A general synthesis of diarylketones by means of a three-component cross-coupling of aryl and heteroaryl bromides, carbon monoxide, and boronic acids

Article abstract of DOI:10.1002/chem.200800001

Pd(OAc)₂/di-1-adamantyl-n-butylphosphine (cataCXium A) is highly active in the three-component Suzuki carbonylation and represents the most general catalyst system reported up to now. A broad range of aryl/heteroaryl bromides and aryl boronic acids can be coupled to the corresponding diarylketones at low catalyst loadings.

Full text of DOI:10.1002/chem.200800001

FULL PAPER
DOI: 10.1002/chem.200800001
A General Synthesis of Diarylketones by Means of a Three-Component
Cross-Coupling of Aryl and Heteroaryl Bromides, Carbon Monoxide, and
Boronic acids
Helfried Neumann, Anne Brennführer, and Matthias Beller*[a]
Dedicated to Professor Wolfgang A. Herrmann on the occasion of his 60th birthday
Abstract: PdACHTREUNG(OAc)2/di-1-adamantyl-n-butylphosphine (cataCXium A) is highly
Keywords:
diarylketones
catalysis
component reactions
carbon monoxide
·
active in the three-component Suzuki carbonylation and represents the most gen-
eral catalyst system reported up to now. A broad range of aryl/heteroaryl bromides
and aryl boronic acids can be coupled to the corresponding diarylketones at low
catalyst loadings.
·
homogeneous
·
palladium
·
three-
Introduction
sertion of carbon monoxide into the Ar–Pd–X species. In
1993, Suzuki et al. introduced the coupling of aryl boronic
acids with aryl iodides in the synthesis of diarylketones
(Suzuki carbonylation).[10] In principle, these reactions pro-
vide a versatile tool for organic synthesis as boronic acids
are generally nontoxic and thermally, air, and moisture
stable. However, the selectivity of the coupling reaction
drops when aryl bromides are used. Although Suzuki et al.
later improved the cross-coupling for aryl triflates and aryl
bromides by using PdCl2 and 1,1’-bis(diphenylphosphino)-
Diarylketones constitute an interesting and versatile struc-
tural motif[1] which is frequently present in natural products
(e.g. Cotoin, Papaveraldine), in non-steroidal anti-inflamma-
tory drugs (e.g. Suprofen, Ketoprofen), and occurs in UV
screens (e.g. Sulisobenzone, Oxybenzone). Typically, diaryl-
ACHTREUNGketones are prepared by Friedel–Crafts acylation of ortho/
para-directing arenes with acyl halides.[2] Unfortunately, this
reaction requires overstoichiometric amounts of Lewis acid
and the regioselectivity is often limited to the para-position.
Other synthetic strategies use cross-coupling reactions of
benzoic halides with organotin compounds,[3] palladium-cat-
alyzed coupling of boronic acids with carboxylic anhydride,[4]
or nickel-catalyzed coupling reactions of aryl iodides with
aromatic aldehydes.[5] An especially versatile approach for
the synthesis of diarylketones[6] is the transition-metal-cata-
lyzed three-component cross-coupling of Aryl-X (X=Br, I,
OTf, N2+) derivatives, carbon monoxide, and arylmetal re-
agents. However, the coupling reaction of organoalumin-
ium,[7] organosilane,[8] or organotin[9] compounds with elec-
tron-poor aryl halides is severely limited due to the forma-
tion of biaryl side products. Here, electron-withdrawing
groups on the aryl ring accelerate the rate of transmetalla-
tion to form the Ar–Pd–Ar intermediate and hinder the in-
AHCTREfUNG errocene as a catalyst, still three equivalents of NaI or KI
were required as an additive.[11]
Until now, relatively few palladium-mediated catalyst sys-
tems have been applied to the carbonylative Suzuki reac-
tion, and limitations of the protocols still remain. Castanet
et al.[12] introduced a catalyst system ([PdCl
CHTRE(UNG PCy3)2]) which
2A
is applicable for carbonylative cross-coupling of pyridyl
halides with phenyl boronic acid in the presence of carbon
monoxide. Pd/thiourea catalysts with phosphine-free
ligand[13] only promote the Suzuki carbonylation of aryl
iodides. More recently, [Pd(PPh3)4] has been applied to aryl
AHCTREUNG
a
A
ACHTREUNG
triflates, but again additional halide salts are needed.[14] To
the best of our knowledge, there is no general method for
the synthesis of diaryl and aryl heteroaryl ketones by means
of a Suzuki-type carbonylative cross-coupling reaction.
Some years ago, we introduced Pd/diadamantylalkyl-
AHCTREpUNG hosphine catalysts for coupling reactions. The most power-
[a] Dr. H. Neumann, A. Brennführer, Prof. Dr. M. Beller
Leibniz-Institut für Katalyse an der Universität Rostock e.V.
Albert-Einstein-Str. 29a, 18059 Rostock (Germany)
Fax : (+49)381-1281-5000
ful system is based on Pd/diadamantyl-n-butylphosphine
(cataCXium A), which is active in Heck,[15] Suzuki,[16] and
Sonogashira coupling reactions,[17] amination of aryl chlor-
ides,[18] as well as a-arylation of ketones with chloro-
E-mail: matthias.beller@catalysis.de
Chem. Eur. J. 2008, 14, 3645 – 3652
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3645

ACHTREUNG
arenes.[19] More recently, we successfully employed this cata-
Table 1. Screening of various ligands for the model reaction.
lyst system in reductive carbonylations[20] and alkoxycarbo-
nylations[21] of aryl and heteroaryl bromides. Encouraged by
these results and in order to overcome the limitations of
known procedures, we started to look at the palladium-cata-
lyzed Suzuki carbonylation. Herein, we describe our investi-
gations which led to a convenient and general method to
synthesize all kinds of symmetrical and unsymmetrical
Entry Ligand Ligand
Conversion Diaryl
Biaryl Selectivity
[mol%] [%][a]
ketone
[%][a]
[%][a]
[%][a]
1
2
3
4
5
6
7
8
1
2
0.75
0.75
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
20
12
6
2
10
6
0
0
0
12
87
92
0
3a
3b
3c
4
5a
5b
5c
6
1
0
0
12
87
99
92
21
26
11
13
51
41
18
7
0
1
5
13
0
90
15
54
44
86
27
0
ACHTREUNGdiarylketones.
9
Results and Discussion
10
11
12
0
0
7
8
1.5
1.5
0
0
0
0
As a starting point the reaction of 4-bromoanisole with
phenyl boronic acid (1.5 equiv) in the presence of carbon
monoxide was investigated (Scheme 1). The experiments on
the model system were carried out in a modified six-fold
Reaction conditions: 4-bromoanisole (2 mmol), PhB(OH)2 (3 mmol), Pd-
(OAc)2 (0.5 mol%), TMEDA (1 equiv), toluene (2 mL), hexadecane (0.2
AHCTREUNG
equiv), 5 bar CO, 1008C, 24 h. [a] Determined by gas chromatography.
Chelating ligands 1,3-bis(di-
phenylphosphino)propane
(dppp, 1) and 1,1’-bis(diphenyl-
phosphino)ferrocene (dppf, 2),
Scheme 1. Carbonylative Suzuki reaction of the model substrate.
which are used in alkoxycarbo-
nylation of aryl halides,[22] gave
parallel autoclave (reaction volume 4 mL) under 5 bar CO
at 1008C. Comparably low catalyst loading (0.5 mol%
only a low conversion (12–20%) and yield (2–10%) of the
desired product (Table 1, entries 1–2). Also a number of
standard monodentate phosphines (3a–c) yielded 4-
Pd
used. Initially, we tested the activity of 12 different
phosphine and carbene ligands. The results of the ligand
screening are shown in Table 1.
ACHTREUNG(OAc)2) and a three-fold excess of ligand (P/Pd 3:1) were
methoxy
ACHRTUNEGbenzoACHTRENUG
A
tries 3–5). In contrast, ACHTREUNG
A), and 5b afforded the target compound in 41–54% yield
and the undesired biaryl side product was obtained in only
5–13% yield, respectively (Table 1, entries 7–8). Interesting-
ly, when we used the sterically and electronically compara-
ble tri-tert-butylphosphine 4, we observed high conversion
(87%), but only low selectivity (13% yield) (Table 1,
entry 6). Dialkyl heteroACHTREaUGN ryl phosphines were significantly
less active or nearly inactive for the desired reaction
(Table 1, entries 10–12).
