February 1998
SYNLETT
209
A Mild, Efficient, and Selective Method for the Desilylation of More Common Trialkylsilyl
Ethers by Cerium(III) Chloride Heptahydrate and Sodium Iodide in Acetonitrile
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Giuseppe Bartoli,* Marcella Bosco, Enrico Marcantoni,* Letizia Sambri and Elisabetta Torregiani
aDipartimento di Scienze Chimiche, via S.Agostino 1, I-62032 Camerino (MC), Italy
bDipartimento di Chimica Organica "A.Mangini", viale Risorgimento 4, I-40136 Bologna, Italy
Fax: 39 737 637345; e-mail: bartoli@ms.fci.unibo.it
Received 21 October 1997
Abstract: Treatment of trialkylsilyl ethers with cerium(III) chloride
heptahydrate and sodium iodide in acetonitrile provides a simple,
convenient, and chemoselective process for desilylation, and the parent
alcohol was obtained in high yield. The trialkylsilyl ethers have been
cleaved selectively in the presence of acetate, benzyl and
tetrahydropyranyl ethers.
The importance of protecting the hydroxyl group in synthetic organic
chemistry is reflected by the currently rather continuous appearance in
the literature of syntheses of biologically active molecules possessing
hydroxyl groups. For this reason, the protection and deprotection of free
hydroxyl groups have become commonplace in organic synthesis. Due
to their ease and recently developed selectivity of attachment, many
trialkylsilyl groups have been commonly used as protection of free
1
-5
hydroxyl groups.
Experience shows that the critical parameters are generally the stability
and the cleavage of the protecting group rather than its introduction. As
with most protecting groups, then, many methods are available for the
2
removal of trialkylsilyl ethers, under a variety of conditions. One of the
most common methods for the cleavage of silyl ethers is the exploitation
of the high affinity that silicon has for fluoride ions. Thus, many routes
for the deprotection of the trialkylsilyl ether involve one form of
fluoride or another. Tetrabutylammonium fluoride (TBAF), which is
6
available commercially as the hydrate, is often used, however, fluoride
ion in aprotic solvent, being a strong base, can effect base sensitive
7
substrates. Indeed, the principal detractions to TBAF are its high cost
were successfully cleaved13 with CeCl3•7H2O and NaI in acetonitrile.
The results are summarized in Table 1, and in all cases, the yields are
and its comparatively high basicity, which can cause undesirable side
8
reactions such as β-elimination or enolate formation leading to further
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14
reactions. There are several other methods for the cleavage of
quantitative.
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10
trialkylsilyl ethers and recently Singh published the facile removal of
TBDMS protecting group using ceric ammonium nitrate (CAN) in
methanol. Although the method is mild, it can not be used in the
presence of other protecting groups for alcohols, such as
tetrahydropyranyl (THP) ethers. We wish to describe herein a mild
method for the desilylation trialkylsilyl-protected primary and
secondary alcohols by the use of cerium(III) chloride heptahydrate and
sodium iodide in acetonitrile (Scheme).
It has been observed that in the case of primary substrates (entry 1), the
desilylation is complete within 18 h at room temperature, but the
hindered substrates (entries 2 and 3) require 24 h at reflux temperature.
It is shown that TBDMS ethers can be selectively cleaved in the
presence of other functional groups, such as nitro and ester functions
(entries 4, 5 and 6). TBDMS ethers can also be cleaved in high yield in
the presence of another acid sensitive protecting group (entry 7) such as
2
the tert-butoxycarbonyl (BOC) group. Further, TBDMS ethers bearing
stereogenic centers (entries 4, 5 and 6) can be cleaved giving the parent
alcohols with complete retention of the original configuration.15
Given these results, a series of trialkylsilyl ethers synthesized varying
the substituents on silicon, were treated with CeCl •7H O and NaI in
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2
acetonitrile using the optimised procedure,14 and the results are
summarized in Table 2.
Tert-butyldiphenylsilyl (TBDPS) ethers16 are generally cleaved under
During the development of new methods for protection and deprotection
of organic functional groups, we found that cerium(III) chloride
functioned as efficient Lewis acid for the cleavage of 1,3-dioxolanes to
1
1
carbonyl compounds. This opened the possibility for it to be
developed as deprotecting agents for silyl ethers, and there are many
advantages to the use of cerium(III) chloride heptahydrate in
acetonitrile; no strongly basic or acidic conditions are used, nor are
expensive reagents required, and no precautions need to be taken to
exclude moisture or oxygen from the reaction system. In the first place,
we synthesized a variety of tert-butyldimethylsilyl (TBDMS) ethers12
with different steric and electronic environment and noted that they
the same conditions as those used for TBDMS ethers, but more drastic
conditions and longer reaction times are necessary (entries 1 and 2).
Consequently, selective removal of TBDMS group in the presence of
TBDPS group was carried out (entry 3). We have also investigated the
possibility of removal of large steric bulk of the triisopropylsilyl (TIPS)
group. Under our conditions TIPS ethers of primary and secondary
alcohols are easily desilylated in good yields (entries 4 and 5).
Unfortunately, it was not possible to deprotect selectively TBDMS
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