Transfer hydrogenation using recyclable polyurea-encapsulated palladium: efficient and chemoselective reduction of aryl ketones.

Article abstract of DOI:10.1039/b300074p

A robust and recyclable palladium catalyst [Pd0EnCat] has been prepared by ligand exchange of polyurea-encapsulated palladium(II) acetate with formic acid, resulting in deposition of Pd(0) in the support material; Pd0EnCat is shown to be a highly efficient transfer hydrogenation catalyst for chemoselective reduction of a wide range of aryl ketones to benzyl alcohols.

Full text of DOI:10.1039/b300074p

Transfer hydrogenation using recyclable polyurea-encapsulated
palladium: efficient and chemoselective reduction of aryl ketones
Jin-Quan Yu, Hai-Chen Wu, Chandrashekar Ramarao, Jonathan B. Spencer* and Steven V. Ley*
University Chemical Laboratories, Lensfield Road, Cambridge, UK CB2 1EW. E-mail: svl1000@cam.ac.uk;
Fax: +44 1223 336442; Tel: +44 1223 336398
Received (in Cambridge, UK) 3rd January 2003, Accepted 4th February 2003
First published as an Advance Article on the web 12th February 2003
A robust and recyclable palladium catalyst [Pd0EnCat] has
been prepared by ligand exchange of polyurea-encapsulated
palladium(II) acetate with formic acid, resulting in deposi-
tion of Pd(0) in the support material; Pd0EnCat is shown to
be a highly efficient transfer hydrogenation catalyst for
chemoselective reduction of a wide range of aryl ketones to
benzyl alcohols.
yields through five successive recycle runs (Table 1). Pleas-
ingly, no traces of methylene compounds from further hydro-
genolysis or products from the over-reduction of the aromatic
ring were detected by either NMR or GC. A clear advantage of
this catalyst over Pd/C was also noticed when propiophenone
was reduced using Pd/C (10%) under otherwise identical
conditions. (Scheme 1).
The newly prepared catalyst [Pd0EnCat] is clearly more
reactive than Pd/C with higher conversion within the same
reaction time (Table 2). A mechanistic study was conducted to
probe the electronic property of this palladium catalyst by using
a reported assay.14 It was found the metal centre is more
electron rich than Pd/C, which could account for this superior
catalytic property.15
The scope of this catalytic method was established by using
a wide range of aryl ketones and in all cases the reactions reach
completion within 21–48 h with exceedingly high yields (Table
2). It is worth noting that the hetero-aromatic ketones are also
reduced in almost quantitative yields.
The selective and rapid reduction of nitro groups in the
presence of carbonyl functionalities is also a highly valuable
transformation in organic synthesis. The development of an
efficient catalytic system to achieve this goal has attracted
considerable effort recently.16 Therefore it was decided to
investigate whether [Pd0EnCat] could provide a better solution
to this challenge. The result showed that [Pd0EnCat] mediated
transfer hydrogenation can effect highly efficient reduction of
nitro groups in the presence of carbonyl functionalities (Scheme
2). Importantly, the chemoselectivity was found to be sig-
nificantly higher than Pd/C catalysed transfer hydrogenation
(99% vs. 85%).17
Reduction of ketones to alcohols is a synthetically important
transformation, both in the laboratory and in industry. A large
number of stoichiometric metal hydride reagents have been
developed to effect this transformation and efforts toward
further improvements continue.1,2 The development of homo-
geneous catalysts for the reduction of carbonyl compounds
using molecular hydrogen or other hydrogen donors has
attracted special attention. Ruthenium-complex catalysed hy-
drogenation or transfer hydrogenation have proved to be
particularly reliable.3,4 However, the current emphasis on
cleaner methods for chemical transformations requires high
selectivity, low cost, easy separation and production of
minimum waste. One of the recent highlights in this area
involved the uncatalysed hydrogen-transfer reductions of
ketones at elevated temperature.5 From a practical point of view
a more attractive approach is to develop a heterogeneous
catalyst that is efficient for this transformation. Although the
reduction of aliphatic ketones using heterogeneous catalysts
remains an unanswered challenge, it has been shown that aryl
ketones can be reduced, typically by Pd/H2.6 The major problem
associated with this system has been the further hydrogenolysis
of the initially formed benzyl alcohol and the over-reduction of
the aromatic ring.6 This was circumvented by adding ethylene-
diamine.7 However, this makes isolation of the product and
recycling the catalyst problematic.
In summary, a highly efficient heterogeneous palladium
catalyst [Pd0EnCat] for transfer hydrogenation was prepared by
treatment of [PdEnCat™] with HCOOH leading to deposition
Palladium(II) acetate microencapsulated in polyurea [PdEn-
Cat™] has been demonstrated to be an accomplished recyclable
catalyst for a number of key transformations.8–10 As part of the
continuous effort to develop environmentally benign catalytic
systems, it was decided to prepare polyurea-encapsulated Pd(0)
[Pd0EnCat] from [PdEnCat™]11 and investigate whether this
could provide a solution to the heterogeneous transfer hydro-
genation of aryl ketones. Our initial efforts were directed to
establishing an efficient preparative procedure for [Pd0EnCat]
that would not only exhibit high reactivity but also resist
leaching. It emerged quickly that formic acid was the best
reducing reagent to produce a catalyst meeting both of these
criteria. It is clear that the rate of the deposition of the Pd(0)
increases when the concentration of formic acid in ether is
raised, and a 1+1 mixture of formic acid and ether was found to
be the best choice.12 Further investigations were carried out to
establish the optimal reaction conditions. It was found that
better performance in terms of reactivity and stability of the
catalyst was achieved by using HCOOH, Et3N in the molar ratio
of 1+1 (instead of 5+2 used conventionally for other cata-
lysts).13 The stability of the catalyst was further improved by
adding ethyl acetate as a solvent.
Table 1 Recycling experimentsa
Run
1
2
3
4
5
Yield (%) 99
Time/h 21
98
22
98
24
97
26
96
28
a Reagents and conditions: 10 mol% Pd0-EnCat, 200 mL EtOAc, 0.8 mmol
HCOOH, 0.8 mmol Et3N, 0.016 mmol acetophenone, 24 °C.
The efficiency and stability of the newly established catalytic
system was examined in detail with acetophenone as a substrate.
Reduction proceeds to completion giving excellent isolated
Scheme 1 (a) Reagents and conditions: 10 mol% Pd/C (10%), 200 mL
EtOAc, 0.8 mmol HCOOH, 0.8 mmol Et3N, 0.016 mmol Propiophenone, 24
°C, 22 h.
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CHEM. COMMUN., 2003, 678–679
This journal is © The Royal Society of Chemistry 2003

