Tetraalkylammonium-free heck olefination of deactivated chloroarenes by using a macrocyclic catalyst precursor

Article abstract of DOI:10.1002/chem.200903331

Palladium reservoir: A macrocyclic dinuclear Pd complex is applied to the Heck coupling of strongly deactivated aryl chlorides. The complex serves as a very stable precatalyst, which releases active Pd under normal reaction conditions (see scheme). The co

Full text of DOI:10.1002/chem.200903331

COMMUNICATION
DOI: 10.1002/chem.200903331
Tetraalkylammonium-Free Heck Olefination of Deactivated Chloroarenes
by Using a Macrocyclic Catalyst Precursor
[
a]
Christoph Rçhlich and Klaus Kçhler*
The palladium-catalyzed olefination of aryl halides (Miz-
oroki–Heck reaction) is a very versatile means of making
new CÀC bonds and continues to gain increasing importance
Pd. In other words, the strong shift of the release–recapture
equilibrium towards bound Pd should protect the catalytic
species from fast deactivation under reaction conditions.
Hence, macrocyclic Pd complexes may be suitable model
systems to further utilize the stabilization of Pd species by
controlled in situ generation from inactive precursors.
[1–3]
in organic chemistry and fine chemical synthesis.
Al-
though seemingly any Pd species can achieve the coupling
of aryl iodides and bromides under appropriate conditions,
the industrially interesting activation of chloroarenes re-
mains a challenging task and demands specific catalytic sys-
Herein, the successful application of this concept for the
Heck olefination of highly deactivated chloroarenes will be
shown. A bimetallic macrocyclic complex of the Robson
[4]
tems. Up to now, it has been stated by several groups that,
unless exceptionally mild reaction conditions are applicable,
[12a]
type
is used as the precatalyst. As this paper will show,
0
any Pd precursor will release underligated free Pd , which is
the new concept allows for very efficient Heck couplings
with low catalyst loadings, even under additive-free condi-
tions.
[4–11]
the actual active species.
This concerns both homogene-
ous and heterogeneous precatalysts. The released Pd species
are unstable and likely to agglomerate and deactivate;
therefore, stabilization is crucial for reasonable catalytic ac-
tivity. As has been shown for heterogeneous Pd sources in
the Heck coupling of aryl chlorides, the dissolution–repreci-
pitation equilibrium can provide sufficient stabilization for
the active species, resulting in high activities. In some of
these cases further stabilizers, such as tetrabutylammonium
The bimetallic Pd complex II was prepared by first pro-
ducing the free ligand I through proton-templated synthesis
and subsequent metalation with two equivalents of palladi-
um acetate (Scheme 1). This protocol gives complex II in
[12b,c]
very good yield and purity as a yellow powder.
[11]
bromide (TBAB) are then unnecessary.
Macrocyclic complexes of Pd are characterized by an ex-
traordinary stability, coordinative saturation of the central
II
atom, and a preference for the Pd oxidation state. Al-
though these qualities imply catalytic inactivity, a new con-
cept of catalyst stabilization can be devised from them: If
Pd was released from such complexes under CÀC coupling
reaction conditions, this release would be very slow and con-
trolled. Recoordination of Pd into the macrocycle may also
be possible and even favored. These processes would be
similar to those for heterogeneous Pd precatalysts; however,
by comparison, the equilibrium would be shifted to bound
Scheme 1. Synthesis of the bimetallic Pd complex II.
As a model reaction for catalytic tests, we have chosen
the Heck coupling of styrene with 4-chloroanisol, a highly
deactivated aryl halide. The reaction was carried out under
conditions that were applied in previous studies and were
found to be suitable for the Heck coupling of aryl chlorides
[
a] Dipl.-Chem. C. Rçhlich, Prof. Dr. K. Kçhler
Department of Chemistry, Catalysis Research Center
Technische Universitꢀt Mꢁnchen
Lichtenbergstr. 4, 85747 Garching (Germany)
Fax : (+49)89-289-13183
E-mail: klaus.koehler@ch.tum.de
[
11]
(
Table 1). The initial catalyst amount was 0.5 mol% of II
[13]
with respect to styrene. Under these conditions 48% con-
version of styrene and 36% yield of 4-methoxy-trans-stil-
bene were obtained; the corresponding cis-stilbene was not
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200903331.
