A facile zirconium(IV) chloride catalysed selective deprotection of t-butyldimethylsilyl (TBDMS) ethers

Article abstract of DOI:10.1016/S0040-4039(03)01088-8

A simple and efficient protocol for the selective deprotection of t-butyldimethylsilyl (TBDMS) ethers using 20 mol% ZrCl₄ in 20-45 min and in high yields, is reported, wherein it is demonstrated that acid and base sensitive groups and allylic and benzylic groups are unaffected.

Full text of DOI:10.1016/S0040-4039(03)01088-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4689–4691
A facile zirconium(IV) chloride catalysed selective deprotection
of t-butyldimethylsilyl (TBDMS) ethersꢀ
G. V. M. Sharma,* B. Srinivas and Palakodety Radha Krishna
D-211, Discovery Laboratory, Organic Chemistry Division-III, Indian Institute of Chemical Technology, Hyderabad 500 007,
India
Received 10 February 2003; revised 9 April 2003; accepted 25 April 2003
Abstract—A simple and efficient protocol for the selective deprotection of t-butyldimethylsilyl (TBDMS) ethers using 20 mol%
ZrCl4 in 20–45 min and in high yields, is reported, wherein it is demonstrated that acid and base sensitive groups and allylic and
benzylic groups are unaffected. © 2003 Elsevier Science Ltd. All rights reserved.
Successful total syntheses of complex natural products
(1)
depend not only on the correct strategy, but also on
the correct choice of protecting groups,1 the ease of
their introduction, their stability towards a variety of
A variety of TBDMS ethers were prepared from sub-
reagents and finally their removal without effecting
strates comprising aliphatic, terpenoidal and sugar alco-
other functional groups present in the molecule. Since
hols, in addition to diols possessing other different
the selective protection and deprotection of functional
protecting groups. Initially, TBDMS ether 1 was sub-
jected to desilylation with 20 mol% of ZrCl4 in CH3CN
at room temperature for 20 min to give 1a in 93% yield.
A similar study on terpenoidal ether 2 resulted in 2a in
20 min (87%). Extension of the same study to substrates
3 and 4 containing TBDMS protected secondary alco-
hols gave the desilylated products 3a (89%) albeit in 2 h,
and 4a (95%) in 40 min, respectively.
groups is always very important in achieving a total
synthesis, several protecting groups of different nature
are available. Ever since the discovery of the t-
butyldimethylsilyl (TBDMS) group by Corey et al.,2
the TBDMS group has occupied a prominent place in
synthetic chemistry and aided in the development of
other related trialkylsilyl reagents as efficient protect-
ing groups. The TBDMS group is one of the most
versatile protecting groups due to its ease of introduc-
tion and ease of removal by TBAF,2 as a result of its
high fluoride ion affinity. A vast array3 of acidic,
basic, reducing, oxidizing and fluoride-based reagents
were developed for the removal of the TBDMS group.
In spite of these, there is still a need to develop new
reagents in order to selectively remove TBDMS that
function catalytically, and without effecting any acid
or base sensitive groups. In continuation of our stud-
ies on the protection and deprotection4 of alcoholic
functional groups by use of Lewis acids, herein, we
report a simple and facile zirconium(IV) chloride (20
mol%) catalyzed deprotection of TBDMS ethers (Eq.
(1)).
The study was then extended to the sugar substrates 5
and 6 possessing 1,3-dioxolane protecting groups. Ini-
tially, reaction of 5 with 20 mol% ZrCl4 at room
temperature gave the expected product, along with the
acetonide cleaved product. However, treatment of 5 with
ZrCl4 at 0°C gave 5a in 83% yield in 45 min, while similar
desilylation of 6 at 0°C gave 6a (80%) in 45 min.
In a further study, desilylation of TBDMS ethers was
attempted on substrates containing both acid and base
sensitive protecting groups. Thus, ethers 7, 8 and 9
possessing the acid sensitive groups THP, MEM and
MDPM, gave the expected products 7a (87%), 8a (76%)
and 9a (81%), respectively, in which the THP, MEM and
MDPM groups remained unaffected during the desilyla-
tion. A similar study with 10 and 11 which possess the
base sensitive acetate and benzoate groups gave the
respective alcohols 10a (92%) and 11a (95%) in 30 min.
Keywords: TBDMS ethers; zirconium(IV) chloride; desilylation; pro-
tecting groups.
ꢀ IICT Communication No. 030202.
* Corresponding author. E-mail: esmvee@iict.ap.nic.in
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01088-8

