Efficient synthesis of arylated flavones by site-selective Suzuki-Miyaura cross-coupling reactions of the bis(triflate) of 5,7- and 7,8-dihydroxyflavone

Article abstract of DOI:10.1002/ejoc.201101491

Suzuki-Miyaura reactions of the bis(triflate) of 5,7- and 7,8-dihydroxyflavone proceed with very good site selectivity in favor of position 7 and allow the synthesis of various arylated flavones. The reaction of 5,7-dihydroxyflavone with one equivalent of triflic anhydride also proceeds with very good site selectivity in favor of position 7. The subsequent Suzuki-Miyaura reaction of the product allows the synthesis of 7-aryl-5-hydroxyflavones. The regioselectivity is discussed based on DFT calculations.

Full text of DOI:10.1002/ejoc.201101491

FULL PAPER
DOI: 10.1002/ejoc.201101491
Efficient Synthesis of Arylated Flavones by Site-Selective Suzuki–Miyaura
Cross-Coupling Reactions of the Bis(triflate) of 5,7- and 7,8-Dihydroxyflavone
Nadi Eleya,[a] Imran Malik,[a,b] Sebastian Reimann,[a,c] Kai Wittler,[d] Martin Hein,[a]
Tamás Patonay,[b] Alexander Villinger,[a] Ralf Ludwig,[c,d] and Peter Langer*[a,c]
Keywords: Synthetic methods / Natural products / Heterocycles / Flavones / Cross-coupling / Palladium / Regioselectivity
Suzuki–Miyaura reactions of the bis(triflate) of 5,7- and 7,8-
dihydroxyflavone proceed with very good site selectivity in
favor of position 7 and allow the synthesis of various arylated
flavones. The reaction of 5,7-dihydroxyflavone with one
equivalent of triflic anhydride also proceeds with very good
site selectivity in favor of position 7. The subsequent Suzuki–
Miyaura reaction of the product allows the synthesis of 7-
aryl-5-hydroxyflavones. The regioselectivity is discussed
based on DFT calculations.
one (1). The regioselectivity observed in these reactions is
discussed based on DFT calculations.
Introduction
Flavones (2-arylchromones) are very important oxygen-
ated heterocyclic compounds, which belong to the flavonoid
group, and occur naturally as secondary metabolites in
fruits, vegetables, seeds, and flowers. They play important
roles in plant development, reproduction, and defense and
possess a wide range of biological and pharmaceutical ac-
tivities. This includes antiviral, anti-inflammatory, hepatop-
rotective, antioxidant, antithrombotic, vasodilating, and an-
ticarcenogenic activity, combining high efficiency and low
toxicity.[1–6] The main synthetic methods include the Kos-
tanecki reaction, Allan–Robinson synthesis, and the Baker–
Venkataraman rearrangement.[7–10] Despite the great phar-
macological importance of flavones and chromones, rela-
tively few applications of palladium-catalyzed cross-cou-
pling reactions to their halides or triflates have been re-
ported to date.[11] Site-selective Suzuki–Miyaura reac-
tions[12] and related palladium-catalyzed cross-coupling re-
actions of polyhalogenated molecules[13] or polytriflates[14]
have been extensively studied in recent years. Recently, we
have reported the synthesis of 7,8-diarylflavones by site-se-
lective Suzuki–Miyaura reactions of the bis(triflate) of 7,8-
dihydroxyflavone (9).[15] Herein, we report full details of
these studies. In addition, we report, for the first time, the
synthesis of 5,7-diarylflavones by site-selective Suzuki–
Miyaura reactions of the bis(triflate) of 5,7-dihydroxyflav-
Results and Discussion
5,7-Dihydroxyflavone (1)
The reaction of 1 with triflic anhydride (Tf2O; 2.4 equiv.)
resulted in the formation of the mono-triflate 2 in 80%
yield (Scheme 1). The expected bis-triflate was not formed.
The yield of 2 slightly dropped when only 1.2 equiv. of
triflic anhydride was employed. The synthesis of 2 and a
Stille reaction of the latter has been previously reported.[16]
The difficulty in preparing the desired bis-triflate is in strik-
ing contrast to the facile synthesis of the bis(triflate) of 9[15]
and might be explained by the formation of a stable intra-
molecular hydrogen bond in the case of 1.
Scheme 1. Synthesis of 2. Conditions: (i) (1) 1 (1.0 equiv.), pyridine
(4.0 equiv.), CH2Cl2, 20 °C; (2) Tf2O (2.4 equiv.), 20 °C, 4 h.
The Suzuki–Miyaura reaction of mono-triflate 2 with
various arylboronic acids, 3a–l, afforded the 7-aryl-5-hy-
droxyflavones 4a–l in 75–90% yields (Scheme 2 and
Table 1). The reactions were carried out under standard
conditions [3 mol-% of [Pd(PPh3)4] as the catalyst, K3PO4
as the base, 1,4-dioxane, 80 °C]. Very good yields were ob-
tained both for electron-rich and -poor arylboronic acids.
The yields for arylboronic acids containing an ortho substit-
uent were slightly lower than those of other arylboronic ac-
ids, presumably due to steric effects.
[a] Department of Chemistry, Organic Chemistry, University of
Rostock,
Albert-Einstein-Str. 3a, 18059 Rostock, Germany
[b] Department of Organic Chemistry, University of Debrecen,
4032 Debrecen, Egyetem tér 1, Hungary
[c] Leibniz Institute for Catalysis at the University of Rostock
e. V. (LIKAT),
Albert-Einstein-Str. 29a, 18059 Rostock, Germany
[d] Department of Chemistry, Physical and Theoretical Chemistry,
University of Rostock,
Dr.-Lorenz-Weg 1, 18059 Rostock, Germany
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Table 2. Synthesis of 6a–i.
3
6
Ar
6 [%][a]
a
b
c
e
f
h
i
a
b
c
d
e
f
g
h
i
4-MeC6H4
3-MeC6H4
3,5-Me2C6H3
4-tBuC6H4
4-(MeO)C6H4
4-CF3C6H4
4-FC6H4
85
80
80
77
90
76
83
85
81
Scheme 2. Synthesis of 4a–l. Conditions: (i) 2 (1.0 equiv.), 3a–l
(1.0 equiv.), K3PO4 (1.5 equiv.), [Pd(PPh3)4] (3 mol-%), 1,4-diox-
ane, 80 °C, 4 h.
j
l
4-ClC6H4
C6H5
Table 1. Synthesis of 4a–l.
3,4
Ar
4 [%][a]
[a] Yields of isolated products.
a
b
c
d
e
f
g
h
i
4-MeC6H4
3-MeC6H4
3,5-Me2C6H3
2-MeC6H4
4-tBuC6H4
4-(MeO)C6H4
3,4-(MeO)2C6H3
4-CF3C6H4
4-FC6H4
90
85
80
77
80
90
85
79
80
86
75
80
Scheme 5. Synthesis of 7a–g. Conditions: (i) 5 (1.0 equiv.), ArB-
(OH)2 (1.0 equiv.), K3PO4 (1.5 equiv.), [Pd(PPh3)4] (3 mol-%), 1,4-
dioxane, 70 °C, 9 h.
j
k
l
4-ClC6H4
2-ClC6H4
C6H5
[a] Yields of isolated products.
Table 3. Synthesis of 7a–g.
5,7-Bis(triflate)flavone (5) could be successfully prepared
from 1 in 90% yield when the reaction was carried out at
40 °C instead of 20 °C (Scheme 3).
3
7
Ar
7 [%][a]
b
c
e
f
g
i
j
a
b
c
d
e
f
3-MeC6H4
3,5-Me2C6H3
4-tBuC6H4
4-(MeO)C6H4
2-(MeO)C6H4
4-FC6H4
85
85
71
83
81
80
82
g
4-ClC6H4
Scheme 3. Synthesis of 5. Conditions: (i) (1) 1 (1.0 equiv.), pyridine
(4.0 equiv.), CH2Cl2, 20 °C; (2) Tf2O (2.4 equiv.), 20 Ǟ 40 °C,
30 min.
[a] Yields of isolated products.
The Suzuki–Miyaura reaction of bis-triflate 5 with
2.0 equiv. of various arylboronic acids 3 afforded the 5,7-
diarylflavones 6a–i in 76–90% yields (Scheme 4 and
Table 2). The reactions were carried out at a higher tem-
perature (115 °C) than that used for the synthesis of prod-
ucts 4 to affect good yields. Very good yields were obtained
for products derived from both electron-rich and -poor ar-
ylboronic acids.
The structure of 7e was independently confirmed by X-
ray crystal-structure analysis (Figure 1).
Scheme 4. Synthesis of 6a–i. Conditions: (i) 5 (1.0 equiv.), Ar-
B(OH)2 (2.0 equiv.), K3PO4 (3.0 equiv.), [Pd(PPh3)4] (6 mol-%), 1,4-
dioxane, 115 °C, 6 h.
Figure 1. Ortep plot of 7e. Ellipses are drawn at the 50% prob-
ability level.[21]
The Suzuki–Miyaura reaction of bis-triflate 5 with
1.0 equiv. of arylboronic acids 3 afforded the 7-aryl-5-(tri-
flate)flavones 7a–g in 71–85% yields (Scheme 5 and
The structure of compound 7g was confirmed by a
Table 3). The reactions were carried out at 70 °C instead of 1H,1H NOESY experiment. The ortho protons of the 4-
115 °C to achieve good yields and to avoid the formation chlorophenyl group correlate with protons H-6 and H-8 of
of 5,7-diarylflavones 6.
the flavone moiety (Figure 2).
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Efficient Synthesis of Arylated Flavones
Table 5. Synthesis of 11a–g.
3
11
R
11 [%][a]
a
c
e
f
a
b
c
d
e
f
4-MeC6H4
3,5-Me2C6H3
4-tBuC6H4
4-(MeO)C6H4
4-FC6H4
4-ClC6H4
4-EtC6H4
74
71
59
68
62
72
70
Figure 2. Diagnostic NOESY interactions of 7g.
i
j
m
The one-pot Suzuki–Miyaura reaction of bis-triflate 5
with two different arylboronic acids 3 (sequential addition
of 1.0 equiv. of each boronic acid) afforded the 5,7-diaryl-
flavones 8a,b in 77–78% yields (Scheme 6 and Table 4). The
reactions were carried out at 70 °C for the first step (to
avoid double coupling) and at 115 °C in the second step.
g
[a] Yields of isolated products.
The Suzuki–Miyaura reaction of 10 with arylboronic ac-
ids 3a,h,j,m,n (1.0 equiv.) afforded the 7-aryl-8-trifluorosulf-
onyloxyflavones 12a–e in 66–76% yield (Scheme 9 and
Table 6). The reaction had to be carried out at 70 °C instead
of 100 °C to obtain a good site selectivity.
Scheme 6. Synthesis of 8a,b. Conditions: (i) (1) 5 (1.0 equiv.), Ar1B-
(OH)2 (1.0 equiv.), K3PO4 (1.5 equiv.), [Pd(PPh3)4] (3 mol-%), 1,4-
dioxane, 70 °C, 9 h; (2) Ar2B(OH)2 (1.0 equiv.), K3PO4 (1.5 equiv.),
[Pd(PPh3)4] (3 mol-%), 1,4-dioxane, 115 °C, 6 h.
Scheme 9. Synthesis of 12a–e. Reagents and conditions: (i) 10
(1.0 equiv.), 3a,h,j,m,n (1.0 equiv.), K3PO4 (1.5 equiv.), [Pd(PPh3)4]
(5 mol-%), 1,4-dioxane, 70 °C, 4 h.
Table 4. Synthesis of 8a,b.
3
8
Ar1
Ar2
8 [%][a]
c,j
j,i
a
b
3,5-Me2C6H3
4-ClC6H4
4-ClC6H4
4-FC6H4
78
77
Table 6. Synthesis of 12a–e.
[a] Yields of isolated products.
3
12
R
12 [%][a]
a
h
j
m
n
a
b
c
d
e
4-MeC6H4
4-(CF3)C6H4
4-ClC6H4
4-EtC6H4
4-(HC=CH2)C6H4
76
69
66
72
74
7,8-Dihydroxyflavone
Bis(triflate) 10 was prepared from commercially available
9 in 76% yield (Scheme 7). The Suzuki–Miyaura reaction
of 10 with arylboronic acids 3a,c,e,f,i,j,m (2.6 equiv.) gave
the 7,8-diarylflavones 11a–g in 59–74% yield (Scheme 8 and
Table 5). The reactions were carried out under conditions
similar to the synthesis of 5,7-diarylflavones. Both electron-
poor and -rich arylboronic acids could be successfully em-
ployed.
[a] Yields of isolated products.
The Suzuki–Miyaura reaction of 12c and 12a with aryl-
boronic acids 3f and 3m, respectively (1.3 equiv.) afforded
the 7,8-diarylflavones 13a and 13b, respectively (Scheme 10
and Table 7). The reactions were carried out at 100 °C.
Scheme 10. Synthesis of 13a,b. Reagents and conditions: (i) 12a,c
(1.0 equiv.), 3f,m (1.3 equiv.), K3PO4 (1.5 equiv.), [Pd(PPh3)4]
(5 mol-%), 1,4-dioxane, 100 °C, 4 h.
Scheme 7. Synthesis of 10. Conditions: (i) 9 (1.0 equiv.), Tf2O
(2.4 equiv.), pyridine (4.0 equiv.), CH2Cl2, –78 Ǟ 0 °C, 4 h.
Table 7. Synthesis of 7,8-diarylflavones 13a,b.
3
12
13
Ar1
Ar2
13 [%][a]
f
m
c
a
a
b
4-ClC6H4
4-MeC6H4
4-(MeO)C6H4
4-EtC6H4
73
66
[a] Yields of isolated products.
All products were characterized by spectroscopic meth-
ods. The constitutions of products 12a–e and 13a,b were
proved by 2D NMR spectroscopy experiments (HMBC,
Scheme 8. Synthesis of 11a–g. Conditions: (i) 10 (1.0 equiv.), 3a,c,e,
f,i,j,m (2.6 equiv.), [Pd(PPh3)4] (5 mol-%), K3PO4 (4.0 equiv.), 1,4-
dioxane, 100 °C, 4 h.
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P. Langer et al.
FULL PAPER
NOESY). The structure of 11a was independently con- Table 8. LUMOs of optimized structures and their largest orbital
firmed by X-ray crystal-structure analysis.[15] Inspection of
coefficients for the reaction centers C5 and C7.
the X-ray structure shows that the flavone unit (including
the phenyl group located at C2) is in the plane; the other
two phenyl groups are twisted out of the plane for steric
reasons.
The structure of 12d was confirmed by 2D NMR spec-
troscopy correlations by using HMQC, HMBC, and
NOESY. The chemical shift values of the carbon atoms
were assigned with the help of an HMQC experiment, δ =
8.21 (125.4, C-5), 7.44 ppm (127.4 ppm, C-6). In the
HMBC spectrum, the aromatic proton of C-6 showed a
strong coupling with C-5 (125.4), C-7 (131.6), C-1Ј
(135.1 ppm). In the NOESY spectrum, the aromatic proton
[δ = 7.44 ppm (C-6)] showed an interaction with proton 5-
H (δ = 8.18 ppm). This information shows that the 4-(Et)-
NBO analysis for compound 5 showed that position C7
C6H4 moiety is attached to carbon atom C-7 (Figure 3).
was electronically less deficient than position C5 (Table 8);
this can be explained by the proximity of C5 to the carbonyl
group. The values of the largest LUMO orbital coefficients
of C5 and C7 do not seem to be the main reason for re-
gioselective attack at C7 (Table 9). The regiodirecting effect
of the carbonyl group of 5 seems to be less effective than in
the case of the bis(triflates) of 1,2- and 1,3-dihydroxy-
anthraquinone. When comparing the bond lengths, the C7–
O bond is longer and therefore weaker than that of the C5–
O bond (Table 8). The lower steric hindrance of position
C7 and the weak C7–O bond might account for regioselec-
tive attack at position 7 (Figure 4). Although the thermo-
dynamic stability of the products is unlikely to have an in-
Figure 3. HMBC (red arrows) and NOESY (blue arrows) corre-
fluence, it is interesting to note that the mono-coupling
lations of 12d.
product derived from the Suzuki reaction of 5 with phen-
ylboronic acid is thermodynamically more stable for attack
at the 7- rather than the 5-position (Table 10).
