New and efficient procedure for the preparation of unsymmetrical silaketals

Article abstract of DOI:10.1021/ol034207j

(Matrix presented) A new and efficient procedure for the preparation of unsymmetrical silaketals via a three-step protocol without isolation of the intermediates is presented. The unsymmetrical silyl ethers and silanes can also be readily obtained via thi

Full text of DOI:10.1021/ol034207j

ORGANIC
LETTERS
2003
Vol. 5, No. 12
2037-2040
New and Efficient Procedure for the
Preparation of Unsymmetrical Silaketals
Marc Petit, Gae1lle Chouraqui, Corinne Aubert,* and Max Malacria*
Laboratoire de Chimie Organique associe´ au CNRS, UniVersite´ Pierre et Marie Curie
(Paris 6), Tour 44-54, Case 229, 4 Place Jussieu, 75252 Paris Cedex 05, France
aubert@ccr.jussieu.fr; malacria@ccr.jussieu.fr
Received February 5, 2003
ABSTRACT
A new and efficient procedure for the preparation of unsymmetrical silaketals via a three-step protocol without isolation of the intermediates
is presented. The unsymmetrical silyl ethers and silanes can also be readily obtained via this sequence of reactions.
Silylated tethers have become very popular in organic
synthesis over the past decade because they allow the
transformation of intermolecular reactions into intramolecular
ones. Furthermore, they are readily and selectively removed
after the reaction, thus providing an easy delivery of the
products.
Different aspects of the chemistry of these silicon linkers
which are generally ethers have been compiled in several
reviews.1 They have been applied to many types of reac-
tions: radical cyclizations,1 [4+2] cycloadditions,1 nucleo-
philic additions,1 and more recently, Pauson-Khand reac-
tions2 and metathesis.3
From a practical point of view, the silicon linkage is
created by simple silylation of a hydroxy group by a
chlorosilane bearing the reactive unit. In addition, the
availability of different dialkyldichlorosilanes has warranted
the use of silaketals as disposable tethers.
Unfortunately, the synthesis of unsymmetrical silaketals
is often complicated by the formation of the undesired
symmetrical silaketals. Indeed, the usual protocol for di-
methylsilaketal formation consists of the silylation of one
alcohol with a large excess of Me2SiCl2, subsequent removal
of the volatile dichlorosilane, and eventual addition of the
second alcohol. However, this method suffers from major
drawbacks: (i) the intermediate monochlorosilane has to be
easily separated from the dichlorosilane and (ii) higher
boiling dialkyldichlorosilanes make this procedure incompat-
ible for the preparation of heavier silaketals. Different
solutions have been proposed to circumvent these problems.
t-Bu2Si(OTf)Cl was introduced for the preparation of di-tert-
butylsilaketals, but the second silylation sometimes proved
difficult due to the bulkiness of the tert-butyl group.4 Stork
used the chlorodimethylamino-dimethylsilane to selectively
prepare alkenyl- and alkynylsilyl ethers,5 but to our knowl-
edge, this procedure has never been applied to unsymmetrical
silaketals. The latter were efficiently prepared by the
activation of 4-pentenyl silyl ethers with iodonium dicollidine
perchlorate in the presence of an alcohol.6 However, this two-
step sequence has been employed only for glycosylations
and requires the formation of the intermediate 4-pentenyl
silyl ethers.
In this paper, we present a new and very efficient
procedure for the preparation of unsymmetrical silaketals via
a three-step protocol without isolation of the intermediates.
This method is based upon the reaction of a first alcohol
with a dialkylchlorosilane, transformation of the resulting
alkoxysilane into the corresponding bromide by reaction with
N-bromosuccinimide, and condensation of the bromide with
a second alcohol. N-Bromosuccinimide has been used
previously to prepare bromoalkylsilanes from trialkylsilanes
in a sequence devoted to the preparation of 1-silyloxy-2,3-
(1) (a) Bols, M.; Skrydstrup, T. Chem. ReV. 1995, 95, 1253-1277. (b)
Fensterbank, L.; Malacria, M.; Sieburth, S. M. Synthesis 1997, 813-854.
(c) Gauthier, D. R. J.; Zandi, K. S.; Shea, K. J. Tetrahedron 1998, 54,
2289-2338. (d) Skrydstrup, T. In Science of Synthesis: Houben-Weyl
Methods of Molecular Transformations; Fleming, I., Ed.; Georg Thieme
Verlag: Stuttgart, Germany, 2001; Vol. 4, pp 439-530. (e) White, J. D.;
Carter, R. G. In Science of Synthesis: Houben-Weyl Methods of Molecular
Transformations; Fleming, I., Ed.; Georg Thieme Verlag: Stuttgart,
Germany, 2001; Vol. 4, pp 371-412.
(2) Brummond, K. M.; Sill, P. C.; Rickards, B.; Geib, S. J. Tetrahedron
Lett. 2002, 43, 3755-3738.
10.1021/ol034207j CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/22/2003

