Low-Temperature Ag/Pd-catalyzed decarboxylative cross-coupling of aryl trflates with aromatic carboxylate salts

Article abstract of DOI:10.1002/chem.200903319

Chemical Equation Presented At 50°C lower than the best known copper catalysts, a catalytic silver(I)/ palladium(II) system allows the decarboxylative cross-coupling of arenecarboxylates with aryl triflates at temper-atures as low as 120°C. Remarkably, polychlorinated and many heterocyclic arenecarboxylates are converted for the first time in high yields. FG = functional group.

Full text of DOI:10.1002/chem.200903319

DOI: 10.1002/chem.200903319
Low-Temperature Ag/Pd-Catalyzed Decarboxylative Cross-Coupling of Aryl
Triflates with Aromatic Carboxylate Salts
Lukas J. Gooßen,* Paul P. Lange, Nuria Rodrꢀguez, and Christophe Linder[a]
Metal-catalyzed decarboxylative couplings are evolving
into powerful synthetic tools for the regioselective formation
[1]
À
of C C bonds. New protocols for Heck-type reactions, oxi-
dative arylations,[2] redox-neutral couplings,[3] and allyla-
tions[4] have provided innovative atom-economic and waste-
minimized pathways among others to biaryls, vinyl arenes,
and aryl ketones starting from readily available carboxylic
acids.[5] These transformations have reached impressive per-
formance levels in terms of selectivity, functional group tol-
erance, and yield.[6] However, their practical applicability is
still somewhat limited by the high reaction temperatures
currently required in the decarboxylation step.[7]
Scheme 1. Ag/Pd-catalyzed decarboxylative cross-coupling. R=(hetero)-
aryl; R’=(hetero)aryl; X=OTf, OTs.
The redox-neutral decarboxylative cross-couplings devel-
À
oped in our group allow a regioselective C C bond forma-
tion between aryl, heteroaryl, or acyl carboxylates and aryl
halides to give biaryls or aryl ketones without resorting to
stoichiometric amounts of organometallic reagents.[8] In-
stead, the carbon nucleophiles are generated in situ via ex-
trusion of CO2 at a copper- or silver-based decarboxylation
catalyst.[9,3a] They are then transmetalated to the palladium
catalyst, where their coupling with the aryl electrophile
takes place (Scheme 1). The decarboxylation cocatalyst is
vital for the conversion of most carboxylic acids. Only a few
particularly reactive derivatives such as certain heteroarene-
2-carboxylic acids[1] or monoalkyl oxalates[3d] can be coupled
by palladium alone, presumably by a different mechanism.
So far, silver-based systems have not presented advantages
over copper ones in terms of reaction temperature or scope
of decarboxylative cross-couplings. In contrast to copper(I),
silver(I) had to be employed in overstoichiometric amounts,
because a salt metathesis between the potassium carboxy-
lates 1 and silver halides a formed within the catalytic cycle
is impossible, precluding further turnover of the silver cata-
lyst.[2a,3a,10]
However, when reevaluating the potential of silver cata-
lysts for protodecarboxylation reactions, we discovered con-
ditions under which silver salts mediate the extrusion of
CO2 from certain arenecarboxylates with higher efficiency
than copper complexes.[11] The new silver-based protodecar-
boxylation proceeds at only 1208C—a temperature more
than 508C below that of the best known copper catalysts.[11]
Larrosa et al. independently discovered a similar protocol.[12]
In addition, we were able to show that decarboxylative
cross-couplings can be performed using aryl electrophiles
with non-coordinating leaving groups such as triflates[13] or
tosylates.[14] We reasoned that the low affinity of these ions
to silver(I) might enable the crucial salt metathesis between
silver sulfonate salts
a and potassium carboxylates 1
(Scheme 1). This prompted us to embark on the search for a
new, low-temperature protocol for the decarboxylative
cross-coupling of aryl sulfonates with potassium carboxy-
lates using a Ag/Pd catalyst system.
We based the catalyst development on the model reaction
of potassium 2-nitrobenzoate (1a) with 4-chlorophenyl tri-
flate (2a) (see Table 1). Using a catalyst analogous to the
copper-based version but employing Ag2CO3 (5 mol%) in-
stead of Cu2O/1,10-phenanthroline, modest turnover was ob-
[a] Prof. Dr. L. J. Gooßen, P. P. Lange, Dr. N. Rodrꢀguez, C. Linder
FB Chemie - Organische Chemie, TU Kaiserslautern
Erwin-Schrçdinger-Strasse Geb. 54, 67663 Kaiserslautern (Germany)
Fax : (+49)631-205-3921
E-mail: goossen@chemie.uni-kl.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200903319.
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Chem. Eur. J. 2010, 16, 3906 – 3909

