Site-selective synthesis of arylated indenones by Suzuki-Miyaura cross-coupling reactions of 2,3,5-tribromoinden-1-one

Article abstract of DOI:10.1002/ejoc.201100313

The first transition-metal-catalyzed cross-coupling reactions of 2,3,5-tribromo-1H-inden-1-one are reported. The Suzuki-Miyaura reaction of 2,3,5-tribromo-1H-inden-1-one with three equivalents of arylboronic acid gave 2,3,5-triaryl-1H-inden-1-ones. The re

Full text of DOI:10.1002/ejoc.201100313

FULL PAPER
DOI: 10.1002/ejoc.201100313
Site-Selective Synthesis of Arylated Indenones by Suzuki–Miyaura Cross-
Coupling Reactions of 2,3,5-Tribromoinden-1-one
Dhafer Saber Zinad,[a] Munawar Hussain,[a] Alexander Villinger,[a] and Peter Langer*[a,b]
Keywords: Homogeneous catalysis / Palladium / Cross-coupling / Regioselectivity / Synthetic methods
The first transition-metal-catalyzed cross-coupling reactions
of 2,3,5-tribromo-1H-inden-1-one are reported. The Suzuki–
Miyaura reaction of 2,3,5-tribromo-1H-inden-1-one with
three equivalents of arylboronic acid gave 2,3,5-triaryl-1H-
inden-1-ones. The reaction with one and two equivalents of
arylboronic acid gave 2,5-dibromo-3-aryl-1H-inden-1-ones
and 5-bromo-2,3-diaryl-1H-inden-1-ones, respectively, with
very good site-selectivity. The one-pot reaction of 2,3,5-tri-
bromo-1H-inden-1-one with one equivalent of two different
arylboronic acids afforded 5-bromo-2,3-diaryl-1H-inden-1-
ones containing two different terminal aryl groups. Other
one-pot reactions allowed the synthesis of 2,3,5-triaryl-1H-
inden-1-ones containing different aryl groups.
Arylated indenones represent a pharmacologically im- closely related to 2,3-dibromoindenones, have been pre-
portant molecular entity.[1] For example, 2,3-diarylind- viously reported by Bellina and co-workers.[9] In general,
enones have been studied as ligands for the estrogen recep- site-selective palladium(0)-catalyzed cross-coupling reac-
tor,[1a] and 3-arylindenone-2-carboxylic acid derivatives tions of polyhalogenated heterocycles are of considerable
have been studied as selective inhibitors of fibroblast current interest in organic chemistry because they allow fac-
growth factor receptor-1 tyrosine kinase.[1d] Indenones also ile assembly of complex heterocycles in only one step.[10–12]
occur in several biologically relevant natural products, such Recently, we have reported site-selective Suzuki–Miyaura
as euplectin, which contains both a benzofuran and an in- (SM)[13] reactions of 2,3-dibromoinden-1-one.[8] Herein, we
den-1-one substructure.[2] Other examples include neo-lig- report, to the best of our knowledge, the first site-selective
nans isolated from the fruits of Virola sebifera.[3] Pauciflo- SM reactions of 2,3,5-tribromoinden-1-one. These reactions
rol F is a 2,3-diarylindanone that has been prepared by pal- provide a convenient approach to various arylated inden-1-
ladium-catalyzed Larock cyclization, hydrogenation, and ones. Interestingly, our starting material, 2,3,5-tribromo-
subsequent epimerization.[4] 2,3-Diarylindenones are avail- inden-1-one, represents a new compound that has, to the
able by classical methods that include, for example, intra- best of our knowledge, not been synthesized or studied be-
molecular Friedel–Crafts acylations,[5a] reactions of phthal- fore.
ides or 1H-indene-1,3(2H)-diones with Grignard rea-
gents,[5b,5c] and synthetic transformations of dibenzo-
ylmethane,[5d] benzophenone derivatives,[5e] or diphenyl
acetylene.[5f] Transition-metal-catalyzed syntheses of 2,3-di-
arylinden-1-ones include the Larock cyclization[4] and re-
lated processes.[6]
Results and Discussion
2,3,5-Tribromoinden-1-one (2) was prepared in 62%
yield by reaction of commercially available 5-bromoindan-
1-one with N-bromosuccinimide (NBS) in the presence of
2,2Ј-azobis(isobutyronitrile) (AIBN) (Scheme 1). Unfortu-
nately, use of toxic benzene is required in this reaction. Tol-
uene cannot be used, due to competing benzylic bromina-
tion. Whereas 2,3-dibromoinden-1-one is known,[14] the
synthesis of 2 has, to the best of our knowledge, not been
previously reported.
Reactions of functionalized indenones, such as hydrogen-
ations, reactions of the carbonyl group, and conjugate ad-
ditions, have been widely studied. We were interested in pal-
ladium-catalyzed cross-coupling reactions of halogenated
inden-1-ones. Whereas reactions of 2,3-dibromo-1H-inden-
1-one with amines, Grignard reagents, and CH-acidic com-
pounds were reported nearly a century ago,[7] transition-
metal-catalyzed reactions of this molecule were unknown
until our recent report[8] in this field. Site-selective palla-
dium-catalyzed reactions of dibromofuranones, which are
[a] Institut für Chemie, Universität Rostock,
Albert Einstein Str. 3a, 18059 Rostock, Germany
[b] Leibniz-Institut für Katalyse an der Universität Rostock e.V.,
Albert Einstein Str. 29a, 18059 Rostock, Germany
Scheme 1. Synthesis of 2. Reagents and conditions: (i) 1 (1.0 equiv.),
NBS (3.5 equiv.), AIBN (10 mol-%), benzene, reflux, 7 h.
4212
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4212–4221

Site-Selective Synthesis of Arylated Indenones
The SM reaction of 2,3,5-tribromoinden-1-one (2) with Table 2. Synthesis of 3-aryl-2,5-dibromoindenones 5a–g.
three equivalents of arylboronic acids 3a–g afforded the
2,3,5-triaryl-1H-inden-1-ones 4a–g in 76–88% yields
(Scheme 2, Table 1). The best yields were obtained using
3.3 equiv. of arylboronic acid, [Pd(PPh3)4] (5 mol-%) as the
catalyst, and K2CO3 (2 m aqueous solution) as the base
(1,4-dioxane, 70 °C, 6 h). Compounds 4 could be prepared
in equally good yields using [Pd(PPh3)2Cl2] as the catalyst.
Similar conditions were used for the SM reactions of 2,3-
dibromoinden-1-one.[8] The reactions were successful for
both electron-rich and electron-poor arylboronic acids.
3
5
Ar
Yield of 5 [%][a]
a
c
e
g
h
i
a
b
c
d
e
f
C6H5
4-tBuC6H4
3-ClC6H4
3-(CF3)C6H4
4-(CF3O)C6H4
4-MeC6H4
4-(MeO)C6H4
83
86
82[b]
80
78
86
92
j
g
[a] Isolated product. [b] [Pd(PPh3)2Cl2] was used.
which showed that the aryl group and the indenone moiety
are twisted out of plane.
Scheme 2. Synthesis of 4a–g. Reagents and conditions: (i) ArB-
(OH)2 3a–e (3.3 equiv.), [Pd(PPh3)4] (5 mol-%), K2CO3 (2 m, 1 mL),
dioxane, 70 °C, 6 h.
Table 1. Synthesis of 2,3,5-triaryl-indenone 4a–g.
3,4
Ar
Yield 4 [%][a]
a
b
c
d
e
f
Ph
83
88
85
76
79
81
78
4-EtC6H4
4-tBuC6H4
3-(MeO)C6H4
3-ClC6H4
4-FC6H4
Figure 1. Molecular structure of 5d.
g
3-(CF3)C6H4
The SM reaction of 2 with arylboronic acids 3b–d, 3f,
3g, 3j, and 3k (2.0 equiv.) afforded the 2,3-diaryl-5-bromo-
1H-inden-1-ones 6a–g in 75–88% yields with very good
site-selectivity (Scheme 4, Table 3). The reactions were
again successful for both electron-rich and electron-poor
arylboronic acids. The first arylation occurred at positions
2 and 3, while the 5-position remained unaffected. The reac-
tions were best carried out at 60 °C using exactly 2.0 equiv.
of boronic acid and 5 mol-% catalyst.
[a] Isolated product.
The SM reaction of 2 with arylboronic acids 3a, 3c, 3e,
and 3g–j (1.0 equiv.) afforded the 3-aryl-2,5-dibromo-1H-
inden-1-ones 5a–g in 78–92% yields with very good site-
selectivity (Scheme 3, Table 2). The first aryl substitution
occurred at the 3-position. The yields dropped when more
than exactly 1.0 equiv. of the boronic acid was used. The
reactions were carried out using [Pd(PPh3)4] (3 mol-%) as
the catalyst, except in case of 5c, for which [Pd(PPh3)2Cl2]
was employed. It proved to be important to carry out the
reactions at 45 °C instead of 70 °C. Significant amounts of
side-products, derived from multifold coupling, were
formed when the temperature was too high. The reactions
could be successfully carried out with both electron-rich
and electron-poor arylboronic acids.
Scheme 4. Synthesis of 6a–g. Reagents and conditions: (i) ArB-
(OH)2 3b–d, 3f, 3g, 3j, and 3k (2.0 equiv.), [Pd(PPh3)4] (5 mol-%),
K3PO4 (3.0 equiv.), dioxane, 60 °C, 6 h.
Table 3. Synthesis of 5-bromo-2,3-diaryl-indenone 6a–g.
3
6
Ar
Yield 6 [%][a]
b
c
d
f
g
j
k
a
b
c
d
e
f
4-EtC6H4
88
83
75
78
77
85
87
Scheme 3. Synthesis of 5a–g. Reagents and conditions: (i) ArB-
(OH)2 3a, 3c, 3e, or 3g–j (1.0 equiv.), [Pd(PPh3)4] or [Pd(PPh3)2Cl2]
(3 mol-%), K3PO4 (1.5 equiv.), dioxane, 45 °C, 9 h.
4-tBuC6H4
3-(MeO)C6H4
4-FC6H4
3-(CF3)C6H4
4-(MeO)C6H4
4-ClC6H4
The structure of all products were confirmed by spectro-
scopic methods. The structure of 5d was independently con-
g
firmed by X-ray crystal structure analysis (Figure 1),[15] [a] Isolated product.
Eur. J. Org. Chem. 2011, 4212–4221
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4213

P. Langer et al.
FULL PAPER
The structure of 6g was independently confirmed by X-
ray crystal structure analysis (Figure 2),[15] which showed
that both aryl groups and the indenone moiety are twisted
out of plane.
Scheme 6. Synthesis of 8a–c. Reagents and conditions: (i) (1) Ar1-
B(OH)2 (2.0 equiv.), [Pd(PPh3)4] (5 mol-%), K3PO4 (4.5 equiv.), di-
oxane, 45 °C, 9 h; (2) Ar2B(OH)2 (2.2 equiv.), 70 °C, 6 h; (ii) Ar2-
B(OH)2 (2.2 equiv.), [Pd(PPh3)4] (3 mol-%), K2CO3 (2 m, 1 mL), di-
oxane, 70 °C, 6 h.
Table 5. Synthesis of 8a–c.
