m, 4 H, 3′′-H, 5′′-H, 3′′′-H, 5′′′-H), 6.91 (s, 1 H, 3-H),
7.09–7.16 (m, 4 H, 2′′-H, 6′′-H, 2′′′-H, 6′′′-H), 7.52–7.56 (m, 3 H, 3′-H,
4′-H, 5′-H), 7.60 (s, 1 H, 8-H), 7.95–7.98 (m, 2 H, 2′-H, 6′-H), 8.22 (s, 1
H, 5-H).
13C NMR (75 MHz, CDCl3): δ = 55.3, 55.4 (C-4′′-OMe, C-4′′′-OMe),
107.7 (C-3), 113.7, 113.8 (C-2′′, C-6′′, C-2′′′, C-6′′′), 119.5 (C-8), 122.6
(C-4a), 126.4 (C-2′, C-6′), 127.2 (C-4′), 129.2 (C-3′, C-6′), 130.9, 131.1
(C-3′′, C-5′′, C-3′′′, C-5′′′), 131.7 (C-5), 132.0 (C-1′), 132.42, 132.44 (C-
1′′, C-1′′′), 138.2 (C-6), 146.5 (C-7), 155.4 (C-8a), 158.8, 159.3 (C-4′′, C-
4′′′), 163.6 (C-2), 178.4 (C-4).
1H NMR (300 MHz, CDCl3): δ = 6.89 (s, 1 H, 3-H), 6.96–7.02 (m, 2 H,
4′′-H, 4′′′-H), 7.16–7.30 (m, 6 H, 2′′-H, 5′′-H, 6′′-H, 2′′′-H, 5′′′-H, 6′′′-H),
7.54–7.57 (m, 3 H, 3′-H, 4′-H, 5′-H), 7.63 (s, 1 H, 8-H), 7.94–7.97 (m, 2
H, 2′-H, 6′-H), 8.24 (s, 1 H, 5-H).
13C NMR (75 MHz, CDCl3): δ = 107.8 (C-3), 120.0 (C-8), 123.2 (C-4a),
126.4 (C-2′, C-6′), 127.5, 127.6 (C-4′′, C-4′′′), 128.0, 128.1 (C-2′′, C-2′′′),
128.2 (C-4′), 129.2 (C-3′, C-5′), 129.4, 129.5 (C-5′′, C-5′′′), 129.6, 129.9
(C-6′′, C-6′′′), 131.6 (C-1′), 131.9 (C-5), 134.2, 134.4 (C-3′′, C-3′′′), 136.8
(C-6), 141.1, 141.2 (C-1′′, C-1′′′), 145.0 (C-7), 155.6 (C-8a), 163.8 (C-2),
177.9 (C-4).
Anal. Calcd for C27H16Cl2O2: C, 73.15; H, 3.64. Found: C, 73.10; H, 3.61.
Anal. Calcd for C29H22O4: C, 80.17; H, 5.10. Found: C, 80.06; H, 5.07.
6,7-Bis(4-chlorophenyl)flavone (7g)
6,7-Bis(3-fluorophenyl)flavone (7d)
Yellow crystals; yield: 100 mg (90%); mp 222–224 °C; Rf = 0.27 (hep-
tane/EtOAc, 4:1).
Pale yellow crystals; yield: 57 mg (56%); mp 177–179 °C; Rf = 0.30
(heptane/EtOAc, 4:1).
IR (ATR): 3056, 2919, 1634, 1616, 1448, 1434, 1355, 1088, 1010, 834,
IR (ATR): 3063, 2918, 1641, 1622, 1611, 1606, 1578, 1575, 1359, 874,
765, 733, 682 cm–1
.
837, 775, 687, 683 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 6.92 (s, 1 H, 3-H), 7.07–7.14 (m, 4 H,
3′′-H, 5′′-H, 3′′′-H, 5′′′-H), 7.23–7.30 (m, 4 H, 2′′-H, 6′′-H, 2′′′-H, 6′′′-H),
7.54–7.58 (m, 3 H, 3′-H, 4′-H, 5′-H), 7.62 (s, 1 H, 5-H), 7.94–7.98 (m, 2
H, 2′-H, 6′-H), 8.24 (s, 1 H, 5-H).
13C NMR (75 MHz, CDCl3): δ = 107.8 (C-3), 119.9 (C-8), 123.0 (C-4a),
126.5 (C-2′, C-6′), 127.6 (C-4′), 128.6, 128.8 (C-2′′, C-6′′, C-2′′′, C-6′′′),
129.3 (C-3′′, C-5′′), 131.0, 131.3 (C-3′′, C-5′′, C-3′′′, C-5′′′), 131.7 (C-1′),
132.1 (C-5), 133.6, 134.3 (C-4′′, C-4′′′), 137.2 (C-6), 137.96, 138.01 (C-
1′′,C-1′′′), 145.5 (C-7), 155.7 (C-8a), 164.1 (C-2), 178.2 (C-4).
1H NMR (300 MHz, CDCl3): δ = 6.86–7.05 (m, 7 H, 3-H, 2′′-H, 5′′-H, 6′′-
H, 2′′′-H, 5′′′-H, 6′′′-H), 7.19–7.30 (m, 2 H, 4′′-H, 4′′′-H), 7.53–7.58 (m,
3 H, 3′-H, 4′-H, 5′-H), 7.66 (s, 1 H, 8-H), 7.95–7.98 (m, 2 H, 2′-H, 6′-H),
8.27 (s, 1 H, 5-H).