epoxyalkanes7 but has been limited to these compounds and
no silaketals have been prepared. The proposed sequence is
carried out in only one solvent at room temperature and in
addition, each step is performed with a stoichiometric amount
of each reagent.
In the case of 5d, the yield is moderate and whatever the
reaction time, the reaction did not go to completion. Alcohols
1d and 4c were recovered.
Having these results in hands, we turned our attention to
the preparation of dimethylsilaketals. As expected, the
corresponding alkoxysilanes and silylbromides are quite
unstable on TLC and, therefore, monitoring of the first two
steps was difficult. In addition, when primary alcohols were
used such as 4a and 4b, the reactions occurred but the
resulting dimethylsilaketals were moderately stable and no
representative yields could be obtained. However, in the case
of menthol 1e and 2-butyn-1-ol 4b, silaketal 6 was isolated
in 81% overall yield (Scheme 2).
We have first chosen chlorodiisopropylsilane for the study
(Scheme 1), because the corresponding silaketals 5 formed
Scheme 1. General Preparation of Silaketals
Scheme 2a
are known to be stable to aqueous workup and chromatog-
raphy.8
The alcohol R1OH was initially treated with 1 equiv of
i-Pr2SiClH in the presence of triethylamine and 4-(dimethyl-
amino)pyridine in CH2Cl2 at room temperature. The reaction
was monitored by TLC until completion. The corresponding
alkoxydiisopropylsilane 2 was then transferred with filtration
into another flask and the filtrate was treated with N-
bromosuccinimide, added pure by small portions. The
resulting solution was transferred into a solution of the
second alcohol R2OH 4 in the presence of triethylamine and
4-(dimethylamino)pyridine in CH2Cl2 to afford silaketals 5
in high overall yield. The results are summarized in Table
1.
a Reagents and conditions: (a) ClSiMe2H (1 equiv), NEt3 (1.1
equiv), DMAP (0.1 equiv), CH2Cl2, rt. (b) NBS (1.1 equiv), CH2Cl2,
rt. (c) 3-Butyn-1-ol, 4b, NEt3 (1.1 equiv), DMAP (0.1 equiv),
CH2Cl2, rt.
Upon use of di-tert-butylchlorosilane, the sequence had
to be modified. Indeed, the alkoxydi-tert-butylsilylbromide
7, derived from alcohol 1a, did not react with 4a under the
previously described conditions. To overcome this lack of
reactivity, we carried out the reaction in the presence of DMF
in different conditions. The results are summarized in Table
2.
Table 1. Preparation of the Diisopropylsilaketals 5
Table 2. Reaction Conditions for the Preparation of the
Di-tert-butylsilaketals
conditions (a)
8 (%)
9 (%)
DMF, NEt3 (1.1 equiv)
DMAP (0.1 equiv)
50
50
DMF, DMAP (2.5 equiv)
DMF (1 equiv), CH2Cl2, K2CO3
DMF
60
0
0
40
100
100
Besides the desired silaketal 8, we observed the formation
of the corresponding silanol 9 in 50% to quantitative yield.
In DMF and without DMAP or NEt3, 9 is the sole product
Table 1 shows that the conditions of the reaction are
compatible with aromatic, allylic, and propargylic alcohols.
2038
Org. Lett., Vol. 5, No. 12, 2003

