Palladium-catalyzed carbonylative heck reaction of aryl bromides with vinyl ethers to 3-alkoxy alkenones and pyrazoles

Article abstract of DOI:10.1002/chem.201103643

Three COming together: The first carbonylative Heck coupling reaction of aryl bromides and vinyl ethers leading to 1-aryl-3-alkoxy-2-propen-1-ones has been established (see scheme). Based on this coupling methodology, a novel one-pot synthesis of aryl-substituted pyrazoles was also realized. Copyright

Full text of DOI:10.1002/chem.201103643

COMMUNICATION
DOI: 10.1002/chem.201103643
Palladium-Catalyzed Carbonylative Heck Reaction of Aryl Bromides with
Vinyl Ethers to 3-Alkoxy Alkenones and Pyrazoles
Johannes Schranck, Xiao-Feng Wu, Helfried Neumann, and Matthias Beller*[a]
Since their discovery in the 1970s and 80s, palladium-cata-
lyzed coupling reactions of aryl halides have become the
most popular tool for the straightforward functionalization
of arenes and heteroarenes.[1] Apart from numerous aca-
demic developments, palladium catalysts also proved to be
successful for the production of intermediates for pharma-
ceuticals, agrochemicals, and fine chemicals on an industrial
scale.[2]
these conditions and, to the best of our knowledge, no such
example has been described until to date.
Obviously, the resulting 1-aryl-3-alkoxy propenones repre-
sent valuable monoprotected 1,3-dicarbonyl equivalents,
which are known to serve as attractive building blocks for
a variety of heterocycles.[9] On the other hand, only few syn-
thetic routes for the synthesis of this class of compounds
have been published.[10] So far, the most convenient proce-
dure makes use of the palladium-catalyzed aroylation of
vinyl ethers with benzoyl chlorides.[10] Owing to the im-
proved stability and commercial availability of aryl bro-
mides compared to benzoyl chlorides, the development of
a general procedure for the direct coupling of inexpensive
aryl bromides with vinyl ethers still represents a challenging
and important goal in coupling chemistry.
Based on our previous work in the field of palladium-cat-
alyzed carbonylations,[11] we initially investigated the reac-
tion of bromobenzene with carbon monoxide and an excess
amount of n-butyl vinyl ether (Table 1). Applying [{(cinna-
myl)PdCl}2]/L9 as the catalyst system, which was previously
optimized for the carbonylative coupling with styrenes, gave
only 24% of the desired 3-butoxy-1-phenyl-2(E)-propen-1-
one (1, Table 1, entry 8). Even lower activity was observed
in the presence of very simple monodentate ligands, such as
triphenylphosphine, tricyclohexylphosphine, tri-tert-butyl-
phosphine, or cataCXium A (Table 1, entries 1–4). Next,
some pyrrole- and imidazole-based ligands with different
electronic and steric properties were tested, but only L8
gave a moderate yield of the desired product (Table 1, en-
tries 5–7 and 9–11). For comparison, SPhos and Xanthphos
were also examined and resulted only in low yields (Table 1,
entries 12–13). Notably, the formation of significant amounts
of benzoic anhydride, N,N-diethylbenzamide, and small
amounts of benzaldehyde were responsible for the high dif-
ferences between conversion and yield.
À
Beside the common two-component C C bond forming
processes, such as Heck and Suzuki reactions, three-compo-
nent carbonylative palladium-catalyzed coupling reactions
became increasingly popular in the last decade.[3] By apply-
ing such carbonylations, the synthesis of (hetero)aromatic
ketones and alkynones, apart from the well-known esters,
amides, and acids, is possible from available (hetero)aryl
halides.[4,5,6] In this respect, our group has developed novel
carbonylative Heck-type coupling reactions in 2010. More
specifically, aryl triflates or aryl halides were reacted with
styrenes in the presence of carbon monoxide to give substi-
tuted chalcones in high yields (Scheme 1).[7] Based on this
work, very recently Skrydstrup and co-workers also de-
scribed carbonylative Heck reactions with in situ generated
CO.[8]
Scheme 1. Palladium-catalyzed carbonylative vinylations.
