Efficient chemoselective deprotection of silyl ethers using catalytic 1-chloroethyl chloroformate in methanol

Article abstract of DOI:10.1016/j.tet.2005.10.043

Fast and chemoselective desilylation of silyl-protected alcohols was achieved using a catalytic amount of 1-chloroethyl chloroformate in methanol. With a minimal amount of 1-chloroethyl chloroformate as the source for anhydrous HCl, extremely efficient cleavage of silyl ethers of primary and secondary alcohols was accomplished, and chemoselective deprotection of one silyl ether in the presence of another silyl or other acid-labile group was possible through controlling the amount of the chloroformate and reaction time.

Full text of DOI:10.1016/j.tet.2005.10.043

Tetrahedron 61 (2005) 12227–12237
Efficient chemoselective deprotection of silyl ethers using catalytic
1-chloroethyl chloroformate in methanol
*
Chang-Eun Yeom, Young Jong Kim, So Young Lee, Yong Je Shin and B. Moon Kim
School of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-747, South Korea
Received 14 July 2005; revised 14 October 2005; accepted 17 October 2005
Available online 11 November 2005
Abstract—Fast and chemoselective desilylation of silyl-protected alcohols was achieved using a catalytic amount of 1-chloroethyl
chloroformate in methanol. With a minimal amount of 1-chloroethyl chloroformate as the source for anhydrous HCl, extremely efficient
cleavage of silyl ethers of primary and secondary alcohols was accomplished, and chemoselective deprotection of one silyl ether in the
presence of another silyl or other acid-labile group was possible through controlling the amount of the chloroformate and reaction time.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
previously reported acidic hydrolyses of silyl ethers in
aqueous alcoholic solvents.9 Two reports exist on the rate of
aq HCl-mediated hydrolysis of silyl ethers. When more than
0.31 equiv of 1% HCl in 95% aq MeOH was employed for the
hydrolysis of n-hexyl tert-butyldiphenylsilyl (TBDPS) ether,
the half-life of desilylation was 225 min.9a The half-life of
n-butyl TBDPS ether hydrolysis was 244 min with 1% HCl in
95% aq EtOH.9b In our case, however, the half-life of n-hexyl
TBDPS ether cleavage was about 20 min when 0.155 equiv of
CEC in methanol (equivalent to 0.31 equiv HCl) was
employed.10
Trialkylsilyl-groups have been widely used as hydroxyl-
protecting agents in organic synthesis1 due to easy
installation,1c,2 stability to most reaction conditions and
selectivity in cleavage reactions. Cleavage of the silyl ethers
can be effected either using acidic conditions or a fluoride
source. However, cleavage using a fluoride ion is often
associated with poor selectivity in the case of compounds
having two different siloxy groups and unwanted side
reactions such as silyl migration.3 Furthermore, use of
excess tetrabutylammonium fluoride (TBAF),4 one of the
most commonly employed deprotection reagents, often
requires extensive chromatography for the removal of
remaining tetrabutylammonium (TBA) salt. Alternatives
to the fluoride ion include acidic or basic conditions,5 Lewis
acid catalysts including transition metals,5 oxidative or
reductive methods,6 and catalytic hydrogenation.7
2. Results and discussion
In general, anhydrous HCl can be generated from a chloride
source such as thionyl chloride in alcoholic solvents.
Though this protocol is conveniently applicable to
desilylation, use of thionyl chloride exhibited lower
chemoselectivity in the deprotection of triethylsily group
in the presence of a tert-butyldimethylsilyl group as
shown in Table 1 (entries 1–3). With 0.1 mol% of thionyl
chloride in methanol, there appeared already a significant
amount of diol even after 90 s. On the other hand, employ-
ment of CEC (0.1 mol%) ensured unusually high level of
chemoselectivity (entry 5). Even with 0.2 mol% CEC,
mono-desilylated product was formed in 93% yield (entry 4).
Upon reaction with methanol, it is expected to yield one
equivalent of HCl and more slowly another equivalent pro-
ducing CO2 and volatile acetaldehyde dimethyl acetal, which
can be later removed by simple evaporation. This slow and
sequential generation of HCl from CEC may be critical for
the observed chemoselectivity, contrary to the rapid
generation of HCl from thionyl chloride.11 Commercially
During our investigation on the desilylation of various silyl
ethers, we have encountered fast cleavage of silyl ethers with
an extremely small amount of 1-chloroethyl chloroformate
(CEC) in methanol: triethylsilyl (TES) ethers were cleaved
completely in as short as 1 min with 0.01 mol% 1-chloroethyl
chloroformate. It is of particular note that 1-chloroethyl
chloroformate, which is often utilized as dealkylating agent of
tertiary amines,8 can readily generate hydrochloric acid in
alcoholic media at rt, and this anhydrous HCl-catalyzed
desilylation in methanol is considerably faster than the
Keywords: 1-Chloroethyl chloroformate; Desilylation; Silyl ethers;
Chemoselective; Catalytic.
Corresponding author. Tel.: C82 2 880 6644; fax: C82 2 872 7505;
e-mail: kimbm@snu.ac.kr
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.10.043

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C.-E. Yeom et al. / Tetrahedron 61 (2005) 12227–12237
possible intermediate.14 When i-PrOH or t-BuOH was used
instead of methanol with 3 mol% of CEC, the reaction was
very slow; only 3.7% yield and trace of products,
respectively, were obtained after 1 h.
Table 1. Results of TES removal in presence of TBDMS group using
thionyl chloride or CEC
HO
OTBDMS
1
cat. SOCl2 or CEC
MeOH, rt, 90 s
TESO
+
OTBDMS
HO
OH
3 mol % HCl (g)
2
Ph
OH
OH
OH
dioxane, 1 h
trace
Entry
HCl source
mol%
Yield of 1a
Yield of 2a
3 mol% ClCOOCHClCH3
i-PrOH, 1 h
1
2
3
4
5
SOCl2
SOCl2
SOCl2
CEC
0.2
0.1
0.05
0.2
0.1
58
68
83
93
95
38
19
6
5
3
Ph
OTBDMS
Ph
3.7 % yield
Ph
3 mol% ClCOOCHClCH3
t-BuOH, 1 h
CEC
a Yields of isolated alcohols.
trace
Scheme 1. Desilylation using various solvents. Yields of isolated alcohols.
available methanolic HCl solution (1.25 M) was also
examined for the selective TES-removal. In this case, it was
difficult to determine optimal amounts of the HCl in methanol
due to extremely high reactivity, and when carefully
controlled amounts of methanolic HCl was employed,
selective removal of TES in the presence of the TBDMS
did take place, however the chemoselectivity of mono-
desilylation was always inferior to that obtained with CEC.12
Since the in situ generated hydrogen halides offer many
advantages,13 we investigated the scope of this new protocol.
Then we examined the deprotection of various silyl ethers
using CEC in methanol (Table 2). First, it was found that the
rate of the silyl ether cleavage depends highly upon the
Lewis basicity of the alcohol oxygen (entry 1), indicating
that the protonation on the silyl oxygen is connected to the
reaction rate. As can be seen in Table 2, fast deprotection of
TES, TBDMS, and TIPS ethers of primary (entries 2a–c)
and secondary alcohols (entries 3a and 3b) was observed
with 0.1w5 mol% of CEC in methanol at rt. Even TBDPS-
protected alcohols (entries 2d and 3c) were cleaved
efficiently using increased amount (8 and 30 mol%,
respectively) of CEC at longer reaction time. This difference
in reactivity could be the basis for chemoselective
desilylation of compounds having two different siloxy
groups. (vide infra). Cleavage of aryl silyl ethers was
relatively slower than that of the aliphatic alcohols (entries
4–6), and the rate was again directly related to the electronic
properties of the ring substituents, electron-donating
methoxy group being more activating than the methoxy-
carbonyl (entries 4 and 5).
First, it was found that the selection of methanol as a solvent
was critical to the observed reactivity of this reaction
(Scheme 1). When desilylation of 3-phenyl-1-propyl
TBDMS ether was carried out using 3 mol% anhydrous
hydrochloric acid in methanol, the cleavage of silyl ether
proceeded in less than 3 min giving 98% yield of the
alcohol, whereas in 1,4-dioxane the alcohol production was
minimal after 1 h. This strongly indicates that the
nucleophilic methanol was required for the desilylation,
thus ruling out the possibility of silyl cation species as a
Table 2. Desilylation of primary, secondary and aryl silyl ethers in methanol
Entry
1
Silyl ether
Chloroformate amount, reaction time
Product and yield (%)a
OTBDMS
OH
R
R
1a: RZOMe
1b: RZMe
1c: RZNO2
3 mol%, !5 min
3 mol%, !5 min
3 mol%, 2.5 h
95
97
91
OH
OR
2
3
2a: RZTES
2b: RZTBDMS
2c: RZTIPS
0.1 mol%, !2 min
3 mol%, !5 min
5 mol%, 1.5 h
95
98
95
94
2d: RZTBDPS
8 mol%, 3 h
RO
N
Cbz
HO
N
Cbz
OH
3a: RZTES
3b: RZTBDMS
3c: RZTBDPS
0.2 mol%, !2 min
5 mol%, 30 min
30 mol%, 7 h
96
97
89
5 mol%, 4 h
MeO
OTBDMS
MeO
4
5
4
5
99
85
10 mol%, 65 h
5 mol%, 20 h
MeO2C
OTBDMS
OTBDMS
MeO2C
OH
OH
6
6
98
a Yields of isolated alcohols.

