Solvent-modulated Pd/C-catalyzed deprotection of silyl ethers and chemoselective hydrogenation

Article abstract of DOI:10.1016/j.tet.2004.05.098

Recently we have reported undesirable and frequent deprotection of the TBDMS protective group of a variety of hydroxyl functions occurred under neutral and mild hydrogenation conditions using 10% Pd/C in MeOH. The deprotection of silyl ethers is susceptible to significant solvent effect. TBDMS and TES protecting groups were selectively cleaved in the presence of acid-sensitive functional groups such as TIPS ether, TBDPS ether and dimethyl acetal under hydrogenation condition using 10% Pd/C in MeOH. In contrast, chemoselective hydrogenation of reducible functional groups such as acetylene, olefin and benzyl ether, proceeds in the presence of TBDMS or TES ethers in AcOEt or MeCN.

Full text of DOI:10.1016/j.tet.2004.05.098

Tetrahedron 60 (2004) 6901–6911
Solvent-modulated Pd/C-catalyzed deprotection of silyl ethers and
chemoselective hydrogenation
*
Takashi Ikawa, Kazuyuki Hattori, Hironao Sajiki and Kosaku Hirota
*
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan
Received 30 April 2004; accepted 27 May 2004
Available online 4 July 2004
Abstract—Recently we have reported undesirable and frequent deprotection of the TBDMS protective group of a variety of hydroxyl
functions occurred under neutral and mild hydrogenation conditions using 10% Pd/C in MeOH. The deprotection of silyl ethers is susceptible
to significant solvent effect. TBDMS and TES protecting groups were selectively cleaved in the presence of acid-sensitive functional groups
such as TIPS ether, TBDPS ether and dimethyl acetal under hydrogenation condition using 10% Pd/C in MeOH. In contrast, chemoselective
hydrogenation of reducible functional groups such as acetylene, olefin and benzyl ether, proceeds in the presence of TBDMS or TES ethers in
AcOEt or MeCN.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
related reaction, we found that the reductive deprotection of
the silyl ether under hydrogenation conditions using 10%
Pd/C was strongly affected by the solvent. Herein, we report
a selective cleavage method of TES and TBDMS ethers
under mild and neutral hydrogenation conditions using 10%
Pd/C in MeOH, and a selective hydrogenation method of
some reducible functionalities in the presence of TES and
TBDMS ethers using 10% Pd/C in MeCN or AcOEt.7
Hydroxyl groups are partial structures of a number of
organic compounds. During oxidation, acylation, halogena-
tion or dehydration reaction of these compounds, the
hydroxyl groups must be protected. Silyl ethers are among
the most frequently used protective groups for alcohols in
organic synthesis,1 because they can be easily installed in
high yield and can withstand a variety of reaction
conditions. Although silyl ethers can be easily deprotected
by treatment with a fluoride anion,2 the strongly basic
conditions make it inappropriate to apply to base-sensitive
substrates.2 Many alternative and mild methods have been
reported for the deprotection of silyl ethers under mild
conditions.1 However, most of these methods suffer from
the use of acidic and basic conditions, strong oxidising and
reducing reagents and complicated workup.3 In this context,
it is very important to develop a novel, neutral and mild
deprotection method of silyl ethers.
2. Results and discussion
Our initial studies focused on the solvent effect toward the
deprotection of TBDMS ethers under hydrogenation
conditions using 10% Pd/C. 1-tert-Butyldimethylsilyloxy-
3-phenyl-2-propene (1a) was hydrogenated with 10% Pd/C
(10% of the weight of the substrate (1a); 2.3 mol% as Pd
metal) for 24 h at room temperature in various solvents
(Table 1). While smooth hydrogenation of the olefin
function and complete deprotection of the TBDMS
protective group of 1a simultaneously proceeded in
MeOH (entry 1), TBDMS cleavage reaction was slightly
depressed in EtOH and strongly inhibited in tBuOH (entries
2 and 3). In spite of the poor water solubility of 1a,
considerable cleavage (77%) of the TBDMS ether was
observed (entry 4). As compared with protic solvents, use of
aprotic solvents is inconvenient for the deprotection of
TBDMS ether (1a) under hydrogenation conditions using
Pd/C (entries 5–11). Especially in toluene, AcOEt and
MeCN, the TBDMS ether was stable and selective
hydrogenation of the olefin was achieved (entries 9–11).
While no deprotection of the TBDMS group was observed
in the absence of hydrogen or 10% Pd/C in MeOH, both
On the other hand, Pd/C is one of the most useful
heterogeneous hydrogenation catalysts in organic syn-
thesis,4 because it can be safely handled and removed
from the reaction mixture by simple filtration. Although it
has been well known that the TBDMS (tert-butyldimethyl-
silyl) ether is inert toward Pd/C-catalyzed hydrogenation
conditions,5 we have recently reported that the TBDMS
ethers are easily and frequently cleaved under hydro-
genation conditions using Pd/C as a catalyst in MeOH.6 In a
Keywords: Silyl ether; Hydrogenation; Palladium on carbon; Solvent effect;
Deprotection.
*
Corresponding authors. Tel.: þ81-58-237-3931; fax: þ81-58-237-5979;
e-mail address: sajiki@gifu-pu.ac.jp
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.05.098

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T. Ikawa et al. / Tetrahedron 60 (2004) 6901–6911
Table 1. Solvent effect toward the deprotection of the TBDMS ether (1a) using 10% Pd/Ca
Entry
Solvent
Relative yield (%)b
2a
3a
1
2
3
4
5
6
7
8
MeOHc
EtOH
0
34
92
23
86
89
87
98
100
66
8
77
14
11
13
2
tBuOH
H2O
Hexane
Cyclohexane
DMF
THF
9
10
11
Toluene
EtOAc
MeCN
100
100
100
0
0
0
a
10% Pd/C was purchased from Aldrich (Aldrich product number 20,569-9).
Determined by 1H NMR.
No reaction was observed under Ar.
b
c
hydrogen and Pd/C were essential for the deprotection of the
TBDMS group.8
small amount of H2O consisted of a homogeneous layer
(single layer) and, no cleavage of the TBDMS ether was
observed (entry 4).
The effect of the addition of a small amount of MeOH or
H2O (0.1 mL of MeOH or H2O/1 mL of EtOAc or MeCN)
into the reaction mixture of TBDMS ether (1a) under 10%
Pd/C-catalyzed hydrogenation conditions in AcOEt or
MeCN is summarized in Table 2. The addition of MeOH
or H2O into the reaction mixture did not affect cleavage of
the TBDMS ether at all and the olefin of 1a was reduced
selectively to form TBDMS ether (2a) in high yield (entries
1, 3 and 4). These data imply that AcOEt or MeCN strongly
coordinates with the Pd metal to compete with the reacting
substance and decreases the catalyst activity toward the
deprotection of the TBDMS ether.10 When a small amount
of H2O was added into the reaction mixture in AcOEt as a
solvent, partial TBDMS deprotection was exceptionally
observed for the following reason (entry 2). The reaction
mixture of entry 2 separated into two layers (H2O and
AcOEt), and the deprotection of TBDMS progressed in the
aqueous layer as well as in Table 1, entry 4. On the other
hand, the reaction mixture in MeCN in the presence of a
To further explore the solvent effect toward the deprotection
of various kinds of silyl ethers, we carried out the Pd/
C-catalyzed hydrogenation reaction of TBDMS, TES
(triethylsilyl), TPS (triphenylsilyl), TBDPS (tert-butyldi-
phenylsilyl) and TIPS (triisopropylsilyl) ethers in several
solvents (Table 3). While TIPS (1d) and TBDPS ethers (1e)
were stable under hydrogenation conditions using Pd/C
even in MeOH (entries 4 and 5), TES (1b) and TPS ethers
(1c) were completely deprotected in MeOH as well as the
TBDMS ether (1a) (entries 1–3). The cleavage of silyl
ethers was apparently depressed in aprotic solvents such as
THF and EtOAc (entries 6–8 and 11–13) and silyl ethers
were nearly stable in MeCN (entries 16–18). Although a
small amount of TBDMS deprotection was observed in
THF, it was entirely stable in AcOEt and MeCN (compare
entries 6 with 11 and 16). In THF and AcOEt, the TES ether
(1b) was partially cleaved, but it was completely suppressed
by the use of MeCN as a solvent (entry 17). On the other
Table 2. Effect of the addition of a small amount of MeOH or H2O into the reaction mixture of TBDMS ether (1a) in AcOEt or MeCN using 10% Pd/Ca as a
catalyst
Entry
Solvent
Additiveb
Product
Yield (%)c
1
2
3
4
EtOAc
EtOAc
MeCN
MeCN
MeOH
H2O
MeOH
H2O
2a
2a (26),d 3a (74)d
2a
2a
86
—
100
75
a
10% Pd/C was purchased from Aldrich (Aldrich product number 20,569-9).
