The reaction of acetal-type protective groups in combination with TMSOTf and 2,2′-bipyridyl; Mild and chemoselective deprotection and direct conversion to other protective groups

Article abstract of DOI:10.1016/j.tet.2011.02.048

A mild and chemoselective deprotection method of various acetal-type protective groups, such as MOM, MEM, BOM, and SEM ethers, has been developed. The combination of TMSOTf and 2,2′-bipyridyl was very effective for the deprotection, and the reaction proceeded via the formation of pyridinium intermediates, which were hydrolyzed to the corresponding alcohols in good to high yields. The features of this method are mild (almost neutral) reaction conditions and the tolerability of acid-sensitive functional groups. This method is also applicable for the direct conversion of MOM ether to BOM or SEM ether using the appropriate alcohols instead of H₂O.

Full text of DOI:10.1016/j.tet.2011.02.048

Tetrahedron 67 (2011) 2949e2960
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The reaction of acetal-type protective groups in combination with TMSOTf and
2,20-bipyridyl; mild and chemoselective deprotection and direct conversion to
other protective groups
*
Hiromichi Fujioka , Yutaka Minamitsuji, Ozora Kubo, Kento Senami, Tomohiro Maegawa
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 January 2011
Received in revised form 16 February 2011
Accepted 17 February 2011
Available online 23 February 2011
A mild and chemoselective deprotection method of various acetal-type protective groups, such as MOM,
MEM, BOM, and SEM ethers, has been developed. The combination of TMSOTf and 2,20-bipyridyl was
very effective for the deprotection, and the reaction proceeded via the formation of pyridinium in-
termediates, which were hydrolyzed to the corresponding alcohols in good to high yields. The features of
this method are mild (almost neutral) reaction conditions and the tolerability of acid-sensitive functional
groups. This method is also applicable for the direct conversion of MOM ether to BOM or SEM ether using
the appropriate alcohols instead of H2O.
Keywords:
Deprotection
Chemoselective
MOM-type ether
2,20-Bipyridyl acetal
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
to the acidity of the reagents. Therefore, a milder deprotection
method is necessary and has been desired.
The protection of functional groups is fundamental in organic
syntheses, especially when constructing complex molecules. A
number of protective groups have been developed to date since
appropriate choice of them is the key for the success of total syn-
thesis. Deprotection is also important and must be conducted under
mild reaction conditions in order to avoid any side reactions with
sensitive functional groups as well as racemization or epimerization
of stereo center because the protective groups are often cleaved at
late stage in the synthesis.1 Many protective groups for the hydroxy
group have been developed,2 and the acetal-type protective groups
are one of the most popular groups and recognized as very
useful. Acetal is known to be stable not only under strongly basic to
neutral conditions but also to the strong nucleophiles including or-
ganometallic and hydride reducing reagents. Various acetal-type
protective groups, such as the methoxymethyl (MOM), tetrahy-
dropyranyl (THP), and methoxyethoxymethyl (MEM) ethers, are
widely used in organic syntheses. In addition, these groups can be
used as directing groups by their chelating ability. The deprotection
of these acetal-type protective groups is generally performed under
mildly acidic conditions. However, rather strongly acidic conditions
are sometimes required to cleave them depending on the substrates
and undesirable side reactions of other functional groups occur due
We have recently developed a novel chemoselective depro-
tection of dimethylacetals using triethylsilyl triflate (TESOTf)/2,4,6-
collidine that allows the ketals to remain intact (Scheme 1).3 The
reaction conditions are mild and the reaction proceeded via the
selective formation of the collidinium intermediates, which are
susceptible to hydrolysis to give the hemiacetal. The chemo-
selectivity toward the acetals arises from the selective coordination
of TESOTf to the less hindered acetal oxygen. Many acid-labile
functional groups, such as trityl ether and TBS ether are tolerable in
this reaction.
TESOTf
TESOTf
OMe
MeO OMe
R
OMe
2,4,6-collidine MeO OMe
N
selective
formation
OMe CH2Cl2, 0 ºC
R
OMe
n
n
OMe
N
MeO OMe
R
O
OMe
MeO OMe
R
H2O MeO OMe
H
rt
OH
R
n
n
n
selective deprotection
of acetal
Scheme 1. Chemoselective deprotection of acetal in the presence of a ketal.
As an extension of this method, we developed the mild depro-
tection of THP ethers in combination with TESOTf/2,4,6-collidine4
* Corresponding author. E-mail address: fujioka@phs.osaka-u.ac.jp (H. Fujioka).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.02.048

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H. Fujioka et al. / Tetrahedron 67 (2011) 2949e2960
as well as the MOM ethers in combination with TMSOTf (or
TESOTf)/2,20-bipyridyl.5 In these reactions, we rationalized that the
silyl triflate also selectively coordinated to the less hindered oxygen
to form the pyridinium salt by attack of the pyridine derivative.
Sequential hydrolysis led to the deprotected alcohol via the hemi-
acetal (Scheme 2).
important role in the formation of the pyridinium salt in-
termediates and hydrolysis. We then investigated the effect of the
pyridines using n-decylmethoxymethyl ether (1a) with TMSOTf
(Table 1).12 The reaction of 2,6-lutidine and 1a followed by H2O
treatment gave a trace amount of the deprotected alcohol (2a) and
the corresponding lutidinium salt as the major product (entry 2).
The more bulky 2,6-di-tert-butylpyridine and 2,6-dichloropyridine
afforded a trace amount of 2a, while the starting material 1a and
byproduct13 were mainly obtained (entries 3 and 4). The depro-
tection effectively proceeded to give the corresponding alcohol (2a)
in 77% yield when 2-chloropyridine was used (entry 5). Surpris-
ingly, the results of the deprotection with the similar 2-substituted
pyridine, 2-phenylpyridine, and 2,20-bipyridyl, were quite different.
The reaction with 2,20-bipyridyl was completed within 6 h and 2a
was obtained in 85%, but 2-phenylpyridine gave 2a in 75% yield
even after 72 h (entries 6 and 7). 4,4-Bipyridyl formed the corre-
sponding pyridinium salt at rt but successive hydrolysis did not
occurred (entry 8).
TESOTf
O
O
OTES
3
R
O
O
O
N
TESOTf (TMSOTf)
Pyridines
R
R
CH2Cl2
R'
R'
O
O
O
O
N
O
N
TESOTf
R'
selective coordination
O
OTES
3
R
H2O
R
OH
OH
R'
OH
O
OH
Table 1
R'
Scheme 2. Mild deprotection of the THP and MOM ethers.
Effect of pyridinesa
Pyridines
(3.0 equiv.)
TMSOTf (2.0 equiv.)
CH2Cl2, 0 ºC, 0.5 h
H2O–Et2O
rt, Time
OH
OMOM
8
8
2a
1a
We were next interested in the deprotection of other acetal-type
protective groups, i.e., MEM, benzyloxymethyl (BOM) and trime-
thylsilylethoxymethyl (SEM) ethers, which have more bulky sub-
stituents than the THP and MOM ethers.
In this paper, we report the mild and efficient deprotection of
acetal-type protective groups, such as the MEM, BOM and SEM
ethers including the MOM ether, and the investigation of the re-
action mechanism in detail. Further application to the direct con-
version of MOM ethers to other protective groups is also described.
Entry
Pyridines
Time [h]
Yield [%]
1
2
3
4
5
6
7
8
2,4,6-Collidine
2,6-Lutidine
24
24
24
24
24
72
6
Traceb
Traceb
Traceb
3
77
75
2,6-Di-tert-butylpyridine
2,6-Dichloropyridine
2-Chloropyridine
2-Phenylpyridine
2,20-Bipyridyl
83
4,40-Bipyridyl
24
Traceb,c
a
Reaction conditions: 1a (1.0 equiv), TMSOTf (2.0 equiv) and the pyridine
(3.0 equiv) in CH2Cl2 (0.2 M) were stirred at 0 ꢁC for 0.5 h, then H2O and Et2O were
added and stirred at rt.
2. Results and discussion
b
Formation of the pyridinium salt was detected by TLC analysis.
2.1. Deprotection of MOM ethers
c
Pyridinium salt was formed at rt for 1 h.
The deprotection of the MOM ether is usually performed under
acidic conditions using protic acids,6 Lewis acids,7 Lewis acid-thiol,8
boron halides,9 and other reagents10 in protic or aprotic media.
However, some methods cause undesirable side reactions of other
functional groups due to the acidity of the reagents. Therefore,
a few methods for the deprotection of the MOM ether with acid-
labile functional groups have been reported,11 but they require
We employed the combination of TMSOTf (or TESOTf) and 2,20-
bipyridyl as the optimized conditions and next examined the
deprotection of diverse MOM ethers (Table 2).
MOM-protected aliphatic primary, secondary, and tertiary al-
cohols were easily deprotected under the stated conditions and the
corresponding alcohols were obtained in high yields (Table 2, en-
tries 1e6). The use of both TMSOTf and TESOTf gave almost similar
results in these cases. However, in the case of the MOM ether of the
allyl alcohol 1d, TMSOTf was more effective (entries 7 and 8). Other
hydroxy protecting groups, such as the acetyl, benzoyl, and benzyl
groups, were tolerated under the stated conditions (entries 9ꢀ14).
It is noteworthy that the selective deprotection of the MOM ether
could be achieved in the presence of acid-sensitive TBS ether, trityl
ether and tert-butyl ester (entries 15e19), while the reaction of the
MOM ether containing a tert-butyl ester resulted in a slight de-
crease of the yield (74%).14 These results indicated that the reaction
conditions are nearly neutral. Some conventional deprotection
methods under acidic conditions are known to cause undesirable
side reactions with acid-sensitive functionalities due to their
acidity.7c,d,15 The presence of a methyl ester, halogen, and amide did
not affect the reaction although the additional TMSOTf and 2,20-
bipyridyl were necessary in the case of the amide (entries 20e23).
The aromatic MOM ether, interestingly, is less reactive under the
stated conditions (entries 24 and 25) and no pyridinium in-
termediate was formed at all for the combination of TESOTf and
a
high reaction temperature or limit the generality of the
substrates.
We first attempted our deprotection method of the THP ether
(TESOTf and 2,4,6-collidine) to the deprotection of the MOM ether,
but only the stable collidinium salt was obtained even after a 24 h-
treatment with H2O (Scheme 3).
