Development of a practical and scalable preparation using sonication of Pd/fibroin catalyst for chemoselective hydrogenation

Article abstract of DOI:10.1080/00397910701577612

A practical and efficient preparation method of palladium-fibroin (Pd/Fib), silk-fibroin-supported Pd(0) by means of sonication, has been developed. The Pd/Fib catalyst could be prepared within 12 h at room temperature starting from commercial silk-fibroin and Pd(OAc)2 in MeOH, whereas our previous preparation method required at least 4 days. The present improved process is applicable to a large-scale preparation of Pd/Fib. The Pd/Fib prepared by the present method also catalyzed chemoselective hydrogenation of acetylenes, olefins, and azides in the presence of aromatic ketones, aldehydes, and halides; N-Cbz protective groups; and benzyl esters, which are readily hydrogenated under the Pd/C- or Pd/C(en)-catalyzed hydrogenation conditions. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701577612

This article was downloaded by: [University of Miami]
On: 24 November 2014, At: 19:57
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
Development of a Practical and Scalable
Preparation using Sonication of Pd/Fibroin
Catalyst for Chemoselective Hydrogenation
Yoshiaki Kitamura a , Asami Tanaka a , Mutsumi Sato b , Keiji Oono b , Takashi
Ikawa a , Tomohiro Maegawa a , Yasunari Monguchi a & Hironao Sajiki a
a Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University ,
Mitahora‐higashi, Gifu, Japan
b Reagent Research Laboratories, Wako Pure Chemical Industries, Ltd. ,
Matoba, Kawagoe, Saitama, Japan
Published online: 14 Dec 2007.
To cite this article: Yoshiaki Kitamura , Asami Tanaka , Mutsumi Sato , Keiji Oono , Takashi Ikawa , Tomohiro
Maegawa , Yasunari Monguchi & Hironao Sajiki (2007) Development of a Practical and Scalable Preparation
using Sonication of Pd/Fibroin Catalyst for Chemoselective Hydrogenation, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:24, 4381-4388, DOI:
10.1080/00397910701577612
To link to this article: http://dx.doi.org/10.1080/00397910701577612
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

Synthetic Communicationsw, 37: 4381–4388, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701577612
Development of a Practical and Scalable
Preparation using Sonication of Pd/Fibroin
Catalyst for Chemoselective Hydrogenation
Yoshiaki Kitamura and Asami Tanaka
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University,
Mitahora-higashi, Gifu, Japan
Mutsumi Sato and Keiji Oono
Reagent Research Laboratories, Wako Pure Chemical Industries, Ltd.,
Matoba, Kawagoe, Saitama, Japan
Takashi Ikawa, Tomohiro Maegawa, Yasunari Monguchi, and
Hironao Sajiki
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University,
Mitahora-higashi, Gifu, Japan
Abstract: A practical and efficient preparation method of palladium-fibroin (Pd/Fib),
silk-fibroin-supported Pd(0) by means of sonication, has been developed. The Pd/Fib
catalyst could be prepared within 12 h at room temperature starting from commercial
silk-fibroin and Pd(OAc)2 in MeOH, whereas our previous preparation method required
at least 4 days. The present improved process is applicable to a large-scale preparation
of Pd/Fib. The Pd/Fib prepared by the present method also catalyzed chemoselective
hydrogenation of acetylenes, olefins, and azides in the presence of aromatic ketones,
aldehydes, and halides; N-Cbz protective groups; and benzyl esters, which are
readily hydrogenated under the Pd/C- or Pd/C(en)-catalyzed hydrogenation
conditions.
Keywords: chemoselective, hydrogenation, Pd/fibroin, practical, sonication
Received January 31, 2007
Address correspondence to Hironao Sajiki, Laboratory of Medicinal Chemistry,
Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan. E-mail:
sajiki@gifu-pu.ac.jp
4381