C.-E. Yeom et al. / Tetrahedron 61 (2005) 12227–12237
12229
Table 3. Chemoselective desilylation of various compounds having two different siloxy groups and silyl ethers possessing acid-labile functionalities
Entry
1
Silyl ether
Reaction conditions
Product and yield (%)a
TESO
HO
OR
OR
7a: RZTBDMS
0.1 mol%, !2 min
0.1 mol%, !2 min
0.1 mol%, !2 min
0.1 mol%, !2 min
0.1 mol%, !2 min
0.1 mol%, !2 min
0.1 mol%, !2 min
0.2 mol%, 15 min
RZTBDMS, 95
TZTIPS, 97
RZTBDPS, 98
RZTHP, 97
RZTrt, 98
RZMOM, 96
RZMEM, 94
RZTs, 97
7b: RZTIPS
7c: RZTBDPS
7d: RZTHP
7e: RZTrt
7f: RZMOM
7 g: RZMEM
7 h: RZTs
TBDMSO
HO
OR
OR
2
8a: RZTIPS
8b: RZTBDPS
8c: RZMOM
8d: RZMEM
8e: RZTs
1 mol%, 15 min
3 mol%, !7 min
3 mol%, !7 min
3 mol%, !7 min
3 mol%, !7 min
RZTIPS, 86
RZTBDPS, 92
RZMOM, 95
RZMEM, 92
RZTs, 96
O
O
OH
3
4
OR
O
O
5
5
9a: RZTES
0.2 mol%, 1.5 min
93
O
O
RO
HO
OMe
OMe
10a: RZTBDMS
10b: RZTBDPS
O
3 mol%, !7 min
8 mol%, 3.5 h
97
93
O
5
RO
HO
OBut
OBut
11a: RZTBDMS
11b: RZTBDPS
3 mol%, !7 min
8 mol%, 3.5 h
92
88
OR
OH
BocHN
BocHN
6
7
12a: RZTBDMS
12b: RZTBDPS
3 mol%, 25 min
8 mol%, 5.5 h
97
75
OR
OH
TeocHN
TeocHN
13a: RZTBDMS
13b: RZTBDPS
3 mol%, 15 min
8 mol%, 5.5 h
3 mol%, 8 min
93
89
BnO
BnO
BnO
OTBDMS
OH
OH
8
9
14a
15a
95
84
3 mol%, 10 min
3 mol%, 7 min
BnO
OTBDMS
OBn
OBn
TBDMSO
HO
10
OH
OH
16a
a Yields of isolated alcohols.
90
Encouraged by the above results, selective desilylation of
compounds having two different siloxy groups and silyl
ethers possessing other acid-sensitive groups was investi-
gated extensively (Table 3). Not many reports exist on
preferential cleavage of TES group in presence of TBDMS
group.5i,6c,15,16 In our case, however, TES ether (7a) was
cleaved cleanly in preference to TBDMS group within
2 min with only 0.1 mol% of CEC, furnishing the desired
product in 86% yield. In presence of TIPS or TBDPS ethers
(7b and 7c), selective deprotection of TES was achieved in
excellent yields. When other acid sensitive hydroxyl-
protecting groups, such as THP (7d), Trt (7e), MOM
(7f), MEM (7g), isopropylidene (9a), and tosyl (7h) groups
were present at other hydroxyl functionalities, all of
them survived the TES removal conditions using
0.1w0.2 mol% CEC. Selective deprotection of TBDMS
group was also achieved successfully in presence of TIPS
(8a), TBDPS (8b), MOM (8c), MEM (8d), Ts (8e), and Bn
(14a and 15a) groups using 3 mol% of CEC (entry 2). Other
acid-sensitive groups such as methyl and t-butyl esters (10a,
10b, 11a, and 11b) survived the TBDMS and TBDPS
removal conditions (entries 4 and 5). Acid-sensitive amine
protecting groups, that is, Boc (entry 6) and Cbz (entry 3,
Table 2) were also stable under these conditions, and all
silyl ethers including TBDPS were preferentially removed.
It is noteworthy that Teoc group, a fluoride-sensitive amine
protecting moiety, also remained intact under TBDMS and
TBDPS cleavage conditions (entry 7). When allylic and
propargylic TBDMS ethers were tested, neither migration of
the silyl group nor reaction on the unsaturated bond was
detected (entries 8 and 9). In the case of a monosilylated
vicinal diol, no 1,2-migration of the primary silyl group to
the secondary alcohol was observed (entry 10).
Chemoselective desilylation of disilyl ethers of aryl and
alkyl alcohols was also tested (Table 4). Generally removal
of alkyl silyl ethers is faster than aryl silyl ethers in acidic
media,5a–d and the reverse is true under basic conditions.5a,e
Additionally, removal of alkyl silyl ethers is faster than aryl
silyl ethers even under neutral hydrogenation condition.17 In
our case, the silyl ethers of aliphatic alcohols were also
removed selectively leaving phenolic silyl ethers in

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C.-E. Yeom et al. / Tetrahedron 61 (2005) 12227–12237
Table 4. Chemoselective desilylation of various aryloxysilyl and alkoxysilyl groups
Entry
1
Silyl ether
Condition
Productivity and yield (%)a
OTES
OH
0.01 mol%, 1 min
TESO
TBDMSO
TBDMSO
TBDPSO
TESO
11a
12a
13a
14a
81
OTBDMS
OTBDMS
OTBDPS
OH
5 mol%, 8 min
3 mol%, 8 min
8 mol%, 5.5 h
TBDMSO
2
3
93
OH
TBDMSO
90
OH
TBDMSO
4
82
a Yields of isolated alcohols.
excellent yields. Furthermore, not only di-TBDMS (entries
2 and 3) but also di-TES (entry 1) and di-TBDPS ethers
(entry 4) showed reasonable chemoselectivity, yielding 81
and 82% yields, respectively, of the mono-desilylated
products.5f,18 It is noteworthy that the aliphatic TES removal
of 2-(4-hydroxyphenyl)ethyl alcohol was extremely fast,
taking only 45 s.
4. Experimental
4.1. General
All reactions were carried out under nitrogen atmosphere
in dried solvents. 1H NMR (300 MHz) and 13C NMR
(75 MHz) spectra were recorded in CDCl3 on Bruker
AM-300 instruments. Chemical shifts were reported in ppm
(d units) downfield of Me4Si (TMS) as the internal
standards, or residual CHCl3. High-resolution mass
(HRMS) were obtained on JEOL JMS 600 mass spec-
trometer. Methylene chloride (CH2Cl2) was dried from
refluxing with CaH2; methanol (MeOH), 1-chloroethyl
chloroformate, and other commercially available materials
were purchased from supplier and used without further
purification. All reactions as well as column chromato-
graphy were monitored routinely by thin-layer chromato-
graphy, which is performed with aluminum backed silica
gel plates coated with a 0.2 mm thickness of silica gel 60
F254 (Merck). Column chromatography was performed with
indicated eluting conditions on silica gel (Merck. 7734 or
9385 Kiesel gel 60).
Based upon the observed experimental results, a plausible
catalytic cycle is presented, which involves the methano-
lysis of silyl ether catalyzed by HCl, and continuous
regeneration of the acid (Fig. 1). The isolation of
TBDPSOMe in over 90% yields from the reaction starting
from a TBDPS ether strongly supports this catalytic cycle.
ROTBS
Ph
Si
H
HCl in Methanol
O
Cl–
R
Ph
4.2. General procedure for the preparation of silyl ethers
from corresponding alcohols
Ph
MeOH
OMe
Si
Ph
To a magnetically stirred solution of the alcohol
(1.00 mmol) in dry CH2Cl2 or DMF (3 mL) was added
imidazole (2.00 mmol) and trialkylsilyl chloride
(1.10 mmol) sequentially. After starting material disap-
peared on TLC, brine was poured into reaction mixture. The
organic layer was washed with brine (2.0 mL) twice,
separated, dried over MgSO4, filtered, and concentrated.
Resulting residue was further purified by flash chromato-
graphy with indicated eluting solvent.
Cl
OMe
Si
H
ROH
Ph
Ph
Figure 1. Plausible catalytic cycle for silyl ether cleavage.
3. Conclusion
A facile, convenient and mild desilylation method was
developed using 1-chloroethyl chloroformate in methanol.
This new method utilizes only a minute amount of
1-chloroethyl chloroformate. No by-products are formed
that require complicated chromatographic purification; only
short filtration through silica gel suffices to provide pure
products. By controlling the amount of the chloroformate
and reaction time, chemoselective desilylation was accom-
plished in presence of bulkier silyl groups and other acid-
sensitive alcohol protecting groups.
4.2.1. tert-Butyl-(4-methoxybenzyloxy)dimethylsilane
(1a).19a (Eluted with n-hexane/EtOAcZ30:1, colorless
oil); H NMR (300 MHz, CDCl3) d 7.25 (m, 2H), 6.88
(m, 2H), 4.68 (s, 2H), 3.81 (s, 3H), 0.94 (s, 9H), 0.10 (s, 6H);
13C NMR (75 MHz, CDCl3) d 158.7, 133.6, 127.5, 113.6,
64.7, 55.3, 26.0, 18.4, K5.2.
1
4.2.2. tert-Butyl-(4-methylbenzyloxy)dimethylsilane
(1b).19b (Eluted with n-hexane/EtOAcZ30:1, colorless
oil); H NMR (300 MHz, CDCl3) d 7.25 (m, 2H), 6.88
1

C.-E. Yeom et al. / Tetrahedron 61 (2005) 12227–12237
12231
(m, 2H), 4.68 (s, 2H), 3.81 (s, 3H), 0.94 (s, 9H), 0.10 (s, 6H);
13C NMR (75 MHz, CDCl3) d 138.0, 137.4, 129.3, 127.2,
65.1, 21.3, 18.7, K4.9.
129.9, 128.2, 127.3, 126.7, 124.3, 122.6, 115.5, 26.3,
18.8, K3.7.
4.2.11. 1-(Triethylsilyloxy)-4-(20,20-dimethyl-10,30-dioxo-
lan-40-yl)-butane (9a). (Eluted with n-hexane/EtOAcZ
15:1, colorless oil); H NMR (300 MHz, CDCl3) d 4.14–
4.2.3.
tert-Butyl-(4-nitrobenzyloxy)dimethylsilane
(1c).19c (Eluted with n-hexane/EtOAcZ10:1, yellowish
1
1
oil); H NMR (300 MHz, CDCl3) d 8.20 (d, JZ9.0 Hz,
4.05 (m, 2H), 3.72 (t, JZ6.4 Hz, 2H), 3.50 (m, 1H), 1.76–
1.26 (m, 13H), 0.97–0.93 (m, 9H), 0.61–0.55 (m, 6H); 13C
NMR (75 MHz, CDCl3) d 108.9, 76.6, 69.9, 63.3, 33.7,
33.0, 27.4, 26.1, 7.2, 4.8; HRMS (CI) Calcd for C26H39O3Si
[MCH]C, 289.2158, found 289.2154.