Computational Studies
Table 9. Partial charges at corresponding carbon atoms obtained
by using natural bond orbital (NBO) population analysis at the
The regioselectivity observed in the Suzuki–Miyaura
B3LYP/6-31G* levels of theory.
cross-coupling reactions of the bis(triflates) of 1 and 9 was
Compound
5
10
1,3-Bis(triflate)-
anthraquinone
investigated by DFT calculations at the B3LYP level of
theory using a 6-31G* basis set. The first attack of site-
selective palladium-catalyzed reactions usually occurs at the
sterically less hindered or electronically more deficient posi-
tion.[19] Recently, we showed that the Suzuki–Miyaura reac-
tions of the bis(triflates) of 1,2- and 1,3-dihydroxyanthra-
quinone proceed by initial attack at C1 (next to the carb-
onyl group), which can be explained by the fact that C1 is
more electronically deficient than C3.[14i,14j] However, con-
sidering the C–O bond lengths, the C1–O bond is assumed
to be stronger than the C3–O bond (Table 8). These results
were confirmed by computational calculations and NBO
analysis (Tables 8 and 9). Furthermore, based on frontier
molecular orbital (FMO) theory,[20] the LUMO coefficient
of the atom attacked by a nucleophile should be as large as
possible. In case of the bis(triflate) of 1,3-dihydroxyanthra-
quinone, the corresponding coefficient of C1 is larger than
Reaction centers
Distance C(X)–O
NBO charges [a.u.] 0.3371 0.3034 0.2342 0.2772 0.3297 0.3047
C5
C7
C8
C7
C1
C3
1.394 1.402 1.400 1.402 1.394 1.400
Figure 4. Possible explanation for the site selectivity of reactions of
bis(triflate) 5.
Similarly, the site-selective formation of 12 can be ex-
that of C3 (Table 9). Therefore, the weaker binding strength plained by the fact that the C7 position of 10 is sterically
of C3–O than C1–O appears to be irrelevant for regioselec- less hindered than position C8. Clearly, both C–O bond
tivity.
strengths are similar, because the bond lengths of C7–O and
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Efficient Synthesis of Arylated Flavones
Table 10. Calculated model products and energies, given in hartrees, of the structures optimized at the B3LYP/6-31G* levels of theory.
tional[22,23] to calculate the structures and vibrational frequencies
C8 are similar (Table 8). In addition, position C7 (located
of the molecules. No imaginary frequencies were found, indicating
that all molecules and fragments represented at least local mini-
mum structures on the potential energy surface. For all molecules,
the calculations were performed with 6-31G* basis sets im-
meta to the ether oxygen atom and para to the carbonyl
group) is considerably more electron deficient than position
1 (located ortho to the ether oxygen atom and meta to the
carbonyl group; Tables 8 and 10 and Figure 5). Although
plemented in Gaussian 09. All calculations were carried out on
the thermodynamic stability of the products is unlikely to
the high-performance computing cluster at the physical chemistry
have an influence, it is again interesting to note that the
mono-coupling product is thermodynamically slightly more
stable for attack at the 7- rather than the 8-position
(Table 10).
section of the University of Rostock.
5-Hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl Trifluoromethanesulf-
one (2): Pyridine (1.3 mL, 15.72 mmol) was added to a solution of
1 (1.0 g, 3.93 mmol) in CH2Cl2 (40 mL) and the solution was
stirred at room temperature. Tf2O (1.5 mL, 9.43 mmol) was then
added to the solution at room temperature and it was stirred for
4 h. The reaction mixture was filtered and the filtrate was concen-
trated in vacuo. The product 2 was isolated by rapid column
chromatography (flash silica gel, heptanes/EtOAc) as a yellow solid
(1.2 g, 80%). M.p. 75–77 °C. 1H NMR (300 MHz, CDCl3): δ = 6.64
(d, J = 2.2 Hz, 1 H, ArH), 6.69 (s, 1 H), 6.88 (d, J = 2.2 Hz, 1 H,
ArH), 7.44–7.52 (m, 3 H, ArH), 7.76–7.80 (m, 2 H, ArH), 12.84
(br. s, 1 H, OH) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 99.8,
104.0, 105.3 (CH), 109.3 (C), 117.6 (d, JF,C = 320.9 Hz, CF3),
Figure 5. Possible explanation for the site selectivity of the reac-
tions of bis(triflate) 10.
125.2, 128.2 (CH), 129.3 (C), 131.5 (CH), 152.2, 155.6, 161.5, 164.2
(C), 181.5 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –72.64 (s,
3 F, CF ) ppm. IR (KBr): ν = 3099, 3082, 3063 (w), 1650 (m),
˜
3
1614, 1582, 1485 (s), 1415 (m), 1420 (s), 1371, 1337 (m), 1324 (w),
1298 (m), 1282 (w), 1264 (m), 1253, 1242 (w), 1229 (m), 1208, 1185,
1128, 1096 (s), 1034 (w), 1020 (s), 1001, 992 (w), 973 (s), 935, 908
(w), 857 (s), 842 (w), 825, 769, 721, 684, 664, 650 (s), 635, 612 (m),
596 (s), 566, 540 (m) cm–1. GC–MS (EI, 70 eV): m/z (%) = 387 (20)
[M + H]+, 386 (100) [M]+, 225 (77), 207 (12), 123 (31), 77 (10).
HRMS (EI, 70 eV): calcd. for C16H9O6F3S [M]+: 386.00664; found
386.006622.
Conclusion
The 5,7 and 7,8-diarylflavones were prepared by Suzuki–
Miyaura reactions of the bis(triflate) of 1 and 9. The reac-
tions proceeded with very good site selectivity: first attack
proceeded at position 7, for electronic or steric reasons, and
was confirmed by results of DFT calculations and NBO
analysis. The reaction of 1 with one equivalent of triflic
anhydride also proceeded with very good site selectivity and
allowed the synthesis of 7-aryl-5-hydroxyflavones.
General Procedure for Synthesis of 4a–l: A solution of 2, K3PO4,
[Pd(PPh3)4], and arylboronic acid 3 1,4-dioxane (3 mL) was stirred
at 80 °C for 4 h. After cooling to 20 °C, distilled water was added,
the organic and the aqueous layers were separated, and the latter
was extracted with CH2Cl2. The combined organic layers were
dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo.
The residue was purified by column chromatography.
Experimental Section
General: All solvents were dried by standard methods and all reac-
tions were carried out under an inert atmosphere. For H and 13C
1
5-Hydroxy-2-phenyl-7-(p-tolyl)-4H-chromen-4-one (4a): Starting
with 2 (80 mg, 0.207 mmol), 3a (28 mg, 0.207 mmol), [Pd(PPh3)4]
(7 mg, 3 mol-%, 0.006 mmol), K3PO4 (65 mg, 0.304 mmol), and
1,4-dioxane (3 mL), compound 4a was isolated as a yellow solid
(61 mg, 90%). M.p. 204–206 °C. 1H NMR (300 MHz, CDCl3): δ =
2.32 (s, 3 H, CH3), 6.63 (s, 1 H), 6.95 (d, J = 1.5 Hz, 1 H, ArH),
7.11 (d, J = 1.5 Hz, 1 H, ArH), 7.16–7.20 (m, 2 H, ArH), 7.43–
7.47 (m, 5 H, ArH), 7.81–7.84 (m, 2 H, ArH), 12.45 (br. s, 1 H,
NMR spectra, the deuterated solvents indicated were used. MS
data were obtained by EI (70 eV), CI (isobutane) or ESI tech-
niques. For preparative-scale chromatography, silica gel 60 (0.063–
0.200 mm, 70–230 mesh) was used.
Computations: Geometry optimizations and NBO[17] population
analysis were carried out by using the Gaussian 09 program pack-
age.[18] We used the B3LYP gradient-corrected hybrid density func-
Eur. J. Org. Chem. 2012, 1639–1652
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P. Langer et al.
FULL PAPER
OH) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 21.2 (CH3), 104.2,
105.1 (CH), 108.5 (C), 108.8, 125.3, 126.0, 128.0, 128.7 (CH), 130.2
(C), 130.9 (CH), 135.3, 137.9, 147.4, 155.6, 159.7, 163.5 (C), 182.1
NMR (62.9 MHz, CDCl3): δ = 105.5, 106.1 (CH), 109.6 (C), 110.1,
124.3, 126.3, 128.0, 128.8, 129.0, 129.6 (CH), 131.2 (C), 131.9
(CH), 138.6, 139.2, 148.6, 156.5, 160.7, 164.5 (C), 183.1 (CO) ppm.
(CO) ppm. IR (KBr): ν = 3074, 2918, 2855, 1894 (w), 1658, 1614,
IR (KBr): ν = 3068, 2916 (w), 1652, 1615 (s), 1591 (m), 1568, 1556,
˜
˜
1591 (s), 1564, 1556, 1538 (w), 1519, 1486 (m), 1450, 1430, 1409, 1537, 1519, 1504 (w), 1494, 1482, 1450, 1411, 1362 (m), 1343, 1312,
1359 (s), 1344, 1309, 1294 (w), 1272 (m), 1254, 1211, 1201, 1189, 1295 (w), 1271, 1255, 1237, 1206 (m), 1167, 1159, 1120, 1054, 1033
1159, 1124 (w), 1093, 1051, 1031 (m), 998 (s), 957, 938 (w), 864 (s),
838 (w), 803 (s), 774 (w), 763 (s), 727, 684 (m), 674 (s), 654, 645,
633, 623, 600, 563 (m), 531 (s) cm–1. GC–MS (EI, 70 eV): m/z (%)
= 329 (22) [M + H]+, 328 (100) [M]+, 300 (12), 155 (10). HRMS
(EI, 70 eV): calcd. for C22H16O3 [M]+: 328.10940; found
328.109336.
(w), 1011, 999 (m), 965, 938, 921 (w), 908, 899, 860, 827, 809, 794
(m), 761 (s), 725, 700, 691, 685 (w), 673 (s), 654, 643 (w), 634 (m),
619, 608, 576, 545 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 329
(24) [M + H]+, 328 (100) [M]+, 300 (9). HRMS (EI, 70 eV): calcd.
for C22H16O3 [M]+: 328.10940; found 328.109232.
7-[4-(tert-Butyl)phenyl]-5-hydroxy-2-phenyl-4H-chromen-4-one (4e):
5-Hydroxy-2-phenyl-7-(m-tolyl)-4H-chromen-4-one (4b): Starting Starting with 2 (80 mg, 0.207 mmol), 3e (37 mg, 0.207 mmol),
with 2 (80 mg, 0.207 mmol), 3b (28 mg, 0.207 mmol), [Pd(PPh3)4] [Pd(PPh3)4] (7 mg, 3 mol-%, 0.006 mmol), K3PO4 (65 mg, 0.304
(7 mg, 3 mol-%, 0.006 mmol), K3PO4 (65 mg, 0.304 mmol), and mmol), and 1,4-dioxane (3 mL), compound 4e was isolated as a
1
1,4-dioxane (3 mL), compound 4b was isolated as a yellow solid
yellow solid (61 mg, 80%). M.p. 196–198 °C. H NMR (300 MHz,
(57 mg, 85%). M.p. 186–188 °C. 1H NMR (300 MHz, CDCl3): δ =
CDCl3): δ = 1.27 (s, 9 H, 3CH3), 6.6 (s, 1 H), 6.95 (d, J = 1.5 Hz,
2.33 (s, 3 H,CH3), 6.62 (s, 1 H), 6.94 (d, J = 1.5 Hz, 1 H, ArH), ArH), 7.10 (d, J = 1.5 Hz, 1 H, ArH), 7.38–7.44 (m, 5 H, ArH),
7.10 (d, J = 1.5 Hz, 1 H, ArH), 7.12–7.15 (m, 1 H, ArH), 7.23– 7.47–7.50 (m, 2 H, ArH), 7.78–7.81 (m, 2 H, ArH), 12.45 (br. s, 1
7.28 (m, 1 H, ArH), 7.35–7.39 (m, 2 H, ArH), 7.40–7.49 (m, 3 H,
H, OH) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 31.3 (3CH3), 34.7
(C), 105.3, 106.1 (CH), 109.5 (C), 109.9, 126.0, 126.4, 126.9, 129.1
ArH), 7.79–7.83 (m, 2 H, ArH), 12.44 (br. s, 1 H, OH) ppm. 13C
NMR (62.9 MHz, CDCl3): δ = 20.4 (CH3), 104.5, 105.0 (CH), (CH), 131.2 (C), 131.9 (CH), 136.2, 148.4, 152.1, 156.6, 160.7,
108.6 (C), 109.0, 123.3, 125.3, 126.9, 127.8, 128.0, 128.5 (CH), 164.5 (C), 183.1 (CO) ppm. IR (KBr): ν = 3063, 2962, 2902, 2859
˜
130.2 (C), 130.9 (CH), 137.6, 138.1, 147.6, 155.5 159.6, 163.5 (C), (w), 1646 (m), 1608 (s), 1590 (m), 1558, 1522, 1505, 1494, 1472,
182.1 (CO) ppm. IR (KBr): ν = 3067, 2916, 2850, 2791 (m), 1652, 1464 (w), 1450 (m), 1428, 1397, 1362, 1352, 1313, 1294 (w), 1263,
˜
1615, 1591 (s), 1568, 1556, 1537, 1504 (w), 1494, 1482 (m), 1450, 1205 (s), 1159, 1118, 1096, 1075, 1050, 1032, 1017 (w), 1002, 997
1411, 1398, 1362 (s), 1342, 1312 (w), 1294 (m), 1270, 1254, 1237, (m), 985, 970, 926, 910 (w), 868 (m), 859, 849, 841 (w), 827, 822
1205 (m), 1179, 1166, 1159 (w), 1120, 1094, 1054, 1032, 1011, 999
(s), 791 (m), 760 (s), 743, 733 (m), 717, 685 (w), 676 (s), 657, 644,
(m), 965, 938, 920 (w), 907, 899, 861, 827, 809, 793 (m), 761 (s), 634, 625, 619, 607, 591 (w), 551 (m) cm–1. GC–MS (EI, 70 eV): m/z
725, 700, 691, 684 (w), 673 (s), 654, 643 (w), 634 (s), 619, 607, 576, (%) = 371 (20) [M + H]+, 370 (100) [M]+, 356 (26), 355 (100), 127
545 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 329 (22) [M +
(12). HRMS (EI, 70 eV): calcd. for C25H22O3 [M]+: 370.15635;
H]+, 328 (100) [M]+. HRMS (EI, 70 eV): calcd. for C22H16O3 found 370.155853.
[M]+: 328.10940; found 328.109336.
