Silyl methallylsulfinates: Efficient and powerful agents for the chemoselective silylation of alcohols, polyols, phenols and carboxylic acids

Article abstract of DOI:10.1039/b417894g

Alcohols, phenols and carboxylic acids are silylated with very good yields in the presence of silyl methallylsulfinates under non-basic conditions and with the formation of volatile co-products. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b417894g

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Silyl methallylsulfinates: efficient and powerful agents for the
chemoselective silylation of alcohols, polyols, phenols and carboxylic
acids{
Xiaogen Huang, Cotinica Craita, Loay Awad and Pierre Vogel*
Received (in Cambridge, UK) 26th November 2004, Accepted 20th January 2005
First published as an Advance Article on the web 1st February 2005
DOI: 10.1039/b417894g
1b and 1c can be prepared by reaction of SO2 with triethyl- and
(tert-butyl)dimethyl(2-methallyl)silane, respectively.16
Alcohols, phenols and carboxylic acids are silylated with
very good yields in the presence of silyl methallylsulfinates
under non-basic conditions and with the formation of volatile
co-products.
The outcome of silylation reactions of a variety of substrates
(Scheme 2), using the reagents 1a–c, are presented in Table 2. In
the presence of one equivalent of 1a–c, primary and secondary
alcohols were silylated completely in less than 5 min in CD2Cl2 or
CDCl3 at 20 uC. The reactions were accompanied by fast evolution
of SO2 gas. Acetonitrile and tetrahydrofuran can also be used as
solvent.
Silylation of alcohols, polyols and phenols1 is one of the most
commonly used methods for their protection.2 Silylation is a classic
way to produce volatile derivatives of polyols, as required for
their vapour phase chromatography/mass spectrometric analysis.3
Classical methods of alcohol and phenol silylation involve
trialkylsilyl halides4 or triflates5 in the presence of a stoichiometric
amount of a tertiary amine. Other methods employ silazanes,6
hexamethyldisilazane,7 hydrosilanes,8 disilanes,9 alkylsilanes,10
methallylsilanes,11 trimethylsilyl azide,12 or silylphosphines13 in
the presence of a suitable catalyst. Because of the co-production of
salts or other side-products (catalyst, etc.) all these methods
necessitate a work-up with, sometimes, a delicate purification step.
Quite often, sterically hindered alcohols react only sluggishly. In
1976, Kuwajima and co-workers showed that the silylation of
alcohols, aldehydes and ketones can be carried out with ethyl
trimethylsilyl acetate in the presence of a catalytic amount of
tetrabutylammonium fluoride and without solvent. Apart from
tetrabutylammonium salts, the side product is ethyl acetate which
is readily eliminated by evaporation.14
Compounds with fragile structures, sensitive to acids or bases,
survived under our silylation conditions (see e.g. 6,17 7, 8). The
Table 1 Synthesis of silyl methallylsulfinates 1a–c
R9(1)
Yield (%)
Temperature
TMS-(1a)a
TES-(1b)
TBS-(1c)
a
54
50
40
240 uC
230 uC
220 uC
Obtained as well at 20 uC, in sealed tubes without Lewis acid.
We are presenting here trialkylsilyl methallylsulfinates (Scheme 1)
as a new class of silylating agents that react with functionalized,
aliphatic, homoallylic, benzylic, phenolic, acidic and sterically
hindered hydroxyl groups. Neither base, nor catalyst are required.
The co-products are fully volatile (SO2 and isobutene) thus
reducing the work-up of the silyl ethers to solvent evaporation.
Recently we have shown that allyl and 2-substituted allyl
(trimethyl)silanes undergo ene reactions with sulfur dioxide and
produce the corresponding b,c-unsaturated silyl sulfinates.15 For
instance, 1a was obtained by reaction of trimethyl-(2-methallyl)-
silane with an excess of SO2 in CH3CN at 240 uC and in the
presence of 0.2 equiv. of TMSOTf. We now report (Table 1) that
Scheme 1 Ene-reaction of SO2 with methallylsilanes.
{ Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b4/b417894g/
*pierre.vogel@epfl.ch
Scheme 2 Variety of hydroxyl groups for silylation reaction (R 5 H).
Chem. Commun., 2005, 1297–1299 | 1297
This journal is ß The Royal Society of Chemistry 2005

View Article Online
been done in order to establish which component of the reaction
Table 2 Silylation of alcohols and phenols; a: R 5 TMS, b: R 5 TES,
c: R 5 TBS
mixture interacts with triethylamine and, thus, slows down the
reaction. Firstly, we examined whether the amine generates
complexes with the reagents. In the presence of Et3N (0.05, 0.5,
1.0 equiv.) no formation of complexes of type 1a–c?Et3N could be
Entry
Alcohol Silyl ethera
Entry Alcohol
Silyl ethera
1
2
2
3
2a
2b
3a
3b
3cb
4c
7
8
8
9
8a
1
9bc
detected by H-NMR. Moreover, no traces of acids (TMSOTf
was used to catalyse the synthesis of 1a–c) were detected by
19F-NMR; this excludes the acid catalysis in our silylation
reaction. We proposed that triethylamine complexes SO2, which
is formed once the silylation takes place. As we shall see a small
amount of SO2 is necessary to catalyze the reaction. This
hypothesis was confirmed by the next experiment. Reaction 18 +
1b A 18b, which requires usually 0.5 h for initiation, was
accelerated on adding at 25 uC a diluted solution of SO2 in CDCl3
(Table 3, entry 3).
3
4
4
5
9
10
10
11
10bd
11b
5b
11ce
12a
5
6
7
6b
11
12
12
13
12b
12cf
13abg
13bch
6
7a
7b
a
At 20 uC, in CD2Cl2 or CDCl3, with 1.1 equiv. of 1a–c, obtained
with 100% 1H-NMR yield, in 5 min. 15 min, 1.4 equiv. of 1c.
89% isolated yield. 92% isolated yield. In 7 h with 1.5 equiv. of
b
All these observations are consistent with the mechanism
proposed in Scheme 4 in which SO2 promotes the silylation.
Thus, silyl group transfer from 1a–c to alcohols is slower than
c
d
e
f
1c. In 10 h with 1.5 equiv. of 1c. In THF-d8. In THF-d8, 3 h.
g
h
silylation of tertiary alcohols with 1c was much slower, most
probably because of steric hindrance. Nevertheless, the use of a
slight excess of reagent led to complete silylation. The excess of
reagent 1c can be destroyed into volatile compounds by adding
MeOH at the end of the reaction.
Table 3 Selective silylation of diols with 1 equiv. of 1b and 1c
Diol
Product
Conditions
CD2Cl2, 20 uC, 5 min
The usefulness of our new silylating reagents is demonstrated
once more in the case of unreactive, sterically hindered alcohols 918
and 10.19 The semi-protected C-linked disaccharide precursor 9
possesses a secondary alcohol moiety that refused to be silylated to
the triethylsilyl ether applying known techniques [e.g.: Et3SiOTf/
lutidine/CH2Cl2, 2 days or Et3SiOTf/pyridine/4-(Me2N)-pyridine,
2 days]. Heating led to product decomposition. We found that the
desired silyl ether can be formed at 25 uC using silylating agent 1b
in CH2Cl2. Protection of alcohol 10 as its silyl ether using classical
conditions is low yielding because of concurrent b-elimination.
With 1b, the alcohol reacts smoothly forming the corresponding
silyl ether with good yield and without the formation of other
products.
THF-d8, or CD3CN,
20 uC, 5 min
For OTBS: CDCl3,
20 uC, 4 h
For OTES: CDCl3,
Triethylsilyl esters are obtained in quantitative yields by treat-
ment of the carboxylic acids 14a–d with our silylating reagent 1b
(1.1 equiv.), in a few minutes at 20 uC (Scheme 3).