8
Ar1
Ar2
Yield 8 [%][a]
a
b
c
4-(MeO)C6H4
4-ClC6H4
4-ClC6H4
4-tBuC6H4
4-EtC6H4
4-(MeO)C6H4
78[b]
81[c]
84[c]
[a] Isolated product. [b] Prepared from 5g. [c] Prepared from 2.
Figure 2. Molecular structure of 6g.
The reaction of 6d with 1.1 equiv. of 3-methoxyphen-
ylboronic acid afforded the 2,3,5-triarylinden-1-one 9a in
88% yield (Scheme 7, Table 6). The one-pot reaction of 2
with 2.2 equiv. of 4-(trifluoromethyl)phenylboronic acid
and with 1.1 equiv. of 4-methoxyphenylboronic acid (se-
quential addition) afforded 2,3,5-triarylinden-1-one 9b in
86% yield. During the optimization of the one-pot reaction,
the temperature (60 °C for the first step and 70 °C for the
second step) and the stoichiometry (2.0 equiv. for the first
step and 1.1 equiv. for the second step) proved to be impor-
tant. The structure of 9b was independently confirmed by
X-ray crystal structure analysis (Figure 3).[15]
The one-pot reaction of 2 with two different arylboronic
acids, which were sequentially added, afforded the unsym-
metrical 2,3-diaryl-5-bromo-1H-inden-1-ones 7a–c, con-
taining two different aryl groups (Scheme 5, Table 4). To
achieve good site-selectivity in favor of position 3 of the
substrate, it proved to be important that the first step was
carried out at 45 °C (9 h) and the second step at 60 °C (6 h).
Scheme 5. One-pot synthesis of 7a–c. Reagents and conditions: (i)
(1) Ar1B(OH)2 (1.0 equiv.), [Pd(PPh3)4] (5 mol-%), K3PO4
(4.5 equiv.), dioxane, 45 °C, 9 h; (2) Ar2B(OH)2 (1.0 equiv.), 60 °C,
6 h.
Table 4. Synthesis of 7a–c.
7
Ar1
Ar2
Yield 8 [%][a]
Scheme 7. Synthesis of 9a and 9b. Reagents and conditions: (i) (1)
Ar1B(OH)2 (2.0 equiv.), [Pd(PPh3)4] (5 mol-%), K3PO4 (4.5 equiv.),
dioxane, 60 °C, 6 h; (2) Ar2B(OH)2 (1.1 equiv.), 70 °C, 6 h; (ii) 6d
(1.0 equiv.), Ar2B(OH)2 (1.1 equiv.), [Pd(PPh3)4] (3 mol-%), K2CO3
(2 m, 1 mL), dioxane, 70 °C, 6 h.
a
b
c
4-Et-C6H4
4-Cl-C6H4
4-Cl-C6H4
4-(MeO)C6H4
4-Et-C6H4
4-(MeO)C6H4
80
79
82
[a] Isolated product.
Table 6. Synthesis of 9a and 9b.
The reaction of 5g with 2.2 equiv. of 4-(tert-butyl)phen-
ylboronic acid afforded the 2,3,5-triarylinden-1-one 8a in
78% yield (Scheme 6, Table 5). The one-pot reaction of 2
with one equivalent of 4-chlorophenylboronic acid and with
2.2 equiv. of a different arylboronic acid (sequential ad-
dition) afforded the 2,3,5-triarylinden-1-ones 8b and 8c,
respectively, in good yields (Scheme 6, Table 5). During the
9
Ar1
Ar2
Yield 9 [%][a]
a
b
4-F-C6H4
4-CF3-C6H4
3-(MeO)C6H4
4-(MeO)C6H4
88[b]
86[c]
[a] Isolated product. [b] Prepared from 6d. [c] Prepared from 2.
The development of a site-selective, one-pot process that
optimization of the one-pot reaction, the temperature and can be used to sequentially introduce three different aryl
stoichiometry were again found to play an important role. groups in one step, failed. However, the synthesis of such
4214
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4212–4221

Site-Selective Synthesis of Arylated Indenones
vides a convenient and site-selective approach to various
arylated inden-1-ones in good yields. The order of the selec-
tivity is C-3Ͼ C-2Ͼ C-5. Position C-3 is the most electron-
deficient, and the first aryl substitution takes place there.
The selectivity in favor of position C-2 can be explained by
chelation of the catalyst to the neighboring carbonyl group.
Experimental Section
2,3,5-Tribromo-1H-inden-1-one (2): A round-bottomed flask was
equipped with a condenser, and a suspension of 5-bromo-indanone
1 (1.50 g, 7.14 mmol), N-bromosuccinamide (4.43 g, 24.89 mmol),
and AIBN (0.12 g, 10-mol-%) in benzene (35 mL) was heated to
reflux under argon for 7 h and then cooled to 20 °C. The reaction
mixture was quenched with triethylamine (1 mL) and benzene was
evaporated in vacuo. The reaction mixture was diluted with water
and extracted with CH2Cl2 (3ϫ25 mL), and the combined organic
layers were dried (Na2SO4), filtered, and the filtrate was concen-
trated in vacuo. The residue was purified by flash chromatography
(silica gel, heptanes). Compound 2 was isolated as a light-yellow
crystalline solid (1.62 g, 62%); m.p. 160–161 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.26 (d, J = 7.7 Hz, 1 H, ArH), 7.28 (d, J
= 1.5 Hz, 1 H, ArH), 7.41 (dd, J = 1.6, 7.7 Hz, 1 H, ArH) ppm.
13C NMR (75.5 MHz, CDCl3): δ = 123.8 (C), 124.0, 124.7 (CH),
127.6, 129.4 (C), 132.6 (CH), 144.1, 144.6 (C), 185.4 (CO) ppm. IR
Figure 3. Molecular structure of 9b.
molecules can be realized by reaction of 2,3-diaryl-5-bro-
moinden-1-ones 7a–c with arylboronic acids.
The order of reactivity of the three different positions of
2,3,5-tribromoinden-1-one is C-3Ͼ C-2Ͼ C-5 (Figure 4).
The site-selectivity can be explained by the fact that posi-
tion 3 is considerably more electron-deficient than positions
2 and 5. The second aryl substitution occurs at position C-
2, which is sterically more hindered than position 5, and
electronically less deficient. This result is surprising because
it does not follow the rule suggested by Handy and Zhang
for the prediction of the site-selectivity of palladium-cata-
lyzed reactions of polyhalogenated substrates.[11] To predict
the selectivity, the 1H NMR spectra of the non-halogenated
parent compounds were studied, which reflects the elec-
tronic situation of the different positions. According to the
rule of the authors, the first arylation should occur at the
position that has the higher chemical shift value of the re-
spective proton. In case of the 1H NMR spectrum of inden-
1-one, which is the parent molecule of 2,3,5-tribromoinden-
1-one (2), the chemical shift of the 5-H proton is signifi-
cantly shifted downfield with regard to the 2-H proton,
which is the most upfield-resonating proton of the mole-
cule. In contrast, proton 3-H resonates most downfield of
all the protons of inden-1-one. Therefore, the rule of Handy
and Zhang correctly predicts the selectivity in favor of posi-
tion 3, but not the selectivity favoring position 2 (with re-
spect to position 5). The selectivity in favor of position 2
versus position 5 might be explained by chelation of the
catalyst to the carbonyl oxygen atom, which may enhance
the rate of the oxidative addition of palladium, favoring
arylation at C-2.
(KBr): ν = 3416, 3084, 3015, 2922, 2850, 2674 (w), 1722, 1594,
˜
1584, 1540, 1438, 1401, 1337 (m), 1260, 1218 (w), 1200 (s), 1094,
1085, 1054, 1041, 933, 876 (m), 831 (s), 811, 764, 691, 680, 618,
593, 577 (m) cm–1. GC-MS (EI, 70 eV): m/z (%) = 370 (13) [M,
81Br, 81Br, 81Br]+, 368 (41) [M, 79Br, 81Br, 81Br]+, 366 (42) [M, 79Br,
79Br, 81Br]+, 287 (100), 259 (23), 178 (17). HRMS (EI, 70 eV): calcd.
for C9H3Br3O [M, 81Br, 81Br, 81Br]+: 369.76671; found 369.76599;
calcd. for C9H3Br3O [M, 79Br, 81Br, 81Br]+: 367.76876; found
367.76801; calcd. for C9H3Br3O [M, 79Br, 79Br, 81Br]+: 365.77081;
found 365.77001, calcd. for C9H3Br3O [M, 79Br, 79Br, 79Br]+:
363.77285; found 363.77181.
Suzuki Cross-Coupling Reactions; General Procedure A: The reac-
tion was carried out in a pressure tube. To a suspension of the
brominated indenone, [Pd(PPh3)4] or [Pd(PPh3)2Cl2] (3–5 mol-%),
and arylboronic acid (1.0–1.1 per cross coupling) in dioxane (3–
5 mL), was added either K3PO4 (1.5 equiv. per cross coupling) or
an aqueous solution of K2CO3 (2 m, 1 mL). The mixture was
heated at the indicated temperature (45–70 °C) under an argon at-
mosphere for the indicated period of time (5–9 h). The reaction
mixture was diluted with water 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; EtOAc/heptanes).
2,3,5-Triphenyl-1H-inden-1-one (4a): Starting with
2 (80 mg,
0.20 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane (3 mL), K2CO3
(2 m, 1 mL), and phenylboronic acid (81 mg, 0.66 mmol), 4a was
isolated as a brownish-yellow solid (60 mg, 83%). Reaction tem-
perature: 70 °C for 6 h; m.p. 182–183 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.17–7.21 (m, 4 H, ArH), 7.26–7.42 (m, 11 H, ArH),
7.46–7.49 (m, 2 H, ArH), 7.57 (d, J = 7.4 Hz, 1 H, ArH) ppm. 13C
NMR (62.9 MHz, CDCl3): δ = 120.5, 123.4, 127.2, 127.5, 127.8,
128.1, 128.3, 128.5, 128.9, 129.3 (CH), 129.5 (C), 130.0 (CH),
130.8, 132.7, 132.2, 140.4, 146.1, 146.8, 154.8 (C), 196.8 (CO) ppm.
Figure 4. Possible explanation for the site-selectivity.
In conclusion, we have reported the site-selective Suzuki–
IR (KBr): ν = 3054, 3030, 2955, 2921, 2849 (w), 1704, 1597 (s),
˜
Miyaura reactions of 2,3,5-tribromo-1H-inden-1-one,
1573, 1467, 1442, 1355, 1340, 1331, 1279, 1263, 1184, 1177, 1097,
which is a novel brominated indenone derivative, that pro- 1079, 1063, 1029, 1012, 939, 917, 894, 850, 837 (w), 793, 778, 758,
4215
Eur. J. Org. Chem. 2011, 4212–4221
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org

P. Langer et al.
FULL PAPER
727 (m), 690 (s), 672, 657, 596 (m) cm–1. GC-MS (EI, 70 eV): m/z K2CO3 (2 m, 1 mL), and 3-chlorophenylboronic acid (103 mg,
(%) = 358 (100) [M]+, 341 (11). 326 (11), 252 (15). HRMS (EI, 0.66 mmol), 4e was isolated as a brownish-yellow solid (73 mg,
70 eV): calcd. for C27H18O [M]+ 358.13522; found 358.135167.
