A novel and efficient method for the silylation of alcohols with methallylsilanes catalyzed by Sc(OTf)3

Article abstract of DOI:10.1016/S0040-4039(00)01545-8

Reaction of alcohols with methallylsilanes in the presence of a catalytic amount of Sc(OTf)₃ provides efficiently the corresponding alkyl silyl ethers. By using microencapsulated (MC) Sc(OTf)₃, which can be easily recovered and reused, yields of alkyl silyl ethers are improved and the work-up process after completion of the reaction is considerably simplified. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01545-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8903–8906
A novel and efficient method for the silylation of alcohols
with methallylsilanes catalyzed by Sc(OTf)3
Takeshi Suzuki, Tsutomu Watahiki and Takeshi Oriyama*
Faculty of Science, Ibaraki University, Bunkyo, Mito 310-8512, Japan
Received 23 August 2000; revised 7 September 2000; accepted 8 September 2000
Abstract
Reaction of alcohols with methallylsilanes in the presence of a catalytic amount of Sc(OTf)3 provides
efficiently the corresponding alkyl silyl ethers. By using microencapsulated (MC) Sc(OTf)3, which can be
easily recovered and reused, yields of alkyl silyl ethers are improved and the work-up process after
completion of the reaction is considerably simplified. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: silylation of alcohols; silyl ethers; catalytic; Sc(OTf)3; MC Sc(OTf)3; methallylsilanes; chemoselectivity.
Silyl ethers are the most popular and useful protecting groups of the hydroxy function in
synthetic organic chemistry, and various types of silyl ethers have been developed.1 Silyl ethers
are usually obtained by the reaction of parent alcohols with the corresponding silyl halide in the
presence of a stoichiometric amount of a base, such as imidazole, 4-dimethylaminopyridine,
triethylamine, etc.1 These silylation methods can give the corresponding silyl ethers in high
yields, but require extraction or a careful filtration process to remove ammonium salts. On the
contrary, metal-catalyzed dehydrogenative alcoholysis of hydrosilanes is a potent way to silyl
ethers with no by-product,2 but hydrosilylation or hydrogenation to a C–C double bond is an
inevitable side-reaction, with the exception of the reaction using a tris(pentafluorophenyl)borane
catalyst.3 It was reported that allylsilane and silyl enol ether could silylate alcohols under the
influence of a catalytic amount of p-toluenesulfonic acid,4,5 iodine6 or trifluoromethanesulfonic
acid.7 In the case where allylsilane was used, the reaction proceeded with evolution of propene
and no other by-product, and did not need a work-up process, such as extraction, filtration and
drying, but it was difficult to recover and reuse the catalysts (Scheme 1).
Scheme 1.
* Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01545-8

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On the other hand, scandium trifluoromethanesulfonate (Sc(OTf)3), which is a stable Lewis
acid in water, has been demonstrated in various useful reactions recently.8 We expected that the
coordination of the hydroxy function of alcohol to Sc(OTf)3 would enhance the acidity of the
hydroxy proton and it would behave as an acid catalyst itself in the silylation of alcohols using
allyltrialkylsilanes.
In this communication, we wish to report a practical and convenient method for the synthesis
of trialkylsilyl ethers from the corresponding alcohols and methallylsilanes in the presence of a
catalytic amount of Sc(OTf)3.
To begin with, we examined the reaction of 3-phenylpropanol with allyl-t-butyldimethylsilane
in the presence of 2 mol% of Sc(OTf)3 in propionitrile (EtCN) and only a trace amount of the
corresponding t-butyldimethylsilyl (TBS) ether was obtained (Table 1, Run 1). On the other
hand, by using t-butylmethallyldimethylsilane,9 which was presumably a more reactive nucleo-
phile than unsubstituted allylsilane, the desired silyl ether was obtained in 98% isolated yield
(Run 2). By using other types of methallylsilanes having a triethylsilyl (TES), triisopropylsilyl
(TIPS), or t-butyldiphenylsilyl (TBDPS) moiety, the corresponding silyl ethers were similarly
formed in high yields (Runs 4–6).
Representative and successful examples of synthesis of various alcohol TBS ethers are
collected in Table 2. As well as primary alcohols, secondary alcohols were readily transformed
into the corresponding TBS ethers in excellent yields (Runs 1–3). It should be noted that the
TBS ether of a tertiary alcohol was also obtained in high yield in 0.5 h (Run 4). In the case of
cinnamyl alcohol (Run 5) and phenols (Runs 6 and 7), although longer reaction times were
required, the corresponding TBS ethers were obtained in >90% yields.
10,11
Next, we investigated the effect of microencapsulated (MC) Sc(OTf)3
instead of
monomeric Sc(OTf)3 (Table 3). In all cases, the corresponding TBS ethers were obtained in high
yields with no drop in the activity of Sc(OTf)3. In the case of alcohols containing other
functional groups, such as ketone, ether, ester, and acetal, yields of the corresponding TBS
ethers were higher than that in the case of using monomeric Sc(OTf)3 (Runs 2–5). Additionally,
by using MC Sc(OTf)3, work-up processes, such as extraction and drying, are excluded, and MC
Sc(OTf)3 can be easily recovered by a simple filtration.
Table 1
Silylation of 3-phenylpropanol
Run
R
Si
Yielda (%)
1
2
3
4
5
6
H
TBS
TBS
TBS
TES
TIPS
TBDPS
Trace
98
Me
Me
Me
Me
Me
84b
83
84c
85c
a Isolated yield.
b MeCN was used as the solvent.
c 5 mol% of Sc(OTf)3 was used. Reaction time: 6 h.

