Efficient and chemoselective reduction of carbonyl compounds with supported gold catalysts under transfer hydrogenation conditions

Article abstract of DOI:10.1039/b807608a

A new heterogeneous catalytic transfer hydrogenation (CTH) system, consisting of a non-flammable supported Au catalyst along with 2-propanol as the hydrogen donor, was proven to be effective for chemoselective reduction of a wide range of aromatic ketones and aldehydes to the corresponding alcohols. The Royal Society of Chemistry.

Full text of DOI:10.1039/b807608a

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Efficient and chemoselective reduction of carbonyl compounds with
supported gold catalysts under transfer hydrogenation conditionsw
Fang-Zheng Su, Lin He, Ji Ni, Yong Cao,* He-Yong He and Kang-Nian Fan
Received (in Cambridge, UK) 6th May 2008, Accepted 4th June 2008
First published as an Advance Article on the web 2nd July 2008
DOI: 10.1039/b807608a
A new heterogeneous catalytic transfer hydrogenation (CTH)
system, consisting of a non-flammable supported Au catalyst
along with 2-propanol as the hydrogen donor, was proven to be
effective for chemoselective reduction of a wide range of aro-
matic ketones and aldehydes to the corresponding alcohols.
hydride complex) of the transfer hydrogenation with respect
to direct hydrogenation, it is conceivable that the supported
gold catalysts may also provide an attractive alternative for
transfer hydrogenation. Herein, we report for the first time a
very efficient, highly selective and rapid method for the
reduction of carbonyl compounds using a supported gold
catalyst. To the best of our knowledge, this study also presents
the first chemoselective reduction of nitro compounds in the
presence of carbonyl groups by transfer hydrogenation using
gold catalysts.
The reduction of carbonyl compounds to the corresponding
alcohols is a synthetically important transformation, both in
the laboratory and industry.1 Although a number of methods
have been developed, the search for new facile, cost-effective
and ecofriendly procedures that avoid the use of stoichiometric
reducing reagents or hazardous molecular hydrogen (H2) has
attracted substantial interest.2 An attractive alternative is the
catalytic transfer hydrogenation (CTH) employing hydrogen
donors, e.g., 2-propanol, which is operationally simple and can
avoid the use of molecular hydrogen.3 Both homogeneous as
well as heterogeneous catalysts for CTH are known.4 From a
practical point of view, it is more desirable to develop a
heterogeneous catalyst that is efficient for this transformation.5
Nevertheless, these processes require flammable or moisture-
sensitive catalysts such as using Raney Ni, Pd/C and PtO2
etc.,6–8 which presents additional handling problems. Although
CTH reactions are generally very facile over these catalysts,
they are, however, not selective toward functional groups such
as –CO, –CX and –NO2 moieties, and almost all labile func-
tional groups undergo reduction under the reaction conditions.
In the continued search for more effective catalysts for the
CTH process, there is a definite need for new easily-handled
heterogeneous catalysts that allow convenient and efficient
transfer reduction under mild conditions.
First of all, a comparative study of Au/support (1.5 wt%
Au/TiO2, 4.5 wt% Au/Fe2O3 and 0.8 wt% Au/C, all provided
by the World Gold Council) and Pd/C (5 wt%, Fluka)
catalysts was carried out with acetophenone as a substrate.