Based on the promising results, we studied the influence
of pressure and base in the model carbonylation in the pres-
ence of 5a more carefully. As shown in Table 2, carbonyla-
tive cross-coupling in the presence of solid bases, for exam-
ple, K2CO3, K3PO4, or NaOEt, gave low selectivity and
yields of the desired product (3–20%, entries 1–3). Applying
trialkylamines showed that a proper choice of the CO pres-
sure is crucial for yield and chemoselectivity. Interestingly,
EtNACTHREU(GN iPr)2 and NEt3 provided an increased product yield at
higher CO pressure than at low pressure (5 bar, 55–88%
versus 2.5 bar, 23–66%, Table 2, entries 4–7). In contrast,
the unwanted Suzuki coupling product is formed predomi-
nantly at low CO pressure (5 bar, 2–7% versus 2.5 bar, 34–
35%). This behavior is not surprising as transmetallation of
the Ar–Pd–X intermediate is suppressed by a higher CO
pressure. Therefore, the yield of the desired diarylketone is
increased. In contrast, TMEDA (TMEDA: N,N,N’,N’-tetra-
methylethylenediamine) yielded more product at 2.5 bar CO
3646
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Chem. Eur. J. 2008, 14, 3645 – 3652

General Synthesis of Diarylketones
FULL PAPER
(60%) than at 5 bar CO
(51%) while the amount of by-
product is low (6–7%) in each
case (Table 2, entries 8–9).
Next, we explored the gen-
erality of our catalyst system
(Pd/cataCXium A) by reacting
different aryl and heteroaryl
Scheme 2. Synthesis of Suprofen.
bromides with aryl boronic acids in the presence of CO.
Table 3 shows that both electron-rich and -poor aryl
tained in 67% yield (Table 3, entry 18). Remarkable exam-
ples for the high selectivity of the catalyst are the cross-
coupling reactions of 4-vinylphenylboronic acid. Despite the
possibility of a competitive Heck-, Suzuki-, and carbonyla-
tive Heck reaction, these couplings proceeded with excellent
selectivity. Thus, 4-bromobenzotrifluoride, 4-bromoanisole,
and 2- and 3-bromothiophene reacted with 4-vinylphenyl-
boronic acid in the presence of CO to give exclusively the
desired diarylketones in 80, 73, 63, and 65% yields, respec-
tively (Table 3, entries 8–9 and 11–12). The resulting diaryl-
Table 2. Influence of different bases on the yield of 4-methoxybenzo-
ACHTREUNG
p
Conversion Diaryl
Biaryl
[%][a]
Selectivity
[%][a]
[bar] [%][a]
ketone
[%][a]
1
2
3
4
5
6
7
8
K2CO3
K3PO4
NaOEt
5.0
5.0
5.0
5.0
2.5
5.0
2.5
5.0
2.5
5.0
2.5
52
61
94
94
99
92
69
98
93
7
20
19
3
88
66
55
23
51
60
0
33
43
65
2
35
7
34
6
7
38
31
4
94
67
60
33
60
76
0
AHCTREkUNG etones are interesting substrates for further refinement to-
wards pharmaceuticals. Hence, 4-vinylphenyl 2-thienyl
ketone (Table 3, entry 12) is easily hydroxycarbonylated[24]
in one step to Suprofen, a commercial nonsteroidal anti-in-
flammatory drug (Scheme 2).
NEt3
EtNACHTREUNG(iPr)2
TMEDA
pyridine
9
10
11
0
0
9
1
11
Conclusion
Reaction conditions: 4-bromoanisole (2 mmol), PhB(OH)2 (3 mmol),
Pd(OAc)2 (0.5 mol%), cataCXium A (1.5 mol%), base (2 equiv), toluene
A
ACHTREUNG
We have developed a general and efficient synthesis of
diaryl-, diheteroaryl-, and aryl heteroaryl ketones by a
three-component cross-coupling reaction of aryl/heteroaryl
bromides, aryl boronic acids, and carbon monoxide. This re-
action offers efficient access to various biologically active
compounds as shown by the two-step preparation of
AHCTRESUNG uprofen. Remarkable features of our catalyst are the high
selectivity and the improved productivity. Furthermore the
system is easily handled (air-stable).
(2 mL), hexadecane (0.2 equiv), 2.5–5.0 bar CO, 1008C, 24 h. [a] Deter-
mined by gas chromatography.
ACHTREUNGbromides and aryl boronic acids were successfully converted
by means of a carbonylative cross-coupling reaction. Nota-
bly, for aryl bromides with electron-withdrawing substitu-
ents, which are known to support direct coupling to give
biaryls, an increased CO pressure of 5 bar often led to
better results. As an example, reaction of 4-bromobenzotri-
fluoride with different boronic acids gave selectively
ACHTREUNG(>99%) the diarylACHTREUNGketones as a single product (Table 3, en-
Experimental Section
tries 3–5). Experiments using 4-chlorobromobenzene, 3-bro-
mopyridine, and 2- and 4-bromobenzonitrile provided the
diarylketone/biaryl in 70/7, 64/4, 60/39, and 89/10% yields,
respectively (Table 3, entries 21, 25–27). When electron-rich
and electron-neutral aryl bromides were employed, the cou-
pling-reaction proceeded with good yields and in almost
every case no biaryl side products were observed (Table 3,
entries 1, 2, 6, 9, 22–24, and 28). From a synthetic viewpoint,
it is important to note that various combinations of hetero-
General information: Toluene was destilled from sodium and benzo-
AHCTREpUNG henone. All reactions were performed by using standard Schlenk tech-
niques (argon). 1H and 13C NMR spectra were recorded on a Bruker AV
300/AV 400 spectrometer at 258C. Chemical shifts (d) are given in ppm
and refer to the residual undeuterated solvent as the internal standard
([D6]DMSO: d=2.50/39.7 ppm). Gas chromatography was performed on
a Hewlett–Packard HP 6890 chromatograph with a HP5 column. Chemi-
cals were purchased from Fluka, Aldrich, Strem and used as received.
The cataCXium A ligand is available from Strem or directly from Evonik
Degussa.
aryl ACHTREUNGbromides with heteroaryl boronic acids can be coupled
General procedure for the 6-fold parallel autoclave: A 50 mL Schlenk
efficiently by our catalyst system. Hence, a carbonylative
Suzuki reaction of 3-bromobenzothiophene, 3-bromothio-
phene, and 3-bromopyridine[23] with 3-thiophene boronic
acid resulted in diarylketone/biaryl in 81/11, 59/0, and 60/
25% yields, respectively (Table 3, entries 13, 17, and 20).
When NEt3 was used as the base, in general the Suzuki
carbonylation occurred with lower selectivity with the ex-
ception that the symmetrical bis(3-thienyl) ketone was ob-
flask was charged with PdACHTRE(UNG OAc)2 (22.5 mg, 0.5 mol%), cataCXium A
(108 mg, 1.5 mol%) and toluene (20 mL). Subsequently, hexadecane
(1.17 mL, internal GC standard) and TMEDA (2.25 mL, 15 mmol) were
added. This clear-yellow stock solution (2.34 mL) was transferred to six
vials (4 mL reaction volume) equipped with a septum, a small cannula, a
stirring bar, 2 mmol of the corresponding aryl bromide, and 3 mmol of
the corresponding boronic acid. The vials were placed in an alloy plate,
which was transferred to a 300 mL autoclave of the 4560 series from Parr
Instruments under an argon atmosphere. After flushing the autoclave
Chem. Eur. J. 2008, 14, 3645 – 3652
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M. Beller et al.
Table 3. Scope and limitations of the carbonylative Suzuki reaction.
Entry
Aryl bromide
Boronic acid
T [8C]
CO [bar]
5.0
Ketone
Yield [%]
70
Biaryl [%]
0
1
100
2
3
100
100
5.0
5.0
63
79
0
0
4
5
100
100
5.0
5.0
73
81
0
0
6[a]
100
2.5
65
0
7[a]
80
80
2.5
2.5
65
80
3
0
8[a]
9[a]
100
100
2.5
5.0
73
43
0
35
10[a],[b]
11[a]
12[a]
100
80
2.5
2.5
63
65
0
0
13[a]
80
100
2.5
5.0
81
26
11
84
14[a],[b]
15[a]
80
100
2.5
5.0
75
28
10
62
16[a],[b]
17[a]
100
110
2.5
5.0
59
67
0
0
18[a],[b]
19[a]
20[a]
100
120
5.0
10
45
60
30
25
21
100
5.0
70
7
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Chem. Eur. J. 2008, 14, 3645 – 3652

General Synthesis of Diarylketones
Table 3. (Continued)
FULL PAPER
Entry
Aryl bromide
Boronic acid
T [8C]
CO [bar]
2.5
Ketone
Yield [%]
60
Biaryl [%]
0
22[a]
100
23
100
100
100
100
100
100
5.0
5.0
5.0
5.0
5.0
5.0
74
73
64
60
89
64
0
0
24
25
4
26[a]
27[a]
28[a]
39
10
0
Reaction conditions: aryl bromide (2 mmol), aryl boronic acid (3 mmol), Pd
ACHTRE(UNG OAc)2 (0.5 mol%), cataCXium A (1.5 mol%), TMEDA (1 equiv), toluene
(2 mL), hexadecane (0.2 equiv), 2.5–5.0 bar CO, 808CÀ1208C, 24 h. [a] Yield determined by gas chromatography. [b] NEt3 (2 equiv) is used as the base.
three times with carbon monoxide a pressure of 2.5 to 5 bar, the carbon
monoxide was adjusted at ambient temperature and the reaction was per-
formed for 24 h at 80–1008C. Before and after the reaction, an aliquot of
the reaction mixture was subjected to GC analysis for determination of
yield and conversion.