These results are attributed to the steric hindrance around the
acetal carbons. The structures of the pyridines may play an
O
R
OTES
2
H2O
N
O
R
R
OH
OH
10 min
OTf
TESOTf
R
n
2,4,6-colli
di e
O
O
H2O
24 h
CH2Cl2, 0 ºC
0.5 h
O
O
N
R
R
OTf
stable
Scheme 3. The reaction of the THP and MOM ethers with TESOTf and 2,4,6-collidine.

H. Fujioka et al. / Tetrahedron 67 (2011) 2949e2960
2951
Table 2
Deprotection of the MOM ether by TMSOTf (TESOTf)/2,20-bipyridyla
TMSOTf or TESOTf (2.0 equiv.)
2,2'-bipyridyl (3.0 equiv.)
H2O–Et2O
rt, Time
R
R
OH
2
OMOM
1
CH2Cl2, 0 ºC, 0.5 h
Entry
1
Substrate
Silyl triflate
Time [h]
6
Yield [%]
85 (2a)
TMSOTf
OMOM
8
(1a)
2
3
TESOTf
6
2
90 (2a)
91 (2b)
TMSOTf
(1b)
OMOM
7
4
5
TESOTf
2
1
81 (2b)
99 (2c)
TMSOTf
6
7
TESOTf
2
92 (2c)
81 (2d)
TMSOTf
10
8
9
TESOTf
7
5
55 (2d)
89 (2e)
TMSOTf
10
11
12
13
14
15
16
17
18b
TESOTf
TMSOTf
TESOTf
TMSOTf
TESOTf
TMSOTf
TESOTf
TMSOTf
TESOTf
5
5
5
5
5
5
4
4
91 (2e)
93 (2f)
86 (2f)
86 (2g)
87 (2g)
88 (2h)
91 (2h)
92 (2i)
82 (2i)
(R¼Bz) (1f)
(R¼Bn) (1g)
(R¼TBS) (1h)
(R¼Tr) (1i)
2.5
19
TMSOTf
8
7
74 (2j)
20
TMSOTf
96 (2k)
21
TMSOTf
TMSOTf
7
9
88 (2l)
22c
86 (2m)
23c
24
TMSOTf
6
94 (2n)
TMSOTf
TESOTf
24
24
19 (2o)
25
n.r.d
a
Reaction conditions: 1 (1.0 equiv), TMSOTf (2.0 equiv) and 2,20-bipyridyl (3.0 equiv) in CH2Cl2 (0.2 M) were stirred at 0 ꢁC for 0.5 h, then H2O and Et2O were added and
stirred at rt.
b
c
The reaction was conducted in CH2Cl2 (0.5 M).
TMSOTf (4.0 equiv) and 6.0 equiv of 2,20-bipyridyl were used.
No pyridinium salt was formed.
d

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H. Fujioka et al. / Tetrahedron 67 (2011) 2949e2960
2,20-bipyridyl (entry 25). Conventional methods could simulta-
neously cleave both the aliphatic and phenolic MOM ethers,7c,d,10d,e
and also the preferential cleavage of the phenolic MOM ether to
that of the aliphatic one was reported in some methods.10c,d Our
results then led us to examine the opposite chemoselective
deprotection between the aliphatic and aromatic MOM ethers. As
a result, the aliphatic MOM ether was preferentially cleaved in the
presence of the aromatic one to give the mono-MOM protected
alcohol (2p) in high yield (Scheme 4).
2.3. Deprotection of BOM and SEM ethers
For further application to other acetal-type protective groups,
we chose the BOM and SEM ethers. Various deprotection methods
for the BOM17 and SEM8b,17d,18 ethers have already been developed.
The BOM ethers can be cleaved by reduction with a metal or
hydrogenolysis17aei as well as by protic or Lewis acids.17jep The SEM
ethers are also cleaved under acidic conditions,8b,18aej and another
effective method is exposure to fluoride species.18ket Although
these cleavage methods are well-established, some require rather
harsh conditions. Therefore, it is worthwhile to develop another
mild method for their deprotection. We were also interested in the
deprotection of these ethers bearing bulky substituents because
a Lewis acid coordinates to the less hindered acetal oxygen, which
seems to be important in our method. We found that the TMSOTf
and 2,20-bipyridyl conditions were effective for the cleavage of the
BOM and SEM ethers (Table 4). Both ethers could be removed within
6 h to afford the corresponding alcohols in good yields, while an
additional 0.5 h stirring was necessary for the complete formation of
the pyridinium salt in the case of the BOM ethers. Other functional
groups including the acid-labile trityl group survived under these
TESOTf (2.0 equiv.)
2,2'-bipyridyl (3.0 equiv.)
MOMO
MOMO
H2O
OH
OMOM
Et2O, rt
14 h
CH2Cl2, 0 ºC, 0.5 h
3
3
1p
2p (85%)
Scheme 4. Selective deprotection of the aliphatic MOM ether in the presence of the
phenolic MOM ether.
2.2. Deprotection of MEM ethers
To expand the utility of our method, we investigated the
deprotection of various acetal-type protective groups. The MEM
group, a similar protective group to MOM, is also widely utilized
and its deprotection is usually conducted under acidic con-
ditions.6d,9b,c,10b,16 We next applied our method to the deprotection
of the MEM ethers (Table 3). The reaction proceeded without any
reaction time increase to give the corresponding alcohols in high
yields. Other functional groups, such as the trityl ether, ester, hal-
ogen, and amide, are tolerable under the stated conditions without
any loss of the functional group (entries 4e7).
Table 4
The deprotection of the BOM and SEM ethers by TMSOTf/2,20-bipyridyla
Entry
1
Substrate
Protecting group (PG)
Time [h]
6
Yield [%]
BOM (4a)
85 (1a)
Table 3
The deprotection of the MEM ether by TMSOTf/2,20-bipyridyla
2
SEM (5a)
BOM (4b)
SEM (5b)
BOM (4c)
SEM (5c)
BOM (4d)
SEM (5d)
BOM (4e)
SEM (5e)
BOM (4f)
SEM (5f)
BOM (4g)
SEM (5g)
4
3
2
1
1
3
3
4
3
5
4
5
4
92 (1a)
82 (2b)
84 (2b)
88 (2c)
87 (2c)
84 (2i)
89 (2i)
95 (2k)
95 (2k)
88 (2l)
92 (2l)
90 (2n)
90 (2n)
3
Entry
1
Substrate
Time [h]
6
Yield [%]
4
90 (2a)
5
2
3
3
1
88 (2b)
91 (2c)
6
7
8
4
5
5
6
87 (2i)
92 (2k)
9
10
11
12
13b
6
5
6
95 (2l)
7b
96 (2n)
14b
a
Reaction conditions:
3
(1.0 equiv), TMSOTf (2.0 equiv) and 2,20-bipyridyl
(3.0 equiv) in CH2Cl2 (0.2 M) were stirred at 0 ꢁC for 0.5 h, then H2O and Et2O were
added and stirred at rt.
a
Reaction conditions: 4 or 5 (1.0 equiv), TMSOTf (2.0 equiv) and 2,20-bipyridyl
(3.0 equiv) in CH2Cl2 (0.2 M) were stirred at 0 ꢁC for 1 h (BOM ether 4) or 0.5 h (SEM
ether 5), then H2O and Et2O were added and stirred at rt.
b
TMSOTf (4.0 equiv) and 6.0 equiv of 2,20-bipyridyl were used.
b
TMSOTf (4.0 equiv) and 6.0 equiv of 2,20-bipyridyl were used.

H. Fujioka et al. / Tetrahedron 67 (2011) 2949e2960
2953
conditions (entries 7e14). This method will provide a new and
complementary deprotection of these protective groups.
2,6-di-tert-butylpyridine did not give the corresponding pyr-
idinium intermediate at all and 2,6-dichloropyridine led to un-
desirable side reactions (Table 1, entries 3 and 4). The successful
deprotection was achieved by using the 2-substituted pyridines
(Table 1, entries 5e7). It is of interest that the substituents at the 2-
position on pyridine ring significantly affected the reaction rate.
The pyridinium intermediate was formed within 0.5 h in each case,
but the hydrolysis is much different. 2,20-Bipyridyl is the most ef-
fective for the hydrolysis affording 2 in 6 h, while 2-chloropyridine
and 2-phenylpyridine yielded 2 in 24 h and 72 h, respectively. It
should be noted that 2,20-bipyridyl and 2-phenylpyridine showed
very different reactivity regardless of their similar structure. We
presumed that the hydrogen bond between H2O and the nitrogen
on the pyridine ring may help to bring the H2O close to the acetal
carbon and make the nucleophilic attack by H2O easier, although
the electronic effect could not be excluded.
2.4. Presumable reaction mechanism of deprotection of
various acetal-type protective groups
The presumable reaction mechanism is shown in Scheme 5.
First, TMSOTf coordinated the less hindered acetal oxygen,19 then
2,20-bipyridyl attacked the activated acetal carbon affording the
pyridinium intermediate. In the case of the BOM and SEM ethers,
the coordination manner may be different since they have bulky
substituents compared to the MOM and MEM ethers. Therefore,
two reaction pathways (paths a and b) are possible for the reaction
of TMSOTf and 2,20-bipyridyl and different intermediates, A and B,
could be generated. The reaction of A with H2O would give the
hemiacetal, which leads to the deprotected alcohol 2. The TMS-
protected alcohol B is also deprotected during the work-up giving 2
as a result. To reveal the major reaction pathway of each protective
group, we carried out the substitution reaction of the pyridinium
intermediates generated from the MOM, MEM, BOM, and SEM
ethers with allyl alcohol as the nucleophile under TMSOTf and 2,20-
bipyridyl conditions (Scheme 6).3b,4a,20 The coordination manner
2.5. Direct conversion of MOM ethers to BOM and SEM ethers
As a furtherextension of this method, we next examined the one-
pot conversion of the MOM ether to other acetal-type protective
groups by the nucleophilic substitution using the appropriate alco-
Me3Si OTf
O
O
N
H2O
R
PG
O
OH
path a
N
O
R
OH
R
H
O
OH
N
2
N
hemiacetal
R
N
N
Me SiOPG
R
OTf
OTf
OH
A
TMSOTf
O
O
R
2,2'-bipyridyl
1
Me3Si OTf
work-up
O
R
O
N
O
PG
R
R
SiMe3
path b
2
B
N
N
O
N
PG
Scheme 5. Presumed reaction mechanism for deprotection of acetal-type protective groups by TMSOTf and 2,20-bipyridyl.
