Efficient carbonylation of aryl and heteroaryl bromides using a palladium/diadamantylbutylphosphine catalyst

Article abstract of DOI:10.1002/adsc.200606044

A general palladium-catalyzed alkoxycarbonylation of aryl and heteroaryl bromides has been developed in the presence of bulky monodentate phosphines. Studies of the butoxycarbonylation of three model substrates revealed the advantages of di-1-adamantyl-n-butylphosphine compared to other ligands. In the presence of this catalyst system various bromoarenes provided the corresponding benzoic acid derivatives (ester, amides, acids) in excellent yield at low catalyst loadings (0.5 mol% Pd or below).

Full text of DOI:10.1002/adsc.200606044

FULL PAPERS
DOI: 10.1002/adsc.200606044
Efficient Carbonylation of Aryl and Heteroaryl Bromides using a
Palladium/Diadamantylbutylphosphine Catalyst
Helfried Neumann,a Anne Brennführer,a Peter Groß,b Thomas Riermeier,b
Juan Almena,b,* and Matthias Bellera,*
a
Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Fax : (+49)-381-1281-5000; e-mail: matthias.beller@ifok-rostock.de
Degussa AG, Rodenbacher Chaussee 4, 63457 Hanau, Germany
b
Fax : (+49)-6181-5978-709; e-mail: juan.almena@degussa.com
Received: February 7, 2006; Accepted: May 8, 2006
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: A general palladium-catalyzed alkoxycar- ous bromoarenes provided the corresponding benzo-
bonylation of aryl and heteroaryl bromides has been ic acid derivatives (ester, amides, acids) in excellent
developed in the presence of bulky monodentate yield at low catalyst loadings (0.5 mol% Pd or
phosphines. Studies of the butoxycarbonylation of below).
three model substrates revealed the advantages of
di-1-adamantyl-n-butylphosphine compared to other Keywords: alkoxycarbonylation; aryl halides; benzo-
ligands. In the presence of this catalyst system vari- ic acid esters; carbonylation; monodentate ligands
Introduction
is reduced, due to the binding of carbon monoxide to
the metal centre. Moreover, clustering and agglomer-
Palladium-catalyzed carbonylations of aryl halides (or ation of Pd atoms is facile in the presence of CO,
halide equivalents) represent a valuable tool for the leading to non-active palladium species.[5] A solution
selective introduction of carboxylic acid derivatives to these problems can be the use of palladium cata-
onto aromatic frameworks.[1] Originally, these reac- lysts containing the highly basic bidentate[6] or mono-
tions were established in the mid-1970s by the pio- dentate phosphines.[7] The drawbacks of these catalyst
neering work of R. F. Heck and co-workers.[2] Since systems for larger scale applications are, however, the
that time, carbonylations of haloarenes have found a difficult synthesis and the highly sensitive nature of
number of applications in organic synthesis,[3] and the often pyrophoric ligands.
even related industrial processes, such as the alk-
For some time we have been involved in the devel-
oxycarbonylation of a benzylic alcohol toward ibu- opment of novel palladium catalysts for various cou-
profen, have been realized on a multi-1000 ton pling reactions of aryl halides, which should be also
scale.[4]
applicable on an industrial scale.[8,9] Recently devel-
In the last decade, significant progress with respect oped ligands from our side which fulfill this require-
to the development of more general and productive ment include di-1-adamantylalkylphosphines,[10] and
palladium catalysts for various coupling reactions has N-arylated 2-heteroaryldialkylphosphines.[11] The cor-
been reported. On the other hand, fewer improve- responding phosphines lead to highly active catalysts,
ments are known regarding the carbonylation of aryl but are comparably stable to air and moisture, and
halides. This is demonstrated by comparing known thus easy to handle. Based on our experience in car-
catalyst productivity (turnover number, TON), e.g., bonylation chemistry,[12] we started a program to ex-
for a simple Suzuki reaction (in general TON= plore the potential of these ligands in different car-
100,000 to 1,000,000) and the carbonylation of bro- bonylation reactions of aryl halides. Initial results
moanisole (typically TON=100).
demonstrated the superiority of di-1-adamantylbutyl-
The difficulty of more efficient palladium catalysis phosphine (cataCXiumꢀ A; Scheme 1) in formylation
in the presence of a large excess of carbon monoxide reactions with synthesis gas.[13] Here, we describe for
is a result of the p-acceptor character of CO. Here, the first time the use of these ligands in carbonyla-
the activity of the catalyst towards oxidative addition tions, which led to a general and efficient palladium
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Helfried Neumann et al.