4382
Y. Kitamura et al.
Catalytic hydrogenation using a heterogeneous catalyst has been a useful and
widely applicable method in synthetic chemistry. Pd/C is one of the most
useful heterogeneous catalysts, because of its stability, ease of separation
from the reaction mixture, and recyclability.[1] However, the great catalyst
activity of Pd/C makes it extremely difficult to accomplish chemoselective
catalytic hydrogenation among reducible functionalities. We have recently
reported preparation and usage of silk-fibroin-supported palladium(0) [Pd/
Fib, commercially available from Wako Pure Chemical Industries, Ltd.,
Japan. Code number of palladium-fibroin (2.5% Pd/Fib): 167-22181 (1 g)
and 163-22183 (5 g).] Soaking silk-fibroin in a MeOH solution of Pd(OAc)2
at room temperature led to the absorption of Pd(II) on the fibroin surface
and the reduction of Pd(II) to Pd(0). The resulting dark-gray Pd/Fib selec-
tively catalyzed the hydrogenation of alkynes, alkenes, and azides without
the reduction of coexisting aromatic ketones and halides, benzyl alcohols,
esters and N-Cbz protective groups, and so on.[2] The Pd/Fib catalyst is
stable for more than 3 years in a capped vial, nonpyrophoric, cut up with
scissors for use, and removed easily from the reaction mixture by simple fil-
tration using a coarse-mesh filter paper. However, the preparation method
required more than 4 days of soaking the silk-fibroin in methanolic
Pd(OAc)2 solution, and it is not practical for industrial application. Herein,
we report a practical and scalable preparation method of Pd/Fib and 10 g–
scale chemoselective hydrogenation using the catalyst.
Ultrasonic irradiation onto soaked silk-fibroin in an MeOH solution of
Pd(OAc)2 was found to greatly accelerate the adsorption and reduction of
Pd(OAc)2. Pd/Fib could be prepared within only 12 h at room temperature
starting from commercial silk-fibroin [Silk-fibroin (commercial name:
Mawata-wrap 100% fibroin) was purchased from Fukada Commercial Co.
Ltd. (Kyoto, Japan).] and Pd(OAc)2 (Scheme 1). Then, the method was
applied to the 100 g–scale Pd/Fib preparation.
To explore the scope of the 2.5% Pd/Fib catalyst prepared by the present
method, the chemoselective hydrogenation of olefin, acetylene, and azide
functionalities in the presence of aromatic halide, ketone, and aldehyde,
N-Cbz, and benzyl ester functionalities within a molecule was investigated
at room temperature. The results shown in Table 1 demonstrate that the hydro-
genation activity toward olefin, acetylene, and azide functional groups was
retained, and no hydrogenation of aromatic ketones (entries 1 and 3),
aromatic halides (entries 1 and 2), or N-Cbz groups (entries 4 and 5)
proceeded. Although practical hydrogenolysis was observed in MeOH in
the case of the benzyl ester under the Pd/Fib-catalyzed hydrogenation
Scheme 1. Preparation of Pd/Fib.

Sonication of Pd/Fibroin Catalyst
4383
Table 1. Chemoselective hydrogenation of olefin, acetylene, and azide functionalities
using 2.5% Pd/Fib catalysta
Entry
1
Substrate
Solvent Time (h)
MeOH 1 (24) f
Product
Yield (%)b
96c (98c) f
2
3
CD3OD 1 (24) f
100d (100d) f
MeOH
24
100
4
5
MeOH 12 (32) f
100 (92e) f
MeOH
THF
12
92
6
7
3 (24) f
91 (98) f
THF-d8 3 (7) f
i-PrCO2Bn
2g
100d (93d) f
8
AcOEt
5
100
aUnless otherwise specified, reactions were performed using 2.5% Pd/Fib with
10 wt.% of the substrate (1 mmol) in MeOH, THF, or AcOEt (5 mL) as the solvent
under ambient hydrogen pressure at room temperature.
bIsolated yield.
cPerformed in 10 mL of MeOH.
1
dThe yield was determined based on the H NMR analysis.
eUnder 3 atm pressure of hydrogen.
fThe results using the preceding preparation catalyst are indicated in the
parentheses.[2c]
conditions, deprotection of the benzyl ester could be avoided by the use of
THF as a solvent (entries 6 and 7).[2,3] Furthermore, chemoselective hydrogen-
ation of alkene was also achieved in AcOEt with the aromatic aldehyde intact
(Entry 8).[2,3]
Next, we examined a 10 g–scale chemoselective hydrogenation using 1 g
of 2.5% Pd/Fib catalyst in THF (Scheme 2). The olefinmoiety of benzyl
cinnamate (1f, 10.0 g) was completely hydrogenated within 5 h without
hydrogenolysis of the benzyl ester to give benzyl dihydrocinnamate (2f,
9.88 g, 98% yield) (see also Table 1, entry 6).