(49), 127 (54), 111 (57), 83 (11), 77 (9); HRMS (EI): m/z: calcd for
C15H10OS: 238.04469; found: 238.04424 [M+].
4-Trifluoromethylbenzophenone: Yield 79%; m.p. 1098C; Rf =0.25
(EtOAc/heptane 0.25:10); 1H NMR (300 MHz; [D6]DMSO): d=7.96–
7.90 (brs, 4H), 7.79–7.76 (m, 2H), 7.75–7.70 (m, 1H), 7.61–7.56 ppm (m,
2H); 13C NMR (75 MHz; [D6]DMSO): d=195.1 (C=O), 140.9, 136.4,
Phenyl thiophen-3-yl methanone: Colorless oil; yield 70%; Rf =0.11
133.5 (CH), 132.1 (q, 2J
ACHTREUNG
1
(EtOAc/heptane 0.25:10); H NMR (300 MHz; [D6]DMSO): d=8.22 (dd,
(CH), 125.7 (q, 3J(C,F)=3.9 Hz, CH), 124.0 ppm (q, 1J
A
ACHTREUNG
J=2.8, 1.3 Hz, 1H), 7.82–7.79 (m, 2H), 7.72 (dd, J=4.9, 2.8 Hz, 1H),
7.70–7.64 (m, 1H), 7.59–7.52 ppm (m, 3H); 13C NMR (75 MHz;
IR (KBr): n˜ =3063 (w), 1652 (vs, C=O), 1598 (m), 1577 (m), 1508 (m),
1448 (m), 1409 (s), 1330 (vs), 1282 (vs), 1169 (vs), 1122 (vs), 1066 (vs),
1017 (s), 943 (s), 925 (s), 858 (vs), 797 (m), 751 (s), 716 (s), 699 (vs), 656
(m), 468 cmÀ1 (m); MS (70 eV): m/z (%): 250 (67) [M+], 231 (12), 181
(9), 173 (42), 145 (54), 125 (9), 105 (100), 95 (11), 77 (50), 51 (21);
HRMS (EI): m/z: calcd for C14H9F3O: 250.06000; found: 250.05946 [M+
].
[D6]DMSO): d=189.3 (C=O), 140.6, 138.3, 135.5 (CH), 132.6 (CH), 129.2
(CH), 128.8 (CH), 128.2 (CH), 127.8 ppm (CH); IR (KBr): n˜ =3106 (m),
2927 (w), 1650 (vs, C=O), 1598 (s), 1577 (m), 1510 (vs), 1446 (s), 1410
(vs), 1388 (s), 1307 (m), 1277 (vs), 1178 (m), 1138 (m), 1075 (m), 1028
(w), 1001 (w), 969 (m), 859 (vs), 821 (s), 781 (s), 718 (vs), 672 cmÀ1 (s);
MS (70 eV): m/z (%): 188 (100) [M+], 160 (6), 111 (93), 105 (31), 83
(14), 77 (40), 51 (21); elemental analysis calcd (%) for C11H8OS: C 70.18,
H 4.28, S 17.03; found: C 70.20, H 4.39, S 16.87.
2-Methoxyphenyl 4-trifluoromethylphenyl methanone: Yield 73%; m.p.
788C; Rf =0.15 (EtOAc/heptane 0.5:10); 1H NMR (400 MHz;
[D6]DMSO): d=7.90–7.85 (m, 4H), 7.59 (quasitd, J=7.9, 1.3 Hz, 1H),
7.41 (dd, J=7.5, 1.3 Hz, 1H), 7.22 (d, J=8.3 Hz, 1H), 7.12 (t, J=7.5 Hz,
1H), 3.66 ppm (s, 3H; OCH3); 13C NMR (75 MHz; [D6]DMSO): d=
Naphthalen-2-yl thiophen-3-yl methanone: Yield 63%; m.p. 109–1108C;
Rf =0.14 (EtOAc/heptane 1:20); 1H NMR (400 MHz; [D6]DMSO): d=
8.44 (brs, 1H), 8.33 (dd, J=2.7, 1.2 Hz, 1H), 8.14 (d, J=8.1 Hz, 1H),
8.08 (d, J=8.5 Hz, 1H), 8.03 (d, J=8.3 Hz, 1H), 7.88 (dd, J=8.5, 1.9 Hz,
1H), 7.75 (dd, J=5.0, 2.7 Hz, 1H), 7.70–7.62 (m, 2H), 7.60 ppm (dd, J=
5.0, 1.2 Hz, 1H); 13C NMR (75 MHz; [D6]DMSO): d=189.3 (C=O),
140.7, 135.6 (CH), 135.5, 134.9, 132.1, 130.8 (CH), 129.7 (CH), 128.6
(CH), 128.5 (CH), 128.3 (CH), 127.8 (CH), 127.8 (CH), 127.1 (CH),
125.2 ppm (CH); IR (KBr): n˜ =3120 (s), 3103 (s), 3090 (s), 3058 (m),
1636 (vs, C=O), 1574 (m), 1510 (vs), 1467 (s), 1411 (vs), 1391 (vs), 1349
(m), 1283 (vs), 1271 (vs), 1237 (vs), 1206 (m), 1184 (vs), 1139 (vs), 1114
(s), 1073 (s), 1019 (w), 980 (m), 960 (m), 918 (s), 887 (vs), 872 (vs), 836
(vs), 830 (vs), 812 (s), 792 (vs), 771 (vs), 732 (vs), 718 (s), 629 (m), 597
(s), 488 cmÀ1 (vs); MS (70 eV): m/z (%): 238 (100) [M+], 210 (9), 155
195.1 (C=O), 157.1, 140.7, 133.1 (CH), 132.6 (q, 2J
(CH), 129.5 (CH), 127.6, 125.8 (q, 3J(C,F)=3.7 Hz, CH), 124.0 (q, 1J-
(C,F)=274 Hz), 121.0 (CH), 112.4 (CH), 55.8 ppm (OCH3); IR (KBr):
ACHTRE(UNG C,F)=31 Hz), 129.9
AHCTREUNG
AHCTREUNG
n˜ =3069 (m), 3013 (w), 2941 (w), 2840 (m), 1677 (vs, C=O), 1601 (vs),
1585 (s), 1510 (m), 1488 (vs), 1468 (vs), 1433 (vs), 1411 (vs), 1327 (vs),
1315 (vs), 1295 (vs), 1265 (vs), 1248 (vs), 1161 (vs), 1139 (vs), 1111 (vs),
1065 (vs), 1048 (s), 1018 (s), 943 (vs), 926 (vs), 864 (vs), 773 (s), 756 (vs),
703 (s), 648 cmÀ1 (s); MS (70 eV): m/z (%): 280 (40) [M+], 263 (22), 211
(12), 173 (17), 145 (39), 135 (100), 121 (10), 92 (16), 77 (27); elemental
analysis calcd (%) for C15H11F3O2: C 64.29, H 3.96; found: C 64.34, H
3.72.