0.1 mL of an additive/1 mL of EtOAc or MeCN.
Isolated yield.
The ratio was determined by 1H NMR.
b
c
d

T. Ikawa et al. / Tetrahedron 60 (2004) 6901–6911
6903
Table 3. Solvent effect toward the deprotection of various kinds of silyl
ethers using 10% Pd/Ca
hand, partial TPS deprotection was observed in THF and
MeCN while no cleavage of the TPS ether (1c) in AcOEt
was achieved. Needless to say, TBDPS and TIPS ethers
were quite stable under Pd/C-catalyzed hydrogenation
condition in aprotic solvents (entries 9, 10, 14, 15, 19 and
20).
Next, we applied the present solvent effect to the
chemoselective hydrogenation of some reducible function-
alities in the presence of silyl ethers in AcOEt or MeCN and
to the mild deprotection method of silyl ethers in MeOH.
TBDMS or TES ethers (1f–m) possessing olefin or
acetylene within a molecule were hydrogenated in MeOH,
AcOEt or MeCN (Table 4). The reduction of olefin and the
deprotection of the alkyl-O-TBDMS ether of 1f or 1g
simultaneously proceeded to afford the corresponding
saturated alcohols (3f or 3g) (entries 1 and 3). However,
the cleavage of the TBDMS group of 1h and 1n–q was
incomplete under the hydrogenation conditions because of
steric hindrance or an electronic factor (entry 5 and Fig. 1).
In AcOEt olefin and benzyl ether functionalities of 1f–h
were hydrogenated chemoselectively to form the corre-
sponding TBDMS ethers (2f–h) (entries 2, 4 and 6).
Entry
Substrate
X
Solvent
Relative yield
(%)b
2a–e
3a
1
2
3
4
5
1a
1b
1c
1d
1e
TBDMS
TES
TPS
TIPS
TBDPS
MeOH
MeOH
MeOH
MeOH
MeOH
0
0
0
100
100
100
100
100
0
0
6
7
8
9
10
1a
1b
1c
1d
1e
TBDMS
TES
TPS
TIPS
TBDPS
THF
THF
THF
THF
THF
98
63
62
100
100
2
37
38
0
0
11
12
13
14
15
1a
1b
1c
1d
1e
TBDMS
TES
TPS
TIPS
TBDPS
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
100
67
100
100
100
0
33
0
0
0
On the other hand, the TES ethers of primary (1i or j),
secondary (1k), tertiary (1l) and phenolic (1m) alcohols
possessing an olefin or acetylene functionality within the
molecule were reduced and cleaved smoothly under the
hydrogenation conditions in MeOH (entries 7, 9, 11, 13 and
15). On the contrary, during the hydrogenation of an olefin
or acetylene functionality, the deprotection of the TES ether
of aliphatic alcohols was not observed in MeCN (entries 8,
10, 12 and 14). While the TBDMS protective group of
16
17
18
19
20
1a
1b
1c
1d
1e
TBDMS
TES
TPS
TIPS
TBDPS
MeCN
MeCN
MeCN
MeCN
MeCN
100
100
97
100
100
0
0
3
0
0
a
10% Pd/C was purchased from Aldrich (Aldrich product number
20,569-9).
b
Determined by 1H NMR.
Table 4. Cleavage of the TBDMS or TES ethers and chemoselective hydrogenation using 10% Pd/Ca
Entry
1
Substrate
Solvent
MeOH
2:3b
Product
Yield (%)c
80
0:100
1f
3f
2f
2
AcOEt
100:0
98
3
4
MeOH
AcOEt
0:100
100:0
71
98
1g
3g
2g
5
6
MeOH
AcOEt
92:8
—
2h þ
1h
3h
2h
100:0
100
(continued on next page)

6904
T. Ikawa et al. / Tetrahedron 60 (2004) 6901–6911
Table 4 (continued)
Entry
Substrate
Solvent
MeOH
2:3b
Product
Yield (%)c
94d (67)e
7
8
0:100
1i
3f
2i
MeCN
100:0
99
9
MeOH
MeCN
0:100
100:0
92d (45)e
1j
3j
2j
10
88
11
12
MeOH
MeCN
0:100
100:0
90d (21)e
1k
3k
2k
93
13
14
MeOH
MeCN
0:100
100:0
96
98
1l
3l
2l
15
16
MeOH
MeCN
0:100
3:97
83
1m
3m
2m
-
þ3m
a
10% Pd/C was purchased from Aldrich (Aldrich product number 20,569-9).
Determined by 1H NMR.
Isolated yield.
Product contaminated with a small amount of TES-OH.
The yield of isolated and analytically pure product is indicated in parentheses. The low isolated yield is due to the volatile nature of the product and difficulty
using silica gel column chromatography.
b
c
d
e
phenolic alcohols (1h and 1q) was quite stable even in
MeOH (entry 5 and Fig. 1), the TES protective group of the
phenolic alcohol (1m) was deprotected easily not only in
MeOH but also even in MeCN (entries 15 and 16).
Manipulation of functional groups is a fundamental process
in synthetic organic chemistry and, hence, the development
of new selective transformations remains of great interest.11
Since hydroxyl groups are quite general functionalities of
organic compounds, the development of a new, selective
removal method of a specific protective group of hydroxyl
groups among various protective groups is extremely
Figure 1. Cleavage of TBDMS ether in MeOH using 10% Pd/C (the ratio of
desilylated mother alcohol was indicated in parentheses).
important.1,12 To examine the scope of our deprotection

T. Ikawa et al. / Tetrahedron 60 (2004) 6901–6911
6905
Table 5. Selective deprotection under hydrogenation conditions in MeOH
using 10% Pd/Ca
distinguished from TBDMS and TES ethers can be achieved
using 10% Pd/C-catalyzed hydrogenation conditions in
AcOEt or MeCN as a solvent. Since catalytic hydrogenation
using Pd/C as a catalyst has found numerous applications in
organic synthesis, the present solvent effect is extremely
important information for synthetic organic chemists. The
present mild and neutral deprotection method of TBDMS
and TES protective groups will serve as a useful
complement to the existing methodologies.
Entry
1
Substrate
Time (h)
30
Product
Yield (%)b
86
1r
1s
1t
3r
3r
2
26
10
36
41
24
61
100
95
3
3r
4. Experimental
4.1. General
4c
5
1u
1v
3u
3v
91
1H and 13C NMR spectra were recorded on a JEOL EX-400
spectrometer, JEOL AL-400 spectrometer (1H: 400 MHz,
13C: 100 MHz), or a GL-270 spectrometer (1H: 270 MHz)
with tetramethylsilane or residual protiated solvent used as a
reference. EI and FAB Mass spectra were taken on a JEOL
JMS-SX102A instrument. Elemental analyses were per-
formed by YANACO CHN CORDER MT-5 instrument.
Column chromatography was performed using Merck silica
gel 60 (230–400 mesh). HPLC grade MeOH and H2O and
anhydrous EtOH were purchased from Wako Pure Chemical
Industries, Ltd. and used without further purification.
Anhydrous hexane, cyclohexane, DMF, toluene, AcOEt
and MeCN were purchased from Kanto Kagaku Co., Ltd.
and used without further purification. THF was distilled
from sodium benzophenone ketyl immediately prior to use.
tBuOH and CH2Cl2 were distilled on CaH2. 10% Pd/C was
purchased from Aldrich (product number: 20,569-9). All
other reagents were purchased from commercial sources
and used without further purification.
6
47d
1w
3w
a
10% Pd/C was purchased from Aldrich (Aldrich product number 20,569-
9).
Isolated yield.
This reaction was performed in EtOAc.