COMMUNICATION
Table 1. Development of the catalyst system.[a]
ratory microwave. Only five minutes of microwave irradia-
tion (1308C, max 150 W) are sufficient to achieve 80% yield
of the biaryl 3aa (Table 1, entry 21). In comparison, previous
copper-based catalyst systems require 1908C to reach such
short reaction times.[13]
Under these optimized conditions (5 mol% Ag2CO3,
3 mol% PdCl2, 9 mol% PPh3, 20 mol% 2,6-lutidine, 1308C),
we investigated the scope of the new protocol with regard to
the potassium carboxylate in its coupling with 4-chlorophen-
yl triflate (2a) (Table 2).
Entry Ag
source
Pd
source
Phosphine
N ligand
T
Yield
[8C] [%]
1
2
3
4
5
6
7
8
Ag2CO3 PdI2
P
P
P
P
P
–
N
–
–
–
–
–
–
–
–
–
–
–
–
–
–
130 17
130
Ag2CO3 [Pd
Ag2CO3 [Pd
U
6
130 54
130 77
130 85
130
130 73
130
130 55
130 75
130 86
130 67
130 68
130 29
130 29
130 82
130 47
Ag2CO3 PdBr2
Ag2CO3 PdCl2
Ag2CO3 PdCl2
Ag2CO3 PdCl2
Ag2CO3 PdCl2
Ag2CO3 PdCl2
Ag2CO3 PdCl2
Ag2CO3 PdCl2
AgOAc PdCl2
AgOTf PdCl2
0
Table 2. Scope with regard to the carboxylate.[a]
P(p-MeOC6H5)3
(o-Tol)3
P
0
9
PiPrPh2
Tol-BINAP
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
10
11
12
13
14
15
16
17
18
19[b]
20[b]
21[c]
Product
Yield [%]
87
Product
Yield [%]
74
Ag2O
PdCl2
Ag2CO3 PdCl2
Ag2CO3 PdCl2
Ag2CO3 PdCl2
Ag2CO3 PdCl2
Ag2CO3 PdCl2
Ag2CO3 PdCl2
Ag2CO3 PdCl2
phen
pyridine
DMAP
2,6-lutidine 130 96
2,6-lutidine 130 74
2,6-lutidine 120 58
2,6-lutidine 130 80
74
76[b]
[a] Conditions: 1 mmol of potassium 2-nitrobenzoate (1a), 2 mmol of 4-
chlorophenyl triflate (2a), 10 mol% of Ag source (5 mol% of Ag2CO3,
Ag2O), 3 mol% of Pd source, 9 mol% of phosphine (4.5 mol% for bi-
dentate phosphines), 20 mol% of N ligand, 4.0 mL of NMP, 16 h. Yields
determined by GC analysis using n-tetradecane as the internal standard.
phen=1,10-phenanthroline. [b] 4 h. [c] mW: 0.5 mmol of potassium car-
boxylate, 1 mmol of 2a, 3 mL NMP, 1308C/150 Watt/5 min.
65[b]
92
84[c]
56[c]
87
80[c]
served already at a temperature of 1308C (Table 1, entry 1).
At such a low temperature, the corresponding Cu/Pd system
had displayed almost no activity.
The nature of the palladium precursor had a profound in-
fluence on the catalyst performance. A switch to PdCl2 re-
sulted in an 85% yield of the desired biaryl (Table 1, en-
tries 2–5). The choice of phosphine also influenced the reac-
60
80
tion outcome. Best results were obtained with P
the inexpensive PPh3. The use of sterically demanding li-
gands such as P(o-Tol)3 had an adverse effect on the decar-
ACHTUNGTERNN(UNG p-Tol)3 or
ACHTUNGTRENNUNG
boxylation step (Table 1, entries 6–11). Among the silver
sources tested, silver carbonate gave the best results, but
other silver salts may be used as well (Table 1, entries 12–
14). The reaction works best in aprotic solvents such as N-
methylpyrrolidone (NMP) or dimethylacetamide (DMAc).
We also probed whether the activity of the silver catalyst
could be enhanced by the addition of nitrogen ligands. Phe-
nanthroline, which was the most effective ligand for copper,
hampered the activity of silver. Better results were obtained
with pyridine-type ligands, and near-quantitative yields were
achieved with the sterically encumbered 2,6-lutidine
(20 mol%) (Table 1, entries 15–18). The reaction is almost
complete within 4 h (Table 1, entry 19), and moderate yields
are achieved even at 1208C (Table 1, entry 20). On small
scales, it is advantageous to perform the reaction in a labo-
89
75
[a] Conditions: 1 mmol of potassium carboxylate, 2 mmol of aryl triflate,
5 mol% of Ag2CO3, 3 mol% of PdCl2, 9 mol% of PPh3, 20 mol% of 2,6-
lutidine, 4 mL of NMP, 1308C, 16 h, isolated yields. [b] 10 mol% of
AgOTf. [c] mW: 0.5 mmol of potassium carboxylate, 1 mmol of triflate,
3 mL of NMP, 1308C/150 Watt/5 min.
Aromatic carboxylates functionalized in the ortho posi-
tion, for example, with chloro, nitro, or ether groups, were
smoothly converted even at this low reaction temperature.
A particular strength of the new catalyst is that it is suitable
for the coupling of polychlorinated carboxylates, which do
not turn over with copper-based catalysts. However, for the
Chem. Eur. J. 2010, 16, 3906 – 3909
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www.chemeurj.org
3907