Chem. Eur. J. 2010, 16, 2363 – 2365
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2363

[
15]
Table 1. Catalytic results for the Heck coupling of styrene and 4-chloro-
anisol with TBAB and the optimized amount of II.
phosphane ligands, or TBAB or comparable additives, in-
[
a]
[16]
cluding ionic liquids.
To further demonstrate the stabilizing effect, two compar-
ison experiments were conducted, in which corresponding
amounts of Pd ACTHUNGTERNN(UNG OAc) (0.075 mol%) were used as the cata-
2
lyst precursor instead of II. Without TBAB, Heck products
were not observed. The addition of TBAB (0.9 mmol) led to
a successful reaction, albeit with significantly lower conver-
sion and selectivity than II without additives (Table 1, en-
tries 7 and 8).
Screening the amount of TBAB even revealed that the
conversions and yields decreased with a higher TBAB/II
ratio (Table 1, entries 2 and 3) and increased when less
TBAB was added (Table 1, entries 4 and 5). We suggest
that, at the high reaction temperature, TBAB is partially
[
b]
[c]
Entry
TBAB [mmol]
Conversion [%]
Yield (t/g) [%]
1
2
3
4
5
6
0.9
3.0
1.4
0.5
0.2
–
81
54
62
71
94
90
28
49
63/5
38/3
47/4
51/5
79/7
75/6
0/0
[
[
d]
d]
7
8
–
0.9
25/2
[
a] Reaction conditions: styrene (1.5 mmol), 4-chloroanisol (3 mmol),
Ca(OH) (0.9 mmol), complex II (0.0375 mol%), N-methylpyrrolidone
NMP, 5 mL), air, 1608C 6 h. [b] Conversion of styrene. [c] GC yields cor-
responding to the trans olefin (t) and the gem olefin (g). [d] Pd(OAc)
0.075 mol%) was used as the catalyst.
converted to tributylamine through S 2 substitution or Hof-
N
2
[14]
mann elimination. Although tributylamine has often been
(
used as a base in Heck couplings, the amine may block coor-
A
H
U
G
R
N
N
2
II
(
dination sites on Pd, and reduce Pd species, which facili-
tates the formation of Pd black.
Apart from the inhibitive effect of tetrabutylammonium
ions, it has been stated in the literature that bromo ligands
stabilize (low-nuclear) Pd species in solution, as well as en-
found in this or any subsequent experiment. A 4% yield of
the geminal-substituted olefin 1-(4-methoxyphenyl)-1-phe-
nylethene was also detected. In the following text the two
Heck products will be regarded as the trans (t) and the gem
product (g).
[17]
hance Pd dissolution from nanoclusters.
Lewis acidic metal ions have been applied to improve chlor-
In addition,
[18]
oarene reactivity in coupling reactions.
The Lewis acid
According to our concept, complex II releases ligand-free
Pd into solution, which enters the catalytic cycle, is recap-
tured, or follows agglomeration pathways. It has been stated
for ligandless Pd precatalysts (in the coupling of aryl bro-
mides) that the catalyst performance highly depends on the
initial Pd amount. Too low concentrations result in slow re-
action progress, whereas higher amounts of catalyst lead to
may coordinate either to the chlorine or to the oxygen of
the methoxy group of chloroanisol. As a result, the CÀCl
bond is weakened, or electron density is drawn from the
donor substituent and, therefore, from the aromatic ring.
Both scenarios would make the oxidative addition of the
0
chloroarene to Pd more feasible. Accordingly, addition of
LiBr improved the reaction to give almost quantitative con-
version. The optimal amount of LiBr was found to be 0.6–
1 mmol for 1.5 mmol of styrene (Table 2, entries 2–4).
Lower amounts of LiBr showed no improvement (Table 2,
entry 1), and higher amounts were inhibitive to the reaction.
Under the optimized conditions, coupling can also be ach-
ieved at temperatures lower than 1608C. At 1508C, reasona-
[5,6]
a more pronounced agglomeration of Pd.
Thus, the same
should apply to the Pd released from complex II. There
should be an ideal initial amount of II that, in turn, gener-
ates the optimal amount of active Pd. A screening of differ-
ent catalyst loadings showed an optimal initial loading of
around 0.0375 mol% of II. With this amount of catalyst,
conversion and yield were approximately doubled compared
with the initial results with 0.5 mol% of catalyst, and the se-
lectivity was also improved (Table 1, entry 1). Conversions
and yields were lower with higher amounts of II. Moreover,
Table 2. Catalytic results for Heck coupling of styrene and 4-chloroanisol
[
a]
with LiBr and the optimized amount of II.