The low isolated yield is due to the volatile nature of the product and
difficulty using silica gel column chromatography.
b
c
d
method using hydrogenation conditions, we have carried out
a selective deprotection of Bn, TBDMS and TES protective
groups of alcohols in the presence of other protective
groups. The stability of the TIPS and TBDPS groups under
the hydrogenation conditions (Table 3, entries 4 and 5) has
been exploited for the selective deprotection of benzyl (1r
and 1u), TBDMS (1s) and TES ethers (1t and 1v) in the
presence of TIPS or TBDPS ether within the molecule. The
results shown in Table 5 demonstrate that the selective
deprotection of benzyl, TBDMS and TES ethers can be
successfully carried out in the presence of TIPS or TBDPS
ether using 10% Pd/C in MeOH or AcOEt as a solvent
(entries 1–5).12 The present procedure can be also applied
to the chemoselective cleavage of a TES ether as
distinguished from an acetal-type protective group (1w)
(entry 6). Accordingly, this method may serve as a useful
component to the existing methodologies and find appli-
cations in the synthesis of complicated molecules.
4.2. General procedure for the synthesis of silyl ethers
Method A. To a solution of an alcohol, DMAP (0.01 equiv.),
and Et3N (1.2 equiv.) in CH2Cl2 (20 mL) was added silyl
chloride (1.1 equiv.). The reaction mixture was stirred at
room temperature for 24 h. The reaction mixture was diluted
with ether (50 mL) and washed with water (50 mL) and
brine (50 mL). The organic layer were dried over Na2SO4,
filtered, and concentrated under reduced pressure. The crude
product was purified by flash column chromatography on
silica gel.
3. Conclusion
Method B. To a solution of an alcohol and imidazole
(1.2 equiv.) in CH2Cl2 (20 mL) was added silyl chloride
(1.2 equiv.). The reaction mixture was stirred at room
temperature for 24 h. The reaction mixture was diluted with
ether (50 mL) and washed with water (50 mL) and brine
(50 mL). The organic layer was dried over Na2SO4, filtered,
and concentrated under reduced pressure. The crude product
was purified by flash column chromatography on silica gel.
In summary, the cleavage of TBDMS, TES and TPS ethers
under hydrogenation conditions using 10% Pd/C indicates
significant solvent effect. While TIPS and TBDPS ethers
were quite stable under the hydrogenation conditions in
MeOH, THF, AcOEt and MeCN, TBDMS and TES
protective groups were readily cleaved in MeOH. Conse-
quently, Pd/C-catalyzed hydrogenation in MeOH can be
applied to the convenient and neutral8 deprotection method
of TBDMS and TES protective groups in the presence of
other protective groups. In contrast, the TBDMS ether was
not deprotected under the hydrogenation conditions in
AcOEt and MeCN at all, and the TES ether was stable in
MeCN. Thus, chemoselective hydrogenation of reducible
functionalities such as olefin, acetylene and benzyl ethers, as
4.2.1. 1-tert-Butyldimethylsilyloxy-3-phenyl-2-propene
(1a).13 With Method A, cinnamyl alcohol (1.34 g,
10.0 mmol), DMAP (48 mg, 0.40 mmol), Et3N (1.21 g,
12.0 mmol), and tert-butyldimethylsilyl chloride (904 mg,
12.0 mmol). The crude product was purified by column
chromatography on silica gel (eluting with hexane) to give
the title compound (1a) as a colorless oil (2.20 g, 90%).

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T. Ikawa et al. / Tetrahedron 60 (2004) 6901–6911
1H NMR (CDCl3): d 7.38–7.20 (m, 5H), 6.59 (d, J¼
15.9 Hz, 1H), 6.28 (dt, J¼4.9, 15.9 Hz, 1H), 4.35 (d, J¼
4.9 Hz, 2H), 0.94 (s, 9H), 0.11 (s, 6H). 13C NMR (CDCl3): d
137.1, 129.5, 129.1, 128.4, 127.3, 126.4, 63.9, 26.0, 18.4,
25.2.
NMR (CDCl3): d 137.2, 135.6, 133.6, 129.7, 129.4, 128.7,
128.5, 127.7, 127.3, 126.4, 64.5, 26.8, 19.3.
4.2.6. 1-tert-Butyldimethylsilyloxy-9-decene (1f).16 With
Method A, 9-decen-1-ol (1.56 g, 10.0 mmol), DMAP
(48 mg, 0.40 mmol), Et3N (1.20 g, 12.0 mmol), and tert-
butyldimethylsilyl chloride (1.66 g, 11.0 mmol). The crude
product was purified by column chromatography on silica
gel (eluting with hexane) to give the title compound (1f) as a
colorless oil (1.81 g, 67%).
4.2.2. 1-Triethylsilyloxy-3-phenyl-2-propene (1b).14 With
Method B, cinnamyl alcohol (671 mg, 5.00 mmol), imida-
zole (408 mg, 6.00 mmol), and triethylsilyl chloride
(904 mg, 1.20 mmol). The crude product was purified by
column chromatography on silica gel (eluting with hexane)
to give the title compound (1b) as a colorless oil (717 mg,
93%).
1H NMR (CDCl3): d 5.89–5.73 (m, 1H), 5.30–4.90 (m,
2H), 3.59 (t, J¼5.6 Hz, 2H), 2.07–2.00 (m, 2H), 1.53–1.29
(m, 12H), 0.89 (s, 9H), 0.05 (s, 6H). 13C NMR (CDCl3): d
139.1, 114.1, 63.3, 33.8, 32.9, 29.5, 29.4, 29.1, 29.0, 26.0,
25.8, 18.4, 25.3.
1H NMR (CDCl3): d 7.37 (d, J¼7.5 Hz, 2H), 7.30 (t, J¼
7.5 Hz, 2H), 7.22 (t, J¼7.5 Hz, 1H), 6.60 (d, J¼16.1 Hz,
1H), 6.29 (dt, J¼5.1, 16.1 Hz, 1H), 4.35 (d, J¼5.1 Hz, 2H),
0.99 (t, J¼7.9 Hz, 9H), 0.66 (q, J¼7.9 Hz, 6H).
4.2.7. 4-tert-Butyldimethylsilyloxy-1-butyl acrylate (1g).
With Method A, 4-hydroxybutyl acrylate (2.88 g,
20.0 mmol), DMAP (98 mg, 0.80 mmol), Et3N (2.23 g,
22.0 mmol), and tert-butyldimethylsilyl chloride (3.17g,
21.0 mmol). The crude product was purified by column
chromatography on silica gel (eluting with hexane) to give
the title compound (1g) as a colorless oil (5.04 g, 98%).
4.2.3. 1-Triphenylsilyloxy-3-phenyl-2-propene (1c). With
Method B, cinnamyl alcohol (671 mg, 5.00 mmol), imida-
zole (408 mg, 6.00 mmol), and triphenylsilyl chloride
(1.77 g, 6.00 mmol). The crude product was purified by
column chromatography on silica gel (eluting with hexane)
to give the title compound (1c) as a colorless needles
(1.14 g, 58%).
1H NMR (CDCl3): d 6.40 (dd, J¼1.3, 17.5 Hz, 1H), 6.12
(dd, J¼1.05, 17.5 Hz, 1H), 4.18 (t, J¼6.5 Hz, 2H), 3.65
(t, J¼6.5 Hz, 2H), 1.78–1.71 (m, 2H), 1.64–1.57 (m, 2H),
0.89 (s, 9H), 0.05 (s, 6H). 13C NMR (CDCl3): d 166.0,
130.2, 128.6, 64.3, 62.4, 29.1, 25.8, 25.2, 18.2, 25.5. MS
(EI) m/z 201 (Mþ2C4H9, 10%), 129 (100), 75 (15), 55 (35).
HRMS (EI) calcd for C9H17O3Si (Mþ2C4H9) 201.0947.
Found 201.0939.
