Pd-catalyzed reduction of aldehydes to alcohols using formic acid as the hydrogen donor

Article abstract of DOI:10.1080/00397911.2013.804575

Facile and selective reduction of aromatic aldehydes as well as aliphatic aldehydes to alcohols was achieved using formic acid as the hydrogen donor in the presence of a catalytic amount of Pd(OAc)² and Cy³P. It was found that both hydrogen atoms in the formic acid molecule can serve as the hydride source. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]

Full text of DOI:10.1080/00397911.2013.804575

This article was downloaded by: [University of Tennessee, Knoxville]
On: 31 August 2013, At: 01:58
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Pd-Catalyzed Reduction of Aldehydes to Alcohols Using
Formic Acid as the Hydrogen Donor
Anwei Wang a , Zhiyong Yang a , Jidan Liu a , Qingwen Gui a , Xiang Chen a , Ze Tan a & Ji-
Cheng Shi b
a State Key Laboratory of Chemo/Biosensing and Chemometrics , College of Chemistry and
Chemical Engineering, Hunan University , Changsha , P. R. China
b School of Chemistry and Life Science , Guangdong University of Petrochemical Technology ,
Maoming , Guangdong , P. R. China
Accepted author version posted online: 27 Aug 2013.
To cite this article: Synthetic Communications (2013): Pd-Catalyzed Reduction of Aldehydes to Alcohols Using Formic Acid
as the Hydrogen Donor, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, DOI: 10.1080/00397911.2013.804575
To link to this article: http://dx.doi.org/10.1080/00397911.2013.804575
Disclaimer: This is a version of an unedited manuscript that has been accepted for publication. As a service
to authors and researchers we are providing this version of the accepted manuscript (AM). Copyediting,
typesetting, and review of the resulting proof will be undertaken on this manuscript before final publication of
the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the
content, and all legal disclaimers that apply to the journal relate to this version also.
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

ACCEPTED MANUSCRIPT
Pd-catalyzed reduction of aldehydes to alcohols using formic acid as the hydrogen
donor
Anwei Wang1, Zhiyong Yang1, Jidan Liu1, Qingwen Gui1, Xiang Chen1, Ze Tan1, Ji-
Cheng Shi2
1State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry
and Chemical Engineering, Hunan University, Changsha, P. R. China
2School of Chemistry and Life Science, Guangdong University of Petrochemical
Technology, Maoming, Guangdong, P. R. China
Correspondence to: Tel: +86 731 88822400; Fax: +86-731-88822484. E-mail:
ztanze@gmail.com, jchshi_mmc@126.com
Abstract
Facile and selective reduction of aromatic aldehydes as well as aliphatic aldehydes to
alcohols was achieved using formic acid as the hydrogen donor in the presence of a
catalytic amount of Pd(OAc)2 and Cy3P. It was found that both hydrogen atoms in the
formic acid molecule can serve as the hydride source.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications® for the following free supplemental resource(s):
Full experimental and spectral details.]
KEYWORDS: palladium-catalyzed, reduction, hydrogen transfer reduction, aldehydes,
formic acid
ACCEPTED MANUSCRIPT
1

ACCEPTED MANUSCRIPT
INTRODUCTION
The reduction of aldehydes and ketones to alcohols is a fundamental transformation in
organic synthesis[1] and the reductions can be easily carried out with metal hydrides[1a]
such as sodium boronhydride[1a,2] and lithium aluminum hydride.[1a,3] Despite the
usefulness and versatility of the metal hydrides, their sensitivity towards moisture and air,
and their incompatibility with certain functional groups have limited their use in certain
cases. Another common method of reduction is hydrogenation.[1b] Though hydrogen can
effectively reduce aldehydes and ketones to alcohols under transition metal catalysis,[4,5]
the need to use a high pressure apparatus has limited its use on small scales.[5] In addition,
this method often suffers from the lack of chemoselectivity and over-reduction of the
resultant alcohols to alkanes. As a result, scientists have developed hydrogen transfer
reduction of aldehydes and ketones using Lewis acid[6,7] and transition metal salts such as
Pd,[8] Fe,[9] Ni[10] and Ru[11,12c] complexes as catalyst. One of most famous examples of
hydrogen transfer reduction is the Meerwein-Ponndorf-Verley reduction using isopropyl
alcohol[7] as the hydrogen donor. With Pd-catalysis, hydrogen transfer reduction of
aldehydes and ketones can also be accomplished with formate salts.[8a] The use of
formates as hydride[8a,12] is particularly attractive because formate salts are not only
cheap, readily available but also compatible with a wide variety of functional groups. For
example, Sasson has shown that benzaldehyde can be reduced to benzyl alcohol with
potassium formate using Pd/C as the catalyst and a quantitative yield was obtained (eq.
1).[8a] However, they also showed that the use of formates in the reduction of aldehydes to
alcohols is not problem free. For example, it was reported that only 10% of hexanal can
be converted to hexanol (eq. 2).[8a] Inspired by a recent report that formic acid could be
ACCEPTED MANUSCRIPT
2

