Aqueous room-temperature gold-catalyzed chemoselective transfer hydrogenation of aldehydes

Article abstract of DOI:10.1002/chem.200901261

A highly efficient, aqueous, room temperature, formate-mediated TH of aldehydes catalyzed by supported gold nanoclusters was reported. A mixture of aldehyde, metal catalysts, and formate salts, water was put into a flask fitted with a magnetic stirring bar and a reflux condenser. After the mixture was stirred at 25°C for a given reaction time, the product mixtures were extracted with Et₂O for 3 times and analyzed. The identification of the products was performed by using a GC-MS spectrometer comparing with commercially pure products. For isolation, the combined organic layer was dried over anhydrous Na₂SO₄, concentrated, and purified by silica gel column chromatography to give the product. A good linear correlation for the rate as a function of CeO₂ surface area was observed.

Full text of DOI:10.1002/chem.200901261

COMMUNICATION
DOI: 10.1002/chem.200901261
Aqueous Room-Temperature Gold-Catalyzed Chemoselective Transfer
Hydrogenation of Aldehydes
Lin He, Ji Ni, Lu-Cun Wang, Feng-Jiao Yu, Yong Cao,* He-Yong He, and
Kang-Nian Fan[a]
Reduction of aldehydes to the corresponding alcohols is
one of the most fundamental and useful reactions that are
important in the pharmaceutical and chemical industry.[1]
Among the various available reduction protocols for the
synthesis of valuable hydroxy compounds,[2] catalytic trans-
fer hydrogenation (TH)[3] has emerged as the most viable,
mainly due to the non-involvement of highly flammable and
explosive molecular hydrogen or highly expensive metal hy-
dride donors. Moreover, TH processes generally involve
easy handling and recovery of products, recycling of catalyst
and minimization of undesired toxic wastes. One of the
recent highlights in this field is the use of cheap and easily
accessible formic acid[4] or its salts[5] as possible in situ hy-
drogen sources, which has attracted special attention owing
to their ease of hydrogen donation as compared to most
other transfer reduction agents. In this context, TH of alde-
hydes in the presence of formate salts is an area of growing
interest.[6] Although many transition-metal-based TH cata-
lysts have been developed,[6b,c] the focus has been largely on
homogeneous rather than heterogeneous catalysis. To the
best of our knowledge, few heterogeneous catalysts have
been reported that enable fast, chemoselective, and produc-
tive TH of aldehydes with inexpensive, eco-friendly for-
mates, and that can tolerate the presence of synthetically