79%). Reaction temperature: 70 °C for 6 h; m.p. 135–137 °C. 1H
NMR (300 MHz, CDCl3): δ = 7.01 (dt, J = 0.9, 7.5 Hz, 1 H, ArH),
7.09–7.30 (m, 5 H, ArH), 7.28–7.44 (m, 8 H, ArH), 7.58 (d, J =
7.4 Hz, 1 H, ArH) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 120.3,
123.8, 125.4, 126.6, 127.3, 128.0, 128.1, 128.2, 128.3, 128.4, 129.5
(CH), 129.6 (C), 129.8, 129.9, 130.2, 130.6 (CH), 131.9, 132.5,
134.0, 134.2, 134.9, 135.2, 141.9, 145.5, 145.6, 154.0 (C), 194.9
2,3,5-Tris(4-ethylphenyl)-1H-inden-1-one (4b): Starting with
2
(80 mg, 0.20 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane (3 mL),
K2CO3 (2 m, 1 mL), and 4-ethylphenylboronic acid (99 mg,
0.66 mmol), 4b was isolated as a brownish-yellow solid (78 mg,
88%). Reaction temperature: 70 °C for 6 h; m.p. 133–134 °C. 1H
NMR (300 MHz, CDCl3): δ = 1.16–1.23 (m, 9 H, 3ϫ CH3), 2.54
(q, J = 7.5 Hz, 2 H, CH2), 2.56–2.66 (m, 4 H, 2ϫ CH2), 7.02 (d,
J = 8.1 Hz, 2 H, ArH), 7.13–7.27 (m, 9 H, ArH), 7.36 (dd, J = 1.4,
7.5 Hz, 1 H, ArH), 7.40 (d, J = 8.3 Hz, 2 H, ArH), 2.53 (d, J =
7.5 Hz, 1 H, ArH) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 14.1,
14.2, 14.5 (CH3), 27.5, 27.6, 27.8 (CH2), 119.3, 122.2, 126.0, 126.1,
126.6 (CH), 127.2 (C), 127.2, 127.3, 127.6 (CH), 128.4 (C), 128.9
(CH), 129.1, 131.7, 136.8, 142.7, 143.5, 144.5, 145.3, 145.6, 153.2
(CO) ppm. IR (KBr): ν = 2955, 2921, 2851 (w), 1699 (s), 1596,
˜
1579, 1561 (m), 1461, 1437, 1423 (w), 1344, 1328, 1297, 1259, 1249,
1186, 1078, 1063, 957, 892, 875, 851, 799, 779, 769, 743, 713, 682,
667 (m), 602, 592 (w) cm–1. GC-MS (EI, 70 eV): m/z (%) = 466 (05)
[M, 37Cl3]+, 464 (37) [M, 37Cl2, 35Cl]+, 462 (98) [M, 37Cl, 35Cl2]+,
460 (100) [M, 35Cl3]+, 425 (42). 362 (21), 326 (31). HRMS (EI,
70 eV): calcd. for C27H15Cl3O [M, 35Cl3]+ 460.01830; found
460.017500.
(C), 195.4 (CO) ppm. IR (KBr): ν = 2962, 2928, 2873 (w), 1698,
˜
1595 (s), 1500, 1455, 1351, 1336, 1259, 1181, 1142, 1116, 1095,
1071, 1048, 1017, 1012, 936, 821 (m), 786 (m), 740, 729, 703, 674,
660, 638, 623 (w), 568 (m) cm–1. GC-MS (EI, 70 eV): m/z (%) =
442 (100) [M]+, 413 (26), 207 (26). HRMS (EI, 70 eV): calcd. for
C33H30O [M]+ 442.22912; found 442.228900.
2,3,5-Tris(4-fluorophenyl)-1H-inden-1-one (4f): Starting with
2
(80 mg, 0.20 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane (3 mL),
K2CO3 (2 m, 1 mL), and 4-fluorophenylboronic acid (93 mg,
0.66 mmol), 4f was isolated as a brownish-yellow solid (67 mg,
81%). Reaction temperature: 70 °C for 6 h; m.p. 236–237 °C. 1H
NMR (300 MHz, CDCl3): δ = 6.91 (t, J = 8.8 Hz, 2 H, ArH), 7.03–
7.10 (m, 4 H, ArH), 7.15–7.20 (m, 3 H, ArH), 7.30–7.34 (m, 2 H,
ArH), 6.91 (dd, J = 1.4, 7.5 Hz, 1 H, ArH), 7.42–7.47 (m, 2 H,
ArH), 6.91 (d, J = 7.4 Hz, 1 H, ArH) ppm. 19F NMR (282.4 MHz,
CDCl3): δ = –113.6, –112.8, –110.3 ppm. 13C NMR (75.5 MHz,
2,3,5-Tris(4-tert-butylphenyl)-1H-inden-1-one (4c): Starting with 2
(80 mg, 0.20 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane (3 mL),
K2CO3 (2 m, 1 mL), and 4-tert-butylphenylboronic acid (118 mg,
0.66 mmol), 4c was isolated as a brownish-yellow solid (89 mg,
85%). Reaction temperature: 70 °C for 6 h; m.p. 98–100 °C. 1H
NMR (300 MHz, CDCl3): δ = 1.23 (s, 9 H, 3ϫ CH3), 1.27 (s, 9 H,
3ϫ CH3), 1.29 (s, 9 H, 3ϫ CH3), 7.16–7.23 (m, 4 H, ArH), 7.28–
7.46 (m, 10 H, ArH), 7.53 (d, J = 7.4 Hz, 1 H, ArH) ppm. 13C
NMR (75.5 MHz, CDCl3): δ = 31.2 (6ϫ CH3), 31.3 (3ϫ CH3),
34.6, 34.7, 34.9 (C), 120.5, 123.2, 125.0, 125.7, 125.8, 126.9, 127.0
(CH), 128.0 (C), 128.3 (CH), 129.5 (C), 129.6 (CH), 129.9, 132.6,
146.4, 146.5, 150.6, 151.4, 152.4, 154.2 (C), 196.6 (CO) ppm. IR
CDCl3): δ = 115.4 (d, JF,C1 = 21.5 Hz, CH), 115.9 (d, JF,C
=
21.6 Hz, CH), 115.9 (d, JF,C = 21.8 Hz, CH), 120.1, 123.6 (CH),
125.4 (d, JF,C = 3.4 Hz, C), 126.5 (CH), 127.3 (d, JF,C = 4.3 Hz,
C), 128.9 (d, JF,C = 8.2 Hz, CH), 128.2 (C), 130.5 (d, JF,C = 8.2 Hz,
CH), 131.8 (d, JF,C = 8.0 Hz, CH), 131.4 (C), 135.3 (d, JF,C
3.4 Hz, C), 144.8, 144.9, 152.5 (C), 161.5 (d, JF,C = 248.8 Hz, C-
F), 161.7 (d, JF,C = 249.3 Hz, C-F), 162.0 (d, JF,C = 250.8 Hz, C-
=
(KBr): ν = 2958, 2927, 2903, 2866 (w), 1704 (s), 1598, 1462, 1362,
˜
F), 194.6 (CO) ppm. IR (KBr): ν = 2956, 2922, 2851 (w), 1697,
˜
1351, 1268, 1187, 1112, 1093, 1069, 1015, 938 (m), 821, 785, 766,
756, 726, 708, 693, 648, 637, 579 (w), 558 (s), 538, 528 (s) cm–1.
GC-MS (EI, 70 eV): m/z (%) = 526 (100) [M]+, 511 (60). 248 (26).
HRMS (EI, 70 eV): calcd. for C39H42O [M]+ 526.32302; found
526.323938.
1592 (s), 1515, 1496, 1463, 1350 (m), 1220 (s), 1185, 1158, 1143,
1094, 1070, 1012, 935, 906, 871, 857 (m), 827, 812, 799 (s), 787,
748, 740 (m), 722, 712, 700, 661 (w), 620, 569, 557, 538 (m) cm–1.
GC-MS (EI, 70 eV): m/z (%) = 412 (100) [M]+, 395 (11), 288 (13).
HRMS (EI, 70 eV): calcd. for C27H15OF3 [M]+ 412.10695; found
412.107062.
2,3,5-Tris(3-methoxyphenyl)-1H-inden-1-one (4d): Starting with 2
(80 mg, 0.20 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane (3 mL),
K2CO3 (2 m, 1 mL), and 3-methoxyphenylboronic acid (101 mg,
0.66 mmol), 4d was isolated as a brownish-yellow solid (68 mg,
76%). Reaction temperature: 70 °C for 6 h; m.p. 163–165 °C. 1H
NMR (300 MHz, CDCl3): δ = 3.60 (s, 3 H, OCH3), 3.65 (s, 3 H,
OCH3), 3.78 (s, 3 H, OCH3), 6.71–6.90 (m, 6 H, ArH), 6.93 (dt, J
= 1.1, 7.5 Hz, 1 H, ArH), 7.00 (t, J = 1.8 Hz, 1 H, ArH), 7.05–7.14
(m, 2 H, ArH), 7.26–7.31 (m, 3 H, ArH), 7.40 (dd, J = 1.4, 7.5 Hz,
1 H, ArH), 7.56 (d, J = 7.5 Hz, 1 H, ArH) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 54.5, 54.7, 54.8 (OCH3), 112.6, 112.7,
113.1, 113.6, 114.3, 114.6, 119.1, 120.0, 120.2, 121.9, 122.7, 127.1,
128.5 (CH), 129.0 (C), 129.3, 129.5 (CH), 131.4, 132.5, 133.4,
141.3, 145.4, 146.1, 154.3, 158.5, 159.2, 159.4 (C), 195.3 (CO) ppm.
2,3,5-Tris[3-(trifluoromethyl)phenyl]-1H-inden-1-one (4g): Starting
with 2 (80 mg, 0.20 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane
(3 mL), K2CO3 (2 m, 1 mL), and 3-(trifluoromethyl)phenylboronic
acid (125 mg, 0.66 mmol), 4g was isolated as a brownish-yellow
solid (88 mg, 78%). Reaction temperature: 70 °C for 6 h; m.p. 155–
156 °C. 1H NMR (300 MHz, CDCl3): δ = 7.21 (d, J = 1.1 Hz, 1
H, ArH), 7.31–7.66 (m, 13 H, ArH), 7.71 (s, 1 H, ArH) ppm. 19F
NMR (282.4 MHz, CDCl3): δ = –63.1, –63.0, –62.7 ppm. 13C
NMR (75.5 MHz, CDCl3): δ = 120.4 (CH), 123.5 (q, JF,C
272.7 Hz, CF3), 123.7 (q, JF,C = 272.0 Hz, CF3), 123.8 (q, JF,C
271.3 Hz, CF3), 123.9 (q, JF,C = 3.8 Hz, CH), 124.1 (CH), 124.9
(q, JF,C = 3.6 Hz, CH), 125.2 (q, JF,C = 3.5 Hz, CH), 125.3 (q, JF,C
=
=
IR (KBr): ν = 2921, 2852, 2830 (w), 1698, 1600, 1581 (s), 1461,
˜
= 3.8 Hz, CH), 126.5 (q, JF,C = 3.8 Hz, CH), 126.7 (q, JF,C
=
1465, 1453, 1440, 1432, 1317, 1351, 1329, 1319, 1301, 1290, 1281,
1262, 1236, 1218, 1182, 1165, 1136, 1101, 1079, 1056, 1046, 1032,
962, 879, 845, 795, 784, 767, 729, 699, 685, 675 (m), 641, 621, 603,
590, 554 (w) cm–1. GC-MS (EI, 70 eV): m/z (%) = 448 (100) [M]+,
417 (11). HRMS (EI, 70 eV): calcd. for C30H24O4 [M]+ 448.16691;
found 448.165998.