2H), 7.49 (d, JZ8.7 Hz, 2H), 4.83 (s, 2H), 0.96 (s, 9H), 0.13
(s, 6H); 13C NMR (75 MHz, CDCl3) d 148.8, 147.4, 130.4,
128.4, 64.2, 24.5, 18.6, K4.3.
4.2.4. 1-Triethylsilyloxy-3-phenylpropane (2a).7b (Eluted
with n-hexane/EtOAcZ30:1, colorless oil); 1H NMR
(300 MHz, CDCl3) d 7.29–7.15 (m, 5H), 3.64 (t, JZ
6.4 Hz, 2H), 2.68 (t, 2H), 1.89–1.82 (m, 2H), 0.96 (t, JZ
8.0 Hz, 9H), 0.60 (q, JZ8.0 Hz, 6H); 13C NMR (75 MHz,
CDCl3) d 142.5, 128.8, 128.7, 126.3, 62.5, 34.5, 32.1, 7.3,
5.3.
4.2.12. Methyl 6-(tert-butyldimethylsilyloxy)hexanoate
(10a).19f (Eluted with n-hexane/EtOAcZ15:1, colorless
oil); 1H NMR (300 MHz, CDCl3) d 3.65 (s, 3H), 3.59 (t, JZ
6.4 Hz, 2H), 2.30 (t, JZ8.0 Hz, 2H), 1.63 (quint, JZ6.4 Hz,
2H), 1.31–1.39 (m, 2H), 0.87 (s, 9H), 0.03 (s, 6H); 13C NMR
(75 MHz, CDCl3) d 174.4, 63.1, 51.6, 34.3, 32.7, 26.2, 25.6,
25.0, 28.5, K5.1.
4.2.5. 1-tert-Butyldimethylsilyloxy-3-phenylpropane
(2b).7b (Eluted with n-hexane/EtOAcZ30:1, colorless
oil); 1H NMR (300 MHz, CDCl3) d 7.67 (dd, JZ1.5,
7.8 Hz, 4H), 7.44–7.15 (m, 1H), 3.69 (t, JZ6.4 Hz, 2H),
2.72 (t, JZ7.8 Hz, 2H), 0.60 (q, JZ8.0 Hz, 6H); 13C NMR
(75 MHz, CDCl3) d 142.7, 129.0, 128.8, 126.2, 62.8, 35.0,
32.6, 26.5, 18.8, K4.8.
4.2.13. Methyl 6-(tert-butyldiphenylsilyloxy)hexanoate
(10b).19g (Eluted with n-hexane/EtOAcZ15:1, colorless
oil); H NMR (300 MHz, CDCl3) d 7.71–7.30 (m, 10H),
3.66 (s, 3H), 3.69–3.61 (m, 2H), 2.29 (t, JZ7.5 Hz, 2H),
1.69–1.30 (m, 6H), 1.04 (s, 9H); 13C NMR (75 MHz,
CDCl3) d 174.2, 136.0, 134.6, 130.0, 128.0, 63.1, 51.6, 34.3,
32.7, 26.2, 25.6, 17.9, 12.0.
1
4.2.6. 1-Triisopropylsilyloxy-3-phenylpropane (2c).17b
(Eluted with n-hexane/EtOAcZ30:1, colorless oil); 1H
NMR (300 MHz, CDCl3) d 7.29–7.17 (m, 5H), 3.71 (t, JZ
6.1 Hz, 2H), 2.71 (t, JZ7.8 Hz, 2H), 1.89–1.82 (m, 2H),
1.12–1.04 (m, 21H); 13C NMR (75 MHz, CDCl3) d 142.8,
128.5, 128.2, 126.2, 62.6, 34.7, 32.1, 18.0, 12.5.
4.2.14. tert-Butyl 6-(tert-butyldimethylsilyloxy)hexano-
ate (11a).19h (Eluted with n-hexane/EtOAcZ15:1, colorless
oil); 1H NMR (300 MHz, CDCl3) d 3.63 (t, JZ6.4 Hz, 2H),
2.20 (t, JZ7.1 Hz, 2H), 1.61–1.33 (m, 6H), 1.44 (s, 9H),
0.90 (s, 9H), 0.02 (s, 6H); 13C NMR (75 MHz, CDCl3)
d 173.1, 79.9, 61.2, 35.4, 32.2, 28.0, 26.0, 25.2, 24.7,
18.3, K5.0.
4.2.7. 1-tert-Butyldiphenylsilyloxy-3-phenylpropane
(2d).7b (Eluted with n-hexane/EtOAcZ30:1, colorless
oil); 1H NMR (300 MHz, CDCl3) d 7.67 (dd, JZ1.5,
7.8 Hz, 4H), 7.44–7.15 (m, 16H), 3.69 (t, JZ6.4 Hz, 2H),
2.72 (t, JZ7.8 Hz, 2H), 1.91–1.84 (m, 2H), 1.07 (s, 9H); 13C
NMR (75 MHz, CDCl3) d 142.8, 136.2, 134.6, 130.2, 129.1,
128.9, 128.3, 126.3, 62.6, 34.7, 32.1, 18.0, 12.0, 11.8.
4.2.15. tert-Butyl 6-(tert-butyldiphenylsilyloxy)hexanoate
(11b). (Eluted with n-hexane/EtOAcZ15:1, colorless oil);
1H NMR (300 MHz, CDCl3) d 7.68–7.65 (m, 4H), 7.44–
7.34 (m, 6H), 3.65 (t, JZ6.3 Hz, 2H), 2.19 (t, JZ7.2 Hz,
2H), 1.62–1.35 (m, 6H), 1.44 (s, 9H), 1.04 (s, 9H); 13C NMR
(75 MHz, CDCl3) d 174.1, 135.8, 134.5, 130.0, 128.2, 79.7,
61.2, 35.4, 32.2, 28.0, 25.9, 25.2, 24.8, 18.5; HRMS (CI)
Calcd for C26H39O3Si [MCH]C, 427.2668, found
427.2665.
4.2.8. 4-(Methoxyphenoxy)-tert-butyldimethylsilane
(4).19d (Eluted with n-hexane/EtOAcZ10:1, colorless oil);
1H NMR (300 MHz, CDCl3) d 6.74 (s, 4H), 3.74 (s, 3H),
0.96 (s, 9H), 0.15 (s, 6H); 13C NMR (75 MHz, CDCl3) d
154.6, 149.8, 121.1, 114.9, 55.9, 26.2, 18.6, K4.1.
4.2.16. N-(tert-Butoxycarbonyl)-3-(tert-butyldimethyl-
silyloxy)propylamine (12a).19i (Eluted with n-hexane/
1
EtOAcZ10:1, colorless oil); H NMR (300 MHz, CDCl3)
4.2.9. Methyl 4-(tert-butyldimethylsilyloxy)benzoate
(5).19e (Eluted with n-hexane/EtOAcZ7:1, colorless oil);
1H NMR (300 MHz, CDCl3) d 7.75 (d, JZ8.6 Hz, 2H), 3.86
(s, 3H), 0.98 (s, 9H), 0.16 (s, 6H); 13C NMR (75 MHz,
CDCl3) d 167.1, 160.4, 131.9, 123.6, 120.2, 52.1, 25.9,
18.6, K4.1.
d 5.12 (br, 1H), 3.64 (t, JZ6.0 Hz, 2H), 3.16 (t, JZ6.5 Hz,
2H), 1.80–1.60 (m, 2H), 1.44 (s, 9H), 0.92 (s, 9H), 0.04 (s,
6H); 13C NMR (75 MHz, CDCl3) d 156.4, 62.6, 39.6, 32.3,
28.8, 26.3, 18.5, K4.3.
4.2.17. N-(tert-Butoxycarbonyl)-3-(tert-butyldiphenyl-
silyloxy)propylamine (12b).19j (Eluted with n-hexane/
EtOAcZ10:1, colorless oil); H NMR (300 MHz, CDCl3)
d 7.71–7.68 (m, 4H), 7.47–7.39 (m, 6H), 5.09 (br, 1H), 3.77
(t, JZ6.0 Hz, 2H), 3.34–3.30 (m, 2H), 1.79–1.72 (m, 2H),
1.46 (s, 9H), 1.05 (s, 9H); 13C NMR (75 MHz, CDCl3) d
156.4, 135.9, 133.8, 130.2, 128.2, 78.8, 63.2, 39.2, 32.5,
28.9, 27.4, 19.6.
4.2.10. 2-(Naphthalenyloxy)-tert-butyldimethylsilane.
(6).19c (Eluted with n-hexane/EtOAcZ10:1, colorless oil);
1H NMR (300 MHz, CDCl3) d 7.76 (d, JZ8.1 Hz, 1H), 7.72
(d, JZ9.0 Hz, 1H), 7.68 (d, JZ8.7 Hz, 1H), 7.38 (t, JZ
7.0 Hz, 1H), 7.30 (t, JZ7.0 Hz), 7.19 (d, JZ2.4 Hz, 1H),
7.07 (dd, JZ3.2 Hz, JZ8.7 Hz, 1H), 1.02 (s, 9H), 0.25
(s, 6H); 13C NMR (75 MHz, CDCl3) d 154.0, 135.3, 135.2,
1

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C.-E. Yeom et al. / Tetrahedron 61 (2005) 12227–12237
4.2.18. (E)-1-(Benzyloxy)-4-[(tert-butyldimethylsilyl)-
oxy]-2-butene (14a).19k (Eluted with n-hexane/EtOAcZ
15:1, colorless oil); H NMR (300 MHz, CDCl3) d 7.35–
4.3.3. 4-(tert-Butyldiphenylsilyloxy)piperidine-1-
carboxylic acid benzyl ester (3c). (Eluted with n-hexane/
EtOAcZ4:1, colorless oil); H NMR (300 MHz, CDCl3) d
1
1
7.28 (m, 5H), 5.81–5.66 (s, 2H), 4.52 (s, 2H), 4.28–4.27 (m,
2H), 4.14–4.12 (m, 2H), 0.96 (s, 9H), 0.07 (s, 6H); 13C NMR
(75 MHz, CDCl3) d 138.6, 133.3, 128.8, 128.1, 128.0,
127.2, 72.6, 66.2, 60.0, 26.4, 18.7, K4.7.