5-Hydroxy-7-(4-methoxyphenyl)-2-phenyl-4H-chromen-4-one (4f):
Starting with 2 (80 mg, 0.207 mmol), 3f (31 mg, 0.207 mmol),
7-(3,5-Dimethylphenyl)-5-hydroxy-2-phenyl-4H-chromen-4-one (4c):
Starting with 2 (80 mg, 0.207 mmol), 3c (31 mg, 0.207 mmol), [Pd(PPh3)4] (7 mg, 3 mol-%, 0.006 mmol), K3PO4 (65 mg,
[Pd(PPh3)4] (7 mg, 3 mol-%, 0.006 mmol), K3PO4 (65 mg, 0.304 mmol), and 1,4-dioxane (3 mL), compound 4f was isolated
0.304 mmol), and 1,4-dioxane (3 mL), compound 4c was isolated
as a yellow solid (56 mg, 80%). M.p. 169–171 °C. 1H NMR (300 MHz, CDCl3): δ = 3.78 (s, 3 H, OCH3), 6.63 (s, 1 H), 6.89–
(300 MHz, CDCl3): δ = 2.29 (s, 6 H, 2CH3), 6.61 (s, 1 H), 6.93 (d, 6.92 (m, 3 H, ArH), 7.09 (d, J = 1.5 Hz, 1 H, ArH), 7.42–7.45 (m,
as a yellow solid (64 mg, 90%). M.p. 173–175 °C. 1H NMR
J = 1.5 Hz, 1 H, ArH), 6.96 (s, 1 H, ArH), 7.10 (d, J = 1.5 Hz, 3 H, ArH), 7.45 (d, J = 6.7 Hz, 2 H, ArH), 7.80–7.90 (m, 2 H,
ArH), 7.15 (br. s, 2 H, ArH), 7.40–7.45 (m, 3 H, ArH), 7.79–7.82 ArH), 12.45 (br. s, 1 H, OH) ppm. 13C NMR (75.4 MHz, CDCl3):
(m, 2 H, ArH), 12.4 (br. s, 1 H, OH) ppm. 13C NMR (75.4 MHz, δ = 55.4 (OCH3), 104.9, 106.1 (CH), 109.3 (C), 109.5, 114.4, 126.3,
CDCl3): δ = 21.4 (2CH3), 105.5, 106.1 (CH), 109.6 (C), 110.1, 128.4, 129.1 (CH), 131.3, 131.5 (C), 131.9 (CH), 148.1, 156.4,
125.1, 126.4, 129.1, 130.5 (CH), 131.2 (C), 131.9 (CH), 138.5, 160.4, 160.7, 164.5 (C), 183.1 (CO) ppm. IR (KBr): ν = 3068, 3046,
˜
139.2, 148.8, 156.5, 160.7, 164.5 (C), 183.1 (CO) ppm. IR (KBr): ν
2995, 2978, 1941, 2914, 2894, 1836 (w), 1656, 1606, 1592 (s), 1572,
= 3066, 3023, 2917, 2863, 2796 (w), 1657, 1619 (s), 1592 (m), 1556, 1558 (m), 1539 (w), 1519, 1490, 1450, 1433, 1417, 1402, 1361, 1345,
˜
1537 (w), 1491 (m), 1449 (s), 1414 (m), 1384 (w), 1295 (m), 1260
(s), 1219 (w), 1200 (m), 1177, 1160 (w), 1119, 1095, 1033, 1022, 999
1294, 1272 (m), 1253 (s), 1214, 1203 (w), 1177 (s), 1122, 1115, 1095,
1051 (w), 1034 (s), 1013 (w), 999 (m), 955, 929 (w), 858 (m), 842
(m), 968, 950 (w), 903 (m), 891 (w), 845, 820, 795 (s), 780, 771 (w), (w), 821, 797, 764 (s), 728, 722, 685 (w), 675 (s), 655, 643, 619 (w),
761 (s), 721, 701 (w), 672, 663, 635 (s), 585 (m), 558, 546 (w) cm–1.
GC–MS (EI, 70 eV): m/z (%) = 343 (28) [M + H]+, 342 (100)
[M]+, 314 (6). HRMS (EI, 70 eV): calcd. for C23H18O3 [M]+:
342.12505; found 342.125397.
603 (m), 566 (w), 534 (m) cm–1. GC–MS (EI, 70 eV): m/z (%) =
345 (24) [M + H]+, 344 (100) [M]+, 301 (8). HRMS (EI, 70 eV):
calcd. for C22H16O4 [M]+: 344.10431; found 344.104996.
5-Hydroxy-7-(3,4-dimethoxyphenyl)-2-phenyl-4H-chromen-4-one
(4g): Starting with 2 (80 mg, 0.207 mmol), 3g (38 mg, 0.207 mmol),
5-Hydroxy-2-phenyl-7-(o-tolyl)-4H-chromen-4-one (4d): Starting
with 2 (80 mg, 0.207 mmol), 3d (28 mg, 0.207 mmol), [Pd(PPh3)4] [Pd(PPh3)4] (7 mg, 3 mol-%, 0.006 mmol), K3PO4 (65 mg,
(7 mg, 3 mol-%, 0.006 mmol), K3PO4 (65 mg, 0.304 mmol), and 0.304 mmol), and 1,4-dioxane (3 mL), compound 4g was isolated
1,4-dioxane (3 mL), compound 4d was isolated as a yellow solid
as a yellow solid (65 mg, 85 %). M.p. 198–200 °C. 1H NMR
(52 mg, 77%). M.p. 150–152 °C. 1H NMR (250 MHz, CDCl3): δ = (300 MHz, CDCl3): δ = 3.85 (s, 3 H, OCH3), 3.87 (s, 3 H, OCH3),
2.33 (s, 3 H, CH3), 6.60 (s, 1 H), 6.93 (d, J = 1.4 Hz, 1 H, ArH), 6.62 (s, 1 H), 6.87 (d, J = 8.3 Hz, 1 H, ArH), 6.92 (d, J = 1.4 Hz,
7.09 (d, J = 1.4 Hz, 1 H, ArH), 7.11–7.14 (m, 1 H, ArH), 7.22– 1 H, ArH), 7.05–7.08 (m, 2 H, ArH), 7.13 (dd, J = 2.0, 8.3 Hz, 1
7.28 (m, 1 H, ArH), 7.31–7.34 (m, 2 H, ArH), 7.41–7.43 (m, 3 H,
H, ArH), 7.43–7.47 (m, 3 H, ArH), 7.80–7.84 (m, 2 H, ArH), 12.4
ArH), 7.78–7.81 (m, 2 H, ArH), 12.4 (br. s, 1 H, OH) ppm. 13C
(br. s, 1 H, OH) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 56.0,
1644
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1639–1652

Efficient Synthesis of Arylated Flavones
56.0 (2OCH3), 105.0, 106.1 (CH), 109.3 (C), 109.6, 110.2, 111.4,
H, OH) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 105.4, 106.2
119.9, 126.4, 129.1 (CH), 131.2, 131.9 (C), 132.0 (CH), 148.3, (CH), 109.8 (C), 109.9, 126.4, 128.5, 129.1, 129.2 (CH), 131.1 (C),
149.3, 149.9, 156.6, 160.7, 164.5 (C), 183.1 (CO) ppm. IR (KBr): ν 132.1 (CH), 135.0, 137.7, 147.2, 156.6, 160.9, 164.7 (C), 183.1 (CO)
= 3436, 3070, 3000, 2937, 2916, 2837 (w), 1651, 1608, 1587 (s), ppm. IR (KBr): ν = 3071, 3053, 1900 (w), 1656, 1619 (s), 1593 (m),
˜
˜
1522 (m), 1492 (s), 1468 (w), 1450, 1434 (s), 1398 (w), 1347 (s),
1322, 1301, 1291 (w), 1252, 1247 (s), 1218, 1203, 1192 (w), 1170
(m), 1129, 1096 (s), 1049 (w), 1018, 1006, 999 (7), 973, 949, 923,
904 (w), 864, 837 (m), 820, 802, 769 (s), 726 (w), 682, 672 (s), 663,
650, 621, 607, 580, 569 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) =
375 (20) [M + H]+, 374 (100) [M]+, 332 (13), 331 (26), 238 (11).
1572, 1557 (w), 1504, 1494, 1485, 1477, 1450, 1430, 1408 (m), 1393
(w), 1356, 1294, 1267, 1216, 1203 (m), 1188, 1160, 1123, 1108 (m),
1093 (s), 1052, 1032, 1015, 1000 (m), 969, 956, 943 (w), 909 (m),
889 (w), 862 (s), 840 (w), 814 (s), 790 (m), 764 (s), 737, 720, 715
(w), 673 (s), 655, 639, 631, 618 (m), 607 (w), 584, 534 (s) cm–1. GC–
MS (EI, 70 eV): m/z (%) = 350 (37Cl, 34) [M]+, 349 (35Cl, 24) [M
HRMS (EI, 70 eV): calcd. for C23H18O5 [M]+: 374.11488; found + H]+, 348 (35Cl, 100) [M]+, 155 (11). HRMS (EI, 70 eV): calcd.
374.1143136.
for C21H1337ClO3 [M]+: 350.05182; found 350.052887, calcd. for
C21H1335ClO3 [M]+: 348.05477 found 348.055573.
5-Hydroxy-2-phenyl-7-[4-(trifluoromethyl)phenyl]-4H-chromen-4-
one (4h): Starting with
2
(80 mg, 0.207 mmol), 3h (39 mg,
5-Hydroxy-7-(2-chlorophenyl)-2-phenyl-4H-chromen-4-one
(4k):
0207 mmol), [Pd(PPh3)4] (7 mg, 3 mol-%, 0.006 mmol), K3PO4
(65 mg, 0.304 mmol), and 1,4-dioxane (3 mL), compound 4h was
isolated as a yellow solid (62 mg, 79%). M.p. 215–217 °C. 1H NMR
Starting with 2 (80 mg, 0.207 mmol), 3k (32 mg, 0.207 mmol),
[Pd(PPh3)4] (7 mg, 3 mol-%, 0.006 mmol), K3PO4 (65 mg,
0.304 mmol), and 1,4-dioxane (3 mL), compound 4k was isolated
(300 MHz, CDCl3): δ = 6.67 (s, 1 H), 6.95 (br. s, 1 H, ArH), 7.13 as a yellow solid (54 mg, 75%). M.p. 186–188 °C. 1H NMR
(br. s, 1 H, ArH), 7.45–7.48 (m, 3 H, ArH), 7.65 (br. s, 4 H, ArH), (250 MHz, CDCl3): δ = 6.68 (s, 1 H), 6.80 (d, J = 1.4 Hz, 1 H,
7.82–7.85 (m, 2 H, ArH), 12.51 (br. s, 1 H, OH) ppm. 13C NMR
ArH), 7.02 (d, J = 1.4 Hz, 1 H, ArH), 7.25–7.29 (m, 3 H, ArH),
(75.4 MHz, CDCl3): δ = 105.8, 106.2 (CH), 110.2 (C), 110.3 (CH), 7.43–7.46 (m, 4 H, ArH), 7.81–7.85 (m, 2 H, ArH), 12.50 (br. s, 1
122.2 [q, J(F,C) = 320.3 Hz, CF3], 125.9 (q, J = 3.7 Hz, CH), 126.4,
129.1 (CH), 130.5, 131.0 (C), 142.8, 146.8, 156.6, 161.0, 164.8 (C),
183.1 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –62.60 ppm.
H, OH) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 106.2, 108.3
(CH), 110.0 (C), 112.8, 126.4, 127.0, 129.1, 129.5, 130.2, 130.9,
131.1 (CH), 132.0, 132.1, 138.9, 146.7, 155.9, 160.2, 164.7 (C),
IR (KBr): ν = 3060, 2922, 2850, 2803 (w), 1650, 1611, 1589 (s), 183.3 (CO) ppm. IR (KBr): ν = 2956, 2851 (w), 1657, 1609, 1591
˜
˜
1557, 1523 (w), 1484, 1450, 1433, 1410, 1355, 1325, 1296, 1284,
(s), 1573, 1556, 1503, 1492, 1462 (m), 1450, 1421, 1396, 1359 (s),
1267 (s), 1249, 1214, 1203 (m), 1167, 1108, 1098, 1068 (s), 1049, 1341 (w), 1296 (s), 1268 (w), 1255, 1246, 1211, 1196, 1186 (s), 1156,
1032, 1015, 997 (m), 975, 958, 930, 906 (w), 845 (m), 822, 766 (s), 1119, 1095 (m), 1078, 1067 (w), 1043 (s), 1034 (w), 998 (m), 970,
754, 724, 699 (w), 686, 676, 656, 633 (s), 611, 593, 580 (w), 531 (m) 954, 921, 907, 869, 861 (w), 844 (s), 828, 817, 766, 751 (s), 734, 727,
cm–1. GC–MS (EI, 70 eV): m/z (%) = 383 (18) [M + H]+, 382 (100) 713 (m), 690, 681, 673, 656, 627 (m), 579 (w), 545 (m) cm–1. GC–
[M]+, 252 (10), 177 (8). HRMS (EI, 70 eV): calcd. for C22H13F3O3 MS (EI, 70 eV): m/z (%) = 350 (37Cl, 35) [M]+, 349 (35Cl, 20) [M
[M]+: 382.08113; found 382.080944.
+ H]+, 348 (35Cl, 100) [M]+, 218 (10), 155 (14). HRMS (EI, 70 eV):
calcd. for C21H1337ClO3 [M]+: 350.05182; found 350.052314, calcd.
for C21H1335ClO3 [M]+: 348.05477 found 348.054378.
7-(4-Fluorophenyl)-5-hydroxy-2-phenyl-4H-chromen-4-one
Starting with 2 (80 mg, 0.207 mmol), 3i (29 mg, 0.207 mmol),
(4i):
[Pd(PPh3)4] (7 mg, 3 mol-%, 0.006 mmol), K3PO4 (65 mg, 5-Hydroxy-2,7-diphenyl-4H-chromen-4-one (4l): Starting with 2
0.304 mmol), and 1,4-dioxane (3 mL), compound 4i was isolated
(80 mg, 0.207 mmol), 3l (25 mg, 0.207 mmol), [Pd(PPh3)4] (7 mg,
as a yellow solid (55 mg, 80%). M.p. 214–216 °C. 1H NMR 3 mol-%, 0.006 mmol), K3PO4 (65 mg, 0.304 mmol), and 1,4-diox-
(300 MHz, CDCl3): δ = 6.66 (s, 1 H), 6.92 (d, J = 1.5 Hz, 1 H, ane (3 mL), compound 4l was isolated as a yellow solid (mg, 80%).
1
ArH), 7.06–7.12 (m, 3 H, ArH), 7.45–7.50 (m, 3 H, ArH), 7.51–
7.56 (m, 2 H, ArH), 7.83–7.86 (m, 2 H, ArH), 12.4 (br. s, 1 H, OH)
ppm. 13C NMR (62.9 MHz, CDCl3): δ = 105.4, 106.2 (CH), 109.6
M.p. 186–188 °C. H NMR (300 MHz, CDCl3): δ = 6.62 (s, 1 H),
6.94 (d, J = 1.5 Hz, 1 H, ArH), 7.11 (d, J = 1.5 Hz, 1 H, ArH),
7.30–7.36 (m, 3 H, ArH), 7.41–7.48 (m, 3 H, ArH), 7.52–7.55 (m,
(C), 110.0, 116.0 (d, J = 21.6 Hz, CH), 126.4, 129.0 (d, J = 8.2 Hz, 2 H, ArH), 7.79–7.782 (m, 2 H, ArH), 12.46 (br. s, 1 H, OH) ppm.
CH), 129.1 (CH), 131.1 (C), 132.0 (CH), 135.4 (d, J = 3.2 Hz, 1 13C NMR (62.9 MHz, CDCl3): δ = 105.6, 106.1 (CH), 109.7 (C),
C), 147.4, 156.6, 160.8 (C), 163.2 (d, JF,C = 248.9 Hz) (CF), 164.6
110.1; 126.4, 127.3, 128.8, 129.0, 129.1 (CH), 131.2 (C), 132.0
(C), 183.1 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –112.90 (CH), 139.2, 148.5, 156.6, 160.8, 164.6 (C), 183.1 (CO) ppm. IR
ppm. IR (KBr): ν = 3074, 3056, 1885 (w), 1657, 1619, 1600 (s),
(KBr): ν = 3075, 3053, 3032, 2926, 2852, 2797 (w), 1656, 1651,
˜
˜
1568, 1556 (w), 1517, 1490, 1450, 1434, 1410 (s), 1398 (w), 1359
(m), 1346, 1300, 1293 (w), 1270 (m), 1254 (w), 1235, 1215, 1202,
1163 (m), 1123, 1095, 1050, 1032, 1015 (w), 999 (s), 952, 937 (w),
909, 862 (s), 842 (w), 817, 807, 798 (s), 775 (w), 764 (s), 727, 718,
684 (w), 674 (s), 654 (m), 641, 632, 618 (w), 600 (m), 561 (w), 533
1613, 1593 (s), 1537 (w), 1508 (m), 1496 (w), 1482, 1450, 1420,
1402, 1361, 1346 (s), 1296 (m), 1270 (s), 1251 (w), 1217, 1207, 1199,
1186 (m), 1160 (w), 1121, 1094, 1075, 1052, 1032, 1002, 997 (m),
946 (w), 910, 903 (m), 872 (w), 850 (s), 835, 825, 794 (m), 752, 727,
684, 674, 654, 639, 630 (s), 616, 575 (w), 535 (m) cm–1. GC–MS
(s) cm–1. GC–MS (EI, 70 eV): m/z (%) = 333 (20) [M + H]+, 332 (EI, 70 eV): m/z (%) = 315 (20) [M + H]+, 314 (100) [M]+, 184 (8).
(100) [M]+, 304 (11), 202 (10), 152 (12). HRMS (EI, 70 eV): calcd.
for C21H13FO3 [M]+: 332.08432; found 332.084347.
HRMS (EI, 70 eV): calcd. for C21H14O3 [M]+: 314.09375; found
314.093679.