13C NMR (75 MHz, CDCl3): δ = 107.8 (C-3), 114.3–114.6, 114.9–115.1
(C-4′′, C-4′′′, J = 20.9 Hz), 116.49–116.76, 116.78–117.05 (C-2′′, C-2′′′,
J = 20.7 Hz), 120.0 (C-8), 123.1 (C-4a), 125.48–125.52, 125.74–125.78
(C-6′′, C-6′′′, J = 3.0 Hz), 126.5 (C-2′, C-6′), 127.7 (C-4′), 129.3 (C-3′, C-
5′), 129.8–129.9, 130.0–130.1 (C-5′′, C-5′′′, J = 8.4 Hz), 131.7 (C-1′),
132.0 (C-5), 137.21–137.23 (C-6, J = 2.0 Hz), 141.6, 141.7 (C-1′′, C-1′′′),
145.39–145.41 (C-7, J = 2.0 Hz), 155.7 (C-8a), 160.96–164.23, 161.02–
164.29 (C-3′′, C-3′′′, J = 245.1 Hz), 164.1 (C-2), 178.1 (C-4).
Anal. Calcd for C27H16Cl2O2: C, 73.15; H, 3.64. Found: C, 73.08; H, 3.63.
6,7-Bis[3-(trifluoromethyl)phenyl]flavone (7h)
Pale yellow crystals; yield: 92 mg (72%); mp 185–187 °C; Rf = 0.30
(heptane/EtOAc, 4:1).
Anal. Calcd for C27H16F2O2: C, 79.02; H, 3.93. Found: C, 78.94; H, 3.92.
IR (ATR): 3065, 3044, 1643, 1622, 1327, 1155, 1118, 1096, 1074, 807,
6,7-Bis(4-fluorophenyl)flavone (7e)
768, 708, 703, 679, 653 cm–1
.
Yellow crystals; yield: 60 mg (59%); mp 207–209 °C; Rf = 0.28 (hep-
tane/EtOAc, 4:1).
1H NMR (360 MHz, CDCl3): δ = 6.93 (s, 1 H, 3-H), 7.32–7.45 (m, 6 H,
2′′-H, 5′′-H, 6′′-H, 2′′′-H, 5′′′-H, 6′′′-H), 7.51–7.57 (m, 5 H, 3′-H, 4′-H, 5′-
H, 2′′-H, 2′′′-H), 7.71 (s, 1 H, 8-H), 7.96–7.99 (m, 2 H, 2′-H, 6′-H), 8.32
(s, 1 H, 5-H).
IR (ATR): 3053, 2920, 1642, 1617, 1605, 1436, 1352, 1214, 909, 831,
771, 691 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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S. Jordán et al.
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Synthesis
13C NMR (75 MHz, CDCl3): δ = 108.0 (C-3), 120.1 (C-8), 122.0–125.7,
122.1–125.7 (C-3′′-CF3, C-3′′′-CF3, J = 270.8 Hz), 123.6 (C-4a), 124.22–
124.27, 124.77–124.82 (C-4′′, C-4′′′), 126.5 (C-2′, C-6′), 126.87, 126.92
(C-2′′, C-2′′′), 127.7 (C-4′), 128.9, 129.1 (C-5′′, C-5′′′), 129.3 (C-3′, C-5′),
130.67–131.10, 130.89–131.32 (C-3′′, C-3′′′, J = 32.3 Hz), 131.6 (C-1′),
132.1 (C-5), 133.0, 133.3 (C-6′′, C-6′′′), 136.9 (C-6), 139.98, 140.05 (C-
1′′, C-1′′′), 145.1 (C-7), 155.9 (C-8a), 164.1 (C-2), 178.0 (C-4).
LC-MS: m/z = 341.4 [M + H+].
Anal. Calcd for C24H20O2: C, 84.68; H, 5.92. Found: C, 84.59; H, 5.94.
Monoarylation of 6,7-Dibromoflavone (5); General Procedure for
9a–e
To a mixture of 6,7-dibromoflavone (5, 95 mg, 0.25 mmol), 2 M aq
Cs2CO3 solution (0.75 mmol), and boronic acid (0.25 mmol) in 1,4-di-
oxane/MeOH (5:1, 6 mL), in a pressure tube under argon, was added
Pd(PPh3)4 (11.6 mg, 0.01 mmol). The mixture was stirred and heated
at 70 °C in an aluminum heating block for the time given in Table 4,
until full conversion. The mixture was dried (MgSO4) and filtered off.
The solvent was removed under reduced pressure; the residue was
purified by column chromatography to give the pure monosubstitut-
ed product 9a–e.
Anal. Calcd for C29H16F6O2: C, 68.24; H, 3.16. Found: C, 68.16; H, 3.15.
6,7-Bis[4-(trifluoromethyl)phenyl]flavone (7i)
The crude product was purified by washing with i-Pr2O (2 × 3 mL);
orange crystals; yield: 97 mg (76%); mp 208–209 °C.