3.9 Hz, CH), 128.6, 128.8, 129.6, 129.9, 130.5 (CH), 130.7 (C),
130.6 (q, JF,C = 22.6 Hz, C-CF3), 130.7 (q, JF,C = 22.4 Hz, C-CF3),
130.6 (q, JF,C = 24.8 Hz, C-CF3), 131.6 (CH), 132.7, 132.9 (C),
133.1 (CH), 140.8, 145.4, 145.7, 154.1 (C), 194.7 (CO) ppm. IR
(KBr): ν = 1706, 1600, 1438, 1429, 1361, 1327, 1314, 1303, 1283,
˜
1241, 1182, 1162 (m), 1112, 1098, 1067 (s), 1031, 999, 955, 917,
907, 895, 849, 817 (w), 798, 782, 769, 738, 698, 689, 677, 654 (m),
636, 621, 601, 533 (w) cm–1. EI (70 eV): m/z (%) = 562 (100) [M]+,
2,3,5-Tris(3-chlorophenyl)-1H-inden-1-one (4e): Starting with
2
(80 mg, 0.20 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane (3 mL),
4216
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4212–4221

Site-Selective Synthesis of Arylated Indenones
493 (16). HRMS (EI, 70 eV): calcd. for C30H15F9O [M]+ 562.09737;
found 562.097569.
a brownish yellow solid (93 mg, 80%). Reaction temperature: 45 °C
for 8 h; m.p. 111–113 °C. 1H NMR (300 MHz, CDCl3): δ = 7.12
(d, J = 1.0 Hz, 2 H, ArH), 7.35–7.42 (m, 2 H, ArH), 7.61–7.74 (m,
32, ArH), 7.81 (br. s, 1 H, ArH) ppm. 19F NMR (282.4 MHz,
CDCl3): δ = –62.8 ppm. 13C NMR (75.5 MHz, CDCl3): δ = 123.6
(q, JF,C = 272.9 Hz, CF3), 124.4 (CH), 125.0 (q, JF,C = 3.9 Hz, CH),
125.1 (CH), 127.2 (q, JF,C = 3.7 Hz, CH), 128.1, 129.1 (C), 129.7,
131.3 (CH), 131.5 (C), 131.6 (q, JF,C = 32.8 Hz, C-CF3), 132.0
2,5-Dibromo-3-phenyl-1H-inden-1-one (5a): Starting with
2
(100 mg, 0.27 mmol), [Pd(PPh3)4] (8 mg, 3 mol-%), dioxane (3 mL),
K3PO4 (86 mg, 0.41 mmol), and phenylboronic acid (33 mg,
0.27 mmol), 5a was isolated as a brownish-yellow solid (60 mg,
83%). Reaction temperature: 45 °C for 8 h; m.p. 108–110 °C. 1H
NMR (300 MHz, CDCl3): δ = 7.19–7.20 (m, 1 H, ArH), 7.32–7.38
(m, 2 H, ArH), 7.45–7.57 (m, 5 H, ArH) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 119.1 (C), 124.7, 128.1 (CH), 128.4, 128.8
(C), 128.9 (CH), 130.5 (C), 130.6, 131.6 (CH), 146.3, 155.8 (C),
(CH), 145.8, 154.2 (C), 188.1 (CO) ppm. IR (KBr): ν = 3074, 2959,
˜
2929 (w), 1716, 1595, 1586 (m), 1556, 1491, 1449, 1428, 1404 (w),
1326 (m), 1250, 1165, 1122, 1094, 1073, 1054 (s), 934, 926, 880,
861, 833, 818 (w), 800, 697 (m), 677, 651, 622, 600, 585 (w) cm–1.
GC-MS (EI, 70 eV): m/z (%) = 434 (48) [M, 81Br, 81Br]+, 432 (100)
[M, 79Br, 81Br]+, 430 (51) [M, 79Br, 79Br]+, 351 (35), 244 (36).
HRMS (EI, 70 eV): calcd. for C16H7Br2OF3 [M, 81Br, 81Br]+:
433.8769; found 433.877014, calcd. for C16H7Br2OF3[M, 79Br,
81Br]+: 431.87693; found 431.878784, calcd. for C16H7Br2OF3 [M,
79Br, 79Br]+: 429.88103; found 429.880630.
188.6 (CO) ppm. IR (KBr): ν = 3087, 3062, 2921, 2850 (w), 1728
˜
(s), 1599, 1557, 1486, 1442, 1397, 1342 (m), 1299, 1282 (w), 1266,
1176, 1149, 1098, 1052, 1028 (m), 1000 (w), 931, 917, 875, 833, 814,
769, 755, 714 (w), 688 (s), 663, 634, 611, 586 (m) cm–1. GC-MS
(EI, 70 eV): m/z (%) = 366 (51) [M, 81Br, 81Br]+, 364 (100) [M, 79Br,
81Br]+, 362 (51) [M, 79Br, 79Br]+, 285 (27), 176 (51). HRMS (EI,
70 eV): calcd. for C15H8Br2O [M, 81Br, 81Br]+: 365.88955; found
365.889828, calcd. for C15H8Br2O [M, 79Br, 81Br]+: 363.89160;
found 363.891541, calcd. for C15H8Br2O [M, 79Br, 79Br]+:
361.89364; found 361.893675.
2,5-Dibromo-3-[4-(trifluoromethoxy)phenyl]-1H-inden-1-one
(5e):
Starting with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (8 mg, 3 mol-%),
dioxane (3 mL), K3PO4 (86 mg, 0.41 mmol), and 4-(trifluorometh-
oxy)phenylboronic acid (56 mg, 0.27 mmol), 5d was isolated as a
brownish-yellow solid (69 mg, 78%). Reaction temperature: 45 °C
2,5-Dibromo-3-(4-tert-butylphenyl)-1H-inden-1-one (5b): Starting
with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (8 mg, 3 mol-%), dioxane
(3 mL), K3PO4 (86 mg, 0.41 mmol), and 4-tert-butylphenylboronic
acid (48 mg, 0.27 mmol), 5b was isolated as a brownish-yellow solid
(72 mg, 86%). Reaction temperature: 45 °C for 8 h; m.p. 133–
1
for 8 h; m.p. 102–104 °C. H NMR (300 MHz, CDCl3): δ = 7.24–
7.43 (m, 5 H, ArH), 7.62 (d, J = 8.8 Hz, 2 H, ArH) ppm. 19F NMR
(282.4 MHz, CDCl3): δ = –57.6 ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 118.8 (C), 119.5 (q, JF,C = 258.5 Hz, OCF3), 121.2,
124.1, 125.0 (CH), 127.2, 127.9, 128.0 (C), 130.0, 131.9 (CH),
1
135 °C. H NMR (300 MHz, CDCl3): δ = 1.32 (s, 9 H, 3ϫ CH3),
7.26–7.38 (m, 3 H, ArH), 7.48–7.55 (m, 4 H, ArH) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 31.6 (3ϫ CH3), 35.1, 118.5 (C), 124.6,
124.8, 125.9 (CH), 127.6 (C), 128.0 (CH), 128.6, 128.7 (C), 131.5
144.9, 149.5, 153.3 (C), 188.2 (CO) ppm. IR (KBr): ν = 3087, 2922,
˜
2851 (w), 1729, 1609, 1597, 1590, 1504 (m), 1446 (w), 1303, 1277,
1247, 1205 (m), 1150 (s), 1095, 1053, 1018, 928 (m), 887 (w), 832,
817, 804, 766, 717, 689 (m), 666, 620, 588 (m), 538 (w) cm–1. GC-
MS (EI, 70 eV): m/z (%) = 450 (50) [M, 81Br, 81Br]+, 448 (100) [M,
79Br, 81Br]+, 446 (51) [M, 79Br, 79Br]+, 367 (29), 260 (19). HRMS
(EI, 70 eV): calcd. for C16H7Br2O2F3 [M, 81Br, 81Br]+: 449.87185;
found 449.871344, calcd. for C16H7Br2O2F3[M, 79Br, 81Br]+:
447.87389; found 447.873233, calcd. for C16H7Br2O2F3 [M, 79Br,
79Br]+: 445. 87594; found 445.875324.
(CH), 146.3, 154.2, 155.8 (C), 188.7 (CO) ppm. IR (KBr): ν = 3088,
˜
2960, 2903, 2866 (w), 1720 (s), 1600, 1592, 1565, 1495, 1463, 1448
(m), 1401, 1362, 1339, 1289, 1272, 1191, 1177 (w), 1155, 1106, 1092,
1047, 1017, 930, 878, 834 (m), 812 (s), 770, 717, 686, 632 (m), 588
(w), 550 (m) cm–1. GC-MS (EI, 70 eV): m/z (%) = 422 (25) [M,
81Br, 81Br]+, 420 (49) [M, 79Br, 81Br]+, 418 (24) [M, 79Br, 79Br]+, 405
(100), 202 (11). HRMS (EI, 70 eV): calcd. for C19H16Br2O [M, 79Br,
81Br]+: 419.95420; found 419.954735, calcd. for C19H16Br2O [M,
79Br, 79Br]+: 417.95624; found 417.957228.
2,5-Dibromo-3-p-tolyl-1H-inden-1-one (5f): Starting with 2 (100 mg,
0.27 mmol), [Pd(PPh3)4] (8 mg, 3 mol-%), dioxane (3 mL), K3PO4
(86 mg, 0.41 mmol), and p-tolylboronic acid (37 mg, 0.27 mmol),
5f was isolated as a brownish-yellow solid (87 mg, 86%). Reaction
2,5-Dibromo-3-(3-chlorophenyl)-1H-inden-1-one (5c): Starting with
2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (8 mg, 3 mol-%), dioxane
(3 mL), K3PO4 (86 mg, 0.41 mmol), and 3-chlorophenylboronic
acid (42 mg, 0.27 mmol), 5a was isolated as a brownish-yellow solid
(63 mg, 80%). Reaction temperature: 45 °C for 8 h; m.p. 120–
122 °C. 1H NMR (300 MHz, CDCl3): δ = 7.15 (d, J = 1.1 Hz, 1
H, ArH), 7.35–7.45 (m, 5 H, ArH), 7.52–7.53 (m, 1 H, ArH) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 120.8 (C), 124.5, 125.0, 126.2,
128.0 (CH), 128.5, 129.0 (C), 130.4, 130.6, 131.8 (CH), 132.3,
1
temperature: 45 °C for 8 h; m.p. 129–131 °C. H NMR (300 MHz,
CDCl3): δ = 2.38 (s, 3 H, CH3), 7.21–7.22 (m, 1 H, ArH), 7.29 (d,
J = 8.0 Hz, 2 H, ArH), 7.33–7.37 (m, 2 H, ArH), 7.26 (d, J =
8.1 Hz, 2 H, ArH) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 21.7
(CH3), 118.5 (C), 124.6, 124.7 (CH), 127.66 (C), 128.1 (CH), 128.6,
128.7 (C), 129.6, 131.5 (CH), 141.2, 146.3, 155.9 (C), 188.7
(CO) ppm. IR (KBr): ν = 3089, 3027, 2915, 2850 (w), 1729 (s),
˜
135.1, 145.9, 154.3 (C), 188.2 (CO) ppm. IR (KBr): ν = 3065, 2918,
˜
1599, 1590, 1564, 1556, 1444 (m), 1398 (w), 1343, 1289, 1270, 1184,
1150, 1097, 1053 (m), 1019 (w), 928, 880, 835, 810, 765, 720, 715,
687, 631, 588 (m) cm–1. GC-MS (EI, 70 eV): m/z (%) = 380 (50)
[M, 81Br, 81Br]+, 378 (100) [M, 79Br, 81Br]+, 376 (52) [M, 79Br, 79Br]+,
297 (25), 189 (50). HRMS (EI, 70 eV): calcd. for C16H10Br2O [M,
81Br, 81Br]+: 379.90520; found 379.905770, calcd. for C16H10Br2O
[M, 79Br, 81Br]+: 377.90725; found 377.907387, calcd. for
C16H10Br2O [M, 79Br, 79Br]+: 375.90929; found 375.909178.