7-(4-Chlorophenyl)-5-hydroxy-2-phenyl-4H-chromen-4-one
(4j): 4-Oxo-2-phenyl-4H-chromene-5,7-diyl Bis(trifluoromethanesulfon-
Starting with 2 (80 mg, 0.207 mmol), 3j (32 mg, 0.207 mmol), ate) (5): Pyridine (0.6 mL, 7.86 mmol) was added to a solution of
[Pd(PPh3)4] (7 mg, 3 mol-%, 0.006 mmol), K3PO4 (65 mg, 1 (0.5 g, 1.96 mmol) in CH2Cl2 (20 mL) and the solution was
0.304 mmol), and 1,4-dioxane (3 mL), compound 4j was isolated
stirred at room temperature. Tf2O (0.8 mL, 4.72 mmol) was then
as a yellow solid (62 mg, 86%). M.p. 217–219 °C. 1H NMR added to the solution and the solution was stirred at room tempera-
(250 MHz, CDCl3): δ = 6.68 (s, 1 H), 6.94 (d, J = 1.5 Hz, 1 H, ture for 10 min. Subsequently, the solution was stirred at 40 °C for
ArH), 7.12 (d, J = 1.5 Hz, 1 H, ArH), 7.35–7.40 (m, 2 H, ArH),
30 min. After cooling, the reaction mixture was concentrated in
7.48–7.52 (m, 5 H, ArH), 7.83–7.87 (m, 2 H, ArH), 12.5 (br. s, 1
vacuo. Product 5 was isolated by rapid column chromatography
Eur. J. Org. Chem. 2012, 1639–1652
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1645

P. Langer et al.
FULL PAPER
(flash silica gel, heptanes/EtOAc) as a white solid (0.90 g, 90%).
M.p. 182–184 °C. H NMR (300 MHz, CDCl3): δ = 6.76 (s, 1 H),
646, 635, 631 (m), 612, 587, 578, 556 (w) cm–1. GC–MS (EI, 70 eV):
m/z (%) = 403 (12) [M + H]+, 402 (38) [M]+, 401 (100), 201 (18),
185 (10). HRMS (EI, 70 eV): calcd. for C29H21O2 [M – H]+:
401.15361; found 401.153486.
1
7.07 (d, J = 2.2 Hz, 1 H, ArH), 7.47–7.52 (m, 3 H, ArH), 7.55 (d,
J = 2.2 Hz, 1 H, ArH), 7.80–7.83 (m, 2 H, ArH) ppm. 13C NMR
(75.4 MHz, CDCl3): δ = 109.0, 112.3, 113.2 (CH), 117.7 (C), 118.6
(q, JC,F = 320 Hz, CF3), 118.7 (q, JC,F = 320 Hz, CF3), 126.4, 129.3
(CH), 130 (C), 132.5 (CH), 147.8, 150.8, 157.4, 163.4 (C), 174.6
(CO) ppm. 19F NMR (282.4 MHz. CDCl3): δ = –72.27 (3 F, CF3),
5,7-Bis(3,5-dimethylphenyl)-2-phenyl-4H-chromen-4-one (6c): Start-
ing with 5 (75 mg, 0.145 mmol), 3c (93 mg, 0.29 mmol), [Pd-
(PPh3)4] (10 mg, 6 mol-%, 0.009 mmol), K3PO4 (92 mg,
0.435 mmol), and 1,4-dioxane (3 mL), compound 6c was isolated
as a white solid (49 mg, 80%). Reaction temperature: 115 °C for
–72.96 (3 F, CF ) ppm. IR (KBr): ν = 3111, 3093, 3068, 2958, 2924,
˜
3
2855 (w), 1651, 1617 (s), 1572, 1496, 1467, 1450 (w), 1427, 1363
(s), 1338, 1301, 1279 (w), 1248, 1216, 1202, 1135, 1129, 1097 (s),
1067, 1035 (m), 1006, 972 (s), 929 (w), 892, 872, 848, 812 (s), 782
(w), 773 (s), 761, 713, 705, 689 (m), 680 (w), 661 (m), 650, 641 (w),
612 (s), 596 (w), 586 (s), 569, 545 (m) cm–1. GC–MS (EI, 70 eV):
m/z (%) = 519 (23) [M + H]+, 518 (100) [M]+, 454 (12). HRMS (EI,
70 eV): calcd. for C17H8F6O8S2 [M]+: 517.95593; found 517.95651.
1
6 h. M.p. 171–173 °C. H NMR (300 MHz, CDCl3): δ = 2.29 (s, 6
H, 2CH3), 2.30 (s, 6 H, 2CH3), 6.62 (s, 1 H), 6.93–6.97 (m, 4 H,
ArH), 7.23 (br. s, 2 H, ArH), 7.35 (d, J = 1.8 Hz, 1 H, ArH), 7.41–
7.45 (m, 3 H, ArH), 7.67 (d, J = 1.8 Hz, 1 H, ArH), 7.84–7.87 (m,
2 H, ArH) ppm. 13C NMR (74.5 MHz, CDCl3): δ = 21.3, 21.4 (4
CH3), 108.9, 115.2 (CH), 119.9 (C), 125.2, 126.1, 126.5, 127.4,
128.9, 129.0, 130.3, 131.3 (CH), 131.7, 136.8, 138.6, 138.7, 141.3,
General Procedure for Synthesis of 6a–i and 7a–g: A solution of 5,
K3PO4, [Pd(PPh3)4], and arylboronic acid 3 in 1,4-dioxane (3 mL)
was stirred at 70 or 115 °C for 6–9 h. After cooling to 20 °C, dis-
tilled water was added, the organic and the aqueous layers were
separated, and the latter was extracted with CH2Cl2. The combined
organic layers were dried (Na2SO4), filtered, and the filtrate was
concentrated in vacuo. The residue was purified by column
chromatography.
143.7, 145.4, 157.7 (C), 161.7 (CO) ppm. IR (KBr): ν = 3062, 3006,
˜
2914, 2858, 2732 (w), 1645, 1597 (s), 1574, 1557 (w), 1483 (m), 1463
(w), 1447 (m), 1433 (w), 1371 (s), 1304, 1284, 1262, 1246, 1231,
1188, 1157 (w), 1137, 1110, 1062 (m), 1029, 1012, 998, 983, 954,
925, 911, 901, 868 (w), 846 (s), 790 (m), 765 (s), 746 (m), 707 (w),
690, 680 (s), 645, 637, 617, 586 (m), 563, 541, 531 (w) cm–1. GC–
MS (EI, 70 eV): m/z (%) = 430 (25) [M]+, 429 (100), 416 (9), 199
(43). HRMS (EI, 70 eV): calcd. for C31H25O2 [M – H]+: 429.18491;
found 429.184637.
2-Phenyl-5,7-di(p-tolyl)-4H-chromen-4-one (6a): Starting with 5
(75 mg, 0.145 mmol), 3a (39 mg, 0.29 mmol), [Pd(PPh3)4] (10 mg, 5,7-Bis[4-(tert-butyl)phenyl]-2-phenyl-4H-chromen-4-one (6d): Start-
6 mol-%, 0.009 mmol), K3PO4 (92 mg, 0.435 mmol), and 1,4-diox- ing with 5 (75 mg, 0.145 mmol), 3e (52 mg, 0.29 mmol), [Pd-
ane (3 mL), compound 6a was isolated as a white solid (49 mg,
85%). Reaction temperature: 115 °C for 6 h. M.p. 236–238 °C. H
(PPh3)4] (10 mg, 6 mol-%, 0.009 mmol), K3PO4 (92 mg,
0.435 mmol), and 1,4-dioxane (3 mL), compound 6d was isolated
as a white solid (54 mg, 77%). Reaction temperature: 115 °C for
1
NMR (300 MHz, CDCl3): δ = 2.32 (s, 3 H, CH3), 2.34 (s, 3 H,
CH3), 6.6 (s, 1 H), 7.13–7.16 (m, 3 H, ArH), 7.19–7.22 (m, 3 H,
ArH), 7.36 (d, J = 1.8 Hz, 1 H, ArH), 7.42–7.44 (m, 3 H, ArH),
7.52 (d, J = 8.1 Hz, 2 H, ArH), 7.66 (d, J = 1.8 Hz, 1 H, ArH),
7.83–7.86 (m, 2 H, ArH) ppm. 13C NMR (62.9 MHz, CDCl3): δ =
1
6 h. M.p. 204–206 °C. H NMR (300 MHz, CDCl3): δ = 1.29 (s, 9
H, 3CH3), 1.31 (s, 9 H, 3CH3), 6.62 (s, 1 H), 7.25 (d, J = 8.4 Hz,
2 H, ArH), 7.36 (d, J = 8.4 Hz, 2 H, ArH), 7.41 (d, J = 1.8 Hz, 1
H, ArH), 7.55 (d, J = 8.5 Hz, 2 H, ArH), 7.69 (d, J = 1.7 Hz, 1 H,
21.2, 21.3 (CH3), 108.9, 114.9 (CH), 119.8 (C), 126.1, 127.1, 127.1, ArH), 7.84–7.87 (m, 2 H, ArH) ppm. 13C NMR (75.4 MHz,
128.2, 128.6, 128.9, 129.8, 131.3 (CH), 131.7, 135.8, 136.8, 138.8,
CDCl3): δ = 31.3, 31.4 (CH3), 34.6, 34.7 (C), 108.8, 115.0, 124.4
(CH), 125.6 (C), 126.0, 126.2, 127.0, 127.4, 128.5, 129.0, 131.4
(CH), 131.7, 135.8, 138.3, 143.6, 145.1, 149.8, 152.0, 157.9, 161.9
143.5, 145.1, 157.9, 161.7 (C), 178.0 (CO) ppm. IR (KBr): ν = 3063,
˜
2915, 2858 (w), 1643, 1605 (s), 1574, 1552, 1537 (w), 1519, 1495,
1484, 1463, 1448, 1423 (w), 1372 (s), 1311, 1286, 1271, 1225, 1203,
1191 (w), 1138, 1108 (m), 1081, 1064 (w), 1033, 1023, 1015, 965,
(C), 178.1 (CO) ppm. IR (KBr): ν = 3071, 3039 (w), 2957, 2947
˜
(m), 2900, 2863 (w), 1644, 1604 (s), 1576, 1548 (w), 1520 (m), 1496
941 (w), 929, 909, 877, 861 (m), 843 (w), 809, 773 (s), 725, 711 (w), (w), 1462, 1449, 1422 (m), 1402 (w), 1375 (s), 1318, 1309, 1287 (w),
692, 678 (s), 645, 616, 603, 596 (m), 568 (w), 546 (s) cm–1. GC–MS
(EI, 70 eV): m/z (%) = 403 (11) [M + H]+, 402 (43) [M]+, 401 (100).
HRMS (EI, 70 eV): calcd. for C29H21O2 [M – H]+: 401.15361;
found 401.1534321.
1268 (m), 1211, 1193, 1157, 1144 (w), 1108 (m), 1081, 1064, 1034,
1023, 1012, 999, 970, 942 (w), 929, 909, 873, 863, 843 (m), 825 (s),
815 (m), 769 (s), 750, 740, 729 (w), 693, 679 (s), 659, 644, 613, 604,
588 (w), 566 (m), 545, 535 (w) cm–1. GC–MS (EI, 70 eV): m/z (%)
= 487 (17) [M + H]+, 486 (57) [M]+, 485 (100), 471 (26), 455 (12).
HRMS (EI, 70 eV): calcd. for C35H33O2 [M – H]+: 485.24751;
found 485.247625.
2-Phenyl-5,7-di(m-tolyl)-4H-chromen-4-one (6b): Starting with 5
(75 mg, 0.145 mmol), 3b (39 mg, 0.29 mmol), [Pd(PPh3)4] (10 mg,
6 mol-%, 0.009 mmol), K3PO4 (92 mg, 0.435 mmol), and 1,4-diox-
ane (3 mL), compound 6b was isolated as a white solid (46 mg,
5,7-Bis(4-methoxyphenyl)-2-phenyl-4H-chromen-4-one (6e): Starting
with 5 (75 mg, 0.145 mmol), 3f (44 mg, 0.29 mmol), [Pd(PPh3)4]
(10 mg, 6 mol-%, 0.009 mmol), K3PO4 (92 mg, 0.435 mmol), and
1,4-dioxane (3 mL), compound 6e was isolated as a white solid
(56 mg, 90%). Reaction temperature: 115 °C for 6 h. M.p. 211–
1
80%). Reaction temperature: 115 °C for 6 h. M.p. 122–124 °C. H
NMR (300 MHz, CDCl3): δ = 2.33 (s, 3 H, CH3), 2.34 (s, 3 H,
CH3), 6.60 (s, 1 H), 7.09–7.16 (m, 5 H, ArH), 7.20–7.30 (m, 2 H,
ArH), 7.36 (d, J = 1.8 Hz, 1 H, ArH), 7.40–7.44 (m, 5 H, ArH),
7.69 (d, J = 1.8 Hz, 1 H, ArH), 7.83–7.86 (m, 2 H, ArH) ppm. 13C 212 °C. 1H NMR (300 MHz, CDCl3): δ = 3.75 (s, 3 H, OCH3),
NMR (75.4 MHz, CDCl3): δ = 21.5, 21.5 (2CH3), 108.9, 115.4,
124.4, 126.0, 126.2, 127.3, 127.9, 128.1, 129.0, 129.3, 129.56, 131.4
(CH), 131.7, 137.0, 138.7, 138.7, 141.3, 143.7, 145.3, 157.8, 161.8
3.77 (s, 3 H, OCH3), 6.57 (s, 1 H), 6.87 (d, J = 8.7 Hz, 2 H, ArH),
6.90 (d, J = 8.8 Hz, 2 H, ArH), 7.24 (d, J = 8.7 Hz, 2 H, ArH),
7.31 (d, J = 1.8 Hz, 1 H, ArH), 7.40–7.43 (m, 3 H, ArH), 7.55 (d,
J = 8.8 Hz, 2 H, ArH), 7.60 (d, J = 1.8 Hz, 1 H, ArH), 7.81–7.84
(C), 178.0 (CO) ppm. IR (KBr): ν = 3068, 3060, 3033, 2952 (m),
˜
2920, 2852 (m), 1642 (s), 1622 (w), 1602 (s), 1574, 1557 (w), 1495, (m, 2 H, ArH) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 55.2, 55.4
1462, 1447 (m), 1371 (s), 1302, 1286, 1260, 1193, 1169 (w), 1130 (OCH3), 108.9, 113.0, 114.4, 114.5 (CH), 119.5 (C), 126.1, 127.0,
(m), 1106, 1091, 1078, 1063, 1041, 1028, 998, 971, 948, 928, 900
128.4, 129.0, 130.0 (CH), 131.1 (C), 131.3 (CH), 131.7, 133.6,
(w), 876, 862, 854, 820, 790 (m), 780, 770 (s), 717 (m) 687, 676 (s) 143.2, 144.7, 158.0, 158.9, 160.3, 161.6 (C), 178.1 (CO) ppm. IR
1646
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1639–1652

Efficient Synthesis of Arylated Flavones
(KBr): ν = 3066, 3011, 2957, 2933, 2904, 2836 (w), 1643, 1600 (s),
1576, 1552 (m), 1511 (s), 1461, 1448, 1427 (m), 1371 (s), 1346, 1313
= 8.6 Hz, 2 H, ArH), 7.29–7.33 (m, 3 H, ArH), 7.40 (d, J = 8.6 Hz,
2 H, ArH), 7.44–7.49 (m, 3 H, ArH), 7.55 (d, J = 8.6 Hz, 2 H,
˜
(w), 1291, 1282, 1254 (m), 1236 (s), 1205 (m), 1183, 1176 (s), 1157 ArH), 7.7 (d, J = 1.8 Hz, 1 H, ArH), 7.83–7.87 (m, 2 H, ArH)
(w), 1139 (m), 1116 (w), 1106 (m), 1080, 1062 (w), 1028, 1018 (s),
954 (w), 927, 907, 878, 857, 838 (m), 825 (s), 807, 793 (m), 770 (s),
ppm. 13C NMR (62.9 MHz, CDCl3): δ = 108.9, 115.8, 126.2, 127.0,
127.7, 128.6, 129.1, 129.3, 130.1, 131.6 (CH), 131.6, 133.4, 135.2,
730 (m), 693, 677 (s), 645, 616, 596, 550, 535 (m) cm–1. GC–MS 137.0, 139.4, 142.5, 144.1, 157.8, 162.2 (C), 177.8 (CO) ppm. IR
(EI, 70 eV): m/z (%) = 435 (15) [M + H]+, 434 (61) [M]+, 433 (100),
(KBr): ν = 3061, 2954, 2922, 2852 (w), 1639, 1605 (s), 1574, 1552
˜
390 (10), 217 (7). HRMS (EI, 70 eV): calcd. for C29H21O4 [M – H] (w), 1503, 1496, 1463, 1448, 1423 (m), 1398 (w), 1372 (s), 1311,
+: 433.14344; found 433.1143348.