The CTH reactions were carried out as per standard proce-
dures using 2-propanol as the hydrogen donor.w As can be
seen from Table 1, excellent selectivities towards phenyl
ethanol can be attained for all Au catalysts, with the order
of the catalysts with respect to the corresponding yield of
acetophenone being Au/TiO2 4 Au/Fe2O3 4 Au/C. Further-
more, there is no reaction on using Au-free TiO2 catalysts,
illustrating that the presence of gold was indispensable for
high catalytic activity. The reason for the high catalytic
activity of Au/TiO2 is probably the high dispersion of Au
nanoparticles in combination with a beneficial synergetic
interaction with the TiO2 support.14,15 A clear advantage of
the supported gold catalyst over Pd/C was also noticed when
acetophenone was reduced using Pd/C under otherwise iden-
tical conditions. Note that this behaviour is in contrast to
Supported gold nanoparticles9 have recently emerged as
excellent catalysts for a broad range of organic transforma-
tions under mild conditions.10 Despite appreciable work that
has been conducted in several oxidation reactions,11 a number
of recent reports have demonstrated that supported gold
nanoparticles can be highly chemoselective for the direct
hydrogenation of CQO groups of a,b-unsaturated alde-
hydes.12 Very recently, Corma and Serna have established
that the regioselective direct hydrogenation of a nitro group
in the presence of other reducible functions can be achieved by
using supported gold catalysts.13 In view of the microscopic
reverse nature of the key step (i.e., formation of a metal
Table 1 Catalytic results of the transfer hydrogenation of acetophe-
none over different catalystsa
Entry
Catalysts
Time/h
Conversion (%)
Selectivity (%)
1
2
3
4
Au/TiO2
TiO2
Au/Fe2O3
Au/C
Pd/C
4
6
4
4
4
4
99
—
35.3
13.9
63
100
—
99
98
98
100
5
6b
Au/TiO2
98.5
a
Reaction performed under an N2 atmosphere at 82 1C using 2-pro-
panol (10 ml) as the solvent and hydrogen source, 1 mmol substrate,
0.78 mol% metal and 0.3 equiv. KOH. Conversion and selectivity was
Department of Chemistry & Shanghai Key Laboratory of Molecular
Catalysis and Innovative Material, Fudan University, Shanghai
200433, P. R. China. E-mail: yongcao@fudan.edu.cn;
Fax: (+86)-21 65642978; Tel: (+86)-21 55665287
w Electronic supplementary information (ESI) available: Experimental
section. See DOI: 10.1039/b807608a
b
determined by GC using o-xylene as the internal standard. Results
for the fifth run.
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a
Table 2 Catalytic transfer hydrogenation of ketones over Au/TiO2
Table 3 Catalytic transfer hydrogenation of aldehydes over Au/
TiO2
a
Entry Substrate
Product
Time/ Conversion
h
(selectivity)
(%)
Entry Substrate
Product
Time/ Conversion
h
(selectivity)
(%)
1
2
4
99 (100)
98 (99)
92 (99)
93 (98)
60 (98)
1
4
90 (99)
94 (99)
6
2b
6
3
4
5
3.5
8
3
4
5
9
2
8
98 (98)
92 (99)
99 (94)
10
6
2.5
499 (99)
6
7
8
70 (86)
9
8
44 (499)
a
Reaction performed under an N2 atmosphere at 120 1C using
2-propanol (10 ml) as the solvent and hydrogen source, 1 mmol
substrate, 0.78 mol% Au and 0.3 equiv. K2CO3. Conversion and
selectivity was determined by GC using o-xylene as the internal
b
8
31 (98)
standard. Reaction performed at 150 1C with no addition of base.
(Table 2). As illustrated in Table 2, selective reduction of
4-methoxyacetophenone (entry 2) is possible to afford the
corresponding alcohol in excellent yield albeit with a longer
reaction time. Moreover, high yields can also be attained for
4-chloroacetophenone reduction (entry 3), with no evidence of
hydrodechlorination or ring reduction. It is worth noting that
a hetero-aromatic ketone can also be reduced in almost
quantitative yields (entry 4). On the other hand, the reductions
of compounds containing substituents present either on the
aromatic ring or in the a-position (entries 5–7) revealed that
the activity is largely influenced by the presence of an a-bulky
group due to steric hindrance. Such a limitation was also
observed in the reduction of 2-nonanone (entry 8), for which
the observed activity is significantly lower than all other
substrates.
a
Reaction performed under an N2 atmosphere at 82 1C using 2-pro-
panol (10 ml) as the solvent and hydrogen source, 1 mmol substrate,
0.78 mol% Au and 0.3 equiv KOH. Conversion and selectivity was
determined by GC using o-xylene as the internal standard.
recent liquid phase direct hydrogenation studies where Au is
found to be much inferior to Pd as a hydrogenation cata-
lyst.12,13 Although the origin of this exceptional activity is not
clear, a possible explanation might be that under these hydro-
gen transfer conditions the presence of a strong base can
greatly facilitate the hydrogen-delivery rates of the Au
catalyst.