2849, 2156, 2137 (w), 1721 (s), 1598, 1585, 1553 (m), 1470, 1446,
1420, 1397 (m), 1337, 1272, 1180, 1167, 1153 (w), 1097, 1091, 1081,
1050, 951, 884, 835, 817, 786, 767, 712, 705, 682 (m), 650, 638, 600,
588 (w) cm–1. GC-MS (EI, 70 eV): m/z (%) = 400 (63) [M, 81Br,
81Br]+, 398 (100) [M, 79Br, 81Br]+, 396 (43) [M, 79Br, 79Br]+, 319
(33), 210 (20). HRMS (EI, 70 eV): calcd. for C15H7Br2O [M, 81Br,
81Br]+: 399.85058; found 399.850749, calcd. for C15H7Br2ClO [M,
79Br, 81Br]+: 397.85262; found 397.852713, calcd. for C15H7Br2ClO
[M, 79Br, 79Br]+: 395.85467; found 395.855006.
2,5-Dibromo-3-(4-methoxyphenyl)-1H-inden-1-one (5g): Starting
with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (8 mg, 3 mol-%), dioxane
2,5-Dibromo-3-[3-(trifluoromethyl)phenyl]-1H-inden-1-one
(5d):
Starting with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (8 mg, 3 mol-%), (3 mL), K3PO4 (86 mg, 0.41 mmol), and 4-methoxyphenylboronic
dioxane (3 mL), K3PO4 (86 mg, 0.41 mmol), and 3-(trifluoro-
acid (41 mg, 0.27 mmol), 5g was isolated as a brownish-yellow solid
methyl)phenylboronic acid (51 mg, 0.27 mmol), 5d was isolated as
(98 mg, 92%). Reaction temperature: 45 °C for 8 h; m.p. 194–
Eur. J. Org. Chem. 2011, 4212–4221
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4217

P. Langer et al.
FULL PAPER
195 °C. 1H NMR (300 MHz, CDCl3): δ = 3.84 (s, 3 H, OCH3), 7.33–7.39 (m, 2 H, ArH) ppm. 13C NMR (75.5 MHz, CDCl3): δ
6.70 (d, J = 8.8 Hz, 2 H, ArH), 7.26 (d, J = 1.0 Hz, 1 H, ArH), = 55.1, 55.3 (OCH3), 113.7, 114.1, 115.0, 115.3, 120.6, 122.5, 124.1,
7.32–7.7.39 (m, 2 H, ArH), 7.60 (d, J = 8.9 Hz, 2 H, ArH) ppm. 124.8 (CH), 128.4 (C), 129.2 (CH), 129.2 (C), 130.2 (CH), 131.5
13C NMR (62.9 MHz, CDCl3): δ = 55.5 (OCH3), 114.4 (CH), (C), 131.7 (CH), 133.3, 133.5, 147.2, 154.2, 159.2, 159.9 (C), 195.1
117.8, 122.8 (C), 124.5, 124.7 (CH), 128.5, 128.8 (C), 130.0, 131.5 (CO) ppm. IR (KBr): ν = 2954, 2919, 2849, 2833 (w), 1709, 1590,
˜
(CH), 146.3, 155.5, 161.5 (C), 188.7 (CO) ppm. IR (KBr): ν = 3409,
3070, 3025, 2985, 2955, 2921, 2850, 2282, 2035 (w), 1715, 1597,
1575 (s), 1479, 1436, 1426, 1348, 1329, 1286, 1263, 1228, 1171,
1132, 1093 (m), 1042 (s), 960, 929, 919, 887, 979 (w), 786, 772, 721,
˜
1503 (s), 1444, 1419, 1401, 1341, 1307, 1275 (m), 1257, 1173 (s), 688 (m), 646, 647, 593, 566, 556 (w) cm–1. GC-MS (EI, 70 eV): m/z
1152, 1118, 1102, 1091, 1052 (m), 1017 (s), 954 (w), 927 (m), 873 (%) = 422 (71) [M, 81Br]+, 420 (100) [M, 79Br]+, 389 (12), 298 (11),
(w), 822, 813 (s), 782, 766, 732, 712, 690, 632, 621, 576 (m), 528 226 (19). HRMS (EI, 70 eV): calcd. for C23H17BrO3 [M, 81Br]+:
(s) cm–1. GC-MS (EI, 70 eV): m/z (%) = 396 (25) [M, 81Br, 81Br]+,
394 (100) [M, 79Br, 81Br]+, 392 (51) [M, 79Br, 79Br]+, 313 (10), 191
(09), 163 (34). HRMS (EI, 70 eV): calcd. for C16H10Br2O2 [M, 81Br,
81Br]+: 395.90011; found 395.89959, calcd. for C16H10Br2O2 [M,
79Br, 81Br]+: 393.90216; found 393.90172, calcd. for C16H10Br2O2
[M, 79Br, 79Br]+: 391.90421; found 391.90320.
422.003351; found 422.032711, calcd. for C23H17BrO3 [M, 79Br]+:
420.03556; found 420.034466.
5-Bromo-2,3-bis(4-fluorophenyl)-1H-inden-1-one (6d): Starting with
2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane
(3 mL), K3PO4 (172 mg, 0.81 mmol), and 4-fluorophenylboronic
acid (77 mg, 0.54 mmol), 6d was isolated as a brownish-yellow solid
(84 mg, 78%). Reaction temperature: 60 °C for 6 h; m.p. 184–
5-Bromo-2,3-bis(4-ethylphenyl)-1H-inden-1-one (6a): Starting with 2
(100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane 185 °C. 1H NMR (300 MHz, CDCl3): δ = 6.90 (t, J = 8.9 Hz, 2 H,
(3 mL), K3PO4 (172 mg, 0.81 mmol), and 4-ethylphenylboronic
ArH), 7.07 (t, J = 8.8 Hz, 2 H, ArH), 7.13–7.18 (m, 3 H, ArH),
acid (81 mg, 0.54 mmol), 6a was isolated as a brownish-yellow solid
7.24–7.29 (m, 2 H, ArH), 7.34–7.41 (m, 2 H, ArH) ppm. 19F NMR
(98 mg, 88%). Reaction temperature: 60 °C for 6 h; m.p. 102– (282.4 MHz, CDCl3): δ = –1δ = 12.3, –109.8 ppm. 13C NMR
104 °C. 1H NMR (300 MHz, CDCl3): δ = 1.15 (t, J = 7.6 Hz, 3 H,
CH3), 1.23 (t, J = 7.6 Hz, 3 H, CH3), 2.55 (q, J = 7.6 Hz, 2 H, (d, JF,C = 21.9 Hz, CH), 124.3, 124.6 (CH), 126.1 (d, JF,C = 3.6 Hz,
(75.5 MHz, CDCl3): δ = 11δ = 5.4 (d, JF,C = 21.6 Hz, CH), 116.4
CH2), 2.64 (q, J = 7.6 Hz, 2 H, CH2), 7.03 (d, J = 8.4 Hz, 2 H,
ArH), 7.14 (d, J = 8.3 Hz, 2 H, ArH), 7.17–7.24 (m, 5 H, ArH),
7.33–7.38 (m, 2 H, ArH) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
14.1, 14.2 (CH3), 28.7, 28.8 (CH2), 123.9, 124.6, 127.7 (CH), 128.1
C), 128.0 (d, JF,C = 3.5 Hz, C), 128.5, 129.1 (C), 130.4 (d, JF,C
8.4 Hz, CH), 131.8 (d, JF,C = 7.6 Hz, CH), 131.9 (CH), 132.5,
146.9, 152.9 (C), 162.9 (d, JF,C = 249.3 Hz, CF), 163.2 (d, JF,C
251.2 Hz, CF), 194.9 (CO) ppm. IR (KBr): ν = 3076, 3047, 2922,
=
=
˜
(C), 128.4, 128.5 (CH), 129.5, 129.6 (C), 129.9, 131.4 (CH), 132.9, 2852, 2158, 1895 (w), 1709 (s), 1596, 1584, 1575, 1511, 1499, 1456,
144.1, 145.9, 147.5, 153.6 (C), 195.0 (CO) ppm. IR (KBr): ν = 2961, 1404, 1351, 1330, 1224, 1178, 1159 (m), 1093, 1065 (w), 1050 (m),
˜
2923, 2851 (w), 1702 (s), 1590, 1576, 1501, 1454, 1411, 1350 (m), 1015, 941 (m), 927, 880, 864, 856, 845 (w), 825, 818 (s), 800, 776,
1328 (w), 1259, 1174, 1116, 1095, 1068, 1047, 1017 (m), 961 (w),
930, 883, 862, 837, 819, 801 (m), 743 (w), 699, 661, 648, 638, 582,
744, 732, 694, 662, 631, 619, 592, 567, 547, 532 (m) cm–1. GC-MS
(EI, 70 eV): m/z (%) = 398 (98) [M, 81Br]+, 398 (100) [M, 79Br]+,
564, 536 (w) cm–1. GC-MS (EI, 70 eV): m/z (%) = 418 (98) [M, 317 (52), 288 (79). HRMS (EI, 70 eV): calcd. for C21H11BrOF2 [M,
81Br]+, 416 (100) [M, 79Br]+, 387 (36), 263 (23). HRMS (EI, 70 eV):
calcd. for C25H21BrO [M, 79Br]+ 416.07703; found 416.077060.
81Br]+: 397.99354; found 397.993349, calcd. for C21H11BrOF2 [M,
79Br]+: 395.99559; found 395.995342.
5-Bromo-2,3-bis(4-tert-butylphenyl)-1H-inden-1-one (6b): Starting
5-Bromo-2,3-bis[3-(trifluoromethyl)phenyl]-1H-inden-1-one
(6e):
with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane Starting with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg, 5 mol-
(3 mL), K3PO4 (172 mg, 0.81 mmol), and 4-tert-butylphenylbor-
onic acid (97 mg, 0.54 mmol), 6b was isolated as a brownish-yel-
low solid (78 mg, 83%). Reaction temperature: 60 °C for 6 h; m.p.