TMSOTf
2,2'-bipyridyl
hol to the pyridinium salt. A direct conversion of one protective
group to another one should be a convenient and useful method in
syntheses. A few methods for the direct conversion of the acetal-
type protective group were reported. Magnus and co-worker
reported the direct conversion of the methylthiomethyl ether to
cyanomethyl ether with ZnI2 and TMSCN.22a Corey and co-workers
also reported the conversion of the MEM ether to i-propylthioether
with (i-PrS)2BBr and to cyanomethyl ether with Et2AlCN,16d re-
spectively. The reaction of acetal-type protective groups including
MOM and MEM ethers with Me2BBr were reported by Guindon and
co-workers22b,c and gave rise to the bromo methyl ethers as reactive
intermediates. Successive treatment with alcohols, thiols, and cya-
nide to give the corresponding substituted ethers. However, some of
these reactions must be conducted at ꢀ78 ꢁC. In our case, the MOM
ether was readily converted to the pyridinium salt at 0 ꢁC and the
substitution of the salt with the allyl alcohol gave the desired
product in 76% yield within 24 h at rt (Scheme 6). We then per-
formed the direct conversion of the MOM ether using the appro-
priate alcohols, such as benzyl alcohol and trimethylsilylethanol, to
the BOM and SEM ethers in a one-pot procedure. The successful
conversionwas achieved using an excess amount of R0OH (5.0 equiv)
instead of H2O to give the BOM and SEM ethers in good yields
(Table 5). No significant improvement in the yield and reaction time
was observed by increasing R0OH (10 equiv) (entry 2). Another
functional group within a molecule can be tolerated under these
OH
O
9
O-allyl
OH
9
O
9
O
R
+
CH2Cl2, 0 ºC rt, 24 h
0.5 h
2a
6
R = CH3
CH3OCH2CH2 (MEM)
Bn (BOM)
TMSCH2CH2 (SEM)
(MOM)
76%
78%
72%
40%
7%
10%
20%
49%
Scheme 6. The substitution reaction of acetal-type ethers with allyl alcohol in com-
bination with TMSOTf and 2,20-bipyridyl.
could be estimated by comparison with the yields of the substituted
product (allyloxymethyl ether) 6 and deprotected alcohol 2a de-
rived from TMS-protected alcohol during the reaction.
As expected, the reaction of the MOM and MEM ethers gave 6 as
themainproductandasmallamountofthefreealcohol2a.21 Asimilar
tendency was observed in the case of the BOM ether although the
phenyl ring of the BOM ether seems to be more bulky than the other
side substituent. The SEM ether afforded the comparable mixture of 6
and 2a (4:4.9). Consequently, the deprotection proceeded in both
pathways, but path a is the major one except for the SEM ether.
On the other hand, the bulkiness of the pyridine derivative plays
a very important role in this reaction. The less bulky 2,6-lutidine
and 2,4,6-collidine could form the pyridinium intermediates, but
no hydrolysis occurred (Table 1, entries 1 and 2). The more bulky

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H. Fujioka et al. / Tetrahedron 67 (2011) 2949e2960
DMAP (0.1 equiv) in dry CH2Cl2 (0.2e0.5 M) was stirred at 0 ꢁC to rt
under N2. After disappearance of the alcohol on TLC, the mixture
was evaporated in vacuo. The residue was purified by flash SiO2
column chromatography to give a MOM/ether. 1a,10b 1b,23 1c,24
1d,25 1o,26 and 1p27 are known compounds.
Table 5
The direct conversion of the MOM ether into other acetal-type protective groupsa
TMSOTf (2.0 equiv.)
2,2'-bipyridyl (3.0 equiv.)
O
OR'
R'
OH
R
MOM
O
R
CH2Cl2, 0 ºC, 0.5 h
rt, Time
1
4 or 5
4.2.1.1. Compound 1k. According to the general procedure,
treatment of methyl 1-hydroxydodecanoate 2k28 (1.51 g, 6.56 mmol)
with MOMCl (0.99 mL, 13.1 mmol), iPr2NEt (3.3 mL, 19.7 mmol), and
DMAP (80.6 mg, 0.66 mmol) gave 1k (1.68 g, 93%). Eluent; n-hexane/
AcOEt (15/1). Colorless oil; IR (KBr): 2929, 1730, 1217, 912,
Entry
Substrate
R0
Product
Time [h]
Yield [%]
1
1a
Bn
Bn
4a
4a
5a
4b
5b
4c
5c
4d
5d
4e
5e
4f
22
22
5
6
3
4
1
20
6
14
6
80
81
80
76
82
79
77
73
78
77
84
86
75
82
84
2b
3
TMS(CH2)2
Bn
TMS(CH2)2
Bn
TMS(CH2)2
Bn
TMS(CH2)2
Bn
TMS(CH2)2
Bn
TMS(CH2)2
Bn
4
5
6
7
8
9
10
11
12
13
14c
15c
1b
1c
1i
770 cmꢀ1
; d 1.27e1.36 (m, 14H),
1H NMR (500 MHz, CDCl3):
1.56e1.65 (m, 4H), 2.30 (t, J¼7.5 Hz, 2H), 3.36 (s, 3H), 3.52 (t,
J¼7.0 Hz, 2H), 3.67 (s, 3H), 4.62 (s, 2H) ppm; 13C NMR (125 MHz,
CDCl3):
d 25.0, 26.2, 29.2, 29.3, 29.4, 29.5, 29.6, 29.8, 34.1, 51.4, 55.1,
1k
1l
67.9, 96.4, 174.3 ppm; HRMS (FAB): calcd for C15H31O4 [MþH]þ
275.2222, found 275.2204.
24
6
13
7
5f
4g
5g
1n
4.2.2. Preparation of MOM ether 1eei. MOM ethers 1eei were
TMS(CH2)2
prepared from 12-methoxymethoxydodecanol.29
a
Reaction conditions: 1 (1.0 equiv), TMSOTf (2.0 equiv), 2,20-bipyridyl (3.0 equiv)
in CH2Cl2 (0.2 M) at 0 ꢁC for 0.5 h, then R0OH (5.0 equiv) were added and stirred at rt.
4.2.2.1. Compound 1e. (R¼Ac);
a solution of 12-methoxy-
b
BnOH (10 equiv) was used.
TMSOTf (4.0 equiv) and 6.0 equiv of 2,20-bipyridyl were used.
methoxydodecanol (309 mg, 1.25 mmol), Ac2O (0.21 mL,
2.25 mmol), iPr2NEt (0.78 mL, 4.51 mmol), and DMAP (14.6 mg,
0.120 mmol) in dry CH2Cl2 (6.3 mL) was stirred at rt under N2 for
1 h. The reaction mixture was evaporated in vacuo. The residue was
purified by flash SiO2 column chromatography (n-hexane/
AcOEt¼12/1) to give 1e (352 mg, 97%). Colorless oil, IR (KBr): 2926,
c
conditions. A small amount of the MOM ether was regenerated
during the reaction in each case, which resulted in a decreased yield
since CH3OH re-attacked the generated pyridinium salt.
2855,1742,1468,1238 cmꢀ1; 1H NMR (270 MHz, CDCl3):
d 1.27 (br s,
3. Conclusion
16H), 1.53e1.64 (m, 4H), 2.05 (s, 3H), 3.36 (s, 3H), 3.52 (t, J¼6.5 Hz,
2H), 4.05 (t, J¼6.8 Hz, 2H), 4.62 (s, 2H) ppm; 13C NMR (75 MHz,
We have developed a novel and efficient deprotection method of
various acetal-type protective groups, such as the MOM, MEM, BOM,
and SEM ethers. This method has wide applicability of the substrates
having acid-sensitive groups, esters, halogens, and amides, which
indicated that our conditions are very mild and almost neutral in
contrast to the previous methods (strong acidic con-
ditions).6e10,16,17jep,18aej The one-pot conversion to the BOM and SEM
ethers from the MOM ethers is facile and efficient replacement of the
protectivegroup.Webelievethatthepresentmethodwouldbeuseful
and enhance the utility of the MOM ethers in organic syntheses, and
will also be employed as an alternative in synthetic strategies.
CDCl3): d 20.7, 25.7, 26.0, 28.4, 29.0, 29.23, 29.28, 29.32, 29.34, 29.4,
29.5, 54.8, 64.3, 67.6, 96.1, 170.8 ppm; HRMS (FAB): calcd for
C16H33O4 [MþH]þ: 289.2379, found 289.2377.
4.2.2.2. Compound 1f. (R¼Bz);
a
solution of 12-methoxy-
BzCl (0.28 mL,
methoxydodecanol (330 mg, 1.34 mmol),
2.41 mmol), iPr2NEt (0.82 mL, 4.82 mmol), and DMAP (16.3 mg,
0.133 mmol) in dry CH2Cl2 (6.7 mL) was stirred at rt under N2 for
17.5 h. The mixture was evaporated in vacuo. The residue was pu-
rified by flash SiO2 column chromatography (n-hexane/benzene¼1/
10 to n-hexane/AcOEt¼5/1) to give 1f (440 mg, 94%). Colorless oil,
IR (KBr): 2930, 2855, 1713, 1468, 1279 cmꢀ1 1H NMR (270 MHz,
;
4. Experimental section
4.1. General
CDCl3):
d 1.28e1.43 (m, 16H), 1.51e1.61 (m, 2H), 1.71e1.82 (m, 2H),
3.36 (s, 3H), 3.52 (t, J¼6.8 Hz, 2H), 4.31 (t, J¼6.8 Hz, 2H), 4.62 (s, 2H),
7.40e7.46 (m, 2H), 7.52e7.59 (m, 1H), 8.03e8.07 (m, 2H) ppm; 13C
€
Melting point (mp) was measured by Buchi B-545. Infrared spectra
NMR (100 MHz, CDCl3):
d 25.9, 26.1, 28.6, 29.2, 29.3, 29.41, 29.45,
(IR) were recorded by Shimadzu FTIR 8400 using a diffuse reflectance
29.48, 29.7, 54.9, 65.0, 67.7, 96.3, 128.2, 129.4, 130.4, 132.7,
166.5 ppm; HRMS (FAB): calcd for C21H35O4 [MþH]þ: 351.2535,
found 351.2528.
