Significant supplier-dependent disparity in catalyst activity of commercial Pd/C toward the cleavage of triethylsilyl ether

Article abstract of DOI:10.1016/j.tetlet.2003.08.045

Pd/C catalysts exhibit remarkable supplier-dependent difference in catalyst activity and property. Some commercial Pd/C catalysts are quite acidic. Although a TES ether cleavage reaction using 10% Pd/C in the absence of hydrogen was quite recently published, we could conclude it was only an acid, released from the catalyst, catalyzed solvolysis, and hydrogen is essential for the actual 10% Pd/C-catalyzed cleavage of a TES ether.

Full text of DOI:10.1016/j.tetlet.2003.08.045

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7407–7410
Significant supplier-dependent disparity in catalyst activity of
commercial Pd/C toward the cleavage of triethylsilyl ether
Hironao Sajiki,* Takashi Ikawa and Kosaku Hirota*
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan
Received 22 July 2003; revised 7 August 2003; accepted 11 August 2003
Abstract—Pd/C catalysts exhibit remarkable supplier-dependent difference in catalyst activity and property. Some commercial
Pd/C catalysts are quite acidic. Although a TES ether cleavage reaction using 10% Pd/C in the absence of hydrogen was quite
recently published, we could conclude it was only an acid, released from the catalyst, catalyzed solvolysis, and hydrogen is
essential for the actual 10% Pd/C-catalyzed cleavage of a TES ether.
© 2003 Published by Elsevier Ltd.
Pd/C has been considered as one of the most univer-
sally applicable catalysts for hydrogenation.1 However,
to the best of our knowledge, although there have been
some reports suggesting several distinctive features
among Pd/C catalysts prepared by different methods1
or purchased from different suppliers,2 there have been
no examples of the conflicting reports in the literature
concerning this subject. Here we would like to intro-
duce such discrepant papers, including ours, and to
report on the outcome of the verification of such. We
Scheme 1.
dium-catalyzed cleavage method of TES ethers. In con-
trast to our results, their method allows easy removal of
alkyl TES ethers using 10 wt% of 10% Pd/C5 in MeOH
or 95% EtOH as a solvent without hydrogen conditions
even under an argon atmosphere (Scheme 2).
also caution that catalyst activity and properties of
Pd/C differ greatly depending on the supplier. Because
the acidity of some commercial Pd/C catalysts is quite
high, particular attention should be given to choose and
use them.
Most recently, we have reported3 a remarkable solvent
effect toward the Pd/C-catalyzed cleavage of TES and
TBDMS ethers, and it was applied to the development
of a chemoselective hydrogenation method for other
reducible functionalities distinguished from the TES
and TBDMS protective groups of a hydroxyl group by
the employment of MeCN or EtOAc as a solvent.
While, particularly, TES ethers can be easily cleaved
under mild hydrogenation conditions using 10 wt%
(versus substrate) of 10% Pd/C (Aldrich product num-
ber 20,569-9) in MeOH at room temperature under an
ambient hydrogen atmosphere, the desilylation did not
occur in the absence of hydrogen (Scheme 1).
Scheme 2.
Prompted by the great discrepancy between the two
papers, we pursued the reaction in further detail. From
their results it occurred to us that certain distinctions of
the property of various commercial 10% Pd/C catalysts
might have caused the serious conflicting results. Actu-
ally, the reaction of 1-triethylsilanoxydecane (1a) in the
presence of 10 wt% of 10% Pd/C purchased from
various suppliers in MeOH without hydrogen at room
temperature for 24 h gave scattered results (Table 1).
Complete cleavage of the TES protective group, as well
as Prunet’s report,4 took place in 1 h when 10% Pd/C
(Merck or ACROS) was used in 10 wt% of the sub-
On the other hand, Rotulo-Sims and Prunet published4
during the review of our manuscript,3 a simple palla-
* Corresponding authors. Tel: +81-58-237-3931; fax: +81-58-237-
5979; e-mail: sajiki@gifu-pu.ac.jp
0040-4039/$ - see front matter © 2003 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2003.08.045

