Palladium-containing perovskites: Recoverable and reuseable catalysts for Suzuki couplings

Article abstract of DOI:10.1039/b308465e

Palladium-containing perovskites (LaFe_0.57 Co_0.38Pd_0.05O₃) have been exploited as recoverable and reuseable catalysts in Suzuki coupling reactions; residual levels of Pd after removal of the catalyst by filtration are low (2 ppm) despite evidence that the reaction is occurring via a homogeneous process.

Full text of DOI:10.1039/b308465e

Palladium-containing perovskites: recoverable and reuseable catalysts
for Suzuki couplings†
Martin D. Smith, Antonia F. Stepan, Chandrashekar Ramarao‡, Paul E. Brennan§ and Steven V.
Ley*
University Chemical Laboratory, Department of Chemistry, Lensfield Road, Cambridge, UK CB2 1EW.
E-mail: svl1000@cam.ac.uk; Fax: +44 1223336442; Tel: +44 1223 336398
Received (in Cambridge, UK) 23rd July 2003, Accepted 10th September 2003
First published as an Advance Article on the web 30th September 2003
Palladium-containing perovskites (LaFe0.57Co0.38Pd0.05O3)
have been exploited as recoverable and reuseable catalysts in
Suzuki coupling reactions; residual levels of Pd after
removal of the catalyst by filtration are low (2 ppm) despite
evidence that the reaction is occurring via a homogeneous
process.
focussed on Suzuki reactions between aryl halides and boronic
acids. Preliminary screening of solvents and reaction conditions
demonstrated that aqueous alcohols were effective (non-
aqueous solvent mixtures were unsuccessful) and that heating to
80 °C was sufficient for most substrates. Under these condi-
tions, the coupling of aryl bromides in the presence of 0.05
mol% Pd catalyst and K2CO3 as base (K3PO4 and Cs2CO3 were
also effective) proceeded smoothly to afford the requisite
biaryls in high yields, Table 1. The catalyst can be removed
from the reaction mixture by a simple filtration or decantation.
Substituents in the ortho position were tolerated in both
coupling partners without any undue increase in reaction time,
or decrease in yields. The addition of tetra-n-butylammonium
bromide3 (TBAB) proved only to be beneficial in a few difficult
cases such as the coupling of 3,4,5-trimethoxyphenylboronic
acid. In an attempt to ascertain the scope and limitations of the
catalyst under these conditions, a reaction utilising 1 g of
4-methoxybromobenzene and 1 mg of catalyst (0.0038 mol%
Pd) was attempted. This led to a 93% conversion (estimated by
LC integration, 91% isolated yield) corresponding to a turnover
number of 27000. Attempts to utilise vinyl boronic acids were
unsuccessful when aryl bromides were used as coupling
partners, but aryl iodides proved to be viable substrates for these
transformations. This enabled the formation of the function-
alised olefins described in Table 2. Similarly, sulfur-containing
Perovskite-based catalysts are under investigation for use in
automotive emissions control, and have been dubbed ‘in-
telligent’ by virtue of their ability to self-regenerate under
oxidative and reductive conditions, whilst suppressing the
growth of metallic Pd-particles.1 These properties could
promote activity and longevity in catalysts used in organic
synthesis programmes where similar problems of catalyst
deactivation are encountered.2 It was thus considered that
palladium-containing
perovskites
such
as
LaFe0.57Co0.38Pd0.05O3 could function as a new class of
catalysts for cross coupling reactions. Initial investigations
† Electronic supplementary information (ESI) available: experimental
details. See http://www.rsc.org/suppdata/cc/b3/b308465e/
‡ Current address: Avra Laboratories Pvt. Ltd., Avra House, 7-102/54, Sai
Enclave, Habshiguda, Hyderabad-500 007, India.
§ Current address: Amgen Inc., One Amgen Center Drive, Mailstop
29-1-B, Thousand Oaks CA, 91320, USA.
Table 1 Suzuki coupling reactions with aryl bromidesa
Isolated
Aryl halide
Boronic acid
Product
Base
Additive
Mol% Pd
Time/h
yield (%)
K2CO3
Cs2CO3
None
None
0.05
0.0038
0.5
39
95
91
K2CO3
K2CO3
None
None
0.05
0.05
0.5
18
95
85
K2CO3
K2CO3
None
None
0.05
0.05
1
89
92
18
K2CO3
K2CO3
TBAB
None
0.05
0.05
18
18
93
60b
a Reagents and conditions: LaFe0.57Co0.38Pd0.05O3 (0.05 mol% Pd), IPA–H2O (1 : 1, v/v), 80 °C, 3 eq. base, 1.5 eq. boronic acid. b Estimated conversion by
1H NMR.
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CHEM. COMMUN., 2003 2652–2653
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Table 2 Suzuki coupling reactions with aryl iodides a
Isolated
Aryl halide
Boronic acid
Product