measurement of samples dispersed in KBr powder. 1H NMR and 13
C
NMRspectrawererecordedonaJEOLJNM-LA500, JNM-ECS400,JNM-
AL 300 JMN-EX 270 spectrometer in CDCl3 with tetramethylsilane as
an internal standard. Data are reported as follows: chemical shift in
4.2.2.3. Compound 1g. (R¼Bn); to a solution of 12-methoxy-
methoxydodecanol (308 mg, 1.25 mmol) in dry THF (3.1 mL), BnBr
(0.22 mL, 1.88 mmol), and NaH (76.8 mg, 1.92 mmol) were added
successively at rt under N2 and stirred for 20 h. H2O was added to
the reaction mixture and the resulting solution was extracted with
CH2Cl2. The organic layer was dried over Na2SO4, filtered, and
evaporated in vacuo. The residue was purified by flash SiO2 column
chromatography (n-hexane/AcOEt¼15/1) to give 1g (364 mg, 86%).
parts per million (
d
), integration, multiplicity (s¼singlet, d¼doublet,
t¼triplet, q¼quartet, m¼multiplet, br s¼broad singlet) and coupling
constant (Hz). Mass spectra were obtained on a Shimadzu GCeMS-QP
5000 instrument with ionization voltages of 70 eV. Column chroma-
tography and TLC were carried out on Merck Silica gel 60
(230e400 mesh), Kanto kagaku Silica gel 60 N (40e50 mm, spherical,
neutral), and Merck silica gel F254 plates (0.25 mm), respectively. The
commercially available reagents were used without further purifica-
tion. Alcohols 2aed, 2l, and 2o are commercially available.
Colorless oil, IR (KBr): 2926, 2853, 1454, 1209 cmꢀ1 1H NMR
;
(300 MHz, CDCl3):
3.44e3.54 (m, 4H), 4.50 (s, 2H), 4.62 (s, 2H), 7.26e7.35 (m, 5H)
ppm; 13C NMR (75 MHz, CDCl3):
26.11, 26.14, 29.36, 29.39, 29.5,
d 1.26 (br s, 16H), 1.56e1.61 (m, 4H), 3.36 (s, 3H),
4.2. Preparation of MOM ethers 1
d
29.66, 29.68, 54.9, 67.7, 70.4, 72.7, 96.2, 127.3, 127.5, 128.2,
138.6 ppm; HRMS (FAB): calcd for C21H36O3Na [MþNa]þ: 359.2562,
found 359.2563.
4.2.1. Preparation of 1aed, 1k, 1o, and 1p10b. A solution of an al-
cohol (1 equiv), MOMCl (1.5e1.8 equiv), iPr2NEt (3e3.6 equiv), and

H. Fujioka et al. / Tetrahedron 67 (2011) 2949e2960
2955
4.2.2.4. Compound 1h. (R¼TBS); a solution of 12-methoxy-
methoxydodecanol (308 mg, 1.25 mmol), TBSCl (332 mg,
2.21 mmol), iPr2NEt (0.78 mL, 4.50 mmol), and DMAP (15.0 mg,
0.123 mmol) in dry CH2Cl2 (6.3 mL) was stirred at rt under N2 for
4 h. The mixture was evaporated in vacuo. The residue was purified
by flash SiO2 column chromatography (n-hexane/AcOEt¼25/1,
neutral) to give 1h (428 mg, 95%). Colorless oil, IR (KBr): 2856, 2251,
28.2, 28.8, 29.37, 29.40, 29.5, 29.8, 32.3, 33.9, 55.1, 67.9, 96.5 ppm.
Anal. Calcd for C12H25BrO2: C, 51.25; H, 8.96; Br, 28.41, found: C,
51.39; H, 8.81; Br, 28.08.
4.2.5. Preparation of MOM ethers 1m and 1n. MOM ethers 1m and n
were prepared from 1,9-nonanediol in three steps via 9-methox-
ymethoxy-1-nonanol 7 and 1-amino-9-methoxymethoxynonane 8.
1794, 1470, 1385 cmꢀ1 1H NMR (400 MHz, CDCl3):
; d 0.04 (s, 6H),
0.89 (s, 9H), 1.27 (br s, 16H), 1.47e1.63 (m, 4H), 3.36 (s, 3H), 3.52 (t,
J¼6.8 Hz, 2H), 3.60 (t, J¼6.8 Hz, 2H), 4.62 (s, 2H) ppm; 13C NMR
(100 MHz, CDCl3):
d
ꢀ5.3, 18.4, 25.8, 26.0, 26.2, 29.4, 29.56, 29.58,
29.61, 29.7, 32.9, 55.1, 63.3, 67.8, 96.3 ppm; HRMS (FAB): calcd for
C20H45O3Si [MþH]þ: 361.3138, found 361.3162.
4.2.2.5. Compound 1i. (R¼Tr);
a solution of 12-methoxy-
methoxydodecanol (232 mg, 0.942 mmol), TrCl (485 mg,
1.74 mmol), iPr2NEt (0.60 mL, 3.51 mmol) and TBAI (35.0 mg,
0.095 mmol) in dry CH2Cl2 (1.0 mL) was stirred at rt under N2 for
24 h. The mixture was evaporated in vacuo. The residue was puri-
fied by flash SiO2 column chromatography (n-hexane/AcOEt¼15/1,
neutral) to give 1i (448 mg, 97%). Colorless oil, IR (KBr): 2926, 2853,
4.2.5.1. Synthesis of 9-methoxymethoxy-1-nonanol 7. A solution
of 1,9-nonanediol (4.01 g, 25.0 mmol), MOMCl (1.88 mL,
25.0 mmol), and iPr2NEt (12.8 mL, 75.0 mmol) in dry CH2Cl2
(70 mL) was stirred at 0 ꢁC to rt under N2 for 15 h. After disap-
pearance of diol on TLC, the mixture was added to satd NH4Cl aq
and the resulting solution was extracted with CH2Cl2. The organic
layer was dried over Na2SO4 and evaporated in vacuo. The residue
was purified by flash column chromatography (n-hexane/AcOEt¼2/
1) to give 7 (2.96 g, 58%).
1448, 1217, 1150 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d 1.24 (br s, 16H),
1.54e1.64 (m, 4H), 3.03 (t, J¼6.6 Hz, 2H), 3.36 (s, 3H), 3.51 (t,
J¼6.6 Hz, 2H), 4.62 (s, 2H), 7.19e7.46 (m, 9H), 7.43e7.46 (m, 6H)
ppm; 13C NMR (100 MHz, CDCl3):
d 26.20, 26.24, 29.4, 29.5, 29.56,
29.58, 29.7, 30.0, 55.1, 63.7, 67.8, 86.2, 96.4, 126.7, 127.6, 128.7,
144.5 ppm; HRMS (FAB): calcd for C33H44O3 [M]þ: 488.3290, found
488.3290.
Compound 7: Colorless oil; IR (KBr): 3443, 2932, 1385, 1041, 912,
742 cmꢀ1 1H NMR (500 MHz, CDCl3):
; d 1.25 (s, 1H), 1.31e1.36 (m,
10H), 1.55e1.62 (m, 4H), 3.63 (s, 3H), 3.52 (t, J¼7.0 Hz, 2H),
4.2.3. Preparation of MOM ether 1j. To a solution of MOM ether 1k
3.63e3.68 (m, 2H), 4.62 (s, 2H) ppm; 13C NMR (125 MHz, CDCl3):
(1.37 g, 5.00 mmol) in MeOH (10 mL) was added 2 M NaOH aq at
0
d 25.6, 26.1, 29.3, 29.4, 29.6, 32.7, 55.0, 62.8, 67.8, 96.3 ppm; HRMS
ꢁC and the mixture was stirred at rt overnight. The reaction
(FAB): calcd for C11H25O3 [MþH]þ 205.1804, found 208.1815.
mixture was acidified with diluted HCl aq and extracted with
AcOEt. The organic layer was dried over Na2SO4 and evaporated in
vacuo to give the carboxylic acid, which was used without further
purification. To a solution of the carboxylic acid in CH2Cl2 (15 mL)
were added tBuOH (631.5 mg, 8.52 mmol), EDCI (1.63 g,
8.52 mmol), and DMAP (52.5 mg, 0.43 mmol) at 0 ꢁC and the
mixture was stirred at rt for 12 h. The reaction mixture was evap-
orated and H2O was added to the residue and extracted with AcOEt.
The organic layer was washed with satd NaHCO3 aq, dried over
Na2SO4, and evaporated in vacuo. The residue was purified by
column chromatography (n-hexane/AcOEt¼10/1) to give tert-butyl
ester 1j (two steps: 270.6 mg, 17%).
4.2.5.2. Synthesis of 1-amino-9-methoxymethoxynonane 8. To
a solution of 9-methoxymethoxy-1-nonanol 7 (2.96 g, 14.5 mmol) in
dry CH2Cl2 (60 mL) were added Et3N (2.41 mL, 17.4 mmol) and MsCl
(1.35 mL, 17.4 mmol) at 0 ꢁC and the reaction mixture was stirred at
rt under N2 for 30 min. The reaction mixture was then evaporated in
vacuo to afford the crude mesylate, which was used for the next
reaction without further purification. NaN3 (2.83 g, 43.5 mmol) was
added to the solution of mesylate in DMF (50 mL) at 0 ꢁC and the
reaction mixture was stirred at rt for 14 h. The reaction mixture was
quenched by H2O at 0 ꢁC and extracted with Et2O. The organic phase
was dried over Na2SO4, filtered through the short column of SiO2
silica gel, and evaporated in vacuo to afford the crude azide. To the
azide in THF (60 mL) and H2O (5 mL) was added PPh3 (9.51 g,
36.3 mmol) at 0 ꢁC and the reaction mixture was stirred at rt for 22 h.
The mixture was then evaporated in vacuo, and the residue was
purified by flash column chromatography (CH2Cl2/MeOH¼10/1 to
CH2Cl2/MeOH/Et3N¼100/20/1) to give 1-amino-9-methoxymetho-
xynonane 8 (2.34 g, 80%; three steps).