of the reaction. We have noticed that bromosilane 7, which
is quite stable upon aqueous workup, led instantaneously to
silanol 9 when first treated by DMF and then hydrolyzed.
Thus, in DMF, the products 8 and 9 arose probably from
intermediate 10 (Figure 1) which comes from the reaction
Scheme 3a
a Reagents and conditions: (a) HCtCMgBr (1 equiv), THF,
ClSi(i-Pr)2H (1 equiv), rt, 6 h. (b) EtMgBr (1 equiv), ClSi(i-Pr)2H
(1 equiv), overnight. (c) NBS (2.2 equiv), CH2Cl2, rt, 15 min. (d)
HCtCCH2OH (2 equiv), NEt3 (2.2 equiv), DMAP (0.2 equiv),
CH2Cl2, rt.
Figure 1. Possible intermediate 10.
between the bromosilane and DMF. Such an intermediate
already has been invoked.9
We then extended this procedure to the easy preparation
of diisopropylsilyl ethers. In connection with our studies on
[2+2+2] cyclizations,10 we have chosen alcohols exhibiting
triple bonds and heteroatomic tethers.
Condensation of 1-hexynyllithium 11 with chlorodiiso-
propylsilane in THF quantitatively furnished the correspond-
ing silane 12. After evaporation of THF, 12 was added into
a solution of NBS in CH2Cl2 leading very quickly (15 min)
to the silylbromide 13. The solution of 13 was transferred
to a solution of alcohols 14a-d under the conditions
described above to give the corresponding silyl ethers 15a-d
in very good yields (Table 3).
ethyne 16 (Scheme 3), which was prepared in a two-step
sequence: addition of ethynyl Grignard to a THF solution
of ClSi(i-Pr)2H/deprotonation of the resulting product with
ethyl Grignard and condensation with ClSi(i-Pr)2H. Com-
pound 16 was then transformed into the disilyl ether 18
through the already described sequence in 60% overall yield.
Finally, we extended this procedure to the preparation of
silanes. Few consecutive alkylations of dichlorosilanes are
described in the literature.11 As for the synthesis of unsym-
metrical silaketals, the products of the reaction are usually
contaminated with the undesired symmetrical compounds.
On the contrary, in the sequence described in Scheme 4, no
Scheme 4a
Table 3. Preparationa of Diisopropylsilyl Ethers 15
a Reagents and conditions: (a) n-BuLi (1 equiv), THF, -78 °C.
(b) NBS (1.1 equiv), CH2Cl2, 15 min, rt. (c) Transolvatation,
HCtCCH2MgBr (1.6 equiv), Et2O, 0 °C.
symmetrical product was isolated. Indeed, the addition of
1-hexynyllithium to a solution of dimethylchlorosilane in
(3) (a) Chang, S.; Grubbs, R. H. Tetrahedron Lett. 1997, 38, 4757-
4760. (b) Van de Weghe, P.; Aoun, D.; Boiteau, J. G.; Eustache, J. Org.
Lett. 2002, 4, 4105-4108 and reference cited therein.
(4) (a) Gillard, J. W.; Fortin, R.; Morton, H. E.; Yoakim, C.; Quesnelle,
C. A.; Daignault, S.; Guindon, Y. J. Org. Chem. 1988, 53, 2602-2608. (b)
Gillard, J. W.; Fortin, R.; Grimm, E. L.; Maillard, M.; Tjepkema, M.;
Bernstein, M. A.; Glaser, R. Tetrahedron Lett. 1991, 32, 1145-1148.
(5) Stork, G.; Keitz, P. F. Tetrahedron Lett. 1989, 30, 6981-6984.
(6) Colombier, C.; Skrydstrup, T.; Beau, J. M. Tetrahedron Lett. 1994,
35, 8167-8170.
a Reagents and conditions: (a) n-BuLi, THF, -78 °C, ClSi(i-Pr)2H (1.2
equiv). (b) NBS (1.1 equiv), CH2Cl2, rt, 15 min. (c) 14a-d (1 equiv), NEt3,
DMAP, rt, CH2Cl2.
(7) Tanino, K.; Honda, Y.; Miyashita, M. Tetrahedron Lett. 2000, 41,
9281-9285.
(8) Hutchinson, J. H.; Daynard, T. S.; Gillard, J. W. Tetrahedron Lett.
1991, 32, 573-576.
(9) Simchen, G.; Kober, W. Synthesis 1976, 259-261.
(10) Petit, M.; Chouraqui, G.; Phansavath, P.; Aubert, C.; Malacria, M.
Org. Lett. 2002, 4, 1027-1029.
By using this procedure, we also were able to prepare a
disilyl ether 18 derived from 1,2-bis(diisopropylsilanyl)-
(11) Coelho, P. J.; Blanco, L. Synlett 2001, 1455-1457.
Org. Lett., Vol. 5, No. 12, 2003
2039

THF furnished quantitatively the corresponding silane 19.
Subsequent transformation into the silylbromide 2012 and
then condensation with propargyl Grignard led to the
dimethylsilylated compound 21 in 85% overall yield.
In summary, a new and efficient procedure for the
preparation of unsymmetrical silaketals in a three-step
protocol without isolating the intermediates was developed.
Yields are high particularly when diisopropylchlorosilane was
employed. We have also shown that this procedure can be
extended to silylated ethers and silanes with only a few
modifications. Use of the silaketals as disposable tethers in
[2+2+2] cyclizations is under investigation in our laboratory
and will be reported in due course.
Acknowledgment. Financial support was provided by
CNRS and MRES. M.P. thanks Aventis-CNRS for a fel-
lowship.
Supporting Information Available: Experimental pro-
cedures and characterization data for 5a-d, 6, 15a-d, 16,
18, and 21. This material is available free of charge via the
Internet at http://pubs.acs.org.
(12) Some chloroalkynyksilyanes have been prepared by using SO2Cl2,
see: Buynak, J. D.; Strickland, J. B.; Lamb, G. W.; Khasnis, D.; Modi, S.;
Williams, D.; Zhang, H. J. Org. Chem. 1991, 56, 7076-7083.
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