1H NMR (CDCl3): d 7.67 (dd, J¼1.47, 7.82 Hz, 6H), 7.48–
7.19 (m, 14H), 6.59 (d, J¼15.9 Hz, 1H), 6.29 (dt, J¼5.1,
15.9 Hz, 1H), 4.51 (dd, J¼1.47, 4.63 Hz, 2H). 13C NMR
(CDCl3): d 136.9, 135.4, 134.0, 130.1, 130.1, 128.4, 128.2,
127.9, 127.3, 126.4, 64.5. MS (EI) m/z 392 (Mþ, 24%), 314
(22), 260 (22), 259 (100), 236 (23), 199 (45), 181 (22), 117
(16), 115 (15). Anal. Calcd for C27H24OSi: C, 82.61; H,
6.16. Found C, 82.49; H, 6.19.
4.2.8. 1-tert-Butyldimethylsilyloxy-2-(2-propenyl)ben-
zene (1h).17 With Method B, 2-allylphenol (1.34 g,
10.0 mmol), imidazole (1.36 g, 20.0 mmol), and tert-
butyldimethylsilyl chloride (1.80 g, 12.0 mmol). The
crude product was purified by column chromatography on
silica gel (eluting with hexane) to give the title compound
(1h) as a colorless oil (1.89 g, 76%).
4.2.4. 1-Triisopropylsilyloxy-3-phenyl-2-propene (1d).
With Method B, cinnamyl alcohol (671 mg, 5.00 mmol),
imidazole (408 mg, 6.00 mmol), and triisopropylsilyl
chloride (1.16 g, 6.00 mmol). The crude product was
purified by column chromatography on silica gel (eluting
with hexane) to give the title compound (1d) as a colorless
oil (1.22 g, 85%).
1H NMR (CDCl3): d 7.13 (d, J¼7.6 Hz, 1H), 7.08 (t,
J¼7.6 Hz, 1H), 6.89 (t, J¼7.6 Hz, 1H), 6.78 (d, J¼7.6 Hz,
1H), 6.02–5.92 (m, 1H), 5.05 (s, 1H), 5.02 (d, J¼3.9 Hz,
1H), 3.37 (d, J¼6.8 Hz, 2H), 1.01 (s, 9H), 0.23 (s, 6H). 13C
NMR (CDCl3): d 153.4, 137.0, 130.7, 130.2, 127.0, 121.1,
118.4, 115.4, 34.4, 25.8, 18.3, 24.1.
1H NMR (CDCl3): d 7.42–7.24 (m, 5H), 6.67 (d, J¼
15.6 Hz, 1H), 6.34 (dt, J¼15.6, 4.9 Hz, 1H), 4.46 (dd,
J¼4.9, 1.5 Hz, 2H), 1.21–1.12 (m, 3H and 18H). 13C NMR
(CDCl3): d 137.3, 129.4, 129.0, 128.5, 127.2, 126.4, 63.9,
18.0, 12.1. MS (EI) m/z 290.5 (Mþ, 20%), 248 (21), 247
(100), 117 (47), 115 (15). HRMS (EI) calcd for C18H30OSi
(Mþ) 290.2066. Found 290.2057.
4.2.9. 1-Triethylsilyloxy-9-decene (1i). With Method A,
9-decene-1-ol (753 mg, 4.80 mmol), DMAP (110 mg,
0.90 mmol), triethylsilyl chloride (1.00 g, 7.23 mmol) in
pyridine (10 mL) used as a solvent instead of CH2Cl2. The
crude product was purified by column chromatography on
silica gel (eluting with hexane) to give the title compound
(1i) as a colorless oil (1.11 g, 85%).
4.2.5. 1-tert-Butyldiphenylsilyloxy-3-phenyl-2-propene
(1e).15 With Method B, cinnamyl alcohol (335 mg,
2.50 mmol), imidazole (204 mg, 3.00 mmol), and tert-
butyldiphenylsilyl chloride (825 mg, 3.00 mmol). The
crude product was purified by column chromatography on
silica gel (eluting with hexane) to give the title compound
(1e) as a colorless oil (799 mg, 86%).
1H NMR (CDCl3): d 5.86–5.76 (m, 1H), 4.99 (dd, J¼2.0,
17.1 Hz, 1H), 4.92 (dd, J¼2.0, 10.3 Hz, 1H), 3.59 (t, J¼
6.8 Hz, 2H), 2.03 (q, J¼7.0 Hz, 2H), 1.55–1.51 (m, 2H),
1.37–1.29 (m, 10H), 0.95 (t, J¼8.0 Hz, 9H), 0.60 (q, J¼
8.0 Hz, 6H). 13C NMR (CDCl3): d 139.2, 114.1, 63.0, 33.8,
32.9, 29.5, 29.4, 29.1, 28.9, 25.8, 6.8, 4.5. MS (EI) m/z 271
1H NMR (CDCl3): d 7.71 (dd, J¼1.5, 7.8 Hz, 4H), 7.45–
7.20 (m, 11H), 6.64 (d, J¼15.6 Hz, 1H), 6.28 (dt, J¼4.9,
15.6 Hz, 1H), 4.38 (d, J¼4.9 Hz, 2H), 1.09 (s, 9H). 13C

T. Ikawa et al. / Tetrahedron 60 (2004) 6901–6911
6907
(Mþ2C2H5), 213 (15%), 103 (100), 75 (33), 57 (15), 55
(14). HRMS (EI) calcd for C16H34OSi (Mþ2C2H5)
241.1975. Found 241.1988.
2H), 1.00 (t, J¼7.7 Hz, 6H), 0.77 (q, J¼7.7 Hz, 9H). 13C
NMR (CDCl3): d 153.5, 137.1, 130.6, 130.0, 127.0, 121.0,
118.2, 115.3, 34.5, 6.7, 5.3. MS (FAB, NBA) m/z 249
(MþþH, 10%), 248 (15), 219 (11). HRMS (EI) calcd for
C15H24OSi (Mþ) 248.1597. Found 248.1623.
4.2.10. Geranyl triethylsilyl ether (1j).18 With Method
B, geraniol (771 mg, 5.00 mmol), imidazole (409 mg,
6.00 mmol), and triethylsilyl chloride (904 mg, 6.00
mmol). The crude product was purified by column
chromatography on silica gel (eluting with hexane) to give
the title compound (1j) as a colorless oil (1.07 g, 86%).
4.2.14. 1-tert-Butyldimethylsilyloxy-2-phenylethane
(1n).19 With Method B, 2-phenylethan-1-ol (335 mg,
2.50 mmol), imidazole (204 mg, 3.00 mmol), and tert-
butyldimethyl chloride (825 mg, 3.00 mmol). The crude
product was purified by column chromatography on silica
gel (eluting with hexane) to give the title compound (1n) as
a colorless oil (799 mg, 86%).
1H NMR (CDCl3): d 5.33 (t, J¼6.0 Hz, 1H), 5.10 (t,
J¼7.3 Hz, 1H), 4.18 (d, J¼6.0 Hz, 2H), 2.10 (q, J¼7.3 Hz,
2H), 2.01 (t, J¼7.3 Hz, 2H), 1.67 (s, 3H), 1.63 (s, 3H), 1.60
(s, 3H), 0.97 (t, J¼8.0 Hz, 9H), 0.61 (q, J¼8.0 Hz, 6H).
HRMS (EI) calcd for C16H32OSi (Mþ): 268.2222. Found:
268.2230.
1H NMR (CDCl3): d 7.67 (dd, J¼1.5, 7.8 Hz, 4H), 7.44–
7.15 (m, 16H), 3.69 (t, J¼6.4 Hz, 2H), 2.72 (t, J¼7.8 Hz,
2H), 1.91–1.84 (m, 2H), 1.07 (s, 9H).
4.2.11. 7-Methyl-5-triethylsilyloxy-3-octyne (1k). With
Method B, 2-methyl-5-octyne-4-ol (701 mg, 5.00 mmol),
imidazole (408 mg, 6.00 mmol), and triethylsilyl chloride
(904 mg, 6.00 mmol). The crude product was purified by
column chromatography on silica gel (eluting with hexane)
to give the title compound (1k) as a colorless oil (1.09 g,
86%).
4.2.15. 1-tert-Butyldimethylsilyloxy-4-tert-butylcyclo-
hexane (1o).15 With Method A, 4-tert-butylcyclohexanol
(781 mg, 5.00 mmol), DMAP (48 mg, 0.40 mmol), Et3N
(607 mg, 6.00 mmol), and tert-butyldimethylsilyl chloride
(904 mg, 6.00 mmol). The crude product was purified by
column chromatography on silica gel (eluting with hexane)
to give the title compound (1o) as a colorless oil (718 mg,
53%).