2,5-Dimethoxyphenyl 4-trifluoromethylphenyl methanone: Yield 81%;
m.p. 85–868C; Rf =0.08 (EtOAc/heptane 0.5:10); 1H NMR (400 MHz;
Chem. Eur. J. 2008, 14, 3645 – 3652
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3649

M. Beller et al.
[D6]DMSO): d=7.88 (brs, 4H), 7.15 (brs, 2H), 6.98 (brs, 1H), 3.75 (s,
3H, OCH3), 3.59 ppm (s, 3H, OCH3); 13C NMR (75 MHz; [D6]DMSO):
elemental analysis calcd (%) for C16H14O2: C 80.65, H 5.92; found: C
80.66, H 5.80.
d=194.7 (C=O), 153.4, 151.1, 140.6, 132.3 (q, 2J
ACHTREUNG
Thiophen-3-yl 4-vinylphenyl methanone: Yield 63%; m.p. 45–468C; Rf =
0.26 (EtOAc/heptane 1:20); 1H NMR (400 MHz; [D6]DMSO): d=8.24
(dd, J=2.8, 1.4 Hz, 1H), 7.79 (quasid, J=8.3 Hz, 2H), 7.72 (dd, J=5.1,
2.8 Hz, 1H), 7.65 (quasid, J=8.3 Hz, 2H), 7.53 (dd, J=5.1, 1.4 Hz, 1H),
6.85 (dd, J=17.7, 10.9 Hz, 1H), 6.02 (d, J=17.7 Hz, 1H), 5.44 ppm (d,
J=10.9 Hz, 1H); 13C NMR (75 MHz; [D6]DMSO): d=188.7 (C=O),
141.2, 140.6, 137.4, 136.0 (CH), 135.2 (CH), 129.8 (CH), 128.2 (CH),
127.8 (CH), 126.4 (CH), 117.3 ppm (CH2); IR (KBr): n˜ =3102 (m), 3082
(s), 2925 (w), 1635 (vs, C=O), 1603 (vs), 1558 (m), 1511 (s), 1411 (vs),
1387 (s), 1308 (m), 1281 (vs), 1232 (m), 1202 (w), 1180 (m), 1138 (s), 1118
(m), 1077 (w), 995 (s), 972 (s), 914 (s), 880 (m), 864 (vs), 855 (vs), 813 (s),
766 (vs), 717 (vs), 701 cmÀ1 (vs); MS (70 eV): m/z (%): 214 (100) [M+],
186 (9), 152 (3); elemental analysis calcd (%) for C13H10OS: C 72.87, H
4.70, S 14.96; found: C 72.52, H 4.96, S 14.56.
(CH), 128.2, 125.8 (q, 3J
A
ACHTREUNG
118.1 (CH), 114.2 (CH), 113.8 (CH), 56.2 (OCH3), 55.8 ppm (OCH3); IR
(KBr): n˜ =3067 (w), 2963 (w), 2836 (m), 1954 (w), 1677 (vs, C=O), 1588
(m), 1495 (vs), 1473 (s), 1445 (s), 1425 (vs), 1410 (s), 1325 (vs), 1313 (vs),
1290 (vs), 1263 (s), 1236 (vs), 1219 (vs), 1171 (vs), 1139 (vs), 1112 (s),
1064 (vs), 1048 (vs), 1023 (vs), 967 (vs), 867 (vs), 850 (s), 810 (vs), 777
(s), 726 (s), 705 cmÀ1 (s); MS (70 eV): m/z (%): 310 (100) [M+], 293 (23),
252 (17), 173 (25), 165 (57), 151 (34), 145 (55), 122 (8), 107 (13), 95 (8),
77 (10); elemental analysis calcd (%) for C16H13F3O3: C 61.94, H 4.22;
found: C 61.99, H 4.02.
1-[4-(4-Methoxybenzoyl)phenyl]-ethanone: Yield 57%; m.p. 105–1068C;
Rf =0.17 (EtOAc/heptane 1:5); 1H NMR (400 MHz; [D6]DMSO): d=
8.09 (quasid, J=8.5 Hz, 2H), 7.78 (quasid, J=8.5 Hz, 2H), 7.76 (quasid,
J=9.0 Hz, 2H), 7.10 (quasid, J=9.0 Hz, 2H), 3.87 (s, 3H; OCH3),
2.65 ppm (s, 3H; COCH3); 13C NMR (75 MHz; [D6]DMSO): d=197.7
(C=O), 193.9 (C=O), 163.3, 141.5, 138.9, 132.3 (CH), 129.3 (CH), 128.9,
128.2 (CH), 114.0 (CH), 55.6 (OCH3), 27.0 ppm (COCH3); IR (KBr): n˜ =
2967 (m), 2938 (m), 2843 (m), 1685 (vs, C=O), 1642 (vs, C=O), 1603 (vs),
1576 (m), 1509 (m), 1497 (m), 1417 (m), 1403 (m), 1358 (m), 1307 (vs),
1291 (vs), 1258 (vs), 1175 (s), 1149 (s), 1119 (m), 1028 (s), 963 (w), 932
(s), 862 (s), 850 (s), 837 (s), 766 (vs), 684 (s), 652 cmÀ1 (m); MS (70 eV):
m/z (%): 254 (58) [M+], 239 (28), 211 (8), 147 (6), 136 (9), 135 (100), 107
(6), 92 (16), 77 (16); elemental analysis calcd (%) for C16H14O3: C 75.57,
H 5.55; found: C 75.35, H 5.31.
Thiophen-2-yl 4-vinylphenyl methanone: Yield 60%; m.p. 47–488C; Rf =
0.22 (EtOAc/heptane 1:20); 1H NMR (400 MHz; [D6]DMSO): d=8.12
(dd, J=4.9, 1.1 Hz, 1H), 7.83 (quasid, J=8.3 Hz, 2H), 7.74 (dd, J=3.8,
1.1 Hz, 1H), 7.67 (quasid, J=8.3 Hz, 2H), 7.29 (dd, J=4.9, 3.8 Hz, 1H),
6.85 (dd, J=17.7, 10.9 Hz, 1H), 6.02 (d, J=17.7 Hz, 1H), 5.45 ppm (d,
J=10.9 Hz, 1H); 13C NMR (75 MHz; [D6]DMSO): d=186.7 (C=O),
142.8, 141.0, 136.6, 135.8 (CH), 135.6 (CH), 135.3 (CH), 129.4 (CH),
128.8 (CH), 126.3 (CH), 117.2 ppm (CH2); IR (KBr): n˜ =3084 (m), 1623
(vs, C=O), 1602 (s), 1510 (m), 1411 (s), 1355 (s), 1294 (s), 1233 (w), 1183
(w), 1056 (w), 1003 (w), 928 (m), 884 (m), 860 (s), 780 (m), 740 (s),
714 cmÀ1 (s); MS (70 eV): m/z (%): 214 (100) [M+], 197 (9) 187 (11), 152
(2); elemental analysis calcd (%) for C13H10OS: C 72.87, H 4.70, S 14.96;
found: C 73.06, H 4.63, S 14.61.
1-{4-[4-(trifluoromethyl)benzoyl]phenyl}-ethanone: Yield 56%; m.p. 124–
1
1258C; Rf =0.16 (EtOAc/heptane 1:7); H NMR (400 MHz; [D6]DMSO):
d=8.12 (quasid, J=8.6 Hz, 2H), 7.95 (brs, 4H), 7.88 (quasid, J=8.6 Hz,
2H), 2.66 ppm (s, 3H; COCH3); 13C NMR (75 MHz; [D6]DMSO): d=
Benzo[b]thiophen-3-yl thiophen-3-yl methanone: Yield 40%; m.p. 86–
878C; Rf =0.21 (EtOAc/heptane 1:20); H NMR (300 MHz; [D6]DMSO):
1
197.9 (C=O), 194.8 (C=O), 140.3, 139.9, 139.9, 132.5 (q, 2J
ACHTREUNG
d=8.62 (brs, 1H), 8.41–8.40 (m, 1H), 8.36 (dd, J=2.8, 1.4 Hz, 1H), 8.14–
8.11 (m, 1H), 7.74 (dd, J=5.1, 2.8 Hz, 1H), 7.60 (dd, J=5.1, 1.4 Hz, 1H),
7.56–7.46 ppm (m, 2H); 13C NMR (75 MHz; [D6]DMSO): d=183.7 (C=
O), 142.0, 139.8, 139.1 (CH), 137.1, 134.6 (CH), 134.4, 128.0 (CH), 127.8
(CH), 125.7 (CH), 124.4 (CH), 123.1 ppm (CH); IR (KBr): n˜ =3104 (s),
2925 (w), 1635 (vs, C=O), 1591 (s), 1557 (m), 1507 (vs), 1494 (vs), 1459
(vs), 1425 (vs), 1351 (s), 1261 (vs), 1243 (vs), 1202 (s), 1180 (vs), 1152
(m), 1134 (m), 1090 (s), 1051 (s), 1019 (m), 938 (w), 864 (s), 834 (vs), 789
(vs), 767 (vs), 737 (vs), 719 (vs), 706 (vs), 636 (m), 568 cmÀ1 (m); MS
(70 eV): m/z (%): 244 (100) [M+], 227 (7), 211 (29), 171 (13), 161 (43);
HRMS (EI): calcd for C13H8OS2: 244.00111; found: 244.00110 [M+].