IR (ATR): 3066, 2919, 2848, 1645, 1617, 1608, 1436, 1405, 1324, 1158,
1106, 1066, 839, 774, 690 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 6.88 (s, 1 H, 3-H), 7.26–7.33 (m, 4 H,
2′′-H, 6′′-H, 2′′′-H, 6′′′-H), 7.51–7.58 (m, 7 H, 3′-H, 4′-H, 5′-H, 3′′-H, 5′′-
H, 3′′′-H, 5′′′-H), 7.66 (s, 1 H, 8-H), 7.93–7.96 (dd, 2 H, 2′′-H, 6′′-H),
8.27 (s, 1 H, 5-H).
6-Bromo-7-(4-fluorophenyl)flavone (9a)
White crystals; yield: 53 mg (53%); mp 206–208 °C; Rf = 0.32 (hex-
ane/CH2Cl2/EtOAc, 7:4:1).
13C NMR (90 MHz, CDCl3): δ = 108.0 (C-3), 120.3 (C-8), 122.5, 122.6
(C-4′′-CF3, C-4′′′-CF3), 123.6 (C-4a), 125.36–125.39, 125.53–125.55 (C-
3′′, C-5′′, C-3′′′, C-5′′′, J = 3.6 Hz), 126.4 (C-2′, C-6′), 128.0 (C-4′), 129.3
(C-3′, C-5′), 129.5–129.9 (C-4′′, C-4′′′, J = 32.7 Hz), 130.1, 130.3 (C-2′′,
C-6′′, C-2′′′, C-6′′′), 131.6 (C-1′), 132.0 (C-5), 136.8 (C-6), 143.0 (C-1′′,
C-1′′′), 145.0 (C-7), 155.8 (C-8a), 163.9 (C-2), 177.8 (C-4).
IR (KBr): 3444, 3042, 1645, 1618, 1604, 1517, 1450, 1423, 1396, 1359,
1227, 915, 835, 769, 686 cm–1
.
1H NMR (360 MHz, CDCl3): δ = 6.83 (s, 1 H, 3-H), 7.15–7.19 (t, 2 H, 3′′-
H, 5′′-H), 7.43–7.54 (m, 6 H, 8-H, 3′-H, 4′-H, 5′-H, 2′′-H, 6′′-H), 7.89–
7.91 (d, J = 5.4 Hz, 2 H, 2′-H, 6′-H), 8.48 (s, 1 H, 5-H).
13C NMR (90 MHz, CDCl3): δ = 107.7 (C-3), 115.3–115.6 (C-3′′, C-5′′, J =
21.6 Hz), 119.4 (C-6), 120.7 (C-8), 124.2 (C-4a), 126.4 (C-2′, C-6′),
129.2 (C-3′, C-5′), 130.1 (C-4′), 131.1–131.2 (C-2′′, C-6′′, J = 8.3 Hz),
131.5 (C-1′), 132.0 (C-5), 135.5 (C-1′′), 147.1 (C-7), 155.0 (C-8a),
161.6–164.3 (C-4′′, J = 247.2 Hz), 163.9 (C-2), 176.9 (C-4).
Anal. Calcd for C29H16F6O2: C, 68.24; H, 3.16. Found: C, 70.27; H, 3.15.
7-(2,6-Dimethylphenyl)flavone (8a)
Pale yellow crystals; yield: 32 mg (39%); mp 194–194 °C; Rf = 0.37
(heptane/EtOAc, 8:1).
GC-MS: m/z (%) = 394.0 [M+], 368.0, 291.9, 257.0, 207.0, 182.9, 157.0
[100], 128.7, 102.0, 76.0.
IR (ATR): 3051, 3022, 2951, 2919, 1636, 1607, 1418, 828, 771, 761,
677 cm–1
.
Anal. Calcd for C21H12BrFO2: C, 63.82; H, 3.06. Found: C, 63.76; H, 3.03.
1H NMR (300 MHz, CDCl3): δ = 2.09 (s, 6 H, 2′′-Me, 6′′-Me), 6.91 (s, 1
H, 3-H), 7.14–7.26 (m, 4 H, 6-H, 3′′-H, 4′′-H, 5′′-H), 7.420–7.424 (d, J =
1.2 Hz, 1 H, 8-H), 7.52–7.57 (m, 3 H, 3′-H, 4′-H, 5′-H), 7.94–7.97 (m, 2
H, 2′-H, 6′-H), 8.30–8.33 (d, J = 8.1 Hz, 1 H, 5-H).
6-Bromo-7-[4-(trifluoromethyl)phenyl]flavone (9b)
White crystals; yield: 42 mg (38%); mp 230–232 °C; Rf = 0.40 (hep-
tane/EtOAc, 6:1).
13C NMR (75 MHz, CDCl3): δ = 20.8 (C-2′′-Me, C-6′′-Me), 107.8 (C-3),
118.5 (C-8), 122.7 (C-4a), 126.0 (C-6), 126.4 (C-2′, C-6′), 126.8 (C-4′′),
127.7 (C-3′′, C-5′′), 127.9 (C-4′), 129.2 (C-3′, C-5′), 131.7 (C-5), 131.9
(C-1′), 135.6 (C-2′′, C-6′′), 140.0 (C-1′′), 147.8 (C-7), 156.6 (C-8a),
163.6 (C-2), 178.4 (C-4).