4384
Y. Kitamura et al.
Scheme 2.
In summary, we have developed a practical and scalable preparation
method for 2.5% Pd/Fib catalyst under sonication conditions. The sonication
markedly reduced the preparation time to less than 12 h from 4 days. Pd/Fib
(2.5%) prepared by the present method worked as a chemoselective hydrogen-
ation catalyst for alkene, alkyne, and azide functionalities in the presence of
other reducible functional groups as well as conventional 2.5% Pd/Fib
catalyst prepared by more than the method of soaking for 4 days.[2]
EXPERIMENTAL SECTION
Materials
Silk-fibroin (commercial name: Mawata-wrap 100% fibroin) was purchased
from Fukuda Commercial Co. Ltd. (Kyoto, Japan). Unless otherwise stated,
commercially obtained materials were used without further purification.
MeOH and anhydrous THF and AcOEt were purchased from Wako Pure
Chemical Industries, Ltd. (Osaka, Japan) and used without any further purifi-
cation. CH2Cl2 was distilled from calcium hydride. The sonication was
carried out at 47 or 78 kHz using Bransonicw Ultrasonic Cleaner (Branson,
Danbury, CT).
1H and 13C NMR spectra were recorded on a Jeol JNM EX-400 or Jeol
1
JNM AL-400 spectrometer (400 MHz for H NMR and 100 MHz for 13C
NMR). All 1H NMR spectra were reported in parts per million (ppm)
relative to TMS (internal standard) in CDCl3. All 13C NMR spectra
1
reported in ppm relative to CDCl3 (77.0 ppm) were obtained with H decou-
pling. EI mass spectra were taken on a Jeol JMS-SX102A instrument.
Elemental analyses were performed on a Yanaco MT-5 instrument. Flash-
column chromatography was performed using Kanto Chemical Co., Inc.
silica gel 60 N, spherical neutral (63–210mm).
Preparation of 2.5% Pd/Fib
Preparation of 2.5% Pd/Fib (100 g scale)
In a rust-colored solution of palladium acetate (5.27 g, 23.5 mmol) in MeOH
(2 L) under nitrogen at room temperature, colorless silk-fibroin (100 g) was
soaked, which had been shredded into around 5-mm-long pieces with