In our previous work, aromatic olefins reacted well with
different types of aryl halides. However, the carbonylative
coupling of aryl bromides with vinyl ethers failed under
To improve the model system, several different solvents
were tested (Table 2, entries 1–4). It is worth noting that
changing the solvent from DMF to acetonitrile or 1,4-diox-
ane increased the yield to 46 and 44%, respectively. At
lower temperature (1008C), conversion and yield dropped
[a] J. Schranck, X.-F. Wu, Dr. H. Neumann, Prof. Dr. M. Beller
Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock
Albert-Einstein-Straße 29a, 18059 Rostock (Germany)
Fax : (+49)381-1281-5000
À
because the C Br bond was not activated efficiently
(Table 2, entry 5). An increased temperature (1308C) did
not show a significant influence on the yield, since full con-
version was already achieved at 1208C (Table 2, entries 6
and 9). While the application of different bases in the model
reaction did not lead to any progress, modifications of the
E-mail: Matthias.Beller@catalysis.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103643.
Chem. Eur. J. 2012, 18, 4827 – 4831
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4827

Table 1. Palladium-catalyzed coupling of bromobenzene with butyl vinyl
ether: Variation of ligands.[a]
Table 2. Optimization of the model system: Variation of temperature,
pressure, and solvent.[a]
Entry Ligand Solvent
CO [bar] Conv. [%][b] Yield [%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
L9
L9
L9
L9
L9
L9
L9
L9
L9
L9
L9
L9
L10
L4
L5
DMF
toluene
acetonitrile
1,4-dioxane 10
1,4-dioxane 10
1,4-dioxane 20
1,4-dioxane
1,4-dioxane
10
10
10
100
70
99
100
70
100
99
100
100
100
100
100
96
24
24
46
44
24[c]
43[d]
46
5
5
48[e]
45
1,4-dioxane 20
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
acetonitrile
5
5
5
5
5
5
53[f]
56[g]
60[h]
58[h]
76[h]
52[h]
97
100
Entry
Ligand
Conv. [%][b]
Yield 1 [%][b]
[a] General reaction conditions: bromobenzene (1 mmol), n-butyl vinyl
ether (6 mmol), [{(cinnamyl)PdCl}2] (0.017 mmol), ligand (0.08 mmol),
NEt3 (2 mmol), solvent (0.5 mL), 1208C, 20 h. [b] Conversion and yield
were determined by GC based on bromobenzene using hexadecane as
the internal standard. [c] 1008C. [d] 1308C. [e] PdBr2 (0.033 mmol).
[f] PdBr2 (0.033 mmol), CO (5 bar), N2 (45 bar). [g] PdBr2 (0.033 mmol),
CO (5 bar), N2 (55 bar). [h] PdBr2 (0.033 mmol), CO (5 bar), N2 (75 bar).
1
2
3
4
5
PPh3
nBuP(Ad)2
PACHTUNGTRENNUNG(tBu)3·HBF4
PCy3
L1
72
100
95
42
75
13
14
15
6[c]
9
6
7
L2
L3
27
67
11
1
8
9
L9
L6
100
46
24
7
10
11
12
13
L7
L8
L11
Xantphos
91
99
40
100
17
24
10[c]
6
naphthyl (L9) or ortho-substituted N-aryl-moieties (L4, L5),
seem to be crucial.
The generality of the protocol was demonstrated in the
carbonylative coupling of sixteen different aryl bromides
with n-butyl vinyl ether. Notably, in all cases only the trans
coupling product was detected and less than 5% of the
Heck coupling product was observed. The reaction proceed-
ed in a highly regioselective manner and no products incor-
porating external double bonds were detected. Para-, meta-,
and even ortho-substituted aryl bromides gave the desired
products in moderate to good yields (Table 3, entries 1–12).
Electron-rich and slightly electron-deficient aryl bromides
led to the corresponding 1-aryl-3-butoxy-2-(E)-propen-1-
ones in 50–70% yield (Table 3, entries 2–9). Surprisingly,
stronger electron-poor aryl bromides, such as 4-bromoben-
zonitrile, -acetophenone, and -benzaldehyde, gave lower
yields (Table 3, entries 10–12). Nevertheless, 2-bromonaph-
thalene and some heteroaromatic substrates were coupled
smoothly in moderate to good yields (Table 3, entries 13–
16).
[a] General reaction conditions: bromobenzene (1 mmol), n-butyl vinyl
ether (6 mmol), [{(cinnamyl)PdCl}2] (0.017 mmol), ligand (0.08 mmol),
NEt3 (2 mmol), DMF (0.5 mL), CO (10 bar), 1208C, 20 h; Ad=adaman-
tyl; Cy=cyclohexyl. [b] Conversion and yield were determined by GC
based on bromobenzene using hexadecane as the internal standard.