L. Gooßen et al.
coupling of meta- and para- substituted carboxylates, the
silver-based system is less effective than the copper-based
one. Heteroarenes with the carboxylate group directly adja-
cent to any ring heteroatom were also coupled in high
yields. The coupling of such compounds with other catalyst
it was impossible to avoid transesterification even at the low
temperatures used in this protocol.
We therefore probed whether more robust aryl tosylates
could also be converted. With slight adaptations of the pro-
tocol, we were indeed able to obtain an encouraging 31%
yield of 5-(2-naphthyl)-2,4-dimethyl-1,3-thiazole (3ld) when
coupling potassium 2,4-dimethyl-1,3-thiazole-5-carboxylate
(1l) with 2-naphthyl tosylate (4d) (Scheme 2). Unfortunate-
ly, the currently most effective palladium ligand (XPhos) in-
terferes with the decarboxylation step, so that further ligand
design is required to bring this transformation to synthetic
maturity.
systems requires much higher temperatures (1708C).[1]
A
benefit of the lower reaction temperature is that transesteri-
fication between the aryl triflates and nucleophilic ben-
zoates is suppressed, so that the protodecarboxylation of the
carboxylates by traces of residual water is the only remain-
ing side reaction. While the heterobiaryls are thus formed
more cleanly by using silver rather than at copper catalysts,
the scope of the copper protocol is wider, because it in-
cludes heteroarenes with the carboxylate group in the 3-po-
sition.
As illustrated by the examples in Table 3, there are very
few restrictions with regard to the aryl triflate coupling part-
ner. Sterically demanding substrates, and triflates with
common functionalities such as halides, esters, ketones, and
heterocycles were all converted in high yields with potassi-
um 2-nitrobenzoate (1a). The current performance limit is
reached with ester, acyl, and nitro groups in the 4-positions
of the aryl triflate. For such triflates of very acidic phenols,
Scheme 2. Successful coupling of an aryl tosylate.
Overall, we have developed a new Ag/Pd catalyst system
that allows the decarboxylative biaryl synthesis of potassium
arenecarboxylates and aryl triflates at only 120–1308C. This
low-temperature protocol, which is particularly suitable for
halogenated and heterocyclic arenecarboxylate substrates,
represents an important milestone in the evolution of decar-
boxylative cross-couplings into true synthetic alternatives to
traditional couplings of preformed organometallic reagents.
Table 3. Scope for the coupling of 2-nitrobenzoate with electrophiles.[a]
Product
Yield [%]
73
Product
Yield [%]
82
Experimental Section
Preparative-scale synthesis of 4’-chloro-2-nitrobiphenyl (3aa) [CAS
6271–80–3]: An oven-dried, nitrogen-flushed 60 mL vessel was charged
with potassium 2-nitrobenzoate (1a) (2.05 g, 10.0 mmol), silver carbonate
(138 mg, 0.50 mmol), palladium(II) chloride (53.7 mg, 0.30 mmol), and
triphenylphosphine (236 mg, 0.90 mmol). Under a nitrogen atmosphere, a
degassed solution of 4-chlorophenyl triflate (2a) (5.21 g, 20.0 mmol) and
2,6-lutidine (214 mg, 2.0 mmol) in NMP (40 mL) was added by using a sy-
ringe. The resulting mixture was stirred at 1308C for 8 h. After the reac-
tion was complete, the mixture was cooled to room temperature, diluted
with aqueous HCl (1molLÀ1, 100 mL) and extracted with ethyl acetate
(3ꢂ100 mL). The combined organic layers were washed with aqueous
NaHCO3 and brine, dried over MgSO4, filtered, and the volatiles were re-
moved in vacuo. The residue was purified by column chromatography
(SiO2, ethyl acetate/hexane 1:20) yielding the corresponding biaryl 3aa
(2.02 g, 87%).
72
49
64
72
81
49
36
76
Acknowledgements
We thank the Deutsche Forschungsgemeinschaft, Saltigo GmbH, and
NanoKat for funding and the Alexander von Humboldt Foundation for a
scholarship to N.R.
64
25
[a] Reaction conditions: 1 mmol of potassium 2-nitrobenzoate (1a),
2 mmol of triflate, 5 mol% of Ag2CO3, 3 mol% of PdCl2, 9 mol% of
PPh3, 20 mol% of 2,6-lutidine, 4 mL of NMP, 1308C, 16 h, isolated yields.
Keywords: aryl triflates · carboxylic acids · cross-coupling ·
palladium · silver
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Cross-Coupling of Aryl Triflates with Aromatic Carboxylate Salts
COMMUNICATION
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Received: December 3, 2009
Published online: March 5, 2010
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