130.6 (CH), 130.2 (CH), 128.6 (CH), 125.9 (q, 3J
124.0 (q, 1J
ACHTREUNG
ACHTREUNG
2850 (w), 1687 (vs, C=O), 1650 (vs, C=O), 1406 (s), 1362 (m), 1330 (vs),
1313 (vs), 1283 (s), 1266 (s), 1173 (s), 1135 (vs), 1068 (vs), 1017 (s), 964
(w), 932 (s), 865 (s), 837 (m), 771 (s), 754 (m), 697 (m), 679 (s), 617 (w),
604 (w), 590 cmÀ1 (m); MS (70 eV): m/z (%): 292 (16) [M+], 277 (100),
201 (10), 180 (6), 173 (24), 145 (26), 76 (7); elemental analysis calcd (%)
for C16H11F3O2: C 65.76, H 3.79; found: C 65.86, H 3.75.
4-Trifluoromethylphenyl 4-vinylphenyl methanone: Yield 30%; m.p. 132–
1338C; Rf =0.47 (EtOAc/heptane 1:10); 1H NMR (400 MHz;
[D6]DMSO): d=7.95–7.90 (m, 4H), 7.76 (d, J=8.4 Hz, 2H), 7.67 (d, J=
8.4 Hz, 2H), 6.86 (dd, J=17.7, 10.9 Hz, 1H), 6.04 (d, J=17.7 Hz, 1H),
5.47 ppm (d, J=10.9 Hz, 1H); 13C NMR (75 MHz; [D6]DMSO): d=194.6
3-Thiophen-3-yl-benzo[b]thiophene: Colorless oil: yield 45%; Rf =0.25
(EtOAc/heptane 0.5:10); 1H NMR (300 MHz; [D6]DMSO): d=8.07–8.03
(m, 2H), 7.88 (brs, 1H), 7.86 (dd, J=2.9, 1.3 Hz, 1H), 7.72 (dd, J=4.9,
2.9 Hz, 1H), 7.50 (dd, J=4.9, 1.3 Hz, 1H), 7.47–7.40 ppm (m, 2H);
13C NMR (75 MHz; [D6]DMSO): d=140.1, 137.3, 135.7, 132.0, 128.1
(CH), 126.9 (CH), 124.9 (CH), 124.8 (CH), 124.4 (CH), 123.4 (CH),
122.9 (CH), 122.5 ppm (CH); IR (KBr): n˜ =3100 (m), 3064 (w), 1559
(m), 1457 (m), 1428 (vs), 1404 (m), 1322 (w), 1259 (m), 1216 (m), 1178
(m), 1082 (s), 1060 (vs), 1022 (m), 883 (w), 837 (s), 791 (s), 773 (vs), 759
(vs), 732 (vs), 648 (vs), 617 cmÀ1 (w); MS (70 eV): m/z (%): 216 (100)
[M+], 184 (8), 171 (30); elemental analysis calcd (%) for C12H8S2: C
66.63, H 3.73, S 29.65; found: C 66.85, H 3.61, S 30.00.
(C=O), 142.0, 141.1, 135.9 (CH), 135.5, 132.1 (q, 2J
(CH), 130.3 (CH), 126.6 (CH), 125.7 (q, 3J
(C,F)=3.7 Hz, CH), 124.0 (q,
1J
(C,F)=273 Hz), 117.9 ppm (CH2); IR (KBr): n˜ =3069 (w), 2855 (w),
ACHTRE(UNG C,F)=32 Hz), 130.6
AHCTREUNG
ACHTREUNG
1940 (w), 1650 (vs, C=O), 1603 (vs), 1579 (w), 1554 (w), 1509 (w), 1408
(vs), 1329 (vs), 1314 (vs), 1287 (vs), 1171 (vs), 1130 (vs), 1110 (vs), 1068
(vs), 1017 (vs), 991 (s), 974 (w), 933 (vs), 865 (vs), 847 (s), 779 (vs), 772
(m), 704 (s), 688 (vs), 600 cmÀ1 (w); MS (70 eV): m/z (%): 276 (70) [M+
], 257 (8), 173 (15), 145 (32), 131 (100), 103 (20), 95 (7), 77 (25); elemen-
tal analysis calcd (%) for C16H11F3O: C 69.56, H 4.01; found: C 69.34, H
4.30.
Phenyl-quinoxalin-6-yl methanone: Yield 65%; m.p. 1178C; Rf =0.11
1
4-Methoxyphenyl 4-vinylphenyl methanone: Yield 53%; m.p. 90–918C;
Rf =0.35 (EtOAc/heptane 1:10); 1H NMR (400 MHz; [D6]DMSO): d=
7.75 (quasid, J=9.0 Hz, 2H), 7.68 (quasid, J=8.6 Hz, 2H), 7.64 (quasid,
J=8.6 Hz, 2H), 7.09 (quasid, J=9.0 Hz, 2H), 6.84 (dd, J=17.8, 11.0 Hz,
1H), 6.01 (d, J=17.8 Hz, 1H), 5.43 (d, J=11.0 Hz, 1H), 3.86 ppm (s, 3H;
OCH3); 13C NMR (75 MHz; [D6]DMSO): d=193.9 (C=O), 162.9, 140.7,
136.9, 135.9 (CH), 132.1 (CH), 129.8 (CH), 129.5, 126.1 (CH), 117.0
(CH2), 113.9 (CH), 55.6 ppm (OCH3); IR (KBr): n˜ =3003 (w), 2964 (m),
2839 (m), 1642 (vs, C=O), 1604 (vs), 1577 (s), 1554 (m), 1504 (s), 1465
(w), 1442 (w), 1416 (m), 1401 (m), 1308 (vs), 1292 (vs), 1251 (vs), 1175
(vs), 1148 (s), 1120 (m), 1032 (s), 996 (m), 968 (w), 932 (s), 859 (vs), 839
(vs), 776 (vs), 739 (m), 693 cmÀ1 (vs); MS (70 eV): m/z (%): 238 (91) [M+
], 207 (11), 195 (6), 165 (6), 135 (100), 103 (12), 92 (16), 77 (30), 63 (7);
(EtOAc/heptane 1:5); H NMR (300 MHz; [D6]DMSO): d=9.07 (dd, J=
4.7, 1.9 Hz, 2H), 8.32 (d, J=1.9 Hz, 1H), 8.26 (d, J=8.5 Hz, 1H), 8.17
(dd, J=8.5, 1.9 Hz, 1H), 7.86–7.83 (m, 2H), 7.77–7.71 (m, 1H), 7.63–
7.58 ppm (m, 2H); 13C NMR (75 MHz; [D6]DMSO): d=195.2 (C=O),
147.8 (CH), 147.2 (CH), 144.0, 141.5, 138.2, 136.7, 133.4 (CH), 131.7
(CH), 130.1 (CH), 130.0 (CH), 129.7 (CH), 128.9 ppm (CH); IR (KBr):
n˜ =3061 (m), 1654 (vs, C=O), 1609 (m), 1597 (s), 1576 (m), 1444 (s), 1421
(m), 1370 (s), 1352 (vs), 1298 (vs), 1279 (vs), 1247 (s), 1207 (w), 1176 (s),
1133 (s), 1113 (vs), 1024 (s), 964 (s), 931 (m), 910 (s), 872 (vs), 843 (m),
784 (m), 729 (vs), 703 (vs), 685 (m), 619 cmÀ1 (s); MS (70 eV): m/z (%):
234 (61) [M+], 205 (45), 157 (66), 129 (36), 105 (100), 102 (31), 77 (77),
51 (29); HRMS (EI): m/z: calcd for C15H10N2O: 234.07876; found:
234.07815 [M+].
3650
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 3645 – 3652

General Synthesis of Diarylketones
FULL PAPER
6-Phenyl-quinoxaline: Yield 26%; m.p. 89–918C; Rf =0.19 (EtOAc/hep-
tane 1:5); H NMR (300 MHz; [D6]DMSO): d=8.96 (dd, J=10.6, 1.9 Hz,
(m, 4H), 7.39–7.33 (m, 1H), 7.29 (dd, J=7.5, 1.7 Hz, 1H), 7.12 (d, J=
8.3 Hz, 1H), 7.03 (td, J=7.5, 1.2 Hz, 1H), 3.76 ppm (s, 3H; OCH3);
13C NMR (75 MHz; [D6]DMSO): d=156.2, 137.1, 131.8, 131.2 (CH),
130.4 (CH), 129.5 (CH), 128.6, 128.2 (CH), 121.0 (CH), 112.0 (CH),
55.7 ppm (OCH3); IR (KBr): n˜ =3067 (w), 2936 (m), 2835 (m), 1502 (m),
1479 (vs), 1463 (s), 1436 (s), 1397 (m), 1256 (s), 1236 (s), 1180 (m), 1162
(m), 1123 (s), 1090 (vs), 1056 (m), 1028 (s), 1004 (s), 829 (m), 801 (w),
747 cmÀ1 (vs); MS (70 eV): m/z (%): 218 (89) [M+], 203 (11), 183 (7),
168 (100), 152 (9), 149 (9), 139 (39); elemental analysis calcd (%) for
C13H11ClO: C 71.40, H 5.07, Cl 16.21; found: C 71.55, H 4.82, Cl 15.9.