IR (ATR): 3072, 3051, 2922, 1646, 1614, 1603, 1419, 1396, 1323, 1164,
1159, 1119, 1108, 1072, 1058, 1016, 910, 833, 771, 682, 625, 617 cm–1
.
1H NMR (250 MHz, CDCl3): δ = 6.85 (s, 1 H, 3-H), 7.52–7.61 (m, 6 H, 8-
H, 3′-H, 4′-H, 5′-H, 2′′-H, 6′′-H), 7.74–7.76 (d, J = 8.3 Hz, 2 H, 3′′-H, 5′′-
H), 7.88–7.91 (m, 2 H, 2′-H, 6′-H), 8.50 (s, 1 H, 5-H).
Anal. Calcd for C23H18O2: C, 84.64; H, 5.56. Found: C, 84.65; H, 5.52.
13C NMR (63 MHz, CDCl3): δ = 107.8 (C-3), 118.9 (C-6), 120.8 (C-8),
124.6 (C-4a), 121.9–126.3 (C-CF3, J = 272.7 Hz), 125.3–125.5 (C-3′′, C-
5′′), 126.4 (C-2′, C-6′), 129.3 (C-3′, C-5′), 129.8 (C-2′′, C-6′′), 130.3 (C-
4′), 130.6–131.1 (C-4′′, J = 32.8 Hz), 131.4 (C-1′), 132.1 (C-5), 143.0 (C-
1′′), 146.6 (C-7), 155.0 (C-8a), 164.1 (C-2), 176.8 (C-4).
7-(2,4,6-Trimethylphenyl)flavone (8b)
Yellow crystals; yield: 36 mg (43%); mp 219–221 °C; Rf = 0.32 (hep-
tane/EtOAc, 8:1).
IR (ATR): 3060, 3026, 2914, 2854, 1635, 1622, 1610, 1418, 1367, 833,
Anal. Calcd for C22H12BrF3O2: C, 59.35; H, 2.72. Found: C, 59.26; H,
2.75.
772, 764, 683 cm–1
.
1H NMR (250 MHz, CDCl3): δ = 2.05 (s, 6 H, 2′′-Me, 6′′-Me), 2.37 (s, 3
H, 4′′-Me), 6.91 (s, 1 H, 3-H), 6.99 (s, 2 H, 3′′-H, 5′′-H), 7.22–7.25 (dd, 1
H, 6-H), 7.40–7.41 (d, J = 1.3 Hz, 1 H, 8-H), 7.52–7.57 (m, 3 H, 3′-H, 4′-
H, 5′-H), 7.94–7.97 (m, 2 H, 2′-H, 6′-H), 8.28–8.31 (d, J = 8.0 Hz, 1 H, 5-
H).
13C NMR (63 MHz, CDCl3): δ = 20.7 (C-2′′-Me, C-6′′-Me), 21.2 (C-4′′-
Me), 107.8 (C-3), 118.7 (C-8), 122.6 (C-4a), 125.9 (C-6), 126.4 (C-2′, C-
6′), 127.2 (C-4′), 128.4 (C-3′′, C-5′′), 129.2 (C-3′, C-5′), 131.7 (C-5),
131.9 (C-1′), 135.5 (C-1′′), 137.2 (C-4′′), 137.6 (C-2′′, C-6′′), 147.9 (C-7),
156.5 (C-8a), 163.6 (C-2), 178.4 (C-4).
6-Bromo-7-(4-methylphenyl)flavone (9c)
White crystals; yield: 56 mg (57%); mp 174–176 °C; Rf = 0.38 (hep-
tane/CH2Cl2/EtOAc, 10:5:1).
IR (ATR): 3033, 2917, 1643, 1599, 1417, 1394, 1357, 814, 764, 682,
621 cm–1
.
1H NMR (360 MHz, CDCl3): δ = 2.38 (s, 3 H, Me), 6.80 (s, 1 H, 3-H),
7.19–7.23 (q, 4 H, 2′′-H, 3′′-H, 5′′-H, 6′′-H), 7.46–7.49 (m, 4 H, 8-H, 3′-
H, 4′-H, 5′-H), 7.83–7.86 (dd, 2 H, 2′-H, 6′-H), 8.44 (s, 1 H, 5-H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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13C NMR (75 MHz, CDCl3): δ = 21.5 (C-Me), 107.7 (C-3), 119.7 (C-6),
120.7 (C-8), 123.9 (C-4a), 126.5 (C-2′, C-6′), 129.1 (C-2′′, C-6′′), 129.2
(C-3′, C-5′), 129.3 (C-3′′, C-5′′), 130.1 (C-4′), 131.6 (C-1′), 132.0 (C-5),
136.8 (C-4′′), 138.7 (C-1′′), 148.3 (C-7), 155.1 (C-8a), 164.0 (C-2),
177.2 (C-4).
6-(3-Methoxyphenyl)-7-[4-(trifluoromethyl)phenyl]flavone (10a)
White crystals; yield: 130 mg (53%); mp 200–201 °C; Rf = 0.29 (hep-
tane/CH2Cl2/EtOAc, 9:4:1).