The Au/TiO2 was stable, reusable and not flammable and
thus could be easily handled or stored under ambient condi-
tions. After the first transfer reduction reaction, the catalyst
was filtrated and washed with acetone, then reused for the
second reaction. The catalytic results indicate that there is no
difference in either activity or selectivity between the first and
fifth runs (Table 1, entries 1 and 6). Au leaching was negligible
during the above recycles. In addition, no change in the Au
particle structure was observed by TEM.w These results de-
monstrate that highly dispersed gold nanoparticles retain their
properties even after completion of the reaction and that the
catalyst is active for several cycles.
Further, for the transfer reduction of aldehydes, we exam-
ined the catalytic activity of Au/TiO2 for the selective reduc-
tion of various substrates and the results are presented in
Table 3. To avoid undesirable Cannizzaro reactions that may
take place in the presence of strong bases, transfer hydrogena-
tion of aldehydes was carried out in the presence of K2CO3.
Although it is well known that aldehydes are difficult to reduce
by catalysts commonly used for CTH,16 transfer hydrogena-
tion of aromatic aldehydes (entries 1, 3–6) could afford
complete conversion to the benzyl alcohols. Moreover, much
higher rates for para and meta isomers relative to the ortho
isomer reveal a tremendous steric effect for p-, o-, or
m-chloroacetaldehyde isomer reductions. It is also important
The scope of the catalyst was established by using a wide
range of aromatic ketones and in many cases the reaction was
completed within 4–10
h with exceedingly high yields
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Scheme 1 Catalytic transfer hydrogenation of 4-nitroacetophenone
over Au/TiO2.
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to note that the transfer hydrogenation of benzaldehyde can
also proceed efficiently under base-free conditions (entry 2),
although a higher reaction temperature is required. This
indicated that the presence of a base is helpful to form the
Au–H complex17 via interaction with the hydrogen donor,
which is believed to be the key active intermediate for transfer
hydrogenation.
The selective and rapid reduction of nitro groups in the
presence of carbonyl functionalities is also a highly valuable
transformation in organic synthesis.18 The development of an
efficient catalytic system to achieve this goal has attracted
considerable effort recently.13,19 Therefore it was decided to
investigate whether Au/TiO2 could provide a viable solution to
this challenge. The result showed that Au/TiO2 mediated
transfer hydrogenation can afford highly efficient reduction
of nitro groups in the presence of carbonyl functionalities
(Scheme 1). It is remarkable that 100% chemoselectivity in
terms of –NO2 reduction can be achieved for 4-aminoaceto-
phenone production. Such reaction exclusivity, notably the
absence of any carbonyl group or ring reduction, is unique
when compared with the conventional catalytic systems.5e,20
In summary, we have demonstrated that the non-flammable
Au/TiO2 regent has great potential for catalytic transfer
hydrogenation. This catalyst has been proven to be highly
efficient and chemoselective in the reduction of carbonyl and
nitro groups. The efficiency and stability of the catalyst has
also been demonstrated convincingly by conducting five suc-
cessive runs without any drop in the reaction rate. Further
application of the Au-based catalytic system to many other
key transformations is currently being explored.
Financial support by the National Natural Science Founda-
tion of China (20421303, 20473021, 20633030), the National
High Technology Research and Development Program of
China (2066AA03Z336), and the National Basic Research
Program of China (2003CB615807), the Shanghai Science &
Technology Committee (07QH14003) and Shanghai Educa-
tion Committee (06SG03) is kindly acknowledged.
Notes and references
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1989, p. 411 ; (b) G. W. Kabalka and R. S. Verma, Comprehensive
Organic Synthesis, ed. B. M. Trost and I Fleming, Pergamon
Press, Oxford, 1991, vol. 8, p. 363.
19. A. Corma, P. Concepcion and P. Serna, Angew. Chem., Int. Ed.,
2007, 46, 7266.
20. P. Selvam, S. U. Sonavan, S. K. Mohapatra and R. V. Jayaram,
Tetrahedron Lett., 2004, 45, 3071.
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Chem. Commun., 2008, 3531–3533 | 3533