7.66–7.63 (m, 4H), 7.45–7.29 (m, 11H), 5.11 (s, 2H), 3.93
(m, 1H), 3.73–3.65 (m, 2H), 3.34–3.26 (m, 2H), 1.57 (m,
4H), 1.06 (s, 9H); 13C NMR (75 MHz, CDCl3) d 155.8,
137.4, 136.4, 136.2, 135.4, 134.6, 130.3, 129.9, 129.0,
128.4, 128.3, 128.2, 128.1, 68.3, 67.5, 41.2, 34.3, 27.5, 19.7;
HRMS (CI) Calcd for C29H36NO3Si [MCH]C, 474.2464,
found 474.2462.
4.2.19. 1-(Benzyloxy)-4-[(tert-butyldimethylsilyl)oxy]-2-
butyne (15a).19l (Eluted with n-hexane/EtOAcZ15:1,
colorless oil); 1H NMR (300 MHz, CDCl3) d 7.40–7.28
(m, 5H), 4.64 (s, 2H), 4.42 (s, 2H), 4.24 (s, 2H), 0.98 (s, 6H),
0.19 (s, 6H); 13C NMR (75 MHz, CDCl3) d 137.9, 128.9,
128.7, 128.3, 127.4, 85.7, 81.2, 72.1, 57.8, 52.2, 26.1,
18.7, K4.7.
4.3.4. Procedure for the preparation of N-[20-(trimethyl-
silyl)ethoxycarbonyl]-3-(tert-butyldimethyl-silyloxy)
propylamine (13a). To a magnetically stirred solution of
(trimethylsilyl)ethanol (0.19 mL, 1.30 mmol) in dry CH2Cl2
(10 mL) 0were added triethylamine (0.90 mL, 6.51 mmol)
and N,N -(disuccinimidyl)carbonate (500 mg, 1.95 mmol)
sequentially. After 2 h, 3-aminopropanol (0.12 mL,
1.56 mmol) was added, and the mixture was stirred for
additional 2 h. Brine (20 mL) was poured into the reaction
mixture, and organic layer was washed with brine (80 mL)
three times, separated, dried over MgSO4, filtered, and
concentrated. Flash chromatography (n-hexane/EtOAcZ
1:2) gave pure Teoc-protected alcohol. (0.21 g, 51%). 3-[20-
(Trimethylsilyl)ethoxycarbonyl)-amino-1-propanol was
dissolved in CH2Cl2 (6 mL). To the solution imidazole
(150 mg, 1.92 mmol) and tert-butyldimethylsilyl chloride
(140 mg, 0.96 mmol) were added and the mixture stirred for
3 h. After the starting material disappeared on TLC, brine
(50 mL) was poured into the reaction mixture. The organic
layer was washed with brine (50 mL) twice, separated, dried
over MgSO4, filtered, and concentrated. Resulting residue
was further purified by flash chromatography (n-hexane/
EtOAcZ12:1) to yield 13a as a colorless oil. (7.4 g, 95%);
1H NMR (300 MHz, CDCl3) d 5.13 (br, 1H), 4.12–4.07 (m,
2H), 3.69–3.65 (m, 2H), 3.26–3.22 (m, 2H), 1.71–1.63 (m,
2H), 0.92–0.83 (m, 2H), 0.86 (s, 9H), 0.02 (s, 6H), 0.00 (s,
9H); 13C NMR (75 MHz, CDCl3) d 157.2, 63.0, 62.3, 39.7,
32.5, 27.2, 26.3, 18.6, K1.1, K4.1; HRMS (CI) Calcd for
C15H36NO3Si2 [MCH]C, 334.2234, found 334.2234.
4.2.20. 6-(Benzyloxy)-1-[(tert-butyldimenylsilyl)oxy]-2-
hexanol (16a).19m (Eluted with n-hexane/EtOAcZ5:1,
colorless oil); 1H NMR (300 MHz, CDCl3) d 7.37–7.25
(m, 5H), 4.48 (s, 2H), 3.7–3.3 (m, 5H), 3.2 (br, 2H), 1.7–1.3
(m, 6H), 0.97 (s, 9H), 0.07 (s, 6H); 13C NMR (75 MHz,
CDCl3) d 138.0, 129.4, 128.8, 128.6, 72.6, 70.6, 67.2, 33.4,
30.0, 26.2, 22.6, 18.8, K4.9.
4.3. General procedure for preparing 4-(trialkylsilyloxy)-
piperidine-1-carboxylic acid benzyl ester
To a magnetically stirred solution of 4-hydroxypiperidine
(1 mmol) and Et3N (1.5 mmol) in dry CH2Cl2 (3 mL) was
added benzyl chloroformate (1.2 mmol) dropwise at 0 8C.
After 20 min, the reaction mixture was allowed to warm to
rt, and stirred for 2 h. It was washed with brine (2 mL), and
the organic layer was dried over MgSO4, filtered, and
concentrated. Resulting residue was dissolved in CH2Cl2
(3 mL) and imidazole (1.5 mmol) and trialkylsilyl chloride
(1.1 mmol) were added and the mixture stirred for 3 h. After
starting material disappeared on TLC, brine (5 mL) was
poured into the reaction mixture. The organic layer was
washed with brine (2 mL) twice, separated, dried over
MgSO4, filtered, and concentrated. Resulting residue was
further purified by flash chromatography (eluted with
n-hexane/EtOAcZ4:1).
4.3.5. N-[20-(Trimethylsilyl)ethoxycarbonyl]-3-(tert-
butyldiphenylsilyloxy)propylamine (13b). (Eluted with
n-hexane/EtOAcZ15:1, colorless oil); 1H NMR (300 MHz,
CDCl3) d 7.71–7.68 (m, 4H), 7.45–7.37 (m, 6H), 5.07 (br,
1H), 4.10 (t, JZ8.3 Hz, 2H), 3.70 (t, JZ6.6 Hz, 2H), 3.31–
3.26 (m, 2H), 1.71 (quint, JZ6.6 Hz, 2H), 1.04 (s, 9H), 0.00
(s, 9H); 13C NMR (75 MHz, CDCl3) d 157.3, 136.1, 133.9,
130.2, 128.2, 63.2, 62.9, 39.4, 32.4, 27.3, 27.1, 19.5, 18.2,
K1.0; HRMS (CI) Calcd for C25H40NO3Si2 [MCH]C,
458.2547, found 458.2547.
4.3.1. 4-(Triethylsilyl)piperidine-1-carboxylic acid ben-
zyl ester (3a). (Eluted with n-hexane/EtOAcZ4:1, color-
less oil); 1H NMR (300 MHz, CDCl3) d 7.40–7.28 (m, 5H),
5.19 (s, 2H), 3.91–3.86 (m, 1H), 3.82–3.74 (m, 2H), 3.35–
3.27 (m, 2H), 1.74 (m, 2H), 1.54–1.52 (m, 2H), 1.00–0.96
(m, 9H), 0.66–0.58 (m, 6H); 13C NMR (75 MHz, CDCl3) d
154.0, 135.3, 135.2, 129.9, 128.2, 127.3, 126.7, 124.3,
122.6, 115.5, 26.3, 18.8, K3.7; HRMS (CI) Calcd for
C19H32NO3Si [MCH]C, 350.2151, found 350.2156.
4.3.6. Preparation of 1-(tert-butyldimethylsilyloxy)-6-
(triethylsilyloxy)-hexane (7a) (a representative pro-
cedure for the preparation of compounds having two
different silyloxy groups). To a magnetically stirred
solution of 1,6-hexanediol (10.0 g, 84.6 mmol) in dry
CH2Cl2 (60 mL) and DMF (30 mL) were added imidazole
(2.9 g, 42.3 mmol) and triethylsilyl chloride (4.80 mL,
28.2 mmol) sequentially. After 5 h, brine (50 mL) was
poured into reaction mixture. The organic layer was washed
with brine (80 mL) twice, separated, dried over MgSO4,
filtered, and concentrated. Flash chromatography
4.3.2. 4-(tert-Butyldimethylsilyloxy)piperidine-1-
carboxylic acid benzyl ester (3b).20 (Eluted with n-hexane/
1
EtOAcZ4:1, colorless oil); H NMR (300 MHz, CDCl3) d
7.36–7.30 (m, 5H), 5.12 (s, 2H), 3.91–3.89 (m, 1H), 3.70–
3.62 (m, 2H), 3.42–3.35 (m, 2H), 1.70 (m, 2H), 1.52
(m, 2H), 0.89 (s, 9H), 0.05 (s, 6H); 13C NMR (75 MHz,
CDCl3) d 155.7, 137.4, 128.9, 128.3, 67.3, 41.0, 34.5, 26.2,
18.5, K4.3.

C.-E. Yeom et al. / Tetrahedron 61 (2005) 12227–12237
12233
(n-hexane/EtOAcZ5:1) gave pure mono-silyl ether. (5.2 g,
78%). 6-(Triethylsilyloxy)hexanol was dissolved in CH2Cl2
(60 mL). To the solution were added midazole (2.30 g,
33.2 mmol) and tert-butyldimethylsilyl chloride (3.70 g,
24.6 mmol) and the mixture stirred for 3 h. After the starting
material disappeared on TLC, brine (50 mL) was poured
into reaction mixture. The organic layer was washed with
brine (50 mL) twice, separated, dried over MgSO4, filtered,
and concentrated. Resulting residue was further purified by
flash chromatography (n-hexane/EtOAcZ25:1) to yield 7a
as a colorless oil. (7.40 g, 95%); 1H NMR (300 MHz,
CDCl3) d 3.58–3.54 (m, 4H), 1.52–1.46 (m, 4H), 1.32–1.27
(m, 4H), 0.97–0.90 (m, 9H), 0.86 (s, 9H), 0.60–0.52 (m,
6H), 0.01 (s, 6H); 13C NMR (75 MHz, CDCl3) d 63.6, 33.3,
26.4, 26.1, 18.8, 7.2, 4.8, K4.9; HRMS (CI) Calcd for
C18H43O2Si2 [MCH]C, 347.2802, found 347.2800.