188–190 °C. 1H NMR (300 MHz, CDCl3): δ = 1.22 (s, 9 H, 3ϫ
%), dioxane (3 mL), K3PO4 (172 mg, 0.81 mmol), and 3-(trifluoro-
methyl)phenylboronic acid (103 mg, 0.54 mmol), 6e was isolated as
a brownish-yellow solid (76 mg, 77%). Reaction temperature: 60 °C
for 6 h; m.p. 150–152 °C. 1H NMR (300 MHz, CDCl3): δ = 7.15
CH3), 1.29 (s, 9 H, 3ϫ CH3), 7.13–7.26 (m, 7 H, ArH), 7.34–7.39 (d, J = 1.0 Hz, 1 H, ArH), 7.32–7.57 (m, 9 H, ArH), 7.15 (br. d, J
(m, 4 H, ArH) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 31.1 (6ϫ = 7.7 Hz, 1 H, ArH) ppm. 19F NMR (282.4 MHz, CDCl3): δ =
CH3), 34.7, 34.9 (C), 123.9, 124.7, 125.1, 125.9 (CH), 127.4 (C),
128.2 (CH), 129.3, 129.5 (C), 129.6, 131.3 (CH), 132.8, 147.7, JF,C = 272.8 Hz, CF3), 123.4 (q, JF,C = 272.6 Hz, CF3), 124.7, 124.8
–63.02, –63.07 ppm. 13C NMR (75.5 MHz, CDCl3): δ = 123.3 (q,
151.0, 152.8, 153.5 (C), 195.7 (CO) ppm. IR (KBr): ν = 2960, 2928,
(CH), 125.1 (q, JF,C = 3.6 Hz, CH), 125.2 (q, JF,C = 3.6 Hz, CH),
126.6 (q, JF,C = 3.7 Hz, CH), 126.7 (q, JF,C = 3.7 Hz, CH), 128.8
(C), 128.9, 130.0 (CH), 130.4 (C), 130.9 (q, JF,C = 32.5 Hz, C-CF3),
131.5 (CH), 132.0 (q, JF,C = 32.9 Hz, C-CF3), 132.5 (CH), 132.5,
˜
2903, 2865 (m), 1708 (s), 1602, 1589, 1577, 1459, 1396, 1362, 1349,
1262 (m), 1199, 1181, 1113, 1104, 1092 (w), 1069, 1050, 1014 (m),
975, 958, 933 (w), 865, 857, 850, 841, 829, 818, 779, 739, 730, 654,
635, 625, 566, 559 (m) cm–1. GC-MS (EI, 70 eV): m/z (%) = 474
132.8, 133.1 (C), 146.2, 153.5 (C), 194.0 (CO) ppm. IR (KBr): ν =
˜
(75) [M, 81Br]+, 472 (73) [M, 79Br]+, 459 (100), 194 (16). HRMS 3070, 2923, 2851, 2143 (w), 1704 (s), 1600, 1583, 1442, 1354 (w),
(EI, 70 eV): calcd. for C29H29BrO [M, 81Br]+: 474.13758; found
474.138018; calcd. for C29H29BrO [M, 79Br]+: 472.13963; found
472.139209.
1324 (s), 1313, 1295, 1276, 1261, 1163 (m), 1120 (s), 1097 (m), 1068
(s), 1051, 951, 911 (m), 881, 861, 840 (w), 806 (m), 781, 770, 740
(w), 721, 698 (m), 659, 650, 642, 631, 595 (w) cm–1. GC-MS (EI,
70 eV): m/z (%) = 498 (98) [M, 81Br]+, 496 (100) [M, 79Br]+, 417
(20), 397 (22), 320 (30). HRMS (EI, 70 eV): calcd. for
C23H11BrOF6 [M, 81Br]+: 497.98715; found 497.986267, calcd. for
C23H11BrOF6 [M, 79Br]+: 495.98920; found 495.988980.
5-Bromo-2,3-bis(3-methoxyphenyl)-1H-inden-1-one (6c): Starting
with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane
(3 mL), K3PO4 (172 mg, 0.81 mmol), and 3-methoxyphenylboronic
acid (82 mg, 0.54 mmol), 6c was isolated as a brownish-yellow solid
(63 mg, 75%). Reaction temperature: 60 °C for 6 h; m.p. 126–
5-Bromo-2,3-bis(4-methoxyphenyl)-1H-inden-1-one (6f): Starting
128 °C. 1H NMR (300 MHz, CDCl3): δ = 3.59 (s, 3 H, OCH3), with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane
3.65 (s, 3 H, OCH3), 6.72–6.89 (m, 6 H, ArH), 7.10 (t, J = 7.7 Hz,
1 H, ArH), 7.18–7.20 (m, 1 H, ArH), 7.31 (t, J = 8.0 Hz, 1 H, ArH),
(3 mL), K3PO4 (172 mg, 0.81 mmol), and 4-methoxyphenylboronic
acid (82 mg, 0.54 mmol), 6f was isolated as a brownish-yellow solid
4218
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4212–4221

Site-Selective Synthesis of Arylated Indenones
(96 mg, 85%). Reaction temperature: 60 °C for 6 h; m.p. 126–
(CH2), 55.2 (OCH3), 113.7 (CH), 122.8 (C), 123.8, 124.4 (CH),
128 °C. 1H NMR (300 MHz, CDCl3): δ = 3.72 (s, 3 H, OCH3), 128.2 (C), 128.4, 128.5 (CH), 129.5, 129.6 (C), 131.2, 131.3 (CH),
3.79 (s, 3 H, OCH3), 6.75 (d, J = 8.9 Hz, 2 H, ArH), 6.88 (d, J =
8.9 Hz, 2 H, ArH), 7.16 (d, J = 8.9 Hz, 2 H, ArH), 7.21 (br. s, 1
H, ArH), 7.26 (d, J = 8.9 Hz, 2 H, ArH), 7.33–7.34 (m, 2 H,
132.5, 145.8, 147.6, 152.8, 159.4 (C), 195.5 (CO) ppm. IR (KBr): ν
˜
= 2962, 2925, 2852, 2836 (w), 1709 (s), 1600, 1589, 1577, 1514,
1500, 1453, 1444 (m), 1400, 1349, 1329, 1293 (w), 1248, 1183, 1065,
ArH) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 55.2, 55.34 (OCH3), 1049, 1029, 1017, 930, 880, 852, 838, 820, 774 (m), 733, 717, 699,
113.1, 113.8 (CH), 122.9 (C), 123.2, 123.8 (CH), 124.6, 128.1, 129.6
(C), 129.4, 130.6, 130.7 (CH), 132.2, 147.6, 152.6, 159.4, 160.5 (C),
681, 660, 649, 632 (w), 582, 561, 540, 526 (m) cm–1. GC-MS (EI,
70 eV): m/z (%) = 420 (100) [M, 81Br]+, 418 (96) [M, 79Br]+, 239
(19). HRMS (EI, 70 eV): calcd. for C24H19BrO2 [M, 79Br]+:
420.05425; found 420.054679; calcd. for C24H19BrO2 [M, 79Br]+:
195.7 (CO) ppm. IR (KBr): ν = 3409, 3071, 3026, 2987, 2956, 2920,
˜
2850, 1898 (w), 1715, 1597, 1555, 1503, 1444 (s), 1420, 1401, 1342,
1307, 1275 (m), 1257, 1173 (s), 1152, 1118, 1103, 1091, 1052 (m), 418.05629; found 418.056241.
1017 (s), 954 (w), 927 (m), 872 (w), 821 (s), 782, 766, 732, 712, 690,
5-Bromo-3-(4-chlorophenyl)-2-(4-ethylphenyl)-1H-inden-1-one (7b):
632, 621, 588, 576 (m), 528 (s) cm–1. GC-MS (EI, 70 eV): m/z (%)
= 422 (98) [M, 81Br]+, 420 (100) [M, 79Br]+, 405 (12), 255 (13),
226 (26). HRMS (EI, 70 eV): calcd. for C23H17BrO3 [M, 81Br]+:
422.003351; found 422.03360, calcd. for C23H17BrO3 [M, 79Br]+:
420.03556; found 420.03547.
Starting with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg, 5 mol-
%), dioxane (3 mL), K3PO4 (172 mg, 0.81 mmol), 4-chlorophen-
ylboronic acid (42 mg, 0.27 mmol), and 4-ethylphenylboronic acid
(41 mg, 0.27 mmol) following general procedure B, 7b was isolated
as a brownish-yellow solid (90 mg, 79%). Reaction temperature:
5-Bromo-2,3-bis(4-chlorophenyl)-1H-inden-1-one (6g): Starting with 45 °C for 9 h then at 60 °C for 6 h; m.p. 133–134 °C. 1H NMR
2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg, 5 mol-%), dioxane (300 MHz, CDCl3): δ = 1.14 (t, J = 7.6 Hz, 3 H, CH3), 2.55 (q, J
(3 mL), K3PO4 (172 mg, 0.81 mmol), and 4-chlorophenylboronic = 7.6 Hz, 2 H, CH2), 7.02–7.13 (m, 6 H, ArH), 7.23 (d, J = 8.6 Hz,
acid (84 mg, 0.54 mmol), 6g was isolated as a brownish-yellow solid
(100 mg, 87%). Reaction temperature: 60 °C for 6 h; m.p. 126–
128 °C. 1H NMR (300 MHz, CDCl3): δ = 7.10 (d, J = 8.8 Hz, 2
H, ArH), 7.14–7.23 (m, 5 H, ArH), 7.33–7.40 (m, 4 H, ArH) ppm.
2 H, ArH), 7.33–7.38 (m, 3 H, ArH) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 14.1 (CH3), 28.7 (CH2), 24.2, 124.3 (CH), 127.2 (C),
127.9 (CH), 128.4, 129.2 (C), 129.4, 129.8, 129.9 (CH), 130.8 (C),
131.6 (CH), 133.8, 135.4, 144.6, 147.1, 152.0 (C), 195.1 (CO) ppm.
13C NMR (75.5 MHz, CDCl3): δ = 124.4, 124.6 (CH), 128.3, 128.6 IR (KBr): ν = 2964, 2917, 2871, 2849 (w), 1705 (s), 1597, 1582,
˜
(C), 128.7 (CH), 129.1 (C), 129.6, 129.7 (CH), 130.3 (C), 131.2, 1574, 1804, 1450, 1396, 1349, 1328, 1171, 1148 (m), 1120, 1108 (w),
132.0 (CH), 132.5, 134.5, 135.9, 146.6, 153.1 (C), 194.5 (CO) ppm.
1088, 1068, 1047, 1012, 969 (m), 951, 930 (w), 875, 860, 853, 827,
IR (KBr): ν = 3075, 2919, 2850 (w), 1715 (s), 1601, 1586, 1574, 819, 779, 742, 733, 716, 692, 654, 637, 620, 589, 69, 534 (m) cm–1.
˜
1557, 1484, 1454, 1395, 1348 (m), 1330, 1305, 1282, 1265 (w), 1174,
1150, 1174, 1150, 1087, 1063, 1045, 1013, 1063, 1046, 1013, 955,
946, 929, 877, 858, 832, 821, 812 (m), 776, 740, 726, 715, 707, 688,
GC-MS (EI, 70 eV): m/z (%) = 426 (26) [M, 37Cl, 81Br]+, 424 (100)
[(M, 35Cl, 81Br)+ or (M, 37Cl, 79Br)+], 4222 (76) [M, 35Cl, 79Br]+,
409 (33), 263 (28). HRMS (EI, 70 eV): calcd. for C23H16BrOCl [M,
647, 630, 626, 618, 589 (w) cm–1. GC-MS (EI, 70 eV): m/z (%) = 37Cl, 79Br]+ 424.00381; found 424.004201.
