Catalytic monosilylation of 1,2-diols

Article abstract of DOI:10.1016/j.tetlet.2011.10.016

The selective monosilylation of 1,2-diols catalyzed by dimethyltin dichloride was successfully developed. This procedure was applied to various 1,2-diols, giving monosilylated products in good to excellent yields with high chemoselectivity.

Full text of DOI:10.1016/j.tetlet.2011.10.016

Tetrahedron Letters 52 (2011) 6646–6648
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Catalytic monosilylation of 1,2-diols
⇑
Tsubasa Takeichi, Masami Kuriyama, Osamu Onomura
Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The selective monosilylation of 1,2-diols catalyzed by dimethyltin dichloride was successfully developed.
This procedure was applied to various 1,2-diols, giving monosilylated products in good to excellent yields
with high chemoselectivity.
Received 8 September 2011
Revised 3 October 2011
Accepted 5 October 2011
Available online 12 October 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Dimethyltin dichloride
1,2-Diols
Silylation
Chemoselectivity
Selective protection of diols is highly important in organic syn-
thesis.1 In the past, a variety of methods for the catalytic monopro-
tection of 1,2-diols, such as acetylation,2 benzoylation,3 tosylation,4
have been developed to achieve high selectivity.5 Especially, the
selective monosilylation of 1,2-diols is quite significant because
silyl groups are one of the most useful protective groups of hydro-
xyl moieties.1 While selective monodeprotection of bis-silyl ethers
has been pursued to obtain silyloxy alcohols,6 organocatalytic
enantioselective methods were recently developed by Snapper7
and Tan8 in addition to the biphasic process.9 However, selective
monosilylation controlled by metal catalysts has not been
reported.
On the other hand, we have already developed the effective
methods for catalytic monoprotection of 1,2-diols with Lewis acid
such as dimethyltin dichloride10 or copper(II) salts11 in the pres-
ence of weak bases. We envisioned this method could be applied
to catalytic monosilylation of 1,2-diols. Herein, we wish to report
the first example of selective monosilylation of 1,2-diols catalyzed
by the metal catalyst.
Our working hypothesis for the catalytic selective monosilyla-
tion of 1,2-diols is shown in Scheme 1. Dimethyltin dichloride
(Me2SnCl2)12 and triethylsilyl chloride (TESCl) 2a represent a cata-
lyst and a silylating reagent, respectively. The monosilylation
would proceed as below. First of all, 1,2-diol 1 is recognized by
the Sn catalyst and the five-membered intermediate A is formed
with the bidentate coordination of 1,2-diol 1 to the Sn catalyst.
Second, the complex A is selectively deprotonated by weak base,
in which the pKa value of 1,2-diol 1 would be lowered due to the
coordination of 1,2-diol 1 to the metal center. Finally, the activated
intermediate B (or B0) with a higher reactivity than 1,2-diol 1 reacts
with TESCl, affording the monosilylated product 3. The difficulty
for 3 in coordinating to the metal center would suppress the
oversilylation.
Based on this concept, we began investigations with the optimi-
zation of reaction conditions using cis-1,2-cyclooctanediol 1a and
TESCl as model substrates (Table 1). In the examination of metal
catalysts, dimethyltin dichloride gave the desired product 3aa in
quantitative yield,13 while Cu and Pd catalysts led to high yields
(entries 1–3). Screening of bases revealed that organic bases were
suitable for this transformation and triethylamine afforded the
superior result (entries 3–6). Whereas the monosilylation in less
R
R
OH
R
R
OH
OH
OTES
Me2SnCl2
3
1
first step
third step
R
TESCl 2a
H
O
H
O
H
O
Cl
R
R
Me
Me
Cl
Cl
R
R
Sn
A
Me
Me
Me
Me
Sn
Sn
O
H
Cl
second step
R
O
B
O
B'
weak
base
−HX
⇑
Corresponding author.
E-mail address: onomura@nagasaki-u.ac.jp (O. Onomura).
Scheme 1. Working hypothesis for chemoselective monosilylation catalyzed by
Me2SnCl2.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.10.016