IR (ATR): 3066, 2945, 2928, 2904, 2831, 1643, 1607, 1446, 1323, 1209,
1127, 1107, 1067, 1016, 837, 779, 690 cm–1
.
LC-MS: m/z = 393.0 [M + H+].
1H NMR (300 MHz, CDCl3): δ = 3.68 (s, 3 H, OMe), 6.70–6.71 (m, 1 H,
2′′-H), 6.73–6.76 (m, 1 H, 4′′-H), 6.81–6.85 (m, 1 H, 6′′-H), 6.95 (s, 1 H,
3-H), 7.16–7.21 (t, 1 H, 5′′-H), 7.36–7.39 (d, J = 8.1 Hz, 2 H, 2′′′-H, 6′′′-
H), 7.55–7.61 (m, 5 H, 3′-H, 4′-H, 5′-H, 3′′′-H, 5′′′-H), 7.68 (s, 1 H, 8-H),
7.97–8.01 (m, 2 H, 2′-H, 6′-H), 8.34 (s, 1 H, 5-H).
Anal. Calcd for C22H15BrO2: C, 67.53; H, 3.86. Found: C, 67.44; H, 3.82.
6-Bromo-7-(4-tert-butylphenyl)flavone (9d)
White crystals; yield: 57 mg (49%); mp 216–219 °C; Rf = 0.24 (hep-
13C NMR (75 MHz, CDCl3): δ = 55.3 (C-OMe), 107.9 (C-3), 113.6 (C-4′′),
115.4 (C-2′′), 119.9 (C-8), 122.4–126.0 (C-CF3, J = 270.5 Hz), 122.6 (C-
6′′), 123.3 (C-4a), 125.2–125.4 (C-3′′′, C-5′′′), 126.5 (C-2′, C-6′), 127.7
(C-4′), 129.3 (C-3′, C-5′), 129.4 (C-5′′), 129.7–130.1 (C-4′′′, J = 32.3 Hz),
130.0 (C-2′′′, C-6′′′), 131.7 (C-1′), 132.0 (C-5), 138.4 (C-6), 140.5 (C-1′′),
143.7 (C-1′′′), 145.2 (C-7), 155.5 (C-8a), 159.5 (C-3′′), 164.0 (C-2),
178.2 (C-4).
tane/CH2Cl2/EtOAc, 10:5:1).
IR (KBr): 3444, 3064, 2961, 1649, 1619, 1604, 1450, 1416, 1395, 1358,
835, 774, 687 cm–1
.
1H NMR (360 MHz, CDCl3): δ = 1.39 (s, 9 H, t-Bu), 6.83 (s, 1 H, 3-H),
7.41–7.43 (d, J = 8.1 Hz, 2 H, 2′′-H, 6′′-H), 7.48–7.55 (m, 6 H, 8-H, 3′-H,
4′-H, 5′-H, 3′′-H, 5′′-H), 7.88–7.90 (d, J = 7.6 Hz, 2 H, 2′-H, 6′-H), 8.49
(s, 1 H, 5-H).
13C NMR (90 MHz, CDCl3): δ = 31.4 [C(CH3)3], 34.8 [C(CH3)3], 107.7 (C-
3), 119.5 (C-6), 120.7 (C-8), 123.9 (C-4a), 125.3 (C-3′′, C-5′′), 126.4 (C-
2′′, C-6′′), 129.0 (C-2′, C-6′), 129.2 (C-3′, C-5′), 130.0 (C-4′), 131.6 (C-
1′), 131.9 (C-5), 136.6 (C-1′′), 148.2 (C-7), 151.8 (C-4′′), 155.1 (C-8a),
163.8 (C-2), 177.1 (C-4).
GC-MS: m/z (%) = 372.1 [M+, 100], 429.1, 403.1, 370.0, 342.0, 283.1,
250.9, 202.0, 102.1.
Anal. Calcd for C29H19F3O3: C, 73.72; H, 4.05. Found: C, 73.65; H, 4.01.
6-(4-Methoxyphenyl)-7-[4-(trifluoromethyl)phenyl]flavone (10b)
Yellow crystals; yield: 85 mg (35%); mp 193–195 °C; Rf = 0.16 (hep-
Anal. Calcd for C25H21BrO2:C, 69.29; H, 4.88. Found: C, 69.34; H, 4.79.
tane/EtOAc, 6:1).
7-(Biphenyl-4-yl)-6-bromoflavone (9e)
IR (ATR): 3062, 3017, 2957, 2937, 2900, 2836, 1643, 1606, 1433, 1246,
1127, 1107, 1068, 843, 830, 780, 692 cm–1
.
Pale yellow crystals; yield: 67 mg (59%); mp 227–228 °C; Rf = 0.30
1H NMR (500 MHz, CDCl3): δ = 3.83 (s, 3 H, OMe), 6.80–6.82 (m, 2 H,
3′′-H, 5′′-H), 6.98 (s, 1 H, 3-H), 7.07–7.09 (m, 2 H, 2′′-H, 6′′-H), 7.36–
7.37 (d, J = 8.0 Hz, 2 H, 2′′′-H, 6′′′-H), 7.57–7.60 (m, 5 H, 3′-H, 4′-H, 5′-
H, 6′′′-H, 5′′′-H), 7.66 (s, 1 H, 8-H), 7.98–8.00 (dd, 2 H, 2′-H, 6′-H), 8.29
(s, 1 H, 5-H).