1
2H), 8.34 (d, J=1.9 Hz, 1H), 8.21 (quasi dd, J=8.7, 1.9 Hz, 1H), 8.17
(quasi dd, J=8.7, 0.8 Hz, 1H), 7.91–7.87 (m, 2H), 7.58–7.52 (m, 2H),
7.49–7.44 ppm (m, 1H); 13C NMR (75 MHz; [D6]DMSO): d=146.4
(CH), 145.8 (CH), 142.7, 141.9, 141.8, 138.8, 129.9 (CH), 129.6 (CH),
129.4 (CH), 128.6 (CH), 127.5 (CH), 126.3 ppm (CH); IR (KBr): n˜ =3066
(w), 3024 (w), 2924 (s), 2853 (m), 1935 (w), 1616 (s), 1578 (m), 1484 (vs),
1454 (s), 1431 (s), 1370 (s), 1348 (m), 1317 (w), 1305 (m), 1245 (w), 1168
(m), 1134 (s), 1078 (m), 1023 (vs), 1013 (vs), 951 (vs), 897 (vs), 885 (m),
866 (vs), 839 (s), 775 (vs), 766 (vs), 698 (vs), 665 (m), 608 (w), 560 (w),
496 (m), 409 cmÀ1 (s); MS (70 eV): m/z (%): 206 (100) [M+], 179 (4), 152
(34), 102 (28), 76 (10), 63 (5); HRMS (EI): m/z: calcd for C14H10N2:
206.08385; found: 206.08402 [M+].
4-Methoxybenzophenone: Yield 75%; m.p. 528C; Rf =0.2 (EtOAc/
heptane 1:10); 1H NMR (300 MHz; [D6]DMSO): d=7.76 (quasid, J=
9.0 Hz, 2H), 7.70–7.62 (m, 3H), 7.57–7.52 (m, 2H), 7.09 (quasid, J=
9.0 Hz, 2H), 3.86 ppm (s, 3H; OCH3); 13C NMR (75 MHz; [D6]DMSO):
d=194.5 (C=O), 163.0, 137.8, 132.2 (CH), 132.1 (CH), 129.4, 129.3 (CH),
128.5 (CH), 113.9 (CH), 55.6 ppm (OCH3); IR (KBr): n˜ =3060 (w), 2934
(m), 2840 (m) 1653 (vs, C=O), 1600 (vs), 1577 (vs), 1508 (vs), 1446 (vs),
1420 (s), 1318 (vs), 1282 (vs), 1258 (vs), 1172 (vs), 1149 (m), 1112 (m),
1074 (w), 1029 (vs), 938 (s), 923 (vs), 844 (s), 793 (m), 740 (s), 702 (s),
678 (m), 600 cmÀ1 (s); MS (70 eV): m/z (%): 212 (42) [M+], 135 (100),
105 (8), 92 (10), 77 (21); elemental analysis calcd (%) for C14H12O2: C
79.22, H 5.70; found: C 78.92, H 5.77.
Di[3]thienyl ketone: Yield 43%; m.p. 718C; Rf =0.22 (EtOAc/heptane
1:10); 1H NMR (300 MHz; [D6]DMSO): d=8.36 (quasidd, J=2.4,
1.2 Hz, 2H), 7.71 (quasidd, J=4.9, 2.4 Hz, 2H), 7.55 ppm (quasidd, J=
4.9, 1.2 Hz, 2H); 13C NMR (75 MHz; [D6]DMSO): d=182.6 (C=O),
141.3, 134.3 (CH), 128.0 (CH), 127.7 ppm (CH); IR (KBr): n˜ =3106 (s),
1629 (vs, C=O), 1513 (vs), 1427 (vs), 1394 (w), 1271 (s), 1219 (w), 1178
(w), 1136 (vs), 1078 (m), 984 (w), 916 (w), 883 (s), 850 (vs), 826 (vs), 776
(s), 741 (vs), 697 (vs), 624 cmÀ1 (w); MS (70 eV): m/z (%): 194 (78) [M+
], 166 (6), 111 (100), 83 (18), 57 (7); HRMS (EI): m/z: calcd for
C9H6OS2: 193.98546; found: 193.98529 [M+].
2,4’-Dimethoxybenzophenone: Colorless oil; yield 4%; Rf =0.17 (EtOAc/
heptane 1:5); 1H NMR (300 MHz; [D6]DMSO): d=7.66 (quasid, J=
9.0 Hz, 2H), 7.54–7.48 (m, 1H), 7.26 (dd, J=7.4, 1.9 Hz, 1H), 7.17 (d, J=
8.1 Hz, 1H), 7.07 (dd, J=7.4, 0.9 Hz, 1H), 7.03 (quasid, J=9.0 Hz, 2H),
3.83 (s, 3H; OCH3), 3.68 ppm (s, 3H; OCH3); 13C NMR (75 MHz;
[D6]DMSO): d=194.3 (C=O), 163.5, 156.5, 131.9 (CH), 131.7 (CH),
130.1, 129.1, 128.6 (CH), 120.7 (CH), 114.1 (CH), 112.0 (CH), 55.7
(OCH3), 55.7 ppm (OCH3); IR (KBr): n˜ =3006 (m), 2964 (m), 2938 (m),
2845 (m), 2055 (w), 1918 (w), 1727 (m), 1654 (vs, C=O), 1600 (vs), 1576
(vs), 1509 (vs), 1486 (vs), 1465 (vs), 1450 (vs), 1422 (vs), 1306 (vs), 1296
(vs), 1257 (vs), 1195 (s), 1180 (vs), 1148 (vs), 1109 (s), 1046 (s), 1032 (vs),
942 (s), 925 (vs), 851 (vs), 789 (m), 771 (s), 756 (vs), 698 (m), 635 (m),
610 (vs), 586 (m), 561 (m), 513 cmÀ1 (m); MS (70 eV): m/z (%): 242 (40)
[M+], 225 (43), 211 (19), 197 (10), 135 (100), 121 (25), 107 (11), 92 (28),
77 (36), 64 (11); elemental analysis calcd (%) for C15H14O3: C 74.36, H
5.82; found: C 74.38, H 5.82.
Pyridin-3-ylthiophen-3-yl methanone: Yield 45%; m.p. 688C; Rf =0.16
(EtOAc/heptane 1:2); 1H NMR (300 MHz; [D6]DMSO): d=8.94 (d, J=
1.4 Hz, 1H), 8.83 (dd, J=4.9, 1.4 Hz, 1H), 8.34 (dd, J=2.8, 1.4 Hz, 1H),
8.17 (dt, J=7.9, 2.0 Hz, 1H), 7.75 (dd, J=4.9, 2.8 Hz, 1H), 7.62–7.59 (m,
1H), 7.57 ppm (dd, J=4.9, 1.4 Hz, 1H); 13C NMR (75 MHz;
[D6]DMSO): d=187.9 (C=O), 152.9 (CH), 149.6 (CH), 140.3, 136.7
(CH), 136.6 (CH), 134.0, 128.2 (CH), 127.9 (CH), 123.9 ppm (CH); IR
(KBr): n˜ =3062 (s), 1650 (vs, C=O), 1586 (vs), 1512 (s), 1478 (m), 1419
(vs), 1389 (s), 1336 (w), 1284 (vs), 1197 (m), 1155 (m), 1025 (m), 977 (w),
967 (w), 885 (w), 859 (s), 845 (s), 825 (m), 746 (s), 713 (vs), 694 (s),
623 cmÀ1 (w); MS (70 eV): m/z (%): 189 (97) [M+], 161 (10), 111 (100),
106 (7), 83 (18), 78 (21), 51 (25); HRMS (EI): m/z: calcd for C10H7NOS:
189.02429; found: 189.02382 [M+].
