A Novel, Efficient, and Selective Cleavage of Alkyl tert-Butyldimethylsilyl Ethers Using the BiCl3/NaI System

Full text of DOI:10.1002/1615-4169(20010226)343:2<169::AID-ADSC169>3.0.CO;2-C

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A Novel, Efficient, and Selective Cleavage of Alkyl tert-
Butyldimethylsilyl Ethers Using the BiCl3/NaI
System**
Gowravaram Sabitha,* R. Satheesh Babu, E. Venkata Reddy, R. Srividya, J. S. Yadav
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax: (+91) 40-717 0512; e-mail: sabitha@iict.ap.nic.in
Received September 8, 2000; Accepted November 2, 2000
The protection of the hy-
droxy functional group as
The
alkyl
TBDMS
Keywords: alcohols; bismuth(III) chloride; che-
moselectivity; deprotection; protecting groups;
TBDMS ethers
ethers were cleaved very
effectively with 2.5 equiv.
of BiCl3 and 2.6 equiv. of
NaI in acetonitrile. The
deprotection reaction is
a
tert-butyldimethylsilyl
ether (TBDMS)[1] is most
common and useful in or-
ganic synthesis, because
of its stability towards basic and mild acidic reagents. very fast at room temperature and the corresponding
The importance of any protecting group depends on alcohols were formed in high yields (Table 1). Under
how easily it can be installed and removed. Tetrabutyl- the present reaction conditions the secondary
ammonium fluoride (TBAF)[1,2] is often used for de- TBDMS ethers were also cleanly deprotected in high
protection of TBDMS ethers, but being a strong base yields. The versatility of this procedure has been illu-
it can alter base-sensitive substrates. Several meth- strated by deprotecting the secondary TBDMS group
ods[3] under various reaction conditions have been of menthol without loss of the original configuration.
reported in the literature for the deprotection of ([a]D observed: ±53, (c 10 in methanol), [a]D lit.:
TBDMS ether groups. However, only scattered proce- ±50 ± 1, (c 10 in methanol).
dures[4] exist for the selective cleavage of alkyl
TBDMS ethers over aryl TBDMS ethers. Recently, we
reported the selective cleavage of primary TBDMS
ethers by oxoneÒ in aqueous methanol.[5] But this re-
agent was inert towards the deprotection of second-
Scheme 1.
ary TBDMS ethers. As part of our research program
on the synthetic sequences of complex natural prod-
We have demonstrated the selective cleavage of pri-
mary and secondary alkyl TBDMS groups in the pre-
sence of aryl TBDMS groups. Thus, treatment of the
bis TBDMS ether with 2.5 equiv. of BiCl3 and 2.6
equiv. of NaI at room temperature in acetonitrile
yielded the mono-deprotected product (Scheme 2).
Even after a prolonged reaction time the phenolic
TBDMS ether remained unaffected. A number of sub-
strates have been examined using this protocol and
we found selectivity in all the cases without affecting
the phenolic TBDMS ethers (Table 2). The selective
removal of alkyl TBDMS ethers has also been
achieved in the presence of other functional groups
such as ±OTs, ±NHBOC, ±OMe and ±OBn; therefore,
the present method offers several advantages over
the reported methods.
ucts, we needed to deprotect a secondary TBDMS
ether group selectively in the presence of an aryl
TBDMS ether group. On the other hand, we found
that bismuth(III) chloride was an efficient Lewis acid
for the selective cleavage of acetals and ketals[6] and
many useful reactions using BiCl3 have been devel-
oped.[7]
In this paper we report a highly selective and effi-
cient procedure for the selective cleavage of alkyl
TBDMS groups in the presence of aryl TBDMS groups
using the BiCl3/NaI system under mild reaction con-
ditions (Scheme 1). Although BiCl3 is a weak Lewis
acid, it was possible to increase the catalytic power
of BiCl3 by addition of sodium iodide. There are many
advantages for the use of BiCl3, no strongly basic or
acidic conditions are used, it is a non-toxic,[8] easy to
handle and commercially available compound.
**
IICT Communication No. 4631
Scheme 2.
Adv. Synth. Catal. 2001, 343, No. 2
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Table 1. Deprotection of alkyl TBDMS ethers using the
Table 2. Selective deprotection of alkyl TBDMS ethers
BiCl3/NaI system
Entry
TBDMS Ether
Alcohol
Time Yield
(min) (%)[a]
Entry
TBDMS Ether
Alcohol
Time Yield
(min) (%)[a]
[a] Yields refer to isolated products.
was removed under reduced pressure and the residue ex-
tracted with EtOAc (2 ´ 10 mL), washed with water and brine.
After drying (Na2SO4) and solvent removal, the crude product
was purified by column chromatography. The alcohols ob-
tained were characterized by IR and 1H NMR spectroscopy.
Acknowledgements
RSB, EVR & RSV thank CSIR, New Delhi for the award of fel-
lowships.
[a] Yields refer to isolated products.
References and Notes
[1] E. J. Corey, A. Venkateshwarlu, J. Am. Chem. Soc.
1972, 94, 6190.
In conclusion, we have described the selective
cleavage of primary and secondary tert-butyldi-
methylsilyl ether groups in the presence of aryl tert-
butyldimethylsilyl ethers. The salient features of the
present methodology include 1) the ease of operation,
2) high efficiency, 3) chemoselectivity, and 4) mild re-
action conditions. Therefore, this protocol represents
a valuable alternative to all of the reagents reported
in the literature.
[2] E. J. Corey, B. B. Snider, J. Am. Chem. Soc. 1972, 94, 2549.
[3] (a) K. Tanemura, T. Suzuki, T. Horaguchi, J. Chem.
Soc., Perkin Trans. 1 1992, 2997; (b) A. Duttagupta,
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shong, J. Org. Chem. 1992, 57, 2492.
[4] (a) B. H. Lipshutz, J. Keith, Tetrahedron Lett. 1998, 39,
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1998, 1047; (c) P. A. Grieco, C. J. Markworth, Tetrahe-
dron Lett. 1999, 40, 665.
Experimental Section
[5] G. Sabitha, M. Syamala, J. S. Yadav, Org. Lett. 1999, 1
1701.
[6] G. Sabitha, R. Satheesh Babu, E. Venkata Reddy, J. S.
Yadav, Chem. Lett. 2000, 9, 1074.
[7] H. Robert, B. Garrigues, J. Dubac, Tetrahedron Lett.
1998, 39, 1161 and references cited therein.
[8] (a) N. Irwing-Sax, R. J. Bewis, Dangerous Properties of
Industrial Materials, Van Nostran Reinhold, 1989,
pp. 283, 284, 522, 523; (b) U. Wormser, I. Nir in The
Chemistry of Arsenic, Antimony and Bismuth Com-
pounds (Ed.: S. Patai), Wiley, New York, 1994, pp. 715.
General Procedure for Cleavage
of TBDMS Ether Group
To a mixture of BiCl3 (2.5 mmol) and NaI (2.6 mmol) in aceto-
nitrile (10 mL) was added the TBDMS ether (1 mmol) in acet-
onitrile (2 mL) at room temperature. The reaction mixture
was stirred at room temperature until TLC indicated that
no starting material remained. On completion, the solvent
170
Adv. Synth. Catal. 2001, 343, 169±170