[c] PdBr2 (0.033 mmol), acetonitrile (0.5 mL), CO (5 bar), N2 (75 bar).
palladium source showed that less-expensive palladium bro-
mide gave a slightly increased yield (Table 2, entries 7 and
8). Variations of the CO pressure hardly affected the activity
of the system (Table 2, entries 4, 7, and 9).
For further investigations, the lowest CO pressure (5 bar)
was chosen. To maximize the concentration of the low-boil-
ing vinyl ether in solution, additional nitrogen was pressur-
ized to increase the total pressure. When the total pressure
was slightly raised, the product yield was improved to 60%
(Table 2, entries 10–12).
With the best conditions in hand, we finally tested some
more commercially available ligands. To our delight, several
2-dicyclohexylphosphinopyrroles turned out to be capable li-
gands for our model system (Table 2, entries 13–15). While
cataCXium POMeCy (L4) gave the best result,[12] the struc-
turally similar SPhos ligand (L11) showed only low activity
under the same conditions (Table 2, entry 14 vs. Table 1,
entry 12). Therefore, the electronic properties of dicyclohex-
ylphosphine-substituted pyrrole ligands, as well as the steric
demand caused by substitution (L10) of the pyrrole part, N-
In the following experiments, we turned our attention to
the carbonylative vinylation with other vinyl ethers. As
shown in Scheme 2, several different vinyl ethers could be
applied successfully. Notably, using styrene under our opti-
mized conditions led to the corresponding chalcone in 99%
yield (Scheme 2). Hence, this system should lead to im-
proved yields for other chalcones as well.
Finally, we proved the possibility to transform the ob-
tained 1-aryl-3-butoxy-2-(E)-propen-1-ones in a novel one-
pot synthesis to give aryl-substituted pyrazoles, which are
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Chem. Eur. J. 2012, 18, 4827 – 4831

Palladium-Catalyzed Carbonylative Heck Reaction
COMMUNICATION
Table 3. Palladium-catalyzed coupling of aryl bromides with n-butyl vinyl
ether.[a]
Entry
1
Aryl bromide
Product
Yield [%][b]
75
2
3
4
5
54
70
50
51
Scheme 2. Palladium-catalyzed coupling of aryl bromides with n-butyl
vinyl ether (isolated yields are given).
known to have a broad spectrum of biological activities.[13]
In the past, the synthesis of 1,3-substituted pyrazoles, partic-
ularly by cyclocondensation of N-arylhydrazines with 1,3-di-
carbonyl compounds[14] or ethynyl ketones,[15] has been re-
ported. The reaction of 3-alkoxy-1-phenyl propenones with
phenylhydrazine to give pyrazoles had already been discov-
ered by Panizzi et al. in 1943.[16]
6
7
53
62
57
66
26
Hence, after the palladium-catalyzed coupling process was
finished, substituted hydrazines and molecular sieves were
added and the reaction mixture was heated at 808C for an-
other 3 h. In general, the corresponding 1,3-substituted pyra-
zoles were synthesized in moderate to good overall yields
(Scheme 3). In most cases, less than 10% of the regioisomer-
ic 1,5-disubstituted pyrazoles were detected. Simply by using
an aqueous hydrazine solution, 1-phenylpyrazole was isolat-
ed in 72% yield.
8
9
10
11
12
35
30
13
14
68
70
Scheme 3. One-pot synthesis of pyrazoles.
In conclusion, we have established the first carbonylative
Heck coupling reaction of aryl bromides and vinyl ethers. 19
different 1-aryl-3-alkoxy-2-propen-1-ones were synthesized
in 30–75% yield in a straightforward manner. Our novel
protocol is a valuable extension of the recently published
coupling of aryl halides with styrenes. Furthermore, it is ex-
emplarily shown that the PdBr2/L4 catalyst system also gave
improved yields for the carbonylative coupling of bromo-
benzene with styrene (99% yield). Based on the coupling
process, a one-pot synthesis of 1,3-diarylpyrazoles has been
15
16
56
59
[a] General reaction conditions: aryl bromide (1 mmol), n-butyl vinyl
ether (6 mmol), PdBr2 (0.033 mmol), L4 (0.08 mmol), NEt3 (2 mmol),
acetonitrile (0.5 mL), CO (5 bar), N2 (75 bar), 1208C, 20 h. [b] Isolated
yield.