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Results and Discussion
Initially, the alkoxycarbonylation of 4-bromoanisole
(deactivated aryl bromide) with n-butanol was investi-
gated in the presence of nine different phosphines
(Table 1, entries 1–9). Typically all experiments were
carried out in a 6-fold parallel autoclave (reaction
volume 4 mL), which allows fast testing of catalysts
and variation of reaction conditions. In order to
ensure reproducibility some experiments have been
repeated on a 300 mL scale. For practical relevance
Scheme 1. Structure
(cataCXiumꢀ A).
of
di-1-adamantylbutylphosphine
catalyst for alkoxy-, amino-, and hydroxycarbonyla- the carboxylation experiments were carried out with
tions of aryl and heteroaryl bromides.
0.5 mol% catalyst loading at 1158C and 20 bar of
carbon monoxide. For the stabilization of the palladi-
um catalyst and to prevent the formation of palladium
Table 1. Butoxycarbonylation in the presence of different ligands.[a]
Entry
A
Ligand
TMEDA
[equivs.]
Time
[h]
Conversion by GC
[%]
Yield by GC
[%]
1
2
3
4
5
6
7
cataCXiumꢀ A
PPh3
0.6
0.6
0.6
0.6
0.6
0.6
0.6
18
18
18
18
18
18
18
96
18
100
2
97
32
34
94
18
93
2
84
29
30
P(t-Bu)3
G
PCy3
dppf
dppp
dppb
8
0.6
18
46
79
40
70
9
0.6
18
10
11
cataCXiumꢀ A
0.75
0.75
12
12
86
74
69
56
P
ACHTREUNG
12
13
0.75
0.75
12
12
88
80
79
65
P(t-Bu)3
A
[a]
Reaction conditions: 2 mmol bromo
G
N
standard), 2 mL n-butanol, 20 bar CO, 1158C.
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Carbonylation of Aryl and Heteroaryl Bromides
FULL PAPERS
carbonyl clusters a three-fold excess of the ligand (P/ substituted aryl bromides such as 3-[12c] and 4-bro-
Pd=3:1) was used. moanisoles, 4-bromobenzonitrile, 4-(dimethylamino)-
As shown in Table 1 di-1-adamantyl-n-butylphos- bromobenzene, 4-bromo-chlorobenzene, and 3,4,5-tri-
phine (cataCXiumꢀ A) and P
(t-Bu)3 permit efficient fluorobenzene (Table 2, entries 3, 4, 6, 9, 15, 16). In
AHCTREUNG
butoxycarbonylation of 4-bromoanisole (93–94%; general, there is no difference between electron-rich
Table 1, entries 1, 3). 1,1’-Bis(diphenylphosphino)fer- substrates (bromoanisoles, bromoaniline) and elec-
rocene (dppf) and the dicyclohexyl-2-(N-mesityl)imi- tron-deficient ones (bromobenzonitrile). 2-Bromoben-
dazolylphosphine gave slightly lower yields (70–84%) zonitrile (86%), 1-bromo-3,4-methylendioxobenzene
of the desired product (Table 1, entries 5, 9). On the (83%), and 2,5-bis(trifluoromethyl)benzene (71%)
other hand PPh3, PCy3 and standard bidentate ligands also reacted well. The method works also with differ-
such as 1,3-bis(diphenylphosphino)propane (dppp) or ent heteroaryl halides (3-bromothiophene, 3-bromo-
1,4-bis(diphenylphosphino)butane did not lead to benzothiophene, 2-[15] and 3-bromopyridine[12c], 6-
high conversion (<50%) and ester formation (2– bromoquinoxaline). At this point it is important to
30%) (Table 1, entries 2, 4, 6, 7). Comparing entries 4 note that heteroaromatic carboxylic acid derivatives
and 9 demonstrates the importance of sterically hin- are particularly useful intermediates for the synthesis
dered substituents on the phosphorus atom. Due to of a number of agrochemicals.[16] With respect to min-
the similar performance of di-1-adamantylbutylphos- imization of the catalyst loading one should note that
phine and P(t-Bu)3 both ligands were tested further the model reaction of 4-bromoanisole works well at a
G
with 3-bromopyridine and 4-bromoacetophenone. 0.05 mol% Pd loading, however, a further decrease of
Here a higher yield of the corresponding ester was palladium resulted in a significant decrease of conver-
obtained with di-1-adamantylbutylphosphine as sion.
ligand. Interestingly aryl keto esters resulting from
Finally, we also studied the reaction of 4-bromoani-
double carbonylations were observed as side products sole with different nucleophiles (Table 3). In addition
(5–10%) in these reactions. Therefore, we studied the to methanol, ethanol, primary and secondary amines,
influence of the carbon monoxide pressure more as well as pyrrole and water led to good yield (64–
closely (Figure 1).