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H. Sajiki et al. / Tetrahedron Letters 44 (2003) 7407–7410
Table 1. Supplier-dependent 10% Pd/C catalyst activity
toward the cleavage of the TES ether 1a
(0.014 mmol) of HCl resulted in 87% loss of the TES
protective group of 1a within 1 h without hydrogen at
room temperature (Table 2, entry 1). We then investi-
gated whether the TES cleavage reaction in the absence
of hydrogen conditions4 is certainly a palladium-cata-
lyzed (assisted) reaction or only an acid-catalyzed
solvolysis. The addition of Aldrich’s 10% Pd/C, having
no TES-cleaving tendency under neutral non-hydrogen
conditions, to above acid catalyzed reaction conditions
was examined (entry 2). The cleavage of the TES ether
of 1a was slightly enhanced (98% loss) although the
addition of only activated charcoal (Norit® SX-3) or Pd
black resulted no acceleration of the cleavage (entries 3
or 4). Next, 10% Pd/C (Merck, 6.8 mg) in MeOH (1.0
mL) was stirred at room temperature under several
conditions for 24 h and then the catalyst was filtered off
using a membrane filter (Millipore, Millex®-L9, 0.20
mm). The TES ether (1a, 68.1 mg, 0.25 mmol) was
stirred in the resulting filtrate under an air atmosphere
at room temperature for 24 h. Table 3 summarizes the
effect of various catalyst pretreatments and reaction
conditions on the reaction rate. After stirring the sus-
pension of 10% Pd/C (Merck) for 24 h, partial cleavage
of the TES group of 1a was observed even in the filtrate
(entry 1). When the suspension of 10% Pd/C in MeOH
was sonicated or stirred under an H2 atmosphere before
filtration, enhanced cleavage of the TES group took
place in 24 h (entries 3 and 5), although the addition of
Amberlite® IRA-45 (6.8 mg) into the suspension per-
fectly suppressed the cleavage (entries 2, 4 and 6). On
the other hand, no cleavage was identified under identi-
cal reaction conditions when Aldrich’s Pd/C was used
instead of Merck’s Pd/C (entries 7–9).
Entry
10% Pd/Ca
1a:2a
1
2
3
4
5
6
7
Aldrich (20,569-9)
Wako (163-15272)
N. E. Chemcat (dry)
Nacalai (25928-84)
Kishida (400-59095)
ACROS (19503-0100)
Merck (807104-0010)
100:0b
87:13
78:22
75:25
59:41
0:100c
0:100d
a Supplier’s product number is indicated in parentheses.
b The reproducibility of the data was confirmed in experiments using
different lots of the Pd/C (Lot. AI 05401JS and Lot. KA 13921CA).
c The reaction was completed in approximately 1 h.
d The reaction was completed within 1 h.
strate 1a, respectively (entries 6 and 7). 10% Pd/C
catalysts from Wako, N. E. Chemcat, Nakarai and
Kishida (entries 2–5) were less effective in promoting
the TES cleavage. Needless to say, the cleavage of the
TES protective group of 1a did not proceed upon
employment of 10% Pd/C (Aldrich) while smooth
cleavage was observed under a hydrogen atmosphere.
In view of these undesirable results, we believed that
the cleavage reaction of TES ethers with 10% Pd/C
without hydrogen conditions was promoted by the con-
taminated acid in the Pd/C catalysts although Prunet
asserted aggressively that the cleavage was a palladium-
catalyzed reaction.4 To explore the influence of the
contaminated acid during the production process of the
Pd/C, a basic gel-type resin, Amberlite® IRA-45, as an
acid scavenger was added into the reaction mixture
using 10% Pd/C (Merck). As consequences of the reac-
tion, no desilylation occurred at all even after 24 h6
while no depression of the cleavage of TES ethers using
10% Pd/C (Aldrich) under a hydrogen atmosphere was
observed in the presence of Amberlite® IRA-45
(Scheme 3).
Pd/C catalysts are usually prepared by the reduction of
PdCl2 in the presence of heavy metal-free activated
charcoal in concentrated hydrochloric acid.1 Since the
acidity of the suspension of 10% Pd/C is enhanced
under a hydrogen atmosphere, the retained acids may
be driven away from the fine pores of the charcoal by
the hydrogen molecule7 and/or residual PdCl2 by the
incomplete reduction during the preparation process
maybe reduced by hydrogen.2,8 From these results it is
obviously concluded the TES cleavage reaction in the
absence of hydrogen conditions4 is substantially acid-
catalyzed solvolysis because the TES cleavage reaction
progresses even in the 0.05% HCl–MeOH solution
Further, the acid-catalyzed methanolysis of 1a (0.25
mmol) in the presence of a non-stoichiometric amount
Table 2. Influence of additives toward the acid catalyzed
methanolysis of the TES ether 1a
Entry
Additives
1a:2a
1
2
3
4
None
13:87
2:98
22:78
37:63
10% Pd/C (Aldrich, 6.8 mg)
Norit® SX3 (6.8 mg)
Pd black (Kishida, 0.7 mg)
Scheme 3.