Chem. Eur. J. 2012, 18, 4827 – 4831
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4829

M. Beller et al.
680–695; Angew. Chem. Int. Ed. 2005, 44, 674–688; h) K. C. Nico-
laou, P. G. Bulger, D. Sarlah, Angew. Chem. 2005, 117, 4516–4563;
Angew. Chem. Int. Ed. 2005, 44, 4442–4489; i) I. P. Beletskaya, A. V.
Cheprakov, Coord. Chem. Rev. 2004, 2337–2364; j) R. B. Bedford,
C. S. J. Cazin, D, Holder, Coord. Chem. Rev. 2004, 248, 2283- 2321.
[2] For some reviews on industrial applications, see: a) C. Torborg, M.
Beller, Adv. Synth. Catal. 2009, 351, 3027–3043; b) A. Zapf, M.
Beller, Top. Catal. 2002, 19, 101–109; c) C. E. Tucker, J. G. de Vries,
Top. Catal. 2002, 19, 111–118.
[3] For books and reviews on palladium-catalyzed carbonylation reac-
tions, see: a) A. Brennfꢀhrer, H. Neumann, M. Beller, Angew.
Chem. 2009, 121, 4176–4196; Angew. Chem. Int. Ed. 2009, 48, 4114–
4133; b) C. F. J. Barnard, Organometallics 2008, 27, 5402–5422;
c) M. Beller, in Applied Homogneneous Catalysis with Organometal-
lic Compounds, 2nd ed. (Eds.: B. Cornils, W. A. Herrmann), Wiley-
VCH, Weinheim, 2002, pp. 145–156; d) R. Skoda-Fçldes, L. Kollꢃr,
Curr. Org. Chem. 2002, 6, 1097–1119; e) J. Tsuji, Palladium Re-
agents and Catalysts: Innovations in Organic Synthesis, Wiley, Chi-
chester, 1995; f) M. Beller, B. Cornils, C. D. Frohning, W. C. Kohl-
paintner, J. Mol. Catal. A Chem. 1995, 104, 17–85; g) H. M. Colqu-
houn, D. J. Thomson, M. V. Twigg, Carbonylation, Direct Synthesis
of Carbonyl Compounds, Plenum, New York, 1991.
[4] For selected examples on palladium-catalyzed carbonylations of aryl
halides, see: a) A. Schoenberg, I. Bartoletti, R. F. Heck, J. Org.
Chem. 1974, 39, 3318–3326; b) A. Schoenberg, R. F. Heck, J. Org.
Chem. 1974, 39, 3327–3331; c) A. Schoenberg, I. Bartoletti, R. F.
Heck, J. Am. Chem. Soc. 1974, 96, 7761–7764; d) H. Neumann, A.
Brennfꢀhrer, P. Gross, T. Riermeier, J. Almena, M. Beller, Adv.
Synth. Catal. 2006, 348, 1255–1261; e) S. Klaus, H. Neumann, A.
Zapf, D. Strꢀbing, S. Hꢀbner, 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; f) A.
Brennfꢀhrer, H. Neumann, S. Klaus, T. Riermeier, J. Almena, M.
Beller, Tetrahedron 2007, 63, 6252–6258; g) H. Neumann, A. Brenn-
fꢀhrer, M. Beller, Chem. Eur. J. 2008, 14, 3645–3652.
[5] For carbonylative Suzuki reactions, see: a) H. Neumann, A. Brenn-
fꢀhrer, M. Beller, Chem. Eur. J. 2008, 14, 3645–3652; b) H. Neu-
mann, A. Brennfꢀhrer, M. Beller, Adv. Synth. Catal. 2008, 350,
2437–2442; c) N. A. Bumagin, A. B. Ponomaryov, I. P. Beletskaya,
Tetrahedron Lett. 1985, 26, 4819–4822; d) Y. Hatanaka, S. Fukushi-
ma, T. Hiyama, Tetrahedron 1992, 48, 2113–2126; e) Y. Hatanaka,
T. Hiyama, Synlett 1991, 845–853; f) Y. Hatanaka, T. Hiyama,
Chem. Lett. 1989, 2049–2052; g) T. Ishiyama, H. Kizaki, N. Miyaura,
A. Suzuki, Tetrahedron Lett. 1993, 34, 7595–7598; h) T. Ishiyama,
H. Kizaki, T. Hayashi, A. Suzuki, N. Miyaura, J. Org. Chem. 1998,
63, 4726–4731; i) S. Zheng, L. Xu, C. Xia, Appl. Organomet. Chem.