89%) and good to excellent selectivity (73–>99%).
Excellent conversion (97%) and selectivity (>
99%) is obtained already at 5 bar.[14] High conversion
is seen up to 50 bar, however the selectivity is contin- Conclusions
uously decreased due to the formation of the double
carbonylated product. At higher CO pressure also de- In conclusion, we have presented a general carbonyla-
activation of the catalyst becomes more pronounced. tion procedure for the synthesis of aromatic and het-
Next, we investigated the general scope of our cata- eroaromatic esters, amides, and acids from the corre-
lyst system for the alkoxycarbonylation of different sponding bromides. Best results are obtained at com-
aryl and heteroaryl bromides (Table 2). High conver- paratively low pressure (5 bar) using cataCXiumꢀ
A
sion (>95%) and excellent selectivity (>98%) were as ligand. Due to the efficiency and easy handling of
observed for the alkoxycarbonylation of various mono- the catalyst we believe that this novel carbonylation
protocol will allow one to perform such reactions on
an industrial scale.[17]
Experimental Section
General Remarks
Butanol and toluene were purified by distillation from CaH2
and from Na. Unless otherwise noted, all reagents were
used as received from commercial suppliers. Silica gel
column chromatography was performed with 230–400 mesh
ASTM silica gel from Merck. Melting points were recorded
on a Galen III (Cambridge Instruments) and are uncorrect-
ed. IR spectra of solids were recorded using KBr plates or
KBr pellets on a Nicolet Magna 550. Mass spectra were ob-
Figure 1. Influence of the carbon monoxide pressure on
conversion and yield. Reaction conditions: 2 mmol 4-bro-
tained on an AMD 402/3 of AMD Intectra (EI, 70 eV).
NMR data were recorded on a Bruker ARX 400 with a
QNP probe head (1H, 400.13 MHz; 13C, 100.61 MHz) at
258C. GC analyses were performed on an HP 6890 equip-
ped with a HP-5 capillary column (5% diphenylsiloxane,
moanisole, 0.5 mol% Pd
(OAc)2, 1.5 mol% cataCXiumꢀ A,
A
0.6 equivs. TMEDA, 0.2 equivs. hexadecane (internal stan-
dard), 0.3 mL n-BuOH, 1158C, 16 h.
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Helfried Neumann et al.
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Table 2. Butoxycarbonylation of various aryl and heteroaryl bromides.[a]
Entry Bromo
A
(OAc)2
cataCXiumꢀ
[mol%]
A
Temperature Conversion[b] Ester[b]
Selectivity[b]
[%]
[8C]
[%]
[%]
1
2
3
0.01
0.05
0.5
1
1
1.5
125
125
115
39
85
97
34
82
97
87
96
100
4
0.5
1.5
1.5
115
100
99
99
86
5
0.5
115
100
86
6
7
8
0.5
0.5
0.5
1.5
1.5
1.5
115
115
115
100
100
100
98
91
99
98
91
99
9
0.5
0.5
1.5
1.5
125
115
100
69
99
52
99
75
10
11
0.5
1.5
115
100
84
84
12
13
0.5
0.5
1.5
1.5
115
115
100
100
99
99
99
99
14
15
16
17
0.5
0.5
0.5
0.5
1.5
1.5
1.5
1.5
115
115
115
115
86
83
99
94
98
96
99
98
98
100
96
100
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Carbonylation of Aryl and Heteroaryl Bromides
FULL PAPERS
Table 2. (Continued)
Entry Bromo(hetero)arene Pd
N
U
cataCXiumꢀ
[mol%]
A
Temperature Conversion[b] Ester[b]
Selectivity[b]
[%]
[mol%]
[8C]
[%]
[%]
18
0.5
1.5
115
82
71
87
[a]
Reaction conditions: 2 mmol bromo
n-butanol, 5 bar CO, 16 h.
A
[b] Determined by GC.
Table 3. Carbonylation of 4-bromoanisole with different nucleophiles.[a]
Entry
1
Nucleophile
MeOH
Temperature [8C]
Product
Yield by GC [%]
78
Selectivity by GC [%]
99
115
2
3
4
5
EtOH
115
115
125
115
115
86
63
64
73
89
99
85
80
73
98
piperidine
pyrrole
t-butylamine
H2O[b]
6
[a]
Reaction conditions: 2 mmol 4-bromoanisole, 0.5 mol% Pd
(OAc)2, 1.5 mol% cataCXiumꢀ A, 0.75 equivs. TMEDA,
A
0.2 equivs. hexadecane (internal standard), 0.2 mL toluene, 1.8 mL nucleophile, 5 bar CO, 30 bar N2, 16 h.