434 (07) [M, 81Br, 37Cl, 37Cl]+, 432 (46) [M, 79Br, 37Cl, 37Cl]+, 430
5-Bromo-3-(4-chlorophenyl)-2-(4-methoxyphenyl)-1H-inden-1-one
(100) [M, 79Br, 35Cl, 37Cl]+, 428 (100) [M, 79Br, 35Cl, 35Cl]+, 395
(20), 314 (30), 286 (30), 250 (53). HRMS (EI, 70 eV): calcd. for
C21H11BrOCl2 [M, 79Br, 35Cl, 35Cl]+ 427.93648; found 427.93635.
(7c): Starting with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg,
5 mol-%), dioxane (3 mL), K3PO4 (172 mg, 0.81 mmol), 4-chloro-
phenylboronic acid (42 mg, 0.27 mmol), and 4-methoxyphenyl-
boronic acid (41 mg, 0.27 mmol) following general procedure B, 7c
was isolated as a brownish-yellow solid (90 mg, 82%). Reaction
temperature: 45 °C for 9 h then at 60 °C for 6 h; m.p. 201–203 °C.
1H NMR (250 MHz, CDCl3): δ = 3.71 (s, 3 H, OCH3), 6.74 (d, J
= 8.8 Hz, 2 H, ArH), 7.11–7.18 (m, 3 H, ArH), 7.23 (d, J = 8.6 Hz,
2 H, ArH), 7.31–7.36 (m, 4 H, ArH) ppm. 13C NMR (62.9 MHz,
CDCl3): δ = 54.2 (OCH3), 112.8 (CH), 121.2 (C), 123.1 (CH),
127.4, 128.1 (C), 128.4, 128.8 (CH), 129.9 (C), 130.3, 130.4 (CH),
Suzuki Cross-Coupling Reactions; General Procedure B: The reac-
tion was carried out in a pressure tube. To a suspension of the
brominated indenone, [Pd(PPh3)4] or [Pd(PPh3)2Cl2] (5 mol-%) and
Ar1B(OH)2 (1.0 equiv. per cross-coupling) in dioxane (3–5 mL),
was added either K3PO4 (1.5 equiv. per cross coupling) or an aque-
ous solution of K2CO3 (2 m, 1 mL). The mixture was heated at the
indicated temperature (45–60 °C) under an argon atmosphere for
the indicated period of time (9 h) and cooled to room temperature.
Ar2B(OH)2 (1.0–1.1 equiv. per cross-coupling) was added and the
reaction mixture was heated further (6 h). The reaction mixture was
cooled to room temperature, diluted with water 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; EtOAc/
heptanes).
132.2, 134.3, 146.2, 150.0, 158.6 (C), 194.3 (CO) ppm. IR (KBr): ν
˜
= 2958, 2930, 2838 (w), 1709 (s), 1600, 1576, 1510, 1485, 1455 (m),
1445, 1416, 1407, 1396, 1352, 1329, 1295 (w), 1251, 1174, 1152,
1090, 1065, 1047, 1024, 1013 (m), 974, 957 (w), 946, 879, 846, 828,
812, 779, 742, 734, 717 (m), 691, 654, 643, 632, 618, 590 (w), 566,
536 (m) cm–1. GC-MS (EI, 70 eV): m/z (%) = 426 (100) [M, 37Cl]+,
424 (77) [M, 35Cl]+, 267 (16), 239 (37). HRMS (EI, 70 eV): calcd.
for C22H14BrClO2 [M, 37Cl]+: 425.98397; found 425.983498; calcd.
for C22H14BrClO2 [M, 35Cl]+: 423.98602; found 423.985298.
5-Bromo-3-(4-ethylphenyl)-2-(4-methoxyphenyl)-1H-inden-1-one
(7a): Starting with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg,
5 mol-%), dioxane (3 mL), K3PO4 (172 mg, 0.81 mmol), 4-eth-
ylphenylboronic acid (41 mg, 0.27 mmol), and 4-methoxyphenyl-
boronic acid (41 mg, 0.27 mmol) following general procedure B, 7a
2,5-Bis(4-tert-butylphenyl)-3-(4-methoxyphenyl)-1H-inden-1-one
(8a): Starting with 5g (78 mg, 0.20 mmol), [Pd(PPh3)4] (9 mg,
3 mol-%), dioxane (3 mL), K2CO3 (2 m, 1 mL), and 4-tert-but-
was isolated as a brownish-yellow solid (90 mg, 80%). Reaction ylphenylboronic acid (79 mg, 0.44 mmol), following the general
temperature: 45 °C for 9 h then at 60 °C for 6 h; m.p. 120–122 °C.
procedure A, 8a was isolated as a brownish-yellow solid (78 mg,
1
1H NMR (300 MHz, CDCl3): δ = 1.21 (t, J = 7.6 Hz, 3 H, CH3), 78%). Reaction temperature: 70 °C for 6 h. M. p. 188–190 °C. H
2.63 (q, J = 7.6 Hz, 2 H, CH2), 3.71 (s, 3 H, OCH3), 6.73 (d, J = NMR (300 MHz, CDCl3): δ = 1.22 (s, 9 H, 3ϫ CH3), 1.27 (s, 9 H,
8.9 Hz, 2 H, ArH), 7.13–7.23 (m, 7 H, ArH), 7.30–7.35 (m, 2 H,
3ϫ CH3), 3.77 (s, 3 H, OCH3), 6.85 (d, J = 8.8 Hz, 2 H, ArH),
7.15–7.23 (m, 4 H, ArH), 7.29–7.44 (m, 8 H, ArH), 7.52 (d, J =
ArH) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 15.2 (CH3), 28.8
Eur. J. Org. Chem. 2011, 4212–4221
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4219

P. Langer et al.
FULL PAPER
7.3 Hz, 1 H, ArH) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 30.2,
19F NMR (282.4 MHz, CDCl3): δ = –112.9, –110.4 ppm. 13C NMR
30.3 (3ϫ CH3), 33.5, 33.6 (C), 55.3 (OCH3), 114.3, 120.3, 123.2 (62.9 MHz, CDCl3): δ = 55.4 (OCH3), 113.2, 113.3, 115.3 (d, JF,C
(CH), 123.3 (C), 125.1, 125.8, 126.9, 127.0 (CH), 128.1 (C), 129.6, = 21.5 Hz, CH), 116.3 (d, JF,C = 21.7 Hz, CH), 119.7, 120.4, 123.5
130.2 (CH), 132.2, 137.6, 146.3, 146.3, 150.5, 150.7, 154.0, 160.3
(CH), 126.5 (d, JF,C = 3.5 Hz, C), 127.8 (CH), 128.5 (d, JF,C =
(C), 195.4 (CO) ppm. IR (KBr): ν = 2958, 2923, 2855 (w), 1700 (s),
3.5 Hz, C), 129.4 (C), 130.0 (CH), 130.3 (d, JF,C = 8.3 Hz, CH),
127.9 (d, JF,C = 8.1 Hz, CH), 132.3, 141.7, 145.7, 146.8, 153.6,
˜
1597, 1499, 1463, 1352, 1248, 1175, 1111, 1092, 1070, 1023 (m),
821 (s), 808, 784, 740, 729, 573, 543, 534 (m) cm–1. GC-MS (EI, 160.0 (C), 162.4 (d, JF,C = 248.6 Hz, C), 163.2 (d, JF,C = 250.3 Hz,
70 eV): m/z (%) = 500 (100) [M]+, 485 (70), 235 (21). HRMS (EI,
C), 195.7 (CO) ppm. IR (KBr): ν = 2919, 2850 (w), 1704, 1596 (s),
˜
70 eV): calcd. for C36H36O2 [M]+ 500.27098; found 500.271551.
1575, 1510, 1495, 1463, 1351 (m), 1279, 1223, 1211, 1186, 1171,
1160, 1101, 1080, 1071, 1049, 1023, 965, 951, 944, 877, 849, 838,
816, 800, 772, 747, 736, 712, 696, 676, 666, 629, 608, 581, 568, 548,
536 cm–1. EI (70 eV): m/z (%) = 424 (100) [M]+. HRMS (EI, 70 eV):
calcd. for C28H18O2F2 [M]+ 424.12694; found 424.126918.
3-(4-Chlorophenyl)-2,5-bis(4-ethylphenyl)-1H-inden-1-one (8b):
Starting with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg, 5 mol-
%), dioxane (3 mL), K3PO4 (172 mg, 0.81 mmol), 4-chlorophen-
ylboronic acid (42 mg, 0.27 mmol), and 4-ethylphenylboronic acid
(90 mg, 0.60 mmol), following general procedure B, 8b was isolated
as a brownish-yellow solid (98 mg, 81%). Reaction temperature:
45 °C for 9 h then at 70 °C for 6 h; m.p. 133–134 °C. 1H NMR
(300 MHz, CDCl3): δ = 1.15 (t, J = 7.6 Hz, 3 H, CH3), 1.19 (t, J
= 7.6 Hz, 3 H, CH3), 2.55 (q, J = 7.5 Hz, 2 H, CH2), 2.61 (q, J =
7.5 Hz, 2 H, CH2), 7.04 (d, J = 8.2 Hz, 2 H, ArH), 7.12 (d, J =
8.2 Hz, 2 H, ArH), 7.17–7.21 (m, 3 H, ArH), 7.26–7.34 (m, 3 H,
ArH), 7.37–7.41 (m, 3 H, ArH), 7.54 (d, J = 7.3 Hz, 2 H,
ArH) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 14.2, 14.5 (CH3),
27.5, 27.6 (CH2), 119.0, 122.5, 126.1, 126.2 (CH), 126.6 (C), 126.7,
127.4 (CH), 128.1 (C), 128.2, 128.8, 129.0 (CH), 130.4, 132.5,
134.0, 136.6, 143.2, 143.7, 144.9, 145.8, 151.6 (C), 195.0 (CO) ppm.
5-(4-Methoxyphenyl)-2,3-bis[4-(trifluoromethyl)phenyl]-1H-inden-1-
one (9b): Starting with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg,
5 mol-%), dioxane (3 mL), 2 m K2CO3 (1 mL), 4-(trifluoromethyl)-
phenylboronic acid (102 mg, 0.54 mmol), and 4-methoyphenyl-
boronic acid (41 mg, 0.60 mmol), following the general procedure
B, 9b was isolated as a yellow solid (122 mg, 86%). Reaction tem-
1
perature: 60 °C for 9 h then at 70 °C for 6 h; m.p. 200–201 °C. H
NMR (300 MHz, CDCl3): δ = 3.76 (s, 3 H, OCH3), 6.89 (d, J =
8.8 Hz, 2 H, ArH), 7.18 (m, 1 H, ArH), 7.28 (d, J = 8.1 Hz, 2 H,
ArH), 7.41–7.48 (m, 7 H, ArH), 7.59 (d, J = 7.5 Hz, 1 H, ArH),
7.65 (d, J = 8.1 Hz, 2 H, ArH) ppm. 19F NMR (282.4 MHz,
CDCl3): δ = –62.8, –62.7 ppm. 13C NMR (62.9 MHz, CDCl3): δ =
55.4 (OCH3), 114.4, 120.2 (CH), 123.6 (q, JF,C = 272.6 Hz, CF3),
IR (KBr): ν = 3391, 3024, 2961, 2926, 2870, 1907, 1789 (w), 1706,
˜
123.8 (q, JF,C = 270.3 Hz, CF3), 124.1 (CH), 125.2 (q, JF,C
=
1595 (s), 1515 (w), 1485, 1462, 1455 (m), 1410, 1373 (w), 1351 (m),
1260 (w), 1181 (m), 1142 (m), 1087 (s), 1069, 1049 (m), 1012 (s),
963, 948, 935, 894, 862, 850 (w), 819 (s), 784, 741, 717 (m), 700,
670, 654, 638, 621, 571 (w) cm–1. GC-MS (EI, 70 eV): m/z (%) =
448 (100) [M]+, 433 (18). HRMS (EI, 70 eV): calcd. for C31H25ClO
[M]+ 448.15884; found 448.15899.