useful functional groups.
compounds by molecular hydrogen.[8] One critical limitation
associated with the present Au-catalyzed hydrogenation pro-
cess, however, is the unfavorably low hydrogen-delivery
rates compared to other noble metals.[8b] Very recently, we
have described the use of a facile gold-catalyzed, 2-propa-
nol-mediated TH strategy that bypasses the inconvenient H2
activation thus enabling fast and chemoselective reduction
of a range of aromatic ketone and nitro groups.[9] From an
environmental and an economic viewpoint, efficient func-
tional transformations under milder conditions would be
most desirable. Herein, we report a highly efficient, aque-
ous, room temperature, formate-mediated TH of aldehydes
catalyzed by supported gold nanoclusters. Our results have
shown that the reaction is general and can proceed at tem-
peratures as low as 258C. Moreover, an inert atmosphere is
not required.
Initially, various heterogeneous catalysts were applied to
the transformation of benzaldehyde to benzyl alcohol in
aqueous HCOOK without inert gas protection at 808C
(Table 1). The benefit of using redox CeO2 as a support,
Table 1. Catalytic results of transfer hydrogenation of benzaldehyde
under various conditions.[a]
Entry Catalyst
%Metal T [oC] Time [h] Yield [%][e]
[mol]
AHCTUNGTRENNUNG
Supported gold nanoclusters have attracted increased in-
terest in the past few years as new generation of advanced
catalysts for a number of organic transformations[7] including
chemoselective reduction of unsaturated carbonyl or nitro
1[b]
2[c]
3
4
5
6
7
8
9
Au/meso-CeO2
1
1
1
1
1
1
1
1
1
3
3
80
80
80
80
80
80
80
80
80
25
25
3
3
3
3
3
3
3
3
3
6
6
>99 (97)
Au/CeO2 (Adnano 90)
Au/TiO2 (WGC)
Au/Fe2O3 (WGC)
Au/C (WGC)
Au/Al2O3 (Mintek)
Pd/C (Alfa Aesar)
Pt/C (Alfa Aesar)
meso-CeO2
21
13
8
1
12
20
17
–
>99
94
[a] L. He, J. Ni, L.-C. Wang, F.-J. Yu, Prof. Dr. Y. Cao,
Prof. Dr. H.-Y. He, Prof. K.-N. Fan
Shanghai Key Laboratory of Molecular Catalysis
and Innovative Materials
10
Au/meso-CeO2
Au/meso-CeO2
11[d]
Department of Chemistry, Fudan University
Shanghai 200433 (P.R. China)
Fax : (+86)21-6564-3774
[a] Reaction conditions: 1 mmol substrate, HCOOK (5 equiv), water
(15 mL), in air. [b] BET surface area of meso-CeO2 is 263 m2 gÀ1. [c] BET
surface area of CeO2 (Adnano 90) is 90 m2 gÀ1. [d] Fifth run. [e] Yield was
determined by GC. Numbers in parenthesis refer to yields of isolated
products.
E-mail: yongcao@fudan.edu.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200901261.
Chem. Eur. J. 2009, 15, 11833 – 11836
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11833