ACCEPTED MANUSCRIPT
used to reduce alkynes to alkenes and alkanes in the presence of Pd-catalyst (eq. 3),[13] we
envision that aliphatic aldehydes can also be reduced with formic acid if an appropriate
ligand is used in combination with suitable Pd-catalyst. The advantage of using of formic
acid in place of formates is that both hydrogen atoms of the formic acid molecule can
potentially be utilized as the hydride source. In addition, the side-product from the
reaction would be carbon dioxide, an innocuous compound. Besides the aforementioned
possible advantages, as far as we know, the use of formic acid for the reduction of
carbonyl compounds using palladium catalyst has not been tested before. Herein we
report that aromatic aldehydes as well as aliphatic aldehydes can be efficiently reduced
with formic acid in the presence of a catalytic amount of Pd(OAc)2 and Cy3P (eq. 4).
RESULTS AND DISCUSSION
We started our reactions using the reduction of benzaldehyde to benzyl alcohol as the
model reaction. When benzaldehyde was treated with 5 equiv of formic acid in the
presence of 5 mol% of Pd(OAc)2 and 7.5 mol% of PPh3 in dioxane (1 mL/mmol) at 90 oC
for 18 h, much to our disappointment, no benzyl alcohol was formed (table 1, entry 1).
When we substituted PPh3 with Cy3P, we did not observe the formation of benzyl alcohol
either (table 1, entry 2). However, when we added 4 equiv of H2O to the reaction mixture,
we were delighted to see that our desired product, benzyl alcohol was indeed formed in
32% yield (table 1, entry 3). It seems that the presence of water is necessary for the
hydrogen transfer process to take place. Subsequent tests showed that better yield (81%)
could be obtained if the ratio of H2O against HCOOH was changed from 4/5 to 4/10
(table 1, entry 4). If we increased the amount of formic acid further, the yield actually
ACCEPTED MANUSCRIPT
3

ACCEPTED MANUSCRIPT
dropped (table 1, entry 5 and 6). Changing the Pd-source from Pd(OAc)2 to PdCl2,
Pd(PPh3)4, or Pd(dba)2 all resulted in miserable yields (table 1, entries 7-9). When the
solvent dioxane was replaced with DMF, THF or DMSO, the reaction gave much lower
yields (47%, 23%, 40%, respectively, table 1, entries 10-12). Control experiment also
showed that Pd catalyst was necessary for the reaction to proceed (table 1, entry 13).
Interestingly, running the reduction under air gave a lot of over-reduction product, i.e.,
toluene, suggesting the actual catalytic species might be different in the presence of O2.
On the basis of these results, we decided to set reacting the aldehyde with 10 equiv of
formic acid and 4 equiv of H2O in the presence of Pd(OAc)2 (0.05 mmol)/PCy3 (0.075
mmol) in dioxane (1.0 mL/mmol) at 90 oC as our standard conditions.
With the standard protocol in hand, we next set out to examine the scope and limitation
of this reaction and the results are shown in Table 2. We found that the reaction worked
very well for a variety of aldehydes, affording the desired alcohols in yields ranging from
30-95%. For aromatic aldehydes, substituents such as methyl, methoxy, ethoxy, hydroxy
group are well tolerated on the benzene ring (table 2, entries 1-5). However, the reduction
of 4-dimethylaminobenzaldehyde afforded the desired alcohol only in 30% yield (table 2,
entry 6). 4-Biphenylcarboxaldehyde and 1-naphthaldehyde could participate in the
reaction as well，furnishing the desired products in 82% and 84% yields, respectively
(Table 2, entries 7 and 8). 2-Pyridine aldehyde, a heteroaryl aldehyde, was also a viable
substrate, affording 2-pyridinemethanol in excellent yield (85%, table 2, entry 9). This
indicated that the protonation of the pyridine ring did not affect the reduction process. We
were disappointed to discover that the reduction of benzaldehydes bearing halogen
ACCEPTED MANUSCRIPT
4