T. Takeichi et al. / Tetrahedron Letters 52 (2011) 6646–6648
6647
Table 1
Table 2
Optimization of reaction conditionsa
Scope of diolsa
R
R
OH
catalyst
OH
R
R
+
TESCl
OH
cat. Me2SnCl2
OH
base
sovent
rt, 1 h
+
OH
OTES
TESCl
n
n
Et3N
CH2Cl2
rt, 1 h
OH
OTES
1a
2a
3aa
1
2a
3
Entry
Catalyst
Base
Solvent
Yieldb (%)
Entry
1
Diol 1
Product
3
Yieldb (%)
1
2
3
4
5
6
7
Cu(OTf)2
Pd(OAc)2
Me2SnCl2
Me2SnCl2
Me2SnCl2
Me2SnCl2
Me2SnCl2
Me2SnCl2
Me2SnCl2
None
Et3N
Et3N
Et3N
(i-Pr)2NEt
DMAP
Pyridine
Et3N
Et3N
Et3N
Et3N
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
AcOEt
CH2Cl2
CH2Cl2
82
72
99
73
60
0
81
96
91
65
OH
1b
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
92
88
99
78
97
99
94
92
88
OTES
OH
2
3
4
5
6
7
8
9
1c
1d
1e
1f
8
OTES
9c
10
OH
a
OTES
OH
Reaction conditions: diol 1a (0.5 mmol), TESCl 2a (1.5 equiv), catalyst
(10 mol %), base (1.5 equiv), solvent (3 mL), rt, 1 h.
b
Isolated yield.
Me2SnCl2 (1 mol %) was used.
c
OTES
OH
OTES
OH
OH
OH
OH
1g
1h
1i
OTES
OH
OTES
1a
3aa
O
Me2SnCl2 (10 mol %)
88% yield
69% (without Sn)
OTES
TESCl
(1.5 equiv)
2a
+
Et3N (1.5 equiv)
CH2Cl2
OH
+
Cbz
Me
N
rt, 1 h
OH
OTES
OTES
OH
1j
3ja
00% yield
59% (without Sn)
OTES
OH
Me
Ph
Scheme 2. Silylation using cis-1,2-cyclooctanediol and cyclooctanol.
10
11
1k
1l
3ka
3la
97
89
OTES
OH
Ph
Ph
polar toluene led to the reduced efficiency, the result in high polar
ethyl acetate was also excellent (entries 7 and 8). The catalyst load-
ing was successfully reduced to 1 mol % with comparable isolated
yield to the reaction with 10 mol % catalyst (entries 3 and 9). On
the other hand, the silylation reaction without dimethyltin dichlo-
ride led to the significant decrease in yield (entry 10).
In addition, this catalytic system showed quite high chemose-
lectivity (Scheme 2). The catalytic silylation with 1:1 mixture of
cis-1,2-cyclooctanediol 1a and cyclooctanol was conducted to give
only the desired monosilylated product 3aa in 88% yield.14 In the
absence of Sn catalyst, the monosilylated product 3aa and the sily-
lated mono-ol were obtained in 69% and 59% yields, respectively.15
With the optimal conditions in hand, we next explored the
scope of 1,2-diols (Table 2). While aliphatic cyclic cis-1,2-diols
1b–d gave the desired product 3ba–da in excellent yields (entries
1–3), the trans-isomer 1e showed the lower reactivity (entry 4).
High yields were observed in the reaction with cyclic cis-1,2-diols
OTES
Ph
MeO2C
OH
12
13
1m
1n
3ma
3na
87
71
OTES
MeO2C
OH
OTES
OH
Me
14
15
1o
1p
3oa
3pa
92
85
Me
Et
OTES
OH
Et
OTES
a
Reaction conditions: diol
(10 mol %), Et3N (1.5 equiv), CH2Cl2 (3 mL), rt, 1 h.
1 (0.5 mmol), TESCl 2a (1.5 equiv), Me2SnCl2
b
Isolated yield.
bearing
p-bonds (entries 5 and 6). The heterocyclic cis-2,3-diols
containing oxygen and nitrogen atoms were also converted effi-
ciently, leading to excellent results (entries 7 and 8). In the mono-
silylation of linear 1,2-diols, both meso- and threo-isomers 1j–l
gave the desired products in high yields (entries 9–11). The 1,2-
diol bearing ester groups 1m showed the high reactivity and cate-
chol 1n was also proved to be a suitable substrate (entries 12 and
13). The 1,3-diols 1o–p were still transformed readily, leading to
high yields (entries 14 and 15). Also, the monosilylation of unsym-
metrical 1,2-diol 1q and 1,3-diol 1r smoothly proceeded to give the
regioselectively monosilylated product 3qa and 3ra in high yields
(Scheme 3).
The investigation of various silylating reagents in the monosily-
lation of cis-1,2-cyclooctanediol 1a was conducted (Table 3).
The more sterically bulky reagent 2b led to no significant de-
crease in yield (entry 1).16 The introduction of silyl groups bearing
olefin moieties, which can be synthetic footholds, was also suc-

