Partial hydrogenation of alkynes to cis-olefins by using a novel Pd 0-polyethyleneimine catalyst

Article abstract of DOI:10.1002/chem.200800535

The creation and application of a new Pd⁰-polyethyleneimine complex catalyst (Pd⁰-PEI) was investigated. The 55 Pd ⁰-PEI catalyst was prepared by introduction of Pd(OAc)₂ directly in the MeOH solution of deaerated PEI under Ar atmosphere. Reactions were carried out using 10 weight % versus substrate of 5% Pd⁰-PEI in 2mL solvent under H₂ atmosphere at room temperature. The generality of the process was shown by disubstituting alkynes. Even for the substrate bearing a conjugated ketone on the alkyne, the serious over-reduction was not observed while significant cistrans isomerization of methyl styryl ketone accompanied the partial hydrogenation on the basis of keto-enol tautomerism. Pd⁰-PEI catalyst is also applicable to the partial hydrogenation of monosubstituted alkynes to monosubstituted olefins.

Full text of DOI:10.1002/chem.200800535

COMMUNICATION
DOI: 10.1002/chem.200800535
0
Partial Hydrogenation of Alkynesto cis-Olefinsby Using a Novel Pd –
Polyethyleneimine Catalyst
Hironao Sajiki,*[a] Shigeki Mori,[a] Tomoyuki Ohkubo,[a] Takashi Ikawa,[a, b]
Akira Kume,[a] Tomohiro Maegawa,[a] and Yasunari Monguchi[a]
The selective partial hydrogenation of alkynes to cis-al-
kenes represents an important class of chemical transforma-
tions that have found extensive use in the construction of an
enormous variety of, for example, bioactive molecules, natu-
ral products, industrial materials.[1] The important transfor-
mation has mainly been accomplished under ordinary hy-
drogen pressure and at room temperature using heterogene-
ous Pd catalysts such as Lindlar catalyst (Pd/CaCO3–Pb-
(terminal) alkynes as substrates. Therefore, the Lindlarꢀs
method is only applicable to the selective chemical transfor-
mation of disubstituted alkynes to cis-alkenes.[10] Thus, there
is a need for the development of novel selective catalyst
that can provide high yields and selectivity without any nu-
cleophilic additives and the chemical pretreatment by an en-
vironmentally harmful materials. Recently, Alonso and Yus
et al. reported an efficient method for the partial hydrogena-
tion of both internal and terminal alkynes using Ni nanopar-
ticles although the adjustment of the amount of the in situ
generated molecular hydrogen source (Li powder and
EtOH or iPrOH) is essential.[11] We now disclose a develop-
ment of very practical catalyst and an efficient partial hydro-
genation controlled by the catalyst activity that overcomes
these serious and longstanding problems.
Recently, we have reported that a Pd/C catalyst formed
an isolable complex with ethylenediamine (en) employed as
the catalytic poison via one-on-one interaction between Pd
metal and en, and the complex catalyst [Pd/C(en)] chemose-
lectively hydrogenated a variety of reducible functionalities
in the presence of an O-benzyl, O-TES or N-Cbz protective
group, benzyl alcohol or epoxide.[12] Besides, we also devel-
oped silk fibroin (Fib)-supported Pd0 catalyst for the chemo-
selective hydrogenation of alkynes, alkenes and azides in
the presence of other reducible functionalities.[13] During our
effort to create a new Pd catalyst for hydrogenation possess-
ing different chemoselectivity, we found that polyethylene-
imine (PEI, branched polymer, average molecular weight
approximately 25000) supported Pd0 catalyst selectively cat-
alyzed hydrogenation of only alkynes including both mono-
and disubstituted alkynes, without the reduction of other re-
ducible functionalities.[14]
ACHTREUNG
(OAc)2 in conjunction with quinoline)[2], Pdc[3] and Ni cata-
lysts such as low-active Raney Ni[4], P-1 Ni[5], P-2 Ni[6], and
Nic[7], and Au nanoparticles[8] and homogeneous Rh and Cr
complexes[9] as a catalyst. In these cases except Lindlar cata-
lyst, the narrow substrate-applicability, concomitant use with
a basic additive, low cis/trans selectivity, pyrophoric property
and/or operational complexity of the catalysts are undesira-
ble as a general synthetic methodology and these are why
such catalysts have never been a common selective catalyst
for the partial hydrogenation of an alkyne to a cis-alkene.