3.7 Hz, CH), 126.2 (q, JF,C = 3.8 Hz, CH), 127.4 (CH), 128.2 (C),
128.3, 128.9 (CH), 130.0 (q, JF,C = 31.5 Hz, C-CF3), 130.2 (CH),
131.5 (q, JF,C = 33.0 Hz, C-CF3), 132.3, 132.7, 133.9, 136.0, 145.2,
146.9, 154.4, 160.2 (C), 194.8 (CO) ppm. IR (KBr): ν = 2962, 2918,
˜
2849, 2837 (w), 1699, 1593, 1520, 1471, 1416, 1410 (m), 1318 (s),
1280, 1264, 1244 (m), 1160, 1120, 1112, 1068, 1058, 1033, 1016 (s),
937, 836, 819, 730, 719, 709, 698, 618, 601, 554 (m) cm–1. GC-MS
(EI, 70 eV): m/z (%) = 524 (100) [M]+. HRMS (EI, 70 eV): calcd.
for C30H18O2F6 [M]+ 524.12055; found 524.120787.
3-(4-Chlorophenyl)-2,5-bis(4-methoxyphenyl)-1H-inden-1-one (8c):
Starting with 2 (100 mg, 0.27 mmol), [Pd(PPh3)4] (14 mg, 5 mol-
%), dioxane (3 mL), K3PO4 (172 mg, 0.81 mmol), 4-chlorophen-
ylboronic acid (42 mg, 0.27 mmol), and 4-ethylphenylboronic acid
(89 mg, 0.60 mmol), following general procedure B, 8c was isolated
as a brownish-yellow solid (102 mg, 84%). Reaction temperature:
45 °C for 9 h then at 70 °C for 6 h; m.p. 133–134 °C. 1H NMR
(250 MHz, CDCl3): δ = 3.81 (s, 3 H, OCH3), 3.85 (s, 3 H, OCH3),
6.74 (d, J = 8.8 Hz, 2 H, ArH), 6.88 (d, J = 8.7 Hz, 2 H, ArH),
7.13–7.18 (m, 3 H, ArH), 7.26–7.36 (m, 5 H, ArH), 7.42 (d, J =
8.7 Hz, 2 H, ArH), 7.52 (d, J = 7.5 Hz, 1 H, ArH) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 55.2 (OCH3), 55.4 (OCH3), 113.8, 114.3,
119.5 (CH), 122.8 (C), 123.5, 126.6, 128.3 (CH), 128.7 (C), 129.3,
130.0, 131.3 (CH), 131.5, 132.7, 133.0, 135.0, 146.1, 146.4, 151.7,
Acknowledgments
Financial support by the Deutscher Akademischer Austauschdienst
(DAAD) (scholarship to D. S. Z.), by the State of Pakistan (Higher
Education Commission scholarship to M. H.) and by the State of
Mecklenburg-Vorpommern (scholarship to M. H.) is gratefully ac-
knowledged.
[1] a) G. M. Anstead, S. R. Wilson, J. A. Katzenellenbogen, J.
Med. Chem. 1989, 32, 2163; b) K. Hajela, R. S. Kapil, Ind. J.
Chem. Sect. B 1995, 34, 361; c) R. E. McDevitt, M. S. Mal-
amas, E. S. Manas, R. J. Unwalla, Z. B. Xu, C. P. Miller, H. A.
Harris, Bioorg. Med. Chem. Lett. 2005, 15, 3137; d) M. R.
Barvian, R. L. Panek, G. H. Lu, A. J. Kraker, A. Amar, B.
Hartl, J. M. Hamby, H. D. H. Showalter, Bioorg. Med. Chem.
Lett. 1997, 7, 2903.
159.4, 160.0 (C), 196.2 (CO) ppm. IR (KBr): ν = 2951, 2925, 2835
˜
(w), 1697, 1591 (s), 1516, 1462, 1455, 1442 (m), 1348, 1331, 1286
(w), 1246, 1173, 1141, 1087, 1071, 1039, 1013 (m), 936, 893, 850
(w), 836, 822, 811, 797, 786, 744, 738, 727, 718, 699, 655, 621, 571,
562 (m) cm–1. EI (70 eV): m/z (%) = 454 (40) [M, 37Cl]+, 452 (100)
[M, 35Cl]+, 226 (12). HRMS (EI, 70 eV): calcd. for C29H21O3Cl [M,
35Cl]+ 452.11737; found 452.118040.
[2] D. Mal, S. Ranjan, Org. Lett. 2009, 11, 4398.
[3] D. C. Harrowven, N. A. Newman, C. A. Knight, Tetrahedron
Lett. 1998, 39, 6757.
2,3-Bis(4-fluorophenyl)-5-(3-methoxyphenyl)-1H-inden-1-one (9a):
Starting with 6d (79 mg, 0.20 mmol), [Pd(PPh3)4] (9 mg, 3 mol-%),
dioxane (3 mL), K2CO3 (2 m, 1 mL), and 3-methoxyphenylboronic
acid (33 mg, 0.22 mmol), following general procedure A, 9a was
isolated as a yellow solid (75 mg, 88 %). Reaction temperature:
[4] J. L. Jeffrey, R. Sarpong, Org. Lett. 2009, 11, 5450.
[5] a) E. Weitz, A. Scheffer, Ber. Dtsch. Chem. Ges. 1921, 54, 2343;
b) E. D. Bergmann, J. Org. Chem. 1956, 21, 461; c) R. L.
Frank, H. Eklund, J. W. Richter, C. R. Vanneman, A. N. Wen-
nerberg, J. Am. Chem. Soc. 1944, 66, 1; d) F. M. Beringer, P. S.
Forgione, M. D. Yudis, Tetrahedron 1960, 8, 49; e) F. Koelsch,
J. Am. Chem. Soc. 1932, 54, 2487; f) J. J. Eisch, W. C. Kaska,
J. Am. Chem. Soc. 1966, 88, 2976.
1
70 °C for 6 h; m.p. 175–177 °C. H NMR (300 MHz, CDCl3): δ =
3.78 (s, 3 H, OCH3), 6.84–6.94 (m, 3 H, ArH), 6.99–7.10 (m, 4 H,
ArH), 7.14–7.21 (m, 3 H, ArH), 7.26–7.35 (m, 3 H, ArH), 7.41 (dd,
J = 1.4, 7.5 Hz, 1 H, ArH), 7.56 (d, J = 7.5 Hz, 1 H, ArH) ppm.
4220
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4212–4221

Site-Selective Synthesis of Arylated Indenones
[6] T. Morimoto, K. Yamasaki, A. Hirano, K. Tsutsumi, N. Ka-
gawa, K. Kakiuchi, Y. Harada, Y. Fukumoto, N. Chatani, T.
Nishioka, Org. Lett. 2009, 11, 1777.
[7] a) C. Liebermann, Ber. Dtsch. Chem. Ges. 1898, 31, 2083; b)
C. Liebermann, Ber. Dtsch. Chem. Ges. 1899, 32, 261; c) C.
Liebermann, Ber. Dtsch. Chem. Ges. 1899, 32, 920; d) C. Lieb-
ermann, Ber. Dtsch. Chem. Ges. 1900, 33, 569; e) H. Simonis,
C. Kirschten, Ber. Dtsch. Chem. Ges. 1912, 45, 567.
Langer, Tetrahedron Lett. 2009, 50, 3929; d) S.-M. Tengho Tog-
uem, M. Hussain, I. Malik, A. Villinger, P. Langer, Tetrahedron
Lett. 2009, 50, 4962; e) M. Hussain, I. Malik, P. Langer, Synlett
2009, 2691; f) T. T. Dang, T. T. Dang, N. Rasool, A. Villinger,
P. Langer, Adv. Synth. Catal. 2009, 351, 1595; g) I. Ullah, R. A.
Khera, M. Hussain, P. Langer, Tetrahedron Lett. 2009, 50,
4651; h) M. Nawaz, M. I. Farooq, A. Obaid-Ur-Rahman,
R. A. Khera, A. Villinger, P. Langer, Synlett 2010, 150.
[8] M. Hussain, T. H. Nguyen, R. A. Khera, A. Villinger, P.
Langer, Tetrahedron Lett. 2011, 52, 184.
[9] a) G. A. Sulikowski, F. Agnelli, R. M. Corbett, J. Org. Chem.
2000, 65, 337; b) F. Bellina, C. Anselmi, S. Viel, L. Mannina,
R. Rossi, Tetrahedron 2001, 57, 9997; c) F. Bellina, C. Anselmi,
R. Rossi, Tetrahedron Lett. 2001, 42, 3851.
[10] For reviews of cross-coupling reactions of polyhalogenated het-
erocycles, see: a) S. Schröter, C. Stock, T. Bach, Tetrahedron
2005, 61, 2245; b) M. Schnürch, R. Flasik, A. F. Khan, M.
Spina, M. D. Mihovilovic, P. Stanetty, Eur. J. Org. Chem. 2006,
3283; c) R. Wang, K. Manabe, Synthesis 2009, 1405.
[11] S. T. Handy, Y. Zhang, Chem. Commun. 2006, 299.
[12] For work from our laboratory, see, for example: a) T. T. Dang,
T. T. Dang, R. Ahmad, H. Reinke, P. Langer, Tetrahedron Lett.
2008, 49, 1698; b) T. T. Dang, A. Villinger, P. Langer, Adv.
Synth. Catal. 2008, 350, 2109; c) M. Hussain, T. H. Nguyen, P.
[13]
[14]
For reviews, see: a) N. Miyaura, A. Suzuki, Chem. Rev. 1995,
95, 2457; b) A. Suzuki, in: Handbook of Organopalladium
Chemistry for Organic Synthesis, vol. III, (Ed.: E. Negishi),
New York, John Wiley & Sons, 2002, p. 249.
For the synthesis of 2,3-dibromoinden-1-one, see: S. Basurto,
S. Garcia, A. G. Neo, T. Torroba, C. F. Marcos, D. Miguel, J.
Barbera, M. Blanca Ros, M. R. de la Fuente, Chem. Eur. J.
2005, 11, 5362.
[15] CCDC-819532 (for 5d), -819533 (for 6g), and -819534 (for 9b)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Received: March 4, 2011
Published Online: June 1, 2011
Eur. J. Org. Chem. 2011, 4212–4221
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4221