1287, 1257, 1212, 1190, 1110 (w), 1087 (s), 1064, 1033, 1019, 1014
(w), 1008 (m), 964, 937 (w), 927, 908, 878, 865 (m), 845, 834 (w),
818, 808, 775 (s), 732, 712 (w), 692, 678, 650 (s), 634, 609, 601, 585,
538 (m) cm–1. GC–MS (EI, 70 eV): m/z (%) = 445 ([35Cl] [37Cl], 12)
[M + H]+, 444 ([35Cl] [37Cl], 23) [M]+, 443 ([35Cl] [35Cl], 68) [M +
H]+, 442 ([35Cl] [35Cl], 36) [M]+, 441 (100). HRMS (EI, 70 eV):
calcd. for C27H15Cl2O2 ([M – H]+, [35Cl] [37Cl]): 443.04141; found
443.041464, calcd. for C27H15 Cl2O2 ([M – H]+, [35Cl] [35Cl]):
441.04436; found 441.044306.
2-Phenyl-5,7-bis(4-trifluoromethylphenyl)-4H-chromen-4-one (6f):
Starting with 5 (75 mg, 0.145 mmol), 3h (55 mg, 0.29 mmol),
[Pd(PPh3)4] (10 mg, 6 mol-%, 0.009 mmol), K3PO4 (92 mg,
0.435 mmol), and 1,4-dioxane (3 mL), compound 6f was isolated
as a yellow solid (56 mg, 76%). Reaction temperature: 115 °C for
1
6 h. M.p. 308–310 °C. H NMR (300 MHz, CDCl3): δ = 6.64 (s, 1
H), 7.35 (br. s, 1 H, ArH), 7.41–7.49 (m, 5 H, ArH), 7.62 (d, J =
7.8 Hz, 2 H, ArH), 7.68–7.76 (m, 4 H, ArH), 7.80 (br. s, 1 H, ArH),
7.88–7.89 (br. m, 2 H, ArH) ppm. 13C NMR (75.4 MHz, CDCl3): 2,5,7-Triphenyl-4-H-chromen-4-one (6i): Starting with 5 (75 mg,
δ = 108.8, 116.7 (CH), 120.6 (q, JC,F = 270 Hz, CF3), 120.8 (q, JCF 0.145 mmol), 3l (35 mg, 0.29 mmol), [Pd(PPh3)4] (10 mg, 6 mol-%,
= 270 Hz, CF3), 124.5 (q, JCF = 3.7 Hz, CH), 126.1 (q, JC,F
=
0.009 mmol), K3PO4 (92 mg, 0.435 mmol), and 1,4-dioxane (3 mL),
3.7 Hz, CH), 126.3, 127.1, 127.7, 129.0, 129.1 (CH), 131.8 (C), compound 6i was isolated as a white solid (43 mg, 81%). Reaction
131.8 (CH), 136.2, 138.9, 142.0, 144.1, 149.8, 152.0, 157.9, 162.5
temperature: 115 °C for 6 h. M.p. 194–195 °C.1H NMR (300 MHz,
CDCl3): δ = 6.60 (s, 1 H), 7.30–7.45 (m, 12 H, ArH), 7.60–7.63 (m,
2 H, ArH), 7.71 (d, J = 1.8 Hz, 1 H, ArH), 7.84–7.87 (m, 2 H,
(C), 177.7 (CO) ppm. 19F NMR (282.4 MHz. CDCl3): δ = –62.39
(3 F, CF ), –62.63 (3 F, CF ) ppm. IR (KBr): ν = 3069 (w), 1645,
˜
3
3
1606 (s), 1578, 1556 (m), 1536, 1498 (w), 1470, 1452, 1427 (m), ArH) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 108.9, 115.5 (CH),
1406 (w), 1375, 1320 (s), 1291, 1260, 1195 (w), 1170, 1163, 1152,
1102, 1066 (s), 1035 (w), 1012 (s), 955, 948 (w), 929 (m), 909, 884 131.4 (CH), 131.6, 138.7, 141.3, 143.6, 145.2, 157.8, 161.9 (C),
(w), 871, 854 (m), 831, 773 (s), 740 (w), 693, 681, 671 (s), 650, 641, 178.0 (CO) ppm. IR (KBr): ν = 3059, 3030 (w), 1644, 1606, 1598
120.0 (C), 126.2, 127.2, 127.3, 127.5, 128.7, 128.8, 129.0, 129.1,
˜
621 (w), 598, 584 (m), 533 (w) cm–1. GC–MS (EI, 70 eV): m/z (%)
(s), 1574, 1556 (m), 1537 (w), 1503, 1495, 1464, 1448 (s), 1440 (m),
= 511 (9) [M + H]+, 510 (44) [M]+, 509 (100). HRMS (EI, 70 eV): 14150, 1393 (w), 1372 (s), 1310, 1287, 1207, 1192, 1157 (w), 1139,
calcd. for C29H16F6O2 [M – H]+: 510.11541; found 510.117632.
1109 (m), 1079, 1072, 1064, 1039, 1030 (w), 1016 (m), 999, 975 (w),
929, 906, 872 (m), 843, 789 (w), 760 (s), 710 (m), 690 (s), 646, 627,
614, 604, 583 (w), 569, 534 (m) cm–1. GC–MS (EI, 70 eV): m/z (%)
= 374 (38) [M]+, 373 (100), 215 (5). HRMS (EI, 70 eV): calcd. for
C24H17F3O5S [M]+: 373.12231; found 373.121759.
5,7-Bis(4-fluorophenyl)-2-phenyl-4H-chromen-4-one (6g): Starting
with 5 (75 mg, 0.145 mmol), 3i (41 mg, 0.29 mmol), [Pd(PPh3)4]
(10 mg, 6 mol-%, 0.009 mmol), K3PO4 (92 mg, 0.345 mmol), and
1,4-dioxane (3 mL), compound 6g was isolated as a white solid
(49 mg, 83%). Reaction temperature: 115 °C for 6 h. M.p. 213–
4-Oxo-2-phenyl-7-(m-tolyl)-4H-chromen-5-yl Trifluoromethanesulf-
onate (7a): Starting with 5 (75 mg, 0.145 mmol), 3b (22 mg,
0.145 mmol), [Pd(PPh3)4] (5 mg, 3 mol-%, 0.004 mmol), K3PO4
(46 mg, 0.217 mmol), and 1,4-dioxane (3 mL), compound 7a was
1
215 °C. H NMR (250 MHz, CDCl3): δ = 6.63 (s, 1 H), 7.06 (dt, J
= 8.7, 17.2 Hz, 4 H, ArH), 7.23–7.29 (m, 3 H, ArH), 7.44–7.47 (m,
3 H, ArH), 7.59 (dd, J = 5.2, 8.8 Hz, 2 H, ArH), 7.67 (d, J =
1.6 Hz, 1 H, ArH), 7.83–7.87 (m, 2 H, ArH) ppm. 13C NMR isolated as a white solid (58 mg, 85%). Reaction temperature: 70 °C
(62.9 MHz, CDCl3): δ = 108.9, 114.5 (d, J = 21.5 Hz, CH), 115.6,
115.2 (d, J = 21.4 Hz, CH), 119.9 (C), 126.1, 127.2, 129.0 (CH), (s, 3 H, CH3), 6.70 (s, 1 H), 7.21–7.24 (m, 1 H, ArH), 7.30–7.36
for 9 h. M.p. 218–221 °C. 1H NMR (300 MHz, CDCl3): δ = 2.38
129.1 (d, J = 8.0 Hz, CH), 130.4 (d, J = 8.0 Hz, CH), 131.4 (C),
131.5 (CH), 134.8 (d, J = 3.3 Hz, 1 C), 136.9 (d, J = 3.3 Hz, 1 C),
142.6, 144.2, 157.8, 162.0 (C), 162.3 (d, JF,C = 245.9 Hz, CF), 163.3
(d, JF,C = 249.1 Hz, CF), 175.8 (CO) ppm. 19F NMR (282 MHz,
(m, 4 H, ArH), 7.44–7.48 (m, 3 H, ArH), 7.72 (J = 1.8 Hz, 1 H,
ArH), 7.81–7.84 (m, 2 H, ArH) ppm. 13C NMR (75.4 MHz,
CDCl3): δ = 108.8 (CH), 116.1 (C), 116.6, 117.7 (CH), 118.9 (q,
JF,C = 320.1 Hz, CF3), 124.3, 126.3, 127.9, 129.1, 129.3, 130.4
(CH), 130.8 (C), 132.0, 137.2 (CH), 139.2, 147.0, 157.3, 162.8 (C),
175.8 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –73.3 ppm. IR
CDCl ): δ = –115.4, –112.7 ppm. IR (KBr): ν = 3065, 2919, 2852,
˜
3
1894, 1743 (w), 1644 (s), 1621 (m), 1606 (s), 1576, 1555 (m), 1509
(s), 1466, 1448, 1425 (m), 1402 (w), 1369 (s), 1346, 1305, 1287,
1271, 1260 (w), 1216 (s), 1189 (w), 1157, 1138 (s), 1108, 1092, 1081,
(KBr): ν = 3061, 2955 (w), 2921 (m), 2852 (w), 1647, 1626, 1614
˜
(s), 1579, 1552 (w), 1495 (m), 1468 (w), 1449 (m), 1430 (s), 1392
1054, 1034, 1020, 1012, 1000, 984, 965 (w), 927 (m), 908, 895 (w), (m), 1368 (s), 1348, 1303, 1287 (w), 1246 (m), 1217, 1193, 1137 (s),
873 (m), 858 (w), 829 (s), 790 (m), 771 (s), 742, 730, 721 (w), 694,
1112 (m), 1080 (w), 1066, 1033 (m), 981 (s), 938, 926, 905, 886 (w),
685, 674 (s), 647, 636 (w), 616, 603, 594, 566, 547 (m) cm–1. GC– 867, 834, 796, 786, 768, 760 (s), 711 (w), 687 (s), 666, 647 (m), 637
MS (EI, 70 eV): m/z (%) = 411 (9) [M + H]+, 410 (44) [M]+, 409 (w), 609, 585, 577 (s), 533 (w) cm–1. GC–MS (EI, 70 eV): m/z (%)
(100), 251 (7). HRMS (EI, 70 eV): calcd. for C27H15F2O2 [M – H]
= 461 (25) [M + H]+, 460 (100) [M]+, 368 (32), 299 (26), 228 (9).
HRMS (EI, 70 eV): calcd. for C23H15F3O5 S [M]+: 460.06346;
found 460.063561.
+: 409.10346; found 409.103561.
5,7-Bis(4-chlorophenyl)-2-phenyl-4H-chromen-4-one (6h): Starting
with 5 (75 mg, 0.145 mmol), 3j (45 mg, 0.29 mmol), [Pd(PPh3)4]
7-(3,5-Dimethylphenyl)-4-oxo-2-phenyl-4H-chromen-5-yl Trifluoro-
(10 mg, 6 mol-%, 0.009 mmol), K3PO4 (92 mg, 0.435 mmol), and methanesulfonate (7b): Starting with 5 (75 mg, 0.145 mmol), 3c
1,4-dioxane (3 mL), compound 6h was isolated as a yellow solid
(22 mg, 0.145 mmol), [Pd(PPh3)4] (5 mg, 3 mol-%, 0.004 mmol),
K3PO4 (46 mg, 0.217 mmol), and 1,4-dioxane (3 mL), compound
(54 mg, 85%). Reaction temperature: 115 °C for 6 h. M.p. 280–
1
282 °C. H NMR (300 MHz, CDCl3): δ = 6.66 (s, 1 H), 7.23 (d, J 7b was isolated as a white solid (58 mg, 85%). Reaction tempera-
Eur. J. Org. Chem. 2012, 1639–1652
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1647

P. Langer et al.
FULL PAPER
ture: 70 °C for 9 h. M.p. 218–221 °C. 1H NMR (300 MHz, CDCl3): (22 mg, 0.145 mmol), [Pd(PPh3)4] (5 mg, 3 mol-%, 0.004 mmol),
δ = 2.34 (s, 3 H, 6CH3), 6.70 (s, 1 H), 7.05 (br., 1 H, ArH), 7.15 K3PO4 (46 mg, 0.217 mmol), and 1,4-dioxane (3 mL), compound
(br., 2 H, ArH), 7.32 (br., 1 H, ArH), 7.45–7.49 (m, 3 H, ArH),
7.72 (d, J = 1.6 Hz, 1 H, ArH), 7.821–7.85 (m, 2 H, ArH) ppm.
7e was isolated as a white solid (55 mg, 81%). Reaction tempera-
ture: 70 °C for 9 h. M.p. 218–220 °C. 1H NMR (300 MHz, CDCl3):
13C NMR (74.5 MHz, CDCl3): δ = 21.3 (2 CH3), 108.7 (CH), 116.0 δ = 3.79 (s, 3 H, OCH3), 6.71 (s, 1 H, CH), 6.95–6.98 (m, 1 H,
(C), 116.3 (CH), 117.3 (q, JF,C = 320.1 Hz, CF3), 117.7, 125.0, ArH), 6.99–7.04 (m, 1 H, ArH), 7.29–7.33 (m, 1 H, ArH), 7.36–
126.2, 129.1 (CH), 130.8 (C), 131.3, 132.0 (CH), 137.2, 139.1, 7.39 (m, 2 H, ArH), 7.42–7.49 (m, 3 H, ArH), 7.70 (d, J = 1.8 Hz,
146.9, 147.2, 157.3, 162.8 (C), 175.8 (CO) ppm. 19F NMR 1 H, ArH), 7.81–7.84 (m, 2 H, ArH) ppm. 13C NMR (74.5 MHz,
(282 MHz, CDCl ): δ = –73.3 ppm. IR (KBr): ν = 3063, 2916, 2859
CDCl3): δ = 55.5 (OCH3), 108.8, 111.5 (CH), 116.0 (C), 118.2 (q,
˜
3
(w), 1639, 1630, 1611 (s), 1579, 1493 (w), 1449 (m), 1425 (s), 1394 JF,C = 285.2 Hz, CF3), 119.1, 120.5, 121.2, 126.3 (CH), 126.5 (C),
(w), 1369 (s), 1348, 1298, 1284, 1249 (w), 1231 (m), 1201, 1138 (s),
1116 (m), 1077 (w), 1064, 1031, 1008 (m), 978 (s), 949, 924, 908,
129.1, 130.4, 130.9 (CH); 131.0 (C), 131.9 (CH), 144.6, 146.1,
156.4, 156.8, 162.7 (C), 175.9 (CO) ppm. 19F NMR (282 MHz,
895, 868, 857, 850 (w), 828, 768, 758 (s), 734, 711, 701 (w), 685, CDCl ): δ = –73.4 ppm. IR (KBr): ν = 3075, 3061, 3011 (w), 2922
˜
3
675, 665 (m), 653 (w), 614, 588 (s), 569, 541 (w) cm–1. GC–MS (EI, (m), 2851 (w), 1647, 1627, 1613, 1598 (s), 1598, 1579 (m), 1544 (w),
70 eV): m/z (%) = 475 (25) [M + H]+, 474 (100) [M]+, 382 (29), 313 1495, 1467, 1450 (m), 1440 (w), 1420, 1405, 1369 (s), 1308 (w), 1266
(25). HRMS (EI, 70 eV): calcd. for C24H17F3O5S [M]+: 474.07433;
found 474.072983.