20 uC, 2.5 h
We explored also the ability of our reagents 1a–c to discriminate
between different kinds of hydroxyl groups (primary, secondary,
tertiary and phenolic) present in the same substrates. As expected
on the basis of steric factors, the reactivity sequence is primary .
secondary . tertiary alcohols. In the case of diols 16, 17 and 18,
exclusive silylation of the primary alcohols was observed using one
equivalent of 1b,c. The greater acidity of phenols versus alcohols
does not make the former function more reactive than the latter.
Kinetic studies on the reaction tert-BuOH(D) + 1c in CDCl3
(1H-NMR, 298 K), showed a first order rate law in tert-BuOH(D)
(1.5 equiv.) and kH/kD 5 1.0 + 0.05. All silylations with 1a–c were
inhibited by Et3N (0.05, 0.5, 1.0 equiv.). A few experiments have
Scheme 4 Possible mechanism of silylation.
Scheme 3 Silylation of carboxylic acids.
1298 | Chem. Commun., 2005, 1297–1299
This journal is ß The Royal Society of Chemistry 2005

View Article Online
5057–5061; (d) I. Saxena, N. Deka, J. C. Sarma and S. Tsuboi,
Synth. Commun., 2003, 33, 4005–4011.
5 T. Morita, Y. Okamoto and H. Sakurai, Tetrahedron Lett., 1980, 21,
835–838; T. Vesoglu and L. A. Mitscher, Tetrahedron Lett., 1981, 22,
1299–1302.
6 Y. Tanabe, M. Murakami, K. Kitaichi and Y. Yoshida, Tetrahedron
Lett., 1994, 35, 8409–8412; D. A. Johnson and L. M. Tauber,
Tetrahedron Lett., 1996, 37, 605–608.
from hydrogenosulfites 19 equilibrating with the alcohols and
sulfur dioxide. The silyl group transfer might imply the formation
of adduct 20 in the rate determining step and it is not assisted
significantly by proton transfer. Alternatively, the rate determining
step could be the formation of intermediates 21. In this hypothesis,
the silyl group transfer is assisted by the O–S bond breaking of the
hydrogenosulfite, but not by proton transfer.
7 N. Azizi and M. R. Saidi, Organometallics, 2004, 23, 1457–1458 and
references cited therein; H. Firouzabadi and B. Karimi, Synth.
Commun., 1993, 23, 1633–1641; P. Kumar, G. C. G. Pais and
A. Keshavaraja, J. Chem. Res., Synop., 1996, 376–377; B. P. Bandgar
and P. P. Wadgaonkar, Synth. Commun., 1997, 27, 2069–2074;
M. Demina, A. Velikanov, A. Medvedeva, L. Larina and
M. Voronkov, J. Organomet. Chem., 1998, 553, 129–133;
J. M. Blackwell, K. L. Foster, V. H. Beck and W. E. Piers, J. Org.
Chem., 1999, 64, 4887–4892; B. P. Bandgar and S. P. Kasture,
Monatsch. Chem., 2001, 132, 1101–1104; M. M. Mojtsahedi, M. R. Saidi,
M. Bolourtchian and M. M. Heravi, Phosphorus, Sulfur Silicon Relat.
Elem., 2002, 177, 289–292; H. Firouzabadi, N. Iranpoor, K. Amani and
F. Nowrouzi, J. Chem. Soc., Perkin Trans. 1, 2002, 2601–2604.
8 F. Le Bideau, T. Coradin, J. He´nique and E. Samuel, Chem. Commun.,
2001, 1408–1409; A. Biffis, E. Castello, M. Zecca and M. Basato,
Tetrahedron, 2001, 57, 10391–10394.
In conclusion we have developed a new method for alcohol,
phenol and carboxylic acid silylation which does not require base,
or other catalysts, and which generates only volatile co-products
reducing the work-up to simple solvent evaporation.