H. Sajiki et al. / Tetrahedron Letters 44 (2003) 7407–7410
Table 3. Cleavage of the TES ether 1a in the filtrate
7409
Entry
10% Pd/C
Conditions
1a:2a
1
2
3
4
5
6
7
8
9
Merck
Merck
Merck
Merck
Merck
Merck
Aldrich
Aldrich
Aldrich
Air
74:26
100:0
67:33a
100:0
23:77a
100:0
100:0
100:0
100:0
Air+Amberlite® IRA-45
Sonication
Sonication+Amberlite® IRA-45
H2 (balloon)
H2 (balloon)+Amberlite® IRA-45
Air
Sonication
H2 (balloon)
a Average of 2 times.
Table 4. Comparison of the acidity of commercial 10%
Pd/C
(Table 2, entry 1) and the Pd/C-free filtrate (Table 3,
entries 1, 3, 5).
Recently, we reported the smooth reduction of Pd(OAc)2
to zero valent palladium by MeOH as a reductant at
room temperature.8 Although Rotulo-Sims and Prunet
also reported in their paper4 the TES cleavage reaction
in the absence of hydrogen conditions could be greatly
enhanced in MeOH by the use of PdCl2 instead of 10%
Pd/C, PdCl2 was presumably reduced to Pd(0) by MeOH
and a very small amount of hydrogen chloride should be
generated during the short reaction period.
Entry
1
10% Pd/C
Conditions
Air
pHa
Merck
4.82 (23.4°C)
4.79 (24.2°C)
2
3
4
5
6
7
ACROS
Aldrich
Merck
Air
5.75 (24.8°C)
5.82 (24.9°C)
Air
6.28 (24.6°C)
6.34 (24.5°C)
In addition, our attention was directed to gaining more
precise insight into the acidity of Pd/C catalysts. Thus,
we determined the pH of the aqueous suspension after
stirring for 24 h (Table 4). As can be seen, the suspension
of 10% Pd/C catalysts purchased from Merck and
ACROS having a high TES-cleaving tendency indicate
a quite acidic property (entries 1, 2, 4 and 5). Surpris-
ingly, the suspension of Merck’s Pd/C recorded pH <3
under the a H2 atmosphere (entry 4)7 while Aldrich’s
Pd/C indicates a rather slightly basic to neutral range
(entries 3 and 6), compared with the pH value of
ion-exchanged water (ca. 6.0, entry 7).9,10
H2 (balloon)
H2 (balloon)
H2 (balloon)
2.96 (26.5°C)
2.88 (26.1°C)
ACROS
Aldrich
3.34 (25.0°C)
3.38 (24.6°C)
5.91 (26.5°C)
5.98 (26.2°C)
pH of ion-exchanged H2Ob
5.92 (23.5°C)
5.99 (23.5°C)
a pH was determined with Horiba D-21 pH meter.
b Ion-exchanged H2O indicates slightly acidic pH by the dissolved
atmospheric CO2.
Since the unexpected loss of other acidic-sensitive protec-
tive groups from the mother molecule would cause
extensive damage to a multi-step synthetic process, the
acid-catalyzed solvolysis of THP ether (3) was also
examined with 10 wt% of 10% Pd/C at room temperature
in MeOH. Although no cleavage of the THP ether (3)
occurred when Pd/C (Aldrich) was used as a catalyst
(Table 5, entries 1 and 2),11 partial deprotection (3:4=
56:44) of the THP ether (3) under atmospheric conditions
(entry 3) and complete cleavage under H2 conditions
(entry 4) proceeded with Merck’s 10% Pd/C. Conse-
quently, the cleavage of TES ethers using 10% Pd/C
under no hydrogen conditions is not a neutral reaction
and restricted the use of acid-sensitive functionalities.
Table 5. Cleavage of the THP ether in the presence of
10% Pd/C
Entry
10% Pd/C
H2 (balloon)
3:2a
1
2
3
4
Aldrich
Aldrich
Merck
Merck
None
ꢀ
None
ꢀ
100:0
100:0
56:44
0:100