1H NMR (CDCl3): d 4.38 (t, J¼7.1 Hz, 1H), 2.20 and 2.19
(each q, J¼7.4 Hz, 1H), 1.84–1.78 (m, 1H), 1.61–1.43 (m,
2H), 1.12 (t, J¼7.4 Hz, 3H), 0.98 (t, J¼7.8 Hz, 9H), 0.91
and 0.90 (each d, J¼6.6 Hz, 3H), 0.72–0.62 (m, 6H). 13C
NMR (CDCl3): d 85.6, 81.4, 61.4, 48.2, 24.6, 22.7, 22.5,
13.8, 12.4, 6.8, 4.9. MS (EI) m/z 225 (Mþ2C2H5, 100%),
197 (35), 171 (18), 141 (20), 111 (36), 103 (21), 75 (19), 44
(24). HRMS (EI) calcd for C15H30OSi (Mþ2C2H5)
225.1634. Found 225.1675.
1H NMR (CDCl3): d 3.51–3.43 (m, 1H), 1.89–1.86 (m,
2H), 1.75–1.72 (m, 2H), 1.29–1.21 (m, 2H), 1.04–0.91 (m,
3H), 0.88 (s, 9H), 0.84 (s, 9H), 0.05 (s, 6H).
4.2.16. (2)-Menthyl tert-butyldimethylsilyl ether (1p).20
With Method A, (2)-menthol (781 mg, 5.00 mmol), DMAP
(48 mg, 0.40 mmol), Et3N (607 mg, 6.00 mmol), and tert-
butyldimethylsilyl chloride (904 mg, 6.00 mmol). The
crude product was purified by column chromatography on
silica gel (eluting with hexane) to give the title compound
(1p) as a colorless oil (639 mg, 47%).
4.2.12. 1-Phenyl-3-methyl-3-triethylsilyloxy-1-pentyne
(1l). With Method B, 1-phenyl-3-methyl-1-pentyne-3-ol
(871 mg, 5.00 mmol), imidazole (613 mg, 9.00 mmol),
and triethylsilyl chloride (1.36 g, 9.00 mmol). The crude
product was purified by column chromatography on silica
gel (eluting with hexane) to give the title compound (1l) as a
colorless oil (1.31 g, 91%).
1H NMR (CDCl3): d 3.37 (dt, J¼4.2, 10.3 Hz, 1H), 3.40–
3.34 (m, 1H), 2.60–2.18 (m, 1H), 1.86–1.83 (m, 1H), 1.64–
1.57 (m, 1H), 1.38–1.32 (m, 1H), 1.58–1.09 (m, 1H), 1.04–
0.77 (m, 4H), 0.90 (s, 6H), 0.88 (s, 9H), 0.72 (d, J¼6.8 Hz,
3H), 0.06 (s, 3H), 0.05 (s, 3H).
1H NMR (CDCl3): d 7.41–7.38 (m, 2H), 7.31–7.29 (m,
3H), 1.79–1.68 (m, 2H), 1.55 (s, 3H), 1.04 (t, J¼7.3 Hz,
3H), 0.98 (t, J¼7.7 Hz, 9H), 0.71 (q, J¼7.7 Hz, 6H). 13C
NMR (CDCl3): d 131.4, 128.3, 128.0, 123.3, 93.8, 83.5,
70.0, 38.2, 30.5, 9.1, 7.1, 6.1. MS (EI) m/z 259 (Mþ2C2H5,
100%), 187 (10), 149 (13), 61 (9), 44 (53). HRMS (EI) calcd
for C16H23OSi (Mþ2C2H5) 259.1518. Found 259.1523.
4.2.17. 1-tert-Butyldimethylsilyloxy-4-tert-butylbenzene
(1q).21 With Method A, 4-tert-butylphenol (751 mg,
5.00 mmol), DMAP (48 mg, 0.40 mmol), Et3N (607 mg,
6.00 mmol), and tert-butyldimethylsilyl chloride (904 mg,
6.00 mmol). The crude product was purified by column
chromatography on silica gel (eluting with hexane) to give
the title compound (1q) as a colorless oil (743 mg, 56%).
4.2.13. 1-Triethylsilyloxy-2-(2-propenyl)benzene (1m).
With Method B, 2-allylphenol (671 mg, 5.00 mmol),
imidazole (408 mg, 6.00 mmol), and triethylsilyl chloride
(904 mg, 6.00 mmol). The crude product was purified by
column chromatography on silica gel (eluting with hexane)
to give the title compound (1m) as a colorless oil (1.27 g,
85%).
1H NMR (CDCl3): d 7.22 and 6.75 (each d, J¼8.3 Hz, 4H),
1.28 (s, 9H), 0.97 (s, 9H), 0.19 (s, 6H).
4.2.18. 1-Benzyloxy-3-triisopropylsilyloxypropane (1r).
With Method B, 3-benzyloxy-1-propanol (831 mg,
5.00 mmol), imidazole (408 mg, 6.00 mmol), and triiso-
propylsilyl chloride (1.16 g, 6.00 mmol). The crude product
was purified by column chromatography on silica gel
(eluting with hexane/ether 10:1) to give the title compound
(1r) as a colorless oil (1.46 g, 91%).
1H NMR (CDCl3): d 7.12 (d, J¼7.6 Hz, 1H), 7.07 (t, J¼
7.6 Hz, 1H), 6.88 (t, J¼7.6 Hz, 1H), 6.78 (d, J¼7.6 Hz, 1H),
6.02–5.92 (m, 1H), 5.07–5.02 (m, 2H), 3.37 (d, J¼6.4 Hz,

6908
T. Ikawa et al. / Tetrahedron 60 (2004) 6901–6911
1H NMR (CDCl3): d 7.34–7.26 (m, 5H), 4.51 (s, 2H), 3.80
(t, J¼6.2 Hz, 2H), 3.60 (t, J¼6.2 Hz, 2H), 1.88–1.82 (m,
2H), 1.11–1.00 (m, 2H). 13C NMR (CDCl3): d 138.7, 128.3,
127.6, 127.4, 73.0, 67.2, 60.2, 33.2, 18.0, 12.0. MS (FAB,
NBA) m/z 323 (MþþH, 12%), 91 (100). HRMS (FAB,
NBA) calcd for C19H35O2Si (MþþH) 323.2406. Found
323.24103.
column chromatography on silica gel (eluting with hexane)
to give the title compound (1u) as a colorless oil (1.26 g,
90%).
1H NMR (CDCl3): d 7.34–7.26 (m, 5H), 4.50 (s, 2H), 3.72
(t, J¼6.4 Hz, 2H), 3.57 (t, J¼6.4 Hz, 2H), 1.82 (m, 2H),
0.89 (s, 9H), 0.05 (s, 6H). 13C NMR (CDCl3): d 138.6,
128.3, 127.6, 127.4, 72.9, 67.0, 59.9, 33.0, 25.9, 18.3, 25.4.
MS (FAB, NBA) m/z 281 (MþþH, 28%), 91 (100), 73 (19).
HRMS (FAB, NBA) calcd for C16H29O2Si (MþþH)
281.1937. Found 281.1933.
4.2.19. 1-tert-Butyldimethylsiyloxy-3-triisopropylsilyl-
oxypropane (1s).22 After two vacuum/H2 cycles to remove
air from the reaction tube, the stirred mixture of 1-benzyl-
oxy-3-triisopropylsilyloxypropane (1r) (1.40 g, 5.00 mmol),
10% Pd/C (70.1 mg, 5 wt% of the substrate) in solvent
(10 mL) was hydrogenated at ambient pressure (balloon)
and temperature (ca. 20 8C) for 24 h. The reaction mixture
was filtered using a membrane filter (Millexw-LG, 0.20 mm)
and the filtrate was concentrated under reduced pressure.