2007, 21, 772–776; j) J.-J. Brunet, R. Chauvin, Chem. Soc. Rev. 1995,
24, 89–95.
developed, demonstrating the usefulness of the synthesized
products as building blocks. Six different pyrazole deriva-
tives were prepared in an effective manner from simple bro-
mobenzene, CO, vinyl ether, and phenylhydrazine. This also
represents a new and easy access to various pyrazoles.
Experimental Section
General information: All reactions were performed by using standard
Schlenk techniques (argon). Gas chromatography was performed on
a Hewlett Packard HP 6890N chromatograph with an HP5 column.
Chemicals were purchased from Fluka, Aldrich, and Strem and used as
received. DMF, acetonitrile, dioxane, toluene, and triethylamine were dis-
tilled from sodium ketyl, CaH2, or P2O5 and stored in Aldrich Sure/store
flasks under argon.
Synthesis of 3-butoxy-1-phenyl-2(E)-propen-1-one: Six 4 mL glass vials
were charged with PdBr2 (3.3 mol%, 8.8 mg), L4 (8 mol%, 30 mg), and
a stirring bar. All vials were put into an alloy plate, equipped with
a septum and an inlet needle, and then flushed with argon. Acetonitrile
(0.5 mL), NEt3 (2 mmol, 277 mL), bromobenzene (1 mmol, 105 mL), and
butyl vinyl ether (6 mmol, 770 mL) were injected into each vial. The alloy
plate with six vials was then placed in a 300 mL autoclave (Parr Instru-
ments 4560 series). At room temperature, the autoclave was flushed with
CO, pressurized with CO to 5 bar, and finally the pressure was increased
to 80 bar by adding nitrogen. Afterwards, the autoclave was heated to
1208C for 20 h, then cooled to room temperature, and the remaining CO
and nitrogen were released slowly. After discharging, water (2 mL) was
added to each vial and the product was extracted with ethyl acetate. The
aqueous phase was extracted three times. After drying the combined or-
ganic phases over sodium sulfate and evaporating the solvent, the crude
product was purified by column chromatography (heptane/ethyl acetate
6:1) to give 3-butoxy-1-phenyl-2(E)-propen-1-one as a yellow oil.
Synthesis of 1,3-diphenylpyrazole: The synthesis of 3-butoxy-1-phenyl-2-
(E)-propen-1-one was carried out as described above. After discharging
the vials from the autoclave, molecular sieves (0.3 nm, 300 mg) and phen-
ACHTUNGTRENNUNGylACHTUNGTRENNUNGhydrazine (6 mmol, 590 mL) were added to the reaction mixture. The
vials were heated to 808C in the alloy plate on a heating plate for 2 h. Fi-
nally, the reaction mixture was cooled to room temperature and purifica-
tion was performed by column chromatography (heptane/ethyl acetate
15:1) to obtain 1,3-diphenyl-pyrazole as a white solid.
Acknowledgements
We thank the state of Mecklenburg-Vorpommern and the Bundesminis-
terium fꢀr Bildung und Forschung (BMBF) for financial support. We also
thank Dr. W. Baumann, Dr. C. Fischer, and S. Buchholz (LIKAT) for an-
alytical support and Mrs. S. Leiminger for technical assistance.
[6] For carbonylative Sonogashira reactions, see: a) T. Kobayashi, M.
Tanaka, J. Chem. Soc., Chem. Commun. 1981, 333–334; b) L. De-
laude, A. M. Masdeu, H. Alper, Synthesis 1994, 1149–1151; c) A.
Arcadi, S. Cacchi, F. Marinelli, P. Pace, G. Sanzi, Synlett 1995, 823–
824; d) B. Liang, M. Huang, Z. You, Z. Xiong, K. Lu, R. Fathi, J.
Chen, Z. Yang, J. Org. Chem. 2005, 70, 6097–6100; e) M. S. M.