On the other hand, the Lindlar catalyst is widely applicable
and used as such a selective catalyst although the pretreat-
ment using environmentally harmful PbACTHRE(UNG OAc)2 and the si-
multaneous use with quinoline is necessary to achieve the
chemoselective and geometrically selective partial hydroge-
nation. Furthermore, the smooth over-reduction to the cor-
responding alkanes efficiently proceeded under the Lindlarꢀs
hydrogenation conditions by the use of monosubstituted
[a] Prof. Dr. H. Sajiki, S. Mori, T. Ohkubo, Dr. T. Ikawa, A. Kume,
Dr. T. Maegawa, Dr. Y. Monguchi
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University
5-6-1 Mitahora-higashi, Gifu 502-8585 (Japan)
Fax : (+81)58-237-5979
E-mail: sajiki@gifu-pu.ac.jp
This paper describes the creation and application of a
novel Pd0–polyethyleneimine complex catalyst (Pd0–PEI).
The 5 % Pd0–PEI catalyst was prepared by introduction of
[b] Dr. T. Ikawa
Current address: Laboratory of Synthetic Organic Chemistry
Department of Pharmaceutics, School of Pharmaceutical Sciences
University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526
(Japan)
PdACHTRE(UNG OAc)2 directly in the MeOH solution of deaerated PEI
under Ar atmosphere (Scheme 1). The resulting rust-colored
solution was stirred under H2 atmosphere at room tempera-
ture for 24 h and the solution changed gradually to black, in-
Supporting information for this article is available on the WWW
under http://www.chemistry.org or from the author.
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Table 1. Solvent effect of partial hydrogenation of diphenyl acetylene
using Pd0–PEI catalyst.
Entry
Solvent
1a/2a/3a/4a[a]
1
2
3
4
cyclohexane (2 mL)
AcOEt (2 mL)
dioxane (2 mL)
100:0:0:0
100:0:0:0
100:0:0:0
0:68:2:30
0:72:4:24
0:82:2:16
0:95:1:4
MeOH (2 mL)
5[b]
6[c]
7
MeOH + dioxane
MeOH + AcOEt
MeOH + AcOEt (1:1)
MeOH + dioxane (1:1)
MeOH + dioxane (1:1)
8
0:97:1:2
0:95:1:4
9[d]
1
[a] Determined by H NMR spectroscopy. [b] MeOH (2 mL) and dioxane
(0.5 mL) used as a solvent. [c] MeOH (2 mL) and AcOEt (0.5 mL) used
as a solvent. [d] The reaction was performed for 12 h.
Table 2. Pd0–PEI-catalyzed partial hydrogenation of disubstituted al-
kynes.
Scheme 1. Preparation of 5% Pd0–PEI catalyst.
dicating the formation of the zero-valent Pd species. After
concentration in vacuo, the obtained black gummy 5% Pd0–
PEI is stable for more than three years in a capped vial and
is nonpyrophoric. The Pd deposition (5 weight%) into the
Entry
1[b]
Substrate
1/2/3/4[a]
0:96:4:0
PEI was based on the incipient ratio of PdCATHRE(UGN OAc)2 and PEI.