ACCEPTED MANUSCRIPT
substituents such as F-, Cl- and Br- group did not produce the desired alcohols. Analysis
of the reaction mixture showed that most of the starting aldehyde remained. Perhaps the
catalytic cycle was shut down because the Pd-catalyst underwent oxidative insertion into
the C-halogen bond and was trapped (table 2, entry 10). Similar result was obtained with
the reduction of 4-nitrobenzaldehyde (not shown in table 2). In addition, acetophenone,
an aromatic ketone, also failed to react (table 2, entry 11). Yet surprisingly, the reduction
of benzophenone was able to provide the desired alcohol in 55% yield (table 2, entry 12).
We were also able to selectively reduce an aldehyde in the presence of a ketone
functionality when both functional groups are present in the same molecule. For example,
under the standard conditions, the reduction of 4-acetylbenzaldehyde produced the
desired 4-acetylbenzylalcohol in 85% yield (Table 2, entry 13). Contrary to the
Pd/C/fomate system, we successfully reduced aliphatic aldehydes to the corresponding
alcohols in good yields and excellent conversions were achieved. For example, the
reduction of 3-phenylpropionaldehyde gave the desired product in 90% yield (table 2,
entry 14). Other simple aliphatic aldehydes worked well as well (table 2, entries 15-20).
The reduction of aldehydes substituted at the α- or β-position of the carbonyl group with
Methyl or ethyl group proceeded without any incident (table 2, entries 15, 19 and 20). In
order to compare the reduction rate of aliphatic aldehydes vs aromatic aldehydes, we
carried out the reduction of a 1/1 mixture of benzaldehyde and 1-nonanal under the
standard condition. At different time intervals, an aliquot of the reaction mixture was
taken out and analyzed with a GC instrument. The results showed that the reduction of
the 1-nonanal was much faster than the reduction of benzaldehyde, only requiring 6 h for
the reaction to reach completion. This might be due to the fact that aromatic aldehydes
ACCEPTED MANUSCRIPT
5

ACCEPTED MANUSCRIPT
are more stable than the aliphatic aldehydes.
In order to see whether the two hydrogen atoms of the formic acid molecule are fully
utilized as hydride source or not, we carried out the reduction of 1-naphthaldehyde using
regular formic acid in the presence of excessive D2O. Analysis of the proton NMR of the
isolated alcohol indicated that 1/4 of the benzylic hydrogens were deuterated. This result
suggested that both hydrogen atoms in the formic acid molecule can serve as hydrogen
donors.
In summary, we have shown that formic acid can be used to reduce aldehydes to alcohols
under palladium catalysis. The use of Cy3P as the ligand and adding a small amount of
water to the reaction mixture were found to be critical to the success of the reaction. In
addition to aromatic aldehydes, aliphatic aldehydes can be also easily reduced whereas
ketones generally are not viable substrates. Studies also indicated that both hydrogen
atoms of the formic acid molecules can act as the hydride source. Efforts are currently
underway to elucidate the reaction mechanism and the results will be reported in due
course.
EXPERIMENTAL
All solvents and reagents were purchased from the suppliers and used without further
purification. 1H NMR and 13C NMR were recorded in CDCl3 at room temperature on the
Varian INOVA-400 spectrometer (400 MHz 1H) and Bruker spectrometer (400 MHz
1H). The chemical-shifts scale is based on internal TMS. All reactions were carried out
under dry nitrogen atmosphere.
ACCEPTED MANUSCRIPT
6