4690
G. V. M. Sharma et al. / Tetrahedron Letters 44 (2003) 4689–4691
In addition, TBDMS ethers 12, 13 and 14, possessing
benzylic, allylic and acid sensitive prenyl protecting
groups, when treated with ZrCl4 at room temperature
in CH3CN, gave the expected products 12a (95%), 13a
(94%) and 14a (88%), respectively.
reagent system. Thus, ZrCl4 (20 mol%) in CH3CN with
simple reaction conditions, shorter reaction times, high
selectivity for the TBDMS group and high yields
should find use in synthetic chemistry as a new and
efficient reagent for the desilylation of TBDMS ethers.
Thus, in conclusion, ZrCl4 in CH3CN provides a mild
and efficient catalytic (20 mol%) system for the highly
selective removal of the TBDMS protecting group. The
study also demonstrated that both acid and base sensi-
tive groups and allylic and benzylic groups were unaf-
fected. Further, it was shown that substrates such as
sugars and terpenes are also unaffected by the present
Typical experimental procedure for deprotection: A solu-
tion of TBDMS ether (1.0 mmol) in CH3CN (10 mL)
was treated with ZrCl4 (0.2 mmol) and stirred at room
temperature for 20–45 min. The reaction mixture was
evaporated and purified by column chromatography
(60–120 mesh silica gel, EtOAc–petroleum ether) to
furnish the desilylated products in 76–95% yields.

G. V. M. Sharma et al. / Tetrahedron Letters 44 (2003) 4689–4691
4691
Spectral data for selected compounds:
2. Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972,
94, 6190–6191.
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Compound 8: H NMR (CDCl3, 200 MHz): l 4.73 (d,
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1028–1029; (c) Lee, A. S. Y.; Yeh, H. C.; Tsai, M. H.
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J=5.92 Hz, 1H), 4.68 (s, 1H), 3.69–3.62 (m, 4H),
3.58–3.41 (m, 4H), 3.39 (s, 3H), 1.60–1.30 (m, 4H) 0.92
(s, 9H) 0.05 (s, 6H); EIMS (m/z): 292 (M+); IR (neat):
2934, 2886, 1513, 1253, 1105, 1036 cm−1.
Compound 10: 1H NMR (CDCl3, 200 MHz): l 4.04–3.93
(t, J=5.9 Hz, 2H), 3.65–3.62 (t, J=5.6 Hz, 2H), 2.1 (s,
3H), 1.69–1.32 (m, 4H), 0.92 (s, 9H), 0.04 (s, 6H); EIMS
(m/z): 246 (M+), 218 (8), 100 (80), 68 (58); IR (neat):
2910, 1750, 1560, 1260, 1039 cm−1.
Compound 14: 1H NMR (CDCl3, 300 MHz): l 5.34–5.29
(t, J=6.6 Hz, 1H), 3.9 (d, J=4.8 Hz, 2H), 3.41–3.39 (t,
J=5.4 Hz, 2H), 3.32 (t, J=5.6 Hz, 2H), 1.72 (s, 3H), 1.68
(s, 3H), 1.61–1.32 (m, 4H) 0.94 (s, 9H), 0.05 (s, 6H);
EIMS (m/z): 272 (M+); IR (neat): 2937, 2858, 2359, 1512,
1180, 1037 cm−1.
1
Compound 8a: H NMR (CDCl3, 200 MHz): l 4.68 (d,
J=5.61 Hz, 1H), 4.64 (s, 1H), 3.66–3.61 (t, J=5.8 Hz,
2H), 3.56–3.44 (m, 6H), 3.41 (s, 3H), 1.64–1.32 (m, 4H);
EIMS (m/z): 178 (M+); IR (neat): 3469, 2926, 1521, 1471
cm−1.
1
Compound 10a: H NMR (CDCl3, 200 MHz): l 4.14–
4.06 (t, J=5.9 Hz, 2H), 3.63–3.59 (t, J=5.9 Hz, 2H), 2.1
(s, 3H), 1.68–1.34 (m, 4H); EIMS (m/z): 132 (M+), 121,
91; IR (neat): 3482, 2910, 1750, 1560, 1260 cm−1.
1
Compound 14a: H NMR (CDCl3, 200 MHz): l 5.38–
4. (a) Sharma, G. V. M.; Mahalingam, A. K.; Nagarajan,
M.; Ilangovan, A.; Radha Krishna, P. Synlett 1999, 8,
1200–1202; (b) Sharma, G. V. M.; Mahalingam, A. K.
J. Org. Chem. 1999, 64, 8943–8944; (c) Sharma, G. V.
M.; Ilangovan, A. Synlett 1999, 12, 1963–1965; (d)
Sharma, G. V. M.; Lavanya, B.; Mahalingam, A. K.;
Radha Krishna, P. Tetrahedron Lett. 2000, 41, 10323–
10326; (e) Sharma, G. V. M.; Prasad, T. R.;
Mahalingam, A. K. Tetrahedron Lett. 2001, 42, 759–761;
(f) Sharma, G. V. M.; Rakesh Tetrahedron Lett. 2001,
42, 5571–5573.
5.32 (t, J=6.6 Hz, 1H), 3.96 (d, J=4.8 Hz, 2H), 3.62 (t,
J=6.4 Hz, 2H), 3.36–3.39 (t, J=6.4 Hz, 2H), 1.71 (s,
3H), 1.66 (s, 3H), 1.62–1.34 (m, 4H); EIMS (m/z): 158
(M+), 141, 83, 69; IR (neat): 3506, 2942, 2861, 1523 cm−1.
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