The crude product was purified by flash column chroma-
tography on silica gel (eluting with hexane/ether 5:1) to
afford 3-triisopropylsilyloxypropan-1-ol (3r) as a colorless
4.2.22. 1-tert-Butyldiphenylsiyloxy-3-triethylsilyloxypro-
pane (1v). To a solution of 1,3-propandiol (761 mg,
10.0 mmol), diisopropylethylamine (1.29 g, 10.0 mmol) in
CH2Cl2 (20 mL) was added tert-butyldiphenylsilyl chloride
(2.75 mg, 10.0 mmol). The reaction mixture was stirred at
room temperature for 19 h. The reaction mixture was diluted
with ether (50 mL) and washed with saturated NH4Cl
solution (50 mL), and brine (50 mL). The organic layer was
dried over Na2SO4, filtered, and concentrated under reduced
pressure. The crude product was purified by flash column
chromatography on silica gel (eluting with hexane/ether
2:1) to afford 3-tert-butyldiphenylsilyloxypropan-1-ol
1
oil (1.70 g, 73%). H NMR (CDCl3): d 3.94 (t, J¼5.4 Hz,
2H), 3.84 (q, J¼5.4 Hz, 2H), 2.76 (t, J¼5.4 Hz, OH), 1.83–
1.78 (m, 2H), 1.17–1.03 (m, 21H). 13C NMR (CDCl3): d
63.6, 62.7, 34.2, 17.9, 11.8. MS (FAB, NBA) m/z 233
(MþþH, 60%), 189 (36). HRMS (FAB, NBA) calcd for
C12H28O2Si (MþþH) 233.1937. Found 233.1930. With
Method A, 3r (403 mg, 1.70 mmol), DMAP (37 mg,
0.30 mmol), Et3N (202 mg, 2.00 mmol), and tert-butyl-
dimethylsilyl chloride (301 mg, 3.00 mmol). The crude
product was purified by column chromatography on silica
gel (eluting with hexane) to give the title compound (1s) as a
colorless oil (449 mg, 67%).
1
(3v)23 as a colorless oil. H NMR (CDCl3): d 7.68 (dd,
J¼1.5, 7.8 Hz, 4H), 7.46–7.38 (m, 6H), 3.87–3.83 (m, 4H),
2.36 (t, J¼5.6 Hz, OH), 1.84–1.78 (m, 2H), 1.06 (s, 9H).
With Method A, 3v (944 mg, 3.00 mmol), DMAP (37 mg,
0.3 mmol), imidazole (245 mg, 3.60 mmol) instead of Et3N,
and triethylsilyl chloride (453 mg, 3.60 mmol). The crude
product was purified by column chromatography on silica
gel (eluting with hexane/ether 20:1) to give the title
compound (1v) as a colorless oil (1.23 g, 96%).
1H NMR (CDCl3): d 3.76 (t, J¼6.1 Hz, 2H), 3.73 (t, J¼
6.1 Hz, 2H), 1.77–1.71 (m, 2H), 1.13–1.01 (m, 21H), 0.89
(s, 9H), 0.05 (s, 6H). 13C NMR (CDCl3): d 60.0, 59.8, 36.1,
25.9, 18.3, 12.0, 25.4. MS (FAB, NBA) m/z 347 (MþþH,
21%), 303 (40), 157 (25), 115 (28), 73 (100). HRMS (FAB,
NBA) calcd for C18H43O2Si2 (Mþ) 347.2817. Found
347.2802.
1H NMR (CDCl3): d 7.67 (dt, J¼1.5, 7.8 Hz, 4H), 7.44–
7.35 (m, 6H), 3.77–3.73 (m, 4H), 1.81–1.74 (m, 2H), 0.94
(t, J¼8.0 Hz, 9H), 0.59 (q, J¼8.0 Hz, 6H). 13C NMR
(CDCl3): d 135.6, 134.0, 129.5, 127.5, 60.6, 59.6, 35.8, 26.8,
19.2, 6.8, 4.4. MS (FAB, NBA) m/z 429 (MþþH, 10%), 371
(29), 197 (12), 87 (35). Anal. Calcd for C25H40O2Si2: C,
70.03; H, 9.40. Found C, 70.19; H, 9.77.
4.2.20. 1-Triethylsilyloxy-3-triisopropylsilyloxypropane
(1t). With Method A, 3-triisopropylsilyloxypropan-1-ol (3r)
(465 mg, 2.00 mmol), DMAP (49 mg, 0.40 mmol), Et3N
(243 mg, 2.40 mmol), and triethylsilyl chloride (362 mg,
2.40 mmol). The crude product was purified by column
chromatography on silica gel (eluting with hexane/ether
10:1) to give the title compound (1t) as a colorless oil
(603 mg, 87%).
4.2.23. 4,4-Dimethoxy-2-methyl-2-triethylsilyloxybutane
(1w). With Method A, 4,4-dimethoxy-2-methyl-2-butanol
(3w) (741 mg, 5.00 mmol), DMAP (61 mg, 0.50 mmol),
imidazole (408 mg, 6.00 mmol), and triethylsilyl chloride
(904 mg, 6.00 mmol). The crude product was purified by
column chromatography on silica gel (eluting with hexane/
ether 10:1) to give the title compound (1w) as a colorless oil
(1.36 g, 91%).
1H NMR (CDCl3): d 3.77 (t, J¼6.2 Hz, 2H), 3.73 (t, J¼
6.2 Hz, 2H), 1.79–1.73 (m, 2H), 1.11–1.00 (m, 21H), 0.96
(t, J¼8.0 Hz, 9H), 0.60 (q, J¼8.0 Hz, 6H). 13C NMR
(CDCl3): d 60.1, 59.7, 36.2, 18.0, 12.0, 6.8, 4.4. MS (FAB,
NBA) m/z 347 (MþþH, 40%), 303 (62), 245 (28), 157 (40),
115 (99), 87 (82), 59 (40). HRMS (FAB, NBA) calcd for
C18H43O2Si2 (MþþH) 347.2802. Found 347.2806.
1H NMR (CDCl3): d 4.60 (t, J¼4.9 Hz, 1H), 3.31 (s, 6H),
1.75 (d, J¼4.9 Hz, 2H), 1.25 (s, 6H), 0.95 (t, J¼7.8 Hz, 9H),
0.58 (q, J¼7.8 Hz, 6H). 13C NMR (CDCl3): d 102.6, 72.0,
52.5, 47.3, 30.4, 7.1, 6.7. MS (EI) 175 (85), 117 (100), 89
(23), 75 (40). Anal. Calcd for C13H30O3Si 1/3H2O: C,
58.16; H, 11.50. Found C, 82.49; H, 6.19.
4.2.21. 3-tert-Butyldimethylsilyloxy-1-propyl benzyl
ether (1u). With Method A, 3-benzyloxy-1-propanol
(831 mg, 5.00 mmol), DMAP (48 mg, 0.40 mmol), Et3N
(607 g, 6.00 mmol), and tert-butyldimethylsilyl chloride
(904 mg, 6.00 mmol). The crude product was purified by
4.3. General procedure for solvent effect toward the
deprotection of the TBDMS ether (1a) using 10% Pd/C
(Table 1)
After two vacuum/H2 cycles to remove air from the reaction

T. Ikawa et al. / Tetrahedron 60 (2004) 6901–6911
6909
tube, the stirred mixture of 1-tert-butyldimethylsilyloxy-3-
phenyl-2-propene (1a) (62.0 mg, 0.25 mmol), 10% Pd/C
(6.2 mg, 10 wt% of the substrate) in solvent (1 mL) was
hydrogenated at ambient pressure (balloon) and temperature
(ca. 20 8C) for 24 h. The reaction mixture was filtered using
a membrane filter (Millexw-LG, 0.20 mm) and the filtrate
was concentrated under reduced pressure to afford a
colorless oil. (When using H2O as a solvent, ether was
added to the reaction mixture and filtrated using a
membrane filter (Millexw-LG, 0.20 mm). The organic
layer was dried over Na2SO4, filtered and concentrated
under reduced pressure to afford the colorless oil. The ratio
of the 1-tert-butyldimethylsilyloxy-3-phenylpropane (2a)
(86%, entry 10) and 3-phenyl-1-propanol (3a) (88%, entry 1)
was confirmed by 1H NMR of the crude mixture in CDCl3.
4H), 3.83 (t, J¼6.9 Hz, 2H), 2.71 (t, J¼6.9 Hz, 2H), 1.92–
1.88 (m, 2H). 13C NMR (CDCl3): d 142.1, 135.4, 135.2,
134.4, 130.0, 128.5, 128.3, 127.9, 125.7, 63.1, 34.1, 32.1.