(m), 1238, 1201, 1190 (s), 1166 (w), 1143, 1134, 1110 (s), 1072,
1066, 1058, 1044 (w), 1029, 1022 (m), 1000 (w), 979 (s), 941 (w),
899, 877 (s), 861, 852 (w), 814 (s), 786, 779, 769 (w), 752 (s), 713
(w), 690 (s), 672, 647, 623 (w), 611, 587 (s), 568, 551 (w) cm–1. GC–
MS (EI, 70 eV): m/z (%) = 478 (9) [M + 1]+, 477 (26) [M]+, 476
(100). HRMS (EI, 70 eV): calcd. for C23H15F3O6S: 476.05359;
found 476.053485.
7-[4-(tert-Butyl)phenyl]-4-oxo-2-phenyl-4H-chromen-5-yl Trifluoro-
methanesulfonate (7c): Starting with 5 (75 mg, 0.145 mmol), 3e
(26 mg, 0.145 mmol), [Pd(PPh3)4] (5 mg, 3 mol-%, 0.004 mmol),
K3PO4 (46 mg, 0.217 mmol), and 1,4-dioxane (3 mL), compound
7c was isolated as a white solid (51 mg, 71%). Reaction tempera-
ture: 70 °C for 9 h. M.p. 185–188 °C. 1H NMR (300 MHz, CDCl3):
δ = 1.30 (s, 9 H, 3 CH3), 6.71 (s, 1 H), 7.35 (br. s, 1 H, ArH), 7.45–
7.54 (m, 7 H, ArH), 7.74 (d, J = 1.5 Hz, 1 H, ArH), 7.83–7.86 (m,
2 H, ArH) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 31.21 (3CH3),
34.8 (C), 108.3, 116.2, 117.5 (CH), 118.7 (q, JF,C = 322.1 Hz, CF3),
126.3, 126.4, 126.9, 129.1 (CH), 130.9 (C), 131.9 (CH), 134.3,
146.7, 147.0, 153.1, 157.4, 162.8 (C), 175.8 (CO) ppm. 19F NMR
7-(4-Fluorophenyl)-4-oxo-2-phenyl-4H-chromen-5-yl Trifluorometh-
anesulfonate (7f): Starting with 5 (75 mg, 0.145 mmol), 3i (20 mg,
0.145 mmol), [Pd(PPh3)4] (5 mg, 3 mol-%, 0.004 mmol), K3PO4
(46 mg, 0.217 mmol), and 1,4-dioxane (3 mL), compound 7f was
isolated as a white solid (53 mg, 80%). Reaction temperature: 70 °C
for 9 h. M.p. 188–189 °C. 1H NMR (300 MHz, CDCl3): δ = 6.71
(s, 1 H, CH), 7.12–7.15 (m, 1 H, ArH), 7.29 (br., 1 H, ArH), 7.45–
7.50 (m, 4 H, ArH), 7.52–7.57 (m, 2 H, ArH), 7.70 (d, J = 1.5 Hz,
1 H ArH), 7.81–7.84 (m, 2 H, ArH) ppm. 13C NMR (74.5 MHz,
CDCl3): δ = 108.8, 116.3 (d, J = 21.6 Hz), 116.4, 117.5 (CH), 118.2
(q, JF,C = 321.1 Hz, CF3), 126.3, 129.1 (d, J = 8.2 Hz), 129.2 (CH),
130.7 (C), 132.1 (CH), 133.4 (d, J = 3.3 Hz), 145.7, 147.1, 157.4,
162.8 (C), 163.7 (d, JF,C = 248.9 Hz) (CF), 175.6 (CO) ppm. 19F
(282 MHz, CDCl ): δ = –73.3 ppm. IR (KBr): ν = 3063, 2962,
˜
3
2866, 2252 (w), 1643, 1630, 1613 (s), 1577, 1546, 1523, 1494, 1474
(w), 1449 (m), 1242 (s), 1400 (m), 1369 (s), 1346, 1301, 1285, 1269
(w), 1242 (m), 1230 (w), 1205, 1137 (s), 1117, 1106, 1065, 1055,
1031 (m), 1016, 1001 (w), 981, 903 (s), 879 (w), 833, 810, 767, 761
(s), 746 (w), 730, 721, 707, 686, 676, 647 (m), 613, 595, 588 (s), 569,
558, 546, 527 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 503 (11)
[M + H]+, 502 (40) [M]+, 487 (27), 488 (100), 326 (10). HRMS (EI,
70 eV): calcd. for C26H21 F3O5S [M]+: 502.10563; found
502.105916.
NMR (282 MHz, CDCl ): δ = –111.2, –73.3 ppm. IR (KBr): ν =
˜
3
3067, 2956, 2922, 2852 (w), 1648, 1627, 1613 (s), 1601 (m), 1578,
1549 (w), 1518 (s), 1495, 1473, 1451 (w), 1431, 1420 (s), 1394 (m),
1372 (s), 1344, 1306, 1288 (w), 1241 (m), 1199 (s), 1161 (m), 1140,
1134 (s), 1116 (m), 1103, 1081 (w), 1068, 1054, 1030 (m), 1014,
1001 (w), 984 (s), 930 (w), 904 (s), 882, 873 (w), 833, 821, 800 (s),
777, 770, 760 (m), 722, 709, 695, 688, 678, 649, 637, 614 (w), 602,
586 (s), 569, 546, 528 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 465
(25) [M + H]+, 464 (100) [M]+, 400 (9), 372 (40), 303 (25), 246 (10).
HRMS (EI, 70 eV): calcd. for C22H12F4O5S [M]+:464.03359; found
464.033814.
7-(4-Methoxyphenyl)-4-oxo-2-phenyl-4H-chromen-5-yl
Trifluoro-
methanesulfonate (7d): Starting with 5 (75 mg, 0.145 mmol), 3f
(22 mg, 0.145 mmol), [Pd(PPh3)4] (5 mg, 3 mol-%, 0.004 mmol),
K3PO4 (46 mg, 0.217 mmol), and 1,4-dioxane (3 mL), compound
7d was isolated as a white solid (57 mg, 83%). Reaction tempera-
ture: 70 °C for 9 h. M.p. 214–216 °C. 1H NMR (300 MHz, CDCl3):
δ = 3.78 (s, 3 H, OCH3), 6.71 (s, 1 H), 6.98 (d, J = 8.8 Hz, ArH),
730 (br., 1 H, ArH), 7.46–7.53 (m, 5 H, ArH), 7.70 (d, J = 1.5 Hz,
1 H, ArH), 7.82–7.85 (m, 2 H, ArH) ppm. 13C NMR (62.9 MHz,
CDCl3): δ = 55.4 (OCH3), 108.7, 114.8, 115.6, 117.1 (CH), 118.7
(q, JF,C = 320.1 Hz, CF3), 126.2, 128.4, 129.1 (CH), 129.9, 130.9
(C), 131.9 (CH), 146.4, 147.1, 157.4, 160.9, 162.7 (C), 175.8 (CO)
7-(4-Chlorophenyl)-4-oxo-2-phenyl-4H-chromen-5-yl Trifluorometh-
anesulfonate (7g): Starting with 5 (75 mg, 0.145 mmol), 3j (22 mg,
0.145 mmol), [Pd(PPh3)4] (5 mg, 3 mol-%, 0.004 mmol), K3PO4
(46 mg, 0.217 mmol), and 1,4-dioxane (3 mL), compound 7g was
isolated as a white solid (57 mg, 82%). Reaction temperature: 70 °C
for 9 h. M.p. 249–252 °C. 1H NMR (300 MHz, CDCl3): δ = 6.72
(s, 1 H), 7.30 (br., 1 H, ArH), 7.42–7.52 (m, 7 H, ArH), 7.72 (d, J
= 1.6 Hz, 1 H, ArH), 7.82–7.85 (m, 2 H, ArH) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 108.8, 116.3, 116.5, 117.5 (CH), 118.2 (q,
JF,C = 320.7 Hz, CF3), 126.2, 128.4, 129.1, 129.6 (CH), 130.7 (C),
132.1 (CH), 135.6, 136.0, 145.5, 147.2, 157.4, 162.9 (C), 175.6 (CO)
ppm. 19F NMR (282 MHz, CDCl ): δ = –73.3 ppm. IR (KBr): ν
˜
3
= 3062, 3006, 2963, 2836 (w), 1647, 1629, 1604 (s), 1578, 1549 (w),
1523 (s), 1495, 1476, 1450 (w), 1429 (s), 1402 (m), 1371 (s), 1346,
1298, 1285 (w), 1257, 1244, 1212, 1201, 1192, 1182 (m), 1161 (w),
1139 (s), 1116, 1090, 1078, 1065, 1054, 1031 (m), 1009, 1001 (w),
982 (s), 923 (w), 904 (s), 877, 866 (w), 822 (s), 797, 789, 766 (m),
732, 713 (w), 686, 676 (m), 657, 645, 613 (w), 604, 586 (s), 569,
549, 528 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 477 (26) [M +
H]+, 476 (100) [M]+, 369 (12), 315 (22). HRMS (EI, 70 eV): calcd.
for C23H15F3O6S [M]+:476.05359; found 476.052814.
ppm. 19F NMR (282 MHz, CDCl ): δ = –73.32 ppm. IR (KBr): ν
˜
3
= 3116, 3063, 2956, 2922, 2852 (w), 1647, 1626, 1614 (s), 1593,
1579, 1574, 1548 (w), 1505, 1494 (m), 1470, 1449 (w), 1432 (s),
1413, 1388 (m), 1367 (s), 1343, 1301, 1282, 1257 (w), 1244, 1214,
1202, 1192, 1183, 1140 (s), 1116, 1091, 1077, 1065, 1053, 1035,
1011, 1001 (m), 982 (s), 922 (w), 901, 870 (s), 842 (w), 820 (s), 779
7-(2-Methoxyphenyl)-4-oxo-2-phenyl-4H-chromen-5-yl
Trifluoro-
methanesulfonate (7e): Starting with 5 (75 mg, 0.145 mmol), 3g
1648
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1639–1652

Efficient Synthesis of Arylated Flavones
(w), 767 (s), 730 (w), 711, 686, 678, 664 (m), 654, 645, 633 (w), 612,
588 (s), 565, 532 (m) cm–1. GC–MS (EI, 70 eV): m/z (%) = 483
(37Cl, 8) [M + H]+, 482 (37Cl, 41) [M]+, 481 (35Cl, 24) [M + H]+,
480 (35Cl, 100) [M]+, 390 (13), 319 (23). HRMS (EI, 70 eV): calcd.
for C22H1235ClF3O5S [M]+: 480:00406; found 480.003734.
(w), 1009 (s), 999, 982, 958 (w), 934, 929, 909 (m), 872, 830, 821
(s), 811 (m), 797 (w), 775 (s), 733, 723 (w), 693, 679 (s), 656, 648,
638, 621, 600 (w), 585, 553, 541 (m) cm–1. GC–MS (EI, 70 eV): m/z
(%) = 428 (37Cl, 15) [M]+, 427 (35Cl, 46) [M + H]+, 426 (35Cl, 49)
[M]+, 425 (100), 388 (11), 386 (17), 384 (23). HRMS (EI, 70 eV):
calcd. for C27H15ClF O2 ([M – H]+, 35Cl): 425.07391; found
425.073196.
General Procedure for the Synthesis of 8a,b: The reaction was car-
ried out in a pressure tube. K3PO4 (46 mg, 0.217 mmol) was added
to a suspension of 5 (75 mg, 0.145 mmol), arylboronic acid
Ar1B(OH)2 (0.145 mmol), and [Pd(PPh3)4] (3 mol-%) in dioxane
(3 mL), and the resultant solution was degassed by bubbling argon
through the solution for 10 min. The mixture was heated at 70 °C
under an argon atmosphere for 9 h. The mixture was cooled to
20 °C. Arylboronic acid Ar2B(OH)2 (0.145 mmol), [Pd(PPh3)4]
(3 mol-%), K3PO4 (46 mg, 0.75 mmol), and dioxane (2 mL) were
added. The reaction mixtures were heated under an argon atmo-
sphere for 6 h at 115 °C. They were diluted with H2O and extracted
with CH2Cl2 (3ϫ25 mL). The combined organic layers were dried
(Na2SO4), filtered, and the filtrate was concentrated in vacuo. The
residue was purified by flash chromatography (silica gel, heptane/
EtAOc).
4-Oxo-2-phenyl-4H-chromene-7,8-diyl Bis(trifluoromethanesulfon-
ate) (10): pyridine (0.32 mL, 4.0 mmol) was added to a solution of
9 (254 mg, 1.0 mmol) in CH2Cl2 (10 mL) at –78 °C under argon
atmosphere. After stirring for 10 min, Tf2O (0.40 mL, 2.4 mmol)
was added at –78 °C. The mixture was warmed to 0 °C and stirred
for 4 h. The reaction mixture was filtered and the filtrate was con-
centrated in vacuo. Product 10 was isolated by rapid column
chromatography (flash silica gel, heptanes/EtOAc) as a white solid
1
(393 mg, 76%). M.p. 142–143 °C. H NMR (300 MHz, CDCl3): δ
= 6.82 (s, 1 H), 7.43–7.52 (m, 4 H, ArH), 7.88–7.91 (m, 2 H, ArH),
8.25 (d, J = 9.4 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
108.3 (CH), 118.6 (q, JF,C = 321.6 Hz, CF3), 118.7 (q, JF,C
=
320.4 Hz, CF3), 118.9 (CH), 124.7 (C), 126.6, 126.7, 129.3 (CH),
129.9, 130.2 (C), 132.6 (CH), 143.9, 149.5, 164.5, 175.3 (C) ppm.
19F NMR (282 MHz, CDCl ): δ = –72.6, –72.8 ppm. IR (KBr): ν
5-(4-Chlorophenyl)-7-(3,5-dimethylphenyl)-2-phenyl-4H-chromen-4-
one (8a): Starting with 5 (75 mg, 0.145 mmol), 3c (22 mg,
0.145 mmol), [Pd(PPh3)4] (5 mg, 3 mol-%, 0.004 mmol), K3PO4
(46 mg, 0.217 mmol), 1,4-dioxane (3 mL), 3j (23 mg, 0.145 mmol),
[Pd(PPh3)4] (5 mg, 3 mol-%, 0.004 mmol), K3PO4 (46 mg,
0.217 mmol), and 1,4-dioxane (2 mL), compound 8a was isolated
as a white solid (49 mg, 78 %). M.p. 226–227 °C. 1H NMR
(300 MHz, CDCl3): δ = 2.33 (s, 6 H, 2CH3), 6.64 (s, 1 H), 7.01 (br.
s, 1 H, ArH), 7.23–7.27 (m, 4 H, ArH), 7.29–7.31 (m, 2 H, ArH),
7.33 (d, J = 1.8 Hz, 1 H, ArH), 7.45–7.47 (m, 3 H, ArH), 7.73 (d,
J = 1.8 Hz, 1 H, ArH), 7.86–7.89 (m, 2 H, ArH) ppm. 13C NMR
(74.5 MHz, CDCl3): δ = 21.3 (2CH3), 107.7, 114.7 (CH), 118.7 (C),
124.1, 125.2, 126.3, 126.6, 128.0, 129.1, 129.5, 130.5 (CH), 132.2,
137.4, 137.7, 138.7, 141.1, 144.7, 156.7, 161.0 (C), 177.0 (CO) ppm.
˜
3
= 3080 (w), 1660 (s), 1613 (m), 1427 (s), 1359 (m), 1210 (s), 1126
(s), 1053 (m), 996 (m), 955 (m), 836 (m), 794 (m), 756 (m), 733 (w),
684 (m) cm–1. GC–MS (EI, 70 eV): m/z (%) = 518 (95) [M]+ 385
(7), 357 (15), 321 (29), 293 (100), 219 (66), 191 (79). HRMS (EI,
70 eV): calcd. for C17H8F6O8S2 [M+]: 517.95700; found 517.95651.
General Procedure for Synthesis of 11a–g, 12a–e, and 13a,b: A solu-
tion of 10 (1.0 equiv.), arylboronic acid 3 (1.0–1.3 equiv. per desired
cross-coupling reaction), K3PO4 (1.5–2.0 equiv. per desired cross-
coupling reaction), and [Pd(PPh3)4] (5 mol-%) in 1,4-dioxane (3–
4 mL) was heated at 70–100 °C for 4 h. After cooling to 20 °C, a
sat. aq. solution of NH4Cl was added, the organic and aqueous
layers were separated, and the latter was extracted with CH2Cl2.
The combined organic layers were dried (Na2SO4), filtered, and
the filtrate was concentrated in vacuo. The residue was purified by
column chromatography.