3 h, satd aq NaHCO3 solution (50 mL) was poured into the
reaction mixture and the organic layer was separated, dried
over MgSO4, filtered, and concentrated. Flash chromato-
graphy (n-hexane/EtOAcZ15:1) gave pure mono-tetra-
hydropyranyl ether (4.8 g, 70%). 6-(Tetrahydro-2H-20-
pyranyloxy)-1-hexanol was dissolved in CH2Cl2 (60 mL),
and to the solution were added imidazole (2.4 g,
35.6 mmol), and chlorotriethylsilane (3.9 g, 26.1 mmol)
and the mixture stirred for 3 h. After the starting material
disappeared on TLC, brine (60 mL) was poured into the
reaction mixture and the organic layer was washed with
brine (50 mL) twice, separated, dried over MgSO4, filtered,
and concentrated. Resulting residue was further purified by
flash chromatography (n-hexane/EtOAcZ20:1) to yield 7d
as a colorless oil. (7.1 g, 95%); 1H NMR (300 MHz, CDCl3)
d 4.58–4.56 (m, 1H), 3.91–3.85 (m, 1H), 3.75–3.69 (m, 1H),
3.60 (t, JZ6.6 Hz, 2H), 3.51–3.50 (m, 1H), 3.42–3.37 (m,
1H), 1.84–1.69 (m, 2H), 1.63–1.54 (m, 8H), 1.38–1.36 (m,
4H), 0.98–0.93 (m, 9H), 0.63–0.55 (m, 6H); 13C NMR
(75 MHz, CDCl3) d 99.2, 68.0, 63.3, 62.7, 33.3, 31.2, 30.1,
26.5, 26.1, 25.9, 20.1, 7.2, 4.8; HRMS (CI) Calcd for
C17H37O3Si [MCH]C, 317.2512, found 317.2513.
4.3.7.
1-(Triethylsilyloxy)-6-(triisopropylsilyloxy)-
hexane (7b). (Eluted with n-hexane/EtOAcZ25:1, colorless
oil); 1H NMR (300 MHz, CDCl3) d 3.67 (t, JZ6.6 Hz, 2H),
3.62 (t, JZ6.7 Hz, 2H), 1.58–1.54 (m, 4H), 1.38–1.36 (m,
4H), 1.10–1.05 (m, 21H), 1.00–0.98 (m, 9H), 0.65–0.57 (m,
6H); 13C NMR (75 MHz, CDCl3) d 63.7, 63.4, 33.4, 33.2,
26.1, 26.0, 18.4, 12.4, 7.2, 4.8; HRMS (CI) Calcd for
C21H49O2Si2 [MCH]C, 389.3271, found 389.3271.
4.4.2. Preparation of 1-(triethylsilyloxy)-6-(triphenyl-
methyloxy)hexane (7e). To a magnetically stirred solution
of 1,6-hexanediol (10 g, 84.6 mmol) in dry CH2Cl2 (70 mL)
and DMF (30 mL) were added diisopropylethylamine
(4.9 mL, 56.4 mmol) and triphenylmethoxymethyl chloride
(3.9 g, 28.2 mmol) sequentially. After 3 h, brine (50 mL)
was poured into reaction mixture, organic layer was
separated, dried over MgSO4, filtered, and concentrated.
Flash chromatography (n-hexane/EtOAcZ5:1) gave pure
mono-Trt ether. (1.9 g, 37%). The product, 6-(triphenyl-
methyloxy)-1-hexanol was dissolved in CH2Cl2 (18 mL)
and to the solution were added imidazole (540 mg,
7.91 mmol), and chlorotriethylsilane (0.97 mL, 5.8 mmol).
The mixture was stirred for 3 h. After the starting material
disappeared on TLC, brine (10 mL) was poured to the
reaction mixture. The organic layer was washed with brine
(10 mL) twice, separated, dried over MgSO4, filtered, and
concentrated. Resulting residue was further purified by flash
chromatography (n-hexane/EtOAcZ25:1) to yield 7e as a
4.3.8. 1-(tert-Butyldiphenylsilyloxy)-6-(triethylsilyloxy)-
hexane (7c). (Eluted with n-hexane/EtOAcZ25:1, colorless
oil); H NMR (300 MHz, CDCl3) d 7.68–7.66 (4H, m),
1
7.39–7.36 (6H, m), 3.68–3.56 (4H, m), 1.61–1.50 (4H, m),
1.37–1.30 (4H, m), 1.05 (9H, s), 0.98–0.93 (9H, m), 0.63–
0.55 (6H, m); 13C NMR (75 MHz, CDCl3) d 136.0, 134.6,
129.9, 128.0, 64.4, 63.3, 33.3, 33.0, 27.3, 26.1, 19.7, 7.2,
4.9; HRMS (CI) Calcd for C28H47O2Si2 [MCH]C,
471.3115, found 471.3117.
4.3.9. 1-(tert-Butyldimethylsilyloxy)-6-(triisopropyl silyl-
oxy)hexane (8a).21a (Eluted with n-hexane/EtOAcZ25:1,
colorless oil); 1H NMR (300 MHz, CDCl3) d 3.63 (2H, JZ
6.5 Hz, t), 3.56 (2H, JZ6.5 Hz, t), 1.52–1.46 (4H, m), 1.31–
1.29 (4H, m), 1.02 (21H, m), 0.85 (9H, s), 0.03 (6H,s); 13C
NMR (75 MHz, CDCl3) d 63.8, 63.6, 26.4, 26.0, 18.8, 18.4,
12.4, K4.9.
1
colorless oil. (2.4 g, 97%); H NMR (300 MHz, CDCl3) d
7.46–7.43 (m, 6H), 7.28–7.16 (m, 9H), 3.58 (t, JZ6.6 Hz,
2H), 3.05 (t, JZ6.6 Hz, 2H), 1.65–1.60 (m, 2H), 1.54–1.49
(m, 2H), 1.41–1.27 (m, 4H), 0.98–0.93 (m, 9H), 0.63–0.55
(m, 6H); 13C NMR (75 MHz, CDCl3) d 145.0, 129.5, 128.2,
127.3, 86.8, 64.1, 63.4, 33.4, 30.6, 26.7, 26.3, 7.3, 4.9;
HRMS (CI) Calcd for C31H43O2Si [MCH]C, 475.3012,
found 475.3008.
4.3.10. 1-(tert-Butyldimethylsilyloxy)-6-(tert-butyldiphenyl-
silyloxy)hexane (8b).21b (Eluted with n-hexane/EtOAcZ
1
25:1, colorless oil); H NMR (300 MHz, CDCl3) d; 13C
NMR (75 MHz, CDCl3) d 7.69–7.66 (m, 4H), 7.43–7.36
(m, 6H), 3.66 (t, JZ6.3 Hz, 2H), 3.59 (t, JZ6.3 Hz, 2H),
1.60–1.49 (m, 4H), 1.37–1.30 (m, 4H), 1.05 (s, 9H), 0.90
(s, 9H), 0.01 (s, 6H); 13C NMR (75 MHz, CDCl3) d 136.0,
134.6, 130.0, 128.0, 64.4, 63.7, 33.3, 33.1, 27.4, 26.5, 26.1,
26.0, 19.7, 18.8, K4.8.
4.4.3. Preparation of 1-(triethylsilyloxy)-6-(methoxy-
methoxy)hexane (7f). To a magnetically stirred solution
of 1,6-hexanediol (6.0 g, 51.3 mmol) in dry CH2Cl2
(70 mL) and DMF (30 mL) were added diisopropylethyl-
amine (5.9 mL, 34.2 mmol) and methoxymethyl chloride
(1.3 mL, 17.1 mmol) sequentially. After 3 h, brine (70 mL)
was poured into the reaction mixture, and the organic layer
was separated, dried over MgSO4, filtered, and concen-
trated. Flash chromatography (n-hexane/EtOAcZ2:1) gave
pure mono-MOM ether. (2.4 g, 88%). To a solution of 6-
(methoxymethyl)-1-hexanol in CH2Cl2 (50 mL) were added
imidazole (2 g, 15.0 mmol) and chlorotriethylsilane
4.4. Preparation and spectroscopic data of silyl ethers
possessing other acid-sensitive functional groups
4.4.1. Preparation of 1-(triethylsilyloxy)-6-(tetrahydro-
2H-20-pyranyloxy)hexane (7d). To a magnetically stirred
solution of 1,6-hexanediol (10.0 g, 84.6 mmol) in dry
CH2Cl2 (60 mL) and DMF (30 mL) were added 3,
4-dihydro-2H-pyran (3.1 mL, 33.8 mmol) and pyridinium
p-toluenesulfonate (850 mg, 3.38 mmol) sequentially. After

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C.-E. Yeom et al. / Tetrahedron 61 (2005) 12227–12237
(2.56 mL, 7.5 mmol) and the mixture stirred for 3 h. After
the starting material disappeared on TLC, brine (40 mL)
was poured into the reaction mixture. The organic layer was
washed with brine (40 mL) twice, separated, dried over
MgSO4, filtered, and concentrated. Resulting residue was
further purified by flash chromatography (n-hexane/
EtOAcZ10:1) to yield 7f as a colorless oil. (1.8 g, 85%);
1H NMR (300 MHz, CDCl3) d 4.62 (s, 2H), 3.60 (t, JZ
6.6 Hz, 2H), 3.52 (t, JZ6.6 Hz, 2H), 3.36 (s, 3H), 1.63–1.54
(m, 4H), 1.38–1.36 (m, 4H), 0.98–0.93 (m, 9H), 0.63–0.55
(m, 6H); 13C NMR (75 MHz, CDCl3) d 96.7, 68.1, 63.3,
55.4, 33.2, 30.1, 26.5, 26.1, 7.2, 4.8; HRMS (CI) Calcd for
C14H33O3Si [MCH]C, 277.2199, found 277.2192.