ACCEPTED MANUSCRIPT
Typical Procedure
An oven-dried pressure tube containing a Teflon-coated stirring bar was charged with
Pd(OAc)2 (11.2 mg, 5 mol%), PCy3 (21 mg, 7.5 mol%) and aldehyde(1 mmol). The tube
was sealed, evacuated and backfilled with N2. 1 mL of dioxane was subsequently
injected. After the mixture was stirred at room temperature for 15 min, H2O (180 mg, 10
equiv) and HCO2H (184 mg, 4 equiv) were injected and the reaction was heated to 90 oC
for 18 h. After the reaction was completed, the solvent was removed under vacuo. The
residues were purified by flash column chromatography on silica gel to afford 87 mg of
benzyl alcohol[9b] in 81 % yield. Colorless liquid; yield: 0.087 g (81%). 1H NMR (CDCl3,
400 MHz): δ = 7.20-7.27 (m, 5 H), 4.56 (s, 2 H), 2.15 (s, 1 H). 13C NMR (CDCl3, 100
MHz): δ = 140.79, 128.47 (2 C), 127.55, 126.93 (2 C), 65.16.
ACKNOWLEGMENTS
Z.T. would like to thank the National Science Foundation of China (No. 21072051), the
NCET program (NCET-09-0334), and the Fundamental Research Funds for the Central
Universities, Hunan University for financial support. J.-C.S. would like to thank the
National Science Foundation of China (No. 20971023) for financial support.
Supporting Information for this article can be found via the “Supplementary Content”
section of this article’s webpage. Included are experimental procedures and 1H NMR and
13C NMR spectra data and references for all the products.
REFERENCES
ACCEPTED MANUSCRIPT
7

ACCEPTED MANUSCRIPT
1 (a) Hudlicky, M. Reductions in Organic Chemistry, 2nd ed.; ACS: Washington, DC,
1996; (b) Rylander, P. N. Hydrogenation Methods; Academic: New York, 1985; (c)
Zassinovich, G.; Mestroni, G. Asymmetric hydrogen transfer reactions promoted by
homogeneous transition metal catalysts. Chem. Rev. 1992, 92, 1051-1069; (d) Moore, J.
C.; Pollard, D. J.; Kosjek, B.; Devine, P. N. Advances in the enzymatic reduction of
ketones. Acc. Chem. Res. 2007, 40, 1412-1419; (e) González, S. D.; Marion, N.; Nolan,
S. P. N-heterocyclic carbenes in late transition metal catalysis. Chem. Rev. 2009, 109,
3612-3676; (f) Alonso, F.; Riente, P.; Yus, M. Nickel nanoparticles in hydrogen transfer
reactions. Acc. Chem. Res. 2011, 44, 379-391; (g) Shang, G.; Li, W.; Zhang, X. M.
Transition Metal-Catalyzed Homogeneous Asymmetric Hydrogenation In Handbook of
Catalytic Asymmetric Synthesis, (Ed.: Iwao Ojima), John Wiley & Sons, Inc. Press,
Canada, 2010.
2 (a) Luche, J, L. Lanthanides in organic chemistry. 1. Selective 1,2 reductions of
conjugated ketones. J. Am. Chem. Soc. 1978, 100, 2226-2227; (b) Luche, J, L.;
Rodriguez-Hahn, L.; Crabbé, P. Reduction of natural enones in the presence of cerium
trichloride. J. Chem. Soc., Chem. Commun. 1978, 14, 601-602; (c) Gemai, A. L; Luche, J.
L. Lanthanoids in organic synthesis. 6. Reduction of α-enones by sodium borohydride in
the presence of lanthanoid chlorides: synthetic and mechanistic aspects. J. Am. Chem.
Soc. 1981, 103, 5454-5459.
3 (a) Felkin, E.; sarda, P. Reductive cleavage of allylic alcohols ethers, or acetates to
olefins. Org. Synth. 1988, 6, 769-769. (b) Barnier, J. P.; Champion, J.; Conia, J. M.
Cyclopropanecarboxaldehyde. Org. Synth. 1990, 7, 129-129.
ACCEPTED MANUSCRIPT
8