MS (FAB, NBA) m/z 395 (MþþH, 40%), 317 (25), 259
(40), 199 (30), 118 (30), 91 (35). Anal. Calcd for C27H26OSi
1/10H2O: C, 81.81; H, 6.66. Found C, 81.87; 6.58.
4.5.3. 1-Triisopropylsilyloxy-3-phenylpropane (2d). 93%
yield as a colorless oil. 1H NMR (CDCl3): d 7.29–7.17 (m,
5H), 3.71 (t, J¼6.1 Hz, 2H), 2.71 (t, J¼7.8 Hz, 2H), 1.89–
1.82 (m, 2H), 1.12–1.04 (m, 3H and 18H). 13C NMR
(CDCl3): d 142.4, 128.5, 128.2, 125.6, 62.6, 34.7, 32.1, 18.0,
12.0, 11.8. MS (EI) m/z 249 (Mþ2C3H7, 100%). HRMS
(EI) calcd for C15H25OSi (Mþ2C3H7) 249.1675. Found
249.1667.
4.3.1. 1-tert-Butyldimethylsilyloxy-3-phenylpropane
1
4.5.4. 1-tert-Butyldiphenylsilyloxy-3-phenylpropane
1
(2a).24 86% yield as a colorless oil (entry 10). H NMR
(2e).25 99% yield as a colorless oil. H NMR (CDCl3): d
(CDCl3): d 7.67 (dd, J¼1.5, 7.8, 4H), 7.44–7.15 (m, 16H),
3.69 (t, J¼6.4 Hz, 2H), 2.72 (t, J¼7.8 Hz, 2H), 1.91–1.84
(m, 2H), 1.07 (s, 9H).
7.67 (dd, J¼1.5, 7.8 Hz, 4H), 7.44–7.15 (m, 16H), 3.69 (t,
J¼6.4 Hz, 2H), 2.72 (t, J¼7.8 Hz, 2H), 1.91–1.84 (m, 2H),
1.07 (s, 9H).
4.4. General procedure for effect of the addition of a
small amount of MeOH or H2O into the reaction mixture
of TBDMS ether (1a) in AcOEt or MeCN using 10% Pd/
C as a catalyst (Table 2)
4.6. General procedure for cleavage of the TBDMS or
TES ethers and chemoselective hydrogenation using
10% Pd/C (Table 4)
After two vacuum/H2 cycles to remove air from the reaction
tube, the stirred mixture of a silyl ether (1f–n) (0.25 mmol),
10% Pd/C (10 wt% of the substrate) in MeOH or AcOEt or
MeCN (1 mL) was hydrogenated at ambient pressure
(balloon) and temperature (ca. 20 8C). The reaction mixture
was filtered using a membrane filter (Millexw-LG, 0.20 mm)
and the filtrate was concentrated under reduced pressure to
afford a colorless oil. The ratio of the corresponding silyl
ether (2f–m) and corresponding alcohol (3f-3m) was
After two vacuum/H2 cycles to remove air from the reaction
tube, the stirred mixture of 1-tert-butyldimethylsilyloxy-3-
phenyl-2-propene (1a) (62.0 mg, 0.25 mmol), 10% Pd/C
(6.2 mg, 10 wt% of the substrate) and MeOH or H2O
(0.1 mL) in EtOAc or MeCN (1 mL) was hydrogenated at
ambient pressure (balloon) and temperature (ca. 20 8C) for
24 h. The reaction mixture was filtered using a membrane
filter (Millexw-LG, 0.20 mm,) and the filtrate was concen-
trated under reduced pressure to afford the colorless oil. The
ratio of the 1-tert-butyldimethylsilyloxy-3-phenylpropane
1
confirmed by H NMR of the crude mixture in CDCl3.
The crude material was purified by flash column chroma-
tography on silica gel (eluting with hexane/ether 20:1 for 3f,
hexane/ether 10:1 for 3g, hexane/ether 10:1 for 3k, hexane/
ether 10:1 for 3l, hexane/ether 20:1 for 3n) to give 3f (80%,
entry 1), 3f (67%, entry 7), 3g (71%), 3k (21%), 3l (96%),
3m (83%) as a colorless oil. 1H NMR were comparable with
each authentic sample.
1
(2a) and 3-phenyl-1-propanol (3a) was confirmed by H
NMR of the crude mixture in CDCl3.
4.5. General procedure for solvent effect toward the
deprotection of the silyl ethers using 10% Pd/C (Table 3)
After two vacuum/H2 cycles to remove air from the reaction
tube, the stirred mixture of a silyl ether (1a–e) (0.25 mmol),
10% Pd/C (10 wt% of the substrate) in solvent (1 mL) was
hydrogenated at ambient pressure (balloon) and temperature
(ca. 20 8C) for 24 h. The reaction mixture was filtered using
a membrane filter (Millexw-LG, 0.20 mm) and the filtrate
was concentrated under reduced pressure to afford the
colorless oil. The ratio of the corresponding silyl ether
(2a–e) and 3-phenyl-1-propanol (3a) was confirmed by 1H
NMR of the crude mixture in CDCl3.
4.6.1. 1-tert-Butyldimethylsilyloxydecane (2f).26 98%
yield as a colorless oil. 1H NMR (CDCl3): d 3.59 (t,
J¼6.6 Hz, 2H), 1.55–1.51 (m, 2H), 1.35–1.26 (m, 14H),
0.89 (s, 9H), 0.88 (t, J¼7.3 Hz, 3H), 0.05 (s, 6H). 13C NMR
(CDCl3): d 63.3, 32.9, 31.9, 29.7, 29.6, 29.5, 29.4, 26.0,
25.8, 22.7, 18.4, 14.1, 25.3.
4.6.2. 4-tert-Butyldimethylsilyloxybutyl propionate (2g).
1
98% yield as a colorless oil. H NMR (CDCl3): d 4.09 (t,
J¼6.3 Hz, 2H), 3.63 (t, J¼6.3 Hz, 2H), 2.32 (q, J¼7.7 Hz,
2H), 1.61–1.56 (m, 2H), 1.16–1.12 (m, 2H), 0.89 (s, 9H),
0.05 (s, 6H). 13C NMR (CDCl3): d 174.5, 64.2, 62.6, 29.2,
27.6, 25.9, 25.2, 18.3, 9.2, 25.3. MS (FAB, NBA) m/z 261
(MþþH, 50%), 203 (37), 187 (62), 131 (139), 73 (45), 57
(38). HRMS (FAB, NBA) calcd for C13H29O3Si (MþþH)
261.1886. Found 261.1886.
4.5.1. 1-Triethylsilyloxy-3-phenylpropane (2b).14 91%
yield as a colorless oil. H NMR (CDCl3): d 7.29–7.15
(m, 5H), 3.64 (t, J¼6.4 Hz, 2H), 2.68 (t, J¼7.8 Hz, 2H),
1.89–1.82 (m, 2H), 0.96 (t, J¼8.0 Hz, 9H), 0.60 (q,
J¼8.0 Hz, 6H).
1
4.5.2. 1-Triphenylsilyloxy-3-phenylpropane (2c). 100%
1
yield as a colorless solid. H NMR (CDCl3): d 7.63 (dd,
J¼1.6, 8.1 Hz, 6H), 7.46–7.36 (m, 10H), 7.26–7.11 (m,
4.6.3. 1-tert-Butyldimethylsilyloxy-2-propylbenzene
1
(2h). 100% yield as a colorless oil. H NMR (CDCl3): d

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T. Ikawa et al. / Tetrahedron 60 (2004) 6901–6911
7.12 (d, J¼7.6 Hz, 1H), 7.05 (t, J¼7.6 Hz, 1H), 6.87 (t,
J¼7.6 Hz, 1H), 6.77 (d, J¼7.6 Hz, 1H), 2.55 (t, J¼7.5 Hz,
2H), 1.58 (hex, J¼7.5 Hz, 2H), 1.02 (s, 9H), 0.94 (t, J¼
7.5 Hz, 3H), 0.23 (s, 6H). 13C NMR (CDCl3): d 153.5,
133.3, 130.2, 126.5, 120.9, 118.3, 32.7, 25.8, 23.3, 18.2,
14.1, 24.2. Anal. Calcd for C15H26OSi: C, 71.93; H, 10.46.