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H. Sajiki et al. / Tetrahedron Letters 44 (2003) 7407–7410
In conclusion, we have clearly demonstrated the unreli-
ability of the palladium-catalyzed cleavage of TES
ethers in the absence of hydrogen conditions.4 The
cleavage should be interpreted as an acid-catalyzed
solvolysis. This methodology will be an attractive tool
for the organic chemist if the supplier of Pd/C is
specified and the reproducibility of the data is indicated
using some different lots of the Pd/C. Furthermore, we
were also able to demonstrate Pd/C catalysts exhibit
remarkable supplier-dependent difference in the prop-
erty and quality. When a Pd/C catalyst is used in an
article, the name of the supplier and the product num-
ber of the catalyst must be clarified. Finally, it is
noteworthy that hydrogen is an obligatory condition
for the real palladium-catalyzed cleavage of silyl ethers
in MeOH and that 10% Pd/C of Aldrich (20,569-9) is a
quite safe and nearly neutral catalyst within our investi-
gation. According to all of the results indicated in this
paper, the 10% Pd/C (Aldrich)-catalyzed TES cleavage
mechanism under hydrogen conditions3 can involve a
direct hydrogenolysis of the silyl group or a true palla-
dium-catalyzed methanolysis by the 10% Pd/C acti-
vated by hydrogen.
7. Maier, W. F.; Chettle, S. J.; Rai, R. S.; Thomas, G. J.
Am. Chem. Soc. 1986, 108, 2608–2616.
8. Sajiki, H.; Ikawa, T.; Yamada, H.; Tsubouchi, K.;
Hirota, K. Tetrahedron Lett. 2003, 44, 171–174.
9. The palladium content of the commercial 10% Pd/C was
determined by the inductively-coupled plasma (ICP) spec-
trometry. As shown in Table 6, some scatter of the Pd
content were obserbed.
Table 6. The palladium content of the commercial 10%
Pd/C
Entry
10% Pd/Ca
Pd content (%)
1
2
3
Merck (807104-0010, Lot: S2328
4835)
ACROS (19503-0100, Lot:
A012028901)
Aldrich (20,569-9, Lot: KA
13921CA)
8.7
8.5
9.2
a Supplier’s product and Lot. numbers are indicated in parentheses.
10. A milky precipitate was formed by addition of one drop
of 0.1 mol/L silver nitrate (AgNO3) solution to the filtrate
of the pH-determined suspention (ca. 2 mL) in Table 4.
An amount of the precipitate was increased with the drop
in pH. Consequently, the causes of the high acidity of the
10% Pd/C purchased from Merck or ACROS are con-
tamination of HCl and PdCl2.
References
1. For reviews, see: (a) Nishimura, S. Handbook of Hetero-
geneous Catalytic Hydrogenation for Organic Synthesis;
John Wiley & Sons: New York, 2001; (b) Rylander, P. N.
Hydrogenation Methods; Academic Press: New York,
1985.
2. Kaisalo, L. H.; Hase, T. A. Tetrahedron Lett. 2001, 42,
7699–7701.
3. Sajiki, H.; Ikawa, T.; Hattori, K.; Hirota, K. Chem.
Commun. 2003, 654–655.
11. Kaisalo and Hase previously reported2 a cleavage reac-
tion of the THP protective group under Pd/C-catalyzed
hydrogenation conditions using an equal amount to the
substrate of 10% Pd/C (Aldrich) in EtOH. In contrast to
their report, no reproducibility of their results was indi-
cated in our study using an equal amount to the substrate
of 10% Pd/C (Aldrich product number 20,569-9). Since
two kinds of dry 10% Pd/C (20,569-9 and 52,088-8,
Engelhard code C3645) is inserted in an Aldrich catalog,
it is contemplated that the different kind of 10% Pd/C
(52,088-8) was used for their reaction [The easy cleavage
of THP ether using 10% Pd/C (Aldrich product number
52,088-8) was confirmed in our laboratory].
4. Rotulo-Sims, D.; Prunet, J. Org. Lett. 2002, 4, 4701–
4704.
5. Supplier of the 10% Pd/C was not indicated in their
paper.4
6. The addition of 68 mg of Amberlite® IRA-45 as an acid
scavenger into the reaction mixture caused no cleavage of
the TES ether (1a), even after 24 h.