21.2 mmol) sequentially and the mixture stirred for 3 h.
After 3 h, brine (70 mL) was poured into the reaction
mixture and the organic layer was separated, dried over
MgSO4, filtered, and concentrated. Flash chromatography
(n-hexane/EtOAcZ5:1) gave pure mono-triethylsilyl ether.
(4.0 g, 81%). To a solution of 6-(triethylsilyloxy)-1-hexanol
(800 mg, 3.44 mmol) in CH2Cl2 (12 mL) were added
triethylamine (0.72 mL, 5.16 mmol), and p-toluenesulfonyl
chloride (660 mg, 3.44 mmol) and the mixture stirred for
3 h. After the starting material disappeared on TLC, brine
(10 mL) was poured into reaction mixture. The organic
layer was washed with brine (10 mL) twice, separated, dried
over MgSO4, filtered, and concentrated. Resulting residue
was further purified by flash chromatography (n-hexane/
EtOAcZ10:1) to yield 7h as a colorless oil. (1.0 g, 75%);
1H NMR (300 MHz, CDCl3) d 7.80–7.76 (m, 2H), 7.35–
7.32 (m, 2H), 4.01 (t, JZ7.2 Hz, 2H), 3.56 (t, JZ6.6 Hz,
2H), 2.40 (s, 3H), 1.66–1.59 (m, 2H), 1.49–1.43 (m, 2H),
1.31–1.26 (m, 4H), 0.99–0.92 (m, 9H), 0.62–0.54 (m, 6H);
13C NMR (75 MHz, CDCl3) d 145.0, 133.5, 130.2, 128.2,
71.0, 62.9, 33.0, 29.2, 25.6, 21.9, 6.2, 4.7; HRMS (CI) Calcd
for C19H35O4SiS [MCH]C, 387.2025, found 387.2026.
4.4.4. 1-(tert-Butyldimethylsilyloxy)-6-(methoxy methoxy)-
hexane (8c).22a (Eluted with n-hexane/EtOAcZ10:1, color-
less oil); 1H NMR (300 MHz, CDCl3) d 4.59 (s, 2H), 3.58 (t,
JZ6.6 Hz, 2H), 3.49 (t, JZ6.6 Hz, 2H), 3.33 (s, 3H), 1.60–
1.48 (m, 4H), 1.35–1.32 (m, 4H), 0.86 (m, 9H), 0.02 (m, 6H);
13C NMR (75 MHz, CDCl3)d96.8,68.1,63.6, 55.4, 33.2, 30.1,
26.4, 26.3, 26.0, 18.7, K4.9.
4.4.5. Preparation of 1-(triethylsilyloxy)-6-(methoxy-
ethoxymethoxy)-hexane (7g). To a magnetically stirred
solution of 1,6-hexanediol (5.3 g, 44.7 mmol) in dry CH2Cl2
(70 mL) and DMF (30 mL) were added diisopropylethyl-
amine (5.2 mL, 29.8 mmol) and MEM chloride (1.7 mL,
14.9 mmol) sequentially. After 3 h, brine (70 mL) was
poured into the reaction mixture and the organic layer was
separated, dried over MgSO4, filtered, and concentrated.
Flash chromatography (n-hexane/EtOAcZ1:2) gave pure
mono-MEM ether (1.7 g, 57%). To a solution of
6-(methoxyethoxymethyl)-1-hexanol in CH2Cl2 (25 mL)
were added imidazole (1.2 g, 16.9 mmol), and chloro-
triethylsilane (1.42 mL, 8.4 mmol) and the mixture stirred
for 3 h. After the starting material disappeared on TLC,
brine (20 mL) was poured into reaction mixture. The
organic layer was washed with brine (20 mL) twice,
separated, dried over MgSO4, filtered, and concentrated.
Resulting residue was further purified by flash chromato-
graphy (n-hexane/EtOAcZ8:1) to yield 7g as a colorless
4.4.8. Toluene-4-sulfonic acid 6-(tert-butyldimethylsilyl-
oxy)hexyl ester (8e).22c (Eluted with n-hexane/EtOAcZ
10:1, colorless oil); H NMR (300 MHz, CDCl3) d 7.80–
7.76 (m, 2H), 7.49–7.46 (m, 2H), 3.98 (t, JZ7.2 Hz, 2H),
3.55 (t, JZ6.6 Hz, 2H), 2.37 (s, 3H), 1.65–1.58 (m, 2H),
1.44–1.40 (m, 2H), 1.27–1.25 (m, 4H), 0.86 (s, 9H), 0.01 (s,
6H); 13C NMR (75 MHz, CDCl3) d 145.0, 133.5, 130.2,
128.2, 71.0, 63.3, 33.0, 29.2, 27.0, 26.3, 25.6, 25.6, 22.0,
18.7, K4.9.
1
4.4.9. Preparation of 1-(triethylsilyloxy)-4-(ethylsilyloxy-
ethyl)-benzene (11a)23d (a representative procedure for
the preparation of compounds having two same silyloxy
groups) To a magnetically stirred solution of an alcohol
(1 mmol) in dry CH2Cl2 (3 mL) or DMF (3 mL) were added
imidazole (2.5 mmol) and triethylsilyl chloride (2.2 mmol)
sequentially. After the starting material disappeared on
TLC, brine (2 mL) was poured into reaction mixture. The
organic layer was washed with brine (2 mL) twice,
separated, dried over MgSO4, filtered, and concentrated.
Resulting residue was further purified by flash chromatog-
raphy (n-hexane/EtOAcZ25:1) to yield 11a as a colorless
oil. (97%); 1H NMR (300 MHz, CDCl3) d 7.05–7.03 (d, JZ
8.3 Hz, 2H), 6.77–6.74 (d, JZ8.3 Hz, 2H), 3.76 (t, JZ
7.2 Hz, 2H), 2.76 (t, JZ7.2 Hz, 2H), 1.02–0.89 (m, 18H),
0.76–0.51 (m, 12H); 13C NMR (75 MHz, CDCl3) d 152.4,
131.8, 130.2, 119.6, 64.6, 38.9, 6.74, 6.62, 4.95, 4.37.
1
oil. (2.1 g, 77%); H NMR (300 MHz, CDCl3) d 4.71 (s,
2H), 3.71–3.68 (m, 2H), 3.62–3.54 (m, 6H), 3.40 (s, 3H),
1.62–1.51 (m, 4H), 1.37–1.35 (m, 4H), 0.98–0.93 (m, 9H),
0.63–0.55 (m, 6H); 13C NMR (75 MHz, CDCl3) d 95.8,
72.2, 68.3, 67.0, 63.2, 59.4, 33.2, 30.1, 26.4, 26.1, 6.99,
4.78; HRMS (CI) Calcd for C16H37O4Si [MCH]C,
321.2461, found 321.2464.
4.4.6. 1-(tert-Butyldimethylsilyloxy)-6-(methoxyethoxy-
methoxy)-hexane (8d).22b (Eluted with n-hexane/
1
EtOAcZ10:1, colorless oil); H NMR (300 MHz, CDCl3)
4.4.10. 1-(tert-Butyldimethylsilyloxy)-4-(tert-butyldi-
methylsilyloxymethyl)benzene (11b).19c (Eluted with
n-hexane/EtOAcZ25:1, colorless oil); 1H NMR
(300 MHz, CDCl3) d 7.17 (d, JZ8.4 Hz, 2H), 6.79 (d, JZ
6.79 Hz, 2H), 4.66 (s, 2H), 0.98 (s, 9H), 0.93 (s, 9H), 0.18 (s,
6H), 0.08 (s, 6H); 13C NMR (75 MHz, CDCl3) d 155.7,
132.3, 129.9, 120.3, 64.6, 25.7, 25.6, 18.4, 18.2, K4.4,
K5.3.
d 4.59 (s, 2H), 3.58 (t, JZ6.6 Hz, 2H), 3.49 (t, JZ6.6 Hz,
2H), 3.33 (s, 3H), 1.60–1.48 (m, 4H), 1.35–1.32 (m, 4H),
0.87 (m, 9H), 0.01 (m, 6H); 13C NMR (75 MHz, CDCl3) d
95.8, 72.2, 68.3, 67.0, 63.2, 59.4, 33.2, 30.1, 26.4, 26.1,
18.7, K4.9.
4.4.7. Preparation of toluene-4-sulfonic acid 6-(triethyl-
silyloxy)-hexyl ester (7h). To a magnetically stirred
solution of 1,6-hexanediol (5.0 g, 42.3 mmol) in dry
CH2Cl2 (70 mL) and DMF (30 mL) were added imidazole
(2.88 g, 42.3 mmol), and chlorotriethylsilane (3.56 mL,
4.4.11.
dimethylsilyloxyethyl)benzene (11c).5j (Eluted with
n-hexane/EtOAcZ25:1, colorless oil); 1H NMR
1-(tert-Butyldimethylsilyloxy)-4-(tert-butyl

C.-E. Yeom et al. / Tetrahedron 61 (2005) 12227–12237
12235
(300 MHz, CDCl3) d 7.04 (d, JZ6.5 Hz, 2H), 6.74 (d, JZ
6.6 Hz, 2H), 3.76 (t, JZ7.0 Hz, 2H), 2.74 (t, JZ7.0 Hz,
2H), 0.97 (s, 9H), 0.86 (s, 9H), 0.16 (s, 6H), K0.02 (s, 6H);
13C NMR (75 MHz, CDCl3) d 152.4, 132.6, 130.4, 120.2,
65.2, 39.2, 26.3, 26.1, 18.6, 18.4, K4.1, K5.0.
4.5.5.
6-(Tetrahydro-2H-2-pyranyloxy)-1-hexanol
(Table 3, entry 1).23d (Eluted with n-hexane/EtOAcZ5:1,
1
colorless oil); H NMR (300 MHz, CDCl3) d 4.56 (s, 1H),
3.88 (m, 2H), 3.53–3.34 (m, 4H), 1.92–1.34 (m, 15H); 13C
NMR (75 MHz, CDCl3) d 99.2, 68.0, 63.3, 62.7, 33.3, 31.2,
30.1, 26.5, 26.1, 25.9, 20.1.