of Pd(0) in the polyurea support material. This catalyst has been
proven to be highly efficient and chemoselective in the
reduction of carbonyl and nitro groups. The stability of the
catalyst has also been demonstrated convincingly by conducting
five successive runs without an obvious drop in the reaction
rate. Further application of the newly constructed catalytic
system to many other key transformations are currently being
explored.
We thank Syngenta (to CR) for financial support and Dr
Stephen C. Smith for useful discussions. We also acknowledge
St John’s College, Cambridge University for a Research
Fellowship (to JQY), and support from the BP Endowment and
the Novartis Research Fellowship (to SVL).
Table 2 Reduction of aromatic ketones using Pd0-EnCat/HCOOH/Et3Nab
Yield
Entry
1
Ketone
Reduced product
Time/h
21
(%)
99
Notes and references
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7
8
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92
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11 The Pd(OAc)2 polyurea encapsulated catalyst PdEnCat™ is available
from Dr D. Pears, Avecial Ltd., P. O. Box 42, Hexagon House,
Blackley, Manchester M9 82S. The cross-linking of the polyurea is
ensured by the addition of ethylene diamine and the material takes the
form of spherical microcapsules. The average loading of Pd is
determined by Inductively Coupled Plasma (ICP) MS to be approx-
10
18
99
imately 0.4 mmol g21
.
12 Preparation of Pd0EnCat: 0.5 g PdEnCat™ was introduced to a mixture
of 3 mL diethyl ether and 1 mL formic acid. The reaction mixture was
allowed to reflux for 5 hours with vigorous stirring. The solvent was
removed by pipette. The black beads (100–200 microns) were washed
by diethyl ether and dried under vacuum overnight.
13 W. Leitner, J. M. Brown and H. Brunner, J. Am. Chem. Soc., 1993, 115,
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11
18
99
a Reagents and conditions: 10 mol% Pd0-EnCat, 200 mL EtOAc, 0.8 mmol
HCOOH, 0.8 mmol Et3N, 0.016 mmol Ketone, 24 °C. b Catalyst was reused
for 5 times.
15 It is also possible that the size of the Pd clusters within the
microcapsules might have a profound effect on the reactivities.
Mearsurement of the size of the Pd clusters in Pd0EnCat using
Transmission Electronic Microscopy suggests the size (@2 microns) is
much smaller than the corresponding clusters from Pd/C (15 mi-
crons).
16 T. T. Upadhya, S. P. Katdare, D. P. Sabde, Veda Ramaswamy and A.
Sudalai, J. Chem. Soc., Chem. Commun., 1997, 1119–1120.
17 D. C. Gowda and S. Gowda, Indian J. Chem. Sect. B, 2000, 39,
709–711.
Scheme 2 (a) Reagents and conditions: 10 mol% Pd0-EnCat, 200 mL
EtOAc, 0.8 mmol HCOOH, 0.8 mmol Et3N, 0.016 mmol acetophenone, 24
°C, 2.5 h.
CHEM. COMMUN., 2003, 678–679
679