Ahmed, A. Mori, Org. Lett. 2003, 5, 3057–3060; f) M. T. Rahman,
T. Fukuyama, N. Kamata, M. Sato, I. Ryu, Chem. Commun. 2006,
2236–2238; g) J. Liu, X. Peng, W. Sun, Y. Zhao, C. Xia, Org Lett.
2008, 10, 3933–3936; h) J. Liu, J. Chen, C. Xia, J. Catal. 2008, 253,
50–56; i) A. S. Karpov, E. Merkul, F. Rominger, T. J. J. Mꢀller,
Angew. Chem. 2005, 117, 7112–7117; Angew. Chem. Int. Ed. 2005,
44, 6951–6956.
Keywords: aryl bromides · carbonylation · palladium ·
pyrazoles · vinyl ethers
À
[1] For selected reviews on palladium-catalyzed C C coupling reactions
since 2004, see: a) F. Alonso, I. P. Beletskaya, M. Yus, Tetrahedron
2008, 64, 3047–3101; b) D. S. Surry, S. L. Buchwald, Angew. Chem.
2008, 120, 6438–6461; Angew. Chem. Int. Ed. 2008, 47, 6338–6361;
c) H. Doucet, J.-C. Hierso, Angew. Chem. 2007, 119, 850–888;
Angew. Chem. Int. Ed. 2007, 46, 834–871; d) A. Roglans, A. Pla-
Quintana, M. Moreno-Manas, Chem. Rev. 2006, 106, 4622–4643;
e) P. Rollet, W. Kleist, V. Dufaud, L. Djakovitch, J. Mol. Catal. A
Chem. 2005, 241, 39–51; f) A. Zapf, M. Beller, Chem. Commun.
2005, 431–440; g) A. Frisch, M. Beller, Angew. Chem. 2005, 117,
[7] a) X.-F. Wu, H. Neumann, M. Beller, Angew. Chem. 2010, 122,
5412–5416; Angew. Chem. Int. Ed. 2010, 49, 5284–5287; b) X.-F.
Wu, H. Neumann, A. Spannenberg, T. Schulz, H. Jiao, M. Beller, J.
Am. Chem. Soc. 2010, 132, 14596–14602; c) X.-F. Wu, H. Jiao, H.
Neumann, M. Beller, ChemCatChem 2011, 3, 726–733.
[8] P. Hermange, T. M. Gøgsig, A. T. Lindhardt, R. H. Taaning, T.
Skrydstrup, Org. Lett. 2011, 13, 2444–2447.
4830
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Palladium-Catalyzed Carbonylative Heck Reaction
COMMUNICATION
[9] For examples using 3-alkoxy alkenones as building blocks, see: a) T.
Hudlicky, H. F. Olivo, M. G. Natchus, J. Org. Chem. 1990, 55, 4767–
4770; b) F. Villar, T. Kolly-Kovac, O. Equey, P. Renaud, Chem. Eur.
J. 2003, 9, 1566–1577; c) Y. Tominaga, Y. Ichihara, T. Mori, C.
Kamio, A. Hosomi, J. Heterocycl. Chem. 1990, 27, 263–268; d) U.
Lienhard, Helv. Chim. Acta 1978, 61, 1609–1621; e) C. D. Ritchie,
A. Kawasaki, J. Org. Chem. 1981, 46, 4704; f) E. Stern, R. Millet, P.
Depreux, J.-P. Henichart, Tetrahedron Lett. 2004, 45, 9257–9259;
g) E. Stern, G. G. Muccioli, B. Bosier, L. Hamtiaux, R. Millet, J. H.
Poupaert, J.-P. Henichart, P. Depreux, J.-F. Goossens, D. M. Lam-
bert, J. Med. Chem. 2007, 50, 5471–5484; h) G. Mross, H. Reinke, P.
Langer, Synlett 2008, 963–966; i) G. Mross, S. Ladzik, H. Reinke, P.
Langer, A. Spannenberg, C. Fischer, Synthesis 2009, 2236–2248;
j) E. Coutouli-Argyropoulou, E. Thessalonikeos, J. Heterocycl.
Chem. 1991, 28, 429–432.
[10] C.-M. Andersson, A. Hallberg, J. Org. Chem. 1988, 53, 4257–4263.
[11] a) W. Mꢁgerlein, A. Indolese, M. Beller, J. Mol. Cat. A Chem. 2000,
156, 213–221; b) K. Kumar, A. Zapf, D. Michalik, A. Tillack, M.