3-Thiophen-3-yl-pyridine: Yield 30%; m.p. 70–718C; Rf =0.24 (EtOAc/
heptane 1:2); 1H NMR (300 MHz; [D6]DMSO): d=8.98 (d, J=1.5 Hz,
1H), 8.49 (dd, J=4.9, 1.2 Hz, 1H), 8.11 (quasidt, J=8.0, 1.2 Hz, 1H),
8.04 (dd, J=2.9, 1.5 Hz, 1H), 7.70 (quasidd, J=4.9, 2.9 Hz, 1H), 7.65
(dd, J=4.9, 1.5 Hz, 1H), 7.43 ppm (quasidd, J=8.0, 4.9 Hz, 1H);
13C NMR (75 MHz; [D6]DMSO): d=148.2 (CH), 147.4 (CH), 138.4,
133.4 (CH), 130.9, 127.8 (CH), 126.2 (CH), 124.1 (CH), 122.4 ppm (CH);
IR (KBr): n˜ =3100 (s), 3077 (s), 3030 (s), 2924 (s), 1574 (s), 1527 (w),
1473 (s), 1431 (s), 1366 (m), 1322 (s), 1260 (m), 1223 (s), 1207 (m), 1182
(s), 1128 (w), 1080 (w), 1020 (s), 983 (w), 949 (m), 895 (m), 862 (vs), 822
(m), 797 (vs), 706 (vs), 641 cmÀ1 (s); MS (70 eV): m/z (%): 161 (100) [M+
], 134 (12), 117 (31), 108 (9), 89 (13), 63 (12); HRMS (EI): m/z: calcd for
C9H7NS: 161.02937; found: 161.02929 [M+].
2-Methoxybenzophenone: Pale-yellow oil; yield 73%; Rf =0.16 (EtOAc/
heptane 1:10); 1H NMR (300 MHz; [D6]DMSO): d=7.71–7.61 (m, 3H),
7.57–7.48 (m, 3H), 7.32 (dd, J=7.5, 1.9 Hz, 1H), 7.19 (d, J=7.9 Hz, 1H),
7.08 (td, J=7.5, 0.9 Hz, 1H), 3.67 ppm (s, 3H; OCH3); 13C NMR
(75 MHz; [D6]DMSO): d=195.9 (C=O), 156.8, 137.3, 133.5 (CH), 132.2
(CH), 129.4 (CH), 128.9 (CH), 128.8 (CH), 128.6, 120.8 (CH), 112.2
(CH), 55.7 ppm (OCH3); IR (KBr): n˜ =3061 (m), 2942 (m), 2838 (m),
1667 (vs, C=O), 1599 (vs), 1581 (s), 1487 (vs), 1463 (vs), 1449 (vs), 1436
(vs), 1316 (vs), 1295 (vs), 1245 (vs), 1181 (m), 1163 (m), 1151 (m), 1110
(m), 1073 (w), 1048 (s), 1024 (s), 926 (vs), 807 (m), 756 (s), 703 (s),
636 cmÀ1 (s); MS (70 eV): m/z (%): 212 (48) [M+], 195 (26), 181 (7), 167
(9), 152 (7), 135 (100), 121 (20), 105 (33), 92 (21), 77 (72), 63 (8), 51 (19);
elemental analysis calcd (%) for C14H12O2: C 79.22, H 5.70; found: C
79.11, H 5.37.
4-Chlorophenyl 2-methoxyphenyl methanone: Yield 70%; m.p. 788C;
Rf =0.2 (EtOAc/heptane 1:10); 1H NMR (400 MHz; [D6]DMSO): d=
7.70–7.67 (m, 2H), 7.59–7.54 (m, 3H), 7.35 (dd, J=7.5, 1.8 Hz, 1H), 7.19
(d, J=8.2 Hz, 1H), 7.09 (td, J=7.5, 1.0 Hz, 1H), 3.67 ppm (s, 3H;
OCH3); 13C NMR (75 MHz; [D6]DMSO): d=194.6 (C=O), 156.7, 138.1,
135.8, 132.3 (CH), 131.0 (CH), 128.9 (CH), 128.8 (CH), 127.8, 120.7
(CH), 112.0 (CH), 55.5 ppm (OCH3); IR (KBr): n˜ =3310 (w), 3086 (w),
3056 (m), 3018 (w), 2939 (m), 2838 (m), 1662 (vs, C=O), 1601 (vs), 1585
(vs), 1489 (vs), 1466 (vs), 1453 (s), 1432 (vs), 1399 (s), 1365 (w), 1304
(vs), 1296 (vs), 1266 (vs), 1244 (vs), 1178 (m), 1152 (s), 1111 (s), 1086
(vs), 1047 (s), 1024 (vs), 1013 (s), 972 (w), 941 (vs), 924 (vs), 848 (vs), 767
(s), 753 (vs), 742 (vs), 684 (m), 655 (s), 562 (m), 536 (m), 506 (s),
486 cmÀ1 (m); MS (70 eV): m/z (%): 246 (100) [M+], 229 (60), 211 (75),
201 (17), 193 (23), 181 (17), 168 (27), 152 (19); HRMS (EI): m/z: calcd
for C14H11ClO2: 246.04421; found: 246.04437 [M+]; elemental analysis
calcd (%) for C14H11ClO2: C 68.16, H 4.49; found: C 68.32, H 4.70.
3-(2-Methoxybenzoyl)pyridine: Yellow oil; yield 64%; Rf =0.1 (EtOAc/
heptane 1:3); 1H NMR (300 MHz; [D6]DMSO): d=8.79–8.77 (m, 2H),
8.03 (quasidt, J=3.4, 1.7 Hz, 1H), 7.63–7.53 (m, 2H), 7.42 (dd, J=7.5,
1.7 Hz, 1H), 7.21 (d, J=8.2 Hz, 1H), 7.12 (td, J=7.5, 0.9 Hz, 1H),
3.67 ppm (s, 3H, OCH3); 13C NMR (75 MHz; [D6]DMSO): d=194.9 (C=
O), 157.1, 153.5 (CH), 150.2 (CH), 136.6 (CH), 133.2 (CH), 132.9, 129.6
(CH), 127.4, 124.0 (CH), 121.0 (CH), 112.4 (CH), 55.8 ppm (OCH3); IR
(KBr): n˜ =3048 (m), 2964 (m), 2944 (m), 2839 (m), 1666 (vs, C=O), 1599
(vs), 1585 (vs), 1487 (vs), 1464 (s), 1437 (s), 1418 (s), 1329 (m), 1302 (vs),
1263 (vs), 1247 (vs), 1195 (w), 1182 (w), 1163 (m), 1112 (m), 1049 (m),
1024 (s), 928 (vs), 757 (vs), 714 (s), 648 cmÀ1 (s); MS (70 eV): m/z (%):
213 (32) [M+], 196 (16), 184 (10), 168 (6), 135 (100), 106 (8), 92 (22), 77
(33), 63 (8), 51 (18); HRMS (EI): m/z: calcd for C13H11NO2: 213.07843;
found: 213.07781 [M+].
4’-Chloro-2-methoxybiphenyl: Pale-yellow oil; yield 31%; Rf =0.46
(EtOAc/heptane 0.5:20); 1H NMR (300 MHz; [D6]DMSO): d=7.51–7.43
3-(2-Methoxyphenyl)pyridine: Pale-yellow oil; yield 4%; Rf =0.18
(EtOAc/heptane 1:3); 1H NMR (300 MHz; CDCl3): d=8.78 (brs, 1H),
Chem. Eur. J. 2008, 14, 3645 – 3652
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3651

M. Beller et al.
8.56 (d, J=3.8 Hz, 1H), 7.87 (dt, J=3.4, 1.8 Hz, 1H), 7.41–7.31 (m, 3H),
7.07 (td, J=7.5, 1.0 Hz, 1H), 7.02 (quasid, J=8.2 Hz, 1H), 3.83 ppm (s,
3H; OCH3); 13C NMR (75 MHz; CDCl3): d=156.7, 150.5 (CH), 148.1
(CH), 137.0 (CH), 134.4, 130.8 (CH), 129.7 (CH), 127.2, 123.1 (CH),
121.2 (CH), 111.4 (CH), 55.7 ppm (OCH3); IR (KBr): n˜ =2937 (w), 2836
(w), 1731 (w), 1599 (m), 1583 (w), 1497 (s), 1463 (s), 1436 (s), 1406 (vs),
1266 (vs), 1237 (vs), 1180 (s), 1122 (vs), 1060 (m), 1049 (m), 1025 (vs),
999 (s), 801 (s), 752 (vs), 711 cmÀ1 (vs); MS (70 eV): m/z (%): 185 (100)
[M+], 170 (58), 141 (6), 115 (30), 89 (8), 63 (8); HRMS (EI): calcd for
C12H11NO: 185.08352; found: 185.08319 [M+].