Sonication of Pd/Fibroin Catalyst
4385
scissors. The mixture was sonicated for 12 h (30 + 38C). The silk fiber
changed gradually from white to dark gray, and the solution also changed
gradually from rust to thoroughly colorless (if the solution was not
colorless, the sonication should be continued). The resulting fiber was
filtered, washed with MeOH (1 L), and dried using a vacuum pump
(ca. 1 mm Hg) at 408C for 15 h to give the 2.5% Pd/Fib (98.2 g) as
dark-gray fiber.
Synthesis of Substrate
4-Benzoylphenylazide (1c)
To a solution of 4-aminobenzophenone (1.97 g, 10.0 mmol) in 10% HCl
(15 mL), a solution of sodium nitrite (0.690 g, 10.0 mmol) in water (3 mL)
was added at 0–58C with vigorous stirring. The mixture was kept colder
than 58C for 30 min, and then a solution of sodium azide (0.72 g,
11.0 mmol) in water (15 mL) was added dropwise while at that temperature.
After being stirred for 1 h, the mixture was warmed to room temperature
and extracted with AcOEt (50 mL) and H2O (50 mL). The organic layer
was washed with brine (50 mL), dried over Na2SO4, and concentrated under
reduced pressure to afford 4-benzoylphenylazide as a pale yellow solid
1
(2.10 g, 95%); mp 75.5–77.08C. H NMR d 7.82 (d, J ¼ 7.6 Hz, 2H), 7.75
(d, J ¼ 8.0 Hz, 2H), 7.57 (t, J ¼ 7.6 Hz, 1H), 7.47 (t, J ¼ 7.6 Hz, 2H), 7.09
(d, J ¼ 8.0 Hz, 2H); 13C NMR d 195.0, 144.3, 137.4, 133.9, 132.2, 131.9,
129.7, 128.2, 118.6; HRMS (EI) calcd. for C13H9N3O (Mþ) 223.0746.
Found 223.0751. Anal. calcd. for C13H9N3O: C, 69.95; H, 4.06; N, 18.82.
Found: C, 70.04; H, 4.24; N, 18.76.
N-(Benzyloxycarbonyl)diallylamine (1d)[2c]
To a solution of diallylamine (1.94 g, 20.0 mmol) in CH2Cl2 (10.0 mL),
N-(benzyloxycarbonyloxy)succinimide (5.48 g, 22.0 mmol) was added. The
solution was stirred at room temperature for 7 h, and the mixture was concen-
trated under reduced pressure. The residue was extracted with AcOEt (50 mL)
and H2O (50 mL). The organic layer was washed successively with H2O
(30 mL), saturated aqueous NaHCO3 solution (30 mL), and brine (30 mL);
dried over MgSO4; and concentrated under reduced pressure to afford N-
(benzyloxycarbonyl)diallylamine as a yellow oil (2.52 g, 55%). 1H NMR d 7.36–
7.30 (m, 5H), 5.83–5.70 (m, 2H), 5.15 (s, 2H), 5.19–5.05 (m, 2H), 3.90–3.87
(m, 2H); 13C NMR d 155.7, 136.6, 133.2, 128.1, 127.6, 127.5, 116.1, 116.4,
66.8, 48.8, 48.2. HRMS (EI) calcd. for C14H18NO2 (Mþ) 232.1337. Found
232.1346.

4386
Y. Kitamura et al.
N-Benzyloxycarbonyl-4-ethynylaniline (1e)[2c]
To a solution of 4-ethynylaniline (0.585 g, 5.00 mmol) in THF (10.0 mL),
N-(benzyloxycarbonyloxy)succinimide (2.18 g, 9.00 mmol) was added. The
solution was stirred at room temperature for 36 h, and the mixture was concen-
trated under reduced pressure. The residue was extracted with AcOEt (50 mL)
and H2O (50 mL). The organic layer was washed successively with H2O
(30 mL), saturated aqueous NaHCO3 solution (30 mL), and brine (30 mL);
dried over MgSO4; and concentrated under reduced pressure. The residue
was purified by flash silica-gel columun chromatography (hexane/
ether ¼ 10:1) to afford N-benzyloxy carbonyl-4-ethynylaniline as
a
colorless solid (1.17 g, 93%); mp 98.5–99.08C. 1H NMR d 7.45–7.34
(m, 9H), 6.70 (brs, NH), 5.20 (s, 2H), 3.02 (s, 1H); 13C NMR d 152.9,
138.3, 135.8, 133.0, 128.7, 128.5, 128.4, 118.2, 116.9, 83.5, 76.5, 67.2;
HRMS (EI) calcd. for C16H13NO2 (Mþ) 251.0946. Found 251.0949. Anal.
calcd for C16H13NO2: C, 76.48; H, 5.21; N, 5.57. Found: C, 76.63; H, 5.24;
N, 5.49.
General Procedure for Chemoselective Hydrogenation using 2.5%
Pd/Fib
Procedure (1 mmol scale)
To a round-bottom flask with a stir bar, a substrate (1.00 mmol), 2.5% Pd/Fib
(10 wt.% of the substrate), and MeOH (5.00 mL) were added, and the flask
was sealed with a septum. The air in the flask was replaced with hydrogen
by two vacuum/H2 cycles, and the mixture was vigorously stirred at room
temperature (ca. 208C) under ambient pressure of hydrogen (balloon). The
reaction mixture was filtered through a filter paper, and the filtrate was concen-
trated under reduced pressure to afford the pure product.
Data
40-Chloro-3-phenylpropiophenone (2a):[2c] Colorless solid; 1H NMR d 7.42,
7.89 (each, d, J ¼ 8.3 Hz, each 2H), 7.32–7.19 (m, 5H), 2.37 (t, J ¼ 7.7 Hz,
2H), 3.06 (t, J ¼ 7.7 Hz, 2H); 13C NMR d 198.0, 141.0, 139.5, 135.2, 129.5,
128.9, 128.5, 128.4, 126.2, 40.4, 30.0; MS (EI) m/z 246 (Mþ, 15%). HRMS
(EI) calcd. for C15H13OCl (Mþ) 244.0655. Found 244.0661.
4-Bromoethylbenzene (2b):[2c] Colorless oil; 1H NMR d 7.39 (d, J ¼ 8.4 Hz,
2H), 7.06 (d, J ¼ 8.4 Hz, 2H), 2.60 (q, J ¼ 7.8 Hz, 2H), 1.21 (t, J ¼ 7.8 Hz,
3H); 13C NMR d 143.1, 131.3, 129.6, 119.2, 28.3, 15.4; MS (EI) m/z 184
(Mþ, 66%). HRMS (EI) calcd. for C8H9Br (Mþ) 183.9888. Found 183.9881.

