Angewandte
Chemie
DOI: 10.1002/anie.201306243
Homogeneous Catalysis Hot Paper
Silver-Catalyzed Hydrogenation of Aldehydes in Water**
Zhenhua Jia, Feng Zhou, Mingxin Liu, Xingshu Li, Albert S. C. Chan, and Chao-Jun Li*
The hydrogenation of organic compounds is one of the most
important classes of reactions for the synthesis of biorenew-
able chemicals and fuels, commodity chemicals, fine chem-
hypothesized that the organic transformation of aldehydes
into alcohols could be realized by using silver complexes as
catalysts. Herein, we report the first silver-catalyzed hydro-
genation of aldehydes in water, revealing an unprecedented
reactivity for silver (Scheme 1).
[1]
icals, and pharmaceuticals. Since the widely known Wilkin-
son catalyst was prepared and used for the hydrogenation of
[
2]
alkenes in the 1960s, a vast number of rhodium, ruthe-
[3]
[4]
[5]
nium, palladium, and iridium catalysts have shown
excellent activity in homogeneous hydrogenation. Recently,
there has also been significant progress in hydrogenation by
using cheaper and more abundant metals (Fe, Co etc.) as
[
6]
catalysts, as well as frustrated Lewis pairs in metal-free
[
7]
systems. Surprisingly, homogeneous complexes of silver, one
of the most important metals throughout history, have never
shown any practical catalytic organotransformation through
[
8]
activating molecular hydrogen, even though Halpern and
2
À
Webster reported that inorganic substrates such as [Cr O ]
2
7
3
+
and Fe could be reduced through catalytic hydrogenation in
aqueous solution. One problem is that silver cannot easily
undergo oxidative addition like other transition metals do
Scheme 1. Silver-catalyzed reduction of aldehydes in water.
[
9]
(
e.g. + 1 to + 3). Traditional catalytic hydrogenations proceed
We began our research by using benzaldehyde (1a) as
a model substrate (Table 1). Given the importance of
bidentate ligands with wide bite angles, bidentate phosphine
through the homolytic oxidative addition of H across a metal
2
catalyst. The ground-breaking work of Noyori on heterolytic
H–H breaking through ruthenium catalysis led to highly
efficient hydrogenations for carbonyls, especially in the
ligands were examined first. Under H (10 bar), 1,1’-bis(di-
2
phenylphosphino)ferrocene (dppf) was tested in water at
1008C with 20% diisopropylethylamine (DIPEA) as a base
additive; to our frustration, benzyl alcohol (2a) was not
detected after 24 h (Table 1, entry 1). Other bidentate ligands
were screened, and the desired product was generated in 5%
yield by using QUINAP as the ligand (Table 1, entries 2–6).
We then turned our attention to the electron-rich mono-
phosphine ligands because they have been proven to enhance
[
1e]
context of asymmetric synthesis . Heterolytic cleavage of
the HÀH bond also allows hydrogenation without changing
the oxidation state of the metal.
In the course of our continuing efforts in developing
metal-mediated or metal-catalyzed reactions in water, we
have discovered that a silver catalyst could activate the CÀH
bond of terminal alkynes, and the resulting intermediates
could further react with carbonyls in water to produce the
[
10b]
the nucleophilicity of nucleophiles.
To our delight, in the
[
10]
7
corresponding addition product.
by Halpern and Webster, it is feasible that molecular hydro-
gen could be activated by silver salts in aqueous media. We
Furthermore, as reported
presence of AgCl and XPhos (L ), the expected product was
detected in 11% yield (Table 1, entry 7). Further screening of
monophosphine ligands revealed that the Buchwald ligands
XPhos (L ) and RuPhos (L ) were more effective than the
others (Table 1, entries 8–12). A series of silver catalysts was
[
9]
7
12
[*] Z.-H. Jia, Dr. F. Zhou, M. Liu, Prof. Dr. C.-J. Li
7
then tested by using XPhos (L ) as the ligand (see the
Department of Chemistry and
Supporting Information). Among these, AgPF was the most
FQRNT Center for Green Chemistry and Catalysis
McGill University, Montreal, Quebec, H3A 0B8 (Canada)
E-mail: cj.li@mcgill.ca
6
promising and delivered the desired product in 56% yield
(Table 1, entry 13). The use of the structurally similar ligand
1
2
Homepage: http://cjli.mcgill.ca/cjpage.htm
RuPhos (L ) gave a slightly lower yield (Table 1, entry 14).
Z.-H. Jia, X.-S. Li, Prof. Dr. A. S. C. Chan
School of Pharmaceutical Sciences
Institute of Drug Synthesis and Pharmaceutical Process
Sun Yat-sen University, Guangzhou 510006 (P.R. of China)
We realized that the pressure of H may be not sufficient to
achieve complete conversion. Subsequently, efforts were
2
made to increase the H pressure to further enhance the
2
catalytic efficiency. Under 20 bar of H , we obtained 2a in
2
[
**] We are grateful to the Canada Research Chair Foundation (to C.-
J.L.), the CFI, FQRNT Center for Green Chemistry and Catalysis,
NSERC, and McGill University for support of our research. Z.-H.J.
thanks the support from the Oversea Study Program of Guangzhou
Elite Project for financial support.
6
5% yield (Table 1, entry 15). We also obtained 2a in 83%
yield under 30 bar of H (Table 1, entry 16). When the H
2
2
pressure was increased to 40 bar, an almost quantitative yield
was generated (Table 1, entry 17). However, lowering the
reaction temperature to 808C resulted in lower efficiency
(Table 1, entry 18).
Angew. Chem. Int. Ed. 2013, 52, 11871 –11874
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
11871