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2-(2-Methoxybenzoyl)benzonitrile: Yield 66%; m.p. 89–908C; Rf =0.07
(EtOAc/heptane 1:5); 1H NMR (300 MHz; [D6]DMSO): d=8.03–8.00
(m, 1H), 7.78 (quasidd, J=5.4, 3.6 Hz, 2H), 7.66–7.60 (m, 1H), 7.58–7.55
(m, 1H), 7.52 (dd, J=7.6, 1.7 Hz, 1H), 7.19 (d, J=8.3 Hz, 1H), 7.13 (td,
J=7.6, 1.0 Hz, 1H), 3.60 ppm (s, 3H; OCH3); 13C NMR (75 MHz;
[D6]DMSO): d=193.8 (C=O), 158.1, 141.5, 134.8 (CH), 134.4 (CH), 133.2
(CH), 132.6 (CH), 130.6 (CH), 130.4 (CH), 126.7, 121.1 (CH), 117.7,
112.7 (CH), 109.7, 55.9 ppm (OCH3); IR (KBr): n˜ =3076 (w), 2959 (m),
2929 (m), 2837 (m), 2227 (s, CN), 1729 (m), 1661 (vs, C=O), 1601 (vs),
1571 (s), 1487 (vs), 1473 (s), 1456 (s), 1437 (s), 1381 (w), 1305 (vs), 1259
(vs), 1190 (m), 1161 (m), 1120 (s), 1098 (w), 1073 (w), 1023 (s), 947 (m),
931 (vs), 811 (m), 774 (vs), 751 (vs), 691 (m), 642 (vs), 558 (w), 493 cmÀ1
(w); MS (70 eV): m/z (%): 237 (72) [M+], 220 (22), 208 (16), 181 (37),
135 (100), 130 (17), 102 (31), 92 (31), 77 (45), 63 (13), 51 (12); elemental
analysis calcd (%) for C15H11NO2: C 75.94, H 4.67, N 5.90; found: C
76.02, H 4.46, N 5.73.
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2113–2126; b) Y. Hatanaka, T. Hiyama, Synlett 1991, 845–853; c) Y.
Hatanaka, T. Hiyama, Chem. Lett. 1989, 2049–2052.
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1565; b) K. Kikukawa, T. Idemoto, A. Katayama, K. Kono, F. Wada,
T. Matsuda, J. Chem. Soc. Perkin Trans. 1 1987, 1511–1514; c) J. K.
Stille, Angew. Chem. 1986, 98, 504–519; Angew. Chem. Int. Ed.
Engl. 1986, 25, 508–524; d) K. Kikukawa, K. Kono, F. Wada, T.
Matsuda, Chem. Lett. 1982, 35–36; e) N. A. Bumagin, I. G. Bumagi-
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261, 1141–1144; f) M. Tanaka, Tetrahedron Lett. 1979, 20, 2601–
2602.
2’-Methoxybiphenyl-2-carbonitrile: Colorless oil; yield 33%; Rf =0.27
1
(EtOAc/heptane 1:5); H NMR (300 MHz; [D6]DMSO): d=7.88 (dd, J=
7.7, 1.0 Hz, 1H), 7.75 (td, J=7.7, 1.3 Hz, 1H), 7.55 (dd, J=7.7, 1.0 Hz,
1H), 7.52–7.43 (m, 2H), 7.26 (dd, J=7.5, 1.7 Hz, 1H), 7.18 (d, J=8.2 Hz,
1H), 7.08 (td, J=7.5, 1.0 Hz, 1H), 3.77 ppm (s, 3H, OCH3); 13C NMR
(75 MHz; [D6]DMSO): d=156.1, 141.9, 133.0 (CH), 132.7 (CH), 130.9
(CH), 130.6 (CH), 130.4 (CH), 127.9 (CH), 126.8, 120.6 (CH), 118.4,
112.4, 111.7 (CH), 55.4 ppm (OCH3); IR (KBr): n˜ =3066 (w), 2935 (m),
2837 (m, OCH3), 2227 (s, CN), 1602 (s), 1583 (m), 1500 (vs), 1479 (vs),
1463 (vs), 1433 (vs), 1281 (vs), 1255 (vs), 1237 (vs), 1181 (m), 1163 (m),
1126 (s), 1100 (m), 1054 (s), 1026 (vs), 1004 (m), 808 (w), 755 (vs), 621
(w), 550 cmÀ1 (m); MS (70 eV): m/z (%): 209 (100) [M+], 194 (11), 181
(51), 166 (18), 152 (10), 140 (35), 113 (7), 63 (7); elemental analysis calcd
(%) for C14H11NO: C 80.40, H 5.30, N 6.69; found: C 77.16, H 5.23, N
6.17.
[10] T. Ishiyama, H. Kizaki, N. Miyaura, A. Suzuki, Tetrahedron Lett.
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[12] a) S. Couve-Bonnaire, J.-F. Carpentier, A. Mortreux, Y. Castanet,
Tetrahedron 2003, 59, 2793–2799; b) E. Maerten, F. Hassouna, S.
Couve-Bonnaire, A. Mortreaux, J.-F. Carpentier, Y. Castanet, Synlett
2003, 1874–1876.
[13] D. Mingji, B. Liang, C. Wang, Z. You, J. Xiang, G. Dong, J. Chen, Z.
Yang, Adv. Synth. Catal. 2004, 346, 1669–1673.
[14] O. Rahman, T. Kihlberg, B Långstrçm, Eur. J. Org. Chem. 2004,
474–478.
[15] A. Ehrentraut, A. Zapf, M. Beller, Synlett 2000, 1589–1592.
[16] A. Zapf, A. Ehrentraut, M. Beller, Angew. Chem. 2000, 112, 4315–
4317; Angew. Chem. Int. Ed. 2000, 39, 4153–4155.
[17] A. Kçllhofer, T. Pullmann, H. Plenio, Angew. Chem. 2003, 115,
1086–1088; Angew. Chem. Int. Ed. 2003, 42, 1056–1058.
[18] a) A. Tewari, M. Hein, A. Zapf, M. Beller, Tetrahedron 2005, 61,
9705–9709; b) A. Ehrentraut, A. Zapf, M. Beller, J. Mol. Catal. A
2002, 182, 515–523.
2,2’-Dimethoxybenzophenone: Yield 52%; m.p. 90–918C; Rf =0.15
(EtOAc/heptane 1:5); 1H NMR (300 MHz; [D6]DMSO): d=7.53–7.47
(m, 2H), 7.39 (dd, J=7.5, 1.9 Hz, 2H), 7.08 (d, J=8.3 Hz, 2H), 7.01 (td,
J=7.5, 0.8 Hz, 2H), 3.58 ppm (s, 6H; 2OCH3); 13C NMR (75 MHz;
[D6]DMSO): d=194.5 (C=O), 158.0, 133.1 (CH), 129.9, 129.7 (CH), 120.4
(CH), 112.2 (CH), 55.8 ppm (OCH3); IR (KBr): n˜ =3103 (m), 3074 (m),
2969 (s), 2944 (s), 2842 (m), 1728 (w), 1629 (vs), 1596 (vs), 1486 (vs),
1461 (vs), 1435 (vs), 1313 (vs), 1282 (vs), 1249 (vs), 1180 (vs), 1161 (vs),
1115 (s), 1049 (s), 1018 (vs), 945 (m), 930 (vs), 793 (m), 759 (vs), 690 (m),
635 (vs), 532 (m), 419 cmÀ1 (s); MS (70 eV): m/z (%): 242 (27) [M+], 225
(15), 211 (17), 181 (11), 135 (100), 121 (23), 92 (26), 77 (37), 63 (11), 51
(8); elemental analysis calcd (%) for C15H14O3: C 74.36, H 5.82; found: C
74.39, H 5.86.
[19] A. Ehrentraut, A. Zapf, M. Beller, Adv. Synth. Catal. 2002, 344,
209–217.
[20] S. Klaus, H. Neumann, A. Zapf, D. Strübing, S. Hübner, J. Almena,
T. Riermeier, P. Groß, M. Sarich, W.-R. Krahnert, K. Rossen, M.
Beller, Angew. Chem. 2006, 118, 161–165; Angew. Chem. Int. Ed.
2006, 45, 154–158.
[21] H. Neumann, A. Brennführer, P. Groß, T. Riermeier, J. Almena, M.
Beller, Adv. Synth. Catal. 2006, 348, 1255–1261.
[22] See for example: a) M. Beller, W. Mägerlein, A. F. Indolese, C.
Fischer, Synthesis 2001, 1098–1109 and cited references therein.
b) H.-U. Blaser, M. Diggelmann, H. Meier, F. Naud, E. Scheppach,
A. Schnyder, M. Studer, J. Org. Chem. 2003, 68, 3725–3728.
[23] In this single case, a higher temperature and pressure (1208C/10 bar
CO) are needed.
Acknowledgements
The authors thank S. Giertz for excellent technical and analytical assis-
tance, as well as Dr. R. Jackstell and Dr. T. Schareina (all at the Leibniz
Institute for Catalysis) for providing ligands and complexes. Generous
[24] I. del Rꢁo, N. Ruiz, C. Claver, L. A. van der Veen, P. W. N. M. van
Leeuwen, J. Mol. Catal. B 2000, 161, 39–48.
ACHTREUNG
A
Received: January 2, 2007
Published online: February 22, 2008
3652
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 3645 – 3652