With 5% Pd0–PEI in hand, its usefulness as catalyst by fo-
cusing on the chemoselective partial hydrogenation of al-
kynes was investigated. Reactions were typically carried out
using 10 weight% versus substrate of 5% Pd0–PEI in 2mL
solvent under H2 atmosphere at room temperature. Al-
though these preliminary studies were frustrated by no cata-
lyst activity of 5% Pd0–PEI in aprotic organic solvents
(Table 1, entries 1–3), using MeOH as a solvent led to a dra-
matic increase in the hydrogenation catalyst activity toward
diphenylacetylene (1a) giving cis-stilbene (2a) as a major
product (68%) together with significant amount of diphe-
nylethane (4a) by over-reduction. Mixing the more coordi-
nating solvent such as dioxane and AcOEt led to a signifi-
cant decrease in over-reduction (Table 1, entries 5–9). In
MeOH/dioxane 1:1, the desired cis-stilbene (2a) was ob-
tained in 97% selectivity and the ratio of products is not
time-dependent (compare Table 1, entries 8 and 9).
To show the generality of the process, the use of various
disubstituted alkynes was investigated (Table 2). The partial
hydrogenation of aromatic disubstituted alkynes proceeded
selectively at room temperature (Table 2, entries 1 and 2), as
well as with aliphatic disubstituted alkynes (Table 2, en-
tries 4–6). Even for the substrate bearing a conjugated
ketone on the alkyne, the serious over-reduction was not ob-
served while significant cis/trans isomerization of methyl
styryl ketone accompanied the partial hydrogenation on the
basis of keto–enol tautomerism (Table 2, entry 3).
2
3
0:94:0:6
0:36:58:6
4
0:100:0:0
5
6
0:100:0:0
0:100:0:0
[a] Determined by 1H NMR spectroscopy. [b] K2CO3 (1 equiv) was used
as an additive.
pare Table 3, entries 11 and 12), these results were well
worth noting given the high propensity of both aromatic
(Table 3, entries 1 and 2) and aliphatic (Table 3, entries 3–
11) monosubstituted alkynes to undergo partial hydrogena-
tion in good to excellent selectivities. Furthermore, other re-
ducible functionalities such as N-Cbz protective group
(Table 3, entry 3), benzyl ester (Table 3, entry 5), benzyl
ether (Table 3, entry 6) and TBS ether (Table 3, entry 10)
under the hydrogenation conditions could universally be tol-
erated.[15]
In summary, we have developed a new and selective cata-
lyst, Pd0–PEI, for the partial hydrogenation of disubstituted
alkynes to cis-olefins. It is noteworthy that Pd0–PEI catalyst
is also applicable to the partial hydrogenation of monosub-
stituted (terminal) alkynes to monosubstituted olefins al-
though such controlled reactions are usually impossible by
the use of Lindlar catalyst.
Amazingly, monosubstituted (terminal) alkynes (5) were
found to be viable substrates (Table 3). Although the solvent
tuning (addition or use of the more coordinating solvent di-
oxane) to obtain better selectivity is necessary (e.g., com-
5110
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Chem. Eur. J. 2008, 14, 5109 – 5111

Partial Hydrogenation of Alkynes
COMMUNICATION
Table 3. Pd0–PEI-Catalyzed partial hydrogenation of monosubstituted al-
kynes.
Keywords: green chemistry · hydrogenation · palladium ·
partial hydrogenation · polyethyleneimine
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Entry Substrate
1
Solvent
5/6/7[a]
dioxane (2 mL)
11:85:4
MeOH (0.25 mL) + dioxane
(1 mL)
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3
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0:93:7
0:83:17
0:98:2
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dioxane (2 mL)
MeOH (1 mL) + AcOEt
(1 mL)
MeOH (0.25 mL) + dioxane
(1 mL)
5
6
0:100:0
0:96:4
MeOH (0.25 mL) + dioxane
(1 mL)
MeOH (2 mL) + dioxane
(0.5 mL)
7[b]
0:100:0
[5] Y. Nitta, T. Imanaka, S. Teranishi, Bull. Chem. Soc. Jpn. 1981, 54,
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76, 5719; c) C. A. Brown, V. K. Ahuja, J. Chem. Soc. Chem.