Compound 1j: Colorless oil; IR (KBr): 2856, 1712,1219, 771 cmꢀ1
;
1H NMR (400 MHz, CDCl3):
d
1.27e1.37 (m, 14H), 1.53 (s, 9H),
1.55e1.62 (m, 4H), 2.20 (t, J¼7.6 Hz, 2H), 3.36 (s, 3H), 3.52 (t,
J¼7.2 Hz, 2H), 4.62 (s, 2H) ppm; 13C NMR (100 MHz, CDCl3):
d 25.1,
26.2, 28.1, 29.1, 29.2, 29.40, 29.48, 29.52, 29.7, 35.6, 55.0, 67.8, 79.8,
96.3, 173.3 ppm; HRMS (FAB): calcd for C18H37O4 [MþH]þ 317.2692,
found 317.2682.
Compound 8: Colorless oil; IR (KBr): 2930, 1581, 1468, 912,
4.2.4. Preparation of MOM ether 1l. MOM ether 1l was prepared
according to the procedure of literature.30 LiBr (189.3 mg,
2.18 mmol) and catalytic amount of TsOH (125.7 mg, 0.73 mmol)
742 cmꢀ1 1H NMR (400 MHz, CDCl3):
; d 1.30e1.45 (m, 14H),
1.55e1.62 (m, 2H), 2.68 (t, J¼6.8 Hz, 2H), 3.36 (s, 3H), 3.52 (t,
J¼6.8 Hz, 2H), 4.62 (s, 2H) ppm; 13C NMR (100 MHz, CDCl3):
d 26.0,
were added to
a
solution of 10-bromo-1-decanol (1.72 g,
26.7, 29.2, 29.3, 29.4, 29.6, 33.6, 42.1, 54.9, 67.7, 96.2 ppm; HRMS
7.25 mmol) in dimethoxymethane (15 mL). The reaction mixture
was stirred at rt for 5 h, treated with brine, and extracted with
hexane. The organic layer was dried over Na2SO4 and evaporated in
vacuo. The residue was purified by flash column chromatography
(n-hexane/AcOEt¼15/1) to give 1-bromo-10-methoxymethoxy-
decane 1l (956.8 mg, 47%).
(FAB): calcd for C11H26NO2 [MþH]þ 204.1964, found 204.1966.
4.2.5.3. Synthesis of 1m. Pyridine (391
mL, 4.85 mmol) and AcCl
(346 L, 4.85 mmol) were added to the solution of 1-amino-9-
m
methoxymethoxynonane 8 (657.3 mg, 3.23 mmol) in dry CH2Cl2
(25 mL) at 0 ꢁC under N2. The reaction mixture was stirred at rt for
18 h, treated with 3.5% HCl aq, and extracted with CH2Cl2. The organic
phase was dried over Na2SO4 and evaporated in vacuo. The residue
was purified by flash column chromatography (n-hexane/AcOEt¼3/1
to CH2Cl2/MeOH¼15/1) to give acetamide 1m (523.3 mg, 66%).
Compound 1l: Colorless oil; IR (KBr): 2855, 1043, 912, 743 cmꢀ1
;
1H NMR (500 MHz, CDCl3):
d
1.30e1.44 (m, 12H), 1.56e1.62 (m, 2H),
1.82e1.88 (m, 2H), 3.36 (s, 3H), 3.40 (t, J¼7.0 Hz, 2H), 3.52 (t,
J¼7.0 Hz, 2H), 4.62 (s, 2H) ppm; 13C NMR (125 MHz, CDCl3):
d 26.2,

2956
H. Fujioka et al. / Tetrahedron 67 (2011) 2949e2960
Compound 1m: Colorless oil; IR (KBr): 3298, 3086, 2928, 1651,
1553,1292,914,742 cmꢀ1;1HNMR(400 MHz,CDCl3):
1.30e1.45 (m,
DMAP (90.4 mg, 0.74 mmol) gave 3e (2.29 g, 97%). Eluent; n-hex-
d
ane/AcOEt (15/1 to 5/1).
10H), 1.47e1.51 (m, 2H), 1.55e1.62 (m, 2H), 1.97 (s, 3H), 3.23 (dt,
J¼12.8, 7.2 Hz, 2H), 3.36(s, 3H), 3.52(t, J¼6.8 Hz, 2H), 4.62(s, 2H), 5.48
Colorless oil; IR (KBr): 2928, 1730, 1219, 771 cmꢀ1 1H NMR
;
(500 MHz, CDCl3):
d 1.27e1.36 (m, 14H), 1.55e1.65 (m, 4H), 2.30 (t,
(br s,1H) ppm;13C NMR (125 MHz, CDCl3):
d
23.2, 26.1, 26.8, 29.1, 29.2,
J¼7.5 Hz, 2H), 3.34 (s, 3H), 3.53e3.57 (m, 4H), 3.66 (s, 3H),
29.4, 29.5, 29.6, 39.9, 67.8, 96.3,170.0 ppm. Anal. Calcd for C13H27NO3:
C, 63.64; H, 11.09; N, 5.71, found: C, 63.41; H, 10.90; N, 5.65.
3.68e3.70 (m, 2H), 4.71 (s, 2H) ppm; 13C NMR (125 MHz, CDCl3):
d
25.0, 26.2, 29.2, 29.3, 29.43, 29.44, 29.5, 29.6, 29.7, 34.1, 51.4, 59.0,
66.7, 68.0, 71.9, 95.5, 174.3 ppm; HRMS (FAB): calcd for C17H35O5
4.2.5.4. Synthesis of 1n. Pyridine (425
m
L, 5.27 mmol) and BzCl
[MþH]þ 319.2484, found 319.2466.
(607 L, 5.27 mmol) were added to the solution of 1-amino-9-
m
methoxymethoxynonane 8 (712.7 mg, 3.51 mmol) in dry CH2Cl2
(30 mL) at 0 ꢁC under N2. The reaction mixture was stirred at rt for
18 h, treatedwith 3.5%HClaq, andextractedwithCH2Cl2. Theorganic
phase was dried over Na2SO4 and evaporated in vacuo. The residue
was purified by flash column chromatography using n-hexane/AcOEt
(5/2) as an eluent to give benzamide 1n (1.06 g, 98%).
4.3.2. Preparation of MEM ethers 3d, 3f, and 3g. TMSOTf (2.0 equiv)
was added dropwise to a solution of MOM ether 1 (1.0 equiv) and
2,20-bipyridyl (3.0 equiv) in CH2Cl2 (0.2 M) at 0 ꢁC under N2 and the
reaction mixture was stirred for 30 min at 0 ꢁC. After disappearance
of 1 on TLC, MeOCH2CH2OH (5.0 equiv) was added to the reaction
mixture and the resulting solution was stirred at rt. After the re-
action was completed, satd NaHCO3 aq was added and the resulting
solution was extracted with CH2Cl2. The organic layer was washed
with 3.5% HCl aq, dried over Na2SO4, and evaporated in vacuo. The
residue was purified by column chromatography to give MEM
ether. For the preparation of 3g, 6.0 equiv of TMSOTf and 4.0 equiv
of 2,20-bipyridyl were used.
Compound 1n: Colorless oil; IR (KBr): 3318, 2928, 1643, 1537,
1307, 912, 742 cmꢀ1 1H NMR (400 MHz, CDCl3):
; d 1.32e1.37 (m,
10H), 1.57e1.66 (m, 4H), 3.36 (s, 3H), 3.45 (dt, J¼12.8, 7.2 Hz, 2H),
3.51 (t, J¼7.2 Hz, 2H), 4.62 (br s, 2H), 7.41e7.44 (m, 2H), 7.47e7.51
(m, 1H), 7.75e7.77 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3):
d 25.9,
26.8, 29.0, 29.1, 29.2, 29.4, 29.5, 39.9, 54.8, 67.6, 96.1, 126.7, 128.1,
130.9,134.6,167.4 ppm. Anal. Calcd for C18H29NO3: C, 70.32; H, 9.51;
N, 4.56, found: C, 70.49; H, 9.40; N, 4.57.
4.3.2.1. Compound 3d. Treatment of 1i (117.7 mg, 0.241 mmol)
with 2,20-bipyridyl (112.9 mg, 0.723 mmol), TMSOTf (87
0.482 mmol), and MeOCH2CH2OH (95 m
m
L,
L, 1.205 mmol) gave 3d
(101.4 mg, 79%). Eluent; n-hexane/AcOEt (12/1).
Colorless oil; IR (KBr): 2926, 912, 742 cmꢀ1; 1H NMR (500 MHz,
CDCl3):
4.3. Preparation of MEM ether 3
4.3.1. Preparation of MEM ethers 3aec, 3e. A solution of alcohol 2
(1.0 equiv), MEMCl (2.0 equiv), iPr2NEt (3.0 equiv), and DMAP
(0.1 equiv) in dry CH2Cl2 (0.2e0.5 M) was stirred at 0 ꢁC to rt under
N2. After disappearance of 2 on TLC, satd NH4Cl aq was added
to the mixture and the resulting solution was extracted with CH2Cl2.
The organic layer was dried over Na2SO4 and evaporated in vacuo.
The residue was purified by flash column chromatography to give
MEM ether 3. 3a is a known compound.10b
d
1.24e1.35 (m, 16H), 1.55e1.63 (m, 4H), 3.04 (t, J¼6.5 Hz,
2H), 3.39 (s, 3H), 3.52e3.57 (m, 4H), 3.69 (t, J¼5.0 Hz, 2H), 4.70 (s,
2H), 7.20e7.28 (m, 9H), 7.43e7.44 (m, 6H) ppm; 13C NMR (125 MHz,
CDCl3): d 25.0, 26.2, 29.2, 29.3, 29.4, 29.5, 29.6, 29.8, 34.1, 51.4, 55.1,
67.9, 96.4,174.3 ppm; HRMS (FAB): C35H48O4Na [MþNa]þ 555.3450,
found 555.3454.
4.3.2.2. Compound 3f. Treatment of 1l (68.2 mg, 0.243 mmol)
4.3.1.1. Compound
3a10b. Treatment
of
2a
(791.5 mg,
with 2,20-bipyridyl (113.9 mg, 0.729 mmol), TMSOTf (88
m
L,
L, 1.215 mmol) gave 3f
(72.9 mg, 92%). Eluent; n-hexane/AcOEt (10/1).