Xiaogen Huang, Cotinica Craita, Loay Awad and Pierre Vogel*
Laboratoire de Glycochimie et de Synthe`se Asyme´trique, Ecole
Polytechnique Fe´de´rale de Lausanne, (EPFL), BCH, CH-1015,
Lausanne, Suisse. E-mail: pierre.vogel@epfl.ch; Fax: (+41)216939375;
Tel: (+41)216939370
Notes and references
1 W. C. Still and M. J. Schneider, J. Am. Chem. Soc., 1977, 99, 948–950;
H. H. Hergott and G. Simchen, Synthesis, 1980, 626–627; J. R. Hwu
and J. A. Roble, J. Chem. Soc., Chem. Commun., 1986, 704–706;
J. D. White and R. G. Carter, in Science of Synthesis, ed. I. Fleming,
Georg Thieme Verlag, Stuttgart, 2001, vol. 4, pp. 371––412.
9 Y. Tanabe, H. Okumura, A. Maeda and M. Murakami, Tetrahedron
Lett., 1994, 35, 8413–8414.
10 A. Hosomi and H. Sakurai, Chem. Lett., 1981, 85–88; G. A. Olah,
A. Husain, B. G. B. Gupta, G. F. Salem and S. C. Narang, J. Org.
Chem., 1981, 46, 5212–5214.
2 T. W. Green and P. G. M. Wuts, Protective Groups in Organic Synthesis,
Wiley, New York, 3rd. edn., 1999; P. Kocienski, Protecting Groups, ed.
D. Anders, R. Noyori and B. M. Trost, Thieme, Stuttgart, 1994;
K. Jarowicki and P. Kocienski, J. Chem. Soc., Perkin Trans. 1, 1999,
1589–1616; V. Pouzar, Chem. Listy, 1988, 82, 715–728.
3 See e.g.: G. Van Ling, J. Chromatogr., 1969, 44, 175–177; J. Kusmierz,
J. J. De George, D. Sweeney, D. May and S. I. Rapoport,
J. Chromatogr., 1989, 497, 39–48; C. F. Poole and A. Zlatkis,
J. Chromatogr. Sci., 1979, 17, 115–123; G. Van Look, G. Simchen
and J. Heberle, Silylating Agents, Fluka, Buchs, Switzerland, 2nd ed.,
1995.
11 T. Suzuki, T. Watahiki and T. Oriyama, Tetrahedron Lett., 2000, 41,
8903–8906.
12 M. Kirihara, T. Katou and A. Hatano, ITE Lett. Batteries,
New Technol. Med., 2002, 3, 225–227.
13 M. Hayashi, Y. Matsuura and Y. Watanabe, Tetrahedron Lett., 2004,
45, 1409–1411.
14 E. Nakamura, T. Murofushi, M. Shimizu and I. Kuwajima, J. Am.
Chem. Soc., 1976, 98, 2346.
15 L. Bouchez and P. Vogel, Synthesis, 2002, 225–231.
16 L. H. Li, D. Wang and T. H. Chan, Tetrahedron Lett., 1991, 32,
2879–2882.
4 (a) M. A. Brook, Silicon in Organic, Organometallics, and
Polymer Chemistry, Wiley, New York, 2000; (b) T. Watahiki,
M. Matsuzaki and T. Oriyama, Green Chem., 2003, 5, 82–84; (c)
B. Hatano, S. Toyota and F. Toca, Green Chem., 2001, 3, 140–142;
B. A. D’Sa, D. McLeod and J. G. Verkade, J. Org. Chem., 1997, 62,
17 J.-M. Roulet, G. Puhr and P. Vogel, Tetrahedron Lett., 1997, 35,
6201–6204.
18 R. Demange, L. Awad and P. Vogel, Tetrahedron: Asymmetry, 2004, 15,
3573–3585.
19 L. Awad, J. Riedner and P. Vogel, Chem. Eur. J., submitted.
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 1297–1299 | 1299