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J . Org. Chem. 2000, 65, 7228-7230
HMDS.11 Although these procedures provide an improve-
Mild a n d High ly Efficien t Meth od for th e
ment, in most cases reaction with hindered alcohols do
not take place,5 or required forceful conditions and
prolonged reaction time.12 In our development of new
methods for functional group transformation, we are
especially interested in exploring the potential use of
various types of neutral or nearly neutral catalyst.13 In
continuation of these studies, herein, we wish to describe
a new protocol for the mild and rapid trimethylsilylation
of a wide variety of alcohols using HMDS and a catalytic
amount of iodine (Scheme 1).
Silyla tion of Alcoh ols Usin g
Hexa m eth yld isila za n e Ca ta lyzed by Iod in e
u n d er Nea r ly Neu tr a l Rea ction Con d ition s
Babak Karimi* and Behzad Golshani
Department of Chemistry, Institute for Advanced Studies in
Basic Sciences (IASBS), P.O.Box 45195-159, Gava Zang,
Zanjan, Iran
Compounds that were trimethylsilylated in this way
are primary, allylic, benzylic, hindered and unhindered
secondary, tertiary, and acid-sensitive tertiary alcohols
(Tables 1 and 2). Generally, in the cases of primary and
secondary alcohols the reactions were completed within
less than 3 min in CH2Cl2 at room temperature ac-
companied by a fast evolution of NH3 gas from the
reaction mixture (Table 1, entries 1-12). However, in a
separate experiment, we observed that HMDS alone (as
solvent) is not suitable for the silylation of benzhydrol
and tertiary alcohols such as adamantanol, and no
reaction occurred even under reflux conditions (Table 1,
entry 13; Table 2, entry 1). On the other hand, the
representative results of the silylation of these substrates
under iodine catalyzed conditions clearly indicate the
remarkable catalytic activity of iodine for such a trans-
formation (Table 1, entry 14; Table 2, entry 2). Recently,
we have shown that ZnCl2 in refluxing acetonitrile and
nitrogen ligand complexes of metal chlorides are highly
efficient catalyst for chemoselective silylation of various
types of alcohols.7,8 However, we found that these cata-
lysts were not suitable for silylation of acid-sensitive
alcohols such as diarylalkyl carbinols, and produce the
corresponding alkenes as sole products.14 This observa-
tion encouraged us to investigate the ability of the
protocol for the efficient conversion of highly crowded
tertiary alcohols to their corresponding trimethylsilyl
ethers.
karimi@iasbs.ac.ir
Received May 21, 2000
The role of silyl groups has already been recognized,
of late, as an important part of organic chemistry from
both analytical and synthetic point of view, especially as
protecting group in many syntheses of reasonable com-
plexity.1 Generally, the formation of silyl ethers carried
out by treatment of alcohols with silyl chlorides or silyl
triflates in the presence of a base,2 Li2S,3 and sometimes
a nonionic super base catalyst.4 However, some of these
methods frequently suffered from drawbacks such as lack
of reactivity or the difficulty in removal of amine salts
derived from the reaction of by-produced acid and co-
bases during the silylation reaction. 1,1,1,3,3,3-Hexa-
methyldisilazane (HMDS) is a stable, commercially
available, and cheap reagent for trimethylsilylation of
hydrogen-labile substrates,1a giving ammonia as the only
byproduct. On the other hand, silylation using this
silazan-type reagent is nearly neutral and does not need
special precautions. However, the low silylating power
of HMDS is a main drawback for its application, which
needs forceful conditions and long reaction times in many
instances. A variety of catalysts such as (CH3)3SiCl,5
sulfonic acids,6 ZnCl2,7 nitrogen ligand complexes of
metalchlorides,8 zirconium sulfophenyl phosphonate,9
K-10 montmorilonite,10 and especial types of catalysts,
having the general formula X1-NH-X2 in which at least
one of the groups X1, X2 is electron-withdrawing such as
ester or amide groups, has also been reported for the
silylation of a wide range of functional groups using
Inspection of the data in Table 2 clearly shows that
different types of highly hindered tertiary alcohols were
successfully converted to the corresponding silyl ethers
in almost quantitative yields at room temperature (Table
2). Due to the nearly neutral nature of the reaction
medium, no elimination by- products were observed at
all. To the best of our knowledge this method describes
the first example of highly efficient trimethylsilylation
of highly acid-sensitive and hindered diarylalkyl carbinols
using HMDS (Table 2, entries 4 and 5).
(1) (a) Lalonde, M.; Chan, T. H. Synthesis 1985, 817. (b) Greene,
T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis,
2nd ed.; Wiley: New York, 1991. (c) Kocienski, P. J . In Protective
Groups; Enders, R., Noyori, R., Trost, B. M., Eds.; Thieme: Stuttgart,
1994.
(2) For example, see: Chaudhary, S. K.; Hernandez, O. Tetrahedron
Lett. 1979, 99.
(3) Olah, G. A.; Gupta, B. G. B.; Narang, S. C.; Malhotra, R. J . Org.
Chem. 1979, 44, 4272.
(4) (a) D Sa, B. A.; McLeod, D.; Verkade, J . G. J . Org. Chem. 1997,
62, 5057. (b) D Sa, B. A.; Verkade, J . G. J . Am. Chem. Soc. 1996, 118,
12832.
(5) (a) Langer, S. H.; Connell, S.; Wender, J . J . Org. Chem. 1958,
23, 50. (b) Gauttret, P.; El-Ghamarti, S.; Legrand, A.; Coutrier, D.;
Rigo, B. Synth. Commun. 1996, 26, 707.
(6) Goldschmidt A. G., T. German Patent 2 758884.
(7) Firouzabadi, H.; Karimi, B. Synth. Commun. 1993, 23, 1633.
(8) Firouzabadi, H.; Sardarian, A. R.; Khayat, Z.; Karimi, B.;
Tangestaninejad, S. Synth. Commun. 1997, 27, 2709.
(9) Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.; Constan-
tino, U. Synth. Commun. 1999, 29, 541.
The mechanism for these transformations is unclear.
One idea may be that I2 produces trace amounts of HI or
TMSI, which might be the actual catalyst for the silyla-
tion reaction. However, a brief survey of the literature
shows that silylation reaction with HMDS in the presence
(11) Bruynes, C. A.; J urriens, T. K. J . Org. Chem. 1982, 47, 3966.
(12) Reference 11, Table 1, entry 10.
(13) (a) Karimi, B.; Ebrahimian, G. R.; Seradj, H. Org. Lett. 1999,
1(11), 1737. (b) Karimi, B.; Seradj, H.; Ebrahimian, G. R. Synlett 1999,
1456. (c) Karimi, B.; Miri Ashtiani, A. Chem. Lett. 1999, 1199. (d)
Firouzabadi, H.; Iranpoor, N.; Karimi, B. Synthesis 1999, 58. (e)
Firouzabadi, H.; Karimi, B.; Eslami, S. Tetrahedron Lett. 1999, 40,
4055. (f) Karimi, B.; Seradj, H. Synlett 2000, 641.
(10) Zhang, Z. H.; Li, T. S.; Yang, F.; Fu, C. G. Synth. Commun.
1998, 28, 3105.
(14) Karimi, B. Unpublished results.
10.1021/jo005519s CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/27/2000