Table 2. The TH reaction of various aldehydes with HCOOK.[a]
especially mesoporous CeO2 (meso-CeO2) with very high
specific surface area (263 m2 gÀ1), became obvious when
comparing the activity of Au/meso-CeO2 with the activities
of Au supported on conventional ceria (Au/CeO2 Adnano
90), Au/TiO2, Au/Fe2O3, Au/C supplied by the World Gold
Council (WGC) and Au/Al2O3 provided by Mintek (Table 1,
entries 1–6). A clear advantage of the Au/meso-CeO2 cata-
lyst over other noble metals was also noticed when benzal-
dehyde was reduced by using Pd/C or Pt/C under otherwise
identical conditions (Table 1, entries 7–8). Note that this be-
havior is in stark contrast to recent liquid phase direct hy-
drogenation studies,[8b,10] where Au was found to be much in-
ferior to Pd or Pt in terms of the hydrogenation rate. Most
remarkably, at room temperature, transfer hydrogenation of
benzaldehyde still could proceed smoothly in the presence
of Au/meso-CeO2 (Table 1, entry 10). No conversion was
found in the absence of catalysts or in the presence of Au-
free meso-CeO2 catalyst under identical conditions (Table 1,
entry 9), illustrating that the presence of gold was indispen-
sable for high catalytic activity.
Au/meso-CeO2 was filtered from the reaction mixture at
50% conversion of benzaldehyde under the conditions in
entry 10 of Table 1. Continued stirring of the filtrate under
similar conditions did not give any products. Inductively
coupled plasma atomic emission spectroscopy (ICP-AES)
analysis of the filtrate showed that no Au was present
(<0.10 ppm). Furthermore, the recovered Au/meso-CeO2
catalyst could be reused at least five runs without apprecia-
ble loss of the original catalytic activity (Table 1, entry 11).
These results rule out any possible contribution of homoge-
neous catalysis by leached gold species.
Entry Aldehyde
Product
Time [h] Yield [%][d]
1
6
99 (97)
2
3
12 99
5
99 (96)
4
5
6
7
4
6
99
98
12 99 (97)
8
6
99
99
8
9[b]
14 84 (82)
10[b]
11
7
80
10 96
12
18 92 (88)
21 90
The Au/meso-CeO2 -catalyzed protocol is equally effective
on a larger scale. For example, the transfer reduction of ben-
zaldehyde (10 mmol) in the presence of Au/meso-CeO2
(1 mol% Au) and 5 equivalents (with respect to benzalde-
hyde) of HCOOK in aqueous media gave the corresponding
benzyl alcohol in 96% isolated yield (Scheme 1).
13[c]
[a] Reaction conditions: 1 mmol substrate, Au/meso-CeO2 (3 mol% Au),
HCOOK (5 equiv), water (15 mL), 258C, in air. [b] 1 mmol substrate, Au/
meso-CeO2 (3 mol% Au), HCOOK (5 equiv), water (15 mL), 808C, in
air. [c] 0.4 mmol substrate, Au/meso-CeO2 (7.5 mol% Au), HCOOK
(5 equiv), water (15 mL), 258C, in air. [d] Yield was determined by GC.
Numbers in parenthesis refer to yields of isolated products.
corresponding benzyl alcohols at ambient conditions
(Table 2, entries 1–8). In the transformations of chloroben-
zaldehydes, the lower reaction rate of o-chlorobenzaldehyde
relative to m- and p-analogues indicated a steric effect (en-
tries 2–4). Moreover, high selectivity could also be attained
for the reduction of halogen substituted benzaldehydes
(Table 2, entries 2–5), with no observation of dehalogenation
or ring reduction. Hetero-aromatic aldehydes could be re-
duced in almost quantitative yield in a short time (Table 2,
entry 11). The less reactive aliphatic ones could also be hy-
drogenated to the corresponding aliphatic alcohols with
longer reaction time (Table 2, entries 12 and 13) at room
temperature. a,b-unsaturated aldehydes were more chal-
lenging as substrates because thermodynamics favors hydro-
genation of C=C over C=O,[10,11] yet the present system
under mild TH condition still led to promising results
Scheme 1. Larger-scale TH of benzaldehyde.
With these findings in hand, we then extended our studies
to various kinds of aldehydes to establish the scope of the
aqueous TH of aldehydes with Au/meso-CeO2. Table 2
showed that the catalyst system was surprisingly versatile.
Various structurally diverse aldehydes, including aromatic,
aliphatic, unsaturated, and heterocyclic aldehydes, could be
transformed into the corresponding alcohols in high to ex-
cellent yields. The transformation of substituted benzalde-
hydes, which contain electron-donating as well as electron-
withdrawing substituents, proceeded efficiently to give the
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Chem. Eur. J. 2009, 15, 11833 – 11836