6648
T. Takeichi et al. / Tetrahedron Letters 52 (2011) 6646–6648
process tolerated a variety of substrates with high chemoselectiv-
ity. Further efforts will be focused on the development of asym-
metric silylation of 1,2-diols in our research group.
OH
OH
OTES
OH
Me2SnCl2 (10 mol %)
+
TESCl
(1.5 equiv)
2a
Ph
Ph
Et3N (1.5 equiv)
CH2Cl2
1q
3qa
85% yield
rt, 1 h
Acknowledgments
OH
OH
OTES
Me2SnCl2 (10 mol %)
+
TESCl
(1.5 equiv)
2a
This research was supported by Grant-in-Aid for Scientific Re-
search on Innovative Areas from The Ministry of Education, Cul-
ture, Sports, Science and Technology (MEXT), Grant-in-Aid for
Young Scientists (B) from The Japan Society for the Promotion of
Science (JSPS).
OH
Et3N (1.5 equiv)
CH2Cl2
Me
Me
1r
3ra
87% yield
rt, 1 h
Scheme 3. Silylation of unsymmetrical 1,2- and 1,3-diols.
References and notes
Table 3
Scope of silylating reagentsa
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Wiley & Sons: New York, 2006.
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C. J. Org. Chem. 2002, 67, 5226–5231; (c) Müller, C. E.; Zell, D.; Schreiner, P. R.
Chem. Eur. J. 2009, 15, 9647–9650; (d) Yoshida, K.; Furuta, T.; Kawabata, T.
Angew. Chem., Int. Ed. 2011, 50, 4888–4892; (e) Lee, D.; Taylor, M. S. J. Am. Chem.
Soc. 2011, 133, 3724–3727.
OH
OH
cat. Me2SnCl2
+
Cl−SiMe2R
Et3N (1.5 equiv)
CH2Cl2
OH
OSiMe2R
3
1a
2
rt, 1 h
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3532; (b) Iwasaki, F.; Maki, T.; Onomura, O.; Nakashima, W.; Matsumura, Y. J.
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Lett. 2007, 9, 1145–1147.
Entry
1
2
Product
3
Yieldb (%)
OH
Me
2b
3ab
91
83
79
89
87
84
82
99
O Si i-Pr
Me
4. Demizu, Y.; Matsumoto, K.; Onomura, O.; Matsumura, Y. Tetrahedron Lett. 2007,
48, 7605–7609.
OH
Me
5. To avoid overacylation, excess amounts of diols have been often used: (a)
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5837–5863; (c) Giesbrecht, H. E.; Knight, B. J.; Tanguileg, N. R.; Emerso, C. R.;
Blakemore, P. R. Synlett 2010, 374–378.
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to marine invertebrates but also for mammals and other animals. The most
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2
2c
2d
2e
2f
3ac
3ad
3ae
3af
3ag
3ah
3ai
O Si
Me
OH
Me
3
O Si
Me
OH
Me
4c
5
O Si Ph
Me
OH
Me
O Si Bn
Me
OH
Me
6c
7
2g
2h
2p
O Si
Me
OH
Me
O Si
Me
OH
Me
O Si
Me
3
Ph
Cl
8
3
CN
a
Reaction conditions: diol 1a (0.5 mmol), silylating reagent
2 (1.2 equiv),
13. Representative procedure. To the mixture of diol 1a (0.5 mmol), triethylamine
(1.5 equiv), and dimethyltin dichloride (10 mol %) in CH2Cl2 (3 mL) was added
TESCl 2a (1.5 equiv). The mixture was stirred for 1 h at rt. After water was
added, the resulting mixture was extracted with ethyl acetate and the
combined organic layers were dried with anhydrous magnesium sulfate.
Me2SnCl2 (10 mol %), Et3N (1.5 equiv), CH2Cl2 (3 mL), rt, 1 h.
b
Isolated yield.
c
Silylating reagent 2 (1.5 equiv) was used.
After filtration, the volatile components were removed with
evaporator. Purification of the crude product through silica gel column
chromatography gave 3aa in 99% yield.
a rotary
ceeded with high yields (entries 2 and 3). The monosilylation using
reagents with phenyl group had no difficulty, leading to excellent
results (entries 4–6). The silylating reagents bearing reactive moi-
eties, such as chlorine and cyano group, reacted efficiently with no
side product (entries 7 and 8).
14. In this case, cyclooctanol was recovered in 99%.
15. By using imidazole (1.5 equiv) without Me2SnCl2, the monosilylated product
3aa and the silylated mono-ol were obtained in 43% and 50% yields,
respectively.
16. The reaction of 1a with tert-butyldimethylsilyl chloride (TBSCl) did not
proceed to recover 1a under the reaction conditions.
In summary, we successfully developed the first selective
monosilylation of 1,2-diols catalyzed by metal complexes. This