[
b]
[c]
a
0
minimum catalyst loading of between 0.005 and
.0125 mol% was found to be necessary for the reaction to
Entry LiBr [mmol] T [8C] t [h] Conversion [%]
Yield (t/g) [%]
1
2
3
4
5
6
7
8
9
0.2
0.6
1.0
0.7
0.7
0.8
0.6
0.6
0.6
160
160
160
140
150
150
160
160
160
6
6
6
16
6
16
6
92
98
97
42
77
100
30
26
77/7
81/8
82/8
20/2
59/5
74/6
<1/0
0/0
occur. All of the subsequent experiments were conducted
with the optimal amount of 0.0375 mol% of II.
If the controlled release and recapture of Pd by the mac-
rocyclic ligand provides sufficient stabilization, it should
render further stabilizers unnecessary. Accordingly, the reac-
tion was also performed without TBAB. Under these addi-
tive-free conditions, a conversion of 90% (Table 1, entry 6)
and a selectivity of 90% for the Heck products was ob-
tained. This is one of the best reaction results reported in lit-
erature for these substrates (styrene and 4-chloroanisol).
Similar results for the coupling of chloroanisol have, to the
best of our knowledge, thus far only been achieved by using
[
[
[
d]
e]
f]
6
6
58
32/3
[a] Reaction conditions: styrene (1.5 mmol), 4-chloroanisol (3 mmol),
Ca(OH) (0.9 mmol), complex II (0.0375 mol%), NMP (5 mL), air.
b] Conversion of styrene. [c] GC yields corresponding to the trans olefin
2
[
(
t) and the gem olefin (g). [d] Ligand I (0.0375 mol%) was added.
II
[
e] Pd –tetraphenylporphyrin (0.075 mol%) was used as the precatalyst.
II
[f] Pd –phthalocyanine (0.075 mol%) was used as the precatalyst.
2364
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Chem. Eur. J. 2032, 38, 2363 – 2365

Tetraalkylammonium-Free Heck Olefination
COMMUNICATION
ble conversions and yields are still obtained (Table 2,
entry 5), and quantitative conversion of styrene can be ach-
ieved by prolonging the reaction time, albeit with lower se-
lectivity (Table 2, entry 6). Heck coupling is also observed at
Acknowledgements
The authors wish to thank the NanoCat graduate school of the Elitenetz-
werk Bayern for financial support.
1
1
408C (Table 2, entry 4). However, at temperatures below
408C the reaction did not occur.
Keywords: Heck reaction
·
homogeneous catalysis
·
Finally, other macrocyclic Pd complexes were employed
macrocyclic ligands · olefination · palladium
II
under these conditions. Pd –tetraphenylporphyrin did not
show activity as a precatalyst. Modest conversion and yield
II
could be achieved by using Pd –phthalocyanine (Table 2,
[1] N. Miyaura, Adv. Synth. Catal. 2004, 346, 1522.
[
2] A. Eisenstadt, D. J. Ager, Fine Chemicals through Heterogeneous
Catalysis, Wiley-VCH, Weinheim, 2001, p. 576.
entries 8 and 9). Clearly, these complexes behave differently
to complex II with respect to Pd release, and may need a
different set of conditions for better performance.
Based on our concept, addition of the free ligand to the
reaction mixture should shift the release–recapture equilibri-
um towards bound Pd and stall the coupling catalysis. In
fact, conducting the reaction by using complex II in the
presence of ligand I (1 equiv) disrupts the Heck reaction
[
[
3] A. Zapf, M. Beller, Top. Catal. 2002, 19, 101.
4] N. Phan, M. van der Sluys, C. Jones, Adv. Synth. Catal. 2006, 348,
609.
[
[
[
[
5] J. G. de Vries, Dalton Trans. 2006, 421.
6] A. F. Schmidt, A. Al Halaiqa, V. V. Smirnov, Synlett 2006, 2861.
7] M. Weck, C. W. Jones, Inorg. Chem. 2007, 46, 1865.
8] C. S. Consorti, F. R. Flores, J. Dupont, J. Am. Chem. Soc. 2005,
1
27(32), 12054.