Gold-Catalyzed Transfer Hydrogenation of Aldehydes
COMMUNICATION
(Table 2, entries 9 and 10), in marked contrast to the unfav-
orably poor selectivity (<30%) as previously achieved for
direct liquid phase crotonaldehyde hydrogenation by gold
supported on CeO2.[11]
pendence on the concentration of aldehydes and a first-
order dependence on the concentration of HCOOK (Figur-
es S6, S7 and S8). This scenario, in conjunction with the sig-
nificantly retarded conversion identified for using other for-
mate sources as the hydrogen donors (Figure S5),[13] further
confirms the CeO2-mediated formate dehydrogenation is
the rate-determining step.
A reaction mechanism based on the mechanistic and ki-
netic experiments for the aqueous formate-mediated TH of
aldehydes by Au/meso-CeO2 was depicted in (Scheme 3).
Ceria sites (Ce3+ and Ce4+ were detectable by XPS, Fig-
ure S2) facilitated by H2O were involved in the rate-deter-
mining dehydrogenation of formate to bicarbonate species
(step 1). The hydrogen species thus formed could transfer to
vicinal Au0 clusters (Figure S2 and S3, data for XPS and CO
adsorption coupled with DRIFTS) via reverse hydrogen
In an intermolecular competitive reaction between ben-
zaldehyde and acetophenone, benzyl alcohol was the only
reduction product without formation of 1-phenylethanol
from acetophenone. The high selectivity for the specific re-
duction of the C=O moiety in a,b-unsaturated aldehydes
was also confirmed by the competitive reaction of benzalde-
hyde and styrene. When the yield of benzyl alcohol was
>99%, the conversion of styrene did not exceed 7%
(Scheme 2). Therefore, the intrinsic higher rate for the re-
duction of the aldehydes group on the gold catalyst is re-
sponsible for the high chemoselectivity observed.
0
[14]
À
spillover to form Au H complexes, which is believed to
be the key active intermediate for transfer hydrogenation
(step 2). Au H complexes were rapidly consumed together
0
À
with a final formation of the alcohol product (step 3).[15]
In summary, we have shown that gold nanoclusters sup-
ported on a mesoporous ceria matrix are highly active and
chemoselective catalysts for the aqueous-phase TH of alde-
hydes at room temperature. Of significant practical impor-
tance is that the catalyst tolerates a wide variety of syntheti-
cally useful functional groups including halogens, ketones,
and olefins. To the best of our knowledge, this aqueous Au-
mediated catalysis represents the most efficient, simple, and
eco-friendly catalytic system for the selective reduction of
aldehydes to date.
Scheme 2. Competitive reaction of benzaldehyde and styrene.
To obtain an insight into the origin of the enhanced Au-
mediated TH activity achieved by using meso-CeO2 as sup-
port, we examined a series of Au/CeO2 samples in which the
surface area of CeO2 was varied by calcination at elevated
temperatures. Interestingly, a good linear correlation for the
rate as a function of CeO2 surface area was observed (Fig-
ure S4). We speculate that the dehydrogenation of formate
salts occurs mainly on the surface of ceria, particularly on
considering that the ceria surface acts as a sink for the reac-
tive formate in the case with water gas shift (WGS) reaction
(Scheme 3).[12] This hypothesis is corroborated by the fact
that the kinetic studies revealed a first-order dependence on
the amount of Au/meso-CeO2 catalysts, a zero-order de-
Experimental Section
General procedure for the TH reaction of aldehydes: A mixture of alde-
hyde (1 mmol), metal catalysts (3 mol% metal), and formate salts
(5 equiv), water (15 mL) was put into a flask (50 mL) fitted with a mag-
netic stirring bar and a reflux condenser. After the mixture was stirred at
258C (808C for a, b-unsaturated aldehydes) for a given reaction time,
the product mixtures were extracted with Et2O for 3 times and analyzed
(the water phase was also analyzed) by using a Shimadzu GC-17 A gas
chromatograph equipped with a HP-FFAP column (30 mꢁ0.25 mm) and
a flame ionization detector (FID). The identification of the products was
performed by using a GC-MS spectrometer comparing with commercially
pure products. For isolation, the combined organic layer was dried over
anhydrous Na2SO4, concentrated, and purified by silica gel column chro-
matography to give the product.
Acknowledgements
This work was support by the National Natural Science Foundation of
China (20633030, 20721063, and 20873026), the National Basic Research
Program of China (2009CB623506), Science & Technology Commission
of Shanghai Municipality (08DZ2270500, 07QH14003) and the Commit-
tee of the Shanghai Education (06SG03).
Keywords: aldehydes
temperature · transfer hydrogenation
·
chemoselectivity
·
gold
·
room
11835
Scheme 3. A tentative mechanism for aqueous formate-mediated TH of
aldehydes over Au/meso-CeO2
Chem. Eur. J. 2009, 15, 11833 – 11836
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org

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[15] Based on the GC-MS analysis, no hydrogen was generated during
the process of the Au/meso-CeO2-catalyzed TH of aldehydes, which
indicates that the encountered reduction was a true hydrogen trans-
fer rather than
AHCTUNGTRENNrGUN eaction.
a
consecutive dehydrogenation-hydrogenation
Received: May 12, 2009
Published online: October 1, 2009
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Chem. Eur. J. 2009, 15, 11833 – 11836