Colorless oil; IR (KBr): 2855, 912, 743 cmꢀ1; 1H NMR (500 MHz,
CDCl3): 1.26e1.36 (m, 10H), 1.39e1.44 (m, 2H), 1.55e1.62 (m, 2H),
i
5.00 mmol) with MEMCl (1.13 mL, 10.0 mmol), Pr2NEt (2.55 mL,
15.0 mmol), and DMAP (61.1 mg, 0.500 mmol) gave 3a (1.04 g, 84%).
Eluent; n-hexane/AcOEt (4/1).
0.486 mmol), and MeOCH2CH2OH (100 m
d
4.3.1.2. Compound 3b. Treatment of 2b (791.5 mg, 5.00 mmol)
with MEMCl (1.13 mL, 10.0 mmol), Pr2NEt (2.55 mL, 15.0 mmol),
1.82e1.88 (m, 2H), 3.396 (s, 3H), 3.402 (t, J¼7.0 Hz, 2H), 3.53e3.57
i
(m, 4H), 3.68e3.70 (m, 2H), 4.71 (s, 2H) ppm; 13C NMR (125 MHz,
and DMAP (61.1 mg, 0.500 mmol) gave 3b (1.17 g, 95%). Eluent; n-
hexane/AcOEt (10/1).
CDCl3): d 26.2, 28.2, 28.7, 29.37, 29.40, 29.5, 29.7, 32.9, 34.0, 59.0,
66.7, 68.0, 71.9, 95.5 ppm; HRMS (FAB): calcd for C14H30O3Br
Colorless oil; IR (KBr): 2926,1456,1377,1043, 771 cmꢀ1; 1H NMR
[MþH]þ 325.1378, found 325.1382.
(400 MHz, CDCl3):
d
0.88 (t, J¼6.8 Hz, 3H), 1.15 (d, J¼6.0 Hz, 3H),
1.26e1.55 (m, 14H), 3.40 (s, 3H), 3.56 (t, J¼6.0 Hz, 2H), 3.69e3.73
4.3.2.3. Compound 3g. Treatment of 1n (70.3 mg, 0.229 mmol)
(m, 3H), 4.75 (d, J¼19.6 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3):
with 2,20-bipyridyl (214.6 mg, 1.374 mmol), TMSOTf (166
0.916 mmol), and MeOCH2CH2OH (90 m
m
L,
L, 1.145 mmol) gave 3g
(68.5 mg, 85%). Eluent; n-hexane/AcOEt (3/2).
Colorless oil; IR (KBr): 3333, 3065, 2930, 1643, 1537, 912,
743 cmꢀ1 1H NMR (500 MHz, CDCl3):
1.31e1.37 (m, 10H),
d
14.0, 20.1, 22.6, 25.5, 29.2, 29.5, 29.6, 31.8, 36.9, 58.9, 66.6, 71.7,
73.0, 93.7 ppm. Anal. Calcd for C14H30O3: C, 68.25; H, 12.27, found:
C, 68.36; H, 12.07.
;
d
4.3.1.3. Compound 3c. Treatment of 2c (492.7 mg, 3.0 mmol)
with MEMCl (0.68 mL, 6.0 mmol), Pr2NEt (1.5 mL, 9.0 mmol), and
1.55e1.62 (m, 4H), 3.40 (s, 3H), 3.45 (dt, J¼13.5, 7.5 Hz, 2H),
3.52e3.58 (m, 4H), 3.69 (t, J¼5.0 Hz, 2H), 4.71 (s, 2H), 6.11 (br s, 1H),
7.42e7.44 (m, 2H), 7.48e7.51 (m, 1H), 7.75e7.76 (m, 2H) ppm; 13C
i
DMAP (36.7 mg, 0.30 mmol) gave 3c (689.0 mg, 91%). Eluent; n-
hexane/AcOEt (5/1).
NMR (125 MHz, CDCl3): d 26.1, 26.9, 29.2, 29.3, 29.4, 29.6, 40.1, 59.0,
Colorless oil; IR (KBr): 2887, 1219, 771 cmꢀ1; 1H NMR (400 MHz,
66.6, 67.9, 71.8, 95.4, 126.8, 128.5, 131.2, 134.8, 167.5 ppm; HRMS
CDCl3):
3H), 3.54 (t, J¼6.0 Hz, 2H), 3.75 (t, J¼6.0 Hz, 2H), 4.85 (s, 2H),
7.15e7.29 (m, 5H); 13C NMR (100 MHz, CDCl3):
26.3, 30.3, 43.7,
d
1.29 (s, 6H), 1.79e1.84 (m, 2H), 2.65e2.69 (m, 2H), 3.38 (s,
(FAB): calcd for C20H34NO4 [MþH]þ 352.2488, found 352.2499.
d
4.4. Preparation of BOM ethers 4
58.9, 66.6, 71.7, 75.9, 89.9, 125.5, 128.2, 142.6 ppm. Anal. Calcd for
C15H24O3: C, 71.39; H, 9.59, found: C, 71.48; H, 9.60.
4.4.1. Preparation of BOM ethers 4aec. A solution of alcohol 2
(1.0 equiv), BOMCl (2.0 equiv), iPr2NEt (3.0 equiv), and DMAP
(0.1 equiv)indry CH2Cl2 (0.3e0.5 M) wasstirredat0 ꢁC to rtunder N2.
After disappearance of 2 onTLC, the mixture was added satd NH4Cl aq
4.3.1.4. Compound 3e. Treatment of 2k8 (1.71 g, 7.42 mmol)
with MEMCl (1.68 mL,14.8 mmol), iPr2NEt (3.8 mL, 22.3 mmol), and

H. Fujioka et al. / Tetrahedron 67 (2011) 2949e2960
2957
and the resulting solution was extracted with CH2Cl2. The organic
layer wasdried overNa2SO4 and evaporatedinvacuo. Theresiduewas
purified by flash column chromatography to give BOM ether 4.
94.7, 127.6, 127.9, 128.4, 138.1, 174.3 ppm; HRMS (FAB): calcd for
C
21H35O4 [MþH]þ 351.2535, found 351.2535.
4.4.2.3. Compound 4f. Treatment of 1l (68.9 mg, 0.245 mmol)
4.4.1.1. Compound 4a. Treatment of 2a (791.5 mg, 5.0 mmol)
with BOMCl (1.37 mL, 10.0 mmol), Pr2NEt (2.55 mL, 15.0 mmol),
with 2,20-bipyridyl (114.8 mg, 0.735 mmol), TMSOTf (89
0.490 mmol), and BnOH (130 mL, 1.225 mmol) gave 4f (84.9 mg,
mL,
i
and DMAP (61.1 mg, 0.50 mmol) gave 4a (1.32 g, 95%). Eluent; n-
hexaneebenzene (5/2).
86%). Eluent; benzene/Et2O (200/1).
Colorless oil; IR (KBr): 2931, 1217, 912, 771 cmꢀ1 1H NMR
;
Colorless oil; IR (KBr): 2942, 1069, 912, 743 cmꢀ1
;
1H NMR
(500 MHz, CDCl3): d 1.26e1.43 (m, 12H), 1.57e1.63 (m, 2H),
(400 MHz, CDCl3):
1.56e1.63 (m, 2H), 3.58 (t, J¼6.8 Hz), 4.60 (s, 2H), 4.76 (s, 2H),
7.27e7.36 (m, 5H) ppm; 13C NMR (100 MHz, CDCl3):
14.1, 22.6,
d
0.88 (t, J¼6.8 Hz, 3H), 1.27e1.38 (m, 14H),
1.82e1.88 (m, 2H), 3.40 (t, J¼6.5 Hz, 2H), 3.58 (t, J¼6.5 Hz, 2H), 4.60
(s, 2H), 4.75 (s, 2H), 7.25e7.36 (m, 5H) ppm; 13C NMR (125 MHz,
d
CDCl3): d 26.2, 28.1, 28.7, 29.3, 29.4, 29.7, 32.8, 33.9, 68.1, 69.3, 94.6,
26.2, 29.3, 29.4, 29.5, 29.6, 29.7, 31.9, 68.0, 69.2, 94.5, 127.6, 127.8,
128.3, 138.0 ppm. Anal. Calcd for C18H30O2: C, 77.65; H, 10.86,
found: C, 77.92; H, 10.75.
127.6, 127.8, 128.4, 138.0 ppm; HRMS (FAB): calcd for
C18H29O279BrNa [MþNa]þ 379.1249, found 379.1205.
4.4.2.4. Compound 4g. Treatment of 1n (60.4 mg, 0.196 mmol)
4.4.1.2. Compound 4b. Treatment of 2b (791.5 mg, 5.0 mmol)
with BOMCl (1.37 mL, 10.0 mmol), Pr2NEt (2.55 mL, 15.0 mmol),
and DMAP (61.1 mg, 0.50 mmol) gave 4b (429.3 mg, 31%). Eluent; n-
with 2,20-bipyridyl (183.7 mg, 1.176 mmol), TMSOTf (142
0.784 mmol), and BnOH (102 m
m
L,
L, 0.980 mmol) gave 4g (61.3 mg,
82%). Eluent; benzene/Et2O (10/1 to 4/1).
Colorless crystal; mp: 46.1e46.2 ꢁC; IR (KBr): 3331, 3061, 2930,
1643, 1537, 1045, 912, 743 cmꢀ1 1H NMR (500 MHz, CDCl3):
i
hexane/AcOEt (5/1).
Colorless oil; IR (KBr): 2856, 1379, 1217, 771 cmꢀ1
;
1H NMR
;
(400 MHz, CDCl3):
d
0.88 (t, J¼6.8 Hz, 3H), 1.18 (d, J¼6.4 Hz, 3H),
d
1.25e1.43 (m, 10H), 1.57e1.62 (m, 4H), 3.45 (dt, J¼13.5, 6.5 Hz,
1.21e1.60 (m, 14H), 3.72e3.80 (m, 1H), 4.62 (dd, J¼14.4, 12.0 Hz,
2H), 3.58 (t, J¼6.5 Hz, 2H), 4.60 (s, 2H), 4.76 (s, 2H), 6.10 (br s, 1H),
2H), 4.78 (d, J¼16.8 Hz), 7.26e7.37 (m, 5H) ppm; 13C NMR
7.26e7.51 (m, 8H), 7.75e7.76 (m, 2H) ppm; 13C NMR (125 MHz,
(100 MHz, CDCl3):
d
14.0, 20.2, 22.6, 25.6, 29.2, 29.6, 29.7, 31.8, 37.0,
CDCl3): d 26.2, 27.0, 29.2, 29.3, 29.5, 29.7, 40.1, 68.1, 69.2, 94.6, 126.8,
69.2, 73.1, 92.8, 127.5, 127.8, 128.3, 138.0 ppm. Anal. Calcd for
C18H30O2: C, 77.65; H, 10.86, found: C, 77.63; H, 10.77.