[b] 0.4 mL H2O in 1.6 mL 1,4-dioxane.
95% dimethylsiloxane, L=30 m, d=250 mm, dfilm =0.25 mm)
General Procedure for the 6-fold Parallel Autoclave
and an FID detector. Quantitative GC analyses were refer-
enced to internal hexadecane. All new compounds were
characterized by 1H and 13C NMR spectroscopy, IR, and
high resolution MS (see Supporting Information). The fol-
lowing compounds have already been reported in the litera-
ture: butyl esters (Table 2, entries 4,[12c] 7,[12c] 8[15]), methyl
and ethyl esters (Table 3, entries 1,[18] 2[18]) and amides
(Table 3, entries 4,[19] 5[20]).
A
50 mL Schlenk flask was charged with Pd(OAc)2
A
(22.5 mg, 0.5 mol%), cataCXiumꢀ A (108 mg, 1.5 mol%)
and n-butanol (20 mL). Subsequently, hexadecane (1.17 mL,
internal GC standard) and TMEDA (N,N,N’,N’-tetramethyl-
ethylenediamine) (2.25 mL, 15 mmol) were added. 2.34 mL
of this clear yellow stock solution were transferred to the 6
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Helfried Neumann et al.
FULL PAPERS
vials (4 mL reaction volume) equipped with a septum, a
small cannula, a stirring bar and 2 mmol of the correspond-
ing aryl bromide. The vials were placed in an alloy plate,
which was transferred to a 300 mL autoclave of the 4560
series from Parr Instrumentsꢀ under an argon atmosphere.
After flushing the autoclave three times with CO a pressure
of 5 bar CO was adjusted at ambient temperature and the
reaction was performed for 16 h at 1158C. Before and after
the reaction an aliquot of the reaction mixture was subject-
ed to GC analysis for determination of yield and conver-
sion.
[7] For carbonylations using P(t-Bu)3, see: S. Couve-Bon-
G
naire, J.-F. Carpentier, A. Mortreux, Y. Castanet, Tetra-
hedron 2003, 59, 2793–2799.
[8] For a personal account, see: A. Zapf, M. Beller, Chem.
Commun. 2005, 431–440.
[9] a) A. Frisch, N. Shaik, A. Zapf, M. Beller, O. Briel, B.
Kayser, J. Mol. Catal. A: Chem. 2004, 214, 231–239;
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4, 3031–3033; c) K. Selvakumar, A. Zapf, A. Spannen-
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Acknowledgements
The authors thank S. Giertzand S. Buchholzfor excellent
technical and analytical assistance. S. Klaus and A. Zapf are
thanked for general discussions. Generous financial support
from Degussa AG, Mecklenburg-Vorpommern, the Fonds der
Chemischen Industrie, and the Bundesministerium für Bil-
dung und Forschung (BMBF) is gratefully acknowledged.
[10] These ligands are commercially available on industrial-
scale under the trade name cataCXiumꢀ A. For catalyt-
ic applications of adamantylphosphines, see: a) A. Eh-
rentraut, A. Zapf, M. Beller, Synlett 2000, 1589–1592;
b) A. Zapf, A. Ehrentraut, M. Beller, Angew. Chem.
2000, 112, 4315–4317; Angew. Chem. Int. Ed. 2000, 39,
4153–4155; c) A. Ehrentraut, A. Zapf, M. Beller, J.
Mol. Cat. A: Chem. 2002, 182–183, 515–523; d) A. Eh-
rentraut, A. Zapf, M. Beller, Adv. Synth. Catal. 2002,
344, 209–217.
[11] These ligands are commercially available up to multi-
kg-scale under the trade name cataCXiumꢀ P. For cata-
lytic applications, see: a) A. Zapf, R. Jackstell, F. Rata-
boul, T. Riermeier, A. Monsees, U. Dingerdissen, M.
Beller, Chem. Commun. 2004, 38–39; b) F. Rataboul,
A. Zapf, R. Jackstell, S. Harkal, T. Riermeier, A. Mon-
sees, U. Dingerdissen, M. Beller, Chem. Eur. J. 2004,
10, 2983–2990; c) S. Harkal, K. Kumar, D. Michalik, A.
Zapf, R. Jackstell, F. Rataboul, T. Riermeier, A. Mon-
sees, M. Beller, Tetrahedron Lett. 2005, 46, 3237–3240.
[12] a) K. Kumar, A. Zapf, D. Michalik, A. Tillack, M. Arlt,
M. Beller, Org. Lett. 2004, 6, 7–10; b) W. Mägerlein,
A. Indolese, M. Beller , Angew. Chem. 2001, 113, 2940–
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c) W. Mägerlein, A. F. Indolese, M. Beller, J. Organo-
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