Arlt, M. Beller, Org. Lett. 2004, 6, 7; c) A. Brennfꢀhrer, H. Neu-
mann, A. Pews-Davtyan, M. Beller, Eur. J. Org. Chem. 2009, 1, 38–
42; d) A. Brennfꢀhrer, H. Neumann, M. Beller, ChemCatChem
2009, 1, 28–41; e) A. Dumrath, X.-F. Wu, H. Neumann, A. Spannen-
berg, M. Beller, Angew. Chem. 2010, 122, 9172–9176; Angew.
Chem. Int. Ed. 2010, 49, 8988–8992; f) S. Gowrisankar, A. G. Ser-
geev, P. Anbarasan, A. Spannenberg, H. Neumann, M. Beller, J.
Am. Chem. Soc. 2010, 132, 11592–11598; g) X.-F. Wu, H. Neumann,
M. Beller, ChemCatChem 2010, 2, 509–513; h) X.-F. Wu, P. Anbara-
san, H. Neumann, M. Beller, Angew. Chem. 2010, 122, 7474–7477;
Angew. Chem. Int. Ed. 2010, 49, 7316–7319; i) X.-F. Wu, H. Neu-
mann, M. Beller, Chem. Eur. J. 2010, 16, 12104–12107; j) X.-F. Wu,
H. Neumann, M. Beller, Tetrahedron Lett. 2010, 51, 6146–6149;
k) X.-F. Wu, B. Sundararaju, H. Neumann, P. H. Dixneuf, M. Beller,
Chem. Eur. J. 2011, 17, 106–110.
[12] For some other applications of this catalyst system, see: a) F. Rata-
boul, A. Zapf, R. Jackstell, S. Harkal, T. Riermeier, A. Monsees, U.
Dingerdissen, M. Beller, Chem. Eur. J. 2004, 10, 2983–2990; b) A.
Zapf, M. Beller, Chem. Commun. 2005, 4, 431–440; c) S. Harkal, F.
Rataboul, A. Zapf, C. Fuhrmann, T. Riermeier, A. Monsees, M.
Beller, Adv. Synth. Catal. 2004, 346, 1742–1748; d) N. Schwarz, A.
Tillack, K. Alex, I. A. Sayyed, R. Jackstell, M. Beller, Tetrahedron
Lett. 2007, 48, 2897; f) C. Torborg, A. Zapf, M. Beller, ChemSu-
sChem 2008, 1, 91.
[13] a) Y. Shiga, I. Okada, Y. Ikeda, E. Takizawa, T. J. Fukuchi, Pestic.
Sci. 2003, 28, 313–314; b) S. D. Lindell, B. A. Moloney, B. D.
Hewitt, C. G. Earnhaw, P. J. Philip, J. E. Dancer, Bioorg. Med.
Chem. Lett. 1999, 9, 1985–1990; c) S. Fustero, R. Romꢃn, J. F. Sanz-
Cervera, A. Simꢄn-Fuentes, J. Bueno, S. Villanova, J. Org. Chem.
2008, 73, 8545–8552; d) N.-T. Ha-Duong, S. Dijols, C. Marques-
Soares, C. Minoletti, P. M. Dansette, D. J. Mansuy, J. Med. Chem.
2001, 44, 3622–3631; e) T. de Paulis, K. Hemstapat, Y. Chen, Y.
Zhang, S. Saleh, D. Alagille, R. M. Baldwin, G. D. Tamagnan, P. J.
Conn, J. Med. Chem. 2006, 49, 3332–3344.
[14] a) A. N. Kost, I. Grandberg, in Advances in Heterocyclic Chemistry
(Eds.: A. R. Katrizky, A. J. Boulton), Academic Press, New York,
1966, pp. 347–429; b) Y. Luo, P. G. Potvin, J. Org. Chem. 1994, 59,
1761–1765; c) F. Gosselin, P. D. OꢅShea, R. A. Webster, R. A.
Reamer, R. D. Tillyer, E. J. J. Grabowski, Synlett 2006, 3267–3270.
[15] M. Bagley, M. C. Lubinu, C. Mason, Synlett 2007, 5, 0704–0708.
[16] Panizzi, S. Siena, Gazz. Chim. Ital. 1943, 73, 355.
Received: November 18, 2011
Revised: January 18, 2012
Published online: March 15, 2012
Chem. Eur. J. 2012, 18, 4827 – 4831
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4831