127.6, 127.9, 128.4, 128.5, 131.3, 134.9, 138.0, 167.5 ppm; HRMS
(FAB): calcd for C24H34NO3 [MþH]þ 384.2539, found 384.2538.
4.4.1.3. Compound 4c. Treatment of 2c (821.2 mg, 5.0 mmol)
with BOMCl (1.37 mL, 10.0 mmol), Pr2NEt (2.55 mL, 15.0 mmol),
4.4.3. General procedure: preparation of SEM ethers 5. TMSOTf
(2.0 equiv) was added dropwise to the solution of MOM ether 1
(1.0 equiv) and 2,20-bipyridyl (3.0 equiv) in CH2Cl2 (0.2 M) at 0 ꢁC
under N2 and the reaction mixture was stirred for 30 min at the same
temperature. After disappearance of 1 on TLC, TMSCH2CH2OH
(5.0 equiv) was added to the reaction mixture and the resulting so-
lutionwasstirredatrt. Afterthereactionwascompleted, satdNaHCO3
aq was added and the resulting solution was extracted with CH2Cl2.
The organic layerwasdried over Na2SO4 and evaporated invacuo. The
residue was purified by column chromatography to give SEM ether 5.
For the preparation of 5g, 6.0 equiv of TMSOTf and 4.0 equiv of 2,20-
bipyridyl were used. Compound 5d is a known compound.5
i
and DMAP (61.1 mg, 0.50 mmol) gave 4c (886.3 mg, 62%). Eluent; n-
hexane/AcOEt (5/1).
Colorless oil; IR (KBr): 2972, 1219, 772 cmꢀ1; 1H NMR (400 MHz,
CDCl3):
2H), 4.89 (s, 2H), 7.15e7.36 (m, 10H) ppm; 13C NMR (100 MHz,
CDCl3): 26.4, 30.3, 43.8, 69.2, 69.4, 76.0, 77.2, 125.6, 127.4, 127.7,
d 1.32 (s, 6H), 1.82e1.87 (m, 2H), 2.68e2.72 (m, 2H), 4.66 (s,
d
128.2, 138.1, 142.6 ppm. Anal. Calcd for C19H24O2: C, 80.24; H, 8.51,
found: C, 80.47; H, 8.49.
4.4.2. Preparation of BOM ethers 4deg. TMSOTf (2.0 equiv) was
added dropwise to the solution of MOM ether 1 (1.0 equiv) and 2,20-
bipyridyl (3.0 equiv) in CH2Cl2 (0.2 M) at 0 ꢁC under N2 and the
reaction mixture was stirred for 30 min at 0 ꢁC. After disappearance
of 1 on TLC, BnOH (5.0 equiv) was added to the reaction mixture
and the resulting solution was stirred at rt. After the reaction was
completed, satd NaHCO3 aq was added and the resulting solution
was extracted with CH2Cl2. The organic layer was dried over Na2SO4
and evaporated in vacuo. The residue was purified by column
chromatography to give BOM ether 4. For the preparation of 4g,
6.0 equiv of TMSOTf and 4.0 equiv of 2,20-bipyridyl were used.
Compound 4d is known compound.5
4.4.3.1. Compound 5a. According to the general procedure,
treatment of 1a (60.7 mg, 0.300 mmol) with 2,20-bipyridyl
(140.6 mg, 0.900 mmol), TMSOTf (108
mL, 0.600 mmol), and
TMSCH2CH2OH (214 L, 1.50 mmol) gave 5a (69.1 mg, 80%). Eluent;
m
n-hexane/benzene (3/1 to 2/1).
Colorless oil; IR (KBr): 2924, 1250, 1061, 914, 743 cmꢀ1; 1H NMR
(400 MHz, CDCl3):
d
0.02 (s, 9H), 0.88 (t, J¼6.4 Hz, 3H), 0.95 (t,
J¼8.8 Hz, 2H), 1.27e1.43 (m, 14H), 1.59e1.99 (m, 2H), 3.53 (t,
J¼6.8 Hz, 2H), 3.61 (t, J¼8.8 Hz, 2H), 4.67 (s, 2H) ppm; 13C NMR
(100 MHz, CDCl3):
d
ꢀ1.44, 14.1, 18.1, 22.7, 26.2, 29.3, 29.45, 29.57,
29.61, 29.8, 31.9, 64.9, 67.9, 94.8 ppm; HRMS (FAB): calcd for
4.4.2.1. Compound 4d5. Treatment of 2i (112.0 mg, 0.229 mmol)
C16H36O2SiNa [MþNa]þ 311.2382, found 311.2378.
with 2,20-bipyridyl (107.2 mg, 0.687 mmol), TMSOTf (83
m
L,
L, 1.150 mmol) gave 4d (95.1 mg,
73%). Eluent; n-hexane/benzene (1/3).
0.458 mmol), and BnOH (120
m
4.4.3.2. Compound 5b. According to the general procedure,
treatment of 1b (41.9 mg, 0.207 mmol) with 2,20-bipyridyl (97.0 mg,
0.621 mmol), TMSOTf (75
(150 L, 1.035 mmol) gave 5b (49.2 mg, 82%). Eluent; benzene/Et2O
(200/1).
Colorless oil; IR (KBr): 2857, 1377, 1259, 912, 743 cmꢀ1; 1H NMR
(500 MHz, CDCl3):
mL, 0.414 mmol), and TMSCH2CH2OH
4.4.2.2. Compound 4e. Treatment of 1k (58.0 mg, 0.211 mmol)
with 2,20-bipyridyl (98.9 mg, 0.633 mmol), TMSOTf (76
L,
0.422 mmol), and BnOH (110 L, 1.055 mmol) gave 4e (56.8 mg,
m
m
m
77%). Eluent; benzene/Et2O (150/1).
d
0.02 (s, 9H), 0.88 (t, J¼7.0 Hz, 3H), 0.94 (t,
Colorless oil; IR (KBr): 2926, 1732, 912, 743 cmꢀ1
;
1H NMR
J¼10.5 Hz, 2H), 1.15 (d, J¼6.0 Hz, 3H), 1.28e1.55 (m, 14H), 3.59e3.69
(500 MHz, CDCl3):
J¼7.5 Hz, 2H), 3.58 (t, J¼6.5 Hz, 2H), 3.67 (s, 3H), 4.60 (s, 2H), 4.76 (s,
2H), 7.27e7.36 (m, 5H) ppm; 13C NMR (125 MHz, CDCl3):
25.0,
26.2, 29.2, 29.3, 29.43, 29.45, 29.53, 29.6, 29.8, 34.1, 51.4, 68.2, 69.3,
d 1.27e1.37 (m, 14H), 1.57e1.64 (m, 4H), 2.30 (t,
(m, 3H), 4.69 (d, J¼20.5 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3):
d
ꢀ1.46, 14.1, 18.1, 20.2, 22.6, 25.6, 29.3, 29.6, 29.7, 31.9, 37.1, 64.8,
d
72.9, 93.0 ppm; HRMS (FAB): calcd for C16H36O2SiLi [MþLi]þ
295.2645, found 295.2622.

2958
H. Fujioka et al. / Tetrahedron 67 (2011) 2949e2960
4.4.3.3. Compound 5c. According to the general procedure,
treatment of 1c (62.2 mg, 0.299 mmol) with 2,20-bipyridyl
(140.1 mg, 0.897 mmol), TMSOTf (108 L, 0.598 mmol), and
TMSCH2CH2OH (210 L, 1.495 mmol) gave 5c (68.0 mg, 77%). Elu-
mmol) were added to the reaction mixture and vigorously stirred.
After disappearance of the high polar component was ascertained by
TLC, the reaction mixture was extracted with CH2Cl2. The organic
layer was washed with 3.5% HCl aq twice (for removal of 2,20-bipyr-
idyl) and with satd NaHCO3 aq. The combined organic layer was dried
over Na2SO4, filtered, and evaporated in vacuo. The residue was pu-
rified by flash column chromatography to give an alcohol 2. Silica gel
60 N (neutral) was used for the purification of substrate having TBS or
m
m
ent; n-hexane/AcOEt (25/1).
Colorless oil; IR (KBr): 2972, 1219, 772 cmꢀ1; 1H NMR (500 MHz,
CDCl3):
(m, 2H), 2.66e2.70 (m, 2H), 3.67 (t, J¼10.5 Hz, 2H), 4.79 (s, 2H),
7.15e7.29 (m, 5H) ppm; 13C NMR (100 MHz, CDCl3):
d
0.02 (s, 9H), 0.94 (t, J¼8.5 Hz, 2H), 1.29 (s, 6H), 1.80e1.83
d
ꢀ1.42, 18.2,
Tr ethers instead of Merck Silica gel 60. Compounds 2e31a, 2f4a, 2g31b
,
26.5, 30.4, 43.8, 64.9, 75.8, 89.3, 125.6, 128.3, 142.8 ppm; HRMS
2h31c, 2i31d, 2j31e, and 2k28 are known compounds.
(FAB): calcd for C17H31O2Si [MþH]þ 295.2093, found 295.2098.
4.5.1. Compound 2m. Colorless crystal; mp: 55.2e55.3 ꢁC; IR (KBr):
4.4.3.4. Compound 5d5. According to the general procedure,
treatment of 1i (119.0 mg, 0.242 mmol) with 2,20-bipyridyl
3286, 3094, 1645, 1557, 1296, 912, 743 cmꢀ1 1H NMR (500 MHz,
;
CDCl3):
1.97 (s, 3H), 3.46 (dd, J¼13.0, 7.0 Hz, 2H), 3.64 (q, J¼6.5 Hz, 2H), 5.43
(br s, 1H) ppm; 13C NMR (125 MHz, CDCl3):
23.3, 25.6, 26.8, 29.1,
d 1.30e1.34 (m, 10H), 1.48e1.50 (m, 2H), 1.54e1.59 (m, 2H),
(113.6 mg, 0.728 mmol), TMSOTf (88
mL, 0.484 mmol), and
TMSCH2CH2OH (170 L, 1.210 mmol) gave 5d (108.0 mg, 78%). El-
m
d
uent; n-hexane/benzene (1/3).