ACCEPTED MANUSCRIPT
4 (a) Hattori, K.; Sajiki, H.; Hirota, K. Chemoselective control of hydrogenation among
aromatic carbonyl and benzyl alcohol derivatives using Pd/C(en) catalyst. Tetrahedron
2001, 57, 4817-4824; (b) Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. Preferential
hydrogenation of aldehydes and ketones. J. Am. Chem. Soc. 1995, 117, 10417-10418; (c)
Ohkuma, T.; Koizumi, M.; Ikehira, H.; Yokozama, T.; Noyori, R. Selective
hydrogenation of benzophenones to benzhydrols. Asymmetric synthesis of
unsymmetrical diarylmethanols. Org. Lett. 2000, 2, 659-662; (d) Ohkuma, T.; Hattori, T.;
Ooka, H.; Inoue, T.; Noyori, R. BINAP/1,4-Diamine-Ruthenium(II) complexes for
efficient asymmetric hydrogenation of 1-Tetralones and analogues. Org. Lett. 2004, 6,
2681-2683; (e) Ohkuma, T.; Tsutsumi, K.; Utsumi, N.; Arai, N.; Noyori, R.; Murata, K.
Asymmetric hydrogenation of r-chloro aromatic ketones catalyzed by 6-Arene/TsDPEN-
Ruthenium(II) complexes. Org. Lett. 2007, 9, 255-257.
5 (a) Sandoval, C. A; Ohkuma, T. K.; Noyori, R. Mechanism of asymmetric
hydrogenation of ketones catalyzed by BINAP/1,2-Diamine-Ruthenium(II) complexes. J.
Am. Chem. Soc. 2003, 125, 13490-13503. (b) Sandoval, C. A.; Noyori, R. The
hydrogenation/transfer hydrogenation network in asymmetric reduction of ketones
catalyzed by [RuCl2(binap)(pica)] complexes. Chem. Asian J. 2008, 3, 1801-1810; (c)
Lin, Y. H.; Zhou, Y. G.; Shi, Q. X.; Ding, K. L.; Noyori, R. An efficient
diphosphine/hybrid-amine combination for Ruthenium(II)-catalyzed asymmetric
hydrogenation of aryl ketones. Adv. Synth. Catal. 2011, 353, 495-500.
6 (a) Meerwein, H.; Schmidt, R. New method for the reduction of aldehydes and
ketones. Justus Liebigs Ann. Chem. 1925, 444, 221-238. (b) Ponndorf, W. The reversible
exchange of oxygen between aldehydes or ketones on the one hand and primary or
ACCEPTED MANUSCRIPT
9

ACCEPTED MANUSCRIPT
secondary alcohols on the other hand. Angew. Chem. 1926, 39, 138-146. (c) Verley, M.
The exchange of functional groups between two molecules. The passage of ketones to
alcohols and the reverse. Bull. Soc. Chim. Fr. 1925, 37, 871-874.
7 (a) Ooi, T.; Miura, T.; Maruoka, K. Highly efficient, catalytic Meerwein-Ponndorf-
Verley reduction with a novel bidentate aluminum catalyst. Angew. Chem. Int. Ed. 1998,
37, 2347-2349; (b) Ooi, T.; Ichikaw, H.; Maruoka, K. Practical approach to the
Meerwein-Ponndorf-Verley reduction of carbonyl substrates with new aluminum
catalysts. Angew. Chem. Int. Ed. 2001, 40, 3610-3612; (c) Ooi, T.; Miura, T.; Itagaki, Y.;
Ichikawa, H.; Maruoka, K. Bronsted acid catalysts other than phosphoric acids. Synthesis
2002, 2, 279-291; (d) Camphbell, J. E.; Zhou, H. Y.; Nguyen, S. T. Enantioselective
synthesis of kedarcidin chromophore aglycon in differentially protected form. Angew.
Chem. Int. Ed. 2002, 41, 1062-1064; (e) Yin, J, J.; Huffman, M. A.; Conrad, K. M.;
Armstrong, J. D. Highly diastereoselective catalytic Meerwein-Ponndorf-Verley
reductions. J. Org. Chem. 2006, 71, 840-843.
8 For examples of Pd-catalyzed hydrogen transfer reduction of aldehydes and ketones,
see: (a) Baidossi, M.; Joshi, A.V.; Mukhopadhyay, S.; Sasson, Y. Pd/C-catalyzed transfer-
hydrogenation of benzaldehydes to benzyl alcohols using potassium formate as the
selective hydrogen donor. Synth. Commun. 2004, 34, 643-650; (b) Cano, R.; Yus, M.;
Ramón, D. J. Impregnated palladium on magnetite as catalyst for multicomponent
reductive amination reactions and other related reducing processes. Tetrahedron 2011, 67,
8079-8085.
9 For examples of Fe-catalyzed hydrogen transfer reduction of aldehydes and ketones,
see : (a) Nishiyama, S.; Furuta, A. An iron-catalysed hydrosilylation of ketones. Chem.
ACCEPTED MANUSCRIPT
10