13C NMR (125 MHz, CDCl3): δ = 55.4 (C-OMe), 107.8 (C-3), 113.9 (C-
3′′, C-5′′), 119.9 (C-8), 123.1–125.3 (C-CF3, J = 270.5 Hz), 123.3 (C-4a),
125.3–125.4 (C-3′′′, C-5′′′), 126.5 (C-2′, C-6′), 127.5 (C-4′), 129.3 (C-3′,
C-5′), 129.7–130.0 (C-4′′′, J = 32.5 Hz), 130.1 (C-2′′′, C-6′′′), 131.2 (C-2′′,
C-6′′), 131.5 (C-1′), 131.8 (C-1′′), 132.0 (C-5), 138.3 (C-6), 143.8 (C-
1′′′), 145.2 (C-7), 155.3 (C-8a), 159.1 (C-4′′), 164.0 (C-2), 178.2 (C-4).
(heptane/CH2Cl2/EtOAc, 12:4:1).
IR (KBr): 3444, 3066, 3031, 1652, 1619, 1448, 1415, 1396, 1355, 768,
687 cm–1
.
1H NMR (360 MHz, CDCl3): δ = 6.85 (s, 1 H, 3-H), 7.36–7.40 (m, 1 H,
4′′′-H), 7.45–7.56 (m, 7 H, 3′-H, 4′-H, 5′-H, 2′′-H, 3′′-H, 5′′-H, 6′′-H),
7.60 (s, 1 H, 8-H), 7.65–7.72 (m, 4 H, 2′′′-H, 3′′′-H, 5′′′-H, 6′′′-H), 7.89–
7.92 (d, J = 7.6 Hz, 2 H, 2′-H, 6′-H), 8.52 (s, 1 H, 5-H).
13C NMR (90 MHz, CDCl3): δ = 107.8 (C-3), 119.4 (C-6), 120.7 (C-8),
124.1 (C-4a), 126.4 (C-2′′, C-6′′), 127.0 (C-3′′, C-5′′), 127.3 (C-2′′′, C-
6′′′), 127.8 (C-4′′′), 129.0 (C-2′, C-6′), 129.2 (C-3′, C-5′), 129.8 (C-3′′′, C-
5′′′), 130.2 (C-4′), 131.5 (C-1′), 132.0 (C-5), 138.5 (C-1′′), 140.4 (C-4′′),
141.5 (C-1′′′), 147.8 (C-7), 155.1 (C-8a), 163.9 (C-2), 177.0 (C-4).
Anal. Calcd for C29H19F3O3: C, 73.72; H, 4.05. Found: C, 73.75; H, 4.07.
Anal. Calcd for C27H17BrO2: C, 71.54; H, 3.78. Found: C, 71.58; H, 3.81.
7-(Biphenyl-4-yl)-6-(4-methoxyphenyl)flavone (10c)
Pale yellow crystals; yield: 137 mg (57%); mp 204–206 °C; Rf = 0.33
(hexane/CH2Cl2/EtOAc, 9:4:2).
Diarylation of 6,7-Dibromoflavone (5) with Different Boronic
Acids; General Procedure for Differently Substituted 6,7-Diaryl-
flavone Derivatives 10a–e
IR (KBr): 3444, 3051, 3030, 1647, 1619, 1608, 1450, 1433, 1357, 1249,
1177, 835, 771 cm–1
.
To a mixture of 6,7-dibromoflavone (5, 190 mg, 0.50 mmol), 2 M aq
Cs2CO3 solution (1.50 mmol), and boronic acid (0.50 mmol) in 1,4-di-
oxane/MeOH (5:1, 6 mL), in a pressure tube under argon, was added
Pd(PPh3)4 (22 mg, 0.02 mmol). The mixture was stirred and heated at
75 °C in an aluminum heating block for the times given in Table 5, un-
til full conversion of the 6,7-dibromoflavone (5). Further Pd(PPh3)4
(34 mg, 0.03 mmol) and the other boronic acid (0.65 mmol) were
added. The mixture was stirred and heated at 100 °C for the times giv-
en in Table 5, until full conversion of the monocoupled product. The
mixture was dried (MgSO4) and filtered. The solvent was removed un-
der reduced pressure; the residue was purified by column chromatog-
raphy to give the differently substituted diarylflavones 10a–e.
1H NMR (360 MHz, CDCl3): δ = 3.76 (s, 3 H, OMe), 6.76–6.78 (d, J = 7.9
Hz, 2 H, 3′′-H, 5′′-H), 6.85 (s, 1 H, 3-H), 7.10–7.12 (d, J = 7.6 Hz, 2 H, 2′′-
H, 6′′-H), 7.26–7.28 (d, J = 7.6 Hz, 2 H, 2′′′-H, 6′′′-H), 7.31–7.35 (m, 1 H,
4′′′′-H), 7.40–7.44 (m, 2 H, 3′′′′-H, 5′′′′-H), 7.51–7.56 (m, 5 H, 3′-H, 4′-
H, 5′-H, 2′′′′-H, 6′′′′-H), 7.58–7.60 (d, J = 7.6 Hz, 2 H, 3′′′-H, 5′′′-H), 7.63
(s, 1 H, 8-H), 7.92–7.94 (d, J = 7.2 Hz, 2 H, 2′-H, 6′-H), 8.24 (s, 1 H, 5-H).