[9] I. P. Beletskaya, A. V. Cheprakov, J. Organomet. Chem. 2004, 689,
055.
(
Table 2, entry 7). However, when corresponding amounts
4
of the ligand I and Pd(OAc) were added to the reaction
AHCTUNGTRENNUNG
2
[
[
10] V. Farina, Adv. Synth. Catal. 2004, 346, 1553.
11] a) S. S. Prçckl, W. Kleist, M. A. Gruber, K. Kçhler, Angew. Chem.
mixture (before heating) instead of the preformed complex
II, 89% conversion of styrene and 75% yield of the Heck
products were still observed under the optimized conditions.
These are comparable results to those obtained by directly
using complex II (Table 2, entries 2 and 3). Thus, the forma-
tion (also in situ) of the macrocyclic complex II leads to
highly effective catalytic coupling. On the other hand, direct
exposure of free Pd to the warm reaction mixture should be
disadvantageous for Heck coupling, even in the presence of
I, because the initially unprotected Pd will enter deactiva-
tion pathways to a significant extent. Hence, adding Pd-
2
004, 116, 1917; Angew. Chem. Int. Ed. 2004, 43, 1881; b) S. S.
Prçckl, W. Kleist, M. A. Gruber, K. Kçhler, Tetrahedron 2005, 61,
855.
9
[
12] a) H. Pilkington, R. Robson, Aust. J. Chem. 1970, 23, 2225; b) B.
Dutta, B. Adhikary, U. Flçrke, K. Nag, Eur. J. Inorg. Chem. 2006,
4
111; c) B. Dutta, P. Bag, B. Adhikary, U. Flçrke, K. Nag, J. Org.
Chem. 2004, 69, 5419.
[13] Note: This loading corresponds to double the amount of Pd, that is,
mol%, since every equivalent of II can theoretically release two
1
Pd atoms.
[
14] a) M. Amirnasr, M. K. Nazeeruddin, M. Grꢀtzel, Thermochim. Acta
2
000, 348, 105; b) M. R. R. Prasad, V. N. Krishnamurthy, Thermo-
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(OAc) after 5 min to an already hot reaction mixture con-
chim. Acta 1991, 185, 1; c) L. V. Malysheva, E. Paukstis, N. S. Kotsar-
enko, J. Catal. 1987, 104, 31.
2
taining ligand I, led to significantly lower conversion (39%)
and yield (15%). Moreover, when the ligand is added after
5
Heck reaction proceeds to a lesser extent, or does not occur
at all.
All of these results are consistent with a controlled re-
lease of active free Pd from complex II under the reaction
conditions. It is this controlled release that prevents the for-
mation of inactive Pd agglomerates under harsh conditions
and leads to high catalytic performance even for deactivated
substrates. Further stabilization by TBAB is then no longer
necessary, and even inhibitive to the reaction.
[
15] For some comparable results by using phosphanes, see: a) A. F.
Littke, G. C. Fu, J. Org. Chem. 1999, 64, 10; b) A. F. Littke, G. C.
Fu, J. Am. Chem. Soc. 2001, 123, 6989; c) D. Morales-Morales, R.
Redꢃn, C. Yung, C. M. Jensen, Chem. Commun. 2000, 1619; d) H.
Huang, H. Liu, H. Jiang, K. Chen, J. Org. Chem. 2008, 73, 6037.
16] For some comparable results by using TBAB or similar additives,
see: a) V. P. W. Bçhm, W. A. Herrmann, Chem. Eur. J. 2000, 6, 1017;
b) B. M. Choudary, S. Madhi, N. S. Chowdari, M. L. Kantam, B.
Sreedhar, J. Am. Chem. Soc. 2002, 124, 14127; c) V. Calꢄ, A. Nacci,
A. Monopoli, P. Cotugno, Angew. Chem. 2009, 121, 6217; Angew.
Chem. Int. Ed. 2009, 48, 6101.
min to the hot reaction mixture containing Pd ACHTUNGTRENNUNG( OAc) , the
2
[
[
[
17] A. F. Schmidt, L. V. Mametova, Kinet. Catal. 1996, 37, 406.
18] A. Sud, R. M. Deshpande, R. V. Chaudhari, Catal. Commun. 2006,
7
, 183.
Received: December 4, 2009
Published online: January 28, 2010
Chem. Eur. J. 2010, 16, 2363 – 2365
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2365