ACCEPTED MANUSCRIPT
Commun. 2007, 7, 760-762; (b) Shaikh, N. S.; Junge, K.; Beller, M. convenient and
general Iron-catalyzed hydrosilylation of aldehydes. Org. Lett. 2007, 9, 5429-5432; (c)
Jiang, F.; Bézier, D.; Sortais, J. B.; Darcel, C. N-heterocyclic carbene piano-stool Iron
complexes as efficient catalysts for hydrosilylation of carbonyl derivatives. Adv. Synth.
Catal. 2011, 353, 239-244. (d) Misal Castro, L. C.; Bézier, D.; Sortais, J. B.; Darcel, C.
Iron dihydride complex as the pre-catalyst for efficient hydrosilylation of aldehydes and
ketones under visible light activation. Adv. Synth. Catal. 2011, 353, 1279-1284; (e)
Zheng, J. X.; Misal Castro, L. C.; Darcel, C.; Sortais, J. B. Iron piano-stool phosphine
complexes for catalytic hydrosilylation reaction. Inorg. Chimi. Acta. 2012, 380, 301-307;
(f) Bézier, D.; Jiang, F.; Sortais, J. B.; Darcel, C. Cyclopentadienyl–NHC Iron complexes
for solvent-free catalytic hydrosilylation of aldehydes and ketones. Eur. J. Inorg. Chem.
2012, 1333-1337.
10 For a example of Ni-catalyzed hydrogen transfer reduction of aldehydes and ketones,
see: Bheeter, L. P.; Henrion, M.; Brelot, L.; Darcel, C.; Chetcuti, M. J.; Sortais, J. B.;
Ritleng, V. Hydrosilylation of aldehydes and ketones catalyzed by an N-heterocyclic
carbene-Nickel hydride complex under mild Conditions. Adv. Synth. Catal. 2012, 354,
2619-2624.
11 For examples of Ru-catalyzed hydrogen transfer reduction of aldehydes and ketones,
see: (a) Haack, K. J.; Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R. The catalyst
precursor, catalyst and intermediate in the RuII-promoted asymmetric hydrogen transfer
between alcohols and ketones. Angew.Chem., Int. Ed. 1997, 36, 285-288. (b) Yamakawa,
M.; Ito, H.; Noyori, R. The metal-ligand bifunctional catalysis: A theoretical study on the
Ruthenium(II)-catalyzed hydrogen transfer between alcohols and carbonyl compounds. J.
ACCEPTED MANUSCRIPT
11

ACCEPTED MANUSCRIPT
Am. Chem. Soc. 2000, 122, 1466-1478; (c) Munihiko, M.; Okano, K.; Miyagi, M.; Iwane,
H.; Noyori, R.; Ikariya, T. A practical stereoselective synthesis of chiral hydrobenzoins
via asymmetric transfer hydrogenation of benzils. Org. Lett. 1999, 1, 1119-1121; (d)
Yamada, I.; Noyori, R. Asymmetric transfer hydrogenation of benzaldehydes. Org. Lett.
2000, 2, 3425-3427.
12 (a) Wiener, H.; Zaidman, B.; Sasson, Y. Storage of energy by solutions of alkali
formate salts. Solar Energy 1989, 43, 291-296; (b) Wiener, H.; Zaidman, B.; Sasson, Y.
Application of aqueous formate salts as hydrogen donors in reduction processes: A
techno-economic comparison with pressurized and electrically generated hydrogen gas.
Int. J. Hydrogen Energy 1989, 14, 365-370. (c) Noyori, R.; Hashiguchi, S. Asymmetric
transfer hydrogenation catalyzed by chiral ruthenium complexes. Acc. Chem. Res. 1997,
30, 97-102.
13 Shen, R. S.; Chen, T. Q.; Zhao, Y. L.; Qiu, R. H.; Zhou, Y. B.; Yin, S. F.; Wang, X.
B.; Goto, M.; Han, L. B. Facile regio- and stereoselective hydrometalation of alkynes
with a combination of carboxylic acids and group 10 transition metal complexes:
Selective hydrogenation of alkynes with formic acid. J. Am. Chem. Soc. 2011, 133,
17037-17044.
ACCEPTED MANUSCRIPT
12