4.4.12. 1-(tert-Butyldiphenylsilyloxy)-4-(tert-butyl-
diphethylsilyloxyethyl)benzene (11d).5f (Eluted with
n-hexane/EtOAcZ25:1, colorless sticky oil); 1H NMR
(300 MHz, CDCl3) d 7.71–7.69 (m, 4H), 7.57–7.54 (m,
4H), 7.36–7.31 (m, 12H), 6.87–6.85 (m, 2H), 6.67–6.64 (m,
2H), 3.75 (t, JZ7.0 Hz, 2H), 2.71 (t, JZ7.0 Hz, 2H), 1.08
(s, 9H), 0.98 (s, 9H); 13C NMR (75 MHz, CDCl3) d 154.3,
136.0, 135.9, 133.5, 131.9, 130.3, 130.2, 129.9, 128.1,
128.0, 126.3, 119.7, 65.6, 38.8, 27.2, 26.9, 19.9, 19.5.
4.5.6. 6-(Triphenylmethyloxy)-1-hexanol (Table 3, entry
1).23e (Eluted with n-hexane/EtOAcZ5:1, colorless oil); 1H
NMR (300 MHz, CDCl3) d 7.55–7.43 (m, 6H), 7.28–7.15
(m, 9H), 3.58 (t, JZ6.0 Hz, 2H), 3.17 (t, JZ6.5 Hz, 2H),
1.65–1.60 (m, 2H), 1.54–1.49 (m, 3H), 1.45–1.25 (m, 4H);
13C NMR (75 MHz, CDCl3) d 145.3, 129.7, 128.1, 127.5,
85.8, 65.1, 63.4, 33.4, 30.6, 26.7, 26.2.
4.5.7. 6-(Methoxymethoxy)-1-hexanol (Table 3, entries 1
and 2).23f (Eluted with n-hexane/EtOAcZ2:1, colorless oil);
1H NMR (300 MHz, CDCl3) d 4.63(s, 2H), 3.63(t, JZ6.6 Hz,
2H), 3.54 (t, JZ6.3 Hz, 2H), 3.36 (s, 3H), 3.14 (br, 1H), 1.62–
1.56 (m, 4H), 1.50–1.39 (m, 4H); 13C NMR (75 MHz, CDCl3)
d 96.2, 67.6, 62.6, 55.0, 32.5, 29.5, 25.9, 25.5.
4.5. Representative procedure for the cleavage of silyl
ether
To a magnetically stirred solution of starting material (silyl
ether) (1 mmol) in methanol (1 mL), was added indicated
amount of 1-chloroethyl chloroformate dropwise at rt. The
mixture was stirred at rt until the starting material
disappeared on TLC, then the reaction was quenched by
addition of satd aq NaHCO3 solution (3 mL), and the
mixture was extracted with ethyl ether (4 mL!2). The
organic layer was dried over anhyd MgSO4, filtered and
concentrated under reduced pressure. The resulting residue
was filtered through a short silica gel column and the
corresponding alcohol was obtained in pure form.
4.5.8. 6-(Methoxyethoxymethoxy)-1-hexanol (Table 3,
entries 1 and 2).23d (Eluted with n-hexane/EtOAcZ1:2,
colorless oil); H NMR (300 MHz, CDCl3) d 4.69 (s, 2H),
1
3.66–3.61 (t, JZ6.0 Hz, 2H), 3.56–3.44 (m, 6H), 3.40 (s,
3H), 2.53 (br, 1H), 1.62–1.54 (m, 4H), 1.40–1.32 (m, 4H);
13C NMR (75 MHz, CDCl3) d 95.7, 72.1, 68.2, 67.0, 62.9,
59.3, 32.9, 29.9, 26.3, 25.9.
4.5.9. Toluene-4-sulfonic acid 6-hydroxyhexyl ester
(Table 3, entries 1 and 2).23 (Eluted with n-hexane/
4.5.1. 4-Hydroxypiperidine-1-carboxylic acid benzyl
1
EtOAcZ2:1, colorless oil); H NMR (300 MHz, CDCl3) d
ester (Table 2, entry 3).23a (Eluted with n-hexane/
7.79–7.75 (m, 2H), 7.37–7.34 (m, 2H), 4.04–3.98 (m, 2H),
3.59–3.53 (m, 2H), 2.54 (s, 1H), 2.45 (s, 3H), 1.66–1.60 (m,
2H), 1.55–1.46 (m, 2H), 1.38–1.26 (m, 4H); 13C NMR
(75 MHz, CDCl3) d 145.2, 133.28, 130.3, 128.2, 71.1, 62.8,
32.7, 29.1, 25.5, 22.0.
1
EtOAcZ1:2, colorless oil); H NMR (300 MHz, CDCl3) d
7.33–7.24 (m, 5H), 5.09 (s, 2H), 3.88–3.72 (m, 4H), 3.12–
3.03 (m, 2H), 1.87–1.78 (m, 2H), 1.46–1.43 (m, 2H); 13C
NMR (75 MHz, CDCl3) d 155.8, 137.0, 128.9, 128.6, 128.2,
67.6, 67.2, 41.9, 34.2.
4.5.10. 4-(20,20-Dimethyl-10,30-dioxolan-40-yl)-butanol
(Table 3, entry 3).23h (Eluted with n-hexane/EtOAcZ7:1,
colorless oil); 1H NMR (300 MHz, CDCl3) d 4.10–4.00 (m,
2H), 3.73 (t, JZ6.5 Hz, 2H), 3.50 (m, 1H), 2.18 (br, 1H),
1.62–1.31 (m, 12H); 13C NMR (75 MHz, CDCl3) d 108.8,
76.4, 69.7, 63.3, 33.7, 33.0, 27.4, 26.1.
4.5.2. 6-(tert-Butyldimethylsilyloxy)-1-hexanol (Table 3,
entries 1 and 2).23b (Eluted with n-hexane/EtOAcZ5:1,
colorless oil); 1H NMR (300 MHz, CDCl3) d 3.81–3.57 (m,
4H), 1.82 (br, 1H), 1.56–1.44 (m, 4H), 1.41–1.31 (m, 4H),
0.90 (s, 9H), 0.11 (s, 6H); 13C NMR (75 MHz, CDCl3) d
63.4, 63.2, 32.8, 31.5, 25.9, 22.5, 18.5, 14.0, K5.3.
4.5.11. Methyl 6-hydroxyhexanoate (Table 3, entry 4).23i
(Eluted with n-hexane/EtOAcZ2:1, colorless oil); 1H NMR
(300 MHz, CDCl3) d 3.67 (s, 3H), 3.64 (m, 2H), 3.01 (br,
1H), 2.34 (t, JZ7.2 Hz, 2H), 1.66 (q, JZ7.4 Hz, 2H), 1.59
(q, JZ7.0 Hz, 2H), 1.45–1.36 (m, 2H); 13C NMR (75 MHz,
CDCl3) d 174.7, 62.5, 51.9, 34.1, 32.5, 25.8, 25.0.
4.5.3. 6-(Triisopropylsilyloxy)-1-hexanol (Table 3,
entries 1 and 2).23c (Eluted with n-hexane/EtOAcZ5:1,
colorless oil); H NMR (300 MHz, CDCl3) d 3.68 (t, JZ
6.6 Hz, 2H), 3.54 (t, JZ6.6 Hz, 2H), 1.95 (br, 1H), 1.60–
1.55 (m, 4H), 1.52–1.36 (m, 4H), 1.16–1.08 (m, 21H); 13C
NMR (75 MHz, CDCl3) d 65.7, 63.0, 33.4, 33.2, 26.0, 25.9,
18.4, 12.4.
1
4.5.12. tert-Butyl 6-hydroxyhexanoate (Table 3, entry
5).19h (Eluted with n-hexane/EtOAcZ4:1, colorless oil); 1H
NMR (300 MHz, CDCl3) d 3.63 (t, JZ6.6 Hz, 2H), 2.37 (br,
1H), 2.23 (t, JZ7.4 Hz, 2H), 1.66–1.53 (m, 4H), 1.46 (s,
9H), 1.48–1.35 (m, 2H); 13C NMR (75 MHz, CDCl3) d
173.4, 79.8, 61.4, 35.4, 32.2, 28.0, 25.2, 24.7.
4.5.4. 6-(tert-Butyldiphenylsilyloxy)-1-hexanol (Table 3,
entries 1 and 2).23c (Eluted with n-hexane/EtOAcZ5:1,
colorless oil); 1H NMR (300 MHz, CDCl3) d 7.70–7.64 (m,
4H), 745–7.31 (m, 6H), 3.67 (t, JZ6.6 Hz, 2H), 3.61 (t, JZ
6.6 Hz, 2H), 1.65–1.50 (m, 4H), 1.46–1.30 (m, 4H), 1.25
(br, 1H), 1.05 (s, 9H); 13C NMR (75 MHz, CDCl3) d 135.3,
133.8, 129.4, 127.5, 63.7, 62.2, 32.3, 32.2, 26.7, 25.4,
25.3, 19.1.
4.5.13. N-[(tert-Butyloxycarbonyl)]-3-amino-1-propanol
(Table 3, entry 6).23j (Eluted with n-hexane/EtOAcZ1:1,
colorless oil); 1H NMR (300 MHz, CDCl3) d 5.21 (br, 1H),

12236
C.-E. Yeom et al. / Tetrahedron 61 (2005) 12227–12237
3.79 (br, 1H), 3.65 (m, 2H), 3.26–3.24 (m, 2H), 1.69–1.66
(m, 2H), 1.44 (s, 9H); 13C NMR (75 MHz, CDCl3) d 157.4,
79.8, 59.6, 37.5, 33.0, 28.7.
Acknowledgements
Generous financial support from the Korea Research Fund
(2004-015-C00273) is gratefully acknowledged.
