[10]
[a]
matic and vinylic carboxylic acid derivatives.
However,
Table 1. Aminocarbonylation of bromobenzene: Variation of ligands
there are only a few known methods for the synthesis of
synthetically useful primary amides. In general, in these re-
actions ammonia synthons are employed as a nucleophilic
partner for the carbonylation. Some such synthons include
hexamethyldisilazane (HMDS), formamide, N-tert-butyla-
mides, hydroxylamine, and even a titanium–nitrogen com-
[
b]
[b]
Entry
1
Ligands [3 mol%]
dppe
Conversion [%]
8
Yield [%]
8
[11]
plex has been described. Surprisingly, until very recently,
the straightforward use of ammonia in Heck carbonylations
was not reported because of the low nucleophilicity of am-
2
52
46
3
4
dpppe
dppm
35
29
10
2
[12,13]
monia and strong coordination with palladium(II).
As part of our continuing interest in palladium-catalyzed
5
1
1
[
14]
carbonylation reactions,
first general synthesis of primary amides starting from aryl
we very recently reported the
6
7
dppf
dppp
100
100
93
87
[
15]
bromides or chlorides. Key to this success was the use of
palladium/nBuP(1-adamantyl) (cataCXiumA) catalyst
a
2
[16]
8
9
80
80
system. In continuance of this work, herein we report an
improved catalyst system based on the commercially avail-
xantphos
diop
dppb
100
100
100
100
88
89
84
86
able Pd ACHTUNGTRENNUNG( OAc) and dppf.
2
1
1
12
0
1
During investigations on the influence of different biden-
tate ligands on the aminocarbonylation of bromobenzene,
which we examined as a benchmark reaction, we discovered
that 1,1’-bis(diphenylphosphino)ferrocene (dppf) gave im-
[c]
n-butylP(adamantyl)2
(cataCXium A)
[
[
c]
c]
1
14
1
1
17
1
3
HP(adamantyl)
PPh
PCy
2
22
65
8
1
100
56
10
47
5
1
96
55
[17]
3
proved results in this transformation.
experiments were performed at a low pressure of CO
2 bar) and NH (2 bar) at 1008C in the presence of 2 mol%
Typically, catalytic
[c]
[c]
5
6
3
P(ortho-tolyl)
dppf
3
[
[
d]
e]
(
3
8
dppf
Pd ACHTUNGTRENNUNG( OAc) and 3 mol% of the respective ligand (Table 1).
2
Whilst 1,2-bis(diphenylphosphino)ethane (dppe), 1,2-bis(di-
phenylphosphino)benzene, 1,5-bis(diphenylphosphino)pen-
tane (dpppe), and 1,2-bis(diphenylphosphino)metane
[a] General conditions: Bromobenzene (1 mmol), CO (2 bar), NH
3
(
2 bar), Pd
A
H
U
G
E
N
N
2
(0.02 mmol), ligand (0.03 mmol), dioxane (2 mL),
1
adecane as an internal standard and are based on bromobenzene. [c] Pd-
(OAc) (0.02 mmol), ligand (0.06 mmol). [d] Pd(OAc) (0.002 mmol),
(OAc) (0.0005 mmol), ligand
(
dppm) gave discouragingly low yields, the addition of 1,2-
A
H
U
G
R
N
U
G
2
A
H
U
G
R
N
U
G
2
bis(diphenyl-phosphinomethyl)benzene afforded moderate
conversion and yield (Table 1, entries 1–5). To our delight,
dppf afforded full conversion and 93% yield of benzamide
ligand (0.008 mmol), 1208C, 16 h. [e] Pd
(0.004 mmol), 1208C, 16 h.
ACHTUNGTRENNUNG
2
(
Table 1, entry 6), which was slightly better than our previ-
ous system (86% yield; Table 1, entry 12). Furthermore, in
the presence of 1,3-bis(diphenylphosphino)propane (dppp),
bis-[2-(diphenylphosphino)-phenyl]ether, xantphos, (+)-2,3-
O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)-
butane (diop), and 1,4-bis(diphenylphosphino)butane
(
dppb) good results were obtained (Table 1, entries 7–11).
Other commercially available monodentate ligands gave
only low conversions and yields (1–47%; Table 1, en-
tries 13–16). Notably, with this novel system also at signifi-
cantly lower catalyst loadings an excellent product yield was
maintained. Hence, in the presence of 0.2 mol% of Pd-
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OAc) , benzamide was obtained in 96% yield (Table 1,
2
entry 17). Even without further optimization, we obtained
5
(
5% of the amide with only 0.05 mol% of Pd
Table 1, entry 18).
In Scheme 4, a proposed mechanism for the aminocarbo-
nylation reaction is shown, based on mechanistic studies of
ACHTUNGTRENNUNG( OAc)
2
Scheme 4. Proposed reaction mechanism.
role in this reaction both as reagent and base to regenerate
the active catalyst.
With suitable reaction conditions in hand (Table 1,
entry 6), more than twenty different aryl and heteroaryl hal-
ides were aminocarbonylated in the presence of dppf. In
general, the corresponding primary amides were obtained in
[18]
similar palladium-catalyzed carbonylations. In agreement
with previous studies, we suppose that the oxidative addition
of the active palladium(0) species is rate-determining, be-
cause aryl chlorides react more sluggishly than aryl bro-
mides (see Table 2). Clearly, ammonia plays an important
Chem. Asian J. 2010, 5, 2168 – 2172
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
2169