ACCEPTED MANUSCRIPT
Table 1. Reaction condition optimizationa
Entry
Pd-
Ligand Solvent
H2O
HCOOH Yield
(equiv)
(%)b
catalyst
(equiv)
1
Pd(OAc)2 PPh3
Pd(OAc)2 PCy3
Pd(OAc)2 PCy3
Pd(OAc)2 PCy3
Pd(OAc)2 PCy3
Pd(OAc)2 PCy3
dioxane 0
5
5
5
0
2
dioxane 0
dioxane 4
dioxane 4
dioxane 4
dioxane 4
dioxane 4
dioxane 4
dioxane 4
0
3
32
81
34
13
< 5
< 5
18
47
23
40
0
4
10
15
20
10
10
10
10
10
10
10
5
6
7
PdCl2
PCy3
8
Pd(PPh3)4 PCy3
Pd(dba)2 PCy3
Pd(OAc)2 PCy3
Pd(OAc)2 PCy3
Pd(OAc)2 PCy3
9
10
11
12
13
DMF
4
4
4
4
THF
DMSO
-
PCy3
DMSO
a Reaction conditions: under N2, benzaldehyde (1.0 mmol), Pd-catalyst (0.05 mmol),
Ligand (0.075 mmol) and solvent (1.0 mL) were stirred at room temperature for 15 min,
then H2O (4 equiv) and HCO2H (10 equiv) were injected and the reaction was heated at
90 oC for 18 h.
b Yields are determined by GC.
ACCEPTED MANUSCRIPT
13

ACCEPTED MANUSCRIPT
Table 2 Reduction of aldehydes to alcohols a
Entr Aldehyde
y
Product
Yield
(%)b
OH
1
86
62
78
65
95
30
82
84
CHO
2
3
4
5
6
7
8
OH
CHO
OH
MeO
CHO
OMe
MeO
OMe
OH
CHO
OEt
OEt
OH
CHO
MeO
N
OH
MeO
OH
OH
CHO
N
OH
CHO
OH
CHO
9
85
OH
N
N
CHO
CHO
OH
10
11
trace
trace
R1=F,Cl,Br
R1
R1
OH
O
ACCEPTED MANUSCRIPT
14

ACCEPTED MANUSCRIPT
O
OH
12
13
14
15
16
55
85
90
71
OH
CHO
O
O
CHO
OH
CHO
OH
CH3(CH2)6CH2CH CH3(CH2)7CH2OH 82
O
17
18
19
CH3(CH2)7CH2CH CH3(CH2)8CH2OH 82
O
CH3(CH2)8CH2CH CH3(CH2)9CH2OH 77
O
74
O
OH
OH
20
73
O
a
Reaction conditions: under N2, aldehyde (1.0 mmol), Pd(OAc)2 (0.05 mmol), PCy3
(0.075 mmol) and dioxane (1.0 mL) were stirred at room temperature for 15 min, then
H2O (4 equiv) and HCO2H (10 equiv) were injected and the reaction was heated at 90 oC
(18 h for aromatic aldehydes, 6 h for aliphatic aldehydes).
b Isolated yields.
ACCEPTED MANUSCRIPT
15

ACCEPTED MANUSCRIPT
Scheme 1. eq.1-4
ACCEPTED MANUSCRIPT
16

ACCEPTED MANUSCRIPT
Scheme 2. deuteration
ACCEPTED MANUSCRIPT
17