4.5.14. N-[(20-Trimethylsilylethyl)oxy]-3-amino-1-pro-
panol (Table 3, entry 7). (Eluted with n-hexane/EtOAcZ
1:1, colorless oil); H NMR (300 MHz, CDCl3) d 5.14 (br,
1
1H), 4.11 (t, JZ8.4 Hz, 2H), 3.63 (m, 2H), 3.31–3.25 (m,
3H), 2.42 (br, 1H), 1.66 (quint, JZ6.6 Hz, 2H), 0.94 (t, JZ
8.4 Hz, 2H), 0.00 (s, 9H); 13C NMR (75 MHz, CDCl3) d
158.2, 63.6, 59.7, 37.9, 33.0, 18.1, K1.1; HRMS (CI) Calcd
for C9H22NO3Si [MCH]C, 220.1369, found 220.1371.
References and notes
1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; Wiley: New York, 1999. (b)
Kocienski, P. J. Protecting groups; George Thieme Verlag:
New York, 1994. (c) Corey, E. J.; Venkateswarlu, A. J. Am.
Chem. Soc. 1972, 94, 6190.
4.5.15. (E)-4-(Benzyloxy)-2-buten-1-ol (Table 3, entry
8).23k (Eluted with n-hexane/EtOAcZ2:1, colorless oil); 1H
NMR (300 MHz, CDCl3) d 7.37–7.26 (m, 5H), 5.81–5.66
(m, 2H), 4.54 (s, 2H), 4.28–4.27 (m, 2H), 4.14–4.12 (m,
2H), 2.24 (br, 1H); 13C NMR (75 MHz, CDCl3) d 138.0,
132.3, 128.3, 127.7, 127.5, 72.6, 70.3, 62.7.
2. For reviews, see: Lalonde, M.; Chan, T. H. Synthesis 1985,
817. (b) Nelson, T. D.; Crouch, R. D. Synthesis 1996, 1031.
3. Ranu, B. C.; Jana, U.; Majee, A. Tetrahedron Lett. 1985, 26, 681.
4. (a) Blass, B. E.; Harris, C. L.; Portlock, D. E. Tetrahedron Lett.
2001, 42, 1611. (b) Kremsky, J. N.; Sinha, N. D. Bioorg. Med.
Chem. Lett. 1994, 4, 2171.
4.5.16. 4-(Benzyloxy)-2-butyn-1-ol (Table 3, entry 9).23l
(Eluted with n-hexane/EtOAcZ2:1, colorless oil); 1H NMR
(300 MHz, CDCl3) d 7.37–7.27 (m, 5H), 4.61 (s, 2H), 4.23 (d,
2H), 4.09 (m, 2H), 1.68 (br, 1H); 13C NMR (75 MHz, CDCl3)
d 137.4, 128.4, 128.1, 127.9, 86.3, 81.7, 71.6, 71.4, 57.4.
5. (a) Crouch, R. D. Tetrahedron 2004, 60, 5833. (b) Grieco,
P. A.; Markworth, C. J. T. Tetrahedron Lett. 1999, 40, 665. (c)
Gopinath, R.; Patel, B. K. Org. Lett. 2000, 2, 4177. (d) Khan,
A. T.; Mondal, E. Synlett 2003, 694. (e) Oyama, K.; Kondo, T.
Org. Lett. 2003, 5, 209. (f) Lipshutz, B. H.; Keith, J.
Tetrahedron Lett. 1998, 39, 2495. (g) Crouch, R. D.;
Romany, C. A.; Kreshock, A. C.; Menconi, K. A.; Zile, J. L.
Tetrahedron Lett. 2004, 45, 1279. (h) Fenteany, G.; Ankala,
S. V. Tetrahedron Lett. 2002, 43, 4729. (i) Rotulo-Sims, D.;
Prunet, J. Org. Lett. 2002, 4, 4701. (j) Crouch, R. D.; Polizzi,
J. M.; Cleiman, R. A.; Yi, C. J.; Romany, C. A. Tetrahedron
Lett. 2002, 43, 7151. (k) Crouch, R. D.; Stieff, M.; Frie, J. L.;
Cadwallader, A. B.; Bevis, D. C. Tetrahedron Lett. 1999, 40,
3133. (l) Bartoli, G.; Bosco, M.; Marcantoni, E.; Sambri, L.;
Torregiani, E. Synlett 1998, 209. (m) Farras, J.; Serra, C.;
Vilarrasa, J. Tetrahedron Lett. 1998, 39, 327.
4.5.17. 6-(Benzyloxy)-1,2-hexanediol (Table 3, entry
10).23m (Eluted with n-hexane/EtOAcZ5:1, colorless oil);
1H NMR (300 MHz, CDCl3) d 7.37–7.25 (m, 5H), 4.48 (s,
2H), 3.76–3.31 (m, 5H), 3.24 (br, 2H), 1.75–1.38 (m, 6H);
13C NMR (75 MHz, CDCl3) d 138.0, 129.4, 128.8, 128.6,
72.6, 70.6, 67.2, 33.4, 30.0, 26.2, 22.6.
4.5.18. 2-[40-(Triethylsilyloxy)phenyl]ethanol (Table 4,
entry 1).22d (Eluted with n-hexane/EtOAcZ6:1, colorless
oil); H NMR (300 MHz, CDCl3) d 7.06–7.04 (m, 2H),
1
6.81–6.77 (m, 2H), 3.76 (t, JZ6.6 Hz, 2H), 2.76 (t, JZ
6.6 Hz, 2H), 2.04 (br, 1H), 1.02–0.97 (m, 9H), 0.77–0.69
(m, 6H); 13C NMR (75 MHz, CDCl3) d 154.5, 131.5, 130.3,
120.4, 64.1, 38.8, 7.0, 5.4.
6. (a) Sabitha, G.; Syamala, M.; Yadav, J. S. Org. Lett. 1999, 1,
1701. (b) Wang, M.; Li, C.; Yin, D.; Liang, X. Tetrahedron
Lett. 2002, 43, 8727. (c) Wu, Y.; Huang, J.; Shen, X.; Tang, C.;
Li, L. Org. Lett. 2002, 4, 2141. (d) Paterson, I.; Cowden, C. J.;
Rahn, V. S.; Woodrow, M. D. Synlett 1998, 915.
4.5.19. 4-(tert-Butyldimethylsilyloxy)benzyl alcohol
(Table 4, entry 2).19c (Eluted with n-hexane/EtOAcZ6:1,
colorless oil); 1H NMR (300 MHz, CDCl3) d 7.23 (m, 2H),
6.84 (m, 2H), 4.60 (s, 2H), 1.74 (br, 1H), 0.98 (s, 9H), 0.18
(s, 6H); 13C NMR (75 MHz, CDCl3) d 155.7, 132.3, 129.9,
120.3, 64.6, 25.6, 18.4, K4.0.
7. (a) Sajiki, H.; Ikawa, T.; Hattori, K.; Hirota, K. Chem.
Commun. 2003, 654. (b) Ikawa, T.; Hattori, K.; Sajiki, H.;
Hirota, K. Tetrahedron 2004, 60, 6901. (c) Kim, S.; Jacobo,
S. M.; Chang, C. T.; Bellone, S.; Powell, W. S.; Rokach, J.
Tetrahedron Lett. 2004, 45, 1973.
8. (a) Olofson, R. A.; Martz, J. T.; Senet, J.-P.; Piteau, M.;
Malfroot, T. J. Org Chem. 1984, 49, 2081. (b) Yang, B. V.;
O’Rouke, D.; Li, J. Synlett 1993, 195.
4.5.20. 2-[40-(tert-Butyldimethylsilyloxy)phenyl]ethanol
(Table 4, entry 3).23n (Eluted with n-hexane/EtOAcZ6:1,
colorless oil); 1H NMR (300 MHz, CDCl3) d 7.08–7.06 (m,
2H), 6.81–6.77 (m, 2H), 3.58 (t, JZ6.6 Hz, 2H), 2.80–2.76
(t, JZ6.6 Hz, 2H), 2.10 (s, 1H), 1.00 (s, 9H), 0.11 (s, 6H);
13C NMR (75 MHz, CDCl3) d 154.6, 131.5, 130.3, 120.5,
64.1, 38.8, 26.1, 18.6, K4.0.
9. (a) Davies, J. S.; Higginbotham, C. L.; Tremeer, E. J.; Brown,
C.; Treadgold, R. C. J. Chem. Soc., Perkin. Trans. 1 1992,
3043. (b) Cunico, R. F.; Bedell, L. J. Org. Chem. 1980, 45,
4797.
10. Determined from GC analysis using HP-5 column (Cross-
linked 5% PH ME Polysiloxane).
4.5.21. 2-[40-(tert-Butyldiphenylsilyloxy)phenyl]ethanol
(Table 4, entry 4).23o (Eluted with n-hexane/EtOAcZ6:1,
colorless oil); 1H NMR (300 MHz, CDCl3) d 7.73–7.70 (m,
4H), 7.41–7.33 (m, 6H), 6.94–6.91 (m, 2H), 6.72–6.69 (m,
2H), 3.77–3.71 (m, 2H), 2.74–2.68(m, 2H), 1.47(br, 1H), 1.09
(s, 9H); 13C NMR (75 MHz, CDCl3) d 154.6, 136.0, 133.4,
131.1, 130.3, 128.2, 126.3, 120.2, 64.1, 38.7, 27.0, 20.0.
11. We examined the selective TES cleavage over TBDMS with
lower amount of thionyl chloride (0.01, 0.02, 0.025 mol%),
and the results were still less desirable than those obtained with
1-chloroethyl chloroformate (83–89% yield vs 93–95%,
respectively).
12. Per suggestion from one of the reviewers, commercially
available 1.25 M HCl in methanol (Fluka) was examined in

C.-E. Yeom et al. / Tetrahedron 61 (2005) 12227–12237
12237
the desilylation. By employing varying amounts of HCl in
methanol from 0.025, 0.05, 0.1, to 0.2 mol%, we obtained
mono-desilylated alcohol (Table 1, 1) in 85, 89, 86, and 76%
yields, respectively, along with diols. These yields were 8–21%
lower than those obtained with CEC. When a very small
amount (w0.01 mol%) of methanolic HCl was employed, the
yield of TES removal was less than 6%, and most starting
material was recovered. We also carried out selective TBDMS
removal over TIPS with 8a with varying amount of HCl, and
yields were 73–83%, which are again lower than those
obtained with CEC.
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