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Table 2
Synthesis of various TBS ethers from alcohols
Previously, we reported a chemoselective deprotection of alkyl silyl ethers in the presence of
aryl silyl ethers by Sc(OTf)3 in water-containing acetonitrile.12 Therefore, we attempted silylation
of the aliphatic and aromatic hydroxyl functions and subsequent chemoselective desilylation in
a one-pot procedure. After treating 3-(4-hydroxyphenyl)propanol with 2.4 equiv. of t-butyl-
methallyldimethylsilane in the presence of Sc(OTf)3, 5 equiv. of H2O were added and the
solution was stirred for 3 h at room temperature. After the usual work-up of the reaction
mixture, the mono TBS ether that was selectively silylated at the phenolic hydroxy function was
obtained in 95% yield (Scheme 2).
Table 3
Synthesis of various TBS ethers using MC Sc(OTf)3

8906
Scheme 2.
In conclusion, we have succeeded in developing a new method for the silylation of alcohols
using methallylsilanes catalyzed by Sc(OTf)3.13 In the case of using MC Sc(OTf)3, the catalyst
was readily recovered, and work-up processes, such as extraction and drying, were not required.
This silylation method has not only an operational advantage, but it also exploits the utility of
Sc(OTf)3 in the activation of the hydroxy function. Further investigation to broaden the scope
and synthetic applications of this efficient silylation is under way in our laboratory.
Acknowledgements
This work was financially supported by the Tokuyama Science Foundation.
References
1. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John Wiley & Sons: New York,
1999; Kocienski, P. J. Protective Groups; Georg Thieme Verlag: New York, 1994.
2. Doyle, M. P.; High, K. G.; Bagheri, V.; Pieters, R. J.; Lewis, P. J.; Pearson, M. M. J. Org. Chem. 1990, 55,
6082–6086 and references cited therein.
3. Blackwell, J. M.; Foster, K. L.; Beck, V. H.; Piers, W. E. J. Org. Chem. 1999, 64, 4887–4892.
4. Morita, T.; Okamoto, Y.; Sakurai, H. Tetrahedron Lett. 1980, 21, 835–838.
5. Veysoglu, T.; Mitscher, L. A. Tetrahedron Lett. 1981, 22, 1299–1302.
6. Hosomi, A.; Sakurai, H. Chem. Lett. 1981, 85–88.
7. Olah, G. A.; Husain, A.; Gupta, B. G. B.; Salem, G. F.; Narang, S. C. J. Org. Chem. 1981, 46, 5212–5214.
8. Hachiya, I.; Kobayashi, S. J. Org. Chem. 1993, 58, 6958–6960; Kawada, A.; Mitamura, S.; Kobayashi, S. Synlett
1994, 545–546; Kobayashi, S. Synlett 1994, 689–701; Kobayashi, S.; Ishitani, H.; Nagayama, S. Synthesis 1995,
1195–1202; Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto, H. J. Am. Chem. Soc. 1995, 117, 4413–4414;
Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto, H. J. Org. Chem. 1996, 61, 4560–4567; Kobayashi, S.;
Nagayama, S. J. Am. Chem. Soc. 1997, 119, 10049–10053; Kajiro, H.; Mitamura, S.; Mori, A.; Hiyama, T.
Synlett 1998, 51–52; Akiyama, T.; Iwai, J. Synlett 1998, 273–274; Kobayashi, S. Eur. J. Org. Chem. 1999, 15–27.
9. Methallylsilanes were prepared from methallylmagnesium bromide and the corresponding trialkylsilyl chlorides.
10. Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1998, 120, 2985–2986.
11. Commercially available from Wako Pure Chemical Industries, Ltd.
12. Oriyama, T.; Kobayashi, Y.; Noda, K. Synlett 1998, 1047–1048.
13. A typical experimental procedure is as follows: To a mixture of scandium trifluoromethanesulfonate (1.0 mg,
0.0020 mmol) and 3-phenylpropanol (55.3 mg, 0.41 mmol) in EtCN (1 ml) was added t-butylmethallyldimethyl-
silane (107.8 ml, 0.49 mmol) at room temperature under an argon atmosphere. The resultant mixture was stirred
for 1 h at room temperature and quenched with saturated sodium hydrogencarbonate. The organic materials
were extracted with Et2O and dried over anhydrous magnesium sulfate. The solvent was evaporated and
1-t-butyldimethylsilyloxy-3-phenylpropane (99.2 mg, 98%) was isolated by thin-layer chromatography on silica
gel (ether:hexane=1:30).
.