Base
Additive
Mol% Pd
Time/h
yield (%)
K2CO3
K2CO3
TBAB
None
0.05
0.05
18
18
89
61
K2CO3
K2CO3
TBAB
None
0.05
0.05
18
18
70
70b
K2CO3
None
0.05
18
92
a Reagents and conditions: IPA–H2O (1 : 1, v/v), 80 °C, LaFe0.57Co0.38Pd0.05O3, 1.5 eq. boronic acid, 3 eq. base. b Estimated conversion by 1H NMR
compounds were investigated and were found to couple in high
yields to aryl iodides, but not to aryl bromides. Application of
standard conditions to the coupling of aryl chlorides proved
troublesome, with heating at 80 °C yielding mixtures of
products. However, it was found that the application of
microwave heating at 135 °C cleanly facilitated the coupling of
4-nitrochlorobenzene in 71% yield. Coupling of deactivated
aryl chlorides was less successful, affording 51% isolated yield
for 4-chlorotoluene, and 26% yield for 4-chloroanisole, Table
3.
As the solid catalyst can be recovered easily, the feasibility of
recovery and reuse of the catalyst was investigated utilising the
coupling of phenylboronic acid and 4-bromoanisole as a test
case. It was found that recovery can be achieved without
compromising the operational simplicity of the procedure, and
five catalyst runs were performed without any demonstrable
loss of catalytic activity, Table 4.
The crude products of this reaction were analysed for Pd
content by ICP-MS, which demonstrated that levels were
uniformly low across four samples (filtration of both hot and
cold reaction mixtures, with and without aqueous washing)
ranging from 0.5–2.4 ppm. A comparison with Pd levels in the
starting materials (0.3 ppm) demonstrates that these levels of
palladium leaching are particularly low. In an attempt to
ascertain whether the catalyst was operating by a homogeneous
or heterogeneous mechanism, a three-phase test, Fig. 1, that has
been elegantly applied to similar problems was utilised.4 This
Fig. 1 Three-phase test
involved preparation of a solid-supported aryl iodide 1 on
Novasyn TGR resin, as described.4
A control experiment under standard conditions (K2CO3,
PhB(OH)2, IPA–H2O, 0.3 mol% Pd) resulted in quantitative
recovery of the amido iodide 2 upon cleavage from the resin
with TFA. In contrast, performing the same reaction in the
presence of 4-bromoanisole led to significant coupling (esti-
mated at 45% by 1H NMR spectroscopy) to afford a mixture of
the iodo amide 2 and the biaryl amide 3 upon cleavage. This
suggests that the presence of an organohalide is necessary for
the generation of a homogeneous catalyst. It thus appears that
Pd-containing perovskites operate at least partially by a
homogeneous mechanism. In the light of the ICP results – that
indicate particularly low levels of residual palladium – this
suggests that the catalyst may operate by a ‘release and capture’
mechanism, with the perovskite acting as a reservoir and
scavenger for the active catalytic species, although this is yet to
be confirmed.
Table 3 Suzuki coupling reactions with aryl chloridesa
In conclusion, it has been demonstrated that the perovskite
LaFe0.57Co0.38Pd0.05O3 functions as an air-stable, reuseable
catalyst for Suzuki cross coupling reactions under mild
conditions, with low levels of Pd leaching. Further reactions of
this and other perovskites will be disclosed in due course.
The authors would like to thank Daihatsu Motor Company1
for a kind gift of perovskite catalyst, the Royal Society for a
URF (to MDS), the Novartis Research Fellowship (to SVL) and
Pfizer Global Research and Development for ICP measure-
ments.
Entry
Transformation
Isolated yield (%)
1
2
3
R = NO2
R = Me
R = OMe
71
51
26
a Reagents and conditions: 0.25 mol% Pd, IPA-H2O (1 : 1, v/v), MW
heating at 135 °C, 3 eq. Na2CO3, 1.5 eq. PhB(OH)2, 1 h.
Table 4 Recycling experimentsa
Notes and references
1 Y. Nishiata, J. Mizuki, T. Akao, H. Tanaka, M. Uenishi, M. Kimura, T.
Okamoto and N. Hamadall, Nature, 2002, 418, 164.
Substrate:
2 R. B. Bedford, S. L. Hazelwood and M. E. Limmert, Chem. Commun.,
2002, 2610.
Run
Yield (%)
Time/h
1
95
1
2
93
0.6
3
93
2
4
95
1
5
93
1
3 N. E. Leadbeater and M. Marco, J. Org. Chem., 2002, 68, 888.
4 I. W. Davies, L. M. Matty, D. L. Hughes and P. J. Reider, J. Am. Chem.
Soc., 2001, 123, 10139; B. H. Lipshutz, S. Tasler, W. Chrisman, B.
Spliethoff and B. Tesche, J. Org. Chem., 2003, 68, 1177; J. A. Widegren
and R. G. Finke, J. Mol. Catal. A, 2003, 198, 317.
a Reagents and conditions: 0.05 mol% Pd, IPA–H2O (1 : 1, v/v), 80 °C, 3 eq.
K2CO3, 1.5 eq. PhB(OH)2.
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