A facile and selective deprotection of tert-butyldimethylsilyl ethers of phenols using triethylamine N-oxide

Article abstract of DOI:10.1016/S0040-4039(02)01452-1

Aryl TBS ethers can be cleaved selectively in high yields in the presence of alkyl TBS ethers by employing triethylamine N-oxide.

Full text of DOI:10.1016/S0040-4039(02)01452-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7277–7279
A facile and selective deprotection of tert-butyldimethylsilyl
ethers of phenols using triethylamine N-oxide
P. K. Zubaidha,* S. V. Bhosale and A. M. Hashmi
School of Chemical Sciences, SRTM University, Nanded 431606, India
Received 14 December 2001; revised 3 July 2002; accepted 12 July 2002
Abstract—Aryl TBS ethers can be cleaved selectively in high yields in the presence of alkyl TBS ethers by employing triethylamine
N-oxide. © 2002 Elsevier Science Ltd. All rights reserved.
In recent years, several protection/deprotection proto-
cols have been reported for temporarily masking
hydroxyl groups because of their significance in multi-
step syntheses of complex synthetic targets of biological
significance.1 Amongst these, the tert-butyldimethylsilyl
(TBS) group remains the method of choice for hydroxyl
protection due to its stability and the ease by which it
can be introduced and removed.2 Furthermore, discrim-
ination between alkyl and aryl silyl ethers facilitates
deprotection of one group in the presence of the other.3
In this regard, a number of methods exist for selective
deprotection of alkyl silyl ethers while the techniques
available for aryl silyl ethers are relatively few.4 Also, it
is worth mentioning that most of the methods reported
for selective desilylation of aryl silyl ethers employ basic
conditions. More recently, Crouch et al. reported the
use of solid NaOH and a phase transfer catalyst to
achieve such a similar selective desilylation under mild
conditions.5
In our hands, the above desilylation using reported
methods3,4 led to formation of unwanted side products
and failed to furnish 2 in reasonable yield. This led us
to investigate the possibility of utilising Et3N-O as an
effective reagent for selective deprotection of aryl silyl
ethers. Accordingly, we synthesised various TBS ethers
and studied their cleavage with Et3N-O. The results are
summarised in Table 1. As can be seen in Table 1,
deprotection proceeded very cleanly in high yield in all
cases. However in the case of entry 10, no trace of
deprotected compound was observed.
It is remarkable that side reactions do not occur during
desilylation under these conditions and consistent yields
were obtained despite the presence of sensitive function-
ality such as a chalcone, an enone or an aldehyde in
some of the examples studied (entries 7, 8 and 9).
We believe that the mechanism of this selective removal
involves nucleophilic attack of the N-oxide on the
silicon with methanol acting as the proton source.
In conjunction with another on-going project in our
laboratory, we had observed that aryl silyl ethers can be
removed selectively in the presence of alkyl silyl ethers
using triethylamine N-oxide in high yield (Scheme 1).
Typical experimental procedure:
To a stirred solution of the substrate 1 (0.448 g, 1
mmol) in methanol (5 ml) was added Et3N-O (0.117g, 1
mmol). The reaction was monitored by TLC. After the
reaction was complete, the solvent was removed under
vacuum. The residue was extracted with a suitable
solvent, and the organic extract was washed with water,
dried and concentrated. The crude product was purified
by column chromatography with ethyl acetate/hexane
as eluent to afford phenol 2 as a colourless oil in 85%
yield. The product obtained was identical with an
Scheme 1.
1
* Corresponding author.
authentic sample by TLC and H NMR.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01452-1

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P. K. Zubaidha et al. / Tetrahedron Letters 43 (2002) 7277–7279
Table 1. Desilylation of aryl silyl ethersa
In summary, triethylamine N-oxide can be used as a
selective reagent for deprotection of aryl silyl ethers. The
mild conditions coupled with high yields and the demon-
strated applicability to functionalised molecules shows
that the protocol will find wide spread use in synthesis.
2. Kocienski, P. J. Protecting Groups; Georg Thieme Verlag:
Stuttgart, 1994.
3. Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972,
94, 6190.
4. (a) Nelson, T. D.; Crouch, R. D. Synthesis 1996, 1031–
1069; (b) Angle, S. R.; Wada, T. Tetrahedron Lett. 1997,
38, 7955–7958; (c) Maiti, G.; Roy, S. C. Tetrahedron Lett.
1997, 38, 495–498; (d) Wilson, N. S.; Keay, B. S. Tetra-
hedron Lett. 1997, 38, 187–190; (e) Jung, M. E.; Jung, Y.
H. Synlett 1995, 563–564; (f) Prakash, C.; Saleh, S.; Blair,
I. A. Tetrahedron Lett. 1994, 35, 7565–7568; (g) Davies, J.
S.; Higginbotham, C. L.; Tremeer, E. J.; Brown, C.;
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