29.2, 29.4, 29.5, 32.7, 39.6, 62.9,170.1 ppm. Anal. Calcd for C11H23NO2:
C, 65.63; H, 11.52; N, 6.96, found: C, 65.27; H, 11.29; N, 6.88.
4.4.3.5. Compound 5e. According to the general procedure,
treatment of 1k (58.4 mg, 0.213 mmol) with 2,20-bipyridyl
4.5.2. Compound 2n. Colorless crystal; mp: 78.0e78.1 ꢁC; IR (KBr):
(99.8 mg, 0.639 mmol), TMSOTf (77
mL, 0.426 mmol), and
3304, 3061, 1643, 1539, 1310, 912, 742 cmꢀ1 1H NMR (400 MHz,
;
TMSCH2CH2OH (150 L, 1.065 mmol) gave 5e (64.3 mg, 84%). Elu-
m
CDCl3):
d
1.26e1.35 (m, 10H), 1.58e1.65 (m, 4H), 3.46 (dd, J¼12.0,
ent; n-hexane/AcOEt (20/1).
6.0 Hz, 2H), 3.64 (t, J¼6.8 Hz, 2H), 6.10 (br s, 1H), 7.41e7.45 (m, 2H),
Colorless oil; IR (KBr): 2930, 1738, 1219, 912, 772 cmꢀ1; 1H NMR
7.48e7.51 (m, 1H), 7.75e7.77 (m, 2H) ppm; 13C NMR (100 MHz,
(500 MHz, CDCl3):
d
0.02 (m, 9H), 0.94 (t, J¼8.5 Hz, 2H), 1.27e1.35
CDCl3): d 25.6, 26.9, 29.1, 29.3, 29.6, 32.7, 40.0, 63.0, 126.8, 128.5,
131.3, 134.8, 167.5 ppm. Anal. Calcd for C16H25NO2: C, 72.96; H, 9.57;
N, 5.32, found: C, 72.52; H, 9.37; N, 5.34.
(m, 14H), 1.55e1.64 (m, 4H), 2.30 (t, J¼7.5 Hz, 2H), 3.52 (t, J¼7.0 Hz,
2H), 3.61 (t, J¼7.5 Hz, 2H), 3.66 (s, 3H), 4.66 (s, 2H) ppm; 13C NMR
(125 MHz, CDCl3):
d
ꢀ1.4, 18.1, 25.0, 26.2, 29.1, 29.2, 29.41, 29.43,
29.5, 29.6, 29.8, 34.1, 51.4, 64.9, 67.9, 94.8, 174.3 ppm; HRMS (FAB):
4.6. Selective deprotection of aliphatic MOM group in the
presence of phenolic MOM group (Scheme 4)
calcd for C19H40O4SiNa [MþNa]þ 383.2594, found 383.2589.
4.4.3.6. Compound 5f. According to the general procedure,
treatment of 1l (78.9 mg, 0.280 mmol) with 2,20-bipyridyl
According to the general procedure for deprotection of MOM
ethers, treatment of 1p27 (39.4 mg, 0.164 mmol) with 2,20-bipyridyl
(131.2 mg, 0.840 mmol), TMSOTf (102
TMSCH2CH2OH (200 L, 1.40 mmol) gave 5f (77.6 mg, 75%). Eluent;
benzene/Et2O (200/1).
Colorless oil; IR (KBr): 2928, 1217, 771 cmꢀ1; 1H NMR (500 MHz,
CDCl3): 0.02 (s, 9H), 1.27e1.36 (m, 14H), 1.56e1.65 (m, 2H),
mL, 0.560 mmol), and
(76.7 mg, 0.491 mmol) and TESOTf (74 m
L, 0.328 mmol) gave 2p32
(27.3 mg, 85%). Eluent; n-hexane/AcOEt (1/1).
m
4.7. The substitution reaction of acetal-type ethers with allyl
alcohol in the combination with TMSOTf-2,20-bipyridyl
(Scheme 6)
d
1.82e1.88 (m, 2H), 3.40 (t, J¼7.0 Hz, 2H), 3.52 (t, J¼6.5 Hz, 2H), 3.62
(t, J¼10.5 Hz, 2H), 4.66 (s, 2H) ppm; 13C NMR (125 MHz, CDCl3):
d
ꢀ1.45, 18.1, 25.0, 26.2, 28.1, 28.7, 29.33, 29.36, 24.44, 29.7, 32.8,
TMSOTf (2.0 equiv) was added dropwise to a solution of MOM-
type ether (1a, 3a, 4a, and 5a) and 2,20-bipyridyl (3.0 equiv) in
CH2Cl2 (0.2 M) at 0 ꢁC under N2 and the reaction mixture was
stirred for 30 min at 0 ꢁC. After disappearance of MOM-type ether
on TLC, allyl alcohol (5.0 equiv) was added to the reaction mixture
and the resulting solution was stirred at rt for 24 h. Then, satd
NaHCO3 aq was added and the resulting solution was extracted
with CH2Cl2. The organic layer was dried over Na2SO4 and evapo-
rated in vacuo. The residue was purified by column chromatogra-
phy to give acetal 6 and alcohol 2a.
33.8, 64.9, 67.8, 94.8 ppm. Anal. Calcd for C16H35BrO2Si: C, 52.30; H,
9.60; Br, 21.75, found: C, 52.34; H, 9.49; Br, 21.60.
4.4.3.7. Compound 5g. According to the general procedure, the
treatment of 1n (70.1 mg, 0.228 mmol) with 2,20-bipyridyl
(213.7 mg, 1.368 mmol), TMSOTf (165
mL, 0.912 mmol), and
TMSCH2CH2OH (162 L,1.320 mmol) gave 5g (75.7 mg, 84%) for 7 h.
m
Eluent; n-hexane/AcOEt (4/1).
Colorless oil; IR (KBr): 3313, 3063, 2928, 1645, 1524, 1058, 912,
743 cmꢀ1; 1H NMR (500 MHz, CDCl3):
2H), 1.31e1.35 (m, 10H), 1.55e1.64 (m, 4H), 3.44 (dt, J¼13.0, 7.0 Hz,
2H), 3.52 (t, J¼6.5 Hz, 2H), 3.61 (t, J¼8.5 Hz, 2H), 4.66 (s, 2H)
7.41e7.44 (m, 2H), 7.48e7.50 (m, 1H), 7.76e7.77 (m, 2H) ppm; 13C
d
0.02 (s, 9H), 0.94 (t, J¼8.5 Hz,
Compound 6: Colorless oil; IR (KBr): 2926, 1468, 1265, 912,
742 cmꢀ1
;
1H NMR (400 MHz, CDCl3):
d
0.88 (t, J¼6.8 Hz, 3H),
1.26e1.37 (m, 14H), 1.55e1.62 (m, 2H), 3.54 (t, J¼6.8 Hz, 2H), 4.08
(dt, J¼6.0, 1.6 Hz, 2H), 4.70 (s, 2H), 5.18 (dq, J¼9.6, 3.2, 1.6 Hz, 1H),
5.30 (dq, J¼17.2, 3.2, 1.6 Hz, 1H), 5.88e5.98 (m, 1H) ppm; 13C NMR
NMR (125 MHz, CDCl3):
d
ꢀ1.46,18.1, 26.2, 26.9, 29.2, 29.3, 29.4, 29.6,
29.7, 40.1, 64.9, 67.8, 94.7, 126.8, 128.5, 131.2, 134.8, 167.5 ppm; HRMS
(100 MHz, CDCl3): d 14.1, 22.7, 26.2, 29.3, 29.4, 29.55, 29.59, 29.7,
(FAB): calcd for C22H40NO3Si [MþH]þ 394.2777, found 394.2778.
31.9, 68.0, 68.2, 94.5, 116.9, 134.4 ppm; Anal. Calcd for C14H28O2: C,
73.63; H, 12.36, found: C, 73.64; H, 12.64.
4.5. Deprotection of MOM, MEM, BOM, or SEM ether by
TMSOTf (TESOTf)/2,20-bipyridyl combination
4.8. General procedure: direct conversion to BOM and SEM
ethers from MOM ethers (Table 5)
TMSOTf or TESOTf (2.0 equiv) was added dropwise to a solution of
MOM,MEM,BOM,orSEMether(1, 3e5)and2,20-bipyridyl(3.0 equiv)
in CH2Cl2 (0.2 M) at 0 ꢁC under N2. The reaction mixture was stirred at
the same temperature. After checking the disappearance of the
starting material on TLC (30 min), H2O (2 mL/mmol) and Et2O (2 mL/
TMSOTf (2.0 equiv) was added dropwise to a solution of MOM
ether 1 (1.0 equiv) and 2,20-bipyridyl (3.0 equiv) in CH2Cl2 (0.2 M)
at 0 ꢁC under N2 and the reaction mixture was stirred for 30 min at
0
ꢁC. After disappearance of 1 on TLC, BnOH or TMSCH2CH2OH

H. Fujioka et al. / Tetrahedron 67 (2011) 2949e2960
2959
Wahlstrom, J. L.; Ronald, R. C. J. Org. Chem. 1998, 63, 6021; (c) Vaino, A. R.;
Szarek, W. A. Synlett 1995, 1157.
(5.0 equiv) was added to the reaction mixture and the resulting
solution was stirred at rt. After the reaction was completed, satd
NaHCO3 aq was added and the resulting solution was extracted
with CH2Cl2. The organic layer was dried over Na2SO4 and evapo-
rated in vacuo. The residue was purified by column chromatogra-
phy to give BOM 4 or SEM ether 5.
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Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Re-
search (B) and for Scientific Research for Exploratory Research from
Japan Society for the Promotion of Science (JSPS) and Special Co-
ordination Funds for Promoting Science and Technology of the
Ministry of Education, Culture, Science and Technology, the Japa-
nese Government. The financial support from The Uehara Memorial
Foundation is also acknowledged.
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