Sonication of Pd/Fibroin Catalyst
4387
4-Aminobenzophenone (2c) Commercially available: Pale yollow solid;
1H NMR d 7.73–7.69 (m, 4H), 7.52 (t, J ¼ 7.4 Hz, 1H), 7.46
(t, J ¼ 7.4 Hz, 2H), 6.67 (d, J ¼ 7.8 Hz, 2H); 13C NMR d 195.3,
151.0, 138.8, 132.9, 131.4, 129.5, 128.0, 127.2, 113.6; MS (EI) m/z
197 (Mþ, 79%). HRMS (EI) calcd. for C13H11NO (Mþ) 197.0841.
Found 197.0832.
N-(Benzyloxycarbonyl)dipropylamine (2d):[2c] Colorless oil; 1H NMR
d 7.36–7.28 (m, 5H), 5.12 (s, 2H), 3.25–3.12 and 1.61–1.49 (each m,
4H), 0.89–0.86 (m, 6H); 13C NMR d 156.2, 137.1, 128.4, 127.7,
127.6, 66.7, 49.2, 48.6, 21.8, 21.3, 11.2; MS (EI) m/z 246 (Mþ, 15%).
HRMS (EI) calcd. for C15H13OCl (Mþ) 236.1650. Found 236.1648.
N-Benzyloxycarbonyl-4-ethylaniline (2e):[2c] Pale yellow powder; 1H NMR
d 7.41–7.26 (m, 7H), 7.13 (d, J ¼ 8.3 Hz, 2H), 6.60 (brs, NH), 5.19 (s, 2H),
2.60 (q, J ¼ 7.6 Hz, 2H), 1.21 (t, J ¼ 7.6 Hz, 3H); 13C NMR d 153.5, 139.6,
136.2, 135.4, 128.6, 128.3, 128.3, 119.0, 66.9, 28.2, 15.7; MS (EI) m/z 255
(Mþ, 14%). HRMS (EI) calcd. for C16H17NO2 (Mþ) 255.1259. Found
255.1268.
Benzyl 3-phenylpropionate (2f):[2c] THF was used as a solvent in place of
1
MeOH. Colorless oil; H NMR d 7.37–7.18 (m, 10H), 5.11 (s, 2H), 2.97
(t, J ¼ 7.8 Hz, 2H), 2.69 (t, J ¼ 7.8 Hz, 2H); 13C NMR d 173.0, 140.7,
136.2, 128.8, 128.6, 128.5, 126.6, 66.6, 36.1, 31.2; MS (EI) m/z 240
(Mþ, 5%). HRMS (EI) calcd. for C16H16O2 (Mþ) 240.1150. Found
240.1145.
Benzyl isobutylate (2g):[2c] THF was used as a solvent in place of
MeOH. Colorless oil; 1H NMR d 7.39–7.29 (m, 5H), 5.12 (s, 2H),
2.60 (h, J ¼ 6.8 Hz, 1H), 1.19 (d, J ¼ 6.8 Hz, 6H); 13C NMR
d 176.9, 136.3, 128.5, 128.1, 127.9, 66.0, 34.0, 19.0; MS (EI) m/z
240 (Mþ, 5%); HRMS (EI) calcd for C11H14O2(Mþ) 178.0994.
Found 178.1002.
4-Propyloxybenzaldehyde (2h):[2c] AcOEt was used as a solvent in place of
MeOH. Pale yellow oil; 1H NMR d 9.88 (s, 1H), 7.83 (d, J ¼ 8.8 Hz, 2H), 7.00
(d, J ¼ 8.8 Hz, 2H), 4.00 (t, J ¼ 6.6 Hz, 2H), 1.87–1.80 (m, 2H), 1.06 (t
J ¼ 7.6 Hz, 3H); 13C NMR d 190.8, 164.2, 132.0, 129.7, 114.7, 69.9, 22.4,
10.4; MS (EI) m/z 164 (Mþ, 30%); HRMS (EI) calcd for C10H12O2 (Mþ)
164.0837. Found 164.0846.
Procedure (10 g scale)
According to the 1 mmol-scale procedure, a mixture of benzyl cinnamate
(10.0 g, 42.0 mmol), 2.5% Pd/Fib (1.00 g) in THF (200 mL) was vigorously