13C NMR (90 MHz, CDCl3): δ = 55.3 (C-OMe), 107.7 (C-3), 113.7 (C-3′′,
C-5′′), 119.7 (C-8), 122.9 (C-4a), 126.4 (C-2′, C-6′), 126.9 (C-3′′′, C-5′′′),
127.1 (C-2′′′, C-6′′′), 127.2 (C-4′′′′), 127.6 (C-2′′′′, C-6′′′′), 128.9 (C-3′, C-
5′), 129.2 (C-3′′′′, C-5′′′′), 130.1 (C-4′), 131.2 (C-2′′, C-6′′), 131.7 (C-5),
131.9 (C-6), 132.2 (C-1′), 138.1 (C-1′′), 139.0 (C-4′′′), 140.3 (C-1′′′′),
140.4 (C-1′′′), 146.2 (C-7), 155.3 (C-8a), 158.8 (C-4′′), 163.5 (C-2),
178.3 (C-4).
Anal. Calcd for C34H24O3: C, 84.98; H, 5.03. Found: C, 85.03; H, 5.01.
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7-(Biphenyl-4-yl)-6-(4-fluorophenyl)flavone (10d)
Wiley and Sons: Chichester, 1999. (c) Middleton, E. Jr.;
Kandaswami, C.; Theoharides, T. C. Pharmacol. Rev. 2000, 52,
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White crystals; yield: 145 mg (62%); mp 212–214 °C; Rf = 0.29 (hex-
ane/CH2Cl2/EtOAc, 9:4:2).
IR (KBr): 3445, 3056, 3030, 1647, 1920, 1606, 1451, 1435, 1357, 838,
818 cm–1
.
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1H NMR (360 MHz, CDCl3): δ = 6.86 (s, 1 H, 3-H), 6.91–6.96 (m, 2 H,
3′′-H, 5′′-H), 7.14–7.17 (m, 2 H, 2′′-H, 6′′-H), 7.23–7.26 (d, J = 7.9 Hz, 2
H, 2′′′-H, 6′′′-H), 7.32–7.36 (m, 1 H, 4′′′′-H), 7.41–7.45 (m, 2 H, 3′′′′-H,
5′′′′-H), 7.51–7.53 (m, 5 H, 3′-H, 4′-H, 5′-H, 2′′′′-H, 6′′′′-H), 7.58–7.60
(d, J = 7.6 Hz, 2 H, 3′′′-H, 5′′′-H), 7.66 (s, 1 H, 8-H), 7.93–7.95 (d, J = 7.2
Hz, 2 H, 2′-H, 6′-H), 8.23 (s, 1 H, 5-H).
13C NMR (90 MHz, CDCl3): δ = 107.8 (C-3), 115.1–115.4 (C-3′′, C-5′′, J =
21.4 Hz), 119.8 (C-8), 123.0 (C-4a), 126.4 (C-2′, C-6′), 127.0 (C-3′′′, C-
5′′′), 127.1 (C-2′′′, C-6′′′), 127.4 (C-4′′′′), 127.7 (C-2′′′′, C-6′′′′), 129.0 (C-
3′, C-5′), 129.2 (C-3′′′′, C-5′′′′), 130.2 (C-4′), 131.6–131.7 (C-2′′, C-6′′, J =
7.7 Hz), 131.8 (C-5), 131.8 (C-1′), 135.9 (C-1′′), 137.4 (C-6), 138.6 (C-
4′′′), 140.1 (C-1′′′′), 140.4 (C-1′′′), 146.3 (C-7), 155.5 (C-8a), 160.8–
163.5 (C-4′′, J = 245.4 Hz), 163.7 (C-2), 178.2 (C-4).
LC-MS: m/z = 469.3 [M + H+].
(4) (a) Ahn, Y. M.; Vogeti, L.; Liu, C.-J.; Santhapuram, H. K. R.; White,
J. M.; Vasandani, V.; Mitscher, L. A.; Lushington, G. H.; Hanson,
P. R.; Powell, D. R.; Himes, R. H.; Roby, K. F.; Ye, Q.; Georg, G. I.
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Sugaya, T.; Ishida, H.; Gomi, K.; Kasai, M. J. Med. Chem. 1996, 39,
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J. Med. Chem. 1994, 37, 3353. (d) Larget, R.; Lockhart, B.; Renard,
P.; Largeron, M. Bioorg. Med. Chem. Lett. 2000, 10, 835.
Anal. Calcd for C33H21FO2: C, 84.60; H, 4.52. Found: C, 84.64; H, 4.49.
7-(Biphenyl-4-yl)-6-[4-(trifluoromethyl)phenyl]flavone (10e)
Yellow crystals; yield: 97 mg (39%); mp 206–208 °C; Rf = 0.33 (hex-
ane/CH2Cl2/EtOAc, 7:5:1).
IR (KBr): 3445, 3059, 3031, 1645, 1620, 1451, 1436, 1357, 1325, 1166,
1124, 1069, 843, 771 cm–1
.