Commun. 1973, 553.
MeOH (0.5 mL) + dioxane
(2 mL)
8
9
0:88:12
0:83:17
[7] a) J. J. Brunet, P. Gallois, P. Caubere, J. Org. Chem. 1980, 45, 1937;
b) P. Gallois, J. J. Brunet, P. Caubere, J. Org. Chem. 1980, 45, 1946.
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[11] F. Alons, I. Osante, M. Yus, Adv. Synth. Catal. 2006, 348, 305.
[12] a) H. Sajiki, K. Hattori, K. Hirota, J. Org. Chem. 1998, 63, 7990–
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Sajiki, K. Hirota, J. Org. Synth. Chem. Jpn. 2001, 59, 109.
MeOH (1.5 equiv) + diox-
ane (2 mL)
10
11
12
MeOH (1 mL)
dioxane (2 mL)
0:100:0
0:88:12
0:0:100
MeOH (1 mL) + AcOEt
(1 mL)
[a] Determined by 1H NMR spectroscopy. [b] K2CO3 (1 equiv) was used
as an additive.
[13] a) H. Sajiki, T. Ikawa, K. Hirota, Tetrahedron Lett. 2003, 44, 171;
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Pure Chemical Industries, Ltd.
Experimental Section
Preparation of 5% Pd0–PEI catalyst: MeOH (100 mL, HPLC grade) was
added to PEI (2.11 g, average Mw ~25000 by LS, average Mn ~10000 by
GPC, high molecular weight, water free, purchased from Aldrich) deaer-
ated for 48 h in vacuo. After PEI homogeneously solved, resulting solu-
tion was quickly poured into round-bottom flask measured PdACHTRE(UNG OAc)2
(225 mg, 1.00 mmol) under argon atmosphere. Next, the round-bottom
flask was replaced with H2 by three vacuum/H2 (balloon) cycles after Pd-
[14] Royer et al. reported the Pd0–PEI “ghost” catalyst prepared by cov-
ering alumina beads with PEI, removing the alumina core by acid or
base-treatment, and encapsulating Pd metal into the resulting PEI
“ghost”. In the preparation of Pd0–PEI ghost catalyst, PEI was used
as a mold for Pd and the catalyst activity was very high and not ap-
plicable to the partial hydrogenation; a) W. E. Meyers, G. P. Royer,
J. Am. Chem. Soc. 1977, 99, 6141; b) G. P. Coleman, G. P. Royer, J.
Org. Chem. 1980, 45, 2268.
ACHTREUNG(OAc)2 completely solved in MeOH/PEI solution. The resulting solution
was stirred for 24 h at room temperature and concentrated in vacuo.
General procedure for the partial hydrogenation of alkynesto olefins
using Pd0–PEI catalyst: In a test tube were placed substrate (1.00 mmol),
5% Pd0–PEI (10 wt% of substrate), a stir bar, and solvent according to
Table 3. The air inside the test tube was replaced with H2 by three
vacuum/H2 (balloon) cycles, and the mixture was vigorously stirred at
ambient temperature. After 24 h, the reaction mixture was partitioned
between Et2O (10 mL) and H2O (10 mL) and the organic layer was
washed with brine (10 mL), dried (MgSO4), and filtered, and concentrat-
[15] In this paper, the authors reported the smooth cleavage of N-Cbz
protecting group during the hydrogenation of a olefin function using
Lindlar catalyst without quinoline. see; A. K. Ghosh, K. Krishnan,
Tetrahedron Lett. 1998, 39, 947.
[16] S. Nishimura, Handbook of Heterogeneous Catalytic Hydrogenation
for Organic Synthesis, Wiley-Interscience, New York, 2001.
Received: March 24, 2008
Published online: April 23, 2008
1
ed in vacuo. The product ratio was determined by H NMR analysis.
Chem. Eur. J. 2008, 14, 5109 – 5111
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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