Found: C, 71.68; H, 10.60.
tube, the stirred mixture of silyl ether (1r–w) (0.25 mmol),
10% Pd/C (10 wt% of the substrate) in MeOH was
hydrogenated at ambient pressure (balloon) and temperature
(ca. 20 8C). The reaction mixture was filtered using a
membrane filter (Millexw-LG or LH, 0.20 mm, 0.45 mm)
and the filtrate was concentrated under reduced pressure to
afford a colorless oil. The crude material was purified by
flash column chromatography on silica gel (eluting with
hexane/ether 5:1 for 3r, hexane/ether 95:5 for 3v, hexane/
ether 10:1 for 3w) to give 3r (86%, entry 1), (61%, entry 2),
(100%, entry 3), 3u (95%), 3v (91%) and 3w (47%) as
colorless oils. These samples were identified with commer-
cial samples.
4.6.4. 1-Triethylsilyloxydecane (2i). 99% yield as a
1
colorless oil. H NMR (CDCl3): d 3.59 (t, J¼6.6 Hz, 2H),
1.54–1.51 (m, 2H), 1.36–1.22 (m, 14H), 0.96 (t, J¼7.9 Hz,
9H), 0.89 (t, J¼6.8 Hz, 3H), 0.55 (q, J¼7.9 Hz, 6H). 13C
NMR (CDCl3): d 63.0, 32.9, 31.9, 29.6, 29.6, 29.5, 29.3,
25.8, 22.7, 14.1, 6.8, 4.4. MS (FAB: NBA) m/z 273 (MþþH,
10%), 271 (8), 243 (25), 214 (42), 115 (22), 103 (20).
HRMS (FAB: NBA) calcd for C16H36OSi (MþþH)
273.2614. Found 273.2610.
4.7.1. 3-tert-Butyldimethylsilyloxy-1-propanol (3u).28
1
95% yield as a colorless oil. H NMR (CDCl3): d 3.84 (t,
J¼5.6 Hz, 2H), 3.84–3.80 (m, 2H), 2.61 (brs, 1H), 1.81–
1.76 (m, 2H), 0.90 (s, 9H), 0.08 (s, 6H). 13C NMR (CDCl3):
d 63.0, 62.5, 34.1, 25.9, 18.2, 25.5.
4.6.5. 3,7-Dimethyl-1-triethylsilyloxyoctane (2j). 88%
1
yield as a colorless oil. H NMR (CDCl3): d 3.67–3.58
(m, 2H), 1.61–1.48 (m, 4H), 1.37–1.31 (m, 4H), 1.28–1.10
(m, 2H), 0.96 (t, J¼7.8 Hz, 9H), 0.88–0.86 (m, 9H), 0.60 (q,
J¼7.8 Hz, 6H). 13C NMR (CDCl3): d 61.2, 40.1, 39.3, 37.4,
29.6, 28.0, 24.7, 22.7, 22.6, 19.8, 6.8, 4.5. MS (EI) 243
(Mþ2C2H5, 100), 205 (46), 83 (83), 57 (53). HRMS (EI)
calcd for C14H31OSi (Mþ2C2H5) 243.2154. Found 243.2144.
References and notes
1. Selected reviews: (a) Greene, T. W.; Wuts, P. G. M. Protective
Groups in Organic Synthesis; 3rd ed.; Wiley-Interscience:
New York, 1999; pp 113–148. (b) Kocienski, P. J. Protecting
Groups; Thieme: Stuttgart, 1994; p 28. (c) In Handbook of
Reagents for Organic Synthesis; Activating Agents and
Protecting Groups; Pearson, A. J., Roush, W. R., Eds.;
Wiley: New York, 1999; p 84.
4.6.6. 2-Methyl-4-triethylsilyloxyoctane (2k). 93% yield
as a colorless oil. 1H NMR (CDCl3): d 3.73–3.67 (m, 1H),
1.72–1.63 (m, 1H), 1.44–1.22 (m, 8H), 0.69 (t, J¼7.9 Hz,
9H), 0.89–0.87 (m, 9H), 0.60 (q, J¼7.9 Hz, 6H). 13C NMR
(CDCl3): d 70.6, 46.7, 37.5, 27.4, 24.5, 23.2, 22.9, 22.8,
14.1, 7.0, 5.2. MS (EI) 229 (Mþ2C2H4, 99%), 201 (55), 173
(22), 115 (26), 103 (100), 87, (21), 75 (37), 44 (20). MS (EI)
m/z 229 (Mþ2C2H5, 99%), 201 (55), 173 (22), 115 (26),
103, (100), 75 (37). HRMS (EI) calcd for C13H29OSi
(Mþ2C2H5) 229.1988. Found 229.1981.
2. Ranu, B. C.; Jana, U.; Majee, A. Tetrahedron Lett. 1999, 40,
1985–1988.
3. For example, see: (a) Tanemura, K.; Suzuki, T.; Horaguchi, T.
J. Chem. Soc., Perkin Trans. 1 1992, 2997–2998. (b) Zhu,
X.-F.; Williams, H. J.; Scott, A. I. J. Chem. Soc., Perkin Trans.
1 2000, 2305–2306. (c) Jiang, Z.-Y.; Wang, Y.-G. Chem. Lett.
2003, 32, 568–569.
4.6.7. 3-Methyl-1-phenyl-3-(triethylsilyl)oxypentane (2l).
98% yield as a colorless oil. 1H NMR (CDCl3): d 7.30–7.27
(m, 2H), 7.26–7.14 (m, 3H), 2.66–2.60 (m, 2H), 1.75–1.68
(m, 2H), 1.55 (q, J¼7.4 Hz, 2H), 1.23 (s, 3H), 0.97 (t,
J¼7.9 Hz, 9H), 0.88 (t, J¼7.4 Hz, 3H), 0.60 (q, J¼7.9 Hz,
6H). 13C NMR (CDCl3): d 143.3, 128.3, 125.5, 75.5, 43.7,
34.8, 30.6, 27.2, 8.8, 7.2, 7.0. MS (EI) m/z 263 (Mþ2C2H5,
93%), 187 (33), 160 (13), 131 (10), 115, (20), 103 (100), 91
(23), 75 (26), 44 (14). HRMS (EI) calcd for C16H27OSi
(Mþ2C2H5) 263.1831. Found 263.1824.
4. For reviews, see: (a) Nishimura, S. Handbook of Hetero-
geneous Catalytic Hydrogenation for Organic Synthesis;
Wiley: New York, 2001; pp 34–38. (b) Rylander, P. N.
Hydrogenation Methods; Academic: New York, 1985; p 10.
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4.6.8. 1-Triethylsilyloxy-2-propylbenzene (2m).27 The
crude material was purified by flash column chroma-
tography on silica gel (eluting with hexane) to afford 2n
8. Although Rotulo-Sims and Prunet have reported a simple
deprotection method of TES ether using 10% Pd/C in MeOH
or 95% EtOH at room temperature in the absence of hydrogen
atmosphere,9 we have disclosed that the deprotection method
in the absence of hydrogen is not palladium-catalyzed reaction
and only an acid-catalyzed solvolysis, and hydrogen is
absolutely essential for the real 10% Pd/C-catalyzed cleavage
of TES ethers, see; (a) Sajiki, H.; Ikawa, T.; Hirota, K.
Tetrahedron Lett. 2003, 44, 7407–7410. (b) Ikawa, T.; Sajiki,
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1
as a colorless oil (3% yield). H NMR (CDCl3): d 7.11 (d,
J¼7.6 Hz, 1H), 7.04 (t, J¼7.6 Hz, 1H), 6.86 (t, J¼7.6 Hz,
1H), 6.76 (d, J¼7.6 Hz, 1H), 2.56 (t, J¼7.6 Hz, 1H), 1.65–
1.54 (m, 2H), 1.00 (t, J¼7.7 Hz, 9H), 0.94 (t, J¼7.6 Hz,
3H), 0.77 (q, J¼7.7 Hz, 6H).
4.7. General procedure for selective deprotection under
the hydrogenation condition in MeOH using 10% Pd/C
(Table 5)
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Hirota, K. Chem. Eur. J. 2000, 6, 2200–2204.
After two vacuum/H2 cycles to remove air from the reaction

T. Ikawa et al. / Tetrahedron 60 (2004) 6901–6911
6911
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´
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