4388
Y. Kitamura et al.
stirred at room temperature (ca. 208C) under ambient pressure of hydrogen
(balloon). The reaction mixture was filtered through a filter paper, and
the filtrate was concentrated under reduced pressure to afford benzyl
3-phenylpropionate (9.88 g, 98%).
ACKNOWLEDGMENT
This work was supported by the Research Foundation of Gifu Pharmaceutical
University and Wako Pure Chemical Industries, Ltd.
REFERENCES
1. For selected reviews on reductions, see (a) Larock, R. C. Comprehensive Organic
Transformations, 2nd edn.; Wiley-VCH: New York, 1999; (b) Nishimura, S.
Handbook of Heterogeneous Catalytic Hydrogenation for Organic Synthesis;
Wiley-Interscience: New York, 2001; (c) Hudlicky, M. Reductions in Organic
Chemistry, 2nd edn.; ACS: Washington, DC, 1996; (d) Rylander, P. N. Hydrogen-
ation Methods; Academic: New York, 1985.
2. (a) Sajiki, H.; Ikawa, T.; Hirota, K. Preparation of silk fibroin-supported Pd(0)
catalyst for chemoselective hydrogenation: reduction of palladium(II) acetate by
methanol on the protein. Tetrahedron Lett. 2003, 44, 171–174; (b) Sajiki, H.;
Ikawa, T.; Hirota, K. Markedly chemoselective hydrogenation with retention of
benzyl ester and N-Cbz functions using a heterogeneous Pd-fibroin catalyst. Tetra-
hedron Lett. 2003, 44, 4837–4839; (c) Ikawa, T.; Sajiki, H.; Hirota, K. Highly che-
moselective hydrogenation method using novel finely dispersed palladium catalyst
on silk-fibroin: its preparation and activity. Tetrahedron 2005, 61, 2217–2231;
(d) Ikawa, T.; Sajiki, H.; Hirota, K. Development of highly chemoselective hydro-
genation using novel palladium(0)-fibroin catalyst. J. Synth. Org. Chem. Jpn. 2005,
63, 1218–1231.
3. (a) Sajiki, H.; Hattori, K.; Hirota, K. The formation of a novel Pd/C-ethylenediamine
complex catalyst: Chemoselective hydrogenation without deprotection of the
O-benzyl and N-Cbz groups. J. Org. Chem. 1998, 63, 7990–7992; (b) Hattori, K.;
Sajiki, H.; Hirota, K. Pd/C(en)-catalyzed chemoselective hydrogenation with
retention of the N-Cbz protective group and its scope and limitations. Tetrahedron
2000, 56, 8433–8441; (c) Sajiki, H.; Hattori, K.; Hirota, K. Highly chemoselective
hydrogenation with retention of the epoxide function using a heterogeneous Pd/C-
ethylenediamine catalyst and THF. Chem. Eur. J. 2000, 6, 2200–2204;
(d) Sajiki, H.; Ikawa, T.; Hattori, K.; Hirota, K. A remarkable solvent effect toward
the Pd/C-catalyzed cleavage of silyl ethers. Chem. Commun. 2003, 654–655.