(5) (a) Konana, N. A.; Lincopana, N.; Díazb, I. E. C.; Jacysync, J. de. F.;
Tibad, M. M. T.; Mendese, J. G. P. A.; Bacchid, E. M.; Spira, B. Exp.
Toxicol. Pathol. 2012, 64, 435. (b) Bedir, E.; Talti, I. I.; Khan, R. A.;
Zhao, J.; Takamatsu, S.; Walker, L. A.; Goldman, P.; Khan, A. A.
J. Agric. Food Chem. 2002, 50, 3150. (c) Beara, I. N.; Lesjak, M. M.;
Cetojevic-Simin, D. D.; Marjanovic, Z. S.; Ristic, J. D.; Mrkonjic, Z.
O.; Mimica-Dukic, N. M. Food Chem 2014, 165, 460. (d) Cherry, J.
J.; Rietz, A.; Malinkevich, A.; Liu, Y.; Xie, M.; Bartolowits, M.;
Davisson, V. J.; Baleja, J. D.; Androphy, E. J. Plos One 2013, 8,
e84506. (e) Park, H.; Dao, T. T.; Kim, H. P. Eur. J. Med. Chem.
2005, 40, 943. (f) Dao, T. T.; Kim, S. B.; Sin, K.-S.; Kim, S.; Kim, H.
P.; Park, H. Arch. Pharmacal Res. 2004, 27, 278. (g) Lu, S.; Sun, S.-
L.; Liu, H.-C.; Chen, Y.-D.; Yuan, H.-L.; Gao, Y.-P.; Lu, P. Y. T.
Chem. Biol. Drug Des. 2012, 80, 328. (h) Finlay, M. R. V.; Griffin,
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1H NMR (360 MHz, CDCl3): δ = 6.89 (s, 1 H, 3-H), 7.24–7.26 (d, J = 7.9
Hz, 2 H, 2′′′-H, 6′′′-H), 7.33–7.38 (m, 3 H, 3′′-H, 5′′-H, 4′′′′-H), 7.43–7.47
(m, 2 H, 3′′′′-H, 5′′′′-H), 7.56–7.61 (m, 7 H, 3′-H, 4′-H, 5′-H, 2′′-H, 6′′-H,
2′′′′-H, 6′′′′-H), 7.59–7.61 (d, J = 7.6 Hz, 2 H, 3′′′-H, 5′′′-H), 7.71 (s, 1 H,
8-H), 7.95–7.97 (m, 2 H, 2′-H, 6′-H), 8.28 (s, 1 H, 5-H).
13C NMR (90 MHz, CDCl3): δ = 107.9 (C-3), 120.1 (C-8), 122.8–125.8
(CF3, J = 270.1 Hz), 123.1 (C-4a), 125.2 (C-3′′, C-5′′), 126.5 (C-2′, C-6′),
127.2 (C-2′′′, C-3′′′, C-5′′′, C-6′′′), 127.8 (C-2′′′′, C-4′′′′, C-6′′′′), 129.0 (C-
2′′, C-6′′), 129.3 (C-3′, C-5′), 129.6 (C-4′′), 130.2 (C-4′), 130.4 (C-3′′′′, C-
5′′′′), 131.8 (C-1′), 131.9 (C-5), 136.9 (C-6), 138.2 (C-4′′′), 140.2 (C-
1′′′′), 140.8 (C-1′′′), 143.6 (C-1′′), 146.3 (C-7), 155.9 (C-8a), 163.8 (C-2),
178.1 (C-4).
Anal. Calcd for C34H21F3O2: C, 78.75; H, 4.08. Found: C, 78.80; H, 4.06.
(6) (a) Miyaura, N.; Suzuki, A. J. Chem. Soc., Chem. Commun. 1979,
866. (b) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett.
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Acknowledgment
(7) (a) Beller, M.; Bolm, C. Transition Metals for Organic Synthesis:
Building Blocks and Fine Chemicals; 2nd ed., Vols. 1-2; Wiley-
VCH: Weinheim, 2004. (b) de Meijere, A.; Diederich, F. Metal-
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Weinheim, 2009. (e) Tsuji, J. Palladium Reagents and Catalysts,
2nd ed.; Wiley: Chichester, 2004. (f) Negishi, E.-i. Handbook of
Organopalladium for Organic Synthesis; Vols. 1–2; Wiley-Inter-
science: New York, 2002. (g) Suzuki, A. Modern Arene Chemistry;
Astruc, D., Ed.; Wiley-VCH: Weinheim, 2002. (h) Suzuki, A. Pure
Appl. Chem. 1985, 57, 1749. (i) Miyaura, N. Top. Curr. Chem.
2002, 219, 11. (j) Suzuki, A. J. Organomet. Chem. 2002, 653, 54.
(k) Corbet, J.-P.; Mignani, G. Chem. Rev. 2006, 106, 2651.
(l) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M.
Chem. Rev. 2002, 102, 1359. (m) Yin, L.; Liebscher, J. Chem. Rev.
Financial support by the Alexander-von-Humboldt Foundation (Insti-
tute partnership program) and by the State of Mecklenburg-Vorpom-
mern (scholarships for S.J. and Z.K.) and the BAROSS REG_EA_09-1-
2009-0028 (LCMS_TAN) projects are gratefully acknowledged.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588376.
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