IR (KBr): ν = 3058, 2961, 2915, 2852 (w), 1640, 1606 (s), 1575,
˜
1557 (w), 1495 (m), 1480 (w), 1447 (m), 1401 (w), 1371 (s), 1324,
1303 (w), 1288, 1261 (m), 1203, 1187, 1140, 1109, 1101 (w), 1085,
1055 (m), 1029 (w), 1014 (m), 999, 949 (w), 920, 880, 872 (m), 850,
823 (s), 788 (w), 767 (s), 733, 713 (w), 690, 680, 638 (s), 599, 283
(w), 537 (s) cm–1. GC–MS (EI, 70 eV): m/z (%) = 438 (37Cl, 16)
[M]+, 437 (35Cl, 41) [M + H]+, 436 (35Cl, 46) [M]+, 435 (100).
HRMS (EI, 70 eV): calcd. for C29H2035Cl O2 [M – H]+: 435.11463;
found 435.11470.
2-Phenyl-7,8-di(p-tolyl)-4H-chromen-4-one (11a): Starting with 10
(259 mg, 0.5 mmol), K3PO4 (424 mg, 2.0 mmol), [Pd(PPh3)4]
(28.8 mg, 5 mol-%, 0.025 mmol), 3a (177 mg, 1.3 mmol), and 1,4-
dioxane (5 mL), compound 11a was isolated as a crystalline light
yellow solid (148 mg, 74%). Reaction temperature: 100 °C for 4 h.
1
M.p. 248–249 °C. H NMR (300 MHz, CDCl3): δ = 2.19 (s, 3 H,
CH3), 2.29 (s, 3 H, CH3), 6.75 (s, 1 H), 6.90–7.04 (m, 8 H, ArH),
7.24–7.33 (m, 3 H, ArH), 7.39 (d, J = 8.2 Hz, 1 H, ArH), 7.48–
7.51 (m, 2 H, ArH), 8.16 (d, J = 8.2 Hz, 1 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21.2, 21.4 (CH3), 106.7 (CH), 122.8 (C),
124.4, 126.2, 127.4, 128.6, 128.7, 128.9, 129.7 (CH), 130.2 (C),
131.0, 131.4 (CH), 131.6, 131.7, 137.0, 137.1, 146.7, 153.9, 163.2
7-(4-Chlorophenyl)-5-(4-fluorophenyl)-2-phenyl-4H-chromen-4-one
(8b): Starting with 5 (75 mg, 0.145 mmol), 3j (20 mg, 0.145 mmol),
[Pd(PPh3)4] (5 mg, 3 mol-%, 0.004 mmol), K3PO4 (46 mg,
0.217 mmol), 1,4-dioxane (3 mL), 3i (23 mg, 0.145 mmol),
[Pd(PPh3)4] (5 mg, 3 mol-%, 0.004 mmol), K3PO4 (46 mg,
0.217 mmol), and 1,4-dioxane (2 mL), compound 8b was isolated
as a white solid (47 mg, 77%). M.p. 256–258 °C. 1H NMR
(300 MHz, CDCl3): δ = 6.63 (s, 1 H), 6.99–7.06 (m, 2 H, ArH),
7.24–7.28 (m, 2 H, ArH), 7.30 (d, J = 1.8 Hz, 1 H, ArH), 7.38 (d,
J = 7.5 Hz, 2 H, ArH), 7.43–7.47 (m, 3 H, ArH), 7.55 (d, J =
8.6 Hz, 2 H, ArH), 7.68 (d, J = 1.8 Hz, 1 H, ArH), 7.84–7.87 (m,
2 H, ArH) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 108.9, 114.5
(d, JF,C = 21.5 Hz), 115.6 (CH), 120.3 (C), 126.2, 127.1, 128.5,
129.0, 129.3, 130.4 (d, JF,C = 8.0 Hz) (CH), 131.4 (C), 131.6 (CH),
135.1, 136.9 (d, JF,C = 3.4 Hz), 137.0, 142.7, 144.0, 157.8, 162.0
(C), 178.6 (CO) ppm. IR (KBr): ν = 2917 (w), 1631 (m), 1592 (w),
˜
1446 (m), 1371 (m), 1238 (w), 1145 (m), 1016 (m), 917 (w), 816 (s),
773 (s), 690 (s), 665 (m) cm–1. GC–MS (EI, 70 eV): m/z (%) = 402
(100) [M]+, 387 (34), 359 (03), 331 (4), 299 (4), 285 (07), 243 (09),
229 (12). HRMS (EI): calcd. for C29H22O2 [M+]: 402.16143; found
402.161442.
7,8-Bis(3,5-dimethylphenyl)-2-phenyl-4H-chromen-4-one
(11b):
Starting with 10 (259 mg, 0.5 mmol), K3PO4 (424 mg, 2.0 mmol),
[Pd(PPh3)4] (28.8 mg, 5 mol-%, 0.025 mmol), 3c (195 mg,
1.3 mmol), and 1,4-dioxane (5 mL), compound 11b was isolated as
(C), 162.3 (d, JF,C = 246.1 Hz, CF), 177.9 (CO) ppm. IR (KBr): ν
˜
= 3062 (m), 1639 (s), 1622 (w), 1606 (s), 1575, 1553 (m), 1503, a colorless crystalline (152 mg, 71%). Reaction temperature: 100 °C
1463, 1449, 1424 (m), 1374 (s), 1311 (w), 1288, 1272 (m), 1257 (w),
1215 (s), 1189 (m), 1157 (s), 1140, 1110, 1091 (s), 1065, 1034, 1021
for 4 h. M.p. 233–235 °C. 1H NMR (300 MHz, CDCl3): δ = 2.13
(s, 6 H, 2CH3), 2.19 (s, 6 H, 2CH3), 6.73 (br. s, 2 H, ArH), 6.77
Eur. J. Org. Chem. 2012, 1639–1652
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1649

P. Langer et al.
FULL PAPER
(br. s, 1 H), 6.80 (br. s, 2 H, ArH), 6.82 (s, 1 H, ArH), 6.87 (br. s,
JC,F = 20 Hz, CH), 132.7, 132.8 (CH), 135.6 (d, JC,F = 3.2 Hz, 1
C), 145.8, 153.7, 163.4 (C), 162.8 (d, JC,F = 247 Hz, CF), 162.9 (d,
1 H, ArH), 7.28–7.37 (m, 3 H, ArH), 7.43 (d, J = 8.2 Hz, 1 H,
ArH), 7.56–7.59 (m, 2 H, ArH), 8.24 (d, J = 8.2 Hz, 1 H, ArH) JC,F = 247 Hz, CF), 178.3 (C) ppm. 19F NMR (282 MHz, CDCl3):
ppm. 13C NMR (75 MHz, CDCl3): δ = 21.2, 21.3 (4CH3), 106.5
δ = –113.3 (ArF), –112.4 (ArF) ppm. IR (KBr): ν = 3062 (w), 1630
˜
(CH), 122.7 (C), 124.2, 126.2, 127.3, 127.7, 128.8, 128.9, 129.0 (s), 1602 (m), 1509 (s), 1449 (m), 1415 (m), 1373 (s), 1219 (s), 1159
(CH), 130.4 (C), 131.4 (CH), 131.7, 134.4, 137.0, 137.2, 139.8,
147.0, 153.8, 163.2 (C), 178.8 (CO) ppm. IR (KBr): ν = 2951 (w),
(s), 1093 (m), 1014 (m), 834 (s), 771 (s) cm–1. GC–MS (EI, 70 eV):
m/z (%) = 410 (100) [M]+, 382 (16), 351 (02), 307 (17), 280 (06),
˜
1709 (m), 1663 (m), 1629 (s), 1593 (m), 1435 (m), 1366 (m), 1332 262 (09), 251 (40), 225 (03). HRMS (EI): calcd. for C27H16 F2O2
(m), 1272 (m), 1190 (s), 1024 (m), 849 (w), 819 (m), 764 (m), 680
(m) cm–1. GC–MS (EI, 70 eV): m/z (%) = 430 (100) [M]+, 415 (73),
402 (07), 355 (05), 313 (09), 285 (06), 239 (07), 164 (17). HRMS
(EI): calcd. for C31H26O2 [M+]: 430.19273; found 430.19366.
[M+]: 410.11129; found 410.11046.
7,8-Bis(4-chlorophenyl)-2-phenyl-4H-chromen-4-one (11f): Starting
with 10 (259 mg, 0.5 mmol), K3PO4 (424 mg, 2.0 mmol), [Pd-
(PPh3)4] (28.8 mg, 5 mol-%, 0.025 mmol), 3j (203 mg, 1.3 mmol),
and 1,4-dioxane (5 mL), compound 11f was isolated as a light yel-
7,8-Bis(4-tert-butylphenyl)-2-phenyl-4H-chromen-4-one (11c): Start-
ing with 10 (259 mg, 0.5 mmol), K3PO4 (424 mg, 2.0 mmol),
[Pd(PPh3)4] (28.8 mg, 5 mol-%, 0.025 mmol), 3e (231 mg, M.p. 192–194 °C. H NMR (300 MHz, CDCl3): δ = 6.82 (s, 1 H),
low solid (160 mg, 72%). Reaction temperature: 100 °C for 4 h.
1
1.3 mmol), and 1,4-dioxane (5 mL), compound 11c was isolated as
7.01 (d, J = 8.8 Hz, 2 H, ArH) 7.10–7.18 (m, 5 H, ArH), 7.29 (d,
J = 8.6 Hz, 2 H, ArH) 7.37–7.43 (m, 3 H, ArH), 7.48–7.53 (m, 2
H, ArH), 8.23 (d, J = 8.2 Hz, 1 H, ArH) ppm. 13C NMR (62 MHz,
a white solid (143 mg, 59%). Reaction temperature: 100 °C for 4 h.
1
M.p. 162–164 °C. H NMR (300 MHz, CDCl3): δ = 1.20 (s, 9 H,
3CH3), 1.28 (s, 9 H, 3CH3), 6.80 (s, 1 H), 7.03–7.17 (m, 7 H, ArH), CDCl3): δ = 107.0 (CH), 123.2 (C), 125.2, 126.1, 127.1, 128.4,
7.23–7.30 (m, 4 H, ArH), 7.44–7.51 (m, 3 H, ArH), 8.18 (d, J = 128.5, 129.1, 131.0 (CH), 131.3 (C), 131.6, 132.4 (CH), 132.8,
8.1 Hz, 1 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 31.2, 133.8, 133.9, 137.9, 143.0, 145.4, 154.0, 163.4 (C), 178.2 (CO) ppm.
31.4 (CH3), 34.4, 34.6 (C), 106.6 (CH), 122.7 (C), 124.3, 124.7,
124.8, 126.2, 127.2, 128.8, 129.5 (CH), 130.4 (C), 130.8, 131.4
(CH), 131.6, 131.8, 136.8, 146.5, 150.3, 150.4, 154.0, 163.0, 178.7
IR (KBr): ν = 3055 (w), 1682 (w), 1587 (w), 1486 (m), 1248 (w),
˜
1088 (m), 1009 (m), 940 (m), 820 (m), 742 (s), 723 (s) cm–1. GC–
MS (EI, 70 eV): m/z (%) = 442 (100) [M]+, 407 (23), 378 (01), 339
(09), 305 (12), 249 (27), 213 (27), 172 (14). HRMS (EI): calcd. for
C27H1635Cl2O2 [M+]: 442.05219; found 442.05234.
(C) ppm. IR (KBr): ν = 3059 (w), 2958 (m), 1635 (s), 1372 (m),
˜
1258 (m), 1142 (w), 1090 (m), 1014 (m), 919 (w), 794 (s), 684 (s)
cm–1. GC–MS (EI, 70 eV): m/z (%) = 486 (95) [M]+, 471 (100), 455
(02), 429 (06), 415 (86), 387 (05), 373 (19), 339 (04), 313 (07), 228
(14), 200 (08), 177 (15). HRMS (EI): calcd. for C35H34O2 [M+]:
486.25533; found 486.25569.
7,8-Bis(4-ethylphenyl)-2-phenyl-4H-chromen-4-one (11g): Starting
with 10 (259 mg, 0.5 mmol), K3PO4 (424 mg, 2.0 mmol), [Pd-
(PPh3)4] (28.8 mg, 5 mol-%, 0.025 mmol), 3m (195 mg, 1.3 mmol),
and 1,4-dioxane (5 mL), compound 11g was isolated as a crystal-
line white solid (150 mg, 70%). Reaction temperature: 100 °C for
7,8-Bis(4-methoxyphenyl)-2-phenyl-4H-chromen-4-one (11d): Start-
ing with 10 (259 mg, 0.5 mmol), K3PO4 (424 mg, 2.0 mmol),
[Pd(PPh3)4] (28.8 mg, 5 mol-%, 0.025 mmol), 3f (197 mg,
1.3 mmol), and 1,4-dioxane (5 mL), compound 11d was isolated as
a white crystalline (147 mg, 68%). Reaction temperature: 100 °C
for 4 h. M.p. 172–174 °C. 1H NMR (300 MHz, CDCl3): δ = 3.71
(s, 3 H, OCH3), 3.77 (s, 3 H, OCH3), 6.70 (d, J = 8.8 Hz, 2 H,
ArH), 6.80 (s, 1 H), 6.82 (d, J = 8.8 Hz, 2 H, ArH), 7.02 (d, J =
8.8 Hz, 2 H, ArH), 7.10 (d, J = 8.8 Hz, 2 H, ArH), 7.32–7.36 (m,
1
4 h. M.p. 148–150 °C. H NMR (300 MHz, CDCl3): δ = 1.11 (t, J
= 7.8 Hz, 3 H, CH3), 1.18 (t, J = 7.4 Hz, 3 H, CH3), 2.50 (q, J =
7.4,15.3 Hz, 2 H, CH2), 2.59 (q, J = 7.4,15.3 Hz, 2 H, CH2), 6.76
(s, 1 H), 6.93–7.07 (m, 8 H, ArH), 7.22–7.35 (m, 3 H, ArH), 7.41
(d, J = 8.3 Hz, 1 H, ArH), 7.46–7.50 (m, 2 H, ArH), 8.16 (d, J =
8.3 Hz, 1 H, ArH) ppm. 13C NMR (62 MHz, CDCl3): δ = 15.3,
15.8 (CH3), 28.4, 28.7 (CH2), 106.6 (CH), 122.7 (C), 124.3, 126.2,
127.3, 127.4, 127.5, 128.8, 129.7 (CH), 130.3 (C), 131.1, 131.4
3 H, ArH), 7.42 (d, J = 8.2 Hz, 1 H, ArH), 7.54–7.58 (m, 2 H, (CH), 131.6, 132.0, 137.2, 143.3, 143.5, 146.6, 154.0, 163.1, 178.7
ArH) 8.17 (d, J = 8.2 Hz, 1 H, ArH) ppm. 13C NMR (75 MHz,
(C) ppm. IR (KBr): ν = 3064 (w), 2966 (w), 1643 (s), 1510 (m),
˜
CDCl3): δ = 55.2, 55.3 (OCH3), 106.7, 113.4, 113.5 (CH), 121.7, 1394 (m), 1370 (m), 1147 (m), 1016 (m), 919 (m), 823 (s), 772 (s),
123.3 (C), 124.3 (CH), 126.0 (C), 126.2, 127.3, 128.9 (CH), 130.4, 689 (s) cm–1. GC–MS (EI, 70 eV): m/z (%) = 430 (100) [M]+, 415
130.7 (C), 131.0, 131.4, 132.4 (CH), 145.5, 153.0, 157.8, 157.9, (09), 401 (51), 373 (03), 344 (02), 313 (09), 239 (09), 156 (03).
162.2, 177.7 (C) ppm. IR (KBr): ν = 2922 (w), 1635 (s), 1512 (m), HRMS (EI): calcd. for C31H26O2 [M+]: 430.19273; found
˜
1423 (m), 1372 (m), 1285 (m), 1243 (s), 1177 (m), 1112 (w), 1017 430.19288.
(m), 916 (w), 822 (s), 769 (s), 687 (s) cm–1. GC–MS (EI, 70 eV):
4-Oxo-2-phenyl-7-p-tolyl-4H-chromen-8-yl Trifluoromethanesulfon-
m/z (%) = 434 (100) [M]+, 403 (07), 331 (04), 281 (09), 253 (05),
ate (12a): Starting with 10 (156 mg, 0.30 mmol), K3PO4 (96 mg,
0.45 mmol), [Pd(PPh3)4] (17.3 mg, 5 mol-%, 0.015 mmol), 3a
(41 mg, 0.30 mmol), and 1,4-dioxane (3 mL), compound 12a was
207 (17), 189(11). HRMS (EI): calcd. for C27H14O6 [M+]:
434.07849; found 434.07952.
7,8-Bis(4-fluorophenyl)-2-phenyl-4H-chromen-4-one (11e): Starting
with 10 (259 mg, 0.5 mmol), K3PO4 (424 mg, 2.0 mmol), [Pd-
isolated as an amorphous white solid (105 mg, 76%). Reaction tem-
perature: 70 °C for 4 h. M.p. 156–158 °C. 1H NMR (300 MHz,
(PPh3)4] (28.8 mg, 5 mol-%, 0.025 mmol), 3i (182 mg, 1.3 mmol), CDCl3): δ = 2.37 (s, 3 H, CH3), 6.78 (s, 1 H), 7.26–7.30 (m, 3 H,
and 1,4-dioxane (5 mL), compound 11e was isolated as a white
ArH), 7.42–7.49 (m, 4 H, ArH), 7.74 (d, J = 8.3 Hz, 1 H, ArH),
7.84–7.88 (m, 2 H, ArH) 8.24 (d, J = 8.3 Hz, 1 H, ArH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 21.3 (CH3), 107.8, 116.4 (CH), 118.2
solid (127 mg, 62%). Reaction temperature: 100 °C for 4 h. M.p.
1
233–235 °C. H NMR (300 MHz, CDCl3): δ = 6.84 (s, 1 H), 6.89
(d, J = 8.7 Hz, 2 H, ArH), 7.01–7.07 (m, 4 H, ArH), 7.12–7.18 (m, (q, JC,F = 320 Hz, CF3), 124.7 (C), 126.4, 126.5, 128.9, 129.2, 129.8
2 H, ArH), 7.34 (d, J = 8.1 Hz, 2 H, ArH), 7.42 (d, J = 8.2 Hz, 2
(CH), 130.6 (C), 131.7 (CH), 131.8, 132.7, 135.0, 145.1, 149.6,
H, ArH) 7.50–7.53 (m, 2 H, ArH), 8.22 (d, J = 8.2 Hz, 1 H, ArH) 164.0, 176.8 (C) ppm. 19F NMR (282 MHz, CDCl3): δ = –74.3
ppm. 13C NMR (62 MHz, CDCl3): δ = 107.0 (CH), 115.2 (d, JC,F ppm. IR (KBr): ν = 2917 (m), 1623 (s), 1389 (m), 1248 (m), 1167
= 21.3 Hz, CH), 123.1 (C), 125.0, 126.1, 127.2, 129.0, (CH), 129.3
(C), 130.4 (d, JC,F = 3.5 Hz, 1 C), 131.3 (CH), 131.4 (C), 131.5 (d,
˜
(s), 1019 (m), 811 (m), 767 (m), 682 (s) cm–1. GC–MS (EI, 70 eV):
m/z (%) = 460 (40) [M]+, 418 (03), 380 (02), 355 (14), 328 (100),
1650
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1639–1652

Efficient Synthesis of Arylated Flavones
300 (04), 262 (02), 226 (73), 211 (22), 198 (10). HRMS (EI): calcd.
for C23H15F3O5S [M+]: 460.06230; found 460.06350.
3n (44 mg, 0.30 mmol), and 1,4-dioxane (3 mL), compound 12e was
isolated as a amorphous white solid (105 mg, 74%). Reaction tem-
perature: 70 °C for 4 h. M.p. 113–115 °C. 1H NMR (300 MHz,
CDCl3): δ = 5.30 (d, J = 11.6 Hz, 1 H), 5.80 (d, J = 16.9 Hz, 1 H),
6.71 (dd, J = 10.8, 17.6 Hz, 1 H), 6.84 (s, 1 H), 7.42–7.50 (m, 8 H,
ArH), 7.94–7.97 (m, 2 H, ArH), 8.19 (d, J = 8.4 Hz, 1 H, ArH)
ppm. 13C NMR (62 MHz, CDCl3): δ = 115.4 (CH2), 108.2 (CH),
117.8 (q, JCF = 319 Hz, CF3), 124.4 (C), 125.2, 126.6, 126.7, 127.2,
129.1, 129.5 (CH), 130.8 (C), 132.1 (CH), 133.6, 135.0 (C), 136.0
(CH), 138.6, 140.2, 149.5, 163.9, 176.7 (C) ppm. 19F NMR
4-Oxo-2-phenyl-7-[4-(trifluoromethyl)phenyl]-4H-chromen-8-yl Tri-
fluoromethanesulfonate (12b): Starting with 10 (156 mg,
0.30 mmol), K3PO4 (96 mg, 0.45 mmol), [Pd(PPh3)4] (17.3 mg,
5 mol-%, 0.015 mmol), 3h (57 mg, 0.30 mmol), and 1,4-dioxane
(3 mL), compound 12b was isolated as a white solid (107 mg, 69%).
Reaction temperature: 70 °C for 4 h. M.p. 176–178 °C. 1H NMR
(300 MHz, CDCl3): δ = 6.85 (s, 1 H), 7.42 (d, J = 8.3 Hz, 2 H,
ArH), 7.49–7.51 (m, 2 H, ArH), 7.60 (d, J = 8.0 Hz, 2 H, ArH),
7.72 (d, J = 8.2 Hz, 2 H, ArH), 7.94–7.97 (m, 2 H, ArH) 8.24 (d,
J = 8.3 Hz, 1 H, ArH) ppm. 13C NMR (62 MHz, CDCl3): δ =
108.3, (CH), 118.3 (q, JC,F = 319 Hz, CF3), 124.2 (q, JC,F = 280 Hz,
CF3), 125.1 (C), 125.5 (q, JC,F = 3.6 Hz, CH), 125.8, 126.7, 127.0,
129.2, 129.7 (CH), 130.1 (q, JC,F = 34.2 Hz, 1 C), 130.6, 132.0 (C),
132.3 (CH), 139.0, 145.3, 149.2, 164.1, 176.4 (C) ppm. 19F NMR
(282 MHz, CDCl ): δ = –74.2 ppm. IR (KBr): ν = 2923 (w), 1645
˜
3
(s), 1484 (w), 1423 (s), 1354 (s), 1216 (s), 1128 (s), 1017 (m), 963
(m), 803 (m), 763 (m), 681 (m) cm–1. GC–MS (EI, 70 eV): m/z (%)
= 472 (16) [M]+, 339 (100), 311 (01), 383 (11), 237 (07), 210 (03),
181 (07). HRMS (EI): calcd. for C24H15F3O5S [M+]: 472.05868;
found 472.05988.
7-(4-Chlorophenyl)-8-(4-methoxyphenyl)-2-phenyl-4H-chromen-4-
one (13a): Starting with 12c (101 mg, 0.22 mmol), K3PO4 (93 mg,
0.44 mmol), [Pd(PPh3)4] (12.7 mg, 5 mol-%, 0.011), 4-methoxy-
phenylboronic acid (44 mg, 0.29 mmol), and 1,4-dioxane (3 mL),
compound 13a was isolated as a yellow solid (60 mg, 73%). Reac-
tion temperature: 100 °C for 4 h. M.p. 152–154 °C. 1H NMR
(300 MHz, CDCl3): δ = 3.81 (s, 3 H, OCH3), 6.82 (s, 1 H), 6.96 (d,
J = 8.8 Hz, 2 H, ArH), 7.01–7.10 (m, 3 H, ArH), 7.40 (d, J =
8.5 Hz, 5 H, ArH), 7.47–7.49 (m, 2 H, ArH), 7.93–7.97 (m, 2 H,
ArH), 8.16 (d, J = 8.3 Hz, 1 H, ArH) ppm. 13C NMR (62 MHz,
CDCl3): δ = 55.4 (OCH3), 108.1, 114.3 (CH), 124.0 (C), 125.0,
126.2, 126.7, 127.2, 128.3, 129.1 (CH), 129.5 (C), 130.6 (CH),
130.8, 131.3 (C), 132.1 (CH), 135.0, 140.3, 145.5, 149.1, 160.6,
(282 MHz, CDCl ): δ = –74.2, –62.8 ppm. IR (KBr): ν = 2923 (w),
˜
3
1649 (m), 1421 (m), 1326 (m), 1205 (m), 1115 (s), 1070 (m), 1017
(m), 963 (m), 829 (m), 802 (s), 763 (m), 682 (m) cm–1. GC–MS (EI,
70 eV): m/z (%) = 514 (19) [M]+, 381 (100), 325 (02), 279 (08), 251
(08), 223 (13), 183 (06). HRMS (EI): calcd. for C23H12F6O5S [M+]:
514.03041; found 514.03132.
7-(4-Chlorophenyl)-4-oxo-2-phenyl-4H-chromen-8-yl Trifluorometh-
anesulfonate (12c): Starting with 10 (156 mg, 0.30 mmol), K3PO4
(96 mg, 0.45 mmol), [Pd(PPh3)4] (17.3 mg, 5 mol-%, 0.015 mmol),
3j (47 mg, 0.30 mmol), and 1,4-dioxane (3 mL), compound 12c was
isolated as a light-yellow amorphous solid (95 mg, 66%). Reaction
temperature: 70 °C for 4 h. M.p. 143–145 °C. 1H NMR (300 MHz,
CDCl3): δ = 6.84 (s, 1 H), 7.39–7.43 (m, 5 H, ArH), 7.48–7.52 (m,
3 H, ArH), 7.93–7.96 (m, 2 H, ArH), 8.20 (d, J = 8.3 Hz, 1 H,
ArH) ppm. 13C NMR (62 MHz, CDCl3): δ = 108.2 (CH), 118.2 (q,
JC,F = 321 Hz, CF3), 124.7 (C), 125.4, 126.7, 127.0, 129.1, 129.2,
130.6 (CH), 130.7 (C), 132.2 (CH), 132.8, 135.8, 139.2, 145.5,
149.0, 164.0, 176.5 (C) ppm. 19F NMR (282 MHz, CDCl3): δ =
163.8, 176.7 ppm. IR (KBr): ν = 3066 (w), 1649 (s), 1519 (m), 1438
˜
(s), 1357 (m), 1246 (m), 1216 (s), 1134 (m), 963 (m), 802 (s), 684
(m) cm–1. GC–MS (EI, 70 eV): m/z (%) = 438 (100) [M]+, 407 (05),
360 (02), 335 (05), 301 (03), 249 (03), 202 (16). HRMS (EI): calcd.
for C28H1935ClO3 [M+]: 438.10230; found 438.10250.
8-(4-Ethylphenyl)-2-phenyl-7-(p-tolyl)-4H-chromen-4-one
(13b):
–74.1 ppm. IR (KBr): ν = 2928 (w), 1656 (s), 1426 (m), 1359 (m),
˜
Starting with 12a (101 mg, 0.22 mmol), K3PO4 (93 mg, 0.44 mmol),
[Pd(PPh3)4] (12.7 mg, 5 mol-%, 0.011 mmol), 3m (44 mg,
0.29 mmol), and 1,4-dioxane (3 mL), compound 13b was isolated
as a yellow solid (60 mg, 66%). Reaction temperature: 100 °C for
1212 (s), 1134 (s), 1090 (m), 1015 (m), 966 (m), 880 (w), 803 (m)
cm–1. GC–MS (EI, 70 eV): m/z (%) = 480 (16) [M]+ 347 (100), 332
(02), 284 (05), 345 (08), 210 (08), 189 (10). HRMS (EI): calcd. for
C22H1235ClF3O5S [M+]: 480.00406; found 480.00345.
1
4 h. M.p. 197–199 °C. H NMR (500 MHz, CDCl3): δ = 1.20 (t, J
7-(4-Ethylphenyl)-4-oxo-2-phenyl-4H-chromen-8-yl Trifluorometh-
anesulfonate (12d): Starting with 10 (156 mg, 0.30 mmol), K3PO4
(96 mg, 0.45 mmol), [Pd(PPh3)4] (17.3 mg, 5 mol-%, 0.015 mmol),
3m (45 mg, 0.30 mmol), and 1,4-dioxane (3 mL), compound 12d
was isolated as a white solid (102 mg, 72%). Reaction temperature:
= 7.9 Hz, 3 H, CH3), 2.23 (s, 3 H, CH3), 2.62 (q, J = 7.5 Hz, 2 H,
CH2), 6.79 (s, 1 H), 6.95–7.01 (m, 4 H, ArH), 7.07–7.12 (m, 4 H,
ArH), 7.26–7.38 (m, 3 H, ArH), 7.43 (dd, J = 3.4, 8.3 Hz, 1 H,
ArH), 7.50–7.54 (m, 2 H, ArH), 8.18 (d, J = 8.3 Hz, 1 H, ArH)
ppm. 13C NMR (125.75 MHz, CDCl3): δ = 15.8, 21.1 (CH3), 28.7
(CH2), 122.8 (C), 124.3, 126.2, 127.4, 128.6, 128.7, 128.8, 128.9,
129.6, 131.0, 131.3 (CH), 131.6, 131.7, 132.0, 137.0, 143.5, 146.5,
1
70 °C for 4 h. M.p. 167–168 °C. H NMR (500 MHz, CDCl3): δ =
1.22 (t, J = 7.7 Hz, 3 H, CH3), 2.66 (q, J = 7.5 Hz, 2 H, CH2), 6.83
(s, 1 H), 7.27 (d, J = 8.0 Hz, 2 H, ArH), 7.38 (d, J = 8.3 Hz, 2 H,
ArH), 7.44 (d, J = 8.3 Hz, 1 H, ArH), 7.46–7.50 (m, 3 H, ArH),
7.95–7.97 (m, 2 H, ArH), 8.18 (d, J = 8.3 Hz, 1 H, ArH) ppm. 13C
NMR (125.76 MHz, CDCl3): δ = 15.5 (CH3), 28.7 (CH2), 108.2
(CH), 118.0 (q, JF,C = 320 Hz, CF3), 124.2 (C), 125.4, 126.7, 127.4,
128.3, 129.1, 129.2 (CH), 130.8, 131.6 (C), 132.1 (CH), 135.1,
140.7, 145.9, 149.0, 163.8 (C), 176.7 (CO) ppm. 19F NMR
146.7, 153.9, 136.1, 178.7 (C) ppm. IR (KBr): ν = 2962 (s), 2923
˜
(s), 1644 (s), 1597 (w), 1371 (m), 1202 (w), 1096 (w), 1016 (w), 815
(m), 771 (m), 688 (w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 416
(100) [M]+, 402 (16), 387 (49), 313 (06), 285 (14), 271 (05), 253 (06),
239 (09). HRMS (EI): calcd. for C30H24O2 [M+]: 416.17783; found
416.17762.
(282 MHz, CDCl ): δ = –74.3 ppm. IR (KBr): ν = 2916 (w), 2850
˜
3
Acknowledgments
(w), 1622 (m), 1568 (m), 1447 (m), 1386 (s), 1271 (m), 1164 (s),
1041 (m), 906 (w), 811 (s), 767 (s), 681 (s), 634 (w) cm–1. GC–MS
(EI, 70 eV): m/z (%) = 474 (40) [M]+, 410 (28), 395 (18), 366 (03),
341 (100), 326 (08), 313 (20), 281 (04). HRMS (EI): calcd. for
C24H17F3O5S [M+]: 474.07471; found 474.07492.
Financial support by the Deutscher Akademischer Austauschdienst
(DAAD) (scholarship to N. E.) and by the State of Pakistan (HEC
scholarship to I. M.) is gratefully acknowledged. S. R. would like
to acknowledge gratefully the University of Rostock (scholarship
of the interdisciplinary faculty of the University of Rostock/De-
4-Oxo-2-phenyl-7-(4-vinylphenyl)-4H-chromen-8-yl Trifluorometh-
anesulfonate (12e): Starting with 10 (156 mg, 0.30 mmol), K3PO4 partment LLM) and the State of Mecklenburg-Vorpommern for
(96 mg, 0.45 mmol), [Pd(PPh3)4] (17.3 mg, 5 mol-%, 0.015 mmol), financial support.
Eur. J. Org. Chem. 2012, 1639–1652
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1651

P. Langer et al.
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Received: October 12, 2011
Published Online: January 30, 2012
1652
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1639–1652