ethers are remarkably more stable and thus can survive many
more synthetic transformations and chromatographic puri-
fications. At the same time, the TES ethers do not introduce
as much steric bulkiness as the tert-butyldimethylsilyl (TBS)
or tert-butyldiphenylsilyl (TBDPS) ethers. In some particular
situations, such as protection of the hydroxyl in Evans’
aldols, masking the OH as a TES ether is often much more
feasible and practical than protection as a TBS ether.
Selective removal of TES protecting groups in the presence
of TBS ethers or other even more stable silyl protecting
groups has been documented in the literature. However, in
most instances, successful cases5 were only one step in the
multistep synthesis of a complex molecule, and the limits
and scope of the recipe were unexplored or unreported. To
our knowledge, there is only one systematic study6 that was
directed toward selective deprotection of TES protecting
groups in the presence of TBS ethers, where mesoporous
silica7 MCM-41 (probably not readily accessible to most
organic chemists) was used as the reagent. The reaction was
run in a heterogeneous system, and essentially no informa-
tion about functional group compatibility was provided
therein.
Scheme 1
Cleavage of sterically hindered TES ethers such as those
in 1 and 4 (entries 1 and 2, Table 1) required longer reaction
times. In the case of deprotection of 1, full consumption of
the starting TES ether took 5 h at 23 °C. Workup and
chromatographic separation gave the alcohol 2 in 65.6%
yield, along with a small amount of ketone 3 (8.1%).
Cleavage of the TES protecting group in 4 was similar. After
4.5 h of reaction at 20 °C, alcohol 5 and aldehyde 6 were
isolated from the product mixture in 60% and 28% yields,
respectively (together with 4.5% of unreacted starting 4).
The reaction with geranyl TES ether (entry 21) was
somewhat peculiar, where oxidation of alcohol 37 appeared
to be more easily oxidized than most other alcohols tested
in this work, giving aldehyde 38 as the main product.
To investigate the large differences in cleavage rates
between TES ethers and TBS ethers using parallel runs with
various individual pairs of TES/TBS ethers, we also per-
formed two intermolecular competition experiments (Scheme
1). Starting with an equimolar mixture of the TES ether 8
and the TBS ether 12,9 the reaction with 1.5 molar equiv of
IBX at 20 °C for 30 min led to alcohol 9 in 93% yield (and
5% of aldehyde 10), with the TBS ether 12 recovered in
98% yield. Switching the functional groups in the two
substrates (using 11 and 39 in place of 8 and 12) did not
change the selectivity. Similar preferential cleavage of TES
ether was also observed with a compound containing both
TES and TBS funtionalities within the same molecule (entry
19, Table 1; because of a solubility problem a 3:4 v/v mixture
of THF and DMSO was used instead of neat DMSO). Again,
the TES was fully cleaved,10 whereas the TBS remained
intact. We note that under Swern oxidation conditions the
same substrate (32) gave11 only aldehyde 34 (rather than
alcohol 33) in 85% yield.
In executing an ongoing project involving reactions using
IBX, we noticed that a TES protecting group was unexpect-
edly cleaved, giving an alcohol (rather than a carbonyl
compound) as the main product. This inspired us to further
examine the reaction of IBX with other TES and TBS ethers.
Preliminary results8 are summarized in Table 1.
It can be seen from Table 1 that unhindered primary TES
ethers were cleaved in high yields within less than 1 h. The
closely related TBS ethers, however, remained untouched
under the same conditions, as shown by TLC monitoring
and the high-yield recovery of the starting materials by
column chromatography. Some commonly employed pro-
tecting groups such as ketal, thioacetal, pivaloyl, benzyl, and
benzoyl groups were not affected to a detectable degree.
In the beginning, IBX caught synthetic chemists’ attention
mainly as an oxidizing agent. The immediate products of
desilylation in this work were alcohols. Therefore, it is not
surprising that the resulting alcohols could be further oxidized
into corresponding carbonyl compounds (in high yields if
excess IBX was present and the reaction time was pro-
longed). What deserves to be noted here is that the rates at
which the alcohols were oxidized were apparently much
lower than those for the silicon-oxygen bond cleavage. Such
significant rate differences between desilylation and oxidation
made it possible in most cases to isolate the alcohols as the
predominant products.
The IBX appeared to be substantially consumed with the
desilylation process. The λmax (259 nm) of IBX in the run
with 8 (starting with 1.0 mmol of 8 and 1.1 mmol of IBX)
decreased by 37% over 35 min (mostly within 15-20 min),
whereas in the absence of 8 (under otherwise identical
(5) See the examples in a recent review: Nelson, T. D.; Crouch, R. D.
Synthesis 1996, 1031-1069.
(6) Itoh, A.; Kodama, T.; Masaki, Y. Synlett 1999, 357-359.
(7) Kresge, C. T.; Leonowicz, M. E.; Roth, W. J.; Vartuli, J. C.; Beck,
J. S. Nature 1992, 359, 710-712.
(8) General Procedure. IBX (1.1 mmol) was added to a solution of the
silyl ether (1 mmol) in DMSO (5 mL) containing added water (90 µL, 5
mmol). The mixture was stirred at 20 °C (TLC monitoring) for the indicated
time (Table 1) before being partitioned between diethyl ether and water.
The organic layer was washed with water and brine and dried over
anhydrous Na2SO4. The solvents were removed by rotary evaporation, and
the products were obtained by flash chromatography on silica gel (eluting
with ethyl acetate/hexanes).
(9) We chose this compund instead of structurely more closely related
TBS ether 11 just for unambiguous identification of the origin of the alcohol
in the product mixture.
(10) It is noteworthy that Dess-Martin periodinane (structurally closely
related to IBX) did not cleave TES while oxidizing alcohols into carbonyls.
See, e.g.: Jones, T. K.; Reamer, R. A.; Desmond, R.; Mills, S. G. J. Am.
Chem. Soc. 1990, 112, 2998-3017.
(11) Tolstikov, G. A.; Miftakhov, M. S.; Vostrikov, N. S.; Komissarov,
N. G.; Alder, M. E.; Kuznetsov, O. M. Zh. Org. Khim. 1988, 24, 224-225
(in Russian); Chem. Abstr. 1989, 110, 7